Microbiologic factors affecting Clostridium difficile recurrence.

PubMed

Chilton, C H; Pickering, D S; Freeman, J

2018-05-01

Recurrent Clostridium difficile infection (rCDI) places a huge economic and practical burden on healthcare facilities. Furthermore, rCDI may affect quality of life, leaving patients in an rCDI cycle and dependant on antibiotic therapy. To discuss the importance of microbiologic factors in the development of rCDI. Literature was drawn from a search of PubMed from 2000 onwards with the search term 'recurrent Clostridium difficile infection' and further references cited within these articles. Meta-analyses and systematic reviews have shown that CDI and rCDI risk factors are similar. Development of rCDI is attendant on many factors, including immune status or function, comorbidities and concomitant treatments. Studies suggest that poor bacterial diversity is correlated with clinical rCDI. Narrow-spectrum gut microflora-sparing antimicrobials (e.g. surotomycin, cadazolid, ridinilazole) are in development for CDI treatment, while microbiota therapeutics (faecal microbiota transplantation, nontoxigenic C. difficile, stool substitutes) are increasingly being explored. rCDI can only occur when viable C. difficile spores are present, either within the gut lumen after infection or when reacquired from the environment. C. difficile spore germination can be influenced by gut environmental factors resulting from dysbiosis, and spore outgrowth may be affected stage by some antimicrobials (e.g. fidaxomicin, ramoplanin, oritavancin). rCDI is a significant challenge for healthcare professionals, requiring a multifaceted approach; optimized infection control to minimize reinfection; C. difficile-targeted antibiotics to minimize dysbiosis; and gut microflora restoration to promote colonization resistance. These elements should be informed by our understanding of the microbiologic factors involved in both C. difficile itself and the gut microbiome. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Optimal control of vaccination rate in an epidemiological model of Clostridium difficile transmission.

PubMed

Stephenson, Brittany; Lanzas, Cristina; Lenhart, Suzanne; Day, Judy

2017-12-01

The spore-forming, gram-negative bacteria Clostridium difficile can cause severe intestinal illness. A striking increase in the number of cases of C. difficile infection (CDI) among hospitals has highlighted the need to better understand how to prevent the spread of CDI. In our paper, we modify and update a compartmental model of nosocomial C. difficile transmission to include vaccination. We then apply optimal control theory to determine the time-varying optimal vaccination rate that minimizes a combination of disease prevalence and spread in the hospital population as well as cost, in terms of time and money, associated with vaccination. Various hospital scenarios are considered, such as times of increased antibiotic prescription rate and times of outbreak, to see how such scenarios modify the optimal vaccination rate. By comparing the values of the objective functional with constant vaccination rates to those with time-varying optimal vaccination rates, we illustrate the benefits of time-varying controls.

The economic impact of Clostridium difficile infection: a systematic review.

PubMed

Nanwa, Natasha; Kendzerska, Tetyana; Krahn, Murray; Kwong, Jeffrey C; Daneman, Nick; Witteman, William; Mittmann, Nicole; Cadarette, Suzanne M; Rosella, Laura; Sander, Beate

2015-04-01

With Clostridium difficile infection (CDI) on the rise, knowledge of the current economic burden of CDI can inform decisions on interventions related to CDI. We systematically reviewed CDI cost-of-illness (COI) studies. We performed literature searches in six databases: MEDLINE, Embase, the Health Technology Assessment Database, the National Health Service Economic Evaluation Database, the Cost-Effectiveness Analysis Registry, and EconLit. We also searched gray literature and conducted reference list searches. Two reviewers screened articles independently. One reviewer abstracted data and assessed quality using a modified guideline for economic evaluations. The second reviewer validated the abstraction and assessment. We identified 45 COI studies between 1988 and June 2014. Most (84%) of the studies were from the United States, calculating costs of hospital stays (87%), and focusing on direct costs (100%). Attributable mean CDI costs ranged from $8,911 to $30,049 for hospitalized patients. Few studies stated resource quantification methods (0%), an epidemiological approach (0%), or a justified study perspective (16%) in their cost analyses. In addition, few studies conducted sensitivity analyses (7%). Forty-five COI studies quantified and confirmed the economic impact of CDI. Costing methods across studies were heterogeneous. Future studies should follow standard COI methodology, expand study perspectives (e.g., patient), and explore populations least studied (e.g., community-acquired CDI).

The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

PubMed Central

Sun, Xingmin; Hirota, Simon A.

2014-01-01

Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

76 FR 14021 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... Project Clostridium difficile Infection (CDI) Surveillance--New--National Center for Emerging and Zoonotic... Description Steady increases in the rate and severity of Clostridium difficile infection (CDI) indicate a clear need to conduct longitudinal assessments of the impact of CDI in the United States. C. difficile...

Isolation of C. difficile Carriers Alone and as Part of a Bundle Approach for the Prevention of Clostridium difficile Infection (CDI): A Mathematical Model Based on Clinical Study Data.

PubMed

Grigoras, Christos A; Zervou, Fainareti N; Zacharioudakis, Ioannis M; Siettos, Constantinos I; Mylonakis, Eleftherios

2016-01-01

Clostridium difficile infection is the most common hospital-acquired infection. Besides infected patients, carriers have emerged as a key player in C. difficile epidemiology. In this study, we evaluated the impact of identifying and isolating carriers upon hospital admission on the incidence of CDI incidence and hospital-acquired C. difficile colonization, as a single policy and as part of bundle approaches. We simulated C. difficile transmission using a stochastic mathematical approach, considering the contribution of carriers based on published literature. In the baseline scenario, CDI incidence was 6.18/1,000 admissions (95% CI, 5.72-6.65), simulating reported estimates from U.S. hospital discharges. The acquisition rate of C. difficile carriage was 9.72/1,000 admissions (95% CI, 9.15-10.31). Screening and isolation of colonized patients on admission to the hospital decreased CDI incidence to 4.99/1,000 admissions (95% CI, 4.59-5.42; relative reduction (RR) = 19.1%) and led to 36.2% reduction in the rate of hospital-acquired colonization. Simulating an antimicrobial stewardship program reduced CDI rate to 2.35/1,000 admissions (95% CI, 2.07-2.65). In sensitivity analysis, CDI incidence was less than 2.32/1,000 admissions (RR = 62.4%) in 95% of 1,000 simulations. The combined bundle, focusing on reducing C. difficile transmission from colonized patients and the individual risk of these patients to develop CDI, decreased significantly the incidence of both CDI and hospital-acquired colonization. Implementation of this bundle to current practice is expected to have an important impact in containing CDI.

Isolation of C. difficile Carriers Alone and as Part of a Bundle Approach for the Prevention of Clostridium difficile Infection (CDI): A Mathematical Model Based on Clinical Study Data

PubMed Central

Grigoras, Christos A.; Zervou, Fainareti N.; Zacharioudakis, Ioannis M.; Siettos, Constantinos I.; Mylonakis, Eleftherios

2016-01-01

Clostridium difficile infection is the most common hospital-acquired infection. Besides infected patients, carriers have emerged as a key player in C. difficile epidemiology. In this study, we evaluated the impact of identifying and isolating carriers upon hospital admission on the incidence of CDI incidence and hospital-acquired C. difficile colonization, as a single policy and as part of bundle approaches. We simulated C. difficile transmission using a stochastic mathematical approach, considering the contribution of carriers based on published literature. In the baseline scenario, CDI incidence was 6.18/1,000 admissions (95% CI, 5.72–6.65), simulating reported estimates from U.S. hospital discharges. The acquisition rate of C. difficile carriage was 9.72/1,000 admissions (95% CI, 9.15–10.31). Screening and isolation of colonized patients on admission to the hospital decreased CDI incidence to 4.99/1,000 admissions (95% CI, 4.59–5.42; relative reduction (RR) = 19.1%) and led to 36.2% reduction in the rate of hospital-acquired colonization. Simulating an antimicrobial stewardship program reduced CDI rate to 2.35/1,000 admissions (95% CI, 2.07–2.65). In sensitivity analysis, CDI incidence was less than 2.32/1,000 admissions (RR = 62.4%) in 95% of 1,000 simulations. The combined bundle, focusing on reducing C. difficile transmission from colonized patients and the individual risk of these patients to develop CDI, decreased significantly the incidence of both CDI and hospital-acquired colonization. Implementation of this bundle to current practice is expected to have an important impact in containing CDI. PMID:27258068

Molecular characteristics of Clostridium difficile strains from patients with a first recurrence more than 8 weeks after the primary infection.

PubMed

Chen, Yijian; Rashid, Mamun Ur; Huang, Haihui; Fang, Hong; Nord, Carl Erik; Wang, Minggui; Weintraub, Andrej

2017-08-01

Nearly all published studies of recurrent Clostridium difficile infections (CDI) report recurrent CDI within 8 weeks after the primary infection. This study explored the molecular characteristics of C. difficile isolates from the first recurrent CDI more than 8 weeks after the primary infection. Consecutive hospitalized patients with a recurrent CDI more than 8 weeks after a primary infection were enrolled prospectively from January 2008 to February 2011. All C. difficile isolates of the primary and recurrent infections were collected and subjected to polymerase chain reaction ribotyping and antimicrobial susceptibility testing. There were 62 cases of CDI in this study, which included 32 cases (51.6%) of recurrence due to the same ribotype of C. difficile, 26 (41.9%) cases due to a different ribotype, and four (6.5%) cases with 2-4 recurrences due to the same or different strains. One hundred and forty C. difficile isolates were obtained, which included 62 primary CDI isolates and 78 recurrent isolates. Ribotype 020 was the most common C. difficile strain in primary and recurrent infections. Ribotype 001 accounted for 15.4% (10/78) of recurrent infections and 3.2% (2/62) of primary infections (p = 0.0447). The minimum inhibitory concentration at 90% (MIC 90 ) values of linezolid, moxifloxacin, and clindamycin against type 001 strains were much higher, compared to the three other common ribotypes. Recurrent CDI more than 8 weeks after a primary infection can be caused by the same or different C. difficile ribotype at similar percentages. Ribotype 001 C. difficile strains, which have a lower susceptibility to antimicrobials, were isolated more frequently in patients with a recurrent CDI. Copyright © 2015. Published by Elsevier B.V.

Current knowledge on the laboratory diagnosis of Clostridium difficile infection.

PubMed

Martínez-Meléndez, Adrián; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Maldonado-Garza, Héctor Jesús; Villarreal-Treviño, Licet; Garza-González, Elvira

2017-03-07

Clostridium difficile ( C. difficile ) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI.

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains.

PubMed

Stoesser, Nicole; Eyre, David W; Quan, T Phuong; Godwin, Heather; Pill, Gemma; Mbuvi, Emily; Vaughan, Alison; Griffiths, David; Martin, Jessica; Fawley, Warren; Dingle, Kate E; Oakley, Sarah; Wanelik, Kazimierz; Finney, John M; Kachrimanidou, Melina; Moore, Catrin E; Gorbach, Sherwood; Riley, Thomas V; Crook, Derrick W; Peto, Tim E A; Wilcox, Mark H; Walker, A Sarah

2017-01-01

Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases. 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0-10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%). In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread.

A Clostridium difficile infection (CDI) stewardship initiative improves adherence to practice guidelines for management of CDI.

PubMed

Jury, Lucy A; Tomas, Myreen; Kundrapu, Sirisha; Sitzlar, Brett; Donskey, Curtis J

2013-11-01

A Clostridium difficile infection (CDI) stewardship initiative reduced inappropriate prescription of empirical CDI therapy and improved timeliness of treatment and adherence to clinical practice guidelines for management of CDI. The initiative required minimal resources and could easily be incorporated into traditional antimicrobial stewardship programs.

Risk for Clostridium difficile Infection After Allogeneic Hematopoietic Cell Transplant Remains Elevated in the Postengraftment Period.

PubMed

Dubberke, Erik R; Reske, Kimberly A; Olsen, Margaret A; Bommarito, Kerry M; Seiler, Sondra; Silveira, Fernanda P; Chiller, Tom M; DiPersio, John; Fraser, Victoria J

2017-04-01

Clostridium difficile infection (CDI) is a frequent cause of diarrhea among allogeneic hematopoietic cell transplant (HCT) recipients. It is unknown whether risk factors for CDI vary by time posttransplant. We performed a 3-year prospective cohort study of CDI in allogeneic HCT recipients. Participants were enrolled during their transplant hospitalizations. Clinical assessments were performed weekly during hospitalizations and for 12 weeks posttransplant, and monthly for 30 months thereafter. Data were collected through patient interviews and chart review, and included CDI diagnosis, demographics, transplant characteristics, medications, infections, and outcomes. CDI cases were included if they occurred within 1 year of HCT and were stratified by time from transplant. Multivariable logistic regression was used to determine risk factors for CDI. One hundred eighty-seven allogeneic HCT recipients were enrolled, including 63 (34%) patients who developed CDI. 38 (60%) CDI cases occurred during the preengraftment period (days 0-30 post-HCT) and 25 (40%) postengraftment (day >30). Lack of any preexisting comorbid disease was significantly associated with lower risk of CDI preengraftment (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.9). Relapsed underlying disease (OR, 6.7; 95% CI, 1.3-33.1), receipt of any high-risk antimicrobials (OR, 11.8; 95% CI, 2.9-47.8), and graft-versus-host disease (OR, 7.8; 95% CI, 2.0-30.2) were significant independent risk factors for CDI postengraftment. A large portion of CDI cases occurred during the postengraftment period in allogeneic HCT recipients, suggesting that surveillance for CDI should continue beyond the transplant hospitalization and preengraftment period. Patients with continued high underlying severity of illness were at increased risk of CDI postengraftment.

Current knowledge on the laboratory diagnosis of Clostridium difficile infection

PubMed Central

Martínez-Meléndez, Adrián; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Maldonado-Garza, Héctor Jesús; Villarreal-Treviño, Licet; Garza-González, Elvira

2017-01-01

Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI. PMID:28321156

Control of Clostridium difficile infection by defined microbial communities

PubMed Central

Collins, James

2017-01-01

Summary Each year in the United States, billions of dollars are spent combating almost half a million Clostridium difficile infections (CDI) and trying to reduce the ~29,000 patient deaths where C. difficile has an attributed role (1). In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion (2). One factor contributing to the significant healthcare burden of C. difficile is the relatively high frequency of recurrent C. difficile infections(3). Recurrent C. difficile infection (rCDI), i.e., a second episode of symptomatic CDI occurring within eight weeks of successful initial CDI treatment, occurs in ~25% of patients with 35-65% of these patients experiencing multiple episodes of recurrent disease(4, 5). Using microbial communities to treat rCDI, either as whole fecal transplants or as defined consortia of bacterial isolates have shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of C. difficile infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways through which that knowledge can be used to rationally-design and test alternative microbe-based therapeutics. PMID:28936948

Clostridium difficile and inflammatory bowel disease: role in pathogenesis and implications in treatment.

PubMed

Nitzan, Orna; Elias, Mazen; Chazan, Bibiana; Raz, Raul; Saliba, Walid

2013-11-21

Clostridium difficile (C. difficile) is the leading cause of antibiotic associated colitis and nosocomial diarrhea. Patients with inflammatory bowel disease (IBD) are at increased risk of developing C. difficile infection (CDI), have worse outcomes of CDI-including higher rates of colectomy and death, and experience higher rates of recurrence. However, it is still not clear whether C. difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment. The burden of CDI has increased dramatically over the past decade, with severe outbreaks described in many countries, which have been attributed to a new and more virulent strain. A parallel rise in the incidence of CDI has been noted in patients with IBD. IBD patients with CDI tend be younger, have less prior antibiotic exposure, and most cases of CDI in these patients represent outpatient acquired infections. The clinical presentation of CDI in these patients can be unique-including diversion colitis, enteritis and pouchitis, and typical findings on colonoscopy are often absent. Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation, and the prognostic implications of CDI in these patients, it is recommended to test all IBD patients hospitalized with a disease flare for C. difficile. Treatment includes general measures such as supportive care and infection control measures. Antibiotic therapy with either oral metronidazole, vancomycin, or the novel antibiotic-fidaxomicin, should be initiated as soon as possible. Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI. The aim of this paper is to review recent data on CDI in IBD: role in pathogenesis, diagnostic methods, optional treatments, and outcomes of these patients.

Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection.

PubMed

Crowther, Grace S; Baines, Simon D; Todhunter, Sharie L; Freeman, Jane; Chilton, Caroline H; Wilcox, Mark H

2013-01-01

First-line treatment options for Clostridium difficile infection (CDI) are limited. NVB302 is a novel type B lantibiotic under evaluation for the treatment of CDI. We compared the responses to NVB302 and vancomycin when used to treat simulated CDI in an in vitro gut model. We used ceftriaxone to elicit simulated CDI in an in vitro gut model primed with human faeces. Vancomycin and NVB302 were instilled into separate gut models and the indigenous gut microbiota and C. difficile total viable counts, spores and toxin levels were monitored throughout. Ceftriaxone instillation promoted C. difficile germination and high-level toxin production. Commencement of NVB302 and vancomycin instillation reduced C. difficile total viable counts rapidly with only C. difficile spores remaining within 3 and 4 days, respectively. Cytotoxin was reduced to undetectable levels 5 and 7 days after vancomycin and NVB302 instillation commenced in vessel 2 and 3, respectively, and remained undetectable for the remainder of the experiments. C. difficile spores were unaffected by the presence of vancomycin or NVB302. NVB302 treatment was associated with faster resolution of Bacteroides fragilis group. Both NVB302 and vancomycin were effective in treating simulated CDI in an in vitro gut model. C. difficile spore recrudescence was not observed following successful treatment with either NVB302 or vancomycin. NVB302 displayed non-inferiority to vancomycin in the treatment of simulated CDI, and had less deleterious effects against B. fragilis group. NVB302 warrants further clinical investigation as a potentially novel antimicrobial agent for the treatment of CDI.

Evaluation of Correlation between Pretest Probability for Clostridium difficile Infection and Clostridium difficile Enzyme Immunoassay Results

PubMed Central

Reske, Kimberly A.; Hink, Tiffany; Dubberke, Erik R.

2016-01-01

ABSTRACT The objective of this study was to evaluate the clinical characteristics and outcomes of hospitalized patients tested for Clostridium difficile and determine the correlation between pretest probability for C. difficile infection (CDI) and assay results. Patients with testing ordered for C. difficile were enrolled and assigned a high, medium, or low pretest probability of CDI based on clinical evaluation, laboratory, and imaging results. Stool was tested for C. difficile by toxin enzyme immunoassay (EIA) and toxigenic culture (TC). Chi-square analyses and the log rank test were utilized. Among the 111 patients enrolled, stool samples from nine were TC positive and four were EIA positive. Sixty-one (55%) patients had clinically significant diarrhea, 19 (17%) patients did not, and clinically significant diarrhea could not be determined for 31 (28%) patients. Seventy-two (65%) patients were assessed as having a low pretest probability of having CDI, 34 (31%) as having a medium probability, and 5 (5%) as having a high probability. None of the patients with low pretest probabilities had a positive EIA, but four were TC positive. None of the seven patients with a positive TC but a negative index EIA developed CDI within 30 days after the index test or died within 90 days after the index toxin EIA date. Pretest probability for CDI should be considered prior to ordering C. difficile testing and must be taken into account when interpreting test results. CDI is a clinical diagnosis supported by laboratory data, and the detection of toxigenic C. difficile in stool does not necessarily confirm the diagnosis of CDI. PMID:27927930

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains

PubMed Central

Godwin, Heather; Pill, Gemma; Mbuvi, Emily; Vaughan, Alison; Griffiths, David; Martin, Jessica; Fawley, Warren; Dingle, Kate E.; Oakley, Sarah; Wanelik, Kazimierz; Finney, John M.; Kachrimanidou, Melina; Moore, Catrin E.; Gorbach, Sherwood; Riley, Thomas V.; Crook, Derrick W.; Peto, Tim E. A.; Wilcox, Mark H.; Walker, A. Sarah

2017-01-01

Background Approximately 30–40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. Methods Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases. Results 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0–10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%). Conclusions In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread. PMID:28813461

Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection.

PubMed

Vincent, Caroline; Miller, Mark A; Edens, Thaddeus J; Mehrotra, Sudeep; Dewar, Ken; Manges, Amee R

2016-03-14

Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and composition of the fecal microbiota in a prospective cohort study of 98 hospitalized patients. Four patients had asymptomatic C. difficile colonization, and four patients developed CDI. We observed dramatic shifts in the structure of the gut microbiota during hospitalization. In contrast to CDI cases, asymptomatic patients exhibited elevated relative abundance of potentially protective bacterial taxa in their gut at the onset of C. difficile colonization. Use of laxatives was associated with significant reductions in the relative abundance of Clostridium and Eubacterium; species within these genera have previously been shown to enhance resistance to CDI via the production of secondary bile acids. Cephalosporin and fluoroquinolone exposure decreased the frequency of Clostridiales Family XI Incertae Sedis, a bacterial family that has been previously associated with decreased CDI risk. This study underscores the detrimental impact of antibiotics as well as other medications, particularly laxatives, on the intestinal microbiota and suggests that co-colonization with key bacterial taxa may prevent C. difficile overgrowth or the transition from asymptomatic C. difficile colonization to CDI.

Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease

PubMed Central

Rao, Krishna; Higgins, Peter D. R.

2016-01-01

Clostridium difficile infection (CDI) is a major source of morbidity and mortality for the US healthcare system, and frequently complicates the course of inflammatory bowel disease (IBD). Patients with IBD are more likely to be colonized with C. difficile and develop active infection than the general population. They are also more likely to have severe CDI and develop subsequent complications such as IBD flare, colectomy, or death. Even after successful initial treatment and recovery, recurrent CDI is common. Management of CDI in IBD is fraught with diagnostic and therapeutic challenges, since the clinical presentations of CDI and IBD flare have considerable overlap. Fecal microbiota transplantation can be successful in curing recurrent CDI when other treatments have failed, but may also trigger IBD flare and this warrants caution. New, experimental treatments including vaccines, monoclonal antibodies, and non-toxigenic strains of C. difficile offer promise but are not yet available for clinicians. A better understanding of the complex relationship between the gut microbiota, CDI, and IBD is needed. PMID:27120571

Probiotics in Clostridium difficile infection: reviewing the need for a multistrain probiotic.

PubMed

Hell, M; Bernhofer, C; Stalzer, P; Kern, J M; Claassen, E

2013-03-01

In the past two years an enormous amount of molecular, genetic, metabolomic and mechanistic data on the host-bacterium interaction, a healthy gut microbiota and a possible role for probiotics in Clostridium difficile infection (CDI) has been accumulated. Also, new hypervirulent strains of C. difficile have emerged. Yet, clinical trials in CDI have been less promising than in antibiotic associated diarrhoea in general, with more meta-analysis than primary papers on CDI-clinical-trials. The fact that C. difficile is a spore former, producing at least three different toxins has not yet been incorporated in the rational design of probiotics for (recurrent) CDI. Here we postulate that the plethora of effects of C. difficile and the vast amount of data on the role of commensal gut residents and probiotics point towards a multistrain mixture of probiotics to reduce CDI, but also to limit (nosocomial) transmission and/or endogenous reinfection. On the basis of a retrospective chart review of a series of ten CDI patients where recurrence was expected, all patients on adjunctive probiotic therapy with multistrain cocktail (Ecologic®AAD/OMNiBiOTiC® 10) showed complete clinical resolution. This result, and recent success in faecal transplants in CDI treatment, are supportive for the rational design of multistrain probiotics for CDI.

Determining the cause of recurrent Clostridium difficile infection using whole genome sequencing.

PubMed

Sim, James Heng Chiak; Truong, Cynthia; Minot, Samuel S; Greenfield, Nick; Budvytiene, Indre; Lohith, Akshar; Anikst, Victoria; Pourmand, Nader; Banaei, Niaz

2017-01-01

Understanding the contribution of relapse and reinfection to recurrent Clostridium difficile infection (CDI) has implications for therapy and infection prevention, respectively. We used whole genome sequencing to determine the relation of C. difficile strains isolated from patients with recurrent CDI at an academic medical center in the United States. Thirty-five toxigenic C. difficile isolates from 16 patients with 19 recurrent CDI episodes with median time of 53.5days (range, 13-362) between episodes were whole genome sequenced on the Illumina MiSeq platform. In 84% (16) of recurrences, the cause of recurrence was relapse with prior strain of C. difficile. In 16% (3) of recurrent episodes, reinfection with a new strain of C. difficile was the cause. In conclusion, the majority of CDI recurrences at our institution were due to infection with the same strain rather than infection with a new strain. Copyright © 2016 Elsevier Inc. All rights reserved.

The Epidemiology and Clinical Features of Clostridium difficile Infection in Liver Transplant Recipients.

PubMed

Sullivan, Timothy; Weinberg, Alan; Rana, Meenakshi; Patel, Gopi; Huprikar, Shirish

2016-09-01

Clostridium difficile infection (CDI) is common after liver transplantation (LT); however, few studies have examined the risk factors, clinical manifestations, and outcomes of CDI in this population. A retrospective study of adults who underwent LT between January 1, 2011, and April 4, 2013, at The Mount Sinai Hospital was conducted. Potential risk factors were evaluated via univariate and multivariable analysis to determine predictors of CDI in this population. The clinical manifestations of CDI and patient outcomes were also reviewed. Clostridium difficile infection occurred in 27 (14%) of 192 patients after LT. In multivariable analysis, CDI was associated with having a model for end-stage liver disease score of 20 or greater (hazards ratio, 2.90; 95% confidence interval, 1.29-6.52; P = 0.010), and receiving a LT from a living donor (hazards ratio, 3.77; 95% confidence interval, 1.47-9.67; P = 0.006). Forty-one percent of CDI cases occurred within 1 week of LT. Seven percent of patients with CDI had a serum white blood cell count greater than 12 000 cells per μL, and 26% had a temperature greater than 38.0°C. After treatment 6 (22%) patients developed CDI relapse, and all were successfully treated. No patients died of CDI after a mean follow-up time of 1.8 years; however, overall survival was significantly lower among those with CDI (78% vs 92%; P = 0.033). Clostridium difficile infection after LT was associated with higher model for end-stage liver disease scores and receiving a LT from a living donor. Clostridium difficile infection often occurred soon after LT and was infrequently associated with leukocytosis or fever. Clostridium difficile infection in LT recipients was associated with lower overall survival.

Impact of recurrent Clostridium difficile infection: hospitalization and patient quality of life.

PubMed

Wilcox, Mark H; Ahir, Harblas; Coia, John E; Dodgson, Andrew; Hopkins, Susan; Llewelyn, Martin J; Settle, Chris; Mclain-Smith, Susan; Marcella, Stephen W

2017-09-01

Data quantifying outcomes of recurrent Clostridium difficile infection (rCDI) are lacking. We sought to determine the UK hospital resource use and health-related quality of life (HRQoL) associated with rCDI hospitalizations. A non-interventional study in six UK acute hospitals collected retrospective clinical and resource use data from medical records of 64 adults hospitalized for rCDI and 64 matched inpatient controls with a first episode only (f)CDI. Patients were observed from the index event (date rCDI/fCDI confirmed) for 28 days (or death, if sooner); UK-specific reference costs were applied. HRQoL was assessed prospectively in a separate cohort of 30 patients hospitalized with CDI, who completed the EQ-5D-3L questionnaire during their illness. The median total management cost (post-index) was £7539 and £6294 for rCDI and fCDI, respectively (cost difference, P = 0.075); median length of stay was 21 days and 15.5 days, respectively (P = 0.269). The median cost difference between matched rCDI and fCDI cases was £689 (IQR=£1873-£3954). Subgroup analysis demonstrated the highest median costs (£8542/patient) in severe rCDI cases. CDI management costs were driven primarily by hospital length of stay, which accounted for >85% of costs in both groups. Mean EQ-5D index values were 46% lower in CDI patients compared with UK population values (0.42 and 0.78, respectively); EQ visual analogue scale scores were 38% lower (47.82 and 77.3, respectively). CDI has considerable impact on patients and healthcare resources. This multicentre study provides a contemporaneous estimate of the real-world UK costs associated with rCDI management, which are substantial and comparable to fCDI costs. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical manifestations of Clostridium difficile infection in a medical center in Taiwan.

PubMed

Lai, Chih-Cheng; Lin, Sheng-Hsiang; Tan, Che-Kim; Liao, Chun-Hsing; Huang, Yu-Tsung; Hsueh, Po-Ren

2014-12-01

To investigate the clinical characteristics of Clostridium difficile infection (CDI) at a medical center in Taiwan. Patients with CDI were identified from medical records at the National Taiwan University Hospital (Taipei, Taiwan). The following information was gathered and analyzed to better understand the clinical manifestations of CDI: age; sex; underlying immunocompromised conditions; laboratory data; in-hospital mortality; and previous use of drugs such as antimicrobial agents, steroids, and antipeptic ulcer agents. During the years 2000-2010, 122 patients were identified as having CDI. This included 92 patients with nontoxigenic CDI (i.e., positive stool culture for C. difficile but negative results for toxins A and B) and 30 patients with toxigenic CDI (i.e., positive stool culture cultures for C. difficile and positive results for toxins A and B). Of the 122 patients, 48 (39%) patients were older than 65 years and most patients acquired the CDI while in the hospital. Active cancer was the most common reason for hospitalization, followed by diabetes mellitus, and end-stage renal disease. More than 90% of the patients had received antibiotics before acquiring CDI. The results of fecal leukocyte examinations were positive in 33 (27%) patients. The overall in-hospital mortality rate was 26.2%. There were no significant differences between patients with nontoxigenic CDI and patients with toxigenic CDI. Clostridium difficile infection can develop in healthcare facilities and in community settings, especially in immunocompromised patients. Copyright © 2013. Published by Elsevier B.V.

Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection

PubMed Central

Bobr, Aleh; Kuskowski, Michael A.; Johnston, Brian D.; Sadowsky, Michael J.; Khoruts, Alexander

2016-01-01

Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficile spores persist in the hospital environment and cause infection, little is known about their potential presence or importance in the household environment. Households of R-CDI subjects in the peri-FMT period and of geographically matched and age-matched controls were analyzed for the presence of C. difficile. Household environmental surfaces and fecal samples from humans and pets in the household were examined. Households of post-FMT subjects were also examined (environmental surfaces only). Participants were surveyed regarding their personal history and household cleaning habits. Species identity and molecular characteristics of presumptive C. difficile isolates from environmental and fecal samples were determined by using the Pro kit (Remel, USA), Gram staining, PCR, toxinotyping, tcdC gene sequencing, and pulsed-field gel electrophoresis (PFGE). Environmental cultures detected C. difficile on ≥1 surface in 8/8 (100%) peri-FMT households, versus 3/8 (38%) post-FMT households and 3/8 (38%) control households (P = 0.025). The most common C. difficile-positive sites were the vacuum (11/27; 41%), toilet (8/30; 27%), and bathroom sink (5/29; 17%). C. difficile was detected in 3/36 (8%) fecal samples (two R-CDI subjects and one household member). Nine (90%) of 10 households with multiple C. difficile-positive samples had a single genotype present each. In conclusion, C. difficile was found in the household environment of R-CDI patients, but whether it was found as a cause or consequence of R-CDI is unknown. If household contamination leads to R-CDI, effective decontamination may be protective. PMID:26921425

Evaluation of Correlation between Pretest Probability for Clostridium difficile Infection and Clostridium difficile Enzyme Immunoassay Results.

PubMed

Kwon, Jennie H; Reske, Kimberly A; Hink, Tiffany; Burnham, C A; Dubberke, Erik R

2017-02-01

The objective of this study was to evaluate the clinical characteristics and outcomes of hospitalized patients tested for Clostridium difficile and determine the correlation between pretest probability for C. difficile infection (CDI) and assay results. Patients with testing ordered for C. difficile were enrolled and assigned a high, medium, or low pretest probability of CDI based on clinical evaluation, laboratory, and imaging results. Stool was tested for C. difficile by toxin enzyme immunoassay (EIA) and toxigenic culture (TC). Chi-square analyses and the log rank test were utilized. Among the 111 patients enrolled, stool samples from nine were TC positive and four were EIA positive. Sixty-one (55%) patients had clinically significant diarrhea, 19 (17%) patients did not, and clinically significant diarrhea could not be determined for 31 (28%) patients. Seventy-two (65%) patients were assessed as having a low pretest probability of having CDI, 34 (31%) as having a medium probability, and 5 (5%) as having a high probability. None of the patients with low pretest probabilities had a positive EIA, but four were TC positive. None of the seven patients with a positive TC but a negative index EIA developed CDI within 30 days after the index test or died within 90 days after the index toxin EIA date. Pretest probability for CDI should be considered prior to ordering C. difficile testing and must be taken into account when interpreting test results. CDI is a clinical diagnosis supported by laboratory data, and the detection of toxigenic C. difficile in stool does not necessarily confirm the diagnosis of CDI. Copyright © 2017 American Society for Microbiology.

Antimicrobial Resistance and Reduced Susceptibility in Clostridium difficile: Potential Consequences for Induction, Treatment, and Recurrence of C. difficile Infection

PubMed Central

Baines, Simon D.; Wilcox, Mark H.

2015-01-01

Clostridium difficile infection (CDI) remains a substantial burden on healthcare systems and is likely to remain so given our reliance on antimicrobial therapies to treat bacterial infections, especially in an aging population in whom multiple co-morbidities are common. Antimicrobial agents are a key component in the aetiology of CDI, both in the establishment of the infection and also in its treatment. The purpose of this review is to summarise the role of antimicrobial agents in primary and recurrent CDI; assessing why certain antimicrobial classes may predispose to the induction of CDI according to a balance between antimicrobial activity against the gut microflora and C. difficile. Considering these aspects of CDI is important in both the prevention of the infection and in the development of new antimicrobial treatments. PMID:27025625

Economic Burden of Clostridium difficile Infection in European Countries.

PubMed

Reigadas Ramírez, Elena; Bouza, Emilio Santiago

2018-01-01

Clostridium difficile infection (CDI) remains a considerable challenge to health care systems worldwide. Although CDI represents a significant burden on healthcare systems in Europe, few studies have attempted to estimate the consumption of resources associated with CDI in Europe. The reported extra costs attributable to CDI vary widely according to the definitions, design, and methodologies used, making comparisons difficult to perform. In this chapter, the economic burden of healthcare facility-associated CDI in Europe will be assessed, as will other less explored areas such as the economic burden of recurrent CDI, community-acquired CDI, pediatric CDI, and CDI in outbreaks.

Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

PubMed Central

Zanella Terrier, Marie Céline; Simonet, Martine Louis; Bichard, Philippe; Frossard, Jean Louis

2014-01-01

Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability. PMID:24966611

A review of the economics of treating Clostridium difficile infection.

PubMed

Mergenhagen, Kari A; Wojciechowski, Amy L; Paladino, Joseph A

2014-07-01

Clostridium difficile infection (CDI) is a costly result of antibiotic use, responsible for an estimated 14,000 deaths annually in the USA according to the Centers for Disease Control and Prevention. Annual costs attributable to CDI are in excess of $US 1 billion. This review summarizes appropriate utilization of prevention and treatment methods for CDI that have the potential to reduce the economic and humanistic costs of the disease. Some cost-effective strategies to prevent CDI include screening and isolation of hospital admissions based on C. difficile carriage to reduce transmission in the inpatient setting, and probiotics, which are potentially efficacious in preventing CDI in the appropriate patient population. The most extensively studied agents for treatment of CDI are metronidazole, vancomycin, and fidaxomicin. Most economic comparisons between metronidazole and vancomycin favor vancomycin, especially with the emergence of metronidazole-resistant C. difficile strains. Metronidazole can only be recommended for mild disease. Moderate to severe CDI should be treated with vancomycin, preferably the compounded oral solution, which provides the most cost-effective therapeutic option. Fidaxomicin offers a clinically effective and potentially cost-effective alternative for treating moderate CDI in patients who do not have the NAP1/BI/027 strain of C. difficile. Probiotics and fecal microbiota transplant have variable efficacy and the US FDA does not currently regulate the content; the potential economic advantages of these treatment modalities are currently unknown.

Community-acquired Clostridium difficile infection in children: A retrospective study.

PubMed

Borali, Elena; Ortisi, Giuseppe; Moretti, Chiara; Stacul, Elisabetta Francesca; Lipreri, Rita; Gesu, Giovanni Pietro; De Giacomo, Costantino

2015-10-01

Community acquired-Clostridium difficile infection (CDI) has increased also in children in the last years. To determine the incidence of community-acquired CDI and to understand whether Clostridium difficile could be considered a symptom-triggering pathogen in infants. A five-year retrospective analysis (January 2007-December 2011) of faecal specimens from 124 children hospitalized in the Niguarda Ca' Granda Hospital for prolonged or muco-haemorrhagic diarrhoea was carried out. Stool samples were evaluated for common infective causes of diarrhoea and for Clostridium difficile toxins. Patients with and without CDI were compared for clinical characteristics and known risk factors for infection. Twenty-two children with CDI were identified in 5 years. An increased incidence of community-acquired CDI was observed, ranging from 0.75 per 1000 hospitalizations in 2007 to 9.8 per 1000 hospitalizations in 2011. Antimicrobial treatment was successful in all 19 children in whom it was administered; 8/22 CDI-positive children were younger than 2 years. No statistically significant differences in clinical presentation were observed between patients with and without CDI, nor in patients with and without risk factors for CDI. Our study shows that Clostridium difficile infection is increasing and suggests a possible pathogenic role in the first 2 years of life. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile Infection: Associations with Chemotherapy, Radiation Therapy, and Targeting Therapy Treatments.

PubMed

Peretz, Avi; Shlomo, Izhar Ben; Nitzan, Orna; Bonavina, Luigi; Schaffer, Pmela M; Schaffer, Moshe

2016-01-01

Although mucositis, diarrhea, and constipation as well as immunosuppression are well recognized side-effects of cancer treatment, the underlying mechanisms including changes in the composition of gut microbiota and Clostridium difficile infection have not yet been thoroughly reviewed. We herein set out to review the literature regarding the relations between cancer chemotherapy, radiation treatment, and Clostridium difficile-associated colitis. Review of the English language literature published from 2008 to 2015 on the association between cancer chemotherapy, radiation treatment, and C. difficile-associated colitis. Certain chemotherapeutic combinations, mainly those containing paclitaxel, are more likely to be followed by C. difficile infection (CDI), while some tumor types are more likely to be complicated by CDI following chemotherapy. CDI following irradiation occurs mostly in patients who were treated for cancer in the head and neck area. Risk factors found were proton pump inhibitors, antibiotics, cytostatic agents, and tube feeding. The drug of choice for an initial episode of mild-to-moderate CDI is metronidazole, whereas vancomycin is reserved for an initial episode of severe CDI. Fidaxomycin is another option for treatment of severe CDI, with fewer recurrences. The influence of CDI on the treatment of oncological patients is not fully acknowledged. Infection with C. difficile is more frequent in those patients treated by antibiotics simultaneously with chemotherapy. Aggressive supportive care with intravenous hydration, antibiotics, and close surgical monitoring for selective intervention can significantly decrease the morbidity and life-threatening complications associated with this infection.

Consequences of Clostridium difficile infection: understanding the healthcare burden.

PubMed

Bouza, E

2012-12-01

Clostridium difficile is the leading cause of infectious nosocomial diarrhoea in developed countries, with a measured incidence of approximately five episodes per 10,000 days of hospital stay in Europe. Accurate diagnosis of C. difficile infection (CDI) is a prerequisite for obtaining reliable epidemiological data, but in many European countries diagnosis is probably suboptimal. A significant percentage of CDI cases are missed because clinicians often fail to request tests for C. difficile toxins in cases of unexplained diarrhoea. In addition, some laboratories continue to use tests of low sensitivity or apply them inappropriately. In one study in Spain, failure to request CDI testing in more than two-thirds of patients with unexplained diarrhoea led to significant underdiagnosis of cases. A recent pan-European survey revealed huge discrepancies in the rate of CDI testing across Europe, which suggests that epidemiological reports underestimate the true incidence of CDI in many parts of Europe. This is important because, as this review of the clinical and economic burden of CDI illustrates, infection with C. difficile imposes a significant burden not only on patients, owing to increased morbidity and mortality, but also on healthcare systems and society in general. On the basis of current incidence rates, annual costs for management of CDI amount to approximately $800 million in the USA and €3000 million in Europe. Moreover, estimates suggest that costs associated with recurrent CDI can exceed those of primary CDI. Measures to more effectively prevent CDI and reduce CDI recurrence rates may help to reduce this burden. © 2012 The Author Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

78 FR 65322 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... days of this notice. Proposed Project Clostridium difficile Infection (CDI) Surveillance (0920-0892... rate and severity of Clostridium difficile infection (CDI) indicate a clear need to conduct longitudinal assessments to continue to monitor changes in CDI epidemiology, including changes in risk factors...

75 FR 53310 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

.... Proposed Project Clostridium difficile Infection (CDI) Surveillance--New--National Center for Emerging and... Brief Description Steady increases in the rate and severity of Clostridium difficile infection (CDI... description of the molecular characteristics of C. difficile strains and the epidemiology of this infection...

Interventions to Reduce the Incidence of Hospital-Onset Clostridium difficile Infection: An Agent-Based Modeling Approach to Evaluate Clinical Effectiveness in Adult Acute Care Hospitals.

PubMed

Barker, Anna K; Alagoz, Oguzhan; Safdar, Nasia

2018-04-03

Despite intensified efforts to reduce hospital-onset Clostridium difficile infection (HO-CDI), its clinical and economic impacts continue to worsen. Many institutions have adopted bundled interventions that vary considerably in composition, strength of evidence, and effectiveness. Considerable gaps remain in our knowledge of intervention effectiveness and disease transmission, which hinders HO-CDI prevention. We developed an agent-based model of C. difficile transmission in a 200-bed adult hospital using studies from the literature, supplemented with primary data collection. The model includes an environmental component and 4 distinct agent types: patients, visitors, nurses, and physicians. We used the model to evaluate the comparative clinical effectiveness of 9 single interventions and 8 multiple-intervention bundles at reducing HO-CDI and asymptomatic C. difficile colonization. Daily cleaning with sporicidal disinfectant and C. difficile screening at admission were the most effective single-intervention strategies, reducing HO-CDI by 68.9% and 35.7%, respectively (both P < .001). Combining these interventions into a 2-intervention bundle reduced HO-CDI by 82.3% and asymptomatic hospital-onset colonization by 90.6% (both, P < .001). Adding patient hand hygiene to healthcare worker hand hygiene reduced HO-CDI rates an additional 7.9%. Visitor hand hygiene and contact precaution interventions did not reduce HO-CDI, compared with baseline. Excluding those strategies, healthcare worker contact precautions were the least effective intervention at reducing hospital-onset colonization and infection. Identifying and managing the vast hospital reservoir of asymptomatic C. difficile by screening and daily cleaning with sporicidal disinfectant are high-yield strategies. These findings provide much-needed data regarding which interventions to prioritize for optimal C. difficile control.

Clostridium difficile colonization and disease in patients undergoing hematopoietic stem cell transplantation.

PubMed

Bruminhent, Jackrapong; Wang, Zi-Xuan; Hu, Carol; Wagner, John; Sunday, Richard; Bobik, Brent; Hegarty, Sarah; Keith, Scott; Alpdogan, Seyfettin; Carabasi, Matthew; Filicko-O'Hara, Joanne; Flomenberg, Neal; Kasner, Margaret; Outschoorn, Ubaldo Martinez; Weiss, Mark; Flomenberg, Phyllis

2014-09-01

There was an increase in the Clostridium difficile infection (CDI) rate in our bone marrow transplantation unit. To evaluate the role of unit-based transmission, C. difficile screening was performed on adult patients admitted for hematopoietic stem cell transplantation (HSCT) over a 2-year period, and C. difficile isolates were typed. C. difficile testing was performed using a 2-step C. difficile glutamate dehydrogenase antigen plus toxin A/B enzyme immunoassay (EIA) and cytotoxin assay (or molecular toxin assay). Multilocus sequence typing (MLST) was performed on toxin-positive whole stool samples. A retrospective chart review was performed on all patients with a positive toxin assay. Sixteen of 150 patients (10.7%) had toxigenic C. difficile colonization (CDC) on admission. The overall incidence of CDI within 100 days after HSCT was 24.7% (37 of 150). The median time to diagnosis of CDI was 3.5 days after HSCT. In an adjusted logistic regression model, CDC on admission was a significant risk factor for CDI (odds ratio, 68.5; 95% confidence interval, 11.4 to 416.2). MLST on 22 unit patient toxin-positive stool specimens revealed 15 distinct strain types. Further analysis identified at least 1 potential cross-transmission event; some events may have been missed because of incomplete typing from other specimens. Despite aggressive infection control interventions, there was no decline in the number of CDI cases during the study period. These data suggest that prior CDC plays a major role in CDI rates in this high-risk patient population. It remains unclear if CDI was cross-transmitted in the unit. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

WSES guidelines for management of Clostridium difficile infection in surgical patients.

PubMed

Sartelli, Massimo; Malangoni, Mark A; Abu-Zidan, Fikri M; Griffiths, Ewen A; Di Bella, Stefano; McFarland, Lynne V; Eltringham, Ian; Shelat, Vishal G; Velmahos, George C; Kelly, Ciarán P; Khanna, Sahil; Abdelsattar, Zaid M; Alrahmani, Layan; Ansaloni, Luca; Augustin, Goran; Bala, Miklosh; Barbut, Frédéric; Ben-Ishay, Offir; Bhangu, Aneel; Biffl, Walter L; Brecher, Stephen M; Camacho-Ortiz, Adrián; Caínzos, Miguel A; Canterbury, Laura A; Catena, Fausto; Chan, Shirley; Cherry-Bukowiec, Jill R; Clanton, Jesse; Coccolini, Federico; Cocuz, Maria Elena; Coimbra, Raul; Cook, Charles H; Cui, Yunfeng; Czepiel, Jacek; Das, Koray; Demetrashvili, Zaza; Di Carlo, Isidoro; Di Saverio, Salomone; Dumitru, Irina Magdalena; Eckert, Catherine; Eckmann, Christian; Eiland, Edward H; Enani, Mushira Abdulaziz; Faro, Mario; Ferrada, Paula; Forrester, Joseph Derek; Fraga, Gustavo P; Frossard, Jean Louis; Galeiras, Rita; Ghnnam, Wagih; Gomes, Carlos Augusto; Gorrepati, Venkata; Ahmed, Mohamed Hassan; Herzog, Torsten; Humphrey, Felicia; Kim, Jae Il; Isik, Arda; Ivatury, Rao; Lee, Yeong Yeh; Juang, Paul; Furuya-Kanamori, Luis; Karamarkovic, Aleksandar; Kim, Peter K; Kluger, Yoram; Ko, Wen Chien; LaBarbera, Francis D; Lee, Jae Gil; Leppaniemi, Ari; Lohsiriwat, Varut; Marwah, Sanjay; Mazuski, John E; Metan, Gokhan; Moore, Ernest E; Moore, Frederick Alan; Nord, Carl Erik; Ordoñez, Carlos A; Júnior, Gerson Alves Pereira; Petrosillo, Nicola; Portela, Francisco; Puri, Basant K; Ray, Arnab; Raza, Mansoor; Rems, Miran; Sakakushev, Boris E; Sganga, Gabriele; Spigaglia, Patrizia; Stewart, David B; Tattevin, Pierre; Timsit, Jean Francois; To, Kathleen B; Tranà, Cristian; Uhl, Waldemar; Urbánek, Libor; van Goor, Harry; Vassallo, Angela; Zahar, Jean Ralph; Caproli, Emanuele; Viale, Pierluigi

2015-01-01

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

How to: Surveillance of Clostridium difficile infections.

PubMed

Krutova, M; Kinross, P; Barbut, F; Hajdu, A; Wilcox, M H; Kuijper, E J

2018-05-01

The increasing incidence of Clostridium difficile infections (CDI) in healthcare settings in Europe since 2003 has affected both patients and healthcare systems. The implementation of effective CDI surveillance is key to enable monitoring of the occurrence and spread of C. difficile in healthcare and the timely detection of outbreaks. The aim of this review is to provide a summary of key components of effective CDI surveillance and to provide some practical recommendations. We also summarize the recent and current national CDI surveillance activities, to illustrate strengths and weaknesses of CDI surveillance in Europe. For the definition of key components of CDI surveillance, we consulted the current European Society of Clinical Microbiology and Infectious Diseases (ESCMID) CDI-related guidance documents and the European Centre for Disease Prevention and Control (ECDC) protocol for CDI surveillance in acute care hospitals. To summarize the recent and current national CDI surveillance activities, we discussed international multicentre CDI surveillance studies performed in 2005-13. In 2017, we also performed a new survey of existing CDI surveillance systems in 33 European countries. Key components for CDI surveillance are appropriate case definitions of CDI, standardized CDI diagnostics, agreement on CDI case origin definition, and the presentation of CDI rates with well-defined numerators and denominators. Incorporation of microbiological data is required to provide information on prevailing PCR ribotypes and antimicrobial susceptibility to first-line CDI treatment drugs. In 2017, 20 European countries had a national CDI surveillance system and 21 countries participated in ECDC-coordinated CDI surveillance. Since 2014, the number of centres with capacity for C. difficile typing has increased to 35 reference or central laboratories in 26 European countries. Incidence rates of CDI, obtained from a standardized CDI surveillance system, can be used as an important quality indicator of healthcare at hospital as well as country level. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Epidemiology, risk factors, and outcome of Clostridium difficile infection in heart and heart-lung transplant recipients.

PubMed

Bruminhent, Jackrapong; Cawcutt, Kelly A; Thongprayoon, Charat; Petterson, Tanya M; Kremers, Walter K; Razonable, Raymund R

2017-06-01

Clostridium difficile is a major cause of diarrhea in thoracic organ transplant recipients. We investigated the epidemiology, risk factors, and outcome of Clostridium difficile infection (CDI) in heart and heart-lung transplant (HT) recipients. This is a retrospective study from 2004 to 2013. CDI was defined by diarrhea and a positive toxigenic C. difficile in stool measured by toxin enzyme immunoassay (2004-2006) or polymerase chain reaction (2007-2013). Cox proportional hazards regression was used to model the association of risk factors with time to CDI and survival with CDI following transplantation. There were 254 HT recipients, with a median age of 53 years (IQR, 45-60); 34% were female. During the median follow-up of 3.1 years (IQR, 1.3-6.1), 22 (8.7%) patients developed CDI. In multivariable analysis, risk factors for CDI were combined heart-lung transplant (HR 4.70; 95% CI, 1.30-17.01 [P=.02]) and retransplantation (HR 7.19; 95% CI, 1.61-32.12 [P=.01]). Acute cellular rejection was associated with a lower risk of CDI (HR 0.34; 95% CI, 0.11-0.94 [P=.04]). CDI was found to be an independent risk factor for mortality (HR 7.66; 95% CI, 3.41-17.21 [P<.0001]). Clostridium difficile infection after HT is more common among patients with combined heart-lung and those undergoing retransplantation. CDI was associated with a higher risk of mortality in HT recipients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Burden of Clostridium difficile on the healthcare system.

PubMed

Dubberke, Erik R; Olsen, Margaret A

2012-08-01

There are few high-quality studies of the costs of Clostridium difficile infection (CDI), and the majority of studies focus on the costs of CDI in acute-care facilities. Analysis of the best available data, from 2008, indicates that CDI may have resulted in $4.8 billion in excess costs in US acute-care facilities. Other areas of CDI-attributable excess costs that need to be investigated are costs of increased discharges to long-term care facilities, of CDI with onset in long-term care facilities, of recurrent CDI, and of additional adverse events caused by CDI.

Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection

PubMed Central

Avila, Meera B.; Avila, Nathaniel P.; Dupont, Andrew W.

2016-01-01

Clostridium difficile infection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies. PMID:26918176

Prevalence of Clostridium difficile infection in hospitalized patients with diarrhoea: Results of a Polish multicenter, prospective, biannual point-prevalence study.

PubMed

Pituch, Hanna; Obuch-Woszczatyński, Piotr; Lachowicz, Dominika; Kuthan, Robert; Dzierżanowska-Fangrat, Katarzyna; Mikucka, Agnieszka; Jermakow, Katarzyna; Pituch-Zdanowska, Aleksandra; Davies, Kerrie

2018-04-13

We aimed to measure the underdiagnosis of Clostridium difficile infection across Poland and the distribution of PCR-ribotypes of C. difficile. Twenty seven Polish healthcare facilities (HCFs) participated in this prospective study. Each HCF systematically sent all diarrhoeal stools received from inpatients at their laboratories on two days (one in January 2013 and one in July 2013), independently of CDI test request, to the National Coordinating Laboratory (NCL) for standardized testing of CDI. Positive samples (using two-stage algorithm), had CDI, confirmed by qPCR and toxigenic culture. C. difficile isolates were characterized by PCR-ribotyping. Hospitals were questioned about their methods and testing policy for CDI during the study period: September 2011 to August 2013. During the study period, participating hospitals reported a mean of 33.2 tests for CDI per 10 000 patient-days and a mean of 8.4 cases of CDI per 10 000 patient-days. The overall prevalence of positive CDI patients at NCL was 16.5%. Due to absence of clinical suspicion, 19.1% of these patients were not diagnosed by the local diagnostic laboratory. We identified 23 different PCR-ribotypes among 87C. difficile strains isolated from patients. PCR-ribotype 027 (48%) was the most prevalent. The incidence of CDI in Poland in study period was very high. It should be noted however, that there is a lack of clinical suspicion and underestimation of the need to perform diagnostic tests for CDI in hospitalized patients. This will have an impact on the reported epidemiological status of CDI in Poland. Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Effectiveness of deep cleaning followed by hydrogen peroxide decontamination during high Clostridium difficile infection incidence.

PubMed

Best, E L; Parnell, P; Thirkell, G; Verity, P; Copland, M; Else, P; Denton, M; Hobson, R P; Wilcox, M H

2014-05-01

Clostridium difficile infection (CDI) remains an infection control challenge, especially when environmental spore contamination and suboptimal cleaning may increase transmission risk. To substantiate the long-term effectiveness throughout a stroke rehabilitation unit (SRU) of deep cleaning and hydrogen peroxide decontamination (HPD), following a high incidence of CDI. Extensive environmental sampling (342 sites on each occasion) for C. difficile using sponge wipes was performed: before and after deep cleaning with detergent/chlorine agent; immediately following HPD; and on two further occasions, 19 days and 20 weeks following HPD. C. difficile isolates underwent polymerase chain reaction ribotyping and multi-locus variable repeat analysis (MLVA). C. difficile was recovered from 10.8%, 6.1%, 0.9%, 0% and 3.5% of sites at baseline, following deep cleaning, immediately after HPD, and 19 days and 20 weeks after HPD, respectively. C. difficile ribotypes recovered after deep cleaning matched those from CDI cases in the SRU during the previous 10 months. Similarly, 10/12 of the positive sites identified at 20 weeks post-HPD harboured the same C. difficile ribotype (002) and MLVA pattern as the isolate from the first post-HPD CDI case. CDI incidence [number of cases on SRU per 10 months (January-October 2011)] declined from 20 before to seven after the intervention. HPD, after deep cleaning with a detergent/chlorine agent, was highly effective for removing environmental C. difficile contamination. Long-term follow-up demonstrated that a CDI symptomatic patient can rapidly recontaminate the immediate environment. Determining a role for HPD should include long-term cost-effectiveness evaluations. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Household Transmission of Clostridium difficile to Family Members and Domestic Pets.

PubMed

Loo, Vivian G; Brassard, Paul; Miller, Mark A

2016-11-01

OBJECTIVE To determine the risk of Clostridium difficile transmission from index cases with C. difficile infection (CDI) to their household contacts and domestic pets. DESIGN A prospective study from April 2011 to June 2013. SETTING Patients with CDI from Canadian tertiary care centers. PARTICIPANTS Patients with CDI, their household human contacts, and pets. METHODS Epidemiologic information and stool or rectal swabs were collected from participants at enrollment and monthly for up to 4 months. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates. Probable transmission was defined as the conversion of a C. difficile culture-negative contact to C. difficile culture-positive contact with a PFGE pattern indistinguishable or closely related to the index case. Possible transmission was defined as a contact with a positive C. difficile culture at baseline with a strain indistinguishable or closely related to the index case. RESULTS A total of 51 patients with CDI participated in this study; 67 human contacts and 15 pet contacts were included. Overall, 9 human contacts (13.4%) were C. difficile culture positive; 1 contact (1.5%) developed CDI; and 8 contacts were asymptomatic. Of 67 human contacts, probable transmission occurred in 1 human contact (1.5%) and possible transmission occurred in 5 human contacts (7.5%). Of 15 pet contacts, probable transmission occurred in 3 (20%) and possible transmission occurred in 1 (6.7%). CONCLUSIONS There was a high proportion of C. difficile culture positivity at 13.4% among human contacts and asymptomatic carriage of domestic pets reached 26.7%. These results suggest that household transmission of C. difficile may be a source of community-associated cases. Infect Control Hosp Epidemiol 2016;1-7.

Burden of Clostridium difficile Infections in French Hospitals in 2014 From the National Health Insurance Perspective.

PubMed

Leblanc, Soline; Blein, Cécile; Andremont, Antoine; Bandinelli, Pierre-Alain; Galvain, Thibaut

2017-08-01

OBJECTIVE To describe the hospital stays of patients with Clostridium difficile infection (CDI) and to measure the hospitalization costs of CDI (as primary and secondary diagnoses) from the French national health insurance perspective DESIGN Burden of illness study SETTING All acute-care hospitals in France METHODS Data were extracted from the French national hospitalization database (PMSI) for patients covered by the national health insurance scheme in 2014. Hospitalizations were selected using the International Classification of Diseases, 10 th revision (ICD-10) code for CDI. Hospital stays with CDI as the primary diagnosis or the secondary diagnosis (comorbidity) were studied for the following parameters: patient sociodemographic characteristics, mortality, length of stay (LOS), and related costs. A retrospective case-control analysis was performed on stays with CDI as the secondary diagnosis to assess the impact of CDI on the LOS and costs. RESULTS Overall, 5,834 hospital stays with CDI as the primary diagnosis were included in this study. The total national insurance costs were €30.7 million (US $33,677,439), and the mean cost per hospital stay was €5,267±€3,645 (US $5,777±$3,998). In total, 10,265 stays were reported with CDI as the secondary diagnosis. The total national insurance additional costs attributable to CDI were estimated to be €85 million (US $93,243,725), and the mean additional cost attributable to CDI per hospital stay was €8,295±€17,163, median, €4,797 (US $9,099±$8,827; median, $5,262). CONCLUSION CDI has a high clinical and economic burden in the hospital, and it represents a major cost for national health insurance. When detected as a comorbidity, CDI was significantly associated with increased LOS and economic burden. Preventive approaches should be implemented to avoid CDIs. Infect Control Hosp Epidemiol 2017;38:906-911.

A case of multiple recurrence of Clostridium difficile infection with severe hematochezia in an immunocompromised host.

PubMed

Zhang, Xuewu; Chen, Yunbo; Gu, Silan; Zheng, Beiwen; Lv, Tao; Lou, Yinjun; Jin, Jie

2016-12-01

Clostridium difficile infection (CDI) is increasing in incidence and severity. Clinically, diarrhea frequently occurs, but severe hematochezia is rarely seen with CDI. We describe here a hematopoietic stem cell transplantation (HSCT) recipient who experienced life-threatening gastrointestinal bleeding due to severe CDI. Subsequent stool surveillance and molecular typing observed the patient who had two episodes of recurrence with a new strain of C. difficile distinct from the initial infection. We analyze C. difficile strains obtained from the patient, and also discuss the diagnosis and treatment of this case. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigation of a cluster of Clostridium difficile infections in a pediatric oncology setting.

PubMed

Dantes, Raymund; Epson, Erin E; Dominguez, Samuel R; Dolan, Susan; Wang, Frank; Hurst, Amanda; Parker, Sarah K; Johnston, Helen; West, Kelly; Anderson, Lydia; Rasheed, James K; Moulton-Meissner, Heather; Noble-Wang, Judith; Limbago, Brandi; Dowell, Elaine; Hilden, Joanne M; Guh, Alice; Pollack, Lori A; Gould, Carolyn V

2016-02-01

We investigated an increase in Clostridium difficile infection (CDI) among pediatric oncology patients. CDI cases were defined as first C difficile positive stool tests between December 1, 2010, and September 6, 2012, in pediatric oncology patients receiving inpatient or outpatient care at a single hospital. A case-control study was performed to identify CDI risk factors, infection prevention and antimicrobial prescribing practices were assessed, and environmental sampling was conducted. Available isolates were strain-typed by pulsed-field gel electrophoresis. An increase in hospital-onset CDI cases was observed from June-August 2012. Independent risk factors for CDI included hospitalization in the bone marrow transplant ward and exposure to computerized tomography scanning or cefepime in the prior 12 weeks. Cefepime use increased beginning in late 2011, reflecting a practice change for patients with neutropenic fever. There were 13 distinct strain types among 22 available isolates. Hospital-onset CDI rates decreased to near-baseline levels with enhanced infection prevention measures, including environmental cleaning and prolonged contact isolation. C difficile strain diversity associated with a cluster of CDI among pediatric oncology patients suggests a need for greater understanding of modes and sources of transmission and strategies to reduce patient susceptibility to CDI. Further research is needed on the risk of CDI with cefepime and its use as primary empirical treatment for neutropenic fever. Published by Elsevier Inc.

Impact of microbial derived secondary bile acids on colonization resistance against Clostridium difficile in the gastrointestinal tract.

PubMed

Winston, Jenessa A; Theriot, Casey M

2016-10-01

Clostridium difficile is an anaerobic, Gram positive, spore-forming bacillus that is the leading cause of nosocomial gastroenteritis. Clostridium difficile infection (CDI) is associated with increasing morbidity and mortality, consequently posing an urgent threat to public health. Recurrence of CDI after successful treatment with antibiotics is high, thus necessitating discovery of novel therapeutics against this pathogen. Susceptibility to CDI is associated with alterations in the gut microbiota composition and bile acid metabolome, specifically a loss of microbial derived secondary bile acids. This review aims to summarize in vitro, ex vivo, and in vivo studies done by our group and others that demonstrate how secondary bile acids affect the different stages of the C. difficile life cycle. Understanding the dynamic interplay of C. difficile and microbial derived secondary bile acids within the gastrointestinal tract will shed light on how bile acids play a role in colonization resistance against C. difficile. Rational manipulation of secondary bile acids may prove beneficial as a treatment for patients with CDI. Published by Elsevier Ltd.

Advances in the Microbiome: Applications to Clostridium difficile Infection

PubMed Central

Culligan, Eamonn P.; Sleator, Roy D.

2016-01-01

Clostridium difficile is a major cause of morbidity and mortality worldwide, causing over 400,000 infections and approximately 29,000 deaths in the United States alone each year. C. difficile is the most common cause of nosocomial diarrhoea in the developed world, and, in recent years, the emergence of hyper-virulent (mainly ribotypes 027 and 078, sometimes characterised by increased toxin production), epidemic strains and an increase in the number of community-acquired infections has caused further concern. Antibiotic therapy with metronidazole, vancomycin or fidaxomicin is the primary treatment for C. difficile infection (CDI). However, CDI is unique, in that, antibiotic use is also a major risk factor for acquiring CDI or recurrent CDI due to disruption of the normal gut microbiota. Therefore, there is an urgent need for alternative, non-antibiotic therapeutics to treat or prevent CDI. Here, we review a number of such potential treatments which have emerged from advances in the field of microbiome research. PMID:27657145

Clostridium difficile

PubMed Central

Curry, Scott R.

2017-01-01

SYNOPSIS Clostridium difficile infections (CDI) have emerged as one of the principal threats to the health of hospitalized and immunocompromised patients. Nucleic acid testing for C. difficile toxin genes has eclipsed traditional clinical diagnostics for CDI in sensitivity and is now widespread in clinical use, but preliminary evidence suggests that this may have come at a cost of substantially reduced positive predictive value. The importance of C. difficile colonization is increasingly recognized not only as a source for false positive clinical testing but also as a source of new infections within hospitals and other healthcare environments. In the last five years, several new treatment strategies that capitalize on the increasing understanding of the altered microbiome and host defenses in CDI patients have completed clinical trials, including fecal microbiota transplantation (FMT). This article highlights the changing epidemiology, laboratory diagnostics, pathogenesis, and treatment of CDI. PMID:20513554

Clostridium difficile infection: management strategies for a difficult disease

PubMed Central

Pardi, Darrell S.

2014-01-01

Clostridium difficile was first described as a cause of diarrhea in 1978 and in the last three decades has reached an epidemic state with increasing incidence and severity in both healthcare and community settings. There also has been a rise in severe outcomes from C. difficile infection (CDI). There have been tremendous advancements in the field of CDI with the identification of newer risk factors, recognition of CDI in populations previously thought not at risk and development of better diagnostic modalities. Several treatment options are available for CDI apart from metronidazole and vancomycin, and include new drugs such as fidaxomicin and other options such as fecal microbiota transplantation. This review discusses the epidemiology, risk factors and outcomes from CDI, and focuses primarily on existing and evolving treatment modalities. PMID:24587820

Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment for Clostridium difficile Infection

PubMed Central

Prabhu, Vimalanand S; Cornely, Oliver A; Golan, Yoav; Dubberke, Erik R; Heimann, Sebastian M; Hanson, Mary E; Liao, Jane; Pedley, Alison; Dorr, Mary Beth; Marcella, Stephen

2017-01-01

Abstract We estimated 30-day all-cause and Clostridium difficile infection (CDI)–associated hospital readmissions in participants at high risk of recurrent CDI enrolled in MODIFY I/II. Bezlotoxumab-treated inpatients experienced fewer CDI-associated readmissions compared with placebo-treated inpatients, notably in participants aged ≥65 years and with severe CDI. Clinical Trials Registration. NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

The morbidity, mortality, and costs associated with Clostridium difficile infection.

PubMed

Kwon, Jennie H; Olsen, Margaret A; Dubberke, Erik R

2015-03-01

Clostridium difficile infection (CDI) is the most common cause of infectious health care-associated diarrhea and is a major burden to patients and the health care system. The incidence and severity of CDI remain at historically high levels. This article reviews the morbidity, mortality, and costs associated with CDI. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of toxigenic Clostridium difficile polymerase chain reaction testing on the clinical microbiology laboratory and inpatient epidemiology.

PubMed

Napierala, Maureen; Munson, Erik; Skonieczny, Patrice; Rodriguez, Sonia; Riederer, Nancy; Land, Gayle; Luzinski, Mary; Block, Denise; Hryciuk, Jeanne E

2013-08-01

Conversion from Clostridium difficile toxin A/B EIA to tcdB polymerase chain reaction for diagnosis of C. difficile infection (CDI) resulted in significant decreases in laboratory testing volume and largely unchanged C. difficile toxin detection rates. Decreases in healthcare-associated CDI rates (P ≤ 0.05) reflected a clinical practice benefit of this conversion. Copyright © 2013 Elsevier Inc. All rights reserved.

Incorrect diagnosis of Clostridium difficile infection in a university hospital in Japan.

PubMed

Mori, Nobuaki; Yoshizawa, Sadako; Saga, Tomoo; Ishii, Yoshikazu; Murakami, Hinako; Iwata, Morihiro; Collins, Deirdre A; Riley, Thomas V; Tateda, Kazuhiro

2015-10-01

Physicians often fail to suspect Clostridium difficile infection (CDI) and many microbiology laboratories use suboptimal diagnostic techniques. To estimate the extent of and reasons for incorrect diagnosis of CDI in Japan, we investigated toxigenic C. difficile isolated from all stool culture samples and clinical course. Over a 12-month period in 2010, all stool culture samples (n = 975) submitted from inpatients in a university hospital in Japan were cultured for C. difficile and routine microbiological testing was conducted. In total, 177 C. difficile isolates were recovered, and 127 isolates were toxigenic. Among the toxin-A-positive/toxin-B-positive isolates, 12 were also positive for the binary toxin gene. However, clinically important ribotypes, such as 027 and 078, were not identified. A total of 58 (45.7%) cases with toxigenic C. difficile had unformed stool, and the incidence CDI was 1.6 cases per 10,000 patient-days. Of these 58 cases, 40 were not diagnosed in routine testing due to a lack of clinical suspicion (24.1%, 14/58) or a negative C. difficile toxin assay result (44.8%, 26/58). A stool toxin assay was performed in 54 patients (78.2%, 54/69) who did not have unformed stool. The present study demonstrated that a significant number of CDI cases in Japan might be overlooked or misdiagnosed in clinical practice due to a lack of clinical suspicion and limitations of microbiological testing for CDI in Japan. Providing education to promote awareness of CDI among physicians is important to improve the accuracy of diagnosis in Japan. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Mathematical Modeling of the Transmission Dynamics of Clostridium difficile Infection and Colonization in Healthcare Settings: A Systematic Review

PubMed Central

Gingras, Guillaume; Guertin, Marie-Hélène; Laprise, Jean-François; Drolet, Mélanie; Brisson, Marc

2016-01-01

Background We conducted a systematic review of mathematical models of transmission dynamic of Clostridium difficile infection (CDI) in healthcare settings, to provide an overview of existing models and their assessment of different CDI control strategies. Methods We searched MEDLINE, EMBASE and Web of Science up to February 3, 2016 for transmission-dynamic models of Clostridium difficile in healthcare settings. The models were compared based on their natural history representation of Clostridium difficile, which could include health states (S-E-A-I-R-D: Susceptible-Exposed-Asymptomatic-Infectious-Resistant-Deceased) and the possibility to include healthcare workers and visitors (vectors of transmission). Effectiveness of interventions was compared using the relative reduction (compared to no intervention or current practice) in outcomes such as incidence of colonization, CDI, CDI recurrence, CDI mortality, and length of stay. Results Nine studies describing six different models met the inclusion criteria. Over time, the models have generally increased in complexity in terms of natural history and transmission dynamics and number/complexity of interventions/bundles of interventions examined. The models were categorized into four groups with respect to their natural history representation: S-A-I-R, S-E-A-I, S-A-I, and S-E-A-I-R-D. Seven studies examined the impact of CDI control strategies. Interventions aimed at controlling the transmission, lowering CDI vulnerability and reducing the risk of recurrence/mortality were predicted to reduce CDI incidence by 3–49%, 5–43% and 5–29%, respectively. Bundles of interventions were predicted to reduce CDI incidence by 14–84%. Conclusions Although CDI is a major public health problem, there are very few published transmission-dynamic models of Clostridium difficile. Published models vary substantially in the interventions examined, the outcome measures used and the representation of the natural history of Clostridium difficile, which make it difficult to synthesize results and provide a clear picture of optimal intervention strategies. Future modeling efforts should pay specific attention to calibration, structural uncertainties, and transparent reporting practices. PMID:27690247

Risk factors for the development of Clostridium difficile infection in hospitalized children.

PubMed

Samady, Waheeda; Pong, Alice; Fisher, Erin

2014-10-01

This article defines the risk factors for Clostridium difficile infection (CDI) in hospitalized children in light of recent studies demonstrating a change in the epidemiology of these infections in both adults and children. Antibiotic exposure within the past 4-12 weeks was noted in a majority of published cases of pediatric CDI, and that remains a key risk factor for infection. Past and/or prolonged hospitalization increase a child's risk for CDI as they increase potential contact with C. difficile spores. Of all CDI, hospital-acquired infection remains more common. Many comorbid conditions have been linked with CDI, with the strongest association existing in children with cancer and inflammatory bowel disease. Severe infections occur infrequently in pediatric patients. Markers established in adults for severe CDI resulting in colectomy or transfer to ICU have not been shown to correlate in pediatric patients. Recent antibiotic exposure and hospitalization remain key risk factors for CDI in the hospitalized pediatric patient. Patients with comorbid conditions such as malignancy and inflammatory bowel disease are at higher risk for CDI. Resistant infections and severe outcomes are not common in the pediatric population.

Update on Clostridium difficile infections.

PubMed

Le Monnier, A; Zahar, J-R; Barbut, F

2014-08-01

Clostridium difficile infections (CDI) occur primarily in hospitalized patients with risk factors such as concomitant or recent use of antibiotics. CDI related additional costs are important for the global population and health-care facilities. CDI epidemiology has changed since 2003: they became more frequent boosted by large outbreaks, more severe, more resistant to antibiotic treatment, and spread to new groups of population without any risk factor. This is partly due to the emergence and worldwide dissemination of new and more virulent C. difficile strains such as the epidemic clone 027/NAP1/BI. The host immune response plays a central role in the pathogenesis of CDI and could also be involved in the occurrence of recurrent or severe forms. New guidelines including new molecular tests (NAAT) have recently clarified and simplified the diagnostic strategies for the microbiological diagnosis of CDI. The CDI incidence was proven to be related to the level of clinical suspicion and the frequency of microbiological screening for C. difficile. The current recommendations for the treatment of CDI mention oral metronidazole as the first line treatment for mild to moderate diarrhea. Oral vancomycin use should be restricted to severe cases. In the absence of consensus, the treatment of multiple recurrences remains a major concern. New and more targeted antibiotics and innovative therapeutic strategies (fecal transplantation, monoclonal antibodies, and vaccination) have emerged as new therapies for CDI. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Prevention of hospital-onset Clostridium difficile infection in the New York metropolitan region using a collaborative intervention model.

PubMed

Koll, Brian S; Ruiz, Rafael E; Calfee, David P; Jalon, Hillary S; Stricof, Rachel L; Adams, Audrey; Smith, Barbara A; Shin, Gina; Gase, Kathleen; Woods, Maria K; Sirtalan, Ismail

2014-01-01

The incidence, severity, and associated costs of Clostridium difficile (C. difficile) infection (CDI) have dramatically increased in hospitals over the past decade, indicating an urgent need for strategies to prevent transmission of C. difficile. This article describes a multifaceted collaborative approach to reduce hospital-onset CDI rates in 35 acute care hospitals in the New York metropolitan region. Hospitals participated in a comprehensive CDI reduction intervention and formed interdisciplinary teams to coordinate their efforts. Standardized clinical infection prevention and environmental cleaning protocols were implemented and monitored using checklists. Monthly data reports were provided to hospitals for facility-specific performance evaluation and comparison to aggregate data from all participants. Hospitals also participated in monthly teleconferences to review data and highlight successes, challenges, and strategies to reduce CDI. Incidence of hospital-onset CDI per 10,000 patient days was the primary outcome measure. Additionally, the incidence of nonhospital-associated, community-onset, hospital-associated, and recurrent CDIs were measured. The use of a collaborative model to implement a multifaceted infection prevention strategy was temporally associated with a significant reduction in hospital-onset CDI rates in participating New York metropolitan regional hospitals. © 2013 National Association for Healthcare Quality.

The impact of Clostridum difficile on surgical rate among ulcerative colitis patients: A systemic review and meta-analysis.

PubMed

Peng, Jiang-Chen; Shen, Jun; Zhu, Qi; Ran, Zhi-Hua

2015-01-01

There is growing recognition of the impact of Clostridum difficile infection (CDI) on patients with inflammatory bowel disease. Clostridium difficile infection causes greater morbidity and mortality. This study aimed to evaluate the impact of C. difficile on surgical risk among ulcerative colitis (UC) patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ACP Journal Club, DARE, CMR, and HTA. Studies were included if fulfilled the following criteria: (1) Cohort or case-control studies, which involved a comparison group that lacked CDI, (2) Patients were given a primary diagnosis of UC, (3) Comorbidity of CDI was evaluated by enzyme immunoassay of stool for C. difficile toxin A and B or C. difficile stool culture, (4) Studies evaluated surgical rate, and (5) Studies reported an estimate of odds ratio, accompanied by a corresponding measure of uncertainty. Five studies with 2380 patients fulfilled the inclusion criteria. Overall, meta-analysis showed that UC with CDI patients had a significant higher surgical rate than patients with UC alone. (OR=1.76, 95% CI=1.36-2.28). C. difficile infection increased the surgical rate in UC patients. However, results should be interpreted with caution, given the limitations of this stud.

Probiotic Saccharomyces boulardii CNCM I-745 prevents outbreak-associated Clostridium difficile-associated cecal inflammation in hamsters

PubMed Central

Koon, Hon Wai; Su, Bowei; Xu, Chunlan; Mussatto, Caroline C.; Tran, Diana Hoang-Ngoc; Lee, Elaine C.; Ortiz, Christina; Wang, Jiani; Lee, Jung Eun; Ho, Samantha; Chen, Xinhua; Kelly, Ciaran P.

2016-01-01

C. difficile infection (CDI) is a common debilitating nosocomial infection associated with high mortality. Several CDI outbreaks have been attributed to ribotypes 027, 017, and 078. Clinical and experimental evidence indicates that the nonpathogenic yeast Saccharomyces boulardii CNCM I-745 (S.b) is effective for the prevention of CDI. However, there is no current evidence suggesting this probiotic can protect from CDI caused by outbreak-associated strains. We used established hamster models infected with outbreak-associated C. difficile strains to determine whether oral administration of live or heat-inactivated S.b can prevent cecal tissue damage and inflammation. Hamsters infected with C. difficile strain VPI10463 (ribotype 087) and outbreak-associated strains ribotype 017, 027, and 078 developed severe cecal inflammation with mucosal damage, neutrophil infiltration, edema, increased NF-κB phosphorylation, and increased proinflammatory cytokine TNFα protein expression. Oral gavage of live, but not heated, S.b starting 5 days before C. difficile infection significantly reduced cecal tissue damage, NF-κB phosphorylation, and TNFα protein expression caused by infection with all strains. Moreover, S.b-conditioned medium reduced cell rounding caused by filtered supernatants from all C. difficile strains. S.b-conditioned medium also inhibited toxin A- and B-mediated actin cytoskeleton disruption. S.b is effective in preventing C. difficile infection by outbreak-associated via inhibition of the cytotoxic effects of C. difficile toxins. PMID:27514478

Prevention program for Clostridium difficile infection: a single-centre Serbian experience.

PubMed

Brkic, Snezana; Pellicano, Rinaldo; Turkulov, Vesna; Radovanovic, Marija; Abenavoli, Ludovico

2016-06-01

Clostridium difficile (C. difficile) diarrhea is a common, iatrogenic, nosocomial disease with a worldwide diffusion. Recent studies reported that the incidence of C. difficile infection (CDI) is rising, due to aging of the population and to greater prevalence of hypervirulent strains. We investigated whether the application of a prevention program lead to a decline in the incidence of intrahospital CDI. The study was designed as observational, to compare the efficacy of Schülke preventive program with the standard protocols, in a period of 4 months. For every patient with community-onset healthcare facility-associated (HCFA) CDI, we randomly selected four controls (1:4) with the same ICD code but without HCFA CDI. For statistical analysis the nonparametric, one-way ANOVA, univariate regression analysis, univariate analysis of variance, and Welch and Brown-Forsythe Test were used. Clinical features of HCFA CDI were typical. HCFA CDI group was significantly older than control group (P=0.008 and F=6.686; Partial Eta Square=0.013). Patients with HCFA CDI stayed significantly longer in hospital (P=0.000 and F=69.379; Partial Eta Square=0.117). Acquiring CDI prolonged the hospitalization of 14.52 days. HCFA CDI significantly increases the total cost of hospitalization as well as each element of the price respectively. With the application of the prevention program the annual incidence of CDI dropped from 49.01 in 2013 to 18.22/10000 bed days in 2014. Applying Schülke preventive program, implemented in 2014, has led to significant savings for the hospital compared to previous methods.

Binary toxin and its clinical importance in Clostridium difficile infection, Belgium.

PubMed

Pilate, T; Verhaegen, J; Van Ranst, M; Saegeman, V

2016-11-01

Binary toxin-producing Clostridium difficile strains such as ribotypes 027 and 078 have been associated with increased Clostridium difficile infection (CDI) severity. Our objective was to investigate the association between presence of the binary toxin gene and CDI severity and recurrence. We performed a laboratory-based retrospective study including patients between January 2013 and March 2015 whose fecal samples were analyzed by polymerase chain reaction (PCR) for the presence of the genes for toxin B and binary toxin and a deletion in the tcdC gene, specific for ribotype 027. Clinical and epidemiological characteristics were compared between 33 binary toxin-positive CDI patients and 33 binary toxin-negative CDI patients. Subsequently, the characteristics of 66 CDI patients were compared to those of 66 diarrhea patients who were carriers of non-toxigenic C. difficile strains. Fifty-nine of 1034 (5.7 %) fecal samples analyzed by PCR were binary toxin-positive, belonging to 33 different patients. No samples were positive for ribotype 027. Binary toxin-positive CDI patients did not differ from binary toxin-negative CDI patients in terms of disease recurrence, morbidity, or mortality, except for a higher peripheral leukocytosis in the binary toxin-positive group (16.30 × 10 9 /L vs. 11.65 × 10 9 /L; p = 0.02). The second part of our study showed that CDI patients had more severe disease, but not a higher 30-day mortality rate than diarrhea patients with a non-toxicogenic C. difficile strain. In our setting with a low prevalence of ribotype 027, the presence of the binary toxin gene is not associated with poor outcome.

Sensitive assays enable detection of serum IgG antibodies against Clostridium difficile toxin A and toxin B in healthy subjects and patients with Clostridium difficile infection.

PubMed

Zhao, Xuemei; Bender, Florent; Shukla, Rajiv; Kang, John J; Caro-Aguilar, Ivette; Laterza, Omar F

2016-04-01

Pathogenic Clostridium difficile produces two proinflammatory exotoxins, toxin A and toxin B. Low level of serum antitoxin IgG antibodies is a risk factor for the development of primary and recurrent C. difficile infection (CDI). We developed and validated two sensitive, titer-based electrochemiluminescence assays for the detection of serum antibody levels against C. difficile toxins A and B. These assays demonstrated excellent precision. The sensitivity of the assays allowed the detection of antitoxin A and antitoxin B IgG antibodies in all tested serum samples during assay validation. The validated titer-based assays enable assessment of antitoxin A and antitoxin B IgG antibodies as potential biomarkers to identify patients with CDI at increased risk for CDI recurrence.

Clostridium difficile colonization and infection in patients with hepatic cirrhosis.

PubMed

Yan, Dong; Chen, Yunbo; Lv, Tao; Huang, Yandi; Yang, Jiezuan; Li, Yongtao; Huang, Jianrong; Li, Lanjuan

2017-10-01

The aim of this study was to investigate the toxigenic Clostridium difficile colonization (CDC, colonization with toxigenic C. difficile but without symptoms) and C. difficile infection (CDI, active C. difficile infection resulting in disease symptoms) in hepatic cirrhosis patients, identify the risk factors of CDC, and determine the correlation between CDC and CDI. The strains of toxigenic C. difficile were isolated from patients with hepatic cirrhosis within 48 h after admission, followed by multilocus sequence typing (MLST). Patients were divided into toxigenic CDC group and noncolonized (NC) group according to the colonization. Logistic regression analysis was performed to analyse the risk factors for the CDC. Besides, the CDI incidence was compared between the two groups. Colonization of toxigenic C. difficile was identified in 104 cases (19.8 %). Eighteen sequence types (STs) were identified, among which ST-3, ST-54, ST-35 and ST-37 were the predominant types. Child-Pugh class C(relative risk, RR, 3.025; 95 % CI: 1.410-6.488), decrease of prothrombin time activity (PTA) (RR 2.180; 95 % CI: 1.368-3.476), decrease of platelet (RR 2.746; 95 % CI: 0.931-8.103) and concurrent hepatic encephalopathy (RR 1.740; 95 % CI: 1.012-2.990) were identified as the risk factors for the hepatic cirrhosis patients with CDC. The CDI incidence in the CDC group was also significantly higher than that of the NC group (26.0 % vs 1.7 %, P<0.001). An carriage rate of 19.8 % was reported in the hepatic cirrhosis patients with C. difficile colonization. Child's class C, decrease of PTA and platelet, and concurrent hepatic encephalopathy were the risk factors for the hepatic cirrhosis patients with C. difficile colonization. Hepatic cirrhosis patients with C. difficile colonization were more susceptible to CDI.

Challenges and opportunities in the management of Clostridium difficile infection.

PubMed

DuPont, Herbert L

2014-11-01

Clostridium difficile infection (CDI) is increasing in all regions of the world where sought. There is no gold standard for diagnosis of CDI, with available tests having limitations. Prevention of CDI will be seen with antibiotic stewardship, improved disinfection of hospitals and nursing homes, chemo- and immuno-prophylaxis and next generation probiotics. The important therapeutic agents are oral vancomycin and fidaxomicin with metronidazole being used only in mild cases or when oral therapy cannot be given. Current therapy of CDI for 10 days is associated with high rate of recurrence that may be prevented by prolonging initial therapy. Future treatment strategies will focus on drugs that inhibit C. difficile, reduce toxin activity and inflammation in the gut, and improve colonic flora diversity.

Strategies for Optimizing the Diagnostic Predictive Value of Clostridium difficile Molecular Diagnostics.

PubMed

Kociolek, Larry K

2017-05-01

Because nucleic acid amplification tests (NAATs) do not distinguish Clostridium difficile infection (CDI) and asymptomatic C. difficile carriage, the diagnostic predictive value of NAATs is limited when used in patients with a low probability of CDI. In this issue of the Journal of Clinical Microbiology , Truong et al. (J. Clin. Microbiol., 55:1276-1284, 2017, https://doi.org/10.1128/JCM.02319-16) report significant reductions in hospital-onset CDI and oral vancomycin utilization at their institution following implementation of a novel intervention that leveraged their clinical bioinformatics resources to prevent C. difficile testing of stools from patients without clinically significant diarrhea and in patients with recent laxative use. Copyright © 2017 American Society for Microbiology.

Clostridium difficile infection: Early history, diagnosis and molecular strain typing methods.

PubMed

Rodriguez, C; Van Broeck, J; Taminiau, B; Delmée, M; Daube, G

2016-08-01

Recognised as the leading cause of nosocomial antibiotic-associated diarrhoea, the incidence of Clostridium difficile infection (CDI) remains high despite efforts to improve prevention and reduce the spread of the bacterium in healthcare settings. In the last decade, many studies have focused on the epidemiology and rapid diagnosis of CDI. In addition, different typing methods have been developed for epidemiological studies. This review explores the history of C. difficile and the current scope of the infection. The variety of available laboratory tests for CDI diagnosis and strain typing methods are also examined. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Rise and Fall of Metronidazole for Clostridium difficile Infection.

PubMed

Chahine, Elias B

2018-06-01

Clostridium difficile is posing urgent health threats. Older studies have shown that metronidazole and vancomycin are equally effective in the treatment of Clostridium difficile infection (CDI). Given its inexpensive cost and low propensity to select antimicrobial resistant organisms, metronidazole became rapidly the drug of choice despite its pharmacokinetic limitations in the treatment of CDI. However, newer studies demonstrated that metronidazole is inferior to vancomycin, prompting clinicians to change their long-standing position on using metronidazole for mild to moderate infections and on reserving vancomycin for severe infections. Moving forward, metronidazole will fall out of favor in the treatment of CDI.

Clostridium difficile PCR ribotypes 001 and 176 - the common denominator of C. difficile infection epidemiology in the Czech Republic, 2014.

PubMed

Krutova, Marcela; Matejkova, Jana; Kuijper, Ed J; Drevinek, Pavel; Nyc, Otakar

2016-07-21

In 2014, 18 hospitals in the Czech Republic participated in a survey of the incidence of Clostridium difficile infections (CDI) in the country. The mean CDI incidence was 6.1 (standard deviation (SD):7.2) cases per 10,000 patient bed-days and 37.8 cases (SD: 41.4) per 10,000 admissions. The mean CDI testing frequency was 39.5 tests (SD: 25.4) per 10,000 patient bed-days and 255.8 tests (SD: 164.0) per 10,000 admissions. A total of 774 C. difficile isolates were investigated, of which 225 (29%) belonged to PCR ribotype 176, and 184 isolates (24%) belonged to PCR ribotype 001. Multilocus variable-number tandem repeat analysis (MLVA) revealed 27 clonal complexes formed by 84% (190/225) of PCR ribotype 176 isolates, and 14 clonal complexes formed by 77% (141/184) of PCR ribotype 001 isolates. Clonal clusters of PCR ribotypes 176 and 001 were observed in 11 and 7 hospitals, respectively. Our data demonstrate the spread of two C. difficile PCR ribotypes within 18 hospitals in the Czech Republic, stressing the importance of standardising CDI testing protocols and implementing mandatory CDI surveillance in the country. This article is copyright of The Authors, 2016.

High colonization rate and prolonged shedding of Clostridium difficile in pediatric oncology patients.

PubMed

Dominguez, Samuel R; Dolan, Susan A; West, Kelly; Dantes, Raymund B; Epson, Erin; Friedman, Deborah; Littlehorn, Cynthia A; Arms, Lesley E; Walton, Karen; Servetar, Ellen; Frank, Daniel N; Kotter, Cassandra V; Dowell, Elaine; Gould, Carolyn V; Hilden, Joanne M; Todd, James K

2014-08-01

Surveillance testing for Clostridium difficile among pediatric oncology patients identified stool colonization in 29% of patients without gastrointestinal symptoms and in 55% of patients with prior C. difficile infection (CDI). A high prevalence of C. difficile colonization and diarrhea complicates the diagnosis of CDI in this population. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era.

PubMed

Polage, Christopher R; Gyorke, Clare E; Kennedy, Michael A; Leslie, Jhansi L; Chin, David L; Wang, Susan; Nguyen, Hien H; Huang, Bin; Tang, Yi-Wei; Lee, Lenora W; Kim, Kyoungmi; Taylor, Sandra; Romano, Patrick S; Panacek, Edward A; Goodell, Parker B; Solnick, Jay V; Cohen, Stuart H

2015-11-01

Clostridium difficile is a major cause of health care-associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox-/PCR+) for CDI. Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. Patients undergoing C difficile testing were grouped by US Food and Drug Administration-approved toxin and PCR tests as Tox+/PCR+, Tox-/PCR+, or Tox-/PCR-. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox-/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P < .001 for all). The median duration of diarrhea was shorter in Tox-/PCR+ patients (2 days; interquartile range, 1-4 days) than in Tox+/PCR+ patients (3 days; interquartile range, 1-6 days) (P = .003) and was similar to that in Tox-/PCR- patients (2 days; interquartile range, 1-3 days), despite minimal empirical treatment of Tox-/PCR+ patients. No CDI-related complications occurred in Tox-/PCR+ patients vs 10 complications in Tox+/PCR+ patients (0% vs 7.6%, P < .001). One Tox-/PCR+ patient had recurrent CDI as a contributing factor to death within 30 days vs 11 CDI-related deaths in Tox+/PCR+ patients (0.6% vs 8.4%, P = .001). Among hospitalized adults with suspected CDI, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method. Exclusive reliance on molecular tests for CDI diagnosis without tests for toxins or host response is likely to result in overdiagnosis, overtreatment, and increased health care costs.

Ridinilazole: a novel therapy for Clostridium difficile infection.

PubMed

Vickers, Richard J; Tillotson, Glenn; Goldstein, Ellie J C; Citron, Diane M; Garey, Kevin W; Wilcox, Mark H

2016-08-01

Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhoea. Recurrent CDI increases disease morbidity and mortality, posing a high burden to patients and a growing economic burden to the healthcare system. Thus, there exists a significant unmet and increasing medical need for new therapies for CDI. This review aims to provide a concise summary of CDI in general and a specific update on ridinilazole (formerly SMT19969), a novel antibacterial currently under development for the treatment of CDI. Owing to its highly targeted spectrum of activity and ability to spare the normal gut microbiota, ridinilazole provides significant advantages over metronidazole and vancomycin, the mainstay antibiotics for CDI. Ridinilazole is bactericidal against C. difficile and exhibits a prolonged post-antibiotic effect. Furthermore, treatment with ridinilazole results in decreased toxin production. A phase 1 trial demonstrated that oral ridinilazole is well tolerated and specifically targets clostridia whilst sparing other faecal bacteria. Phase 2 and 3 trials will hopefully further our understanding of the clinical utility of ridinilazole for the treatment of CDI. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Management of inflammatory bowel disease with Clostridium difficile infection.

PubMed

D'Aoust, Julie; Battat, Robert; Bessissow, Talat

2017-07-21

To address the management of Clostridium difficile ( C. difficile ) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. A systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations. In those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not. Strong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.

Cecal Perforation Associated with Clostridium difficile Infection: A Case Report.

PubMed

Luthe, Sarah Kyuragi; Sato, Ryota

2017-04-01

Various complications are reported with Clostridium difficile infection (CDI), including fulminant CDI. Fulminant CDI is an underappreciated life-threatening condition associated with complications such as toxic megacolon and bowel perforation. A 79-year-old woman presented to the Emergency Department with altered mental status. She was admitted and conservatively treated for a left thalamic hemorrhage. While hospitalized, she developed watery diarrhea due to Clostridium difficile. Although metronidazole was initiated, she developed altered mental status and septic shock. Abdominal x-ray study and computed tomography revealed a significantly dilatated colon and a massive pneumoperitoneum. She underwent subtotal colectomy with a 14-day course of intravenous meropenem. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case suggests that we must be aware of the complications that CDI may present and adequately consider surgical management because early diagnosis and surgical treatment is critical to reduce the mortality of fulminant CDI. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimizing the diagnostic testing of Clostridium difficile infection.

PubMed

Bouza, Emilio; Alcalá, Luis; Reigadas, Elena

2016-09-01

Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhea and is associated with a considerable health and cost burden. However, there is still not a clear consensus on the best laboratory diagnosis approach and a wide variation of testing methods and strategies can be encountered. We aim to review the most practical aspects of CDI diagnosis providing our own view on how to optimize CDI diagnosis. Expert commentary: Laboratory diagnosis in search of C. difficile toxins should be applied to all fecal diarrheic samples reaching the microbiology laboratory in patients > 2 years old, with or without classic risk factors for CDI. Detection of toxins either directly in the fecal sample or in the bacteria isolated in culture confirm CDI in the proper clinical setting. Nuclear Acid Assay techniques (NAAT) allow to speed up the process with epidemiological and therapeutic consequences.

Cost analysis of an outbreak of Clostridium difficile infection ribotype 027 in a Dutch tertiary care centre.

PubMed

van Beurden, Y H; Bomers, M K; van der Werff, S D; Pompe, E A P M; Spiering, S; Vandenbroucke-Grauls, C M J E; Mulder, C J J

2017-04-01

The economic impact of Clostridium difficile infection (CDI) on the healthcare system is significant. From May 2013 to May 2014, an outbreak of C. difficile ribotype 027 occurred in a Dutch tertiary care hospital, involving 72 patients. The primary aim of this study was to provide insight into the financial burden that this CDI outbreak brought upon this hospital. A retrospective analysis was performed to estimate the costs of a one-year-long C. difficile ribotype 027 outbreak. Medical charts were reviewed for patient data. In addition, all costs associated with the outbreak control measures were collected. The attributable costs of the whole outbreak were estimated to be €1,222,376. The main contributing factor was missed revenue due to increased length of stay of CDI patients and closure of beds to enable contact isolation of CDI patients (36%). A second important cost component was extra surveillance and activities of the Department of Medical Microbiology and Infection Control (25%). To the authors' knowledge, this is the first study to provide insight into the attributable costs of CDI in an outbreak setting, and to delineate the major cost items. It is clear that the economic consequences of CDI are significant. The high costs associated with a CDI outbreak should help to justify the use of additional resources for CDI prevention and control. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Breakthrough Clostridium difficile Infection in Cirrhotic Patients Receiving Rifaximin.

PubMed

Reigadas, Elena; Alcalá, Luis; Gómez, Javier; Marín, Mercedes; Martin, Adoración; Onori, Raffaella; Muñoz, Patricia; Bouza, Emilio

2018-03-19

Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is commonly used in cirrhotic patients as prophylaxis for hepatic encephalopathy (HE). Several studies have demonstrated the efficacy of rifaximin in the treatment of CDI; however, resistance to rifaximin has also been reported. Few studies have assessed the risk of developing CDI in cirrhotic patients receiving rifaximin. Our objective was to assess the incidence and characteristics of CDI in patients with cirrhosis, especially in those who received rifaximin. We assessed the incidence and clinical characteristics of CDI in cirrhotic patients over a 6-year period in our hospital. Medical charts were retrospectively reviewed. Ribotyping and antimicrobial susceptibility testing of all strains against rifaximin were performed. A total of 388 cirrhotic patients were included, of whom 127 patients had at least 1 episode of diarrhea in which a sample was sent to the laboratory. CDI was detected in 46 patients. Fourteen patients (30.4%) were receiving rifaximin as prophylaxis for HE. The main ribotypes detected were 001 (30.4%), followed by 014 (19.6%). Resistance to rifaximin was 34.1% overall, and 84.6% in patients who had received rifaximin. Multivariate analysis showed that rifamycin therapy and ribotype 001 were significant risk factors for having a rifaximin-resistant C. difficile strain. A high percentage of CDI cases were detected in cirrhotic patients receiving rifaximin, mostly owing to selection of rifaximin-resistant C. difficile strains. Clinicians should be aware of the risk of CDI in cirrhotic patients, even in those receiving rifaximin.

Effect of Detecting and Isolating Clostridium difficile Carriers at Hospital Admission on the Incidence of C difficile Infections: A Quasi-Experimental Controlled Study.

PubMed

Longtin, Yves; Paquet-Bolduc, Bianka; Gilca, Rodica; Garenc, Christophe; Fortin, Elise; Longtin, Jean; Trottier, Sylvie; Gervais, Philippe; Roussy, Jean-François; Lévesque, Simon; Ben-David, Debby; Cloutier, Isabelle; Loo, Vivian G

2016-06-01

Clostridium difficile infection (CDI) is a major cause of health care-associated infection worldwide, and new preventive strategies are urgently needed. Current control measures do not target asymptomatic carriers, despite evidence that they can contaminate the hospital environment and health care workers' hands and potentially transmit C difficile to other patients. To investigate the effect of detecting and isolating C difficile asymptomatic carriers at hospital admission on the incidence of health care-associated CDI (HA-CDI). We performed a controlled quasi-experimental study between November 19, 2013, and March 7, 2015, in a Canadian acute care facility. Admission screening was conducted by detecting the tcdB gene by polymerase chain reaction on a rectal swab. Carriers were placed under contact isolation precautions during their hospitalization. Changes in HA-CDI incidence level and trend during the intervention period (17 periods of 4 weeks each) were compared with the preintervention control period (120 periods of 4 weeks each) by segmented regression analysis and autoregressive integrated moving average (ARIMA) modeling. Concomitant changes in the aggregated HA-CDI incidence at other institutions in Québec City, Québec (n = 6) and the province of Québec (n = 94) were also examined. Overall, 7599 of 8218 (92.5%) eligible patients were screened, among whom 368 (4.8%) were identified as C difficile carriers. During the intervention, 38 patients (3.0 per 10 000 patient-days) developed an HA-CDI compared with 416 patients (6.9 per 10 000 patient-days) during the preintervention control period (P < .001). There was no immediate change in the level of HA-CDIs on implementation (P = .92), but there was a significant decrease in trend over time of 7% per 4-week period (rate ratio, 0.93; 95% CI, 0.87-0.99 per period; P = .02). ARIMA modeling also detected a significant effect of the intervention, represented by a gradual progressive decrease in the HA-CDI time series by an overall magnitude of 7.2 HA-CDIs per 10 000 patient-days. We estimated that the intervention had prevented 63 of the 101 (62.4%) expected cases. By contrast, no significant decrease in HA-CDI rates occurred in the control groups. Detecting and isolating C difficile carriers was associated with a significant decrease in the incidence of HA-CDI. If confirmed in subsequent studies, this strategy could help prevent HA-CDI.

Bis-Cyclic-Guanidine as a Novel Class of Compounds Potent Against Clostridium Difficile.

PubMed

Li, Chunhui; Teng, Peng; Peng, Zhong; Sang, Peng; Sun, Xingmin; Cai, Jianfeng

2018-05-16

Clostridium difficile infection (CDI) symptoms range from diarrhea to severe toxic megacolon and even death. Due to its rapid acquisition of resistance, C. difficile is listed as an urgent antibiotic-resistant threat, and has surpassed methicillin-resistant Staphylococcus aureus (MRSA) as the most common hospital-acquired infections in the USA. To combat the pathogen, the new structural class of pseudo peptides that exhibit antimicrobial activities could play an important role. Herein, we report that bis-cyclic guanidine compounds that exhibit potent antibacterial activity against C. difficile with decent selectivity. Eight compounds showed high in vitro potency against C. difficile UK6 with MIC of 1.0 μg/mL, and cytotoxic selectivity index (SI) up to 37. Moreover, the most selective compound 13 is also effective upon the treatment of C. difficile-induced diseases in the mouse model of CDI, and appears to be a very promising new candidate for the treatment of CDI. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The potential for emerging therapeutic options for Clostridium difficile infection

PubMed Central

Mathur, Harsh; Rea, Mary C; Cotter, Paul D; Ross, R Paul; Hill, Colin

2014-01-01

Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review. PMID:25564777

Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review

PubMed Central

McFarland, Lynne V.

2015-01-01

Clostridium difficile infections are a global clinical concern and are one of the leading causes of nosocomial outbreaks. Preventing these infections has benefited from multidisciplinary infection control strategies and new antibiotics, but the problem persists. Probiotics are effective in preventing antibiotic-associated diarrhea and may also be a beneficial strategy for C. difficile infections, but randomized controlled trials are scarce. This meta-analysis pools 21 randomized, controlled trials for primary prevention of C. difficile infections (CDI) and four trials for secondary prevention of C. difficile recurrences and assesses the efficacy of specific probiotic strains. Four probiotics significantly improved primary CDI prevention: (Saccharomyces boulardii, Lactobacillus casei DN114001, a mixture of L. acidophilus and Bifidobacterium bifidum, and a mixture of L. acidophilus, L. casei and L. rhamnosus). None of the tested probiotics significantly improved secondary prevention of CDI. More confirmatory randomized trials are needed to establish if probiotics are useful for preventing C. difficile infections. PMID:27025619

Fidaxomicin for the treatment of Clostridium difficile infections.

PubMed

Whitman, Craig B; Czosnowski, Quinn A

2012-02-01

To evaluate the pharmacology, microbiology, safety, and efficacy of fidaxomicin for treatment of Clostridium difficile infections (CDI). Literature was identified through Ovid MEDLINE (1948-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) using the search terms fidaxomicin, OPT-80, PAR-101, OP-118, difimicin, tiacumicin, lipiarmycin, Clostridium difficile, Clostridium difficile infection, Clostridium difficile-associated diarrhea, and cost. Drug monographs were retrieved from manufacturers' Web pages, and the Red Book component of Micromedex was used for cost information. All pertinent Phase 1, 2, and 3 studies published in English were included. Fidaxomicin is a macrocyclic compound bactericidal against C. difficile and inhibits toxin and spore production. It has poor oral absorption with high fecal concentrations. Available Phase 2 and 3 data with fidaxomicin 200 mg orally every 12 hours demonstrate similar effectiveness in treating CDI compared to oral vancomycin. Fidaxomicin was shown to have less frequency of recurrent infections. Adverse effects are uncommon and occur at similar rates as with oral vancomycin. The most frequently reported adverse effects are gastrointestinal, hematologic, and electrolyte disorders. Available data are lacking in several areas, including the efficacy and safety of fidaxomicin compared to established regimens for mild-to-moderate, life-threatening, and recurrent CDIs. The cost of a 10-day course of fidaxomicin is significantly more than that of metronidazole and vancomycin for treatment of mild-to-moderate CDI. Fidaxomicin appears to be an effective and safe alternative to oral vancomycin for treatment of mild-to-moderate and severe CDI. Data on its use compared to guideline-recommended therapies for mild-to-moderate and life-threatening CDI are needed. Further data assessing the cost-effectiveness of fidaxomicin are needed. Currently, it cannot be recommended over vancomycin for treatment of CDI. However, it may be considered for treatment of recurrent infections.

Probiotic Saccharomyces boulardii CNCM I-745 prevents outbreak-associated Clostridium difficile-associated cecal inflammation in hamsters.

PubMed

Koon, Hon Wai; Su, Bowei; Xu, Chunlan; Mussatto, Caroline C; Tran, Diana Hoang-Ngoc; Lee, Elaine C; Ortiz, Christina; Wang, Jiani; Lee, Jung Eun; Ho, Samantha; Chen, Xinhua; Kelly, Ciaran P; Pothoulakis, Charalabos

2016-10-01

C. difficile infection (CDI) is a common debilitating nosocomial infection associated with high mortality. Several CDI outbreaks have been attributed to ribotypes 027, 017, and 078. Clinical and experimental evidence indicates that the nonpathogenic yeast Saccharomyces boulardii CNCM I-745 (S.b) is effective for the prevention of CDI. However, there is no current evidence suggesting this probiotic can protect from CDI caused by outbreak-associated strains. We used established hamster models infected with outbreak-associated C. difficile strains to determine whether oral administration of live or heat-inactivated S.b can prevent cecal tissue damage and inflammation. Hamsters infected with C. difficile strain VPI10463 (ribotype 087) and outbreak-associated strains ribotype 017, 027, and 078 developed severe cecal inflammation with mucosal damage, neutrophil infiltration, edema, increased NF-κB phosphorylation, and increased proinflammatory cytokine TNFα protein expression. Oral gavage of live, but not heated, S.b starting 5 days before C. difficile infection significantly reduced cecal tissue damage, NF-κB phosphorylation, and TNFα protein expression caused by infection with all strains. Moreover, S.b-conditioned medium reduced cell rounding caused by filtered supernatants from all C. difficile strains. S.b-conditioned medium also inhibited toxin A- and B-mediated actin cytoskeleton disruption. S.b is effective in preventing C. difficile infection by outbreak-associated via inhibition of the cytotoxic effects of C. difficile toxins. Copyright © 2016 the American Physiological Society.

The economic burden of Clostridium difficile

PubMed Central

McGlone, S. M.; Bailey, R. R.; Zimmer, S. M.; Popovich, M. J.; Tian, Y.; Ufberg, P.; Muder, R. R.; Lee, B. Y.

2013-01-01

Although Clostridium difficile (C. difficile) is the leading cause of infectious diarrhoea in hospitalized patients, the economic burden of this major nosocomial pathogen for hospitals, third-party payers and society remains unclear. We developed an economic computer simulation model to determine the costs attributable to healthcare-acquired C. difficile infection (CDI) from the hospital, third-party payer and societal perspectives. Sensitivity analyses explored the effects of varying the cost of hospitalization, C. difficile-attributable length of stay, and the probability of initial and secondary recurrences. The median cost of a case ranged from $9179 to $11 456 from the hospital perspective, $8932 to $11 679 from the third-party payor perspective, and $13 310 to $16 464 from the societal perspective. Most of the costs incurred were accrued during a patient’s primary CDI episode. Hospitals with an incidence of 4.1 CDI cases per 100 000 discharges would incur costs ≥$3.2 million (hospital perspective); an incidence of 10.5 would lead to costs ≥$30.6 million. Our model suggests that the annual US economic burden of CDI would be ≥$496 million (hospital perspective), ≥$547 million (third-party payer perspective) and ≥$796 million (societal perspective). Our results show that C. difficile infection is indeed costly, not only to third-party payers and the hospital, but to society as well. These results are consistent with current literature citing C. difficile as a costly disease. PMID:21668576

Fidaxomicin - the new drug for Clostridium difficile infection

PubMed Central

Vaishnavi, Chetana

2015-01-01

Clostridium difficile is one of the many aetiological agents of antibiotic associated diarrhoea and is implicated in 15-25 per cent of the cases. The organism is also involved in the exacearbation of inflammatory bowel disease and extracolonic manifestations. Due to increase in the incidence of C. difficile infection (CDI), emergence of hypervirulent strains, and increased frequency of recurrence, the clinical management of the disease has become important. The management of CDI is based on disease severity, and current antibiotic treatment options are limited to vancomycin or metronidazole in the developing countries. this review article briefly describes important aspects of CDI, and the new drug, fidaxomicin, for its treatment. Fidaxomicin is particularly active against C. difficile and acts by inhibition of RNA synthesis. Clinical trials done to compare the efficacy and safety of fidaxomicin with that of vancomycin in treating CDI concluded that fidaxomicin was non-inferior to vancomycin for treatment of CDI and that there was a significant reduction in recurrences. The bactericidal properties of fidaxomicin make it an ideal alternative for CDI treatment. However, fidaxomicin use should be considered taking into account the potential benefits of the drug, along with the medical requirements of the patient, the risks of treatment and the high cost of fidaxomicin compared to other treatment regimens. PMID:26112840

Quantifying Transmission of Clostridium difficile within and outside Healthcare Settings

PubMed Central

Olsen, Margaret A.; Dubberke, Erik R.; Galvani, Alison P.; Townsend, Jeffrey P.

2016-01-01

To quantify the effect of hospital and community-based transmission and control measures on Clostridium difficile infection (CDI), we constructed a transmission model within and between hospital, community, and long-term care-facility settings. By parameterizing the model from national databases and calibrating it to C. difficile prevalence and CDI incidence, we found that hospitalized patients with CDI transmit C. difficile at a rate 15 (95% CI 7.2–32) times that of asymptomatic patients. Long-term care facility residents transmit at a rate of 27% (95% CI 13%–51%) that of hospitalized patients, and persons in the community at a rate of 0.1% (95% CI 0.062%–0.2%) that of hospitalized patients. Despite lower transmission rates for asymptomatic carriers and community sources, these transmission routes have a substantial effect on hospital-onset CDI because of the larger reservoir of hospitalized carriers and persons in the community. Asymptomatic carriers and community sources should be accounted for when designing and evaluating control interventions. PMID:26982504

Cost-Effectiveness of Fecal Microbiota Transplantation in the Treatment of Recurrent Clostridium Difficile Infection: A Literature Review.

PubMed

Arbel, Leor T; Hsu, Edmund; McNally, Keegan

2017-08-23

Clostridium difficile ( C. difficile ) is a common cause of antibiotic--associated diarrhea (AAD), being responsible for 15--25% of all AAD cases. The purpose of this literature review is to determine the cost-effectiveness of fecal microbiota transplantation (FMT) and how it compares in this regard to the standard treatments of choice for recurrent C. difficile infection (CDI). The review of the literature along with the evaluation of three comparative cost effective analyses yielded findings consistent with the view that FMT is the most cost-effective option in treating recurrent CDI. There are some (but considerably less) data indicating that FMT may be a cost effective strategy in treating initial CDI, as well. The superior cost-effectiveness of FMT as compared to the preferred standards of treatment for recurrent CDI suggest FMT use should become more integrated in routine clinical practice. Increased utilization of FMTs would allow for better control of this increasingly problematic disease as well as lower costs associated with its management.

Hospitalization stay and costs attributable to Clostridium difficile infection: a critical review.

PubMed

Gabriel, L; Beriot-Mathiot, A

2014-09-01

In most healthcare systems, third-party payers fund the costs for patients admitted to hospital for Clostridium difficile infection (CDI) whereas, for CDI cases arising as complications of hospitalization, not all related costs are refundable to the hospital. We therefore aimed to critically review and categorize hospital costs and length of hospital stay (LOS) attributable to Clostridium difficile infection and to investigate the economic burden associated with it. A comprehensive literature review selected papers describing the costs and LOS for hospitalized patients as outcomes of CDI, following the use of statistics to identify costs and LOS solely attributable to CDI. Twenty-four studies were selected. Estimated attributable costs, all ranges expressed in US dollars, were $6,774-$10,212 for CDI requiring admission, $2,992-$29,000 for hospital-acquired CDI, and $2,454-$12,850 where no categorization was made. The ranges for LOS values were 5-13.6, 2.7-21.3, and 2.8-17.9 days, respectively. The categorization of CDI attributable costs allows budget holders to anticipate the cost per CDI case, a perspective that should enrich the design of appropriate incentives for the various budget holders to invest in prevention so that CDI prevention is optimized globally. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile in the ICU: the struggle continues.

PubMed

Bobo, Linda D; Dubberke, Erik R; Kollef, Marin

2011-12-01

Clostridium difficile infection (CDI) management has become more daunting over the past decade because of alarming increases in CDI incidence and severity both in the hospital and in the community. This increase has concomitantly caused significant escalation of the health-care economic burden caused by CDI, and it will likely be translated to increased ICU admission and attributable mortality. Some possible causes for difficulty in management of CDI are as follows: (1) inability to predict and prevent development of severe/complicated or relapsing CDI in patients who initially present with mild symptoms; (2) lack of a method to determine who would have benefited a priori from initiating vancomycin treatment first instead of treatment with metronidazole; (3) lack of sensitive and specific CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a hypervirulent, epidemic C difficile strain associated with increased morbidity and mortality; (5) association of certain high-usage nonantimicrobial medications with CDI; and (6) lack of treatment regimens that leave the normal intestinal flora undisturbed while treating the primary infection. The objective of this article is to present current management and prevention guidelines for CDI based on recommendations by the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America and potential new clinical management strategies on the horizon.

Clostridium difficile in the ICU

PubMed Central

Dubberke, Erik R.; Kollef, Marin

2011-01-01

Clostridium difficile infection (CDI) management has become more daunting over the past decade because of alarming increases in CDI incidence and severity both in the hospital and in the community. This increase has concomitantly caused significant escalation of the health-care economic burden caused by CDI, and it will likely be translated to increased ICU admission and attributable mortality. Some possible causes for difficulty in management of CDI are as follows: (1) inability to predict and prevent development of severe/complicated or relapsing CDI in patients who initially present with mild symptoms; (2) lack of a method to determine who would have benefited a priori from initiating vancomycin treatment first instead of treatment with metronidazole; (3) lack of sensitive and specific CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a hypervirulent, epidemic C difficile strain associated with increased morbidity and mortality; (5) association of certain high-usage nonantimicrobial medications with CDI; and (6) lack of treatment regimens that leave the normal intestinal flora undisturbed while treating the primary infection. The objective of this article is to present current management and prevention guidelines for CDI based on recommendations by the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America and potential new clinical management strategies on the horizon. PMID:22147824

The Cost-efficiency and Care Effectiveness of Probiotic Administration with Antibiotics to Prevent Hospital-Acquired Clostridium difficile Infection.

PubMed

Starn, Emily S; Hampe, Holly; Cline, Thomas

Health care facility-acquired Clostridium difficile infections (HCFA-CDI) have increased over the last several decades despite facilities developing protocols for prescribing probiotics with antibiotics to prevent HCFA-CDI. The literature does not consistently support this. A retrospective medical record review evaluated the care effectiveness of this practice. Care effectiveness was not found; patients receiving probiotics with antibiotics were twice as likely to develop HCFA-CDI (P = .004). Except with glycopeptides, patients were 1.88 times less likely to experience HCFA-CDI (P = .05).

Real-Time Electronic Tracking of Diarrheal Episodes and Laxative Therapy Enables Verification of Clostridium difficile Clinical Testing Criteria and Reduction of Clostridium difficile Infection Rates.

PubMed

Truong, Cynthia Y; Gombar, Saurabh; Wilson, Richard; Sundararajan, Gopalakrishnan; Tekic, Natasa; Holubar, Marisa; Shepard, John; Madison, Alexandra; Tompkins, Lucy; Shah, Neil; Deresinski, Stan; Schroeder, Lee F; Banaei, Niaz

2017-05-01

Health care-onset health care facility-associated Clostridium difficile infection (HO-CDI) is overdiagnosed for several reasons, including the high prevalence of C. difficile colonization and the inability of hospitals to limit testing to patients with clinically significant diarrhea. We conducted a quasiexperimental study from 22 June 2015 to 30 June 2016 on consecutive inpatients with C. difficile test orders at an academic hospital. Real-time electronic patient data tracking was used by the laboratory to enforce testing criteria (defined as the presence of diarrhea [≥3 unformed stools in 24 h] and absence of laxative intake in the prior 48 h). Outcome measures included C. difficile test utilization, HO-CDI incidence, oral vancomycin utilization, and clinical complications. During the intervention, 7.1% (164) and 9.1% (211) of 2,321 C. difficile test orders were canceled due to absence of diarrhea and receipt of laxative therapy, respectively. C. difficile test utilization decreased upon implementation from an average of 208.8 tests to 143.0 tests per 10,000 patient-days ( P < 0.001). HO-CDI incidence rate decreased from an average of 13.0 cases to 9.7 cases per 10,000 patient-days ( P = 0.008). Oral vancomycin days of therapy decreased from an average of 13.8 days to 9.4 days per 1,000 patient-days ( P = 0.009). Clinical complication rates were not significantly different in patients with 375 canceled orders compared with 869 episodes with diarrhea but negative C. difficile results. Real-time electronic clinical data tracking is an effective tool for verification of C. difficile clinical testing criteria and safe reduction of inflated HO-CDI rates. Copyright © 2017 American Society for Microbiology.

Variability in testing policies and impact on reported Clostridium difficile infection rates: results from the pilot Longitudinal European Clostridium difficile Infection Diagnosis surveillance study (LuCID).

PubMed

Davies, K; Davis, G; Barbut, F; Eckert, C; Petrosillo, N; Wilcox, M H

2016-12-01

Lack of standardised Clostridium difficile testing is a potential confounder when comparing infection rates. We used an observational, systematic, prospective large-scale sampling approach to investigate variability in C. difficile sampling to understand C. difficile infection (CDI) incidence rates. In-patient and institutional data were gathered from 60 European hospitals (across three countries). Testing methodology, testing/CDI rates and case profiles were compared between countries and institution types. The mean annual CDI rate per hospital was lowest in the UK and highest in Italy (1.5 vs. 4.7 cases/10,000 patient bed days [pbds], p < 0.001). The testing rate was highest in the UK compared with Italy and France (50.7/10,000 pbds vs. 31.5 and 30.3, respectively, p < 0.001). Only 58.4 % of diarrhoeal samples were tested for CDI across all countries. Overall, only 64 % of hospitals used recommended testing algorithms for laboratory testing. Small hospitals were significantly more likely to use standalone toxin tests (SATTs). There was an inverse correlation between hospital size and CDI testing rate. Hospitals using SATT or assays not detecting toxin reported significantly higher CDI rates than those using recommended methods, despite testing similar testing frequencies. These data are consistent with higher false-positive rates in such (non-recommended) testing scenarios. Cases in Italy and those diagnosed by SATT or methods NOT detecting toxin were significantly older. Testing occurred significantly earlier in the UK. Assessment of testing practice is paramount to the accurate interpretation and comparison of CDI rates.

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation.

PubMed

Kim, Ji Eun; Gweon, Tae-Geun; Yeo, Chang Dong; Cho, Young-Seok; Kim, Gi Jun; Kim, Jae Young; Kim, Jong Wook; Kim, Hyunho; Lee, Hye Won; Lim, Taeseok; Ham, Hyoju; Oh, Hyun Jin; Lee, Yeongbok; Byeon, Jaeho; Park, Sung Soo

2014-09-21

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

Assessment of treatment patterns and patient outcomes before vs after implementation of a severity-based Clostridium difficile infection treatment policy.

PubMed

Jardin, C G M; Palmer, H R; Shah, D N; Le, F; Beyda, N D; Jiang, Z; Garey, K W

2013-09-01

National guidelines recommend oral vancomycin for severe Clostridium difficile infection (CDI) based on results from recent clinical trials demonstrating improved clinical outcomes. However, real-world data to support these clinical trials are scant. To compare treatment patterns and patient outcomes of those treated for CDI before and after implementation of a severity-based CDI treatment policy at a tertiary teaching hospital. This study evaluated adult patients with a positive C. difficile toxin before and after implementation of a policy where patients with severe CDI given metronidazole were switched to oral vancomycin unless contra-indicated. Patients were stratified according to disease severity using a modified published severity score. Treatment patterns based on CDI severity and rates of refractory CDI were assessed. In total, 256 patients with CDI (mean age 66 years, standard deviation 17, 52% female) were evaluated (before implementation: N = 144; after implementation: N = 112). Use of oral vancomycin for severe CDI increased significantly from 14% (N = 8) to 91% (N = 48) following implementation of the policy (P < 0.0001). Refractory disease in patients with severe CDI decreased significantly from 37% to 15% following implementation of the policy (P = 0.035). No significant differences were noted among patients with mild to moderate CDI. A severity-based CDI treatment policy at a tertiary teaching hospital increased the use of oral vancomycin and was associated with decreased rates of refractory CDI. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Comparison of planktonic and biofilm-associated communities of Clostridium difficile and indigenous gut microbiota in a triple-stage chemostat gut model.

PubMed

Crowther, Grace S; Chilton, Caroline H; Todhunter, Sharie L; Nicholson, Scott; Freeman, Jane; Baines, Simon D; Wilcox, Mark H

2014-08-01

Biofilms are characteristic of some chronic or recurrent infections and this mode of growth tends to reduce treatment efficacy. Clostridium difficile infection (CDI) is associated with a high rate of recurrent symptomatic disease. The presence and behaviour of C. difficile within intestinal biofilms remains largely unexplored, but may factor in recurrent infection. A triple-stage chemostat gut model designed to facilitate the formation of intestinal biofilm was inoculated with a pooled human faecal emulsion. Bacterial populations were allowed to equilibrate before simulated CDI was induced by clindamycin (33.9 mg/L, four times daily, 7 days) and subsequently treated with vancomycin (125 mg/L, four times daily, 7 days). Indigenous gut microbiota, C. difficile total viable counts, spores, cytotoxin and antimicrobial activity in planktonic and biofilm communities were monitored during the 10 week experimental period. Vancomycin successfully treated the initial episode of simulated CDI, but ∼18 days after therapy cessation, recurrent infection occurred. Germination, proliferation and toxin production were evident within planktonic communities in both initial and recurrent CDI. In contrast, sessile C. difficile remained in dormant spore form for the duration of the experiment. The effects of and recovery from clindamycin and vancomycin exposure for sessile populations was delayed compared with responses for planktonic bacteria. Intestinal biofilms provide a potential reservoir for C. difficile spore persistence, possibly facilitating their dispersal into the gut lumen after therapeutic intervention, leading to recurrent infection. Therapeutic options for CDI could have increased efficacy if they are more effective against sessile C. difficile. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Molecular Epidemiology of Clostridium difficile Infection in Hospitalized Patients in Eastern China.

PubMed

Jin, Dazhi; Luo, Yun; Huang, Chen; Cai, Jian; Ye, Julian; Zheng, Yi; Wang, Liqian; Zhao, Peng; Liu, Anbing; Fang, Weijia; Wang, Xianjun; Xia, Shichang; Jiang, Jianmin; Tang, Yi-Wei

2017-03-01

Few studies on risk factors for and transmission of Clostridium difficile infection (CDI) in China have been reported. A cross-sectional study was conducted for 3 years in eastern China. Consecutive stool specimens from hospitalized patients with diarrhea were cultured for C. difficile. C. difficile isolates from these patients then were analyzed for toxin genes, genotypes, and antimicrobial resistance. A severity score for the CDI in each patient was determined by a blinded review of the medical record, and these scores ranged from 1 to 6. A total of 397 out of 3,953 patients (10.0%) with diarrhea were found to have CDI. Severity of CDI was mild to moderate, and the average (± standard deviation) severity score was 2.61 ± 1.01. C. difficile was isolated from stool specimens in 432 (10.9%) of all the patients who had diarrhea. C. difficile genotypes were determined by multilocus sequence analysis and PCR ribotyping; sequence type 37 (ST37)/ribotype 017 (RT017) ( n = 68, 16.5%) was the dominant genotype. Eleven patients (16.2%) with this genotype had a CDI severity score of 5. Overall, three RTs and four STs were predominant; these genotypes were associated with significantly different antimicrobial resistance patterns in comparison to all genotypes (χ 2 = 79.56 to 97.76; P < 0.001). Independent risk factors associated with CDI included age greater than 55 years (odds ratio [95% confidence interval], 26.80 [18.76 to 38.29]), previous hospitalization (12.42 [8.85 to 17.43]), previous antimicrobial treatment within 8 weeks (150.56 [73.11 to 310.06]), hospital stay more than 3 days before sampling (2.34 [1.71 to 3.22]), undergoing chemotherapy (3.31 [2.22 to 4.92]), and undergoing abdominal surgery (4.82 [3.54 to 6.55]). CDI is clearly a problem in eastern China and has a prevalence of 10.0% in hospitalized patients. Among risk factors for CDI, the advanced age threshold was younger for Chinese patients than that reported for patients in developed countries. Copyright © 2017 American Society for Microbiology.

Administration of Probiotic Kefir to Mice with Clostridium difficile Infection Exacerbates Disease

PubMed Central

Spinler, Jennifer K.; Brown, Aaron; Ross, Caná L.; Boonma, Prapaporn; Conner, Margaret E.; Savidge, Tor C.

2016-01-01

Lifeway® kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI. PMID:27180007

Clostridium difficile infection: epidemiology, diagnosis and understanding transmission.

PubMed

Martin, Jessica S H; Monaghan, Tanya M; Wilcox, Mark H

2016-04-01

Clostridium difficile infection (CDI) continues to affect patients in hospitals and communities worldwide. The spectrum of clinical disease ranges from mild diarrhoea to toxic megacolon, colonic perforation and death. However, this bacterium might also be carried asymptomatically in the gut, potentially leading to 'silent' onward transmission. Modern technologies, such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis, are helping to track C. difficile transmission across health-care facilities, countries and continents, offering the potential to illuminate previously under-recognized sources of infection. These typing strategies have also demonstrated heterogeneity in terms of CDI incidence and strain types reflecting different stages of epidemic spread. However, comparison of CDI epidemiology, particularly between countries, is challenging due to wide-ranging approaches to sampling and testing. Diagnostic strategies for C. difficile are complicated both by the wide range of bacterial targets and tests available and the need to differentiate between toxin-producing and non-toxigenic strains. Multistep diagnostic algorithms have been recommended to improve sensitivity and specificity. In this Review, we describe the latest advances in the understanding of C. difficile epidemiology, transmission and diagnosis, and discuss the effect of these developments on the clinical management of CDI.

Role of intravenous immune globulin in streptococcal toxic shock syndrome and Clostridium difficile infection.

PubMed

Shah, Punit J; Vakil, Niyati; Kabakov, Anna

2015-06-15

The use of intravenous immune globulin (IVIG) in the management of streptococcal toxic shock syndrome (STSS) and Clostridium difficile infection (CDI) is reviewed. IVIG has a wide range of uses in clinical practice, including STSS and CDI. It is an attractive option for these two infections because both infections are toxin mediated, and IVIG may contain antibodies that neutralize these toxins. For STSS and CDI, IVIG is often considered for use in critically ill patients who are not responding to traditional therapies. Several encouraging case reports and retrospective chart reviews have been published, highlighting the potential benefit of IVIG in such patients. However, its definitive role remains unclear, mainly due to the lack of high-level evidence. Data supporting its use have been extrapolated from retrospective chart reviews and case reports in which profound heterogeneity in patient populations and treatment modalities exist. The use of IVIG must be weighed carefully because it is not a benign product. As with the use of IVIG for STSS, the role of IVIG for CDI is unclear. Nonetheless, IVIG may serve as a useful adjunct therapy for patients suffering from severe complicated CDI (shock, ileus, or megacolon) who do not respond to conventional treatment. Adverse reactions to IVIG are mild and transitory and occur during or immediately after drug infusion. Although randomized, controlled trials supporting the use of IVIG for STSS and CDI are lacking, IVIG may be considered a last-line adjunct therapy in those patients for whom the clinical benefit outweighs the potential adverse effects of therapy. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Fecal microbiota transplantation for management of Clostridium difficile infection.

PubMed

Vaishnavi, Chetana

2014-07-01

The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.

Detection of Clostridium difficile infection clusters, using the temporal scan statistic, in a community hospital in southern Ontario, Canada, 2006-2011.

PubMed

Faires, Meredith C; Pearl, David L; Ciccotelli, William A; Berke, Olaf; Reid-Smith, Richard J; Weese, J Scott

2014-05-12

In hospitals, Clostridium difficile infection (CDI) surveillance relies on unvalidated guidelines or threshold criteria to identify outbreaks. This can result in false-positive and -negative cluster alarms. The application of statistical methods to identify and understand CDI clusters may be a useful alternative or complement to standard surveillance techniques. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting CDI clusters and determine if there are significant differences in the rate of CDI cases by month, season, and year in a community hospital. Bacteriology reports of patients identified with a CDI from August 2006 to February 2011 were collected. For patients detected with CDI from March 2010 to February 2011, stool specimens were obtained. Clostridium difficile isolates were characterized by ribotyping and investigated for the presence of toxin genes by PCR. CDI clusters were investigated using a retrospective temporal scan test statistic. Statistically significant clusters were compared to known CDI outbreaks within the hospital. A negative binomial regression model was used to identify associations between year, season, month and the rate of CDI cases. Overall, 86 CDI cases were identified. Eighteen specimens were analyzed and nine ribotypes were classified with ribotype 027 (n = 6) the most prevalent. The temporal scan statistic identified significant CDI clusters at the hospital (n = 5), service (n = 6), and ward (n = 4) levels (P ≤ 0.05). Three clusters were concordant with the one C. difficile outbreak identified by hospital personnel. Two clusters were identified as potential outbreaks. The negative binomial model indicated years 2007-2010 (P ≤ 0.05) had decreased CDI rates compared to 2006 and spring had an increased CDI rate compared to the fall (P = 0.023). Application of the temporal scan statistic identified several clusters, including potential outbreaks not detected by hospital personnel. The identification of time periods with decreased or increased CDI rates may have been a result of specific hospital events. Understanding the clustering of CDIs can aid in the interpretation of surveillance data and lead to the development of better early detection systems.

Is there a relationship between the presence of the binary toxin genes in Clostridium difficile strains and the severity of C. difficile infection (CDI)?

PubMed

Berry, C E; Davies, K A; Owens, D W; Wilcox, M H

2017-12-01

Some strains of Clostridium difficile produce a binary toxin, in addition to the main C. difficile virulence factors (toxins A and B). There have been conflicting reports regarding the role of binary toxin and its relationship to the severity of C. difficile infection (CDI). Samples, isolates and clinical data were collected as part of a prospective multicentre diagnostic study. Clostridium difficile isolates (n = 1259) were tested by polymerase chain reaction (PCR) assay to detect binary toxin genes cdtA and cdtB. The PCR binary toxin gene results were compared with clinical severity and outcome data, including 30-day all-cause mortality. The 1259 isolates corresponded to 1083 different patients (October 2010 to September 2011). The prevalence of binary toxin positive strains was significantly higher in faecal samples with detectable toxin A/B than in those without toxin but that were positive by cytotoxigenic culture (26.3% vs. 10.3%, p < 0.001). The presence of binary toxin correlated moderately with markers of CDI severity (white cell count, serum albumin concentration and serum creatinine concentration). However, the risk ratio for all-cause mortality was 1.68 for binary toxin positive patients and patients were significantly less likely to survive if they had CDI caused by a binary toxin gene positive strain, even after adjusting for age (p < 0.001). The presence of binary toxin genes does not predict the clinical severity of CDI, but it is significantly associated with the risk of all-cause mortality.

Burden of Clostridium difficile infection: Associated hospitalization in a cohort of middle-aged and older adults.

PubMed

Chen, Yingxi; Glass, Kathryn; Liu, Bette; Korda, Rosemary J; Riley, Thomas V; Kirk, Martyn D

2017-05-01

Clostridium difficile is the principal cause of infectious diarrhea in hospitalized patients. The aim of this study was to describe and compare length of stay (LOS), costs, and in-hospital deaths for C difficile infection (CDI) and non-CDI hospitalizations, in a cohort of middle-aged and older Australians. We used survey data from the 45 and Up Study, linked to hospitalization and death data. We calculated the average LOS and costs per hospitalization, and the proportion of in-hospital deaths for CDI and non-CDI hospitalizations. We then compared hospitalizations with CDI as a secondary diagnosis to non-CDI hospitalizations by stratifying hospitalizations based on principal diagnosis and then using generalized linear models to compare LOS and in-hospital costs, and logistic regression for in-hospital deaths, adjusting for age and sex. There were 641 CDI hospitalizations during 2006-2012. The average LOS was 17 days; the average cost per hospitalization was AUD 12,704; and in 7.3% of admissions (47 out of 641) the patient died. After adjusting for age and sex, hospitalizations with CDI were associated with longer LOS, higher costs, and a greater proportion of in-hospital deaths compared with hospitalizations with similar principal diagnosis but without CDI. CDI places additional burden on the Australian hospital system, with CDI patients having relatively lengthy hospital stays and high costs. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact.

PubMed

Borren, Nienke Z; Ghadermarzi, Shadi; Hutfless, Susan; Ananthakrishnan, Ashwin N

2017-01-01

Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia. We systematically searched PubMed/Medline and Embase for publications from Asia between 2000-16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk. Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%. In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity.

Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer.

PubMed

de Blank, Peter; Zaoutis, Theoklis; Fisher, Brian; Troxel, Andrea; Kim, Jason; Aplenc, Richard

2013-09-01

To study the trend of Clostridium difficile infection (CDI) and risk factors for hospital acquired CDI (HA-CDI) among children with cancer. We analyzed 33 095 first pediatric hospitalizations for malignancy among 43 pediatric hospitals between 1999 and 2011. The effect of demographics, disease characteristics, and weekly drug exposure (antibiotics, antacids, and chemotherapy) on HA-CDI was assessed with multivariate Cox regression. CDI was defined by the combination of International Classification of Diseases, 9th edition-Clinical Modification (ICD-9CM), CDI diagnostic assay billing code, and concurrent administration of a CDI-active antibiotic. HA-CDI was defined as CDI with assay occurring after the sixth hospital day. A total of 1736 admissions with CDI were identified, of which 380 were HA-CDI. CDI incidence increased from 1999-2006 (P = .01); however, CDI testing frequency and disease decreased from 2006-2010 (P < .05). Admissions with HA-CDI had longer lengths of stay compared with those without HA-CDI (35 days vs 12 days, P < .01) and greater risk of inpatient mortality (relative risk 2.3, P < .01). Increased risk of HA-CDI (hazard ratio [95% CI]) was seen after exposure to the following drugs: aminoglycoside (1.357 [1.053-1.749]), third generation cephalosporin (1.518 [1.177-1.959]), cefepime (2.383 [1.839-3.089]), and proton pump inhibiting agent (1.398 [1.096-1.784]) in the prior week, and chemotherapy (1.942 [1.491-2.529]) in the 8-14 days prior to HA-CDI onset. Histamine-2 receptor antagonist exposure in the prior week was associated with decreased risk of HA-CDI (0.730 [0.584-0.912]). Despite an apparent decrease in CDI incidence from 2006-2010, HA-CDI remains prevalent and morbid among children with cancer. Recent exposure to chemotherapy, proton pump inhibitor, and certain antibiotics were independent risk factors for HA-CDI. Copyright © 2013 Mosby, Inc. All rights reserved.

Factors associated with Clostridium difficile infection: A nested case-control study in a three year prospective cohort.

PubMed

Khanafer, Nagham; Vanhems, Philippe; Barbut, Frédéric; Luxemburger, Christine

2017-04-01

Clostridium difficile infection (CDI) is a serious medical condition that is associated with substantial morbidity and mortality. Identification of risk factors associated with CDI and prompt recognition of patients at risk is key to successfully preventing CDI. A 3-year prospective, observational, cohort study was conducted in a French university hospital and a nested case-control study was performed to identify risk factors for CDI. Inpatients aged 18 years or older, suffering from diarrhea suspected to be related to CDI, were asked to participate. A total of 945 patients were included, of which 233 cases had a confirmed CDI. CDI infection was more common in men (58.4%) (P = 0.04) compared with patients with diarrhea not related to C. difficile. Previous hospitalization (P < 0.001), prior treatment with antibiotics (P = 0.001) or antiperistaltics (P = 0.002), liver disease (P = 0.003), malnutrition (P < 0.001), and previous CDI (P < 0.001) were significantly more common in patients with CDI. Multivariate logistic regression analysis showed that exposure to antibiotics in the last 60 days (especially third generation cephalosporins and penicillins with β-lactamase inhibitor), chronic renal or liver disease, malnutrition or previous CDI, were associated with an independent high risk of CDI. Age was not related with CDI. This study showed that antibiotics and some comorbid conditions were predictors of CDI. Patients at high risk of acquiring CDI at the time of admission may benefit from careful monitoring of antibiotic prescriptions and early attention to infection control issues. In future, these "high-risk" patients may benefit from novel agents being developed to prevent CDI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection

PubMed Central

2016-01-01

Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and contain the spread of resistance and to ensure an efficacious therapy for CDI. PMID:26862400

Disease Progression and Resolution in Rodent Models of Clostridium difficile Infection and Impact of Antitoxin Antibodies and Vancomycin.

PubMed

Warn, Peter; Thommes, Pia; Sattar, Abdul; Corbett, David; Flattery, Amy; Zhang, Zuo; Black, Todd; Hernandez, Lorraine D; Therien, Alex G

2016-11-01

Clostridium difficile causes infections of the colon in susceptible patients. Specifically, gut dysbiosis induced by treatment with broad-spectrum antibiotics facilitates germination of ingested C. difficile spores, expansion of vegetative cells, and production of symptom-causing toxins TcdA and TcdB. The current standard of care for C. difficile infections (CDI) consists of administration of antibiotics such as vancomycin that target the bacterium but also perpetuate gut dysbiosis, often leading to disease recurrence. The monoclonal antitoxin antibodies actoxumab (anti-TcdA) and bezlotoxumab (anti-TcdB) are currently in development for the prevention of recurrent CDI. In this study, the effects of vancomycin or actoxumab/bezlotoxumab treatment on progression and resolution of CDI were assessed in mice and hamsters. Rodent models of CDI are characterized by an early severe phase of symptomatic disease, associated with high rates of morbidity and mortality; high intestinal C. difficile burden; and a disrupted intestinal microbiota. This is followed in surviving animals by gradual recovery of the gut microbiota, associated with clearance of C. difficile and resolution of disease symptoms over time. Treatment with vancomycin prevents disease initially by inhibiting outgrowth of C. difficile but also delays microbiota recovery, leading to disease relapse following discontinuation of therapy. In contrast, actoxumab/bezlotoxumab treatment does not impact the C. difficile burden but rather prevents the appearance of toxin-dependent symptoms during the early severe phase of disease, effectively preventing disease until the microbiota (the body's natural defense against C. difficile) has fully recovered. These data provide insight into the mechanism of recurrence following vancomycin administration and into the mechanism of recurrence prevention observed clinically with actoxumab/bezlotoxumab. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Clostridium difficile rates in asymptomatic and symptomatic hospitalized patients using nucleic acid testing.

PubMed

Truong, Cynthia; Schroeder, Lee F; Gaur, Rajiv; Anikst, Victoria Emma; Komo, Ikuko; Watters, Colleen; McCalley, Erin; Kulik, Carole; Pickham, David; Lee, Nancy J; Banaei, Niaz

2017-04-01

The Clostridium difficile rate in symptomatic patients represents both those with C. difficile infection (CDI) and those with colonization. To predict the extent of CDI overdiagnosis, we compared the asymptomatic colonization rate to the symptomatic positivity rate in hospitalized patients using nucleic acid testing. Between July 2014 and April 2015, formed stool samples were collected from asymptomatic patients after admission to 3 hospital wards at the Stanford Hospital. Stool samples from symptomatic patients with suspected CDI in the same wards were collected for testing per provider order. The GeneXpert C. difficile tcdB polymerase chain reaction (PCR) assay (Cepheid, Sunnyvale, CA, USA) was performed on all stool samples and PCR cycle threshold was used as a measure of genomic equivalents. Chart review was performed to obtain clinical history and medication exposure. We found an asymptomatic C. difficile carriage rate of 11.8% (43/365) (95% confidence interval [CI], 8.5-15.1%) and a positivity rate in symptomatic patients of 15.4% (54/351) (95% CI, 11.6-19.2%; P=0.19). The median PCR cycle thresholds was not significantly different between asymptomatic carriers and symptomatic positives (29.5 versus 27.3; P=0.07). Among asymptomatic patients, 11.6% (5/43) of carriers and 8.4% (27/322; P=0.56) of noncarriers subsequently became symptomatic CDI suspects within the same hospitalization. Single and multivariate analysis did not identify any demographic or clinical factors as being significantly associated with C. difficile carriage. Asymptomatic C. difficile carriage rate was similar to symptomatic positivity rate. This suggests the majority of PCR-positive results in symptomatic patients are likely due to C. difficile colonization. Disease-specific biomarkers are needed to accurately diagnose patients with C. difficile disease. Copyright © 2017 Elsevier Inc. All rights reserved.

The economic burden of Clostridium difficile.

PubMed

McGlone, S M; Bailey, R R; Zimmer, S M; Popovich, M J; Tian, Y; Ufberg, P; Muder, R R; Lee, B Y

2012-03-01

Although Clostridium difficile (C. difficile) is the leading cause of infectious diarrhoea in hospitalized patients, the economic burden of this major nosocomial pathogen for hospitals, third-party payers and society remains unclear. We developed an economic computer simulation model to determine the costs attributable to healthcare-acquired C. difficile infection (CDI) from the hospital, third-party payer and societal perspectives. Sensitivity analyses explored the effects of varying the cost of hospitalization, C. difficile-attributable length of stay, and the probability of initial and secondary recurrences. The median cost of a case ranged from $9179 to $11 456 from the hospital perspective, $8932 to $11 679 from the third-party payor perspective, and $13 310 to $16 464 from the societal perspective. Most of the costs incurred were accrued during a patient's primary CDI episode. Hospitals with an incidence of 4.1 CDI cases per 100 000 discharges would incur costs ≥$3.2 million (hospital perspective); an incidence of 10.5 would lead to costs ≥$30.6 million. Our model suggests that the annual US economic burden of CDI would be ≥$496 million (hospital perspective), ≥$547 million (third-party payer perspective) and ≥$796 million (societal perspective). Our results show that C. difficile infection is indeed costly, not only to third-party payers and the hospital, but to society as well. These results are consistent with current literature citing C. difficile as a costly disease. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Infection prevention and control practices related to Clostridium difficile infection in Canadian acute and long-term care institutions.

PubMed

Wilkinson, Krista; Gravel, Denise; Taylor, Geoffrey; McGeer, Allison; Simor, Andrew; Suh, Kathryn; Moore, Dorothy; Kelly, Sharon; Boyd, David; Mulvey, Michael; Mounchili, Aboubakar; Miller, Mark

2011-04-01

Clostridium difficile is an important pathogen in Canadian health care facilities, and infection prevention and control (IPC) practices are crucial to reducing C difficile infections (CDIs). We performed a cross-sectional study to identify CDI-related IPC practices in Canadian health care facilities. A survey assessing facility characteristics, CDI testing strategies, CDI contact precautions, and antimicrobial stewardship programs was sent to Canadian health care facilities in February 2005. Responses were received from 943 (33%) facilities. Acute care facilities were more likely than long-term care (P < .001) and mixed care facilities (P = .03) to submit liquid stools from all patients for CDI testing. Physician orders were required before testing for CDI in 394 long-term care facilities (66%)-significantly higher than the proportions in acute care (41%; P < .001) and mixed care sites (49%; P < .001). A total of 841 sites (93%) had an infection control manual, 639 (76%) of which contained CDI-specific guidelines. Antimicrobial stewardship programs were reported by 40 (29%) acute care facilities; 19 (54%) of these sites reported full enforcement of the program. Canadian health care facilities have widely varying C difficile IPC practices. Opportunities exist for facilities to take a more active role in IPC policy development and implementation, as well as antimicrobial stewardship. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects

PubMed Central

Di Bella, Stefano; Ascenzi, Paolo; Siarakas, Steven; Petrosillo, Nicola; di Masi, Alessandra

2016-01-01

Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies. PMID:27153087

Successful Fecal Microbiota Transplantation in a Patient with Severe Complicated Clostridium difficile Infection after Liver Transplantation.

PubMed

Schneider, Kai Markus; Wirtz, Theresa H; Kroy, Daniela; Albers, Stefanie; Neumann, Ulf Peter; Strowig, Till; Sellge, Gernot; Trautwein, Christian

2018-01-01

Clostridium difficile infection (CDI) represents one of the most common healthcare-associated infections. Due to increasing numbers of recurrences and therapy failures, CDI has become a major disease burden. Studies have shown that fecal microbiota transplantation (FMT) can both be a safe and highly efficacious therapy for patients with therapy-refractory CDI. However, patients undergoing solid organ transplantation are at high risk for CDI due to long-term immunosuppression, previous antibiotic therapy, and proton pump inhibitor use. Additionally, these patients may be especially prone to adverse events related to FMT. Here, we report a successful FMT in a patient with severe therapy-refractory CDI after liver transplantation.

Recognition of Clostridium difficile PCR-ribotypes 001, 027 and 126/078 using an extended MALDI-TOF MS system.

PubMed

Reil, M; Erhard, M; Kuijper, E J; Kist, M; Zaiss, H; Witte, W; Gruber, H; Borgmann, S

2011-11-01

During the last decade, Clostridium difficile infection (CDI) increased markedly inside as well as outside of hospitals. In association with the occurrence of new hypervirulent C. difficile strains, CDI became more important. Until now typing of C. difficile strains has been enabled by PCR-ribotyping. However, this method is restricted to specialized laboratories combined with high maintenance cost. Therefore, we tested MALDI-TOF mass spectrometry for typing of C. difficile to provide a fast method for surveillance of CDI. Using a standard set of 25 different C. difficile PCR ribotypes a database was made by different mass spectra recorded in the SARAMIS software (AnagnosTec, Zossen, Germany). The database was validated with 355 C. difficile strains belonging to 29 different PCR ribotypes collected prospectively from all submitted feces samples in 2009. The most frequent PCR ribotypes were type 001 (70%), 027 (4.8%) and 078/126 (4.7%). All three types were recognized by MALDI-TOF MS. We conclude that an extended MALDI-TOF system was capable to recognize specific markers for ribotypes 001, 027 and 078/126 allowing an effective identification of these strains.

Bezlotoxumab: A Review in Preventing Clostridium difficile Infection Recurrence.

PubMed

Deeks, Emma D

2017-10-01

Bezlotoxumab (Zinplava™) is a fully human monoclonal antibody against Clostridium difficile toxin B indicated for the prevention of C. difficile infection (CDI) recurrence in patients with a high recurrence risk. It is the first agent approved for recurrence prevention and is administered as a single intravenous infusion in conjunction with standard-of-care (SoC) antibacterial treatment for CDI. In well-designed, placebo-controlled, phase 3 trials (MODIFY 1 and 2), a single infusion of bezlotoxumab, given in combination with SoC antibacterial therapy for CDI in adults, was effective in reducing CDI recurrence in the 12 weeks post-treatment, with this benefit being seen mainly in the patients at high recurrence risk. Bezlotoxumab did not impact the efficacy of the antibacterials being used to treat the CDI and, consistent with its benefits on CDI recurrence, appeared to reduce the need for subsequent antibacterials, thus minimizing further gut microbiota disruption. Longer term, there were no further CDI recurrences over 12 months' follow-up among patients who had received bezlotoxumab in MODIFY 2 and entered an extension substudy. Bezlotoxumab has low immunogenicity and is generally well tolerated, although the potential for heart failure in some patients requires consideration; cost-effectiveness data for bezlotoxumab are awaited with interest. Thus, a single intravenous infusion of bezlotoxumab during SoC antibacterial treatment for CDI is an emerging option for reducing CDI recurrence in adults at high risk of recurrence.

Attributable Cost of Clostridium difficile Infection in Pediatric Patients.

PubMed

Mehrotra, Preeti; Jang, Jisun; Gidengil, Courtney; Sandora, Thomas J

2017-12-01

OBJECTIVES The attributable cost of Clostridium difficile infection (CDI) in children is unknown. We sought to determine a national estimate of attributable cost and length of stay (LOS) of CDI occurring during hospitalization in children. DESIGN AND METHODS We analyzed discharge records of patients between 2 and 18 years of age from the Agency for Healthcare Research and Quality (AHRQ) Kids' Inpatient Database. We created a logistic regression model to predict CDI during hospitalization based on demographic and clinical characteristics. Predicted probabilities from the logistic regression model were then used as propensity scores to match 1:2 CDI to non-CDI cases. Charges were converted to costs and compared between patients with CDI and propensity-score-matched controls. In a sensitivity analysis, we adjusted for LOS as a confounder by including it in both the propensity score and a generalized linear model predicting cost. RESULTS We identified 8,527 pediatric hospitalizations (0.53%) with a diagnosis of CDI and 1,597,513 discharges without CDI. In our matched cohorts, the attributable cost of CDI occurring during a hospitalization ranged from $1,917 to $8,317, depending on whether model was adjusted for LOS. When not adjusting for LOS, CDI-associated hospitalizations cost 1.6 times more than non-CDI associated hospitalizations. Attributable LOS of CDI was approximately 4 days. CONCLUSIONS Clostridium difficile infection in hospitalized children is associated with an economic burden similar to adult estimates. This finding supports a continued focus on preventing CDI in children as a priority. Pediatric CDI cost analyses should account for LOS as an important confounder of cost. Infect Control Hosp Epidemiol 2017;38:1472-1477.

Determinants of Clostridium difficile Infection Incidence Across Diverse United States Geographic Locations

PubMed Central

Lessa, Fernanda C.; Mu, Yi; Winston, Lisa G.; Dumyati, Ghinwa K.; Farley, Monica M.; Beldavs, Zintars G.; Kast, Kelly; Holzbauer, Stacy M.; Meek, James I.; Cohen, Jessica; McDonald, L. Clifford; Fridkin, Scott K.

2014-01-01

Background  Clostridium difficile infection (CDI) is no longer restricted to hospital settings, and population-based incidence measures are needed. Understanding the determinants of CDI incidence will allow for more meaningful comparisons of rates and accurate national estimates. Methods  Data from active population- and laboratory-based CDI surveillance in 7 US states were used to identify CDI cases (ie, residents with positive C difficile stool specimen without a positive test in the prior 8 weeks). Cases were classified as community-associated (CA) if stool was collected as outpatients or ≤3 days of admission and no overnight healthcare facility stay in the past 12 weeks; otherwise, cases were classified as healthcare-associated (HA). Two regression models, one for CA-CDI and another for HA-CDI, were built to evaluate predictors of high CDI incidence. Site-specific incidence was adjusted based on the regression models. Results  Of 10 062 cases identified, 32% were CA. Crude incidence varied by geographic area; CA-CDI ranged from 28.2 to 79.1/100 000 and HA-CDI ranged from 45.7 to 155.9/100 000. Independent predictors of higher CA-CDI incidence were older age, white race, female gender, and nucleic acid amplification test (NAAT) use. For HA-CDI, older age and a greater number of inpatient-days were predictors. After adjusting for relevant predictors, the range of incidence narrowed greatly; CA-CDI rates ranged from 30.7 to 41.3/100 000 and HA-CDI rates ranged from 58.5 to 94.8/100 000. Conclusions  Differences in CDI incidence across geographic areas can be partially explained by differences in NAAT use, age, race, sex, and inpatient-days. Variation in antimicrobial use may contribute to the remaining differences in incidence. PMID:25734120

Determinants of Clostridium difficile Infection Incidence Across Diverse United States Geographic Locations.

PubMed

Lessa, Fernanda C; Mu, Yi; Winston, Lisa G; Dumyati, Ghinwa K; Farley, Monica M; Beldavs, Zintars G; Kast, Kelly; Holzbauer, Stacy M; Meek, James I; Cohen, Jessica; McDonald, L Clifford; Fridkin, Scott K

2014-09-01

Clostridium difficile infection (CDI) is no longer restricted to hospital settings, and population-based incidence measures are needed. Understanding the determinants of CDI incidence will allow for more meaningful comparisons of rates and accurate national estimates. Data from active population- and laboratory-based CDI surveillance in 7 US states were used to identify CDI cases (ie, residents with positive C difficile stool specimen without a positive test in the prior 8 weeks). Cases were classified as community-associated (CA) if stool was collected as outpatients or ≤3 days of admission and no overnight healthcare facility stay in the past 12 weeks; otherwise, cases were classified as healthcare-associated (HA). Two regression models, one for CA-CDI and another for HA-CDI, were built to evaluate predictors of high CDI incidence. Site-specific incidence was adjusted based on the regression models. Of 10 062 cases identified, 32% were CA. Crude incidence varied by geographic area; CA-CDI ranged from 28.2 to 79.1/100 000 and HA-CDI ranged from 45.7 to 155.9/100 000. Independent predictors of higher CA-CDI incidence were older age, white race, female gender, and nucleic acid amplification test (NAAT) use. For HA-CDI, older age and a greater number of inpatient-days were predictors. After adjusting for relevant predictors, the range of incidence narrowed greatly; CA-CDI rates ranged from 30.7 to 41.3/100 000 and HA-CDI rates ranged from 58.5 to 94.8/100 000. Differences in CDI incidence across geographic areas can be partially explained by differences in NAAT use, age, race, sex, and inpatient-days. Variation in antimicrobial use may contribute to the remaining differences in incidence.

Comparison of the Vidas C. difficile GDH Automated Enzyme-Linked Fluorescence Immunoassay (ELFA) with Another Commercial Enzyme Immunoassay (EIA) (Quik Chek-60), Two Selective Media, and a PCR Assay for gluD for Detection of Clostridium difficile in Fecal Samples.

PubMed

Davies, K A; Berry, C E; Morris, K A; Smith, R; Young, S; Davis, T E; Fuller, D D; Buckner, R J; Wilcox, M H

2015-06-01

Prevention and management of Clostridium difficile infection (CDI) can be improved by rapid and reliable diagnostics. The Vidas C. difficile glutamate dehydrogenase assay had performance comparable to that of the Quik Chek-60 assay (overall agreement, 95%) and a sensitivity of >93%; thus, it is suitable as the first test in two-stage algorithms for a CDI diagnosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cost-Effectiveness of Fecal Microbiota Transplantation in the Treatment of Recurrent Clostridium Difficile Infection: A Literature Review

PubMed Central

Arbel, Leor T; McNally, Keegan

2017-01-01

Clostridium difficile (C. difficile) is a common cause of antibiotic-­associated diarrhea (AAD), being responsible for 15­-25% of all AAD cases. The purpose of this literature review is to determine the cost-effectiveness of fecal microbiota transplantation (FMT) and how it compares in this regard to the standard treatments of choice for recurrent C. difficile infection (CDI). The review of the literature along with the evaluation of three comparative cost effective analyses yielded findings consistent with the view that FMT is the most cost-effective option in treating recurrent CDI. There are some (but considerably less) data indicating that FMT may be a cost effective strategy in treating initial CDI, as well. The superior cost-effectiveness of FMT as compared to the preferred standards of treatment for recurrent CDI suggest FMT use should become more integrated in routine clinical practice. Increased utilization of FMTs would allow for better control of this increasingly problematic disease as well as lower costs associated with its management. PMID:29067223

The relationship between patient functional status and environmental contamination by Clostridium difficile: a pilot study

PubMed Central

Blakney, Rebekah; Gudnadottir, Unnur; Warrack, Simone; O'Horo, John C.; Anderson, Michael; Sethi, Ajay; Schmitz, Michelle; Wang, Jennifer; Duster, Megan; Ide, Emma; Safdar, Nasia

2016-01-01

Introduction Limited data exist on patient factors related to environmental contamination with Clostridium difficile. Methods We evaluated the association between the functional status of patients with C. difficile infection (CDI) and environmental contamination with C. difficile. Results Contamination of patient rooms was frequent and higher functional status was associated with contaminated surfaces remote from the bed. All but one environmental isolates matched the corresponding patient's stool isolate for the seven patients tested. Conclusion Functional status is a factor that influences environmental contamination with C. difficile. Future studies should evaluate strategies to reduce contamination in CDI patient rooms, taking into account the patient's functional status. PMID:25869819

Faecal lactoferrin and calprotectin in patients with Clostridium difficile infection: a case-control study.

PubMed

Barbut, F; Gouot, C; Lapidus, N; Suzon, L; Syed-Zaidi, R; Lalande, V; Eckert, C

2017-12-01

Calprotectin and lactoferrin are released by the gastrointestinal tract in response to infection and mucosal inflammation. Our objective was to assess the usefulness of quantifying faecal lactoferrin and calprotectin concentrations in Clostridium difficile infection (CDI) patients with or without free toxins in the stools. We conducted a single-centre 22-month case-control study. Patients with a positive CDI diagnosis were compared to two control groups: group 1 = diarrhoeic patients negative for C. difficile and matched (1:1) to CDI cases on the ward location and age, and group 2 = diarrhoeic patients colonised with a non-toxigenic strain of C. difficile. Faecal lactoferrin and calprotectin concentrations in faeces were determined for patients with CDI and controls. Of 135 patients with CDI, 87 (64.4%) had a positive stool cytotoxicity assay (free toxin) and 48 (35.6%) had a positive toxigenic culture without detectable toxins in the stools. The median lactoferrin values were 26.8 μg/g, 8.0 μg/g and 15.8 μg/g in CDI patients and groups 1 and 2, respectively. The median calprotectin values were 218.0 μg/g, 111.5 μg/g and 111.3 μg/g, respectively. Among patients with CDI, faecal lactoferrin and calprotectin levels were higher in those with free toxins in their stools (39.2 vs. 10.2 μg/g, p = 0.003 and 274.0 vs. 166.0 μg/g, p = 0.051, respectively). Both faecal calprotectin and lactoferrin were higher in patients with CDI, especially in those with detectable toxin in faeces, suggesting a correlation between intestinal inflammation and toxins in stools.

Update of treatment algorithms for Clostridium difficile infection.

PubMed

Ooijevaar, R E; van Beurden, Y H; Terveer, E M; Goorhuis, A; Bauer, M P; Keller, J J; Mulder, C J J; Kuijper, E J

2018-05-01

Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, both in healthcare facilities and in the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI. To review novel treatments and approaches for CDI, except probiotics and vaccines. We focused on new antibiotics, antibiotic inactivators, monoclonal antibodies and gut microbiota modulating therapies. A literature review was performed for clinical trials published in PubMed, Embase or Cochrane Library between January 2013 and November 2017. We analysed 28 clinical trials and identified 14 novel agents. Completed phase 2 studies were found for cadazolid, LFF571, ridinilazole and nontoxigenic C. difficile strains. Four phase 3 active comparator studies comparing vancomycin with bezlotoxumab, surotomycin (n = 2) and rifaximin have been published. Seven clinical trials for treatment of multiple recurrent CDI with faecal microbiota transplantation were analysed, describing faecal microbiota transplantation by upper or lower gastrointestinal route (n = 5) or by capsules (n = 2). Metronidazole is mentioned in the ESCMID guideline as first-line therapy, but we propose that oral vancomycin will become the first choice when antibiotic treatment for CDI is necessary. Fidaxomicin is a good alternative, especially in patients at risk of relapse. Vancomycin combined with faecal microbiota transplantation remains the primary therapy for multiple recurrent CDI. We anticipate that new medication that protects the gut microbiota will be further developed and tested to prevent CDI during antibiotic therapy. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Effectiveness of screening hospital admissions to detect asymptomatic carriers of Clostridium difficile: a modeling evaluation.

PubMed

Lanzas, Cristina; Dubberke, Erik R

2014-08-01

Both asymptomatic and symptomatic Clostridium difficile carriers contribute to new colonizations and infections within a hospital, but current control strategies focus only on preventing transmission from symptomatic carriers. Our objective was to evaluate the potential effectiveness of methods targeting asymptomatic carriers to control C. difficile colonization and infection (CDI) rates in a hospital ward: screening patients at admission to detect asymptomatic C. difficile carriers and placing positive patients into contact precautions. We developed an agent-based transmission model for C. difficile that incorporates screening and contact precautions for asymptomatic carriers in a hospital ward. We simulated scenarios that vary according to screening test characteristics, colonization prevalence, and type of strain present at admission. In our baseline scenario, on average, 42% of CDI cases were community-onset cases. Within the hospital-onset (HO) cases, approximately half were patients admitted as asymptomatic carriers who became symptomatic in the ward. On average, testing for asymptomatic carriers reduced the number of new colonizations and HO-CDI cases by 40%-50% and 10%-25%, respectively, compared with the baseline scenario. Test sensitivity, turnaround time, colonization prevalence at admission, and strain type had significant effects on testing efficacy. Testing for asymptomatic carriers at admission may reduce both the number of new colonizations and HO-CDI cases. Additional reductions could be achieved by preventing disease in patients who are admitted as asymptomatic carriers and developed CDI during the hospital stay.

Administration of probiotic kefir to mice with Clostridium difficile infection exacerbates disease.

PubMed

Spinler, Jennifer K; Brown, Aaron; Ross, Caná L; Boonma, Prapaporn; Conner, Margaret E; Savidge, Tor C

2016-08-01

Lifeway(®) kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Invasive listeriosis in a patient with several episodes of antibiotic associated colitis presumably due to Clostridium difficile.

PubMed

Carannante, Novella; Pagliano, Pasquale; Rossi, Marco; Attanasio, Vittorio; Rescigno, Carolina; Corte, Laura; Tascini, Carlo; Cardinali, Gianluigi

2017-06-01

A 62-year-old man developed a blood stream infection and meningitis due to Listeria monocytogenes, 20 days after an episode of pseudo-membranous colitis. The patient, hospitalized for the first time for transurethral prostatectomy, was readmitted 20 days later with watery diarrhea. Pseudo-membranous colitis was diagnosed and treated successfully, without testing for Clostridium difficile infection (CDI). After 15 more days, the patient developed again diarrhea, fever and confusion. Hospitalized again, blood and cerebrospinal fluid cultures resulted positive for L. monocytogenes. The patient was treated successfully and a diagnosis of recurrent CDI was confirmed following culture and nucleic acid amplification assays both positive for C. difficile. This is the first report of an invasive listeriosis after CDI underlines the importance of taking greater awareness in complicated blood stream infections that may arise after CDI.

High prevalence of Clostridium difficile on retail root vegetables, Western Australia.

PubMed

Lim, S C; Foster, N F; Elliott, B; Riley, T V

2018-02-01

The incidence of community-associated Clostridium difficile infection (CA-CDI) in Australia has increased since mid-2011. With reports of clinically important C. difficile strains being isolated from retail foods in Europe and North America, a foodborne source of C. difficile in cases of CA-CDI is a possibility. This study represents the first to investigate the prevalence and genotypes of C. difficile in Australian retail vegetables. A total of 300 root vegetables grown in Western Australia (WA) were collected from retail stores and farmers' markets. Three vegetables of the same kind bought from the same store/market were treated as one sample. Selective enrichment culture, toxin profiling and PCR ribotyping were performed. Clostridium difficile was isolated from 30% (30/100) of pooled vegetable samples, 55·6% of organic potatoes, 50% of nonorganic potatoes, 22·2% of organic beetroots, 5·6% of organic onions and 5·3% of organic carrots. Over half (51·2%, 22/43) the isolates were toxigenic. Many of the ribotypes of C. difficile isolated were common among human and Australian animals. Clostridium difficile could be found commonly on retail root vegetables of WA. This may be potential sources for CA-CDI. This study enhances knowledge of possible sources of C. difficile in the Australian community, outside the hospital setting. © 2017 The Society for Applied Microbiology.

Clostridium difficile infection in returning travellers

PubMed Central

Stevens, A. Michal; Esposito, Douglas H.; Stoney, Rhett J.; Hamer, Davidson H.; Flores-Figueroa, Jose; Bottieau, Emmanuel; Connor, Bradley A.; Gkrania-Klotsas, Effrossyni; Goorhuis, Abraham; Hynes, Noreen A.; Libman, Michael; Lopez-Velez, Rogelio; McCarthy, Anne E.; von Sonnenburg, Frank; Schwartz, Eli; van Genderen, Perry J.J.; Benson, L. Scott; Leung, Daniel T.

2017-01-01

Background There is increasing recognition of the contribution of community-acquired cases to the global burden of Clostridium difficile infection (CDI). The epidemiology of CDI among international travellers is poorly understood, and factors associated with international travel, such as antibiotic use and changes in gut microbiota, could potentially put travellers at higher risk. Methods We summarized demographic, travel-associated and geographic characteristics of travellers with CDI in the GeoSentinel database from 1997 to 2015. We also surveyed GeoSentinel sites to compare various testing indications, approaches, and diagnostic modalities. Results We identified 260 GeoSentinel records, including 187 that satisfied criteria for analysis (confirmed cases in non-immigrant travellers aged >2 years, seen <12 weeks post-travel). CDI was reported in all age groups and in travellers to all world regions; the largest proportions of cases having destinations in Asia (31%), Central/South America or the Caribbean (30%) and Africa (24%). Our site survey revealed substantial heterogeneity of testing approaches between sites; the most commonly used test was the C. difficile toxin gene PCR. Conclusions CDI is encountered in returning international travellers, although there is considerable variability in testing practices. These data underscore the importance of awareness of C. difficile as a potential cause of travel-associated diarrhoea. PMID:28355613

Containment of Clostridium difficile infection without reduction in antimicrobial use in Hong Kong.

PubMed

Cheng, V C C; Chau, P H; So, S Y C; Chen, J H K; Poon, R W S; Wong, S C Y; Hung, I F N; Lee, W M; Tai, J W M; Ho, P L; Yam, W C; Yuen, K Y

2015-07-01

Clostridium difficile ribotype 002 with hypersporulating capacity has been increasingly identified in Hong Kong. Proactive infection control measures are important to prevent the establishment of endemicity of C. difficile ribotype 002. A total of 329 patients with healthcare-associated C. difficile infection (CDI) were recruited in our healthcare network between 1 January 2008 and 30 June 2012 in this study. The incidence rates of healthcare-associated CDI per 10,000 admissions and 10,000 patient-days increased significantly by 15.3 and 17.0%, respectively, per quarter (p < 0.001) from 2008 1Q to 2010 1Q by segmented Poisson regression. With the full implementation of enhanced infection control interventions, there was an immediate significant reduction in both healthcare-associated CDI rates per 10,000 admissions and per 10,000 patient-days by 47% (p < 0.001) in 2010 2Q, followed by a further decline of CDI per 10,000 admissions and CDI per 10,000 patient-days by -19.4 and -19.8% from 2010 2Q to 2012 2Q, respectively (p < 0.001), despite a replacement of hand washing with soap and water by alcohol-based hand rub in the healthcare network. The proportion of C. difficile ribotype 002 was not statistically different (34/177, 19.2% vs. 25/152, 16.4%, p = 0.515), and the consumption of broad-spectrum antibiotics presented as divided daily dose per 1,000 acute bed-day occupancy per quarter remained unchanged (140.9 vs. 152.3) before and after infection control interventions. Our results suggested that the reduction of healthcare-associated CDI was attributable to infection control interventions instead of replacement of ribotypes or reduction in antimicrobial selective pressure.

Clostridium difficile binary toxin CDT

PubMed Central

Gerding, Dale N; Johnson, Stuart; Rupnik, Maja; Aktories, Klaus

2014-01-01

Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed. PMID:24253566

The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact

PubMed Central

Borren, Nienke Z.; Ghadermarzi, Shadi; Hutfless, Susan

2017-01-01

Background Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia. Methods We systematically searched PubMed/Medline and Embase for publications from Asia between 2000–16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk. Results Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%. Conclusions In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity. PMID:28463987

Prevalence of Clostridium difficile infection and colonization in a tertiary hospital and elderly community of North-Eastern Peninsular Malaysia.

PubMed

Zainul, N H; Ma, Z F; Besari, A; Siti Asma, H; Rahman, R A; Collins, D A; Hamid, N; Riley, T V; Lee, Y Y

2017-10-01

Little is known about Clostridium difficile infection (CDI) in Asia. The aims of our study were to explore (i) the prevalence, risk factors and molecular epidemiology of CDI and colonization in a tertiary academic hospital in North-Eastern Peninsular Malaysia; (ii) the rate of carriage of C. difficile among the elderly in the region; (iii) the awareness level of this infection among the hospital staffs and students. For stool samples collected from hospital inpatients with diarrhea (n = 76) and healthy community members (n = 138), C. difficile antigen and toxins were tested by enzyme immunoassay. Stool samples were subsequently analyzed by culture and molecular detection of toxin genes, and PCR ribotyping of isolates. To examine awareness among hospital staff and students, participants were asked to complete a self-administered questionnaire. For the hospital and community studies, the prevalence of non-toxigenic C. difficile colonization was 16% and 2%, respectively. The prevalence of CDI among hospital inpatients with diarrhea was 13%. Out of 22 C. difficile strains from hospital inpatients, the toxigenic ribotypes 043 and 017 were most common (both 14%). In univariate analysis, C. difficile colonization in hospital inpatients was significantly associated with greater duration of hospitalization and use of penicillin (both P < 0·05). Absence of these factors was a possible reason for low colonization in the community. Only 3% of 154 respondents answered all questions correctly in the awareness survey. C. difficile colonization is prevalent in a Malaysian hospital setting but not in the elderly community with little or no contact with hospitals. Awareness of CDI is alarmingly poor.

Association of healthcare exposure with acquisition of different Clostridium difficile strain types in patients with recurrent infection or colonization after clinical resolution of initial infection.

PubMed

Thabit, A K; Housman, S T; Burnham, C D; Nicolau, D P

2016-02-01

Following the resolution of an episode of Clostridium difficile infection (CDI), the factors associated with acquisition of different C. difficile strain types in patients with recurrent infection or persistent colonization have not been evaluated. To explore factors with potential correlation with acquisition of different C. difficile strain types in patients clinically cured of CDI through long-term follow-up across the continuum of care. Polymerase chain reaction ribotyping was performed on C. difficile isolates recovered at baseline and follow-up (days 19-38) from stool samples of patients successfully treated for CDI, and those who had recurrence and/or colonization following symptom resolution. Chart review was conducted to determine factors associated with acquisition of a different C. difficile ribotype. Of 25 patients initially cured of CDI, five had a recurrence and eight were colonized at follow-up. Patients did not differ with regard to age, sex, and whether the initial infection was with the BI/NAP1/027 strain. Ribotyping revealed that two out of five patients had recurrence attributed to a different strain type. Three of the colonized patients demonstrated strain switching compared with five patients who carried the same baseline strain. All patients (both infected and colonized) with different C. difficile ribotypes were exposed to the healthcare system. Exposure to antibiotics and proton pump inhibitors were not related to strain switching. Exposure to healthcare, but not to antibiotics or proton pump inhibitors, was consistently associated with recurrence or colonization with a different C. difficile ribotype. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Mutations associated with reduced surotomycin susceptibility in Clostridium difficile and Enterococcus species.

PubMed

Adams, Hannah M; Li, Xiang; Mascio, Carmela; Chesnel, Laurent; Palmer, Kelli L

2015-07-01

Clostridium difficile infection (CDI) is an urgent public health concern causing considerable clinical and economic burdens. CDI can be treated with antibiotics, but recurrence of the disease following successful treatment of the initial episode often occurs. Surotomycin is a rapidly bactericidal cyclic lipopeptide antibiotic that is in clinical trials for CDI treatment and that has demonstrated superiority over vancomycin in preventing CDI relapse. Surotomycin is a structural analogue of the membrane-active antibiotic daptomycin. Previously, we utilized in vitro serial passage experiments to derive C. difficile strains with reduced surotomycin susceptibilities. The parent strains used included ATCC 700057 and clinical isolates from the restriction endonuclease analysis (REA) groups BI and K. Serial passage experiments were also performed with vancomycin-resistant and vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis. The goal of this study is to identify mutations associated with reduced surotomycin susceptibility in C. difficile and enterococci. Illumina sequence data generated for the parent strains and serial passage isolates were compared. We identified nonsynonymous mutations in genes coding for cardiolipin synthase in C. difficile ATCC 700057, enoyl-(acyl carrier protein) reductase II (FabK) and cell division protein FtsH2 in C. difficile REA type BI, and a PadR family transcriptional regulator in C. difficile REA type K. Among the 4 enterococcal strain pairs, 20 mutations were identified, and those mutations overlap those associated with daptomycin resistance. These data give insight into the mechanism of action of surotomycin against C. difficile, possible mechanisms for resistance emergence during clinical use, and the potential impacts of surotomycin therapy on intestinal enterococci. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores

PubMed Central

Kochan, Travis J.; Kaiser, Alyssa M.; Hastie, Jessica L.; Giordano, Nicole P.; Smith, Ashley D.

2017-01-01

Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C. difficile infection (CDI) typically occurs after ingestion of infectious spores by a patient that has been treated with broad-spectrum antibiotics. While CDI is a toxin-mediated disease, transmission and pathogenesis are dependent on the ability to produce viable spores. These spores must become metabolically active (germinate) in order to cause disease. C. difficile spore germination occurs when spores encounter bile salts and other co-germinants within the small intestine, however, the germination signaling cascade is unclear. Here we describe a signaling role for Ca2+ during C. difficile spore germination and provide direct evidence that intestinal Ca2+ coordinates with bile salts to stimulate germination. Endogenous Ca2+ (released from within the spore) and a putative AAA+ ATPase, encoded by Cd630_32980, are both essential for taurocholate-glycine induced germination in the absence of exogenous Ca2+. However, environmental Ca2+ replaces glycine as a co-germinant and circumvents the need for endogenous Ca2+ fluxes. Cd630_32980 is dispensable for colonization in a murine model of C. difficile infection and ex vivo germination in mouse ileal contents. Calcium-depletion of the ileal contents prevented mutant spore germination and reduced WT spore germination by 90%, indicating that Ca2+ present within the gastrointestinal tract plays a critical role in C. difficile germination, colonization, and pathogenesis. These data provide a biological mechanism that may explain why individuals with inefficient intestinal calcium absorption (e.g., vitamin D deficiency, proton pump inhibitor use) are more prone to CDI and suggest that modulating free intestinal calcium is a potential strategy to curb the incidence of CDI. PMID:28704538

Clostridium difficile Infection in Children: Current State and Unanswered Questions

PubMed Central

Tamma, Pranita D.; Sandora, Thomas J.

2012-01-01

The incidence of Clostridium difficile infection (CDI) in children has increased over the past decade. In recent years, new and intriguing data on pediatric CDI have emerged. Community-onset infections are increasingly recognized, even in children who have not previously received antibiotics. A hypervirulent strain is responsible for up to 20% of pediatric CDI cases. Unique risk factors for CDI in children have been identified. Advances in diagnostic testing strategies, including the use of nucleic acid amplification tests, have raised new questions about the optimal approach to diagnosing CDI in children. Novel therapeutic options are available for adult patients with CDI, raising questions about the use of these agents in children. Updated recommendations about infection prevention and control measures are now available. We summarize these recent developments in pediatric CDI in this review and also highlight remaining knowledge gaps that should be addressed in future research efforts. PMID:23687578

Evaluating the Effectiveness of an Antimicrobial Stewardship Program on Reducing the Incidence Rate of Healthcare-Associated Clostridium difficile Infection: A Non-Randomized, Stepped Wedge, Single-Site, Observational Study.

PubMed

DiDiodato, Giulio; McArthur, Leslie

2016-01-01

The incidence rate of healthcare-associated Clostridium difficile infection (HA-CDI) is estimated at 1 in 100 patients. Antibiotic exposure is the most consistently reported risk factor for HA-CDI. Strategies to reduce the risk of HA-CDI have focused on reducing antibiotic utilization. Prospective audit and feedback is a commonly used antimicrobial stewardship intervention (ASi). The impact of this ASi on risk of HA-CDI is equivocal. This study examines the effectiveness of a prospective audit and feedback ASi on reducing the risk of HA-CDI. Single-site, 339 bed community-hospital in Barrie, Ontario, Canada. Primary outcome is HA-CDI incidence rate. Daily prospective and audit ASi is the exposure variable. ASi implemented across 6 wards in a non-randomized, stepped wedge design. Criteria for ASi; any intravenous antibiotic use for ≥ 48 hrs, any oral fluoroquinolone or oral second generation cephalosporin use for ≥ 48 hrs, or any antimicrobial use for ≥ 5 days. HA-CDI cases and model covariates were aggregated by ward, year and month starting September 2008 and ending February 2016. Multi-level mixed effect negative binomial regression analysis was used to model the primary outcome, with intercept and slope coefficients for ward-level random effects estimated. Other covariates tested for inclusion in the final model were derived from previously published risk factors. Deviance residuals were used to assess the model's goodness-of-fit. The dataset included 486 observation periods, of which 350 were control periods and 136 were intervention periods. After accounting for all other model covariates, the estimated overall ASi incidence rate ratio (IRR) was 0.48 (95% 0.30, 0.79). The ASi effect was independent of antimicrobial utilization. The ASi did not seem to reduce the risk of Clostridium difficile infection on the surgery wards (IRR 0.87, 95% CI 0.45, 1.69) compared to the medicine wards (IRR 0.42, 95% CI 0.28, 0.63). The ward-level burden of Clostridium difficile as measured by the ward's previous month's total CDI cases (CDI Lag) and the ward's current month's community-associated CDI cases (CA-CDI) was significantly associated with an increased risk of HA-CDI, with the estimated CDI Lag IRR of 1.21 (95% 1.15, 1.28) and the estimated CA-CDI IRR of 1.10 (95% CI 1.01, 1.20). The ward-level random intercept and slope coefficients were not significant. The final model demonstrated good fit. In this study, a daily prospective audit and feedback ASi resulted in a significant reduction in the risk of HA-CDI on the medicine wards, however, this effect was independent of an overall reduction in antibiotic utilization. In addition, the ward-level burden of Clostridium difficile was shown to significantly increase the risk of HA-CDI, reinforcing the importance of the environment as a source of HA-CDI.

Clostridium difficile infection in the elderly: an update on management.

PubMed

Asempa, Tomefa E; Nicolau, David P

2017-01-01

The burden of Clostridium difficile infection (CDI) is profound and growing. CDI now represents a common cause of health care-associated diarrhea, and is associated with significant morbidity, mortality, and health care costs. CDI disproportionally affects the elderly, possibly explained by the following risk factors: age-related impairment of the immune system, increasing antibiotic utilization, and frequent health care exposure. In the USA, recent epidemiological studies estimate that two out of every three health care-associated CDIs occur in patients 65 years or older. Additionally, the elderly are at higher risk for recurrent CDI. Existing therapeutic options include metronidazole, oral vancomycin, and fidaxomicin. Choice of agent depends on disease severity, history of recurrence, and, increasingly, the drug cost. Bezlotoxumab, a recently approved monoclonal antibody targeting C. difficile toxin B, offers an exciting advancement into immunologic therapies. Similarly, fecal microbiota transplantation is gaining popularity as an effective option mainly for recurrent CDI. The challenge of decreasing CDI burden in the elderly involves adopting preventative strategies, optimizing initial treatment, and decreasing the risk of recurrence. Expanded strategies are certainly needed to improve outcomes in this high-risk population. This review considers available data from prospective and retrospective studies as well as case reports to illustrate the merits and gaps in care related to the management of CDI in the elderly.

Clostridium difficile infection in the elderly: an update on management

PubMed Central

Asempa, Tomefa E; Nicolau, David P

2017-01-01

The burden of Clostridium difficile infection (CDI) is profound and growing. CDI now represents a common cause of health care–associated diarrhea, and is associated with significant morbidity, mortality, and health care costs. CDI disproportionally affects the elderly, possibly explained by the following risk factors: age-related impairment of the immune system, increasing antibiotic utilization, and frequent health care exposure. In the USA, recent epidemiological studies estimate that two out of every three health care–associated CDIs occur in patients 65 years or older. Additionally, the elderly are at higher risk for recurrent CDI. Existing therapeutic options include metronidazole, oral vancomycin, and fidaxomicin. Choice of agent depends on disease severity, history of recurrence, and, increasingly, the drug cost. Bezlotoxumab, a recently approved monoclonal antibody targeting C. difficile toxin B, offers an exciting advancement into immunologic therapies. Similarly, fecal microbiota transplantation is gaining popularity as an effective option mainly for recurrent CDI. The challenge of decreasing CDI burden in the elderly involves adopting preventative strategies, optimizing initial treatment, and decreasing the risk of recurrence. Expanded strategies are certainly needed to improve outcomes in this high-risk population. This review considers available data from prospective and retrospective studies as well as case reports to illustrate the merits and gaps in care related to the management of CDI in the elderly. PMID:29123385

A population-based longitudinal study of Clostridium difficile infection-related hospitalization in mid-age and older Australians.

PubMed

Chen, Y; Glass, K; Liu, B; Riley, T V; Korda, R; Kirk, M D

2017-02-01

Clostridium difficile is the principal cause of infectious diarrhoea in hospitalized patients. We investigated the incidence and risk factors for hospitalization due to C. difficile infection (CDI) in older Australians. We linked data from a population-based prospective cohort study (the 45 and Up Study) of 266 922 adults aged ⩾45 years recruited in New South Wales, Australia to hospitalization and death records for 2006-2012. We estimated the incidence of CDI hospitalization and calculated days in hospital and costs per hospitalization. We also estimated hazard ratios (HR) for CDI hospitalization using Cox regression with age as the underlying time variable. Over a total follow-up of 1 126 708 person-years, 187 adults had an incident CDI hospitalization. The crude incidence of CDI hospitalization was 16·6/100 000 person-years, with a median hospital stay of 6 days, and a median cost of AUD 6102 per admission. Incidence increased with age and year of follow-up, with a threefold increase for 2009-2012. After adjustment, CDI hospitalization rates were significantly lower in males than females (adjusted HR 0·6, 95% confidence interval 0·4-0·7). CDI hospitalization rates increased significantly over 2009-2012. There is a need to better understand the increasing risk of CDI hospitalization in women.

Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

PubMed Central

McFarland, Lynne Vernice; Ozen, Metehan; Dinleyici, Ener Cagri; Goh, Shan

2016-01-01

Antibiotic-associated diarrhea (AAD) and Clostridum difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics. PMID:27003987

Role of cephalosporins in the era of Clostridium difficile infection.

PubMed

Wilcox, Mark H; Chalmers, James D; Nord, Carl E; Freeman, Jane; Bouza, Emilio

2017-01-01

The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011-12 to 2012-13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Economic burden and cost-effective management of Clostridium difficile infections.

PubMed

Heimann, S M; Cruz Aguilar, M R; Mellinghof, S; Vehreschild, M J G T

2018-02-01

Clostridium difficile infection (CDI) is the most important cause of healthcare-associated infectious diarrhea in industrialized countries. We performed a literature review of the overall economic burden of initial and recurrent CDI as well as of the cost-effectiveness of the various treatment strategies applied in these settings. Even though analysis of health economic data is complicated by the limited comparability of results, our review identified several internationally consistent results. Authors from different countries have shown that recurrent CDI disproportionally contributes to the overall economic burden of CDI and therefore offers considerable saving potential. Subsequent cost-effectiveness analyses almost exclusively identified fidaxomicin as the preferred treatment option for initial CDI and fecal microbiota transplant (FMT) for recurrent CDI. Among the various FMT protocols, optimum results were obtained using early colonoscopy-based FMT. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Recent Progress for the Effective Prevention and Treatment of Recurrent Clostridium difficile Infection.

PubMed

Ramsay, Isobel; Brown, Nicholas M; Enoch, David A

2018-01-01

Recurrence occurs in approximately 25% of all cases of Clostridium difficile infection (CDI) and poses a unique clinical challenge. Traditionally, treatment options of CDI have been limited to regimes of established antibiotics (eg, pulsed/tapered vancomycin) but faecal transplantation is emerging as a useful alternative. In recent years, promising new strategies have emerged for effective prevention of recurrent CDI (rCDI) including new antimicrobials (eg, fidaxomicin) and monoclonal antibodies (eg, bezlotoxumab). Despite promising progress in this area, obstacles remain for making the best use of these resources due to uncertainty over patient selection. This commentary describes the current epidemiology of rCDI, its clinical impact and risk factors, some of the measures used for treating and preventing rCDI, and some of the emerging treatment options. It then describes some of the obstacles that need to be overcome.

Burden of Clostridium difficile-associated disease among patients residing in nursing homes: a population-based cohort study.

PubMed

Yu, Holly; Baser, Onur; Wang, Li

2016-11-25

Clostridium difficile (C. difficile) infection (CDI) is the leading cause of nosocomial diarrhea in the United States. This study aimed to examine the incidence of CDI and evaluate mortality and economic burden of CDI in an elderly population who reside in nursing homes (NHs). This was a population-based retrospective cohort study focusing on US NHs by linking Medicare 5% sample, Medicaid, Minimum Data Set (MDS) (2008-10). NH residents aged ≥65 years with continuous enrollment in Medicare and/or Medicaid Fee-for-Service plan for ≥12 months and ≥2 quarterly MDS assessments were eligible for the study. The incidence rate was calculated as the number of CDI episodes by 100,000 person-years. A 1:4 propensity score matched sample of cohorts with and without CDI was generated to assess mortality and health care costs following the first CDI. Among 32,807 NH residents, 941 residents had ≥1 episode of CDI in 2009, with an incidence of 3359.9 per 100,000 person-years. About 30% CDI episodes occurred in the hospital setting. NH residents with CDI (vs without CDI) were more likely to have congestive heart failure, renal disease, cerebrovascular disease, hospitalizations, and outpatient antibiotic use. During the follow-up period, the 30-day (14.7% vs 4.3%, P < 0.001), 60-day (22.7% vs 7.5%, P < 0.001), 6-month (36.3% vs 18.3%, P < 0.001), and 1-year mortality rates (48.2% vs 31.1%, P < 0.001) were significantly higher among the CDI residents vs non-CDI residents. Total health care costs within 2 months following the first CDI episode were also significantly higher for CDI residents ($28,621 vs $13,644, P < 0.001). CDI presents a serious public health issue in NHs. Mortality, health care utilization, and associated costs were significant following incident CDI episodes.

Current Trends in the Epidemiology and Outcomes of Clostridium difficile Infection.

PubMed

Evans, Charlesnika T; Safdar, Nasia

2015-05-15

Clostridium difficile is the most frequently identified cause of nosocomial diarrhea and has been associated with epidemics of diarrhea in hospitals and long-term care facilities. The continued increase in C. difficile infection (CDI) suggests that it has surpassed other pathogens in causing healthcare-associated infections. The Centers for Disease Control and Prevention recently identified CDI as an "urgent threat" in its recent report on antibiotic resistance threats in the United States, highlighting the need for urgent and aggressive action to prevent this infection. The impact of antibiotics as a risk factor for new-onset CDI is well established; however, recognizing classes of antibiotics with the highest risks and reducing unnecessary antibiotic use are important strategies for prevention of CDI and subsequent recurrence. In addition, the recognition of the community as an important setting for onset of CDI presents a challenge and is an area for future research. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Cost-effectiveness in Clostridium difficile treatment decision-making

PubMed Central

Nuijten, Mark JC; Keller, Josbert J; Visser, Caroline E; Redekop, Ken; Claassen, Eric; Speelman, Peter; Pronk, Marja H

2015-01-01

AIM: To develop a framework for the clinical and health economic assessment for management of Clostridium difficile infection (CDI). METHODS: CDI has vast economic consequences emphasizing the need for innovative and cost effective solutions, which were aim of this study. A guidance model was developed for coverage decisions and guideline development in CDI. The model included pharmacotherapy with oral metronidazole or oral vancomycin, which is the mainstay for pharmacological treatment of CDI and is recommended by most treatment guidelines. RESULTS: A design for a patient-based cost-effectiveness model was developed, which can be used to estimate the cost-effectiveness of current and future treatment strategies in CDI. Patient-based outcomes were extrapolated to the population by including factors like, e.g., person-to-person transmission, isolation precautions and closing and cleaning wards of hospitals. CONCLUSION: The proposed framework for a population-based CDI model may be used for clinical and health economic assessments of CDI guidelines and coverage decisions for emerging treatments for CDI. PMID:26601096

Cost-effectiveness in Clostridium difficile treatment decision-making.

PubMed

Nuijten, Mark Jc; Keller, Josbert J; Visser, Caroline E; Redekop, Ken; Claassen, Eric; Speelman, Peter; Pronk, Marja H

2015-11-16

To develop a framework for the clinical and health economic assessment for management of Clostridium difficile infection (CDI). CDI has vast economic consequences emphasizing the need for innovative and cost effective solutions, which were aim of this study. A guidance model was developed for coverage decisions and guideline development in CDI. The model included pharmacotherapy with oral metronidazole or oral vancomycin, which is the mainstay for pharmacological treatment of CDI and is recommended by most treatment guidelines. A design for a patient-based cost-effectiveness model was developed, which can be used to estimate the cost-effectiveness of current and future treatment strategies in CDI. Patient-based outcomes were extrapolated to the population by including factors like, e.g., person-to-person transmission, isolation precautions and closing and cleaning wards of hospitals. The proposed framework for a population-based CDI model may be used for clinical and health economic assessments of CDI guidelines and coverage decisions for emerging treatments for CDI.

High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection.

PubMed

Wadhwa, A; Al Nahhas, M F; Dierkhising, R A; Patel, R; Kashyap, P; Pardi, D S; Khanna, S; Grover, M

2016-09-01

Infectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post-infectious IBS (PI-IBS) development following CDI and the host- and infection-related risk factors are not known. To determine the incidence and risk factors for PI-IBS following CDI. A total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI-IBS development. A total of 315 CDI cases responded (46% response rate) and 205 were at-risk (no pre-CDI IBS) for PI-IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS-mixed was most common followed by IBS-diarrhoea. In comparison to those without subsequent PI-IBS, greater percentage of PI-IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI-IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06). In this cohort study, new-onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI-IBS. This chronic sequela should be considered during active management and follow-up of patients with CDI. © 2016 John Wiley & Sons Ltd.

Risk Factors, Clinical Characteristics, and Treatment Differences Between Residents With and Without Nursing Home- and Non-Nursing Home-Acquired Clostridium difficile Infection.

PubMed

Zarowitz, Barbara J; Allen, Carrie; O'Shea, Terrence; Strauss, Marcie E

2015-07-01

The incidence of Clostridium difficile infection (CDI) in nursing home residents is believed to be high because of the prevalence of predisposing factors such as decreased immune response, multiple comorbidities, medications, increased risk of infection, close proximity of residents, and recent hospitalization. Yet, specific information on CDI in this population is scarce.  To investigate differences in clinical and demographic characteristics, treatment, and underlying comorbidities in residents who acquired CDI preadmission (non-nursing home-acquired [NNH-Acquired]) compared with those who acquired CDI after admission to a nursing home (nursing home-acquired [NH-Acquired]) and matched controls. We conducted a retrospective case-control study of CDI in nursing home residents with a cross-sectional and longitudinal aspect of linked and de-identified pharmacy claims and Minimum Data Set data (MDS) 2.0 records from October 1, 2009, to September 30, 2010. The control group was frequency matched 1:1 for gender, race, and age range to residents with CDI.  Of 195,498 residents, 5,044 (2.6%) had a diagnosis of CDI. Compared with controls, CDI patients had less severe cognitive impairment (P  less than  0.01) and more severe functional impairment (P  less than  0.01), incontinence (P  less than  0.01), and diarrhea (P  less than  0.01). They were more likely to (a) have diabetes, stroke, heart failure, cancer, renal failure, and infections; (b) be treated with antibiotics, corticosteroids, megestrol, and proton pump inhibitors; and (c) be discharged to the hospital (29.3% vs. 14.7%, P = 0.001) than controls. NNH-Acquired CDI was 3 times more prevalent than NH-Acquired CDI. Most residents with NNH-Acquired CDI (85.0%) came from acute care hospitals and were more likely to have heart disease, cancer, and infections, while those with NH-Acquired CDI tended to have more cognitive impairment, reliance on staff for activities of daily living, incontinence, and stroke. Thirty-day retreatment rates for NH-Acquired CDI and NNH-Acquired CDI with metronidazole were 72.7% and 68.4%, and with vancomycin were 83.9% and 69.3%, respectively. The facility (Medicare Part A) was the payer for 93.6% of NNH-Acquired CDI and 75% of NH-Acquired CDI treatment; Medicare Part D was the prevalent secondary payer for NNH-Aquired CDI (19.4%) and NH-Acquired CDI (37.5%). Residents with CDI had more comorbidities, and the NNH-Acquired group bore a higher burden of illness, resulting in differing treatment patterns and outcomes than the NH-Acquired CDI group.

Clostridium difficile infection in Thailand.

PubMed

Putsathit, Papanin; Kiratisin, Pattarachai; Ngamwongsatit, Puriya; Riley, Thomas V

2015-01-01

Clostridium difficile is the aetiological agent in ca. 20% of cases of antimicrobial-associated diarrhoea in hospitalised adults. Diseases caused by this organism range from mild diarrhoea to occasional fatal pseudomembranous colitis. The epidemiology of C. difficile infection (CDI) has changed notably in the past decade, following epidemics in the early 2000s of PCR ribotype (RT) 027 infection in North America and Europe, where there was an increase in disease severity and mortality. Another major event has been the emergence of RT 078, initially as the predominant ribotype in production animals in the USA and Europe, and then in humans in Europe. Although there have been numerous investigations of the epidemiology of CDI in North America and Europe, limited studies have been undertaken elsewhere, particularly in Asia. Antimicrobial exposure remains the major risk factor for CDI. Given the high prevalence of indiscriminate and inappropriate use of antimicrobials in Asia, it is conceivable that CDI is relatively common among humans and animals. This review describes the level of knowledge in Thailand regarding C. difficile detection methods, prevalence and antimicrobial susceptibility profile, as well as the clinical features of, treatment options for and outcomes of the disease. In addition, antimicrobial usage in livestock in Thailand will be reviewed. A literature search yielded 18 studies mentioning C. difficile in Thailand, a greater number than from any other Asian country. It is possible that the situation in Thailand in relation to CDI may mirror the situation in other developing Asians countries. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

[Individualized treatment strategies for Clostridium difficile infections].

PubMed

Solbach, P; Dersch, P; Bachmann, O

2017-07-01

Upon hospitalization, up to 15.5% of patients are already colonized with a toxigenic Clostridium difficile strain (TCD). The rate of asymptomatic colonization is 0-3% in healthy adults and up to 20-40% in hospitalized patients. The incidence and mortality of C. difficile infection (CDI) has significantly increased during recent years. Mortality lies between 3 and 14%. CDI is generally caused by intestinal dysbiosis, which can be triggered by various factors, including antibiotics or immune suppressants. If CDI occurs, ongoing antibiotic therapy should be discontinued. The choice of treatment is guided by the clinical situation: Mild courses of CDI should be treated with metronidazole. Oral vancomycin is suitable as a first-line therapy of mild CDI occurring during pregnancy and lactation, as well as in cases of intolerance or allergy to metronidazole. Severe courses should be treated with vancomycin. Recurrence should be treated with vancomycin or fidaxomicin. Multiple recurrences should be treated with vancomycin or fidaxomicin; if necessary, a vancomycin taper regimen may also be used. An alternative is fecal microbiota transplant (FMT), with healing rates of more than 80%. Bezlotoxumab is the first available monoclonal antibody which neutralizes the C. difficile toxin B, and in combination with an antibiotic significantly reduces the rate of a new C. difficile infection compared to placebo. A better definition of clinical and microbiota-associated risk factors and the ongoing implementation of molecular diagnostics are likely to lead to optimized identification of patients at risk, and an increasing individualization of prophylactic and therapeutic approaches.

Laboratory diagnosis of Clostridium difficile infection: Comparison of Techlab C. diff Quik Chek Complete, Xpert C. difficile, and multistep algorithmic approach.

PubMed

Seo, Ja Young; Jeong, Ji Hun; Kim, Kyung Hee; Ahn, Jeong-Yeal; Park, Pil-Whan; Seo, Yiel-Hea

2017-11-01

Clostridium difficile is a major pathogen responsible for nosocomial infectious diarrhea. We explored optimal laboratory strategies for diagnosis of C. difficile infection (CDI) in our clinical settings, a 1400-bed tertiary care hospital. Using 191 fresh stool samples from adult patients, we evaluated the performance of Xpert C. difficile (Xpert CD), C. diff Quik Chek Complete (which simultaneously detects glutamate dehydrogenase [GDH] and C. difficile toxins [CDT]), toxigenic culture, and a two-step algorithm composed of GDH/CDT as a screening test and Xpert CD as a confirmatory test. Clostridium difficile was detected in 35 samples (18.3%), and all isolates were toxigenic strains. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of each assay for detecting CDI were as follows: Quik Chek Complete CDT (45.7%, 100%, 100%, 89.1%), Quik Chek Complete GDH (97.1%, 99.4%, 97.1%, 99.4%), Xpert CD (94.3%, 100%, 100%, 98.7%), and toxigenic culture (91.4%, 100%, 100%, 98.1%). A two-step algorithm performed identically with Xpert CD assay. Our data showed that most C. difficile isolates from adult patients were toxigenic. We demonstrated that a two-step algorithm based on GDH/CDT assay followed by Xpert CD assay as a confirmatory test was rapid, reliable, and cost effective for diagnosis of CDI in an adult patient setting with high prevalence of toxigenic C. difficile. © 2017 Wiley Periodicals, Inc.

Clostridium difficile contamination of health care workers' hands and its potential contribution to the spread of infection: Review of the literature.

PubMed

Jullian-Desayes, Ingrid; Landelle, Caroline; Mallaret, Marie-Reine; Brun-Buisson, Christian; Barbut, Frédéric

2017-01-01

Clostridium difficile infection (CDI) can be transmitted from patient to patient by the hands of health care workers (HCWs); however, the relative importance of this route in the spread of C difficile in the hospital is currently unknown. Our aim was to review studies examining HCWs' hand carriage and its potential role in CDI transmission. First, English-speaking references addressing HCWs' hand sampling obtained from the PubMed database were reviewed. Second, C difficile outbreaks definitely or probably implicating HCWs were retrieved from the Outbreak Database Web site (www.outbreak-database.com). Finally, cases of C difficile occurring in HCWs after contact with an infected patient were retrieved from PubMed. A total of 11 studies dealing with HCWs' hand carriage were selected and reviewed. Between 0% and 59% of HCWs' hands were found contaminated with C difficile after caring for a patient with CDI. There were several differences between studies regarding site of hands sampling, timing after contact, and bacteriologic methods. Only 2 C difficile outbreaks implicating HCWs and 6 series of cases of transmission from patients to HCWs have been reported. This review shows that HCWs' hands could play an important role in the transmission of C difficile. Hand hygiene and reduction of environmental contamination are essential to control C difficile transmission. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Severity and frequency of community-onset Clostridium difficile infection on an Australian tertiary referral hospital campus.

PubMed

Clohessy, Penny; Merif, Juan; Post, Jeffrey John

2014-12-01

Clostridium difficile infection (CDI) is increasingly being found in populations without traditional risk factors. We compared the relative frequency, risk factors, severity, and outcomes of community-onset CDI with hospital-acquired infection. This was a retrospective, observational study of CDI at a tertiary hospital campus in Sydney, Australia. Patients aged 15 years and older with a first episode of CDI from January 1 to December 31, 2011 were included. CDI was defined as the presence of diarrhoea with a positive enzyme immunoassay in conjunction with a positive cell cytotoxicity assay, toxin culture, or organism culture. Main outcome measures were onset of infection (hospital or community), risk factors, markers of severity, and outcomes for the two groups. One hundred and twenty-nine cases of CDI infection were identified, of which 38 (29%) were community-onset. The community-onset infection group were less likely to have a recent history of antibiotic use (66% vs. 98%; p<0.001) or proton pump inhibitor use (38% vs. 69%; p=0.03) than the hospital-acquired infection group. Markers of severity and outcomes were similar in the two groups, with an overall mortality of 9%. Community-onset CDI accounts for a large proportion of C. difficile infections and has a similar potential for severe disease as hospital-acquired infection. Using a history of previous antibiotic use, proton pump inhibitor use, or recent hospitalization to predict cases is unreliable. We recommend that patients with diarrhoea being investigated in emergency departments and community practice are tested for Clostridium difficile infection. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile Associated Risk of Death Score (CARDS): A novel severity score to predict mortality among hospitalized patients with Clostridium difficile infection

PubMed Central

Kassam, Zain; Fabersunne, Camila Cribb; Smith, Mark B.; Alm, Eric J.; Kaplan, Gilaad G.; Nguyen, Geoffrey C.; Ananthakrishnan, Ashwin N.

2016-01-01

Background Clostridium difficile infection (CDI) is public health threat and associated with significant mortality. However, there is a paucity of objectively derived CDI severity scoring systems to predict mortality. Aims To develop a novel CDI risk score to predict mortality entitled: Clostridium difficile Associated Risk of Death Score (CARDS). Methods We obtained data from the United States 2011 Nationwide Inpatient Sample (NIS) database. All CDI-associated hospitalizations were identified using discharge codes (ICD-9-CM, 008.45). Multivariate logistic regression was utilized to identify independent predictors of mortality. CARDS was calculated by assigning a numeric weight to each parameter based on their odds ratio in the final logistic model. Predictive properties of model discrimination were assessed using the c-statistic and validated in an independent sample using the 2010 NIS database. Results We identified 77,776 hospitalizations, yielding an estimate of 374,747 cases with an associated diagnosis of CDI in the United States, 8% of whom died in the hospital. The 8 severity score predictors were identified on multivariate analysis: age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease and ICU admission, with weights ranging from −1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1.2% with a CARDS of 0 compared to 100% with CARDS of 18. The model performed equally well in our validation cohort. Conclusion CARDS is a promising simple severity score to predict mortality among those hospitalized with CDI. PMID:26849527

Diversity and Evolution in the Genome of Clostridium difficile

PubMed Central

Knight, Daniel R.; Elliott, Briony; Chang, Barbara J.; Perkins, Timothy T.

2015-01-01

SUMMARY Clostridium difficile infection (CDI) is the leading cause of antimicrobial and health care-associated diarrhea in humans, presenting a significant burden to global health care systems. In the last 2 decades, PCR- and sequence-based techniques, particularly whole-genome sequencing (WGS), have significantly furthered our knowledge of the genetic diversity, evolution, epidemiology, and pathogenicity of this once enigmatic pathogen. C. difficile is taxonomically distinct from many other well-known clostridia, with a diverse population structure comprising hundreds of strain types spread across at least 6 phylogenetic clades. The C. difficile species is defined by a large diverse pangenome with extreme levels of evolutionary plasticity that has been shaped over long time periods by gene flux and recombination, often between divergent lineages. These evolutionary events are in response to environmental and anthropogenic activities and have led to the rapid emergence and worldwide dissemination of virulent clonal lineages. Moreover, genome analysis of large clinically relevant data sets has improved our understanding of CDI outbreaks, transmission, and recurrence. The epidemiology of CDI has changed dramatically over the last 15 years, and CDI may have a foodborne or zoonotic etiology. The WGS era promises to continue to redefine our view of this significant pathogen. PMID:26085550

Predicting the risk for hospital-onset Clostridium difficile infection (HO-CDI) at the time of inpatient admission: HO-CDI risk score.

PubMed

Tabak, Ying P; Johannes, Richard S; Sun, Xiaowu; Nunez, Carlos M; McDonald, L Clifford

2015-06-01

To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission Retrospective data analysis Six US acute care hospitals Adult inpatients We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations. Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76-0.81) with good calibration. Among 79% of patients with risk scores of 0-7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001). Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.

Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children.

PubMed

Sammons, Julia Shaklee; Localio, Russell; Xiao, Rui; Coffin, Susan E; Zaoutis, Theoklis

2013-07-01

Clostridium difficile infection (CDI) is associated with significant morbidity and mortality among adults. However, outcomes are poorly defined among children. A retrospective cohort study was performed among hospitalized children at 41 children's hospitals between January 2006 and August 2011. Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed) based on the probability of developing CDI (propensity score derived from patient characteristics). Exposed subjects were stratified by C. difficile test date, suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were analyzed for matched subjects. We identified 5107 exposed and 693 409 unexposed subjects. Median age was 6 years (interquartile range [IQR], 2-13 years) for exposed and 8 years (IQR, 3-14 years) for unexposed subjects. Of these, 4474 exposed were successfully matched to 8821 unexposed by propensity score. In-hospital mortality differed significantly (CDI, 1.43% vs matched unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and matched subjects. However, mortality rates were significantly greater among HO-CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval {CI}, 3.77-12.02]). Mean differences in length of stay (LOS) and total cost were significant: 5.55 days (95% CI, 4.54-6.56 days) and $18 900 (95% CI, $15 100-$22 700) for CO-CDI, and 21.60 days (95% CI, 19.29-23.90 days) and $93 600 (95% CI, $80 000-$107 200) for HO-CDI. Pediatric CDI is associated with increased mortality, longer LOS, and higher costs. These findings underscore the importance of antibiotic stewardship and infection control programs to prevent this disease in children.

Clostridium difficile Infection Is Associated With Increased Risk of Death and Prolonged Hospitalization in Children

PubMed Central

Sammons, Julia Shaklee; Localio, Russell; Xiao, Rui; Coffin, Susan E.; Zaoutis, Theoklis

2013-01-01

Background Clostridium difficile infection (CDI) is associated with significant morbidity and mortality among adults. However, outcomes are poorly defined among children. Methods A retrospective cohort study was performed among hospitalized children at 41 children's hospitals between January 2006 and August 2011. Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed) based on the probability of developing CDI (propensity score derived from patient characteristics). Exposed subjects were stratified by C. difficile test date, suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were analyzed for matched subjects. Results We identified 5107 exposed and 693 409 unexposed subjects. Median age was 6 years (interquartile range [IQR], 2–13 years) for exposed and 8 years (IQR, 3–14 years) for unexposed subjects. Of these, 4474 exposed were successfully matched to 8821 unexposed by propensity score. In-hospital mortality differed significantly (CDI, 1.43% vs matched unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and matched subjects. However, mortality rates were significantly greater among HO-CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval {CI}, 3.77–12.02]). Mean differences in length of stay (LOS) and total cost were significant: 5.55 days (95% CI, 4.54–6.56 days) and $18 900 (95% CI, $15 100–$22 700) for CO-CDI, and 21.60 days (95% CI, 19.29–23.90 days) and $93 600 (95% CI, $80 000–$107 200) for HO-CDI. Conclusions Pediatric CDI is associated with increased mortality, longer LOS, and higher costs. These findings underscore the importance of antibiotic stewardship and infection control programs to prevent this disease in children. PMID:23532470

Diverticular disease of the colon does not increase risk of repeat C. difficile infection.

PubMed

Feuerstadt, Paul; Das, Rohit; Brandt, Lawrence J

2013-01-01

Studies have suggested that colonic diverticulosis might increase the likelihood of repeat Clostridium difficile infection (CDI). Our study was designed to compare rates of repeat infection in patients with and without colon diverticula. Patients who had a positive C. difficile toxin assay and colonoscopic evidence of diverticulosis were classified as CDI and diverticulosis (CDI-D), whereas those with a positive toxin assay but no such colonoscopic evidence were classified as CDI and no diverticulosis (CDI-ND). Various clinical and epidemiologic factors were recorded for each patient. Primary outcomes were "relapse" (repeat CDI within 3 mo of initial infection) and "recurrent" infection (repeat CDI≥3 mo after initial infection). Secondary outcomes 30 days after diagnosis were mortality, intensive care unit transfer, and continuous hospitalization. A total of 128 patients were classified as CDI-D, whereas 137 had CDI-ND. There were no significant differences between CDI-D and CDI-ND when comparing frequencies of repeat infection and its subclassifications, relapse or recurrence. There were, however, statistical associations seen between diverticulosis of the ascending colon and increased recurrence rates [hazard ratio (HR): 1.4±0.38, P<0.05] and decreased rates of relapse in diverticular disease of the descending (HR: 0.40±0.46, P<0.05), and sigmoid colon (HR: 0.39±0.49, P<0.05). The ascending colon association is limited by a small patient population. There were no significant differences in any of the 30-day outcomes including intensive care unit requirement, hospitalization stay, or mortality. Patients with diverticular disease of the colon are not at increased risk of repeat CDI.

An agent-based simulation model for Clostridium difficile infection control.

PubMed

Codella, James; Safdar, Nasia; Heffernan, Rick; Alagoz, Oguzhan

2015-02-01

Control of Clostridium difficile infection (CDI) is an increasingly difficult problem for health care institutions. There are commonly recommended strategies to combat CDI transmission, such as oral vancomycin for CDI treatment, increased hand hygiene with soap and water for health care workers, daily environmental disinfection of infected patient rooms, and contact isolation of diseased patients. However, the efficacy of these strategies, particularly for endemic CDI, has not been well studied. The objective of this research is to develop a valid, agent-based simulation model (ABM) to study C. difficile transmission and control in a midsized hospital. We develop an ABM of a midsized hospital with agents such as patients, health care workers, and visitors. We model the natural progression of CDI in a patient using a Markov chain and the transmission of CDI through agent and environmental interactions. We derive input parameters from aggregate patient data from the 2007-2010 Wisconsin Hospital Association and published medical literature. We define a calibration process, which we use to estimate transition probabilities of the Markov model by comparing simulation results to benchmark values found in published literature. In a comparison of CDI control strategies implemented individually, routine bleach disinfection of CDI-positive patient rooms provides the largest reduction in nosocomial asymptomatic colonization (21.8%) and nosocomial CDIs (42.8%). Additionally, vancomycin treatment provides the largest reduction in relapse CDIs (41.9%), CDI-related mortalities (68.5%), and total patient length of stay (21.6%). We develop a generalized ABM for CDI control that can be customized and further expanded to specific institutions and/or scenarios. Additionally, we estimate transition probabilities for a Markov model of natural CDI progression in a patient through calibration. © The Author(s) 2014.

Prevalence of Clostridium difficile infection among the patients attending a tertiary care teaching hospital.

PubMed

Segar, Lavanya; Easow, Joshy M; Srirangaraj, Sreenivasan; Hanifah, Mohammad; Joseph, Noyal M; Seetha, K S

2017-01-01

Clostridium difficile, a most important nosocomial enteric pathogen, is recognized globally as responsible for antibiotic-associated diarrhea and colitis. It is associated with considerable morbidity and mortality due to widespread use of antibiotics. The study was done to determine the prevalence of C. difficile infection (CDI) among the patients attending a tertiary care teaching hospital in Puducherry. We performed a prospective cohort study in Mahatma Gandhi Medical College and Research Institute. Around 150 patients were evaluated along with the patient details. C. difficile toxin detection was done as per the standard algorithm using the C. Diff Quik Chek Complete® assay (TECHLAB, Blacksburg, VA, USA). Analysis was done using statistics software (SPSS 16.0, SPSS Inc., Chicago, IL, USA). The prevalence of CDI was found to be 4%. More toxin-positive cases were between 50 and 60 years of age, and there was no difference in gender. Intensive Care Unit showed more toxin-positive cases; however, there was no significant association between the occurrence of CDI and the primary diagnosis of the patients. The prevalence of CDI in our hospital was found to be 4%, which was relatively lower compared to other Indian studies. However, awareness of the risk factors may assist in identifying patients at higher risk for CDI, guide implementation of appropriate preventive measures, and modulate potential intervention measure during management.

Clostridium difficile infection in returning travellers.

PubMed

Michal Stevens, A; Esposito, Douglas H; Stoney, Rhett J; Hamer, Davidson H; Flores-Figueroa, Jose; Bottieau, Emmanuel; Connor, Bradley A; Gkrania-Klotsas, Effrossyni; Goorhuis, Abraham; Hynes, Noreen A; Libman, Michael; Lopez-Velez, Rogelio; McCarthy, Anne E; von Sonnenburg, Frank; Schwartz, Eli; van Genderen, Perry J J; Scott Benson, L; Leung, Daniel T

2017-05-01

There is increasing recognition of the contribution of community-acquired cases to the global burden of Clostridium difficile infection (CDI). The epidemiology of CDI among international travellers is poorly understood, and factors associated with international travel, such as antibiotic use and changes in gut microbiota, could potentially put travellers at higher risk. We summarized demographic, travel-associated and geographic characteristics of travellers with CDI in the GeoSentinel database from 1997 to 2015. We also surveyed GeoSentinel sites to compare various testing indications, approaches, and diagnostic modalities. We identified 260 GeoSentinel records, including 187 that satisfied criteria for analysis (confirmed cases in non-immigrant travellers aged >2 years, seen <12 weeks post-travel). CDI was reported in all age groups and in travellers to all world regions; the largest proportions of cases having destinations in Asia (31%), Central/South America or the Caribbean (30%) and Africa (24%). Our site survey revealed substantial heterogeneity of testing approaches between sites; the most commonly used test was the C. difficile toxin gene PCR. CDI is encountered in returning international travellers, although there is considerable variability in testing practices. These data underscore the importance of awareness of C. difficile as a potential cause of travel-associated diarrhoea. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Clostridium difficile Infection and Fecal Microbiota Transplant

PubMed Central

Liubakka, Alyssa; Vaughn, Byron P.

2017-01-01

Clostridium difficile infection (CDI) is a major source of morbidity and mortality for hospitalized patients. Although most patients have a clinical response to existing antimicrobial therapies, recurrent infection develops in up to 30% of patients. Fecal microbiota transplant is a novel approach to this complex problem, with an efficacy rate of nearly 90% in the setting of multiple recurrent CDI. This review covers the current epidemiology of CDI (including toxigenic and nontoxigenic strains, risk factors for infection, and recurrent infection), methods of diagnosis, existing first-line therapies in CDI, the role of fecal microbiota transplant for multiple recurrent CDIs, and the potential use of fecal microbial transplant for patients with severe or refractory infection. PMID:27959316

Recent Progress for the Effective Prevention and Treatment of Recurrent Clostridium difficile Infection

PubMed Central

Ramsay, Isobel; Brown, Nicholas M; Enoch, David A

2018-01-01

Recurrence occurs in approximately 25% of all cases of Clostridium difficile infection (CDI) and poses a unique clinical challenge. Traditionally, treatment options of CDI have been limited to regimes of established antibiotics (eg, pulsed/tapered vancomycin) but faecal transplantation is emerging as a useful alternative. In recent years, promising new strategies have emerged for effective prevention of recurrent CDI (rCDI) including new antimicrobials (eg, fidaxomicin) and monoclonal antibodies (eg, bezlotoxumab). Despite promising progress in this area, obstacles remain for making the best use of these resources due to uncertainty over patient selection. This commentary describes the current epidemiology of rCDI, its clinical impact and risk factors, some of the measures used for treating and preventing rCDI, and some of the emerging treatment options. It then describes some of the obstacles that need to be overcome. PMID:29535530

Clostridium difficile infection in solid organ transplant recipients.

PubMed

Nanayakkara, Deepa; Nanda, Neha

2017-08-01

Clostridium difficile infection (CDI) is a major healthcare-associated infection that causes significant morbidity and an economic impact in the United States. In this review, we provide an overview of Clostridium difficile infection in solid organ transplant recipients with an emphasis on recent literature. C. difficile in solid organ transplant population has unique risk factors. Fecal microbiota transplantation has shown favorable results in treatment of recurrent C. difficile in this population. Preliminary data from animal studies suggests excellent efficacy with immunization against C. difficile toxins. Over the last decade, number of individuals receiving solid organ transplants has increased exponentially making peri-transplant complications a common occurrence.C. difficile is a frequent cause of morbidity in solid organ transplant recipients. Early and accurate diagnosis of C. difficile requires a stepwise approach. Differentiating between asymptomatic carriage and infection is a diagnostic challenge. Microbial diversity is inversely proportional to risk of C. difficile infection. Antimicrobial stewardship programs help to retain microbial diversity in individuals susceptible to CDI. Recurrent or relapsing C. difficile infection require fecal microbiota transplantation for definitive cure.

Correlation between hospital-level antibiotic consumption and incident health care facility-onset Clostridium difficile infection.

PubMed

Crew, Page E; Rhodes, Nathaniel J; O'Donnell, J Nicholas; Miglis, Cristina; Gilbert, Elise M; Zembower, Teresa R; Qi, Chao; Silkaitis, Christina; Sutton, Sarah H; Scheetz, Marc H

2018-03-01

The purpose of this single-center, ecologic study is to characterize the relationship between facility-wide (FacWide) antibiotic consumption and incident health care facility-onset Clostridium difficile infection (HO-CDI). FacWide antibiotic consumption and incident HO-CDI were tallied on a monthly basis and standardized, from January 2013 through April 2015. Spearman rank-order correlation coefficients were calculated using matched-months analysis and a 1-month delay. Regression analyses were performed, with P < .05 considered statistically significant. FacWide analysis identified a matched-months correlation between ceftriaxone and HO-CDI (ρ = 0.44, P = .018). A unit of stem cell transplant recipients did not have significant correlation between carbapenems and HO-CDI in matched months (ρ = 0.37, P = .098), but a significant correlation was observed when a 1-month lag was applied (ρ = 0.54, P = .014). Three statistically significant lag associations were observed between FacWide/unit-level antibiotic consumption and HO-CDI, and 1 statistically significant nonlagged association was observed FacWide. Antibiotic consumption may convey extended ward-level risk for incident CDI. Consumption of antibiotic agents may have immediate and prolonged influence on incident CDI. Additional studies are needed to investigate the immediate and delayed associations between antibiotic consumption and C difficile colonization, infection, and transmission at the hospital level. Published by Elsevier Inc.

Reducing Clostridium difficile in the inpatient setting: A systematic review of the adherence to and effectiveness of C. difficile prevention bundles

PubMed Central

Barker, Anna; Ngam, Caitlyn; Musuuza, Jackson; Vaughn, Valerie M.; Safdar, Nasia

2017-01-01

Background Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea and its prevention is an urgent public health priority. However, reduction of CDI is challenging, because of its complex pathogenesis, large reservoirs of colonized patients, and persistence of infectious spores. The literature lacks high quality evidence for evaluating interventions, and many hospitals have implemented bundled interventions to reduce CDI with variable results. Thus, we conducted a systematic review to examine the components of CDI bundles, their implementation processes, and their impact on CDI rates. Methods We conducted a comprehensive literature search of multiple computerized databases from their date of inception through April 30, 2016. The protocol was registered in PROSPERO. Bundle effectiveness, adherence, and study quality was assessed for each study meeting criteria for inclusion. Results In the 26 studies that met inclusion criteria for this review, we found that implementation and adherence factors to interventions were variably and incompletely reported, making study reproducibility and replicability challenging. Despite contextual differences and the variety of bundle components utilized, all 26 studies reported an improvement in CDI rates. However, given the lack of randomized controlled trials in the literature, assessing a causal relationship between bundled interventions and CDI rates is currently impossible. Conclusions Cluster randomized trials that include a rigorous assessment of the implementation of bundled interventions are urgently needed to causally test the effect of intervention bundles on CDI rates. PMID:28343455

Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study, 2013.

PubMed

van Dorp, Sofie M; Kinross, Pete; Gastmeier, Petra; Behnke, Michael; Kola, Axel; Delmée, Michel; Pavelkovich, Anastasia; Mentula, Silja; Barbut, Frédéric; Hajdu, Agnes; Ingebretsen, André; Pituch, Hanna; Macovei, Ioana S; Jovanović, Milica; Wiuff, Camilla; Schmid, Daniela; Olsen, Katharina Ep; Wilcox, Mark H; Suetens, Carl; Kuijper, Ed J

2016-07-21

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a 'minimal' option (aggregated hospital data), a 'light' option (including patient data for CDI cases) and an 'enhanced' option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe. This article is copyright of The Authors, 2016.

[Treatment of acute and recurrent Clostridium difficile infections : What is new?

PubMed

von Braun, A; Lübbert, C

2018-05-01

The incidence of clostridium difficile infections (CDI) remains on a high level globally. In Germany, the number of severe or even lethal cases continues to increase. The main risk factor for the development of CDI is exposure to broad spectrum antibiotics, which disturb the physiological microbiome and therefore enable colonization with C. difficile. According to the updated US and European guidelines, orally administered vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin but has the advantage of a lower rate of recurrence. Furthermore, recent clinical studies were able to demonstrate that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. In recent years, several new antibiotics with narrow-spectrum acitivity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI; however, pivotal clinical trials have so far not been completed.

Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance

PubMed Central

Shah, Dhara; Dang, Minh-Duc; Hasbun, Rodrigo; Koo, Hoonmo L; Jiang, Zhi-Dong; DuPont, Herbert L; Garey, Kevin W

2010-01-01

Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospitalized patients. The incidence and severity of CDIs are increasing. The increased incidence and severity of the disease has sparked interest in the optimal treatment of CDI as well as the use of new therapies and drug discovery. Current treatment strategies are inadequate with decreased response rates to metronidazole, and high recurrence rates with the use of metronidazole and oral vancomycin. Although incidence rates continue to be low, in vitro resistance to antibiotics used for the treatment of CDI has been noted. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new antibiotic treatment options for CDI. This review will focus primarily on scientific studies published in the last 36 months in order to provide an up-to-date review on the topic. PMID:20455684

Clostridium difficile infection among children across diverse US geographic locations.

PubMed

Wendt, Joyanna M; Cohen, Jessica A; Mu, Yi; Dumyati, Ghinwa K; Dunn, John R; Holzbauer, Stacy M; Winston, Lisa G; Johnston, Helen L; Meek, James I; Farley, Monica M; Wilson, Lucy E; Phipps, Erin C; Beldavs, Zintars G; Gerding, Dale N; McDonald, L Clifford; Gould, Carolyn V; Lessa, Fernanda C

2014-04-01

Little is known about the epidemiology of Clostridium difficile infection (CDI) among children, particularly children ≤3 years of age in whom colonization is common but pathogenicity uncertain. We sought to describe pediatric CDI incidence, clinical presentation, and outcomes across age groups. Data from an active population- and laboratory-based CDI surveillance in 10 US geographic areas during 2010-2011 were used to identify cases (ie, residents with C difficile-positive stool without a positive test in the previous 8 weeks). Community-associated (CA) cases had stool collected as outpatients or ≤3 days after hospital admission and no overnight health care facility stay in the previous 12 weeks. A convenience sample of CA cases were interviewed. Demographic, exposure, and clinical data for cases aged 1 to 17 years were compared across 4 age groups: 1 year, 2 to 3 years, 4 to 9 years, and 10 to 17 years. Of 944 pediatric CDI cases identified, 71% were CA. CDI incidence per 100,000 children was highest among 1-year-old (66.3) and white (23.9) cases. The proportion of cases with documented diarrhea (72%) or severe disease (8%) was similar across age groups; no cases died. Among the 84 cases interviewed who reported diarrhea on the day of stool collection, 73% received antibiotics during the previous 12 weeks. Similar disease severity across age groups suggests an etiologic role for C difficile in the high rates of CDI observed in younger children. Prevention efforts to reduce unnecessary antimicrobial use among young children in outpatient settings should be prioritized.

Prevention and treatment of Clostridium difficile associated diarrhea by reconstitution of the microbiota.

PubMed

Eliakim-Raz, Noa; Bishara, Jihad

2018-05-21

This review summarizes the latest advances in treating and preventing Clostridium difficile infection (CDI), the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. As customary antibiotic therapies against C. difficile, metronidazole and vancomycin, are broad spectrum, they affect greatly the gut microbiota, which result in very high recurrence rates. Therefore, new strategies are researched intensively. New therapies focus on limiting further destruction of the gut microbiota or restoring the microbiota to its pre-destructed state. These include new antibiotics, such as fidaxomicin, which demonstrates reduced CDI recurrences, among other new drugs, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally, monoclonal antibodies against C. difficile toxins which offer protection against recurrences.

Clostridium difficile: Investigating Transmission Patterns between Infected and Colonized Patients using whole Genome Sequencing.

PubMed

Kong, L Y; Eyre, D W; Corbeil, J; Raymond, F; Walker, A S; Wilcox, M H; Crook, D W; Michaud, S; Toye, B; Frost, E; Dendukuri, N; Schiller, I; Bourgault, A M; Dascal, A; Oughton, M; Longtin, Y; Poirier, L; Brassard, P; Turgeon, N; Gilca, R; Loo, V G

2018-05-28

Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006 - 2007 at six Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Five hundred and fifty-four isolates were sequenced successfully, 353 from colonized and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide variants to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.

Perceptions of Clostridium difficile infections among infection control professionals in Taiwan.

PubMed

Hung, Yuan-Pin; Lee, Jen-Chieh; Lin, Hsiao-Ju; Chiu, Chun-Wei; Wu, Jia-Ling; Liu, Hsiao-Chieh; Huang, I-Hsiu; Tsai, Pei-Jane; Ko, Wen-Chien

2017-08-01

High Clostridium difficile colonization and infection rates among hospitalized patients had been noted in Taiwan. Nevertheless, the cognition about clinical diagnosis and management of CDI among infection control professionals in Taiwan is not clear. A 24-item survey questionnaire about the diagnosis, therapy, or infection control policies toward CDI was distributed in the annual meeting of the Infectious Disease Society of Taiwan (IDST) in October 2015 and Infectious Control Society of Taiwan (ICST) in April 2016. Totally 441 individuals responded to the survey, and 280 (63.5%) participants would routinely monitor the prevalence of CDI and 347 (78.7%) reported the formulation of infection control policies of CDI in their hospital, including contact precaution (75.7%), wearing gloves (88.9%) or dressing (80.0%) at patient care, single room isolation (49.7%), preference of soap or disinfectant-based sanitizer (83.2%) and avoidance of alcohol-based sanitizer (63.3%), and environmental disinfection with 1000 ppm bleach (87.1%). For the timing of contact precaution discontinuation isolation for CDI patients, most (39.9%) participants suggested the time point of the absence of C. difficile toxin in feces. To treat mild CDI, most (61.9%) participants preferred oral metronidazole, and for severe CDI 26.1% would prescribe oral vancomycin as the drug of choice. There were substantial gaps in infection control polices and therapeutic choices for CDI between international guidelines and the perceptions of medical professionals in Taiwan. Professional education program and the setup of guideline for CDI should be considered in Taiwan. Copyright © 2017. Published by Elsevier B.V.

Fatal course of takotsubo cardiomyopathy in a female with recurrent Clostridium difficile infection.

PubMed

Elikowski, Waldemar; Małek-Elikowska, Małgorzata; Lisiecka, Monika; Mozer-Lisewska, Iwona

2017-06-23

Among diverse triggering factors of stress-induced takotsubo cardiomyopathy (TC), a viral or bacterial infection is rarely observed. Sepsis is an exception, regardless of the etiologic pathogen, in which case an excess of catecholamines may result in acute left ventricular dysfunction. TC precipitated by Clostridium difficile infection (CDI) has been reported only in two patients so far. The authors describe another case of TC triggered this time by recurrent C. difficile colitis which occurred in a 72-yearold female. Severe heart failure developed on the second day of a new episode of diarrhea. Echocardiography revealed apical ballooning, a typical form of TC, while the coronary arteries in coronary angiography were normal. Despite proper treatment of CDI, the course of the disease was fatal due to heart failure progression. In considerations of TC pathogenesis in the case presented, the impact of C. difficile toxins should be taken into account. One should remember about the potential extraintestinal complications of CDI, including sudden myocardial depression.

Management of Clostridium difficile Infection

PubMed Central

Al-Jashaami, Layth S.

2016-01-01

Since the discovery of Clostridium difficile infection (CDI) in the 1970s, there has been an increase in the incidence, severity, and recurrence rate of the disease. We reviewed the recent CDI literature in PubMed published before February 28, 2016 that focused on advances in therapy. Despite a large number of studies describing methods for diagnosing the disease, there is currently no definitive test that identifies this infection with certainty, which complicates therapy. Recommended therapy for CDI includes oral metronidazole for mild cases and oral vancomycin or fidaxomicin for moderate to severe cases, each given for 10 to 14 days. For infection with spore-forming C difficile, this length of treatment may be insufficient to lead to cure; however, continuing antibiotics for longer periods of time may unfavorably alter the microbiome, preventing recovery. Treatment with metronidazole has been associated with an increasing failure rate, and the only clear recommended form of metronidazole for treatment of CDI is the intravenous formulation for patients unable to take oral medications. For vancomycin or fidaxomicin treatment of first CDI recurrences, the drug used in the initial bout can be repeated. For second or future recurrences, vancomycin can be given in pulsed or tapered doses. New modalities of treatment, such as bacteriotherapy and immunotherapy, show promise for the treatment of recurrent CDI. PMID:27917075

Healthcare resource utilization for recurrent Clostridium difficile infection in a large university hospital in Houston, Texas.

PubMed

Aitken, Samuel L; Joseph, Tiby B; Shah, Dhara N; Lasco, Todd M; Palmer, Hannah R; DuPont, Herbert L; Xie, Yang; Garey, Kevin W

2014-01-01

There are limited data examining healthcare resource utilization in patients with recurrent Clostridium difficile infection (CDI). Patients with CDI at a tertiary-care hospital in Houston, TX, were prospectively enrolled into an observational cohort study. Recurrence was assessed via follow-up phone calls. Patients with one or more recurrence were included in this study. The location at which healthcare was obtained by patients with recurrent CDI was identified along with hospital length of stay. CDI-attributable readmissions, defined as a positive toxin test within 48 hours of admission and a primary CDI diagnosis, were also assessed. 372 primary cases of CDI were identified of whom 64 (17.2%) experienced at least one CDI recurrence. Twelve of 64 patients experienced 18 further episodes of CDI recurrence. Of these 64 patients, 33 (50.8%) patients with recurrent CDI were readmitted of which 6 (18.2%) required ICU care, 29 (45.3%) had outpatient care only, and 2 (3.1%) had an ED visit. Nineteen (55.9%) readmissions were defined as CDI-attributable. For patients with CDI-attributable readmission, the average length of stay was 6 ± 6 days. Recurrent CDI leads to significant healthcare resource utilization. Methods of reducing the burden of recurrent CDI should be further studied.

The rise of Clostridium difficile infection in lung transplant recipients in the modern era.

PubMed

Lee, Janet T; Hertz, Marshall I; Dunitz, Jordan M; Kelly, Rosemary F; D'Cunha, Jonathan; Whitson, Bryan A; Shumway, Sara J

2013-01-01

Clostridium difficile infection (CDI) rates have been rising in recent years. We aimed to characterize CDI in lung transplant recipients in the modern era and hypothesized that CDI would increase the mortality risk. We performed a retrospective chart review of patients undergoing transplantation at our center from 1/2006 to 7/2011. Attributes of CDI+ and CDI- groups were compared using Student's t- and chi-square tests (α = 0.05). Multivariate Cox proportional hazard models were used to control for confounding factors. Overall CDI incidence was 22.5%. Seven of 151 patients (4.6%) developed CDI during the initial hospitalization after transplantation (mean time 10.6 ± 6 d) while 27 patients (19.7%) developed CDI after discharge (mean time 467 ± 471 d). Incidence rate was 224.6 cases/100 000 patient-days compared to 110 cases/100 000 patient-days (rate for entire hospital). CDI was not predictive of mortality (HR 2.06, 95% CI 0.94-4.52). CDI rates in lung transplant recipients are high in the modern era. No risk factors for CDI were identified. Although not statistically significant, CDI+ patients had a higher risk of death. The economic burden of CDI and trend toward worse outcomes for CDI patients have important implications for post-operative surveillance of CDI-related complications and need for CDI prophylaxis. © 2013 John Wiley & Sons A/S.

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis

PubMed Central

Grewal, Suman; LaComb, Joseph F.; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M.; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E.; Frank, Daniel N.; Li, Ellen

2018-01-01

Background Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). Method V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Results Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. Conclusion The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients. PMID:29385143

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

PubMed

Mintz, Michael; Khair, Shanawaj; Grewal, Suman; LaComb, Joseph F; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E; Frank, Daniel N; Li, Ellen

2018-01-01

Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

A Comprehensive Study of Costs Associated With Recurrent Clostridium difficile Infection.

PubMed

Rodrigues, Rodrigo; Barber, Grant E; Ananthakrishnan, Ashwin N

2017-02-01

BACKGROUND Clostridium difficile infection (CDI) is the most common healthcare-associated infection and is associated with considerable morbidity. Recurrent CDI is a key contributing factor to this morbidity. Despite an estimated 83,000 recurrences annually in the United States, there are few accurate estimates of costs associated with recurrent CDI. OBJECTIVE We performed this study (1) to identify the health consequences of recurrent CDI including need for repeat hospitalization, intensive care unit (ICU) stay, and surgery; (2) to determine costs associated with recurrent CDI and identify determinants of such costs; and (3) to compare the outcomes and costs of recurrent CDI to those who develop reinfection. METHODS We identified all patients with confirmed recurrent CDI between January to December 2013 at a single referral center. Healthcare burden associated with recurrence including diagnostic testing, pharmacologic treatment, and inpatient and outpatient healthcare visits were identified in the 12 months following the first recurrence. Total healthcare costs were calculated, and the predictors of high healthcare utilization were identified. RESULTS Our study population included 98 patients with recurrent CDI. The median interval between the initial infection and recurrence was 37 days. The mean age of the cohort was 67 years, two-thirds were women (62%), and the mean Charlson index was 8.6. During the year following the first recurrence of CDI, each patient underwent a mean of 4.4 stool C. difficile toxin tests and received a mean of 2.5 prescriptions for oral vancomycin (range, 0-6). Most patients (84%) with recurrence had a CDI-related hospitalization, and 6% underwent colectomy. The mean total CDI-associated cost was $34,104 per patient, with hospitalization costs accounting for 68%, surgery 20%, and drug treatment 8% of this cost, respectively. Extrapolating to the United States overall, we estimate an annual cost of $2.8 billion related to recurrent CDI. CONCLUSION Recurrent CDI is associated with considerable morbidity and cost. Infect Control Hosp Epidemiol 2017;38:196-202.

Attributable inpatient costs of recurrent Clostridium difficile infections.

PubMed

Dubberke, Erik R; Schaefer, Eric; Reske, Kimberly A; Zilberberg, Marya; Hollenbeak, Christopher S; Olsen, Margaret A

2014-11-01

To determine the attributable inpatient costs of recurrent Clostridium difficile infections (CDIs). Retrospective cohort study. Academic, urban, tertiary care hospital. A total of 3,958 patients aged 18 years or more who developed an initial CDI episode from 2003 through 2009. Data were collected electronically from hospital administrative databases and were supplemented with chart review. Patients with an index CDI episode during the study period were followed up for 180 days from the end of their index hospitalization or the end of their index CDI antibiotic treatment (whichever occurred later). Total hospital costs during the outcome period for patients with recurrent versus a single episode of CDI were analyzed using zero-inflated lognormal models. There were 421 persons with recurrent CDI (recurrence rate, 10.6%). Recurrent CDI case patients were significantly more likely than persons without recurrence to have any hospital costs during the outcome period (P < .001). The estimated attributable cost of recurrent CDI was $11,631 (95% confidence interval, $8,937-$14,588). The attributable costs of recurrent CDI are considerable. Patients with recurrent CDI are significantly more likely to have inpatient hospital costs than patients who do not develop recurrences. Better strategies to predict and prevent CDI recurrences are needed.

Evaluation of the performance of C. DIFF QUIK CHEK COMPLETE and its usefulness in a hospital setting with a high prevalence of Clostridium difficile infection.

PubMed

Chung, Hae-Sun; Lee, Miae

2017-01-01

Rapid and accurate diagnosis of Clostridium difficile infection (CDI) is crucial for patient care, infection control, and efficient surveillance. We evaluated C. DIFF QUIK CHEK COMPLETE (QCC; TechLab), which detects glutamate dehydrogenase (GDH) antigen (QCC-Ag) and toxin A/B (QCC-Tox) simultaneously, and compared it to the laboratory diagnostics for CDI currently in use in a tertiary hospital setting with a high prevalence of CDI. QCC, RIDASCREEN C. difficile toxin A/B assay (Toxin EIA; R-Biopharm AG), chromID C. difficile agar (bioMérieux) culture (ChromID culture), and Xpert C. difficile PCR assay (Xpert PCR; Cepheid) were performed according to the manufacturers' instructions. Performances of the assays were compared against that of Xpert PCR as a reference. Of the 231 loose stool specimens, 83 (35.9%) were positive by Xpert PCR. The sensitivity, specificity, and positive and negative predictive values were 97.6%, 93.9%, 90.0%, and 98.6%, respectively, for QCC-Ag and 55.4%, 100%, 100%, and 80.0%, respectively, for QCC-Tox. The median threshold cycle values of the QCC-Tox(+) specimens were lower than those of the QCC-Tox(-) specimens. Results of QCC as an initial screening test were confirmed in 81.0% (187/231) of samples; these specimens did not require further testing. QCC is a rapid, easy, and cost-effective method that would be a useful first-line screening assay for laboratory diagnosis of CDI in a tertiary hospital with a high prevalence of CDI. A two-step algorithm using QCC as an initial screening tool, followed by Xpert PCR as a confirmatory test, is a practical and cost-effective approach. Copyright © 2016 American Federation for Medical Research.

A microbiological study to investigate the carriage and transmission-potential of Clostridium difficile spores on single-use and reusable sharps containers.

PubMed

Grimmond, Terry; Neelakanta, Anu; Miller, Barbara; Saiyed, Asif; Gill, Pam; Cadnum, Jennifer; Olmsted, Russell; Donskey, Curtis; Pate, Kimberly; Miller, Katherine

2018-05-22

A 2015 study matching use of disposable and reusable sharps containers (DSCs, RSCs) with Clostridium difficile infection (CDI) incidence found a decreased incidence with DSCs. We conducted microbiologic samplings and examined the literature and disease-transmission principles to evaluate the scientific feasibility of such an association. (i) 197 RSCs were sampled for C. difficile at processing facilities; (ii) RSCs were challenged with high C. difficile densities to evaluate efficacy of automated decontamination; and (iii) 50 RSCs and 50 DSCs were sampled in CDI patient rooms in 7 hospitals. Results were coupled with epidemiologic studies, clinical requirements, and chain-of-infection principles, and tests of evidence of disease transmission were applied. C. difficile spores were found on 9 of 197 (4.6%) RSCs prior to processing. Processing completely removed C. difficile. In CDI patient rooms, 4 of 50 RSCs (8.0%) and 8 of 50 DSCs (16.0%) had sub-infective counts of C. difficile (P = .27). DSCs were in permanent wall cabinets; RSCs were removed and decontaminated frequently. With C. difficile bioburden being sub-infective on both DSCs and RSCs, sharps containers being no-touch, and glove removal required after sharps disposal, we found 2 links in the chain of infection to be broken and 5 of 7 tests of evidence to be unmet. We conclude that sharps containers pose no risk of C. difficile transmission. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Clostridium difficile Infection in Production Animals and Avian Species: A Review.

PubMed

Moono, Peter; Foster, Niki F; Hampson, David J; Knight, Daniel R; Bloomfield, Lauren E; Riley, Thomas V

2016-12-01

Clostridium difficile is the leading cause of antibiotic-associated diarrhea and colitis in hospitalized humans. Recently, C. difficile infection (CDI) has been increasingly recognized as a cause of neonatal enteritis in food animals such as pigs, resulting in stunted growth, delays in weaning, and mortality, as well as colitis in large birds such as ostriches. C. difficile is a strictly anaerobic spore-forming bacterium, which produces two toxins A (TcdA) and B (TcdB) as its main virulence factors. The majority of strains isolated from animals produce an additional binary toxin (C. difficile transferase) that is associated with increased virulence. C. difficile is ubiquitous in the environment and has a wide host range. This review summarizes the epidemiology, clinical presentations, risk factors, and laboratory diagnosis of CDI in animals. Increased awareness by veterinarians and animal owners of the significance of clinical disease caused by C. difficile in livestock and avians is needed. Finally, this review provides an overview on methods for controlling environmental contamination and potential therapeutics available.

Therapy for Clostridium difficile infection - any news beyond Metronidazole and Vancomycin?

PubMed

Manthey, C F; Eckmann, L; Fuhrmann, V

2017-11-01

Infections with Clostridium difficile (CDI) represent a major burden for the health care system. Treatment is generally by antibiotic therapy with metronidazole and vancomycin, but efficacy remains suboptimal. Areas covered: This review discusses established and emerging treatment options for CDI, and current therapeutic guidelines, taking into account disease severity and risk of relapse. Expert commentary: New therapeutic approaches, including antibodies and new classes of antibiotics, and new measures for preventing infection with vaccines are under development in phase II/III clinical trials. We performed a systematic literature review using the search terms 'Clostridium difficile' and 'treatment'.

Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

PubMed

Chmielewska, M; Zycinska, K; Lenartowicz, B; Hadzik-Błaszczyk, M; Cieplak, M; Kur, Z; Wardyn, K A

2017-01-01

One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

Clostridium difficile in Crete, Greece: epidemiology, microbiology and clinical disease.

PubMed

Samonis, G; Vardakas, K Z; Tansarli, G S; Dimopoulou, D; Papadimitriou, G; Kofteridis, D P; Maraki, S; Karanika, M; Falagas, M E

2016-01-01

We studied the epidemiology and microbiology of Clostridium difficile and the characteristics of patients with C. difficile infection (CDI) in Crete in three groups of hospitalized patients with diarrhoea: group 1 [positive culture and positive toxin by enzyme immunoassay (EIA)]; group 2 (positive culture, negative toxin); group 3 (negative culture, negative toxin). Patients in group 1 were designated as those with definitive CDI (20 patients for whom data was available) and matched with cases in group 2 (40 patients) and group 3 (40 patients). C. difficile grew from 6% (263/4379) of stool specimens; 14·4% of these had positive EIA, of which 3% were resistant to metronidazole. Three isolates had decreased vancomycin susceptibility. Patients in groups 1 and 2 received more antibiotics (P = 0·03) and had more infectious episodes (P = 0·03) than patients in group 3 prior to diarrhoea. Antibiotic administration for C. difficile did not differ between groups 1 and 2. Mortality was similar in all three groups (10%, 12·5% and 5%, P = 0·49). CDI frequency was low in the University Hospital of Crete and isolates were susceptible to metronidazole and vancomycin.

Asymptomatic Carriers of Toxigenic C. difficile in Long-Term Care Facilities: A Meta-Analysis of Prevalence and Risk Factors

PubMed Central

Ziakas, Panayiotis D.; Zacharioudakis, Ioannis M.; Zervou, Fainareti N.; Grigoras, Christos; Pliakos, Elina Eleftheria; Mylonakis, Eleftherios

2015-01-01

Background The impact of Clostridium difficile colonization in C. difficile infection (CDI) is inadequately explored. As a result, asymptomatic carriage is not considered in the development of infection control policies and the burden of carrier state in long-term care facilities (LTCFs) is unknown. Purpose To explore the epidemiology of C. difficile colonization in LTCFs, identify predisposing factors and describe its impact on healthcare management. Data Sources PubMed, Embase and Web of Science (up to June 2014) without language restriction, complemented by reference lists of eligible studies. Study Selection All studies providing extractable data on the prevalence of toxigenic C. difficile colonization among asymptomatic residents in LTCFs. Data Extraction Two authors extracted data independently. Statistical Methods The pooled colonization estimates were calculated using the double arcsine methodology and reported along with their 95% random-effects confidence intervals (CIs), using DerSimonian-Laird weights. We assessed the impact of patient-level covariates on the risk of colonization and effects were reported as odds ratios (OR, 95% CI). We used the colonization estimates to simulate the effective reproduction number R through a Monte Carlo technique. Results Based on data from 9 eligible studies that met the specified criteria and included 1,371 subjects, we found that 14.8% (95%CI 7.6%-24.0%) of LTCF residents are asymptomatic carriers of toxigenic C. difficile. Colonization estimates were significantly higher in facilities with prior CDI outbreak (30.1% vs. 6.5%, p = 0.01). Patient history of CDI (OR 6.07; 95% CI 2.06–17.88; effect derived from 3 studies), prior hospitalization (OR 2.11; 95% CI 1.08–4.13; derived from 3 studies) and antimicrobial use within previous 3 months (OR 3.68; 95% CI 2.04–6.62; derived from 4 studies) were associated with colonization. The predicted colonization rate at admission was 8.9%. Conclusion Asymptomatic carriage of toxigenic C. difficile represents a significant burden in LTCFs and is associated with prior CDI outbreaks in the facility, a history of CDI, prior hospitalization and antimicrobial use. These findings can impact infection control measures at LTCFs. PMID:25707002

[Prevalence of Clostridium difficile infection in hospitalized patients with diarrhea: results of a French prospective multicenter bi-annual point prevalence study].

PubMed

Barbut, Frédéric; Ramé, Laetitia; Petit, Amandine; Suzon, Laina; de Chevigny, Alix; Eckert, Catherine

2015-04-01

Clostridium difficile infections represent the major cause of healthcare-associated diarrhea. The objective of the study was to determine the incidence of C. difficile infection (CDI) in 2012 and to assess the under-estimation of the disease in France. Seventy healthcare facilities participated in a prospective point prevalence study. Each laboratory was requested to send all the diarrheal stool samples from hospitalized patients during 2 days (one in December 2012 and one in July 2013) to the National Reference Laboratory (NRL) for C. difficile, irrespective of a medical request for C. difficile. At the NRL, stool samples were analyzed using the Quik Chek Complete assay (Alere). Positive samples for glutamate deshydrogenase or toxins were confirmed by the toxigenic culture. Results obtained by the NRL were then compared to those given by each healthcare facility. Incidence of CDI in 2012 was provided by each healthcare facility through a specific questionnaire. Mean incidence of CDI reported in 2012 by the HCF was 3.6 ± 2.9 per 10,000 patient-days; the incidence was positively correlated to the density testing (defined by the number of tests per 10,000 patient-days), which varied across the HCF (median 29.0 per 10,000 patient-days, IQR 19-50). During the bi-annual point prevalence survey, 651 stool samples were included and 90 were positive for C. difficile in culture. The overall prevalence of patients infected by a toxigenic C. difficile strain was 9.7% (63/651) and the prevalence of patients colonized by a non-toxigenic strain was 4.2% (27/651). Among the 65 cases of CDI detected by the NRL, 35 (55.6%) were missed by the participating HCF because of a lack of sensitivity of the methods used for the diagnosis (16/63, 25.4%) or because of a lack of clinical suspicion (19/63, 30.2%). The incidence of CDI in 2012 has increased in France compared to that of 2009 but is still underestimated because of a lack of clinical suspicion or a lack of sensitivity of methods used for toxin detection. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Hospital Clostridium difficile infection (CDI) incidence as a risk factor for hospital-associated CDI

PubMed Central

Miller, Aaron C.; Polgreen, Linnea A.; Cavanaugh, Joseph E.; Polgreen, Philip M.

2016-01-01

Background Environmental risk factors for Clostridium difficile infections (CDIs) have been described at the room or unit level but not the hospital level. To understand the environmental risk factors for CDI, we investigated the association between institutional- and individual-level CDI. Methods We performed a retrospective cohort study using the Healthcare Cost and Utilization Project state inpatient databases for California (2005–2011). For each patient’s hospital stay, we calculated the hospital CDI incidence rate corresponding to the patient’s quarter of discharge, while excluding each patient’s own CDI status. Adjusting for patient and hospital characteristics, we ran a pooled logistic regression to determine individual CDI risk attributable to the hospital’s CDI rate. Results There were 10,329,988 patients (26,086 cases and 10,303,902 noncases) who were analyzed. We found that a percentage point increase in the CDI incidence rate a patient encountered increased the odds of CDI by a factor of 1.182. Conclusions As a point of comparison, a 1-percentage point increase in the CDI incidence rate that the patient encountered had roughly the same impact on their odds of acquiring CDI as a 55.8-day increase in their length of stay or a 60-year increase in age. Patients treated in hospitals with a higher CDI rate are more likely to acquire CDI. PMID:26944007

The host immune response to Clostridium difficile infection

PubMed Central

2013-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

A population-based spatio-temporal analysis of Clostridium difficile infection in Queensland, Australia over a 10-year period.

PubMed

Furuya-Kanamori, Luis; Robson, Jenny; Soares Magalhães, Ricardo J; Yakob, Laith; McKenzie, Samantha J; Paterson, David L; Riley, Thomas V; Clements, Archie C A

2014-11-01

To identify the spatio-temporal patterns and environmental factors associated with Clostridium difficile infection (CDI) in Queensland, Australia. Data from patients tested for CDI were collected from 392 postcodes across Queensland between May 2003 and December 2012. A binomial logistic regression model, with CDI status as the outcome, was built in a Bayesian framework, incorporating fixed effects for sex, age, source of the sample (healthcare facility or community), elevation, rainfall, land surface temperature, seasons of the year, time in months and spatially unstructured random effects at the postcode level. C. difficile was identified in 13.1% of the samples, the proportion significantly increased over the study period from 5.9% in 2003 to 18.8% in 2012. CDI peaked in summer (14.6%) and was at its lowest in autumn (10.1%). Other factors significantly associated with CDI included female sex (OR: 1.08; 95%CI: 1.01-1.14), community source samples (OR: 1.12; 95%CI: 1.05-1.20), and higher rainfall (OR: 1.09; 95%CI: 1.02-1.17). There was no significant spatial variation in CDI after accounting for the fixed effects in the model. There was an increasing annual trend in CDI in Queensland from 2003 to 2012. Peaks of CDI were found in summer (December-February), which is at odds with the current epidemiological pattern described for northern hemisphere countries. Epidemiologically plausible explanations for this disparity require further investigation. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

All-cause mortality in hospitalized patients with infectious diarrhea: Clostridium difficile versus other enteric pathogens in Austria from 2008 to 2010.

PubMed

Schmid, D; Kuo, H W; Simons, E; Kanitz, E E; Wenisch, J; Allerberger, F; Wenisch, C

2014-01-01

Clostridium difficile infection is the leading cause of gastroenteritis-associated deaths in the industrialized world, followed by infection with norovirus. Using a cohort study design, we compared 90 inpatients with diarrhea due to C. difficile infection (CDI) with 180 inpatients with diarrhea due to other infectious agents (including 55% with norovirus infection) with respect to complications and all-cause mortality. The effects of age, severity of underlying diseases and additional infections were assessed by stratified analyses. Diarrhea recurrence occurred 8.9 (95%CI: 2.9-27.3) times more often in CDI independent of age and severity of comorbidities. The all-cause mortality in CDI patients pre-discharge and at 30 and 180 days, respectively, was 20.0%, 17.0% and 42.3% versus 7.2%, 6.7% and 22.5% in non-CDI diarrhea patients. Among those patients with low comorbidities, who were younger than 65 years and without additional infections, the all-cause pre-discharge, 30-day and 180-day mortality risks were significantly higher for the CDI diarrhea patients than the non-CDI diarrhea patients. This association was not observed among patients with an older age, more severe comorbidities or additional infections. CDI results in higher all-cause mortality than diarrhea due to other infectious agents in younger patients with low comorbidities. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics

PubMed Central

Kujawa-Szewieczek, Agata; Adamczak, Marcin; Kwiecień, Katarzyna; Dudzicz, Sylwia; Gazda, Magdalena; Więcek, Andrzej

2015-01-01

Background: Lactobacillus plantarum 299v (LP299v) has been used in order to reduce gastrointestinal symptoms during antibiotic exposure. However, it remains controversial whether or not probiotics are effective in the prevention of Clostridium difficile infections (CDI) among patients receiving antibiotics. The aim of this study was to analyze the CDI among patients receiving antibiotics and hospitalized in the period before and after starting routine use of LP299v as a prevention of this infection. Methods: Among 3533 patients hospitalized in the nephrology and transplantation ward during a two-year period, 23 patients with CDI were diagnosed and enrolled in this retrospective study. Since November 2013, prevention of CDI with oral use of LP299v was performed in all patients treated with antibiotics and who were at a high risk of developing CDI. The observation period was divided into two twelve-month intervals before and after initiation of the use of LP299v as a prophylactic against CDI. Results: A significant (p = 0.0001) reduction of the number of cases of CDI was found after routinely using LP299v (n = 2; 0.11% of all hospitalized patients) compared with the previous twelve-month period of observation (n = 21; 1.21% of all hospitalized patients). Conclusions: Routine use of LP299v during treatment with antibiotics may prevent C. difficile infection in the nephrology and transplantation ward. PMID:26690209

Incidence and Costs of Clostridium difficile Infections in Canada.

PubMed

Levy, Adrian R; Szabo, Shelagh M; Lozano-Ortega, Greta; Lloyd-Smith, Elisa; Leung, Victor; Lawrence, Robin; Romney, Marc G

2015-09-01

Background.  Limited data are available on direct medical costs and lost productivity due to Clostridium difficile infection (CDI) in Canada. Methods.  We developed an economic model to estimate the costs of managing hospitalized and community-dwelling patients with CDI in Canada. The number of episodes was projected based on publicly available national rates of hospital-associated CDI and the estimate that 64% of all CDI is hospital-associated. Clostridium difficile infection recurrences were classified as relapses or reinfections. Resource utilization data came from published literature, clinician interviews, and Canadian CDI surveillance programs, and this included the following: hospital length of stay, contact with healthcare providers, pharmacotherapy, laboratory testing, and in-hospital procedures. Lost productivity was considered for those under 65 years of age, and the economic impact was quantified using publicly available labor statistics. Unit costs were obtained from published sources and presented in 2012 Canadian dollars. Results.  There were an estimated 37 900 CDI episodes in Canada in 2012; 7980 (21%) of these were relapses, out of a total of 10 900 (27%) episodes of recurrence. The total cost to society of CDI was estimated at $281 million; 92% ($260 million) was in-hospital costs, 4% ($12 million) was direct medical costs in the community, and 4% ($10 million) was due to lost productivity. Management of CDI relapses alone accounted for $65.1 million (23%). Conclusions.  The largest proportion of costs due to CDI in Canada arise from extra days of hospitalization. Interventions reducing the severity of infection and/or relapses leading to rehospitalizations are likely to have the largest absolute effect on direct medical costs.

Incidence and Costs of Clostridium difficile Infections in Canada

PubMed Central

Levy, Adrian R.; Szabo, Shelagh M.; Lozano-Ortega, Greta; Lloyd-Smith, Elisa; Leung, Victor; Lawrence, Robin; Romney, Marc G.

2015-01-01

Background. Limited data are available on direct medical costs and lost productivity due to Clostridium difficile infection (CDI) in Canada. Methods. We developed an economic model to estimate the costs of managing hospitalized and community-dwelling patients with CDI in Canada. The number of episodes was projected based on publicly available national rates of hospital-associated CDI and the estimate that 64% of all CDI is hospital-associated. Clostridium difficile infection recurrences were classified as relapses or reinfections. Resource utilization data came from published literature, clinician interviews, and Canadian CDI surveillance programs, and this included the following: hospital length of stay, contact with healthcare providers, pharmacotherapy, laboratory testing, and in-hospital procedures. Lost productivity was considered for those under 65 years of age, and the economic impact was quantified using publicly available labor statistics. Unit costs were obtained from published sources and presented in 2012 Canadian dollars. Results. There were an estimated 37 900 CDI episodes in Canada in 2012; 7980 (21%) of these were relapses, out of a total of 10 900 (27%) episodes of recurrence. The total cost to society of CDI was estimated at $281 million; 92% ($260 million) was in-hospital costs, 4% ($12 million) was direct medical costs in the community, and 4% ($10 million) was due to lost productivity. Management of CDI relapses alone accounted for $65.1 million (23%). Conclusions. The largest proportion of costs due to CDI in Canada arise from extra days of hospitalization. Interventions reducing the severity of infection and/or relapses leading to rehospitalizations are likely to have the largest absolute effect on direct medical costs. PMID:26191534

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

PubMed

Prabhu, Vimalanand S; Dubberke, Erik R; Dorr, Mary Beth; Elbasha, Elamin; Cossrow, Nicole; Jiang, Yiling; Marcella, Stephen

2018-01-18

Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Engaging patients in the prevention of health care-associated infections: a survey of patients' awareness, knowledge, and perceptions regarding the risks and consequences of infection with methicillin-resistant Staphylococcus aureus and Clostridium difficile.

PubMed

Ottum, Andrew; Sethi, Ajay K; Jacobs, Elizabeth; Zerbel, Sara; Gaines, Martha E; Safdar, Nasia

2013-04-01

Methicillin-resistant Staphylococcus aureus (MRSA) infections and Clostridium difficile infections (CDI) are major health care-associated infections (HAIs). Little is known about patients' knowledge of these HAIs. Therefore, we surveyed patients to determine awareness, knowledge, and perceptions of MRSA infections and CDI. An interviewer-administered questionnaire. A tertiary care academic medical center. Adult patients who met at least one of the following criteria: at risk of CDI or MRSA infection, current CDI or colonization or current MRSA infection or colonization, or history of CDI or MRSA infection. Two unique surveys were developed and administered to 100 patients in 2011. Overall, 76% of patients surveyed were aware of MRSA, whereas 44% were aware of C difficile. The strongest predictor of patients' awareness of these infections was having a history of HAI. Patients with a history of HAI were significantly more likely to have heard of both MRSA (odds ratio, 13.29; 95% confidence interval, 2.84-62.14; P = .001) and C difficile (odds ratio, 9.78; 95% confidence interval, 2.66-35.95; P = .001), than those patients without a history of HAI. There was also a significant positive association between having a history of HAI and greater knowledge of the risk factors, health consequences, and prevention techniques relative to CDI and MRSA infections. There are additional opportunities to engage patients about the risks and consequences of MRSA and CDIs, particularly those without a history of HAI. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

The role of toxins in Clostridium difficile infection.

PubMed

Chandrasekaran, Ramyavardhanee; Lacy, D Borden

2017-11-01

Clostridium difficile is a bacterial pathogen that is the leading cause of nosocomial antibiotic-associated diarrhea and pseudomembranous colitis worldwide. The incidence, severity, mortality and healthcare costs associated with C. difficile infection (CDI) are rising, making C. difficile a major threat to public health. Traditional treatments for CDI involve use of antibiotics such as metronidazole and vancomycin, but disease recurrence occurs in about 30% of patients, highlighting the need for new therapies. The pathogenesis of C. difficile is primarily mediated by the actions of two large clostridial glucosylating toxins, toxin A (TcdA) and toxin B (TcdB). Some strains produce a third toxin, the binary toxin C. difficile transferase, which can also contribute to C. difficile virulence and disease. These toxins act on the colonic epithelium and immune cells and induce a complex cascade of cellular events that result in fluid secretion, inflammation and tissue damage, which are the hallmark features of the disease. In this review, we summarize our current understanding of the structure and mechanism of action of the C. difficile toxins and their role in disease. Published by Oxford University Press on behalf of FEMS 2017.

Correlation between fecal calprotectin levels, disease severity and the hypervirulent ribotype 027 strain in patients with Clostridium difficile infection.

PubMed

Peretz, Avi; Tkhawkho, Linda; Pastukh, Nina; Brodsky, Diana; Halevi, Chen Namimi; Nitzan, Orna

2016-06-22

Clostridium difficile is the most common infectious etiology of nosocomial diarrhea. Fecal calprotectin (fc) is a sensitive marker of intestinal inflammation, found to be associated with enteric bacterial infections and inflammatory bowel disease. We evaluated fc levels using a Chemiluminescent immunoassay method, in hospitalized patients with C. difficile infection (CDI) diagnosed by molecular stool examination and assessed correlation with virulent ribotype 027 strain infection, antibiotic susceptibility by gradient Etest strip performed on C. difficile colonies and clinical and laboratory measures of disease severity. Statistical analysis was performed for correlation of fc levels with clinical and laboratory parameters, disease severity and patient outcomes. Overall 29 patients with CDI were admitted at the Poria medical center in northern Israel, during June 2014-May 2015. Resistance to metronidazole was found in 3 (10.3 %) isolates and to vancomycin in 5 (17.2 %) isolates. Regarding patient outcomes, within 30 days of CDI diagnosis, recurrence of disease occurred in 10 (34.5 %) patients and 2 patients (6.9 %) died. Seven (24.1 %) isolates were C. difficile ribotype 027. Mean fc level was 331.4 μg/g (21-932). Higher fc levels were found in patients with C. difficile ribotype 027 (p < 0.0005). Fc levels were also correlated with elevated peripheral blood white cell count (p = 0.0007). A trend for higher fc levels was found in patients with a higher clostridium severity score index (p = 0.0633). No correlation was found between fecal calprotectin levels and age, sex, functional status, community versus hospital acquired CDI, antibiotic susceptibility, fever, and creatinine levels. Our study highlights the fact that fc has a potential role as a biomarker of disease severity and binary toxin producing ribotype associated disease.

Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease.

PubMed

Hourigan, S K; Chen, L A; Grigoryan, Z; Laroche, G; Weidner, M; Sears, C L; Oliva-Hemker, M

2015-09-01

Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis. To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD. Children with a history of recurrent CDI (≥3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT at 2-10 weeks, 10-20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed. Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10-20 weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased. Six months post-FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months in IBD-negative patients more closely approximated donor composition compared to IBD-positive patients. FMT gives sustained C. difficile eradication in children with and without IBD. FMT-restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome diversity. © 2015 John Wiley & Sons Ltd.

Clinical update for the diagnosis and treatment of Clostridium difficile infection

PubMed Central

IV, Edward C Oldfield; III, Edward C Oldfield; Johnson, David A

2014-01-01

Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies. PMID:24729930

Emerging therapies for Clostridium difficile infection – focus on fidaxomicin

PubMed Central

Chaparro-Rojas, Fredy; Mullane, Kathleen M

2013-01-01

The epidemiology of Clostridium difficile infections (CDI) has evolved during the last decades, with an increase in the reported incidence, severity of cases, and rate of mortality and relapses. These increases have primarily affected some special populations including the elderly, patients requiring concomitant antibiotic therapy, patients with renal failure, and patients with cancer. Until recently, the treatment of CDI was limited to either metronidazole or vancomycin. New therapeutic options have emerged to address the shortcomings of current antibiotic therapy. Fidaxomicin stands out as the first-in-class oral macrocyclic antibiotic with targeted activity against C. difficile and minimal collateral damage on the normal colonic flora. Fidaxomicin has demonstrated performance not inferior to what is considered the “gold standard” available therapy for CDI, vancomycin, in two separate Phase III clinical trials, but with significant advantages, including fewer recurrences and higher rates of sustained clinical cures. Fidaxomicin constitutes an important development in targeted antibiotic therapy for CDI and must be considered as a first-line agent for patients with risk factors known to portend relapse and severe infection. PMID:23843696

Annual Surveillance Summary: Clostridium difficile Infections in the Military Health System (MHS), 2016

DTIC Science & Technology

2017-06-01

factors related to CD. Health Level 7 (HL7)-formatted microbiology and chemistry data identified CDI. These infections were matched to HL7-formatted...resistant organisms . iii C. difficile in the MHS: Annual Summary 2016 Prepared June 2017 EpiData Center Department NMCPHC-EDC-TR-364...been discussed in a previous report (CY 2015 CDI annual report 1 ). The EDC also monitors other multidrug-resistant organisms (MDROs) of interest

Emerging therapies for Clostridium difficile infections.

PubMed

McFarland, Lynne V

2011-09-01

Clostridium difficile infection (CDI) is the leading identifiable gastrointestinal disease in healthcare institutions, but the response rates to the two standard therapies for CDI are declining and so innovative therapies are being developed for CDI. The purpose of this paper is to review the data on the efficacy and safety of emerging therapies for CDI and assess their potential for effectiveness based on the clinical phase of development and marketing challenges. Emerging therapies for CDI are reviewed including new antibiotics, peptides, immune regulators, probiotics and toxin binders. PubMed, Medline and Google Scholar and online clinical trial registers are searched from 1976 to 2010 for articles unrestricted by language. Secondary searches by author, manufacturing companies and FDA websites are also performed. Of the emerging therapies for CDI, several may ultimately reduce the incidence of CDI and the economic burden of this disease on the healthcare system. Several emerging treatments (fidaxomicin, rifaximin and mAbs) show the most promise, although only one is currently being actively developed. Use of other clostridial strains, probiotic strains and immune enhancers have great potential as therapies, but require further development.

In vitro activity of cadazolid against clinically relevant Clostridium difficile isolates and in an in vitro gut model of C. difficile infection.

PubMed

Chilton, C H; Crowther, G S; Baines, S D; Todhunter, S L; Freeman, J; Locher, H H; Athanasiou, A; Wilcox, M H

2014-03-01

We investigated the in vitro activity of cadazolid against 100 Clostridium difficile isolates and its efficacy in a simulated human gut model of C. difficile infection (CDI). MICs of cadazolid, metronidazole, vancomycin, moxifloxacin and linezolid were determined using agar incorporation for 100 C. difficile isolates, including 30 epidemic strains (ribotypes 027, 106 and 001) with reduced metronidazole susceptibility, 2 linezolid-resistant isolates and 2 moxifloxacin-resistant isolates. We evaluated the efficacy of two cadazolid dosing regimens (250 versus 750 mg/L twice daily for 7 days) to treat simulated CDI. Microflora populations, C. difficile total viable counts and spores, cytotoxin titres, possible emergence of cadazolid, linezolid or quinolone resistance, and antimicrobial concentrations were monitored throughout. Cadazolid was active against all (including linezolid- and moxifloxacin-resistant) C. difficile strains (MIC90 0.125, range 0.03-0.25 mg/L). The cadazolid geometric mean MIC was 152-fold, 16-fold, 9-fold and 7-fold lower than those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively. Both cadazolid dosing regimens rapidly reduced C. difficile viable counts and cytotoxin with no evidence of recurrence. Cadazolid levels persisted at 50-100-fold supra-MIC for 14 days post-dosing. Cadazolid inhibition of enumerated gut microflora was limited, with the exception of bifidobacteria; Bacteroides fragilis group and Lactobacillus spp. counts were unaffected. There was no evidence for selection of strains resistant to cadazolid, quinolones or linezolid. Cadazolid activity was greater than other tested antimicrobials against 100 C. difficile strains. Cadazolid effectively treated simulated CDI in a gut model, with limited impact on the enumerated gut microflora and no signs of recurrence or emergence of resistance within the experimental timeframe.

Clostridium difficile infection in pediatric acute myeloid leukemia: from the Canadian Infections in Acute Myeloid Leukemia Research Group.

PubMed

Price, Victoria; Portwine, Carol; Zelcer, Shayna; Ethier, Marie-Chantal; Gillmeister, Biljana; Silva, Mariana; Schindera, Christina; Yanofsky, Rochelle; Mitchell, David; Johnston, Donna L; Lewis, Victor; Dix, David; Cellot, Sonia; Michon, Bruno; Bowes, Lynette; Stobart, Kent; Brossard, Josee; Beyene, Joseph; Sung, Lillian

2013-06-01

The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes.

Economic burden of primary compared with recurrent Clostridium difficile infection in hospitalized patients: a prospective cohort study.

PubMed

Shah, D N; Aitken, S L; Barragan, L F; Bozorgui, S; Goddu, S; Navarro, M E; Xie, Y; DuPont, H L; Garey, K W

2016-07-01

Few studies have investigated the additional healthcare costs of recurrent C. difficile infection (CDI). To quantify inpatient treatment costs for CDI and length of stay among hospitalized patients with primary CDI only, compared with CDI patients who experienced recurrent CDI. This was a prospective, observational cohort study of hospitalized adult patients with primary CDI followed for three months to assess for recurrent CDI episodes. Total and CDI-attributable hospital length of stay (LOS) and hospitalization costs were compared among patients who did or did not experience at least one recurrent CDI episode. In all, 540 hospitalized patients aged 62±17 years (42% males) with primary CDI were enrolled, of whom 95 patients (18%) experienced 101 recurrent CDI episodes. CDI-attributable median (interquartile range) LOS and costs (in US$) increased from 7 (4-13) days and $13,168 (7,525-24,456) for patients with primary CDI only versus 15 (8-25) days and $28,218 (15,050-47,030) for patients with recurrent CDI (P<0.0001, each). Total hospital median LOS and costs increased from 11 (6-22) days and $20,693 (11,287-41,386) for patients with primary CDI only versus 24 (11-48) days and $45,148 (20,693-82,772) for patients with recurrent CDI (P<0.0001, each). The median cost of pharmacological treatment while hospitalized was $60 (23-200) for patients with primary CDI only (N=445) and $140 (30-260) for patients with recurrent CDI (P=0.0013). This study demonstrated that patients with CDI experience a significant healthcare economic burden attributed to CDI. Economic costs and healthcare burden increased significantly for patients with recurrent CDI. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Attributable Healthcare Resource Utilization and Costs for Patients With Primary and Recurrent Clostridium difficile Infection in the United States.

PubMed

Zhang, Dongmu; Prabhu, Vimalanand S; Marcella, Stephen W

2018-04-17

The economic burden of Clostridium difficile infection (CDI), the leading cause of nosocomial infectious diarrhea, is not well understood. The objective of this study was to estimate the healthcare resource utilization (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). This is a database (MarketScan) study. Patients without CDI were matched 1:1 by propensity score to those with primary CDI but no recurrences to obtain HCRU and costs attributable to primary CDI. Patients with primary CDI but no recurrences were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for incremental cumulative hospitalized days and healthcare costs over a 6-month follow-up period were obtained by generalized linear models with a Poisson or gamma distribution and a log link. Bootstrapping was used to obtain 95% confidence intervals (CIs). A total of 55504 eligible CDI patients were identified. Approximately 25% of these CDI patients had rCDI. The cumulative hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up period were 5.20 days (95% CI, 5.01-5.39) and 1.95 days (95% CI, 1.48-2.43), respectively. The healthcare costs attributable to primary CDI and rCDI over the 6-month follow-up period were $24205 (95% CI, $23436-$25013) and $10580 (95% CI, $8849-$12446), respectively. The HCRU and costs attributable to primary CDI and rCDI are quite substantial. It is necessary to reduce the burden of CDI, especially rCDI.

Attributable Healthcare Resource Utilization and Costs for Patients With Primary and Recurrent Clostridium difficile Infection in the United States

PubMed Central

Zhang, Dongmu; Prabhu, Vimalanand S; Marcella, Stephen W

2018-01-01

Abstract Background The economic burden of Clostridium difficile infection (CDI), the leading cause of nosocomial infectious diarrhea, is not well understood. The objective of this study was to estimate the healthcare resource utilization (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). Methods This is a database (MarketScan) study. Patients without CDI were matched 1:1 by propensity score to those with primary CDI but no recurrences to obtain HCRU and costs attributable to primary CDI. Patients with primary CDI but no recurrences were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for incremental cumulative hospitalized days and healthcare costs over a 6-month follow-up period were obtained by generalized linear models with a Poisson or gamma distribution and a log link. Bootstrapping was used to obtain 95% confidence intervals (CIs). Results A total of 55504 eligible CDI patients were identified. Approximately 25% of these CDI patients had rCDI. The cumulative hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up period were 5.20 days (95% CI, 5.01–5.39) and 1.95 days (95% CI, 1.48–2.43), respectively. The healthcare costs attributable to primary CDI and rCDI over the 6-month follow-up period were $24205 (95% CI, $23436–$25013) and $10580 (95% CI, $8849–$12446), respectively. Conclusions The HCRU and costs attributable to primary CDI and rCDI are quite substantial. It is necessary to reduce the burden of CDI, especially rCDI. PMID:29360950

Outcomes associated with Clostridium difficile infection in patients with chronic liver disease.

PubMed

Dotson, Kierra M; Aitken, Samuel L; Sofjan, Amelia K; Shah, Dhara N; Aparasu, Rajender R; Garey, Kevin W

2018-05-09

Patients with chronic liver disease (CLD) have frequent exposure to Clostridium difficile infection (CDI) risk factors but the incidence and aetiology of CDI on this population is poorly understood. The aim of this study was to assess the incidence, disease presentation and outcomes of CDI in patients with underlying CLD. The Health Care and Utilization Project National Inpatient Sample (HCUP-NIS) 2009 dataset was used to identify patients with CLD who developed CDI along with matched non-CLD patients with CDI. Using the NIS dataset, the incidence rate of CDI was 189.4/10 000 discharges in CLD patients vs. 83.7/10 000 discharges in the non-CLD matched cohort (P < 0.001). Compared with non-CLD, comorbidity-matched controls with CDI, CLD patients with CDI had higher likelihood of in-hospital mortality (8.8% vs. 18.6%, P < 0.001), increased length of stay by 1.19 days (P < 0.001) and increased total costs by $8632 (P < 0.001). In separate analyses using a tertiary case database of hospitalised patients in Houston, Texas (2006-2016) with CLD and CDI (n = 41) compared with patients with CDI but not CLD (n = 111), CLD patients had significantly higher Charlson comorbidity index (P < 0.0001) but similar risk factors for CDI and CDI-related disease presentation compared with non-CLD patients. In conclusion, CDI-related risk factors were almost universally present in the CLD population. CDI resulted in worse outcomes in this population.

Hospital Clostridium difficile infection (CDI) incidence as a risk factor for hospital-associated CDI.

PubMed

Miller, Aaron C; Polgreen, Linnea A; Cavanaugh, Joseph E; Polgreen, Philip M

2016-07-01

Environmental risk factors for Clostridium difficile infections (CDIs) have been described at the room or unit level but not the hospital level. To understand the environmental risk factors for CDI, we investigated the association between institutional- and individual-level CDI. We performed a retrospective cohort study using the Healthcare Cost and Utilization Project state inpatient databases for California (2005-2011). For each patient's hospital stay, we calculated the hospital CDI incidence rate corresponding to the patient's quarter of discharge, while excluding each patient's own CDI status. Adjusting for patient and hospital characteristics, we ran a pooled logistic regression to determine individual CDI risk attributable to the hospital's CDI rate. There were 10,329,988 patients (26,086 cases and 10,303,902 noncases) who were analyzed. We found that a percentage point increase in the CDI incidence rate a patient encountered increased the odds of CDI by a factor of 1.182. As a point of comparison, a 1-percentage point increase in the CDI incidence rate that the patient encountered had roughly the same impact on their odds of acquiring CDI as a 55.8-day increase in their length of stay or a 60-year increase in age. Patients treated in hospitals with a higher CDI rate are more likely to acquire CDI. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

First clinical and microbiological characterization of Clostridium difficile infection in a Croatian University Hospital.

PubMed

Novak, Anita; Spigaglia, Patrizia; Barbanti, Fabrizio; Goic-Barisic, Ivana; Tonkic, Marija

2014-12-01

Clinical background and molecular epidemiology of Clostridium difficile infection (CDI) in the University Hospital Centre Split were investigated from January 2010 to December 2011. In total, 54 patients with first episode of CDI were consecutively included in the study based on the positive EIA test specific for A and B toxins. Demographic and clinical data were prospectively analyzed from medical records. CDI incidence rate was 0.6 per 10,000 patient-days. Thirty six cases (70.6%) were healthcare-associated, twelve cases (23.5%) were community-associated and three (5.9%) were indeterminate. Six patients (11.7%) had suffered one or more recurrences and 37 patients (72.5%) showed severe CDI. Prior therapy with third generation cephalosporin was significantly associated with severe CDI (P<0.021). Fifty four toxigenic C. difficile strains were isolated and 50 of them were available for PCR-ribotyping. Sixteen different PCR-ribotypes were identified. The most prevalent were PCR-ribotype 001 (27.8%) and 014/020 (24.1%). Twenty three strains were resistant to at least one of the antibiotics tested. Among resistant strains, three (13.0%)--all PCR-ribotype 001--were multi-resistant. Resistance to fluoroquinolones was significantly higher in strains that caused infection after previous use of fluoroquinolones (P=0.04). Copyright © 2014 Elsevier Ltd. All rights reserved.

Epidemiology of Clostridium difficile infection.

PubMed

Depestel, Daryl D; Aronoff, David M

2013-10-01

There has been dramatic change in the epidemiology of Clostridium difficile infection (CDI) since the turn of the 21st century noted by a marked increase in incidence and severity, occurring at a disproportionately higher frequency in older patients. Historically considered a nosocomial infection associated with antibiotic exposure, CDI has now also emerged in the community in populations previously considered low risk. Emerging risk factors and disease recurrence represent continued challenges in the management of CDI. The increased incidence and severity associated with CDI has coincided with the emergence and rapid spread of a previously rare strain, ribotype 027. Recent data from the United States and Europe suggest that the incidence of CDI may have reached a crescendo in the recent years and is perhaps beginning to plateau. The acute care direct costs of CDI were estimated to be US$4.8 billion in 2008. However, nearly all the published studies have focused on CDI diagnosed and treated in the acute care hospital setting and fail to measure the burden outside the hospital, including recently discharged patients, outpatients, and those in long-term care facilities. Enhanced surveillance methods are needed to monitor the incidence, to identify populations at risk, and to characterize the molecular epidemiology of strains causing CDI.

Epidemiology of Clostridium difficile Infection

PubMed Central

DePestel, Daryl D.; Aronoff, David M.

2014-01-01

There has been dramatic change in the epidemiology of Clostridium difficile infection (CDI) since the turn of the 21st Century noted by a marked increase in incidence and severity, occurring at a disproportionately higher frequency in older patients. Historically considered a nosocomial infection associated with antibiotic exposure, CDI has now also emerged in the community in populations previously considered low risk. Emerging risk factors and disease recurrence represent continued challenges in the management of CDI. The increased incidence and severity associated with CDI has coincided with the emergence and rapid spread of a previously rare strain, ribotype 027. Recent data from the U.S. and Europe suggest the incidence of CDI may have reached a crescendo in recent years and is perhaps beginning to plateau. The acute-care direct costs of CDI were estimated to be $4.8 billion in 2008. However, nearly all the published studies have focused on CDI diagnosed and treated in acute-care hospital setting and fail to measure the burden outside the hospital, including recently discharged patients, outpatients, and those in long-term care facilities. Enhanced surveillance methods are needed to monitor the incidence, identify populations at risk, and characterize the molecular epidemiology of strains causing CDI. PMID:24064435

[Clostridium difficile infection (CDI) in the course of time - an issue only for the internist?].

PubMed

Weis, S; John, E; Lippmann, N; Mössner, J; Lübbert, C

2014-08-01

Toxigenic strains of Clostridium (C.) difficile are the most prevalent pathogens of antibiotic associated intestinal disease and nosocomial diarrhoea. During the last 10 years, incidences of C. difficile infection (CDI) have increased worldwide. With clinical and microbiological original data for 2002-2012 from the University Hospitals Leipzig and Halle (Saale), Germany, the authors illustrate the current situation regarding CDI in the states of Saxony and Saxony-Anhalt and exemplify the latest developments in terms of incidence, prevalence of resistance, diagnosis and treatment strategies regarding CDI with an emphasis on surgical options. Following the general trend, at the University Hospitals of Leipzig and Halle (Saale) there was also an increase in incidence of CDI, especially of severe clinical courses. In primary and secondary care facilities, prevention of CDI is based on hygiene management and restricted usage of antibiotics, preferably as "Antibiotic Stewardship" programmes. In 2012, the new macrocyclic antibiotic Fidaxomicin was approved in the European Union for the treatment of CDI. The therapeutic armamentarium, previously based on metronidazole or vancomycin, has now been enriched by a substance that presumably will reduce the rate of recurrence of CDI. Moreover, early data from case series and controlled trials suggest that the re-establishment of eubiosis in the colon of patients with recurrent CDI by stool transplantation from healthy donors is an alternative to antibiotics. Standard surgical intervention for refractory CDI is subtotal colectomy with terminal ileostomy. In patients with adequate life expectancy and without organ dysfunction, a colon-saving surgical technique should be considered. Taking antibiotics for most remains the main risk factor for suffering from symptomatic CDI. With the introduction of Fidaxomicin there is hope for an improvement in the conservative treatment of CDI. Stool transplants from healthy donors are now considered to be better than giving antibiotics for severe CDI, but this treatment has not found broad acceptance yet. In cases with a lack of early treatment success, the surgeon must be consulted. Here, the evidence for preferably colon-saving surgical procedures is so far unfortunately low. Georg Thieme Verlag KG Stuttgart · New York.

Impact of real-time notification of Clostridium difficile test results and early initiation of effective antimicrobial therapy.

PubMed

Polen, Christian B; Judd, William R; Ratliff, Patrick D; King, Gregory S

2018-05-01

Clostridium difficile is a prominent nosocomial pathogen and is the most common causative organism of health care-associated diarrhea. To our knowledge, no studies have investigated the impact of real-time notification of culture results with rapid antimicrobial stewardship program (ASP) intervention in the setting of C difficile infection (CDI). The purpose of this study was to assess the impact of real-time notification of detection of toxigenic C difficile by DNA amplification results in patients with confirmed CDI. This is a single-center, retrospective cohort study at a 433-bed tertiary medical center in central Kentucky. The study consisted of 2 arms: patients treated for CDI prior to implementation of real-time provider notification and patients postimplementation. The primary outcome was time to initiation of effective antimicrobial therapy. The median time to initiation of effective antimicrobial therapy decreased from 5.75 hours in the preimplementation cohort to 2.05 hours in the postimplementation cohort (P = .001). ASP intervention also resulted in a shorter time from detection of CDI to order entry of effective antimicrobial therapy in the patient's electronic medical record (3.0 vs 0.6 hours; P = .001). The implementation of a real-time notification system to alert a pharmacist-led ASP of toxigenic CDI resulted in statistically significant shorter times to order entry and subsequent initiation of effective antimicrobial therapy and contact precautions. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The Role of Rho GTPases in Toxicity of Clostridium difficile Toxins

PubMed Central

Chen, Shuyi; Sun, Chunli; Wang, Haiying; Wang, Jufang

2015-01-01

Clostridium difficile (C. difficile) is the main cause of antibiotic-associated diarrhea prevailing in hospital settings. In the past decade, the morbidity and mortality of C. difficile infection (CDI) has increased significantly due to the emergence of hypervirulent strains. Toxin A (TcdA) and toxin B (TcdB), the two exotoxins of C. difficile, are the major virulence factors of CDI. The common mode of action of TcdA and TcdB is elicited by specific glucosylation of Rho-GTPase proteins in the host cytosol using UDP-glucose as a co-substrate, resulting in the inactivation of Rho proteins. Rho proteins are the key members in many biological processes and signaling pathways, inactivation of which leads to cytopathic and cytotoxic effects and immune responses of the host cells. It is supposed that Rho GTPases play an important role in the toxicity of C. difficile toxins. This review focuses on recent progresses in the understanding of functional consequences of Rho GTPases glucosylation induced by C. difficile toxins and the role of Rho GTPases in the toxicity of TcdA and TcdB. PMID:26633511

Survey of diagnostic and typing capacity for Clostridium difficile infection in Europe, 2011 and 2014.

PubMed

van Dorp, Sofie M; Notermans, Daan W; Alblas, Jeroen; Gastmeier, Petra; Mentula, Silja; Nagy, Elisabeth; Spigaglia, Patrizia; Ivanova, Katiusha; Fitzpatrick, Fidelma; Barbut, Frédéric; Morris, Trefor; Wilcox, Mark H; Kinross, Pete; Suetens, Carl; Kuijper, Ed J

2016-07-21

Suboptimal laboratory diagnostics for Clostridium difficile infection (CDI) impedes its surveillance and control across Europe. We evaluated changes in local laboratory CDI diagnostics and changes in national diagnostic and typing capacity for CDI during the European C. difficile Infection Surveillance Network (ECDIS-Net) project, through cross-sectional surveys in 33 European countries in 2011 and 2014. In 2011, 126 (61%) of a convenience sample of 206 laboratories in 31 countries completed a survey on local diagnostics. In 2014, 84 (67%) of these 126 laboratories in 26 countries completed a follow-up survey. Among laboratories that participated in both surveys, use of CDI diagnostics deemed 'optimal' or 'acceptable' increased from 19% to 46% and from 10% to 15%, respectively (p  < 0.001). The survey of national capacity was completed by national coordinators of 31 and 32 countries in 2011 and 2014, respectively. Capacity for any C. difficile typing method increased from 22/31 countries in 2011 to 26/32 countries in 2014; for PCR ribotyping from 20/31 countries to 23/32 countries, and specifically for capillary PCR ribotyping from 7/31 countries to 16/32 countries. While our study indicates improved diagnostic capability and national capacity for capillary PCR ribotyping across European laboratories between 2011 and 2014, increased use of 'optimal' diagnostics should be promoted. This article is copyright of The Authors, 2016.

Hospitalized Patients with Cirrhosis Should Be Screened for Clostridium difficile Colitis.

PubMed

Saab, Sammy; Alper, Theodore; Sernas, Ernesto; Pruthi, Paridhima; Alper, Mikhail A; Sundaram, Vinay

2015-10-01

Clostridium difficile infection (CDI) is an important public health problem in hospitalized patients. Patients with cirrhosis are particularly at risk of increased associated morbidity, mortality, and healthcare utilization from CDI. The aim of this study was to assess the pharmacoeconomic impact of CDI screening on hospitalized patients with cirrhosis. A Markov model was used to compare costs and outcomes of two strategies for the screening of CDI. The first strategy consisted of screening all patients for CDI and treating if detected (screening). In the second strategy, only patients found to have symptomatic CDI were treated (no screening). The probability of underlying CDI prevalence, symptomatic CDI infection, and likelihood of recurrent infection were varied in a sensitivity analysis. The costs of antibiotics and hospitalization were also assessed. Differences in outcome were expressed in ratio of the total costs associated with screening to the total costs associated without screening. The results of our model showed that screening for CDI was consistently associated with improved healthcare outcomes and decreased healthcare utilization across all variables in the one- and two-way sensitivity analyses. Using baseline assumptions, the costs associated with the no screening strategy were 3.54 times that of the screening strategy. Moreover, the mortality for symptomatic CDI was lower in the screening strategy than the no screening strategy. The screening strategy results in less healthcare utilization and improved clinical outcomes. Screening for CDI measures favorably.

Risk Factors for Hospital-acquired Clostridium difficile Infection Among Pediatric Patients With Cancer.

PubMed

Daida, Atsuro; Yoshihara, Hiroki; Inai, Ikuko; Hasegawa, Daisuke; Ishida, Yasushi; Urayama, Kevin Y; Manabe, Atsushi

2017-04-01

Hospital-acquired Clostridium difficile infection (CDI) may cause life-threatening colitis for children with cancer, making identification of risk factors important. We described characteristics of pediatric cancer patients with primary and recurring CDI, and evaluated potential risk factors. Among 189 cancer patients, 51 cases (27%) of CDI and 94 matched controls of cancer patients without CDI were analyzed. Multivariable logistic regression was used to evaluate the association between CDI and several potential risk factors. Median age of CDI cases was lower (3.3 y; 0.60 to 16.2) than controls (7.7 y; 0.4 to 20.5). Median duration of neutropenia before CDI was longer for CDI cases (10.0 d; 0.0 to 30.0) compared with duration calculated from reference date in controls (6.0 d; 0.0 to 29.0). Multivariable analysis showed that older age was associated with reduced risk (≥7 vs. 0 to 3 y, odds ratio=0.11; 95% confidence interval, 0.02-0.54), and prolonged neutropenia was associated with increased risk (odds ratio=1.11; 95% confidence interval, 1.01-1.22). CDI recurred in 26% of cases. Younger age and prolonged neutropenia were risk factors for CDI in children with cancer. Increasing awareness to these risk factors will help to identify opportunities for CDI prevention in cancer patients.

Survey of Clostridium difficile infection surveillance systems in Europe, 2011.

PubMed

Kola, Axel; Wiuff, Camilla; Akerlund, Thomas; van Benthem, Birgit H; Coignard, Bruno; Lyytikäinen, Outi; Weitzel-Kage, Doris; Suetens, Carl; Wilcox, Mark H; Kuijper, Ed J; Gastmeier, Petra

2016-07-21

To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol. This article is copyright of The Authors, 2016.

Association Between Outpatient Antibiotic Prescribing Practices and Community-Associated Clostridium difficile Infection

PubMed Central

Dantes, Raymund; Mu, Yi; Hicks, Lauri A.; Cohen, Jessica; Bamberg, Wendy; Beldavs, Zintars G.; Dumyati, Ghinwa; Farley, Monica M.; Holzbauer, Stacy; Meek, James; Phipps, Erin; Wilson, Lucy; Winston, Lisa G.; McDonald, L. Clifford; Lessa, Fernanda C.

2015-01-01

Background. Antibiotic use predisposes patients to Clostridium difficile infections (CDI), and approximately 32% of these infections are community-associated (CA) CDI. The population-level impact of antibiotic use on adult CA-CDI rates is not well described. Methods. We used 2011 active population- and laboratory-based surveillance data from 9 US geographic locations to identify adult CA-CDI cases, defined as C difficile-positive stool specimens (by toxin or molecular assay) collected from outpatients or from patients ≤3 days after hospital admission. All patients were surveillance area residents and aged ≥20 years with no positive test ≤8 weeks prior and no overnight stay in a healthcare facility ≤12 weeks prior. Outpatient oral antibiotic prescriptions dispensed in 2010 were obtained from the IMS Health Xponent database. Regression models examined the association between outpatient antibiotic prescribing and adult CA-CDI rates. Methods. Healthcare providers prescribed 5.2 million courses of antibiotics among adults in the surveillance population in 2010, for an average of 0.73 per person. Across surveillance sites, antibiotic prescription rates (0.50–0.88 prescriptions per capita) and unadjusted CA-CDI rates (40.7–139.3 cases per 100 000 persons) varied. In regression modeling, reducing antibiotic prescribing rates by 10% among persons ≥20 years old was associated with a 17% (95% confidence interval, 6.0%–26.3%; P = .032) decrease in CA-CDI rates after adjusting for age, gender, race, and type of diagnostic assay. Reductions in prescribing penicillins and amoxicillin/clavulanic acid were associated with the greatest decreases in CA-CDI rates. Conclusions and Relevance. Community-associated CDI prevention should include reducing unnecessary outpatient antibiotic use. A modest reduction of 10% in outpatient antibiotic prescribing can have a disproportionate impact on reducing CA-CDI rates. PMID:26509182

Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature.

PubMed

Ogielska, Maja; Lanotte, Philippe; Le Brun, Cécile; Valentin, Anne Sophie; Garot, Denis; Tellier, Anne-Charlotte; Halimi, Jean Michel; Colombat, Philippe; Guilleminault, Laurent; Lioger, Bertrand; Vegas, Hélène; De Toffol, Bertrand; Constans, Thierry; Bernard, Louis

2015-08-01

Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhoea. People in the general community are not usually considered to be at risk of CDI. CDI is associated with a high risk of morbidity and mortality. The risk of severity is defined by the Clostridium Severity Index (CSI). The cases of 136 adult patients with CDI treated at the University Hospital of Tours, France between 2008 and 2012 are described. This was a retrospective study. Among the 136 patients included, 62 were men and 74 were women. Their median age was 64.4 years (range 18-97 years). Twenty-six of the 136 (19%) cases were community-acquired (CA) and 110 (81%) were healthcare-acquired (HCA). The major risk factors for both groups were long-term treatment with proton pump inhibitors (54% of CA, 53% of HCA patients) and antibiotic treatment within the 2.5 months preceding the CDI (50% of CA, 91% of HCA). The CSI was higher in the CA-CDI group (1.56) than in the HCA-CDI group (1.39). Intensive care was required for 8% of CA-CDI and 16.5% of HCA-CDI patients. CDI can cause community-acquired diarrhoea, and CA-CDI may be more severe than HCA-CDI. Prospective studies of CDI involving people from the general community without risk factors are required to confirm this observation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical and Microbiologic Characteristics of Clostridium difficile Infection Caused by Binary Toxin Producing Strain in Korea.

PubMed

Kim, Jieun; Seo, Mi-Ran; Kang, Jung Oak; Choi, Tae Yeal; Pai, Hyunjoo

2013-06-01

Binary toxin-producing Clostridium difficile infections (CDI) are known to be more severe and to cause higher case fatality rates than those by binary toxin-negative isolates. There has been few data of binary toxin-producing CDI in Korea. Objective of the study is to characterize clinical and microbiological trait of CDI cause by binary-toxin producing isolates in Korea. From September 2008 through January 2010, clinical characteristics, medication history and treatment outcome of all the CDI patients were collected prospectively. Toxin characterization, PCR ribotyping and antibiotic susceptibility were performed with the stool isolates of C. difficile. During the period, CDI caused by 11binary toxin-producing isolates and 105 toxin A & toxin B-positive binary toxin-negative isolates were identified. Comparing the disease severity and clinical findings between two groups, leukocytosis and mucoid stool were more frequently observed in patients with binary toxin-positive isolates (OR: 5.2, 95% CI: 1.1 to 25.4, P = 0.043; OR: 7.6, 95% CI: 1.6 to 35.6, P = 0.010, respectively), but clinical outcome of 2 groups did not show any difference. For the risk factors for acquisition of binary toxin-positive isolates, previous use of glycopeptides was the significant risk factor (OR: 6.2, 95% CI: 1.4 to 28.6, P = 0.019), but use of probiotics worked as an inhibitory factor (OR: 0.1, 95% CI: 0.0 to 0.8; P = 0.026). PCR ribotypes of binary toxinproducing C. difficile showed variable patterns: ribotype 130, 4 isolates; 027, 3 isolates; 267 and 122, 1 each isolate and unidentified C1, 2 isolates. All 11 binary toxin-positive isolates were highly susceptible to clindamycin, moxifloxacin, metronidazole, vancomycin and piperacillin-tazobactam, however, 1 of 11 of the isolates was resistant to rifaximin. Binary toxin-producing C. difficile infection was not common in Korea and those isolates showed diverse PCR ribotypes with high susceptibility to antimicrobial agents. Glycopeptide use was a risk factor for CDI by those isolates.

Clinical and Microbiologic Characteristics of Clostridium difficile Infection Caused by Binary Toxin Producing Strain in Korea

PubMed Central

Kim, Jieun; Seo, Mi-ran; Kang, Jung Oak; Choi, Tae Yeal

2013-01-01

Background Binary toxin-producing Clostridium difficile infections (CDI) are known to be more severe and to cause higher case fatality rates than those by binary toxin-negative isolates. There has been few data of binary toxin-producing CDI in Korea. Objective of the study is to characterize clinical and microbiological trait of CDI cause by binary-toxin producing isolates in Korea. Materials and Methods From September 2008 through January 2010, clinical characteristics, medication history and treatment outcome of all the CDI patients were collected prospectively. Toxin characterization, PCR ribotyping and antibiotic susceptibility were performed with the stool isolates of C. difficile. Results During the period, CDI caused by 11binary toxin-producing isolates and 105 toxin A & toxin B-positive binary toxin-negative isolates were identified. Comparing the disease severity and clinical findings between two groups, leukocytosis and mucoid stool were more frequently observed in patients with binary toxin-positive isolates (OR: 5.2, 95% CI: 1.1 to 25.4, P = 0.043; OR: 7.6, 95% CI: 1.6 to 35.6, P = 0.010, respectively), but clinical outcome of 2 groups did not show any difference. For the risk factors for acquisition of binary toxin-positive isolates, previous use of glycopeptides was the significant risk factor (OR: 6.2, 95% CI: 1.4 to 28.6, P = 0.019), but use of probiotics worked as an inhibitory factor (OR: 0.1, 95% CI: 0.0 to 0.8; P = 0.026). PCR ribotypes of binary toxinproducing C. difficile showed variable patterns: ribotype 130, 4 isolates; 027, 3 isolates; 267 and 122, 1 each isolate and unidentified C1, 2 isolates. All 11 binary toxin-positive isolates were highly susceptible to clindamycin, moxifloxacin, metronidazole, vancomycin and piperacillin-tazobactam, however, 1 of 11 of the isolates was resistant to rifaximin. Conclusions Binary toxin-producing C. difficile infection was not common in Korea and those isolates showed diverse PCR ribotypes with high susceptibility to antimicrobial agents. Glycopeptide use was a risk factor for CDI by those isolates. PMID:24265965

Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum

PubMed Central

Koon, Hon Wai; Ho, Samantha; Hing, Tressia C.; Cheng, Michelle; Chen, Xinhua; Ichikawa, Yoshi; Kelly, Ciarán P.

2014-01-01

Clostridium difficile infection (CDI) is a common, debilitating infection with high morbidity and mortality. C. difficile causes diarrhea and intestinal inflammation by releasing two toxins, toxin A and toxin B. The macrolide antibiotic fidaxomicin was recently shown to be effective in treating CDI, and its beneficial effect was associated with fewer recurrent infections in CDI patients. Since other macrolides possess anti-inflammatory properties, we examined the possibility that fidaxomicin alters C. difficile toxin A-induced ileal inflammation in mice. The ileal loops of anesthetized mice were injected with fidaxomicin (5, 10, or 20 μM), and after 30 min, the loops were injected with purified C. difficile toxin A or phosphate-buffered saline alone. Four hours after toxin A administration, ileal tissues were processed for histological evaluation (epithelial cell damage, neutrophil infiltration, congestion, and edema) and cytokine measurements. C. difficile toxin A caused histologic damage, evidenced by increased mean histologic score and ileal interleukin-1β (IL-1β) protein and mRNA expression. Treatment with fidaxomicin (20 μM) or its primary metabolite, OP-1118 (120 μM), significantly inhibited toxin A-mediated histologic damage and reduced the mean histology score and ileal IL-1β protein and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with vancomycin (20 μM) and metronidazole (20 μM) did not alter toxin A-induced histologic damage and IL-1β protein expression. In addition to its well known antibacterial effects against C. difficile, fidaxomicin may possess anti-inflammatory activity directed against the intestinal effects of C. difficile toxins. PMID:24890583

Measuring the severity of Clostridium difficile infection: implications for management and drug development.

PubMed

Belmares, Jaime; Gerding, Dale N; Tillotson, Glenn; Johnson, Stuart

2008-12-01

The appropriate management of Clostridium difficile infection (CDI) has become a growing clinical and economic issue, as a new epidemic strain with enhanced virulence is causing increased morbidity and mortality. Presently, only two antibiotics (metronidazole and vancomycin) are routinely used to treat CDI. Both increasing disease severity and recurrent infections have been an impetus not only to develop new agents, but also to better recognize which patients are at highest risk for treatment failure and/or recurrence so that treatments can be optimized from the outset. The availability of a standardized and validated system for stratifying CDI severity could improve patient management and potentially accelerate the development of new treatment agents.

Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection.

PubMed

Mora, Andrea L; Salazar, Miguel; Pablo-Caeiro, Juan; Frost, Craig P; Yadav, Yashoo; DuPont, Herbert L; Garey, Kevin W

2012-04-01

Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P < 0.0001). One hundred of 21,396 (0.47%) patients who did not receive opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P < 0.0001). Similar results were observed using a multivariate Cox proportional hazard model. Moderate to high use of opioid analgesics were associated with an increased risk of CDI.

Identification of target risk groups for population-based Clostridium difficile infection prevention strategies using a population attributable risk approach.

PubMed

Oh, Sung-Hee; Kang, Hye-Young

2018-01-01

We aimed to determine risk factors associated with Clostridium difficile infection (CDI) and assess the contributions of these factors on CDI burden. We conducted a 1:4 matched case-control study using a national claims dataset. Cases were incident CDI without a history of CDI in the previous 84 days, and were age- and sex-matched with control patients. We ascertained exposure, defined as a history of morbidities and drug use within 90 days. The population attributable risk (PAR) percent for risk factors was estimated using odds ratios (ORs) obtained from the case-control study. Overall, the strongest CDI-associated risk factors, which have significant contributions to the CDI burden as well, were the experience of gastroenteritis (OR=5.08, PAR%=17.09%) and use of antibiotics (OR=1.69, PAR%=19.00%), followed by the experiences of female pelvic infection, irritable bowel syndrome, inflammatory bowel disease, and pneumonia, and use of proton-pump inhibitors (OR=1.52-2.37, PAR%=1.95-2.90). The control of risk factors that had strong association with CDI and affected large proportions of total CDI cases would be beneficial for CDI prevention. We suggest performing CDI testing for symptomatic patients with gastroenteritis and implementing antibiotics stewardship. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Prevention of Clostridium difficile infection in rural hospitals.

PubMed

Haun, Nicholas; Hofer, Adam; Greene, M Todd; Borlaug, Gwen; Pritchett, Jenny; Scallon, Tina; Safdar, Nasia

2014-03-01

Prevention of Clostridium difficile infection (CDI) remains challenging across the spectrum of health care. There are limited data on prevention practices for CDI in the rural health care setting. An electronic survey was administered to 21 rural facilities in Wisconsin, part of the Rural Wisconsin Health Cooperative. Data were collected on hospital characteristics and practices to prevent endemic CDI. Fifteen facilities responded (71%). Nearly all respondent facilities reported regular use of dedicated patient care items, use of gown and gloves, private patient rooms, hand hygiene, and room cleaning. Facilities in which the infection preventionist thought the support of his/her leadership to be "Very good" or "Excellent" employed significantly more CDI practices (13.3 ± 2.4 [standard deviation]) compared with infection preventionists who thought there was less support from leadership (9.8 ± 3.0, P = .033). Surveillance for CDI was highly variable. The most frequent barriers to implementation of CDI prevention practices included lack of adequate resources, lack of a physician champion, and difficulty keeping up with new recommendations. Although most rural facilities in our survey reported using evidence-based practices for prevention of CDI, surveillance practices were highly variable, and data regarding the impact of these practices on CDI rates were limited. Future efforts that correlate CDI prevention initiatives and CDI incidence will help develop evidence-based practices in these resource-limited settings. Published by Mosby, Inc.

The presence of IL-8 +781 T/C polymorphism is associated with the parameters of severe Clostridium difficile infection.

PubMed

Czepiel, Jacek; Biesiada, Grażyna; Dróżdż, Mirosław; Gdula-Argasińska, Joanna; Żurańska, Justyna; Marchewka, Jakub; Perucki, William; Wołkow, Paweł; Garlicki, Aleksander

2018-01-01

There is large variation in the clinical manifestations of Clostridium difficile infection (CDI). We also still can not predict which patients are more susceptible to reinfection with CDI. The aim of our study was to evaluate the effect of gene single nucleotide polymorphisms (SNP) of proinflammatory cytokines, specifically IL-1β, IL-8 on the development, clinical course and recurrence of CDI. We performed a prospective study of adults (130 people ≥ 18 years) including 65 patients with CDI treated in tertiary hospital and 65 healthy persons. The following 3 variants were analyzed for the occurrence of gene polymorphisms in patients with CDI versus the control group: IL-1β +3953 A/G (rs1143634), IL-1β -31 A/G (rs1143627), and IL-8 +781 T/C (rs2227306). Then, we assessed the correlation between these genetic polymorphisms and biochemical parameters important in CDI course, CDI severity as well as CDI recurrence. The presence of genetic polymorphisms of IL-1β +3953 A/G, -31 A/G and IL-8 +781 T/C did not have an effect on the development or recurrence of CDI. The presence of IL-8 +781 T/C polymorphism is associated with the severe CDI. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Comparison of Current Guidelines of Five International Societies on Clostridium difficile Infection Management.

PubMed

Fehér, Csaba; Mensa, Josep

2016-09-01

Clostridium difficile infection (CDI) is increasingly recognized as an emerging healthcare problem of elevated importance. Prevention and treatment strategies are constantly evolving along with the apperance of new scientific evidence and novel treatment methods, which is well-reflected in the differences among consecutive international guidelines. In this article, we summarize and compare current guidelines of five international medical societies on CDI management, and discuss some of the controversial and currently unresolved aspects which should be addressed by future research.

Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value.

PubMed

D'Ostroph, Amanda R; So, Tsz-Yin

2017-01-01

The incidence of Clostridium difficile infection (CDI) in pediatric patients continues to rise. Most of the pediatric recommendations for CDI treatment are extrapolated from the literature and guidelines for adults. The American Academy of Pediatrics recommends oral metronidazole as the first-line treatment option for an initial CDI and the first recurrence if they are mild to moderate in severity. Oral vancomycin is recommended to be used for severe CDI and the second recurrent infection. Additional pulsed regimen of oral vancomycin, which is tapered, may increase efficacy in refractory patients. However, there is lack of large studies evaluating the use of fidaxomicin in pediatrics to know whether it could be a safe and effective treatment option for difficult-to-treat patients. Fidaxomicin is associated with higher total drug costs compared to metronidazole and vancomycin, but the literature supports its use due to a lower rate of CDI recurrence, which may result in cost savings. Further studies are warranted to evaluate the use of fidaxomicin in patients <18 years old and to understand its role in the standard of care for pediatric patients with CDI.

The impact of horizontal gene transfer on the biology of Clostridium difficile.

PubMed

Roberts, Adam P; Allan, Elaine; Mullany, Peter

2014-01-01

Clostridium difficile infection (CDI) is now recognised as the main cause of healthcare associated diarrhoea. Over the recent years there has been a change in the epidemiology of CDI with certain related strains dominating infection. These strains have been termed hyper-virulent and have successfully spread across the globe. Many C. difficile strains have had their genomes completely sequenced allowing researchers to build up a very detailed picture of the contribution of horizontal gene transfer to the adaptive potential, through the acquisition of mobile DNA, of this organism. Here, we review and discuss the contribution of mobile genetic elements to the biology of this clinically important pathogen. © 2014 Elsevier Ltd All rights reserved.

Economic healthcare costs of Clostridium difficile infection: a systematic review.

PubMed

Ghantoji, S S; Sail, K; Lairson, D R; DuPont, H L; Garey, K W

2010-04-01

Clostridium difficile infection (CDI) is the leading cause of infectious diarrhoea in hospitalised patients. CDI increases patient healthcare costs due to extended hospitalisation, re-hospitalisation, laboratory tests and medications. However, the economic costs of CDI on healthcare systems remain uncertain. The purpose of this study was to perform a systematic review to summarise available studies aimed at defining the economic healthcare costs of CDI. We conducted a literature search for peer-reviewed studies that investigated costs associated with CDI (1980 to present). Thirteen studies met inclusion and exclusion criteria. CDI costs in 2008 US dollars were calculated using the consumer price index. The total and incremental costs for primary and recurrent CDI were estimated. Of the 13, 10 were from the USA and one each from Canada, UK, and Ireland. In US-based studies incremental cost estimates ranged from $2,871 to $4,846 per case for primary CDI and from $13,655 to $18,067 per case for recurrent CDI. US-based studies in special populations (subjects with irritable bowel disease, surgical inpatients, and patients treated in the intensive care unit) showed an incremental cost range from $6,242 to $90,664. Non-US-based studies showed an estimated incremental cost of $5,243 to $8,570 per case for primary CDI and $13,655 per case for recurrent CDI. Economic healthcare costs of CDI were high for primary and recurrent cases. The high cost associated with CDI justifies the use of additional resources for CDI prevention and control. Copyright (c) 2009 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

High Rate of Alternative Diagnoses in Patients Referred for Presumed Clostridium difficile Infection

PubMed Central

Jackson, Melissa; Olefson, Sidney; Machan, Jason T.; Kelly, Colleen R.

2015-01-01

Goals We evaluated a cohort of patients referred to our center for presumed recurrent Clostridium difficile infection (CDI) to determine final diagnoses and outcomes. Background As rates of CDI have increased, more patients are diagnosed with recurrent CDI and other sequelae of the infection. Distinguishing symptomatic patients with CDI from those who are colonized with an alternative etiology of diarrheal symptoms may be challenging. Methods We performed a retrospective review of 117 patients referred to our center for recurrent CDI between January 2013 and June 2014. Data collected included demographics, referring provider, previous anti-CDI treatment, and significant medical conditions. Additionally we gathered data on atypical features of CDI and investigations obtained to investigate etiology of symptoms. Outcomes included rates of alternative diagnoses and the accuracy of CDI diagnosis by referral source. Results The mean age was 61 years and 70% were female. 29 patients (25%) were determined to have a non-CDI diagnosis. Most common alternative diagnoses included irritable bowel syndrome (18 patients: 62%) and inflammatory bowel disease (3:10 %). Age was inversely correlated with rate of non-CDI diagnosis (p=0.016). Of the remaining 88 (75%) patients with a confirmed diagnosis of CDI, 25 (28%) received medical therapy alone and 63 (72%) underwent fecal microbiota transplantation (FMT). Conclusion Among patients referred to our center for recurrent CDI, a considerable percentage did not have CDI, but rather an alternative diagnosis, most commonly IBS. The rate of alternative diagnosis correlated inversely with age. Providers should consider other etiologies of diarrhea in patients presenting with features atypical of recurrent CDI. PMID:26565971

Cysteine desulfurase IscS2 plays a role in oxygen resistance in Clostridium difficile.

PubMed

Giordano, Nicole; Hastie, Jessica L; Smith, Ashley D; Foss, Elissa D; Gutierrez-Munoz, Daniela F; Carlson, Paul E

2018-06-04

Clostridium difficile is an anaerobic, spore-forming bacterium capable of colonizing the gastrointestinal tract of humans following disruption of the normal microbiota, typically from antibiotic therapy for an unrelated infection. With approximately 500,000 confirmed infections leading to 29,000 deaths per year in the United States, C. difficile infection (CDI) is an urgent public health threat. We previously determined C. difficile survives in up to 3% oxygen. Low levels of oxygen are present in the intestinal tract with the higher concentrations being associated with the epithelial cell surface. Additionally, antibiotic treatment, the greatest risk factor for CDI, increases intestinal oxygen concentration. Therefore, we hypothesized that the C. difficile genome encodes mechanisms for survival during oxidative stress. Previous data have shown that cysteine desulfurases involved in iron-sulfur cluster assembly are involved in protecting bacteria from oxidative stress. In this study, deletion of a putative cysteine desulfurase ( Cd 630_12790/IscS2) involved in the iron sulfur cluster (Isc) system caused a severe growth defect in the presence of 2% oxygen. Additionally, this mutant delayed colonization in a conventional mouse model of CDI, and failed to colonize in a germ-free model, which has higher intestinal oxygen levels. These data imply an undefined role for this cysteine desulfurase in protecting C. difficile from low levels of oxygen in the gut. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Notice to Readers: The Effect of Falsified Clostridium difficile Infections Surveillance Data on Results Reported in MMWR.

PubMed

2015-09-11

In 2012, MMWR published the report, "Vital Signs: Preventing Clostridium difficile Infections," which examined Clostridium difficile infection (CDI) surveillance data. This report contained several errors pertaining to Emerging Infections Program (EIP) data. These errors occurred as a result of scientific misconduct by a former employee of the Oregon Health Authority. The Public Health Service Office of Research Integrity has determined that the former employee falsified or fabricated data for 56 Oregon EIP CDI case report forms (https://ori.hhs.gov/content/case-summary-asherin-ryan). The authors re-analyzed the EIP data to determine if the removal of all Oregon CDI cases (57 total cases) from the 10,342 cases included in the original publication altered the previously reported results. It did not. Re-analysis confirms the conclusions in the original report. Data in the original report from sources other than the Oregon Health Authority (i.e., from other EIP sites, the National Healthcare Safety Network, and Illinois, Massachusetts, and New York CDI prevention programs) were not involved in the research misconduct.Errata for the 2012 report have been published in this issue of MMWR.

Clostridium difficile infection seasonality: patterns across hemispheres and continents - a systematic review.

PubMed

Furuya-Kanamori, Luis; McKenzie, Samantha J; Yakob, Laith; Clark, Justin; Paterson, David L; Riley, Thomas V; Clements, Archie C

2015-01-01

Studies have demonstrated seasonal variability in rates of Clostridium difficile infection (CDI). Synthesising all available information on seasonality is a necessary step in identifying large-scale epidemiological patterns and elucidating underlying causes. Three medical and life sciences publication databases were searched from inception to October 2014 for longitudinal epidemiological studies written in English, Spanish or Portuguese that reported the incidence of CDI. The monthly frequency of CDI were extracted, standardized and weighted according to the number of follow-up months. Cross correlation coefficients (XCORR) were calculated to examine the correlation and lag between the year-month frequencies of reported CDI across hemispheres and continents. The search identified 13, 5 and 2 studies from North America, Europe, and Oceania, respectively that met the inclusion criteria. CDI had a similar seasonal pattern in the Northern and Southern Hemisphere characterized by a peak in spring and lower frequencies of CDI in summer/autumn with a lag of 8 months (XCORR = 0.60) between hemispheres. There was no difference between the seasonal patterns across European and North American countries. CDI demonstrates a distinct seasonal pattern that is consistent across North America, Europe and Oceania. Further studies are required to identify the driving factors of the observed seasonality.

Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study.

PubMed

Zhang, Shanshan; Palazuelos-Munoz, Sarah; Balsells, Evelyn M; Nair, Harish; Chit, Ayman; Kyaw, Moe H

2016-08-25

Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset CDI ($20,095 [90 % CI: $4991, $35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range: $1.9-$7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed.

An economic evaluation of Clostridium difficile infection management in an Italian hospital environment.

PubMed

Magalini, S; Pepe, G; Panunzi, S; Spada, P L; De Gaetano, A; Gui, D

2012-12-01

Clostridium difficile infection (CDI) accounts for the majority of nosocomial cases of diarrhea, and with recent upsurge of multidrug-resistant strains, morbidity and mortality have increased. Data on clinical impact of CDI come mostly from Anglo-Saxon countries, while in Italy only two studies address the issue and no economic data exist on costs of CDI in the in hospital setting. A retrospective cross-sectional study with pharmacoeconomic analysis was performed on the CDI series of the Policlinico Gemelli of Rome, a major 1400 bed Hospital. The clinical charts of 133 patients in a 26 month period were reviewed. All costs of the involved resources were calculated and statistical analysis was carried out with means and standard deviations, and categorical variables as number and percentages. The results show the significant sanitary costs of CDI in an Italian hospital setting. The cost analysis of the various elements (exams, imaging studies, therapies, etc.) shows that none independently influences the high cost burden of CDI, but that it is the simple length of hospital stay that represents the most important factor. Prevention of CDI is the most cost-effective approach. The major break-through in cost reduction of CDI would be a therapeutical intervention or procedure that shortens hospital length of stay.

Antibiotic Treatment of Hospitalized Patients with Pneumonia Complicated by Clostridium Difficile Infection.

PubMed

Zycinska, K; Chmielewska, M; Lenartowicz, B; Hadzik-Blaszczyk, M; Cieplak, M; Kur, Z; Krupa, R; Wardyn, K A

2016-01-01

Clostridium difficile infection (CDI) is one of the most common gastrointestinal complication after antimicrobial treatment. It is estimated that CDI after pneumonia treatment is connected with a higher mortality than other causes of hospitalization. The aim of the study was to assess the relationship between the kind of antibiotic used for pneumonia treatment and mortality from post-pneumonia CDI. We addressed the issue by examining retrospectively the records of 217 patients who met the diagnostic criteria of CDI. Ninety four of those patients (43.3 %) came down with CDI infection after pneumonia treatment. Fifty of the 94 patients went through severe or severe and complicated CDI. The distribution of antecedent antibiotic treatment of pneumonia in these 50 patients was as follows: ceftriaxone in 14 (28 %) cases, amoxicillin with clavulanate in 9 (18 %), ciprofloxacin in 8 (16.0 %), clarithromycin in 7 (14 %), and cefuroxime and imipenem in 6 (12 %) each. The findings revealed a borderline enhancement in the proportion of deaths due to CDI in the ceftriaxone group compared with the ciprofloxacin, cefuroxime, and imipenem groups. The corollary is that ceftriaxone should be shunned in pneumonia treatment. The study demonstrates an association between the use of a specific antibiotic for pneumonia treatment and post-pneumonia mortality in patients who developed CDI.

A multi-institutional cohort study confirming the risks of Clostridium difficile infection associated with prolonged antibiotic prophylaxis.

PubMed

Kirkwood, Katherine A; Gulack, Brian C; Iribarne, Alexander; Bowdish, Michael E; Greco, Giampaolo; Mayer, Mary Lou; O'Sullivan, Karen; Gelijns, Annetine C; Fumakia, Nishit; Ghanta, Ravi K; Raiten, Jesse M; Lala, Anuradha; Ladowski, Joseph S; Blackstone, Eugene H; Parides, Michael K; Moskowitz, Alan J; Horvath, Keith A

2018-02-01

The incidence and severity of Clostridium difficile infection (CDI) have increased rapidly over the past 2 decades, particularly in elderly patients with multiple comorbidities. This study sought to characterize the incidence and risks of these infections in cardiac surgery patients. A total of 5158 patients at 10 Cardiothoracic Surgical Trials Network sites in the US and Canada participated in a prospective study of major infections after cardiac surgery. Patients were followed for infection, readmission, reoperation, or death up to 65 days after surgery. We compared clinical and demographic characteristics, surgical data, management practices, and outcomes for patients with CDI and without CDI. C difficile was the third most common infection observed (0.97%) and was more common in patients with preoperative comorbidities and complex operations. Antibiotic prophylaxis for >2 days, intensive care unit stay >2 days, and postoperative hyperglycemia were associated with increased risk of CDI. The median time to onset was 17 days; 48% of infections occurred after discharge. The additional length of stay due to infection was 12 days. The readmission and mortality rates were 3-fold and 5-fold higher, respectively, in patients with CDI compared with uninfected patients. In this large multicenter prospective study of major infections following cardiac surgery, CDI was encountered in nearly 1% of patients, was frequently diagnosed postdischarge, and was associated with extended length of stay and substantially increased mortality. Patients with comorbidities, longer surgery time, extended antibiotic exposure, and/or hyperglycemic episodes were at increased risk for CDI. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

A combination of the probiotic and prebiotic product can prevent the germination of Clostridium difficile spores and infection.

PubMed

Rätsep, M; Kõljalg, S; Sepp, E; Smidt, I; Truusalu, K; Songisepp, E; Stsepetova, J; Naaber, P; Mikelsaar, R H; Mikelsaar, M

2017-10-01

Clostridium difficile infection (CDI) is one of the most prevalent healthcare associated infections in hospitals and nursing homes. Different approaches are used for prevention of CDI. Absence of intestinal lactobacilli and bifidobacteria has been associated with C. difficile colonization in hospitalized patients. Our aim was to test a) the susceptibility of C. difficile strains of different origin and the intestinal probiotic Lactobacillus plantarum Inducia (DSM 21379) to various antimicrobial preparations incl. metronidazole, vancomycin; b) the susceptibility of C. difficile strains to antagonistic effects of the probiotic L. plantarum Inducia, prebiotic xylitol (Xyl) and their combination as a synbiotic (Syn) product; c) the suppression of germination of C. difficile spores in vitro and in vivo in animal model of C. difficile infection with Inducia, Xyl and Syn treatment. The VPI strain 10463 (ATCC 43255), epidemic strain (M 13042) and clinical isolates (n = 12) of C. difficile from Norway and Estonia were susceptible and contrarily L. plantarum Inducia resistant to vancomycin, metronidazole and ciprofloxacin. The intact cells of Inducia, natural and neutralized cell free supernatant inhibited in vitro the growth of tested C. difficile reference strain VPI and Estonian and Norwegian clinical isolates of C. difficile after co-cultivation. This effect against C. difficile sustained in liquid media under ampicillin (0.75 μg/ml) and Xyl (5%) application. Further, incubation of Inducia in the media with 5% Xyl fully stopped germination of spores of C. difficile VPI strain after 48 h. In infection model the 48 hamsters were administered ampicillin (30 mg/kg) and 10-30 spores of C. difficile VPI strain. They also received five days before and after the challenge a pretreatment with a synbiotic (single daily dose of L. plantarum Inducia 1 ml of 10 10  CFU/ml and 20% xylitol in 1 ml by orogastric gavage). The survival rate of hamsters was increased to 78% compared to 13% (p = 0.003) survival rate of hamsters who received no treatment. When administered Xyl the survival rate of hamsters reached 56% vs.13% (p = 0.06). In both Syn (6/9, p = 0.003) and Xyl (3/9, p = 0.042) groups the number of animals not colonized with C. difficile significantly increased. In conclusion, the combination of xylitol with L. plantarum Inducia suppresses the germination of spores and outgrowth into vegetative toxin producing cells of C. difficile and reduces the colonization of gut with the pathogen. Putative therapeutical approach includes usage of the synbiotic during antimicrobial therapy for prevention of CDI and its potential to reduce recurrences of CDI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection

PubMed Central

Vincent, Caroline; Manges, Amee R.

2015-01-01

Clostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material. PMID:27025623

Impact of a Multi-disciplinary C. difficile Action Team

PubMed Central

Heil, Emily; Sivasailam, Bharathi; Park, SoEun; Diaz, Jose; Von Rosenvinge, Erik; Claeys, Kimberly; Hopkins, Teri; Leekha, Surbhi

2017-01-01

Abstract Background Clostridium difficile infection (CDI) is associated with increased length of hospital stay, morbidity, mortality, and cost of hospitalization. Early intervention by experts from multiple areas of practice such as gastroenterology (GI), infectious diseases (ID) and surgery can be essential to optimize care and increase utilization of novel treatment modalities such as fecal microbiota transplant (FMT) and minimally invasive, colon-preserving surgical management. Methods A multi-disciplinary C. difficile action team (MD-CAT) was implemented at University of Maryland Medical Center (UMMC) in March 2016 to engage appropriate specialty consultants in the care of CDI patients. The MD-CAT reviews positive C. difficile tests at UMMC and provides guidance and suggestions to the primary team including optimal antibiotic treatment (for CDI and any concomitant infection), and consultant involvement including ID, surgery, and GI, when appropriate. Using retrospective chart review, CDI patient management and outcomes were compared before and after implementation of the MD-CAT. Differences in the time to consults and frequency of interventional treatment was compared using Chi-square or Wilcoxon Rank-sum test. Results We compared 48 patients with CDI in the pre-intervention with 89 patients in the post-intervention period. Demographic and clinical characteristics of the groups were similar. MD-CAT intervention was associated with frequent (73%) modification or discontinuation of concomitant antibiotics. Median time to GI and ID consults was significantly shorter in the post group (P = 0.007 and P = 0.004, respectively). Five of 89 (5.6%) of patients received FMT or colon-preserving surgical intervention in the post-intervention group compared with no patients in the pre-intervention group. There was no difference in 30-day all-cause mortality or CDI recurrence between groups. Conclusion Early, multi-disciplinary action on patients with CDI increased the proportion of patients undergoing active specialty consultation and improved use of concomitant antibiotics. A larger sample size is needed to determine the effects of such a team on other clinical outcomes. Figure 1 Time to GI Consult Figure 2 Time to ID Consult Disclosures All authors: No reported disclosures.

Hospital-onset Clostridium difficile infection among solid organ transplant recipients.

PubMed

Donnelly, J P; Wang, H E; Locke, J E; Mannon, R B; Safford, M M; Baddley, J W

2015-11-01

Clostridium difficile infection (CDI) is a considerable health issue in the United States and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can affect both graft and patient survival. However, little is known about the impact of CDI on health services utilization posttransplantation. We examined hospital-onset CDI from 2012 to 2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the United States. Infection was five times more common among transplant recipients than among general medicine inpatients (209 vs 40 per 10 000 discharges), and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional risk-standardized CDI varied more than 3-fold across high-volume hospitals (infection ratio 0.54-1.82, median 1.04, interquartile range 0.78-1.28). CDI was associated with increased 30-day readmission, transplant organ complications, cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were substantially higher than risk-standardized expected values (40 094 vs 22 843 days, costs $198 728 368 vs $154 020 528). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Decreasing Clostridium difficile Infections by an Antimicrobial Stewardship Program That Reduces Moxifloxacin Use

PubMed Central

Equiluz-Bruck, Susanne; Fudel, Marta; Reiter, Ingun; Schmid, Andrea; Singer, Erna; Chott, Andreas

2014-01-01

Clostridium difficile infections (CDI) in hospitalized patients are known to be closely related to antibiotic exposure. Although several substances can cause CDI, the risk differs between individual agents. In Vienna and other eastern parts of Austria, CDI ribotype 027 is currently highly prevalent. This ribotype has the characteristic of intrinsic moxifloxacin resistance. Therefore, we hypothesized that moxifloxacin restriction can decrease the number of CDI cases in hospitalized patients. Our antibiotic stewardship (ABS) group applied an information campaign on CDI and formal restriction of moxifloxacin in Wilhelminenspital (Vienna, Austria), a 1,000- bed tertiary care hospital. The preintervention period (period 1) was January through May 2013, and the intervention period (period 2) was June through December 2013. We recorded the defined daily doses (DDD) of moxifloxacin and the number of CDI patients/month. Moxifloxacin use was reduced from a mean (± standard error of the mean [SEM]) of 1,038 ± 109 DDD per month (period 1) to 42 ± 10 DDD per month (period 2) (P = 0.0045). Total antibiotic use was not affected. The mean (±SEM) numbers of CDI cases in period 1 were 59 ± 3 per month and in period 2 were 32 ± 3 per month (46% reduction; P = 0.0044). Reducing moxifloxacin use in combination with providing structured information on CDI was associated with an immediate decrease in CDI rates in this large community teaching hospital. PMID:24936597

Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland.

PubMed

Czepiel, J; Kędzierska, J; Biesiada, G; Birczyńska, M; Perucki, W; Nowak, P; Garlicki, A

2015-11-01

Over the past two decades Clostridium difficile infection (CDI) has appeared as a major public health threat. We performed a retrospective study based on the records of patients hospitalized for CDI at the University Hospital in Krakow, Poland, between 2008 and 2014. In the study period, CDI occurred in 1009 individuals. There were 790 (78%) individuals who developed infection only once, whereas 219 (22%) developed infection more than once. The percentage of deaths within 14 days of CDI confirmation was 2·4%, with a mean age of 74·2 ± 15·9 years. Crude mortality was 12·9% in medical wards, 5·6% for surgical wards and 27·7% in the ICU setting. The time span between diagnosis and death was 5·1 days on average. Between 2008 and 2012 a 6·5-fold increase of CDI frequency with a posterior stabilization and even reduction in 2013 and 2014 was observed. According to the data analysed, 2/3 patients in our population developed CDI during their hospitalization even though they were admitted for different reasons. Medical wards pose a significantly higher risk of CDI than the surgical ones. Age is a risk factor for CDI recurrence. In the case of patients who died, death occurred shortly after diagnosis. The first CDI episode poses much higher risk of mortality than the consecutive ones.

n-3 and n-6 Fatty Acid Changes in the Erythrocyte Membranes of Patients with 658240251 Clostridium difficile Infection.

PubMed

Czepiel, Jacek; Gdula-Argasińska, Joanna; Garlicki, Aleksander

2016-01-01

The implications of circulating essential fatty acids (FA) on the inflammatory risk profile and clinical outcome are still unclear. In order to gain a deeper understanding of the role of polyunsaturated fatty acids (PUFA) in the pathogenesis of acute infection, we analyzed the FA content in red blood cell (RBC) membranes of patients with Clostridium difficile infection (CDI) and controls. We prospectively studied 60 patients including 30 patients with CDI and 30 controls to assess lipid concentrations in erythrocyte membranes using gas chromatography. We observed a higher level of saturated fatty acids (SFA) in RBC membranes from patients with CDI. In patients with CDI, we also noticed a higher level of 20:4 n-6 FA and only a small amounts of C20:2n-6, C20:3n-6 FAs, arachidonic acid (AA) precursors, which suggest an intense inflammatory reaction in the organism during infection. We also noticed low levels of n-3 FA in the RBC membranes of patients infected with CDI. There is a deficit of n-3 FA in patients with CDI. n-3 FA are probably used during CDI as precursors of pro-resolving mediators that may indicate a therapeutic role of n-3 PUFAs in CDI. The changes in fatty acids in erythrocyte membranes during CDI alter their functions which may have an impact on the clinical outcome.

Clostridium difficile infection

PubMed Central

Smits, Wiep Klaas; Lyras, Dena; Lacy, D. Borden; Wilcox, Mark H.; Kuijper, Ed J.

2017-01-01

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis — the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota. PMID:27158839

Can a toxin gene NAAT be used to predict toxin EIA and the severity of Clostridium difficile infection?

PubMed

Garvey, Mark I; Bradley, Craig W; Wilkinson, Martyn A C; Holden, Elisabeth

2017-01-01

Diagnosis of C. difficile infection (CDI) is controversial because of the many laboratory methods available and their lack of ability to distinguish between carriage, mild or severe disease. Here we describe whether a low C. difficile toxin B nucleic acid amplification test (NAAT) cycle threshold (CT) can predict toxin EIA, CDI severity and mortality. A three-stage algorithm was employed for CDI testing, comprising a screening test for glutamate dehydrogenase (GDH), followed by a NAAT, then a toxin enzyme immunoassay (EIA). All diarrhoeal samples positive for GDH and NAAT between 2012 and 2016 were analysed. The performance of the NAAT CT value as a classifier of toxin EIA outcome was analysed using a ROC curve; patient mortality was compared to CTs and toxin EIA via linear regression models. A CT value ≤26 was associated with ≥72% toxin EIA positivity; applying a logistic regression model we demonstrated an association between low CT values and toxin EIA positivity. A CT value of ≤26 was significantly associated ( p  = 0.0262) with increased one month mortality, severe cases of CDI or failure of first line treatment. The ROC curve probabilities demonstrated a CT cut off value of 26.6. Here we demonstrate that a CT ≤26 indicates more severe CDI and is associated with higher mortality. Samples with a low CT value are often toxin EIA positive, questioning the need for this additional EIA test. A CT ≤26 could be used to assess the potential for severity of CDI and guide patient treatment.

Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection.

PubMed

Weingarden, Alexa R; Chen, Chi; Bobr, Aleh; Yao, Dan; Lu, Yuwei; Nelson, Valerie M; Sadowsky, Michael J; Khoruts, Alexander

2014-02-15

Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.

Prevalence of Clostridium difficile infection presenting to US EDs.

PubMed

Smith, Aaron M; Wuerth, Brandon A; Wiemken, Timothy L; Arnold, Forest W

2015-02-01

The objective of the study is to determine the prevalence of Clostridium difficile infection (CDI) presenting to emergency departments (EDs) in the United States. Secondary objectives included defining the burden of CDI. This is a retrospective, observational cohort study of 2006-2010 Nationwide Emergency Department Sample database of 980 US hospital EDs in 29 states. Prevalence, mortality rate, length of stay, hospital charges, and endemicity were measured. A total of 474513 patients with CDI-related ED visits were identified. From 2006 to 2010, the prevalence of CDI increased from 26.2 to 33.1 per 100,000 population (P<.001). The number of CDI-related ED cases increased 26.1% (P<.001) over the study period: 18.6% from 2006 to 2007 (P<.001), 4.3% from 2007 to 2008 (P=.46), 1.8% from 2008 to 2009 (P=.73), and 0.13% from 2009 to 2010 (P=.95). Emergency department visits occurred more frequently with individuals 85 years or older (relative risk [RR], 13.74; P<.001), females (RR, 1.77; P<.001) and in the northeast United States (RR, 1.42; P<.001). From 2009 to 2010, the mortality rate decreased 17.9% (P=.01). The prevalence of CDI presenting to EDs increased each year from 2006 to 2010; however, the rate of increase slowed from each year to the next. The mortality rate increased from 2006 to 2009 and decreased significantly from 2009 to 2010. C difficile infection visits presenting to EDs occurred more frequently with older individuals, females, and in the northeast. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of five assays for detection of Clostridium difficile toxin.

PubMed

Chapin, Kimberle C; Dickenson, Roberta A; Wu, Fongman; Andrea, Sarah B

2011-07-01

Performance characteristics of five assays for detection of Clostridium difficile toxin were compared using fresh stool samples from patients with C. difficile infection (CDI). Assays were performed simultaneously and according to the manufacturers' instructions. Patients were included in the study if they exhibited clinical symptoms consistent with CDI. Nonmolecular assays included glutamate dehydrogenase antigen tests, with positive findings followed by the Premier Toxin A and B Enzyme Immunoassay (GDH/EIA), and the C. Diff Quik Chek Complete test. Molecular assays (PCR) included the BD GeneOhm Cdiff Assay, the Xpert C. difficile test, and the ProGastro Cd assay. Specimens were considered true positive if results were positive in two or more assays. For each method, the Youden index was calculated and cost-effectiveness was analyzed. Of 81 patients evaluated, 26 (32.1%) were positive for CDI. Sensitivity of the BD GeneOhm Cdiff assay, the Xpert C. difficile test, the ProGastro Cd assay, C. Diff Quik Chek Complete test, and two-step GDH/EIA was 96.2%, 96.2%, 88.5%, 61.5%, and 42.3%, respectively. Specificity of the Xpert C. difficile test was 96.4%, and for the other four assays was 100%. Compared with nonmolecular methods, molecular methods detected 34.7% more positive specimens. Assessment of performance characteristics and cost-effectiveness demonstrated that the BD GeneOhm Cdiff assay yielded the best results. While costly, the Xpert C. difficile test required limited processing and yielded rapid results. Because of discordant results, specimen processing, and extraction equipment requirements, the ProGastro Cd assay was the least favored molecular assay. The GDH/EIA method lacked sufficient sensitivity to be recommended. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Molecular, microbiological and clinical characterization of Clostridium difficile isolates from tertiary care hospitals in Colombia.

PubMed

Salazar, Clara Lina; Reyes, Catalina; Atehortua, Santiago; Sierra, Patricia; Correa, Margarita María; Paredes-Sabja, Daniel; Best, Emma; Fawley, Warren N; Wilcox, Mark; González, Ángel

2017-01-01

In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed. From a total of 913 stool samples collected during 2013-2014, 775 were included in the study. The frequency of A/B toxins-positive samples was 9.7% (75/775). A total of 143 isolates of C.difficile were recovered from culture, 110 (76.9%) produced cytotoxic effect in cell culture, 100 (69.9%) were tcdA+/tcdB+, 11 (7.7%) tcdA-/tcdB+, 32 (22.4%) tcdA-/tcdB- and 25 (17.5%) CDTa+/CDTb+. From 37 ribotypes identified, ribotypes 591 (20%), 106 (9%) and 002 (7.9%) were the most prevalent; only one isolate corresponded to ribotype 027, four to ribotype 078 and four were new ribotypes (794,795, 804,805). All isolates were susceptible to vancomycin and metronidazole, while 85% and 7.7% were resistant to clindamycin and moxifloxacin, respectively. By multivariate analysis, significant risk factors associated to CDI were, staying in orthopedic service, exposure to third-generation cephalosporins and staying in an ICU before CDI symptoms; moreover, steroids showed to be a protector factor. These results revealed new C. difficile ribotypes and a high diversity profile circulating in Colombia different from those reported in America and European countries.

Molecular, microbiological and clinical characterization of Clostridium difficile isolates from tertiary care hospitals in Colombia

PubMed Central

Salazar, Clara Lina; Reyes, Catalina; Atehortua, Santiago; Sierra, Patricia; Correa, Margarita María; Paredes-Sabja, Daniel; Best, Emma; Fawley, Warren N.; Wilcox, Mark

2017-01-01

In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed. From a total of 913 stool samples collected during 2013–2014, 775 were included in the study. The frequency of A/B toxins-positive samples was 9.7% (75/775). A total of 143 isolates of C.difficile were recovered from culture, 110 (76.9%) produced cytotoxic effect in cell culture, 100 (69.9%) were tcdA+/tcdB+, 11 (7.7%) tcdA-/tcdB+, 32 (22.4%) tcdA-/tcdB- and 25 (17.5%) CDTa+/CDTb+. From 37 ribotypes identified, ribotypes 591 (20%), 106 (9%) and 002 (7.9%) were the most prevalent; only one isolate corresponded to ribotype 027, four to ribotype 078 and four were new ribotypes (794,795, 804,805). All isolates were susceptible to vancomycin and metronidazole, while 85% and 7.7% were resistant to clindamycin and moxifloxacin, respectively. By multivariate analysis, significant risk factors associated to CDI were, staying in orthopedic service, exposure to third-generation cephalosporins and staying in an ICU before CDI symptoms; moreover, steroids showed to be a protector factor. These results revealed new C. difficile ribotypes and a high diversity profile circulating in Colombia different from those reported in America and European countries. PMID:28902923

Comparison of Five Assays for Detection of Clostridium difficile Toxin

PubMed Central

Chapin, Kimberle C.; Dickenson, Roberta A.; Wu, Fongman; Andrea, Sarah B.

2011-01-01

Performance characteristics of five assays for detection of Clostridium difficile toxin were compared using fresh stool samples from patients with C. difficile infection (CDI). Assays were performed simultaneously and according to the manufacturers' instructions. Patients were included in the study if they exhibited clinical symptoms consistent with CDI. Nonmolecular assays included glutamate dehydrogenase antigen tests, with positive findings followed by the Premier Toxin A and B Enzyme Immunoassay (GDH/EIA), and the C. Diff Quik Chek Complete test. Molecular assays (PCR) included the BD GeneOhm Cdiff Assay, the Xpert C. difficile test, and the ProGastro Cd assay. Specimens were considered true positive if results were positive in two or more assays. For each method, the Youden index was calculated and cost-effectiveness was analyzed. Of 81 patients evaluated, 26 (32.1%) were positive for CDI. Sensitivity of the BD GeneOhm Cdiff assay, the Xpert C. difficile test, the ProGastro Cd assay, C. Diff Quik Chek Complete test, and two-step GDH/EIA was 96.2%, 96.2%, 88.5%, 61.5%, and 42.3%, respectively. Specificity of the Xpert C. difficile test was 96.4%, and for the other four assays was 100%. Compared with nonmolecular methods, molecular methods detected 34.7% more positive specimens. Assessment of performance characteristics and cost-effectiveness demonstrated that the BD GeneOhm Cdiff assay yielded the best results. While costly, the Xpert C. difficile test required limited processing and yielded rapid results. Because of discordant results, specimen processing, and extraction equipment requirements, the ProGastro Cd assay was the least favored molecular assay. The GDH/EIA method lacked sufficient sensitivity to be recommended. PMID:21704273

Disproportionate rise in Clostridium difficile-associated hospitalizations among US youth with inflammatory bowel disease, 1997-2011.

PubMed

Sandberg, Kelly C; Davis, Matthew M; Gebremariam, Achamyeleh; Adler, Jeremy

2015-04-01

Our aim was to characterize the temporal changes in burden that Clostridium difficile infection (CDI) added to the hospital care of children and young adults with inflammatory bowel disease (IBD) in the United States. Retrospective analysis of annual, nationally representative samples of children and young adults with IBD. There was a 5-fold increase in IBD hospitalizations with CDI from 1997 to 2011 (P for trend <0.01). During the same period, IBD hospitalizations without CDI increased 2-fold (P for trend <0.01). Mean length of stay for IBD hospitalizations with CDI was consistently longer than that for hospitalizations without CDI and did not significantly change over time (P for trend = 0.47). CDI-related total hospital days in the United States rose from 1702 to 10,194 days per million individuals per year from 1997 to 2011 (P for trend <0.01). Children and young adults hospitalized with CDI had a significantly lower odds of colectomy (0.31) compared with those without CDI. Total charges for CDI-related hospitalizations among children and young adults in the United States rose from $8.7 million in 1997 to $68.2 million in 2011. A widening gap in burden has opened between IBD hospitalizations with and without CDI during the last decade and a half. CDI-related hospitalizations are associated with disproportionately longer lengths of stay, more hospital days, and more charges than hospitalizations without CDI over time. Further work within health systems, hospitals, and practices can help us better understand this enlarging gap to improve clinical care for this vulnerable population.

Risk Factors for Recurrent Clostridium difficile Infection in Pediatric Inpatients.

PubMed

Schwab, Elyse M; Wilkes, Jacob; Korgenski, Kent; Hersh, Adam L; Pavia, Andrew T; Stevens, Vanessa W

2016-06-01

The purpose of this study was to identify the risk factors during the incident Clostridium difficile infection (CDI) episode, associated with developing recurrent CDI within 60 days, among hospitalized children that may be amenable to intervention. This was a retrospective cohort study of pediatric patients hospitalized at a freestanding children's hospital from January 1, 2003, to December 31, 2010. Patients were eligible if they were <18 years of age at admission and had a new diagnosis of CDI. Patients <1 year of age and those with a history of CDI in the previous 60 days were excluded. Age, gender, race, complex chronic conditions, and other information were collected. Multivariable logistic regression was used to evaluate predictors of recurrent CDI. During the study period, there were 612 unique patients with an incident CDI episode; 65 (10.6%) experienced at least 1 recurrence. Patients with any complex chronic condition were 4.0 (95% confidence interval [CI]: 1.2-13.9) times more likely to experience recurrence. Patients with a malignancy and those who received non-CDI antibiotics at any time during CDI treatment were 2.3 (95% CI: 1.3-4.0) and 2.8 (95% CI: 1.2-6.9) times more likely to experience recurrence, respectively. The presence of underlying comorbidities, malignancies, and treatment with non-CDI antibiotics during CDI treatment were the most important risk factors for recurrence. Efforts to reduce unnecessary courses of non-CDI antibiotics could lower the risk of CDI recurrence. Copyright © 2016 by the American Academy of Pediatrics.

Clostridium difficile infection in patients hospitalized with type 2 diabetes mellitus and its impact on morbidity, mortality, and the costs of inpatient care.

PubMed

Olanipekun, Titilope O; Salemi, Jason L; Mejia de Grubb, Maria C; Gonzalez, Sandra J; Zoorob, Roger J

2016-06-01

Type 2 diabetes mellitus (T2DM) is often complicated by infections leading to hospitalization, increased morbidity, and mortality. Not much is known about the impact of Clostridium difficile infection (CDI) on health outcomes in hospitalized patients with T2DM. We estimated the prevalence and temporal trends of CDI; evaluated the associations between CDI and in-hospital mortality, length of stay (LOS), and the costs of inpatient care; and compared the impact of CDI with that of other infections commonly seen in patients with T2DM. We conducted a cross-sectional analysis using data from the Nationwide Inpatient Sample among patients ⩾18years with T2DM and generalized linear regression was used to analyze associations and jointpoint regression for trends. The prevalence of CDI was 6.8 per 1000 hospital discharges. Patients with T2DM and CDI had increased odds of in-hospital mortality (OR, 3.63; 95% CI 3.16, 4.17). The adjusted mean LOS was higher in patients with CDI than without CDI (11.9 vs. 4.7days). That translated to average hospital costs of $23,000 and $9100 for patients with and without CDI, respectively. The adjusted risk of mortality in patients who had CDI alone (OR 3.75; 95% CI 3.18, 4.41) was similar to patients who had CDI in addition to other common infections (OR 3.25; 95% CI 2.58, 4.10). CDI is independently associated with poorer health outcomes in patients with T2DM. We recommend close surveillance for CDI in hospitalized patients and further studies to determine the cost effectiveness of screening for CDI among patients with T2DM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clostridium difficile infection in hospitalized patients with inflammatory bowel disease: Prevalence, risk factors, and prognosis.

PubMed

Maharshak, Nitsan; Barzilay, Idan; Zinger, Hasya; Hod, Keren; Dotan, Iris

2018-02-01

To evaluate the frequency, possible risk factors, and outcome of Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD) patients.There has been an upsurge of CDI in patients with IBD who has been associated with increased morbidity and mortality. Various risk factors have been found to predispose IBD patients to CDI.A retrospective case-control study on IBD patients admitted with exacerbation and tested for CDI at the Tel Aviv Medical Center in 2008 to 2013. Epidemiologic, laboratory, and prognostic data were retrieved from electronic files and compared between patients who tested positive (CDI+) or negative (CDI-) for CDI.CDI was identified in 28 of 311 (7.31%) IBD patients hospitalized with diarrhea. IBD-specific risk factors (univariate analysis) for CDI included: use of systemic steroids therapy (odds ratio [OR] = 3.6, 95% confidence interval [CI] 1.2-10.6) and combinations of ≥2 immunomodulator medications (OR = 2.6, 95% CI 1.1-6.3). Additional risk factors for CDI that are common in the general population were hospitalization in the preceding 2 months (OR = 6.0, 95% CI 2.6-14.1), use of antacids (OR = 3.8, 95% CI 1.7-8.4), and high Charlson comorbidity score (OR = 2.5, 95% CI 1.1-5.7). A multivariate analysis confirmed that only hospitalization within the preceding 2 months and use of antacids were significant risk factors for CDI. The prognosis of CDI+ patients was similar to that of CDI- patients.Hospitalized IBD patients with exacerbation treated with antacids or recently hospitalized are at increased risk for CDI and should be tested and empirically treated until confirmation or exclusion of the infection.

A prospective cohort study on hospital mortality due to Clostridium difficile infection.

PubMed

Wenisch, J M; Schmid, D; Tucek, G; Kuo, H-W; Allerberger, F; Michl, V; Tesik, P; Laferl, H; Wenisch, C

2012-10-01

Although an increase in burden of disease has frequently been reported for Clostridium difficile infection (CDI), specific data on the effect of CDI on a patient's risk of death or overall hospital mortality are scarce. Therefore, we performed a prospective cohort study to analyse the effect of CDI on the risk of pre-discharge all-cause death in all inpatients with CDI compared to all inpatients without CDI during 2009 in a single hospital. Clostridium difficile infection was defined as by the European Society of Clinical Microbiology and Infectious Diseases. Data were collected from the medical charts of CDI patients and from the hospital discharge data of non-CDI and CDI patients. The effect measures of CDI used to compute the risk of pre-discharge all-cause death were risk ratio, attributable risk, mortality fraction (%) and population attributable risk percentage. Co-morbidity was categorized using the Charlson co-morbidity score in which a value of ≤2 was defined as low co-morbidity and that of >2 as moderate/severe co-morbidity. A stratified analysis and a Poisson regression model were applied to adjust for the effects of the risk factors sex, age and severity of co-morbidity. A total of 185 hospitalized patients with CDI were compared to 38,644 other hospitalized patients without CDI admitted between 1 January 2009 and 31 December 2009. The mean age of the CDI and non-CDI patients was 74.3 (range 72.3-76.4) and 51.9 (range 51.6-52.1) years, respectively. Of the 185 CDI, 136 (73.5%) and 49 (26.5%) were categorized with low and high co-morbidity, respectively, versus 32,107 (83.4%) and 6,352 (16.5%), respectively, in non-CDI patients. Overall, 24 of the 185 CDI patients (13%) versus 1,021 of the 38,459 non-CDI patients (2.7%) died during their hospital stay, resulting in a relative risk of pre-discharge death of 4.89 [95% confidence interval (CI) 3.35-7.13] for CDI patients, a CDI attributable risk of death of 10.3 per 100 patients and a CDI attributable fraction of 79.5 % (95% CI 70.1-86 %). After adjustment for age, sex and co-morbidity the relative risk of pre-discharge death was 2.74 (95% CI 1.82-4.10; p < 0.0001) for patients with CDI, and the proportion of hospital deaths due to CDI was 1.72 (95% CI 1.22-2.05). The results of this study lead to the conclusion that hospitalized patients with CDI are--independent of age, sex and co-morbidity severity--2.74-fold more likely to die during their hospital stay than all other hospitalized patients. The eradication of CDI in the hospital could have prevented 1.72% of in-hospital deaths in our study population during the 1 year of the study.

Probiotics and prevention of Clostridium difficile infection.

PubMed

Goldstein, E J C; Johnson, S J; Maziade, P-J; Evans, C T; Sniffen, J C; Millette, M; McFarland, L V

2017-06-01

The role of probiotics as adjunctive measures in the prevention of Clostridium difficile infection (CDI) has been controversial. However, a growing body of evidence has suggested that they have a role in primary prevention of CDI. Elements of this controversy are reviewed and the proposed mechanisms of action, the value and cost effectiveness of probiotics are addressed with a focus on three agents, Saccharomyces boulardii, Lactobacillus rhamnosus GG and the combination of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, Lactobacillus rhamnosus CLR2 (Bio-K+). Copyright © 2016 Elsevier Ltd. All rights reserved.

Microbiome manipulation with faecal microbiome transplantation as a therapeutic strategy in Clostridium difficile infection

PubMed Central

Marchesi, J.R.; Thursz, M.R.; Williams, H.R.T.

2015-01-01

Faecal microbiome transplantation (FMT) has generated huge recent interest as it presents a potential solution to a significant clinical problem—the increasing incidence of Clostridium difficile infection (CDI). In the short term, however, there remain many practical questions regarding its use, including the optimal selection of donors, material preparation and the mechanics of delivery. In the longer term, enhanced understanding of the mechanisms of action of FMT may potentiate novel therapies, such as targeted manipulation of the microbiome in CDI and beyond. PMID:25193538

Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.

PubMed

Peer, Xavier; An, Gary

2014-10-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of personalized medicine.

Agent-based model of Fecal Microbial Transplant effect on Bile Acid Metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection

PubMed Central

Peer, Xavier; An, Gary

2014-01-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the Clostridium difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, Fecal Microbial Transplant (FMT). The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of personalized medicine. PMID:25168489

The projected effectiveness of Clostridium difficile vaccination as part of an integrated infection control strategy.

PubMed

van Kleef, Esther; Deeny, Sarah R; Jit, Mark; Cookson, Barry; Goldenberg, Simon D; Edmunds, W John; Robotham, Julie V

2016-11-04

Early clinical trials of a Clostridium difficile toxoid vaccine show efficacy in preventing C. difficile infection (CDI). The optimal patient group to target for vaccination programmes remains unexplored. This study performed a model-based evaluation of the effectiveness of different CDI vaccination strategies, within the context of existing infection prevention and control strategies such as antimicrobial stewardship. An individual-based transmission model of CDI in a high-risk hospital setting was developed. The model incorporated data on patient movements between the hospital, and catchment populations from the community and long-term care facilities (LTCF), using English national and local level data for model-parameterisation. We evaluated vaccination of: (1) discharged patients who had an CDI-occurrence in the ward; (2) LTCF-residents; (3) Planned elective surgical admissions and (4) All three strategies combined. Without vaccination, 10.9 [Interquartile range: 10.0-11.8] patients per 1000 ward admissions developed CDI, of which 31% were ward-acquired. Immunising all three patient groups resulted in a 43% [42-44], reduction of ward-onset CDI on average. Among the strategies restricting vaccination to one target group, vaccinating elective surgical patients proved most effective (35% [34-36] reduction), but least efficient, requiring 146 [133-162] courses to prevent one ICU-onset case. Immunising LTCF residents was most efficient, requiring just 13 [11-16] courses to prevent one case, but considering this only comprised a small group of our hospital population, it only reduced ICU-onset CDI by 9% [8-11]. Vaccination proved most efficient when ward-based transmission rates and antimicrobial consumption were high. Strategy success depends on the interaction between hospital and catchment populations, and importantly, consideration of importations of CDI from outside the hospital which we found to substantially impact hospital dynamics. Vaccination may be most desirable in settings or patient groups where levels of broad-spectrum antimicrobial use are high and difficult to reduce. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fidaxomicin: A novel agent for the treatment of Clostridium difficile infection

PubMed Central

Zhanel, George G; Walkty, Andrew J; Karlowsky, James A

2015-01-01

BACKGROUND: Due to the limitations of existing treatment options for Clostridium difficile infection (CDI), new therapies are needed. OBJECTIVE: To review the available data on fidaxomicin regarding chemistry, mechanisms of action and resistance, in vitro activity, pharmacokinetic and pharmacodynamic properties, efficacy and safety in clinical trials, and place in therapy. METHODS: A search of PubMed using the terms “fidaxomicin”, “OPT-80”, “PAR-101”, “OP-1118”, “difimicin”, “tiacumicin” and “lipiarmycin” was performed. All English-language articles from January 1983 to November 2014 were reviewed, as well as bibliographies of all articles. RESULTS: Fidaxomicin is the first macrocyclic lactone antibiotic with activity versus C difficile. It inhibits RNA polymerase, therefore, preventing transcription. Fidaxomicin (and its active metabolite OP-1118) is bactericidal against C difficile and exhibits a prolonged postantibiotic effect (approximately 10 h). Other than for C difficile, fidaxomicin demonstrated only moderate inhibitory activity against Gram-positive bacteria and was a poor inhibitor of normal colonic flora, including anaerobes and enteric Gram-negative bacilli. After oral administration (200 mg two times per day for 10 days), fidaxomicin achieved low serum concentration levels but high fecal concentration levels (mean approximately 1400 μg/g stool). Phase 3 clinical trials involving adults with CDI demonstrated that 200 mg fidaxomicin twice daily for 10 days was noninferior to 125 mg oral vancomycin four times daily for 10 days in regard to clinical response at the end of therapy. Fidaxomicin was, however, reported to be superior to oral vancomycin in reducing recurrent CDI and achieving a sustained clinical response (assessed at day 28) for patients infected with non-BI/NAP1/027 strains. CONCLUSION: Fidaxomicin was noninferior to oral vancomycin with regard to clinical response at the end of CDI therapy. Fidaxomicin has been demonstated to be as safe as oral vancomycin, but superior to vancomycin in achieving a sustained clinical response for CDI in patients infected with non-BI/NAP1/027 strains. Caution should be exercised in using fidaxomicin monotherapy for treatment of severe complicated CDI because limited data are available. Whether fidaxomicin is cost effective (due to its significantly higher acquisition cost versus oral vancomycin) depends on the acceptable willingness to pay threshold per quality-adjusted life year as a measure of assessing cost effectiveness. PMID:26744587

Fidaxomicin: A novel agent for the treatment of Clostridium difficile infection.

PubMed

Zhanel, George G; Walkty, Andrew J; Karlowsky, James A

2015-01-01

Due to the limitations of existing treatment options for Clostridium difficile infection (CDI), new therapies are needed. To review the available data on fidaxomicin regarding chemistry, mechanisms of action and resistance, in vitro activity, pharmacokinetic and pharmacodynamic properties, efficacy and safety in clinical trials, and place in therapy. A search of PubMed using the terms "fidaxomicin", "OPT-80", "PAR-101", "OP-1118", "difimicin", "tiacumicin" and "lipiarmycin" was performed. All English-language articles from January 1983 to November 2014 were reviewed, as well as bibliographies of all articles. Fidaxomicin is the first macrocyclic lactone antibiotic with activity versus C difficile. It inhibits RNA polymerase, therefore, preventing transcription. Fidaxomicin (and its active metabolite OP-1118) is bactericidal against C difficile and exhibits a prolonged postantibiotic effect (approximately 10 h). Other than for C difficile, fidaxomicin demonstrated only moderate inhibitory activity against Gram-positive bacteria and was a poor inhibitor of normal colonic flora, including anaerobes and enteric Gram-negative bacilli. After oral administration (200 mg two times per day for 10 days), fidaxomicin achieved low serum concentration levels but high fecal concentration levels (mean approximately 1400 μg/g stool). Phase 3 clinical trials involving adults with CDI demonstrated that 200 mg fidaxomicin twice daily for 10 days was noninferior to 125 mg oral vancomycin four times daily for 10 days in regard to clinical response at the end of therapy. Fidaxomicin was, however, reported to be superior to oral vancomycin in reducing recurrent CDI and achieving a sustained clinical response (assessed at day 28) for patients infected with non-BI/NAP1/027 strains. Fidaxomicin was noninferior to oral vancomycin with regard to clinical response at the end of CDI therapy. Fidaxomicin has been demonstated to be as safe as oral vancomycin, but superior to vancomycin in achieving a sustained clinical response for CDI in patients infected with non-BI/NAP1/027 strains. Caution should be exercised in using fidaxomicin monotherapy for treatment of severe complicated CDI because limited data are available. Whether fidaxomicin is cost effective (due to its significantly higher acquisition cost versus oral vancomycin) depends on the acceptable willingness to pay threshold per quality-adjusted life year as a measure of assessing cost effectiveness.

Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value

PubMed Central

D’Ostroph, Amanda R; So, Tsz-Yin

2017-01-01

The incidence of Clostridium difficile infection (CDI) in pediatric patients continues to rise. Most of the pediatric recommendations for CDI treatment are extrapolated from the literature and guidelines for adults. The American Academy of Pediatrics recommends oral metronidazole as the first-line treatment option for an initial CDI and the first recurrence if they are mild to moderate in severity. Oral vancomycin is recommended to be used for severe CDI and the second recurrent infection. Additional pulsed regimen of oral vancomycin, which is tapered, may increase efficacy in refractory patients. However, there is lack of large studies evaluating the use of fidaxomicin in pediatrics to know whether it could be a safe and effective treatment option for difficult-to-treat patients. Fidaxomicin is associated with higher total drug costs compared to metronidazole and vancomycin, but the literature supports its use due to a lower rate of CDI recurrence, which may result in cost savings. Further studies are warranted to evaluate the use of fidaxomicin in patients <18 years old and to understand its role in the standard of care for pediatric patients with CDI. PMID:29089778

An in silico evaluation of treatment regimens for recurrent Clostridium difficile infection

PubMed Central

Blanco, Natalia; Foxman, Betsy; Malani, Anurag N.; Zhang, Min; Walk, Seth; Rickard, Alexander H.

2017-01-01

Background Clostridium difficile infection (CDI) is a significant nosocomial infection worldwide, that recurs in as many as 35% of infections. Risk of CDI recurrence varies by ribotype, which also vary in sporulation and germination rates. Whether sporulation/germination mediate risk of recurrence and effectiveness of treatment of recurring CDI remains unclear. We aim to assess the role of sporulation/germination patterns on risk of recurrence, and the relative effectiveness of the recommended tapered/pulsing regimens using an in silico model. Methods We created a compartmental in-host mathematical model of CDI, composed of vegetative cells, toxins, and spores, to explore whether sporulation and germination have an impact on recurrence rates. We also simulated the effectiveness of three tapered/pulsed vancomycin regimens by ribotype. Results Simulations underscored the importance of sporulation/germination patterns in determining pathogenicity and transmission. All recommended regimens for recurring CDI tested were effective in reducing risk of an additional recurrence. Most modified regimens were still effective even after reducing the duration or dosage of vancomycin. However, the effectiveness of treatment varied by ribotype. Conclusion Current CDI vancomycin regimen for treating recurrent cases should be studied further to better balance associated risks and benefits. PMID:28800598

Clostridium difficile Infection Seasonality: Patterns across Hemispheres and Continents – A Systematic Review

PubMed Central

Furuya-Kanamori, Luis; McKenzie, Samantha J.; Yakob, Laith; Clark, Justin; Paterson, David L.; Riley, Thomas V.; Clements, Archie C.

2015-01-01

Background Studies have demonstrated seasonal variability in rates of Clostridium difficile infection (CDI). Synthesising all available information on seasonality is a necessary step in identifying large-scale epidemiological patterns and elucidating underlying causes. Methods Three medical and life sciences publication databases were searched from inception to October 2014 for longitudinal epidemiological studies written in English, Spanish or Portuguese that reported the incidence of CDI. The monthly frequency of CDI were extracted, standardized and weighted according to the number of follow-up months. Cross correlation coefficients (XCORR) were calculated to examine the correlation and lag between the year-month frequencies of reported CDI across hemispheres and continents. Results The search identified 13, 5 and 2 studies from North America, Europe, and Oceania, respectively that met the inclusion criteria. CDI had a similar seasonal pattern in the Northern and Southern Hemisphere characterized by a peak in spring and lower frequencies of CDI in summer/autumn with a lag of 8 months (XCORR = 0.60) between hemispheres. There was no difference between the seasonal patterns across European and North American countries. Conclusion CDI demonstrates a distinct seasonal pattern that is consistent across North America, Europe and Oceania. Further studies are required to identify the driving factors of the observed seasonality. PMID:25775463

Point-Counterpoint: What Is the Optimal Approach for Detection of Clostridium difficile Infection?

PubMed Central

Wilcox, Mark H.

2017-01-01

INTRODUCTION In 2010, we published an initial Point-Counterpoint on the laboratory diagnosis of Clostridium difficile infection (CDI). At that time, nucleic acid amplification tests (NAATs) were just becoming commercially available, and the idea of algorithmic approaches to CDI was being explored. Now, there are numerous NAATs in the marketplace, and based on recent proficiency test surveys, they have become the predominant method used for CDI diagnosis in the United States. At the same time, there is a body of literature that suggests that NAATs lack clinical specificity and thus inflate CDI rates. Hospital administrators are taking note of institutional CDI rates because they are publicly reported. They have become an important metric impacting hospital safety ratings and value-based purchasing; hospitals may have millions of dollars of reimbursement at risk. In this Point-Counterpoint using a frequently asked question approach, Ferric Fang of the University of Washington, who has been a consistent advocate for a NAAT-only approach for CDI diagnosis, will discuss the value of a NAAT-only approach, while Christopher Polage of the University of California Davis and Mark Wilcox of Leeds University, Leeds, United Kingdom, each of whom has recently written important articles on the value of toxin detection in the diagnosis, will discuss the impact of toxin detection in CDI diagnosis. PMID:28077697

Use of tigecycline for the management of Clostridium difficile colitis in oncology patients and case series of breakthrough infections.

PubMed

Brinda, B J; Pasikhova, Y; Quilitz, R E; Thai, C M; Greene, J N

2017-04-01

Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhoea in adults. Cancer patients, in particular, are at a higher risk for CDI. Limited clinical data exist regarding the use of tigecycline for the treatment of CDI, especially in patients with oncologic and haematologic malignancies. To characterize the use of tigecycline for treatment of CDI in oncology patients at an academic cancer centre. This was a retrospective, single-centre, single-arm, chart review evaluating the use of tigecycline for the management of CDI in oncology patients at an academic cancer centre. The median age of CDI diagnosis in this patient group (N=66) was 65 years (range: 16-84) and the majority of patients had solid tumour malignancies. Fifty-six percent of patients had severe CDI, 70.3% of which were classified as having severe complicated disease. The median time to initiation of tigecycline therapy was 2 days (mean: 3.83) and the median number of tigecycline doses was 13 (range: 1-50). Twelve non-CDI breakthrough infections were observed, and four patients developed CDI while receiving tigecycline for non-CDI indications. The rate of death was 18% and the recurrence rate was 15.2%. Tigecycline did not lead to overt benefits in outcomes of oncology patients with CDI when compared to historical data. In addition, several breakthrough CDIs were observed in patients who received the drug for a non-CDI indication. Further prospective research is needed to validate the use of tigecycline for management of CDI. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

The burden of healthcare-associated Clostridium difficile infection in a non-metropolitan setting.

PubMed

Bond, S E; Boutlis, C S; Yeo, W W; Pratt, W A B; Orr, M E; Miyakis, S

2017-04-01

Healthcare-associated Clostridium difficile infection (HCA-CDI) remains a major cause of morbidity and mortality in industrialized countries. However, few data exist on the burden of HCA-CDI in multi-site non-metropolitan settings. This study examined the introduction of an antimicrobial stewardship programme (ASP) in relation to HCA-CDI rates, and the effect of HCA-CDI on length of stay (LOS) and hospital costs. A comparative before-and-after intervention study of patients aged ≥16 years with HCA-CDI from December 2010 to April 2016 across the nine hospitals of a non-metropolitan health district in New South Wales, Australia was undertaken. The intervention comprised a multi-site ASP supported by a clinical decision support system, with subsequent introduction of email feedback of HCA-CDI cases to admitting medical officers. HCA-CDI rates, comparative LOS and hospital costs, prior use of antimicrobials and proton pump inhibitors, and appropriateness of CDI treatment. HCA-CDI rates rose from 3.07 to 4.60 cases per 10,000 occupied bed-days pre-intervention, and remained stable at 4 cases per 10,000 occupied bed-days post-intervention (P=0.24). Median LOS (17 vs six days; P<0.01) and hospital costs (AU$19,222 vs $7861; P<0.01) were significantly greater for HCA-CDI cases (N=91) than for matched controls (N=172). Half of the patients with severe HCA-CDI (4/8) did not receive initial appropriate treatment (oral vancomycin). HCA-CDI placed a significant burden on the regional and rural health service through increased LOS and hospital costs. Interventions targeting HCA-CDI could be employed to consolidate the effects of ASPs. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Hospital management of Clostridium difficile infection: a review of the literature.

PubMed

Khanafer, N; Voirin, N; Barbut, F; Kuijper, E; Vanhems, P

2015-06-01

The emergence of the epidemic Clostridium difficile 027 strain has renewed interest in infection control practices. To review the effectiveness of different practices to reduce hospital C. difficile infection (CDI) in non-outbreak settings. Data sources were identified by a MEDLINE search in English and French. The ORION statement was used to extract key data from articles describing interventions to manage CDI. Twenty-one studies, published between 1982 and December 2013, were reviewed. Most studies were before-after interventions, and a few studies were planned, formal, prospective investigations. The effects of the following single or combined interventions were described: antibiotic management; environmental disinfection and/or cleaning; hand hygiene; bathing; surveillance; cohorting; and isolation of infected patients in private rooms. With many methodological weaknesses and some inadequate research reporting, the observed reduction in CDI may not be entirely attributable to interventions. Although infection control programmes involving education and handwashing/gloving protocols were found to have contributed to a reduction in the incidence of CDI, these measures were usually a component of multi-faceted interventions that did not provide for evaluation of the relative impact of each factor. Appropriate environmental disinfection and antibiotic stewardship would appear to offer the most effective benefits. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Compliance with Clostridium difficile treatment guidelines: effect on patient outcomes.

PubMed

Crowell, K T; Julian, K G; Katzman, M; Berg, A S; Tinsley, A; Williams, E D; Koltun, W A; Messaris, E

2017-08-01

Guidelines for the severity classification and treatment of Clostridium difficile infection (CDI) were published by Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA) in 2010; however, compliance and efficacy of these guidelines has not been widely investigated. This present study assessed compliance with guidelines and its effect on CDI patient outcomes as compared with before these recommendations. A retrospective study included all adult inpatients with an initial episode of CDI treated in a single academic center from January 2009 to August 2014. Patients after guideline publication were compared with patients treated in 2009-2010. Demographic, clinical, and laboratory data were collected to stratify for disease severity. Outcome measures included compliance with guidelines, mortality, length of stay (LOS), and surgical intervention for CDI. A total of 1021 patients with CDI were included. Based upon the 2010 guidelines, 42 (28·8%) of 146 patients treated in 2009 would have been considered undertreated, and treatment progressively improved over time, as inadequate treatment decreased to 10·0% (15/148 patients) in 2014 (P = 0·0005). Overall, patient outcomes with guideline-adherent treatment decreased CDI attributable mortality twofold (P = 0·006) and CDI-related LOS by 1·9 days (P = 0·0009) when compared with undertreated patients. Compliance with IDSA/SHEA guidelines was associated with a decreased risk of mortality and LOS in hospitalized patients with CDI.

Genome-Based Comparison of Clostridioides difficile: Average Amino Acid Identity Analysis of Core Genomes.

PubMed

Cabal, Adriana; Jun, Se-Ran; Jenjaroenpun, Piroon; Wanchai, Visanu; Nookaew, Intawat; Wongsurawat, Thidathip; Burgess, Mary J; Kothari, Atul; Wassenaar, Trudy M; Ussery, David W

2018-02-14

Infections due to Clostridioides difficile (previously known as Clostridium difficile) are a major problem in hospitals, where cases can be caused by community-acquired strains as well as by nosocomial spread. Whole genome sequences from clinical samples contain a lot of information but that needs to be analyzed and compared in such a way that the outcome is useful for clinicians or epidemiologists. Here, we compare 663 public available complete genome sequences of C. difficile using average amino acid identity (AAI) scores. This analysis revealed that most of these genomes (640, 96.5%) clearly belong to the same species, while the remaining 23 genomes produce four distinct clusters within the Clostridioides genus. The main C. difficile cluster can be further divided into sub-clusters, depending on the chosen cutoff. We demonstrate that MLST, either based on partial or full gene-length, results in biased estimates of genetic differences and does not capture the true degree of similarity or differences of complete genomes. Presence of genes coding for C. difficile toxins A and B (ToxA/B), as well as the binary C. difficile toxin (CDT), was deduced from their unique PfamA domain architectures. Out of the 663 C. difficile genomes, 535 (80.7%) contained at least one copy of ToxA or ToxB, while these genes were missing from 128 genomes. Although some clusters were enriched for toxin presence, these genes are variably present in a given genetic background. The CDT genes were found in 191 genomes, which were restricted to a few clusters only, and only one cluster lacked the toxin A/B genes consistently. A total of 310 genomes contained ToxA/B without CDT (47%). Further, published metagenomic data from stools were used to assess the presence of C. difficile sequences in blinded cases of C. difficile infection (CDI) and controls, to test if metagenomic analysis is sensitive enough to detect the pathogen, and to establish strain relationships between cases from the same hospital. We conclude that metagenomics can contribute to the identification of CDI and can assist in characterization of the most probable causative strain in CDI patients.

The impact of Clostridium difficile infection on resource use and costs in hospitals in Spain and Italy: a matched cohort study.

PubMed

Asensio, Angel; Di Bella, Stefano; Lo Vecchio, Andrea; Grau, Santiago; Hart, Warren M; Isidoro, Beatriz; Scotto, Ricardo; Petrosillo, Nicola; Watt, Maureen; Nazir, Jameel

2015-07-01

To assess the impact of Clostridium difficile infection (CDI) on hospital resources and costs in Spain and Italy. CDI data were collected from institutions in Spain and Italy. Each patient was matched with two randomly selected uninfected controls in the same institution. Patient outcomes were assessed for the first and second episodes of CDI and for patients aged ≤65 and >65 years. The impact of CDI on hospital length of stay (LOS) was used to calculate CDI-attributable costs. A multivariate analysis using duration of stay as the continuous outcome variable assessed the independent effect of CDI on hospital costs and LOS. LOS attributable to CDI ranged from 7.6-19.0 days in adults and was 5.0 days in children; the increases were greater in adults in Italy than in Spain. Attributable costs per adult patient ranged from €4396 in Madrid to €14 023 in Rome, with the majority of the cost being due to hospitalization. For children, the total attributable cost was €3545/patient. These data show that the burden of CDI is considerable in Spain and Italy. Treatments that can reduce LOS, disease severity, and recurrence rates, as well as effective infection control measures to prevent transmission, have the potential to reduce the burden of CDI. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Decreasing Clostridium difficile infections by an antimicrobial stewardship program that reduces moxifloxacin use.

PubMed

Wenisch, Judith Maria; Equiluz-Bruck, Susanne; Fudel, Marta; Reiter, Ingun; Schmid, Andrea; Singer, Erna; Chott, Andreas

2014-09-01

Clostridium difficile infections (CDI) in hospitalized patients are known to be closely related to antibiotic exposure. Although several substances can cause CDI, the risk differs between individual agents. In Vienna and other eastern parts of Austria, CDI ribotype 027 is currently highly prevalent. This ribotype has the characteristic of intrinsic moxifloxacin resistance. Therefore, we hypothesized that moxifloxacin restriction can decrease the number of CDI cases in hospitalized patients. Our antibiotic stewardship (ABS) group applied an information campaign on CDI and formal restriction of moxifloxacin in Wilhelminenspital (Vienna, Austria), a 1,000- bed tertiary care hospital. The preintervention period (period 1) was January through May 2013, and the intervention period (period 2) was June through December 2013. We recorded the defined daily doses (DDD) of moxifloxacin and the number of CDI patients/month. Moxifloxacin use was reduced from a mean (±standard error of the mean [SEM]) of 1,038±109 DDD per month (period 1) to 42±10 DDD per month (period 2) (P=0.0045). Total antibiotic use was not affected. The mean (±SEM) numbers of CDI cases in period 1 were 59±3 per month and in period 2 were 32±3 per month (46% reduction; P=0.0044). Reducing moxifloxacin use in combination with providing structured information on CDI was associated with an immediate decrease in CDI rates in this large community teaching hospital. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

An environmental disinfection odyssey: evaluation of sequential interventions to improve disinfection of Clostridium difficile isolation rooms.

PubMed

Sitzlar, Brett; Deshpande, Abhishek; Fertelli, Dennis; Kundrapu, Sirisha; Sethi, Ajay K; Donskey, Curtis J

2013-05-01

OBJECTIVE. Effective disinfection of hospital rooms after discharge of patients with Clostridium difficile infection (CDI) is necessary to prevent transmission. We evaluated the impact of sequential cleaning and disinfection interventions by culturing high-touch surfaces in CDI rooms after cleaning. DESIGN. Prospective intervention. SETTING. A Veterans Affairs hospital. INTERVENTIONS. During a 21-month period, 3 sequential tiered interventions were implemented: (1) fluorescent markers to provide monitoring and feedback on thoroughness of cleaning facility-wide, (2) addition of an automated ultraviolet radiation device for adjunctive disinfection of CDI rooms, and (3) enhanced standard disinfection of CDI rooms, including a dedicated daily disinfection team and implementation of a process requiring supervisory assessment and clearance of terminally cleaned CDI rooms. To determine the impact of the interventions, cultures were obtained from CDI rooms after cleaning and disinfection. RESULTS. The fluorescent marker intervention improved the thoroughness of cleaning of high-touch surfaces (from 47% to 81% marker removal; P < .0001). Relative to the baseline period, the prevalence of positive cultures from CDI rooms was reduced by 14% (P=.024), 48% (P <.001), and 89% (P=.006) with interventions 1, 2, and 3, respectively. During the baseline period, 67% of CDI rooms had positive cultures after disinfection, whereas during interventions periods 1, 2, and 3 the percentages of CDI rooms with positive cultures after disinfection were reduced to 57%, 35%, and 7%, respectively. CONCLUSIONS. An intervention that included formation of a dedicated daily disinfection team and implementation of a standardized process for clearing CDI rooms achieved consistent CDI room disinfection. Culturing of CDI rooms provides a valuable tool to drive improvements in environmental disinfection.

Antimicrobial activity of natural products against Clostridium difficile in vitro.

PubMed

Roshan, N; Riley, T V; Hammer, K A

2017-05-10

To investigate the antimicrobial activity of various natural products against Clostridium difficile in vitro. The antibacterial activity of 20 natural products was determined by the agar well diffusion and broth microdilution assays against four C. difficile strains, three comparator organisms and four gastrointestinal commensal organisms. Of the raw natural products, garlic juice had the highest activity. The most active processed products were peppermint oil and the four pure compounds trans-cinnamaldehyde, allicin, menthol and zingerone. Furthermore, Bacteroides species had similar susceptibility to C. difficile to most natural products; however, Lactobacillus casei was less susceptible. The combined effect of natural products with vancomycin or metronidazole was determined using the conventional checkerboard titration method and the fractional inhibitory concentration index was calculated. The results showed a possible synergism between trans-cinnamaldehyde and vancomycin and partial synergy between trans-cinnamaldehyde and metronidazole. The study indicates a range of antimicrobial activity of natural products against C. difficile and suggests that they may be useful as alternative or complementary treatments for C. difficile infection (CDI), particularly as most are able to be given orally. This study encourages further investigation of natural products for treatment of CDI. © 2017 The Society for Applied Microbiology.

Mucosal Antibodies to the C Terminus of Toxin A Prevent Colonization of Clostridium difficile

PubMed Central

Hong, Huynh A.; Hitri, Krisztina; Hosseini, Siamand; Kotowicz, Natalia; Bryan, Donna; Mawas, Fatme; Wilkinson, Anthony J.; van Broekhoven, Annie; Kearsey, Jonathan

2017-01-01

ABSTRACT Mucosal immunity is considered important for protection against Clostridium difficile infection (CDI). We show that in hamsters immunized with Bacillus subtilis spores expressing a carboxy-terminal segment (TcdA26–39) of C. difficile toxin A, no colonization occurs in protected animals when challenged with C. difficile strain 630. In contrast, animals immunized with toxoids showed no protection and remained fully colonized. Along with neutralizing toxins, antibodies to TcdA26–39 (but not to toxoids), whether raised to the recombinant protein or to TcdA26–39 expressed on the B. subtilis spore surface, cross-react with a number of seemingly unrelated proteins expressed on the vegetative cell surface or spore coat of C. difficile. These include two dehydrogenases, AdhE1 and LdhA, as well as the CdeC protein that is present on the spore. Anti-TcdA26–39 mucosal antibodies obtained following immunization with recombinant B. subtilis spores were able to reduce the adhesion of C. difficile to mucus-producing intestinal cells. This cross-reaction is intriguing yet important since it illustrates the importance of mucosal immunity for complete protection against CDI. PMID:28167669

Use of intravenous tigecycline in patients with severe Clostridium difficile infection: a retrospective observational cohort study.

PubMed

Gergely Szabo, B; Kadar, B; Szidonia Lenart, K; Dezsenyi, B; Kunovszki, P; Fried, K; Kamotsay, K; Nikolova, R; Prinz, G

2016-12-01

There are only a limited number of antimicrobials for treating severe Clostridium difficile infection (sCDI). Tigecycline shows significant in vitro effect against C. difficile and is approved for management of complicated intra-abdominal infections. Our aim was to analyse the efficacy of tigecycline compared with standard therapy (oral vancomycin plus intravenous metronidazole) in adults treated for sCDI. A retrospective cohort study of such patients hospitalized at our department from January 2014 to December 2015 was performed. Patients receiving tigecycline monotherapy were compared with patients treated with standard therapy alone. Diagnosis and severity of CDI were determined according to guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Primary outcome was clinical recovery, secondary outcomes were in-hospital and 90-day all-cause mortality and relapse, colectomy, and complication rates. Of the 359 patients hospitalized for sCDI, 90 (25.0%) were included, 45 in each group. Patients treated with tigecycline had significantly better outcomes of clinical cure (34/45, 75.6% vs. 24/45, 53.3%; p 0.02), less complicated disease course (13/45, 28.9% vs. 24/45, 53.3%; p 0.02), and less CDI sepsis (7/45, 15.6% vs. 18/45, 40.0%; p 0.009) compared with patients receiving standard therapy. Tigecycline usage was not associated with adverse drug reactions or need for colectomy. Rates of ileus, toxic megacolon, mortality, and relapse were similar between the two groups. Favourable outcomes suggest that tigecycline might be considered as a potential candidate for therapeutic use in cases of sCDI refractory to standard treatment. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Bezlotoxumab for the prevention of Clostridium difficile recurrence.

PubMed

Couture-Cossette, Antoine; Carignan, Alex; Ilangumaran, Subburaj; Valiquette, Louis

2017-11-01

Clostridium difficile infection is a major economic and clinical burden, due to its high frequency of recurrence. Currently recommended treatments are not efficient for prevention and may contribute to the risk of recurrent infection. In recent years, research has focused on strategies to lessen this risk. Bezlotoxumab is a monoclonal antibody that prevents recurrences of C. difficile infection through the antagonism of toxin B. Areas covered: In this review, the authors discuss the burden of C. difficile infection and its recurrences, the mechanisms underlying the recurrences, and current C. difficile treatments. They subsequently analyze the strategic therapeutic rationale for bezlotoxumab use, as well as the supporting clinical evidence. Expert opinion: Bezlotoxumab is an attractive solution for reducing the unacceptable level of recurrence that occurs with the currently recommended C. difficile treatments and other alternative therapies under consideration. Even though bezlotoxumab has not been tested in large-scale trials exclusively in cases of already established recurrent C.difficile infection (rCDI), it has an advantage over current treatments in that it does not interfere with the patient's gut flora while directly neutralizing the key virulence factor. Although cost remains an important factor against its widespread use, simpler administration, fewer side-effects, and better social acceptability justify its consideration for treating rCDI.

Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts.

PubMed

Kuntz, Jennifer L; Smith, David H; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Barton, Tracy; Barton, Karen; Labreche, Matthew; Spindel, Steven J; Johnson, Eric S

2016-01-01

Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. We identified 721 CDIs following 54,186 hospital admissions-a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning.

European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection.

PubMed

Crobach, M J T; Planche, T; Eckert, C; Barbut, F; Terveer, E M; Dekkers, O M; Wilcox, M H; Kuijper, E J

2016-08-01

In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was launched. Since then newer tests for diagnosing CDI have become available, especially nucleic acid amplification tests. The main objectives of this update of the guidance document are to summarize the currently available evidence concerning laboratory diagnosis of CDI and to formulate and revise recommendations to optimize CDI testing. This update is essential to improve the diagnosis of CDI and to improve uniformity in CDI diagnosis for surveillance purposes among Europe. An electronic search for literature concerning the laboratory diagnosis of CDI was performed. Studies evaluating a commercial laboratory test compared to a reference test were also included in a meta-analysis. The commercial tests that were evaluated included enzyme immunoassays (EIAs) detecting glutamate dehydrogenase, EIAs detecting toxins A and B and nucleic acid amplification tests. Recommendations were formulated by an executive committee, and the strength of recommendations and quality of evidence were graded using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. No single commercial test can be used as a stand-alone test for diagnosing CDI as a result of inadequate positive predictive values at low CDI prevalence. Therefore, the use of a two-step algorithm is recommended. Samples without free toxin detected by toxins A and B EIA but with positive glutamate dehydrogenase EIA, nucleic acid amplification test or toxigenic culture results need clinical evaluation to discern CDI from asymptomatic carriage. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clostridium difficile infection: current, forgotten and emerging treatment options.

PubMed

Drekonja, Dimitri M

2014-09-01

Clostridium difficile infection (CDI) has increased in incidence and severity, and is now among the most common nosocomial infections. Several agents are available for the initial treatment of CDI, some of which are rarely used, and none of which is clearly superior for initial clinical cure. Fidaxomicin appears to offer a benefit in terms of preventing recurrent disease, although the cost-benefit ratio is debated. Recurrent CDI is a major challenge, occurring after 15-30% of initial episodes. The treatment of recurrent CDI is difficult, with sparse evidence available to support any particular agent. Fecal microbiota therapy, also known as 'stool transplantation', appears to be highly effective, although availability is currently limited, and the regulatory environment is in flux. Synthetic stool products and an orally available fecal microbiota therapy product are both under investigation, which may address the problem of availability. As with most infectious diseases, an effective vaccine would be a welcome addition to our armamentarium, but none is currently available.

Risk factors for Clostridium difficile infections - an overview of the evidence base and challenges in data synthesis.

PubMed

Eze, Paul; Balsells, Evelyn; Kyaw, Moe H; Nair, Harish

2017-06-01

Recognition of a broad spectrum of disease and development of Clostridium difficile infection (CDI) and recurrent CDI (rCDI) in populations previously considered to be at low risk has renewed attention on differences in the risk profile of patients. In the absence of primary prevention for CDI and limited treatment options, it is important to achieve a deep understanding of the multiple factors that influence the risk of developing CDI and rCDI. We conducted a review of systematic reviews and meta-analyses on risk factors for CDI and rCDI published between 1990 and October 2016. 22 systematic reviews assessing risk factors for CDI (n = 19) and rCDI (n = 6) were included. Meta-analyses were conducted in 17 of the systematic reviews. Over 40 risk factors have been associated with CDI and rCDI and can be classified into three categories: pharmacological risk factors, host-related risk factors, and clinical characteristics or interventions. Most systematic reviews and meta-analyses have focused on antibiotic use (n = 8 for CDI, 3 for rCDI), proton pump inhibitors (n = 8 for CDI, 4 for rCDI), and histamine 2 receptor antagonists (n = 4 for CDI) and chronic kidney disease (n = 4 for rCDI). However, other risk factors have been assessed. We discuss the state of the evidence, methods, and challenges for data synthesis. Several studies, synthesized in different systematic review, provide valuable insights into the role of different risk factors for CDI. Meta-analytic evidence of association has been reported for factors such as antibiotics, gastric acid suppressants, non-selective NSAID, and some co-morbidities. However, despite statistical significance, issues of high heterogeneity, bias and confounding remain to be addressed effectively to improve overall risk estimates. Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted-CDI clinical management procedures, prevention, and research.

Treatment of recurrent Clostridium difficile infection using fecal microbiota transplantation in patients with inflammatory bowel disease.

PubMed

Newman, Krista M; Rank, Kevin M; Vaughn, Byron P; Khoruts, Alexander

2017-05-04

We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.

Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study.

PubMed

Ianiro, G; Valerio, L; Masucci, L; Pecere, S; Bibbò, S; Quaranta, G; Posteraro, B; Currò, D; Sanguinetti, M; Gasbarrini, A; Cammarota, G

2017-05-01

Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). Although a single faecal infusion is usually sufficient to eradicate CDI, a considerable number of patients need multiple infusions to be cured. The aim of this study was to identify predictors of failure after single faecal infusion in patients with recurrent CDI. We included patients with recurrent CDI prospectively treated with FMT by colonoscopy. By means of univariate and multivariate analysis, variables including female gender, age, number of CDI recurrences, severity of CDI, hospitalization, inadequate bowel preparation, unrelated donor, and use of frozen faeces, were assessed to predict failure after single faecal infusion. Sixty-four patients (39 women; mean age 74 years) were included. Of them, 44 (69%) were cured by a single faecal infusion, whereas 20 (31%) needed repeat infusions. Overall, FMT cured 62 of 64 (97%) patients. In the subgroup of patients with severe CDI, only eight of 26 (30%) were cured with a single infusion. At multivariate analysis, severe CDI (OR 24.66; 95% CI 4.44-242.08; p 0.001) and inadequate bowel preparation (OR 11.53; 95% CI 1.71-115.51; p 0.019) were found to be independent predictors of failure after single faecal infusion. Severe CDI and inadequate bowel preparation appear to be independent predictors of failure after single faecal infusion in patients treated with FMT by colonoscopy for recurrent CDI. Our results may help to optimize protocols and outcomes of FMT in patients with recurrent CDI. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Epidemiological and economic burden of Clostridium difficile in the United States: estimates from a modeling approach.

PubMed

Desai, Kamal; Gupta, Swati B; Dubberke, Erik R; Prabhu, Vimalanand S; Browne, Chantelle; Mast, T Christopher

2016-06-18

Despite a large increase in Clostridium difficile infection (CDI) severity, morbidity and mortality in the US since the early 2000s, CDI burden estimates have had limited generalizability and comparability due to widely varying clinical settings, populations, or study designs. A decision-analytic model incorporating key input parameters important in CDI epidemiology was developed to estimate the annual number of initial and recurrent CDI cases, attributable and all-cause deaths, economic burden in the general population, and specific number of high-risk patients in different healthcare settings and the community in the US. Economic burden was calculated adopting a societal perspective using a bottom-up approach that identified healthcare resources consumed in the management of CDI. Annually, a total of 606,058 (439,237 initial and 166,821 recurrent) episodes of CDI were predicted in 2014: 34.3 % arose from community exposure. Over 44,500 CDI-attributable deaths in 2014 were estimated to occur. High-risk susceptible individuals representing 5 % of the total hospital population accounted for 23 % of hospitalized CDI patients. The economic cost of CDI was $5.4 billion ($4.7 billion (86.7 %) in healthcare settings; $725 million (13.3 %) in the community), mostly due to hospitalization. A modeling framework provides more comprehensive and detailed national-level estimates of CDI cases, recurrences, deaths and cost in different patient groups than currently available from separate individual studies. As new treatments for CDI are developed, this model can provide reliable estimates to better focus healthcare resources to those specific age-groups, risk-groups, and care settings in the US where they are most needed. (Trial Identifier ClinicaTrials.gov: NCT01241552).

Excess Length of Stay Attributable to Clostridium difficile Infection (CDI) in the Acute Care Setting: A Multistate Model.

PubMed

Stevens, Vanessa W; Khader, Karim; Nelson, Richard E; Jones, Makoto; Rubin, Michael A; Brown, Kevin A; Evans, Martin E; Greene, Tom; Slade, Eric; Samore, Matthew H

2015-09-01

Standard estimates of the impact of Clostridium difficile infections (CDI) on inpatient lengths of stay (LOS) may overstate inpatient care costs attributable to CDI. In this study, we used multistate modeling (MSM) of CDI timing to reduce bias in estimates of excess LOS. A retrospective cohort study of all hospitalizations at any of 120 acute care facilities within the US Department of Veterans Affairs (VA) between 2005 and 2012 was conducted. We estimated the excess LOS attributable to CDI using an MSM to address time-dependent bias. Bootstrapping was used to generate 95% confidence intervals (CI). These estimates were compared to unadjusted differences in mean LOS for hospitalizations with and without CDI. During the study period, there were 3.96 million hospitalizations and 43,540 CDIs. A comparison of unadjusted means suggested an excess LOS of 14.0 days (19.4 vs 5.4 days). In contrast, the MSM estimated an attributable LOS of only 2.27 days (95% CI, 2.14-2.40). The excess LOS for mild-to-moderate CDI was 0.75 days (95% CI, 0.59-0.89), and for severe CDI, it was 4.11 days (95% CI, 3.90-4.32). Substantial variation across the Veteran Integrated Services Networks (VISN) was observed. CDI significantly contributes to LOS, but the magnitude of its estimated impact is smaller when methods are used that account for the time-varying nature of infection. The greatest impact on LOS occurred among patients with severe CDI. Significant geographic variability was observed. MSM is a useful tool for obtaining more accurate estimates of the inpatient care costs of CDI.

Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium difficile Infection Among Medicare Beneficiaries.

PubMed

Drozd, Edward M; Inocencio, Timothy J; Braithwaite, Shamonda; Jagun, Dayo; Shah, Hemal; Quon, Nicole C; Broderick, Kelly C; Kuti, Joseph L

2015-11-01

The management of Clostridium difficile infection (CDI) among hospitalized patients is costly, and ongoing payment reform is compelling hospitals to reduce its burden. To assess the impact of CDI on mortality, hospital costs, healthcare use, and Medicare payments for beneficiaries who were discharged with CDI listed as a secondary International Classification of Diseases , Ninth Revision , Clinical Modification claim diagnosis. Data were analyzed from the 2009 to 2010 5% random sample Medicare Standard Analytic Files of beneficiary claims. Patients with index hospitalizations with CDI as a secondary diagnosis and no previous hospitalization within 30 days were identified. Outcomes included inpatient and 30-day mortality, inpatient costs, index hospital payments, all-provider payments, net hospital losses, payment to cost ratio, length of stay (LOS), and 30-day readmission; outcomes were each risk adjusted using propensity score matching and regression modeling techniques. A total of 3262 patients with CDI were identified after matching to patients without a CDI diagnosis. After risk adjustment, secondary CDI was associated with statistically significantly (all P < 0.05) greater inpatient mortality (3.1% vs. 1.7%), 30-day mortality (4.1% vs. 2.2%), longer LOS (7.0 days vs. 3.8 days), higher rates of 30-day hospital readmissions (14.8% vs. 10.4%), and greater hospital costs ($16,184 vs. $13,954) compared with the non-CDI cohort. The risk-adjusted payment-to-cost ratio was shown to be lower for patients with CDI than those without (0.76 vs. 0.85). Secondary CDI is associated with greater adjusted mortality, costs, LOS, and hospital readmissions, while receiving similar hospital reimbursement compared with patients without CDI in a Medicare population.

Mortality and Costs in Clostridium difficile Infection Among the Elderly in the United States.

PubMed

Shorr, Andrew F; Zilberberg, Marya D; Wang, Li; Baser, Onur; Yu, Holly

2016-11-01

OBJECTIVE To examine attributable mortality and costs of Clostridium difficile infection (CDI) in the Medicare population. DESIGN A population-based cohort study among US adults aged at least 65 years in the 2008-2010 Medicare 5% sample, with follow-up of 12 months. PATIENTS Incident CDI episode was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code of 008.45 and no other occurrences within the preceding 12 months. To quantify the adjusted mortality and costs we developed a 1:1 propensity-matched sample of CDI and non-CDI patients. RESULTS Among 1,165,165 patients included, 6,838 (0.6%) had a CDI episode in 2009 (82.5% healthcare-associated). Patients with CDI were older (mean [SD] age, 81.0±8.0 vs 77.0±7.7 years, P<.001), were more likely to come from the Northeast (27.4% vs 18.6%, P<.001), and had a higher comorbidity burden (Charlson score, 4.6±3.3 vs 1.7±2.1, P<.001). Hospitalizations (63.2% vs 6.0%, P<.001) and antibiotics (33.9% vs 12.5%, P<.001) within the prior 90 days were more common in the group with CDI. In the propensity-adjusted analysis, CDI was associated with near doubling of both mortality (42.6% vs 23.4%, P<.001) and total healthcare costs ($64,807±$66,480 vs $38,128±$46,485, P<.001). CONCLUSIONS Among elderly patients, CDI is associated with an increase in adjusted mortality and healthcare costs following a CDI episode. Nationwide annually this equals 240,000 patients with CDI, 46,000 potential deaths, and more than $6 billion in costs. Infect Control Hosp Epidemiol 2016;1-6.

Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium difficile Infection Among Medicare Beneficiaries

PubMed Central

Drozd, Edward M.; Inocencio, Timothy J.; Braithwaite, Shamonda; Jagun, Dayo; Shah, Hemal; Quon, Nicole C.; Broderick, Kelly C.; Kuti, Joseph L.

2015-01-01

Background The management of Clostridium difficile infection (CDI) among hospitalized patients is costly, and ongoing payment reform is compelling hospitals to reduce its burden. To assess the impact of CDI on mortality, hospital costs, healthcare use, and Medicare payments for beneficiaries who were discharged with CDI listed as a secondary International Classification of Diseases, Ninth Revision, Clinical Modification claim diagnosis. Methods Data were analyzed from the 2009 to 2010 5% random sample Medicare Standard Analytic Files of beneficiary claims. Patients with index hospitalizations with CDI as a secondary diagnosis and no previous hospitalization within 30 days were identified. Outcomes included inpatient and 30-day mortality, inpatient costs, index hospital payments, all-provider payments, net hospital losses, payment to cost ratio, length of stay (LOS), and 30-day readmission; outcomes were each risk adjusted using propensity score matching and regression modeling techniques. Results A total of 3262 patients with CDI were identified after matching to patients without a CDI diagnosis. After risk adjustment, secondary CDI was associated with statistically significantly (all P < 0.05) greater inpatient mortality (3.1% vs. 1.7%), 30-day mortality (4.1% vs. 2.2%), longer LOS (7.0 days vs. 3.8 days), higher rates of 30-day hospital readmissions (14.8% vs. 10.4%), and greater hospital costs ($16,184 vs. $13,954) compared with the non-CDI cohort. The risk-adjusted payment-to-cost ratio was shown to be lower for patients with CDI than those without (0.76 vs. 0.85). Conclusions Secondary CDI is associated with greater adjusted mortality, costs, LOS, and hospital readmissions, while receiving similar hospital reimbursement compared with patients without CDI in a Medicare population. PMID:27885315

Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study.

PubMed

Carstensen, Jeppe West; Chehri, Mahtab; Schønning, Kristian; Rasmussen, Steen Christian; Anhøj, Jacob; Godtfredsen, Nina Skavlan; Andersen, Christian Østergaard; Petersen, Andreas Munk

2018-05-03

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 10 9 , Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

Risk factors and outcomes associated with severe clostridium difficile infection in children.

PubMed

Kim, Jason; Shaklee, Julia F; Smathers, Sarah; Prasad, Priya; Asti, Lindsey; Zoltanski, Joan; Dul, Michael; Nerandzic, Michelle; Coffin, Susan E; Toltzis, Philip; Zaoutis, Theoklis

2012-02-01

The incidence and severity of Clostridium difficile infection (CDI) is increasing among adults; however, little is known about the epidemiology of CDI among children. We conducted a nested case-control study to identify the risk factors for and a prospective cohort study to determine the outcomes associated with severe CDI at 2 children's hospitals. Severe CDI was defined as CDI and at least 1 complication or ≥2 laboratory or clinical indicators consistent with severe disease. Studied outcomes included relapse, treatment failure, and CDI-related complications. Isolates were tested to determine North American pulsed-field gel electrophoresis type 1 lineage. We analyzed 82 patients with CDI, of whom 48 had severe disease. Median age in years was 5.93 (1.78-12.16) and 1.83 (0.67-8.1) in subjects with severe and nonsevere CDI, respectively (P = 0.012). All patients with malignancy and CDI had severe disease. Nine subjects (11%) had North American pulsed-field gel electrophoresis type 1 isolates. Risk factors for severe disease included age (adjusted odds ratio [95% confidence interval]: 1.12 [1.02, 1.24]) and receipt of 3 antibiotic classes in the 30 days before infection (3.95 [1.19, 13.11]). If infants less than 1 year of age were excluded, only receipt of 3 antibiotic classes remained significantly associated with severe disease. Neither the rate of relapse nor treatment failure differed significantly between patients with severe and nonsevere CDI. There was 1 death. Increasing age and exposure to multiple antibiotic classes were risk factors for severe CDI. Although most patients studied had severe disease, complications were infrequent. Relapse rates were similar to those reported in adults.

Enhanced surveillance of Clostridium difficile infection occurring outside hospital, England, 2011 to 2013.

PubMed

Fawley, Warren N; Davies, Kerrie A; Morris, Trefor; Parnell, Peter; Howe, Robin; Wilcox, Mark H

2016-07-21

There are limited national epidemiological data for community-associated (CA)-Clostridium difficile infections (CDIs). Between March 2011 and March 2013, laboratories in England submitted to the Clostridium difficile Ribotyping Network (CDRN) up to 10 diarrhoeal faecal samples from successive patients with CA-CDI, defined here as C. difficile toxin-positive diarrhoea commencing outside hospital (or less than 48 hours after hospital admission), including those cases associated with community-based residential care, with no discharge from hospital within the previous 12 weeks. Patient demographics and C. difficile PCR ribotypes were compared for CA-CDIs in our study and presumed healthcare-associated (HA) CDIs via CDRN. Ribotype diversity indices, ranking and relative prevalences were very similar in CA- vs HA-CDIs, although ribotypes 002 (p ≤ 0.0001),020 (p = 0.009) and 056 (p < 0.0001) predominated in CA-CDIs; ribotype 027 (p = 0.01) predominated in HA-CDIs. Epidemic ribotypes 027 and 078 predominated in institutional residents with CDI (including care/nursing homes) compared with people with CDI living at home. Ribotype diversity decreased with increasing age in HA-CDIs, but not in CA-CDIs. Ribotype 078 CA-CDIs were significantly more common in elderly people (3.4% (6/174) vs 8.7% (45/519) in those aged < 65 and ≥ 65 years, respectively; p = 0.019). No antibiotics were prescribed in the previous four weeks in about twofold more CA-CDI vs HAs (38.6% (129/334) vs 20.3% (1,226/6,028); p < 0.0001). We found very similar ribotype distributions in CA- and HA-CDIs, although a few ribotypes significantly predominated in one setting. These national data emphasise the close interplay between, and likely common reservoirs for, CDIs, particularly when epidemic strains are not dominant. This article is copyright of The Authors, 2016.

Surveillance of Clostridium difficile Infections: Results from a Six-Year Retrospective Study in Nine Hospitals of a North Italian Local Health Authority

PubMed Central

Roncarati, Greta; Dallolio, Laura; Leoni, Erica; Panico, Manuela; Zanni, Angela; Farruggia, Patrizia

2017-01-01

Clostridium difficile is an emerging cause of healthcare associated infections. In nine hospitals of an Italian Local Health Authority the episodes of C. difficile infection (CDI) were identified using the data registered by the centralized Laboratory Information System, from 2010 to 2015. CDI incidence (positive patients for A and/or B toxins per patients-days) was analysed per year, hospital, and ward. A number of cases approximately equivalent to the mean of identified cases per year were studied retrospectively to highlight the risk factors associated to CDI and their severity. Nine hundred and forty-two patients affected by CDI were identified. The overall incidence was 3.7/10,000 patients-days, with a stable trend across the six years and the highest rates observed in smaller and outlying hospitals (up to 17.8/10,000), where the admitted patients were older and the wards with the highest incidences (long-term-care: 7.6/10,000, general medicine: 5.7/10,000) were more represented. The mean age of patients in each hospital was correlated with CDI rates. Of the 101 cases selected for the retrospective study, 86.1% were healthcare associated, 10.9% community acquired; 9.1% met the criteria for recurrent case and 23.8% for severe case of CDI. The overall mortality rate was 28.7%. Comorbidity conditions occurred in 91.1%, previous exposure to antibiotics in 76.2%, and proton pump inhibitors in 77.2%. Recurrent and severe cases were significantly associated with renal insufficiency and creatinine levels ≥2 mg/dL. The survey based on the centralized laboratory data was useful to study CDI epidemiology in the different centres in order to identify possible weaknesses and plan control strategies, in particular the reinforcement of staff training, mainly targeted at compliance with contact precautions and hand hygiene. PMID:28075419

Investigation to identify a resource-efficient case-control methodology for determining antibiotics associated with Clostridium difficile infection.

PubMed

Chung, Philip; Currie, Brian; Guo, Yi; Talansky, Moshe; Brown, Shakara; Ostrowsky, Belinda

2014-10-01

Antimicrobial exposure remains an important risk factor for developing Clostridium difficile infection (CDI). Efficient method to identify antibiotics associated with CDI is important for formulating strategies to curtail their use. As a prelude to a more extensive Agency for Healthcare Research and Quality-funded project (Evaluation & Research on Antimicrobial Stewardship's Effect on Clostridium difficile), we undertook an exploratory evaluation to determine a resource-efficient method for identifying antibiotic targets for antimicrobial stewardship interventions. The study compared a series of 6 focused case-control studies. Cases consisted of patients with laboratory-confirmed CDI admitted from July-October 2009. Controls were selected from patients without CDI hospitalized during the same period. Five groups of controls were matched to cases (2:1 ratio) using group-specific matching criteria, including admission date, age, type of admission, length of stay (LOS) to discharge, and/or LOS to CDI diagnosis. The final control group was selected from patients who received antibiotics during hospitalization. Data, including demographics and antibiotic usage, were compared between case and control groups. A total of 126 cases were matched to 6 groups of 252 controls. For control groups 1-5, the use of piperacillin and tazobactam, ceftriaxone or cefepime, ciprofloxacin or moxifloxacin, intravenous vancomycin, azithromycin, and antibiotics of last resort were significantly more frequent in case than control patients. For the final control group, the associations between ceftriaxone or cefepime, and ciprofloxacin or moxifloxacin use and CDI no longer persisted. This could in part be explained by differences in comorbidities between case and control patients even with stringent matching criteria. Use of a simple matching strategy to conduct case-control studies is an efficient and feasible compromise strategy, especially in resource-limited settings, to identify high-risk antibiotics associated with CDI. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

76 FR 6624 - Anti-Infective Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

... FIDAXOMICIN tablets, submitted by Optimer Pharmaceuticals, Inc., for the requested indication of treatment of adults with Clostridium difficile infection (CDI), also known as Clostridium difficile-associated..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31...

Clostridium difficile infection in low- and middle-human development index countries: a systematic review.

PubMed

Forrester, Joseph D; Cai, Lawrence Z; Mbanje, Chenesa; Rinderknecht, Tanya N; Wren, Sherry M

2017-10-01

To describe the impact and epidemiology of Clostridium difficile infection (CDI) in low- and middle-human development index (LMHDI) countries. Prospectively registered, systematic literature review of existing literature in the PubMed, Ovid and Web of Science databases describing the epidemiology and management of C. difficile in LMHDI countries. Risk factors were compared between studies when available. Of the 218 abstracts identified after applying search criteria, 25 studies were reviewed in detail. The weighted pooled infection rate among symptomatic non-immunosuppressed inpatients was 15.8% (95% CI 12.1-19.5%) and was 10.1% (95% CI 3.0-17.2%) among symptomatic outpatients. Subgroup analysis of immunosuppressed patient populations revealed pooled infection rates similar to non-immunosuppressed patient populations. Risk factor analysis was infrequently performed. While the percentages of patients with CDI in LMHDI countries among the reviewed studies are lower than expected, there remains a paucity of epidemiologic data evaluating burden of C. difficile infection in these settings. © 2017 John Wiley & Sons Ltd.

Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials.

PubMed

Crook, Derrick W; Walker, A Sarah; Kean, Yin; Weiss, Karl; Cornely, Oliver A; Miller, Mark A; Esposito, Roberto; Louie, Thomas J; Stoesser, Nicole E; Young, Bernadette C; Angus, Brian J; Gorbach, Sherwood L; Peto, Timothy E A

2012-08-01

Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%-51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%-60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13-40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI.

High morbidity and mortality of Clostridium difficile infection and its associations with ribotype 002 in Hong Kong.

PubMed

Wong, Sunny H; Ip, Margaret; Hawkey, Peter M; Lo, Norman; Hardy, Katie; Manzoor, Susan; Hui, Wyman W M; Choi, Kin-Wing; Wong, Rity Y K; Yung, Irene M H; Cheung, Catherine S K; Lam, Kelvin L Y; Kwong, Thomas; Wu, William K K; Ng, Siew C; Wu, Justin C Y; Sung, Joseph J Y; Lee, Nelson

2016-08-01

We aim to study the disease burden, risk factors and severity of Clostridium difficile infection (CDI) in Hong Kong. We conducted a prospective, case-control study in three acute-care hospitals in Hong Kong. Adult inpatients who developed CDI diarrhoea confirmed by PCR (n = 139) were compared with the non-CDI controls (n = 114). Ribotyping of isolates and antimicrobial susceptibility testing were performed. The estimated crude annual incidence of CDI was 23-33/100,000 population, and 133-207/100,000 population among those aged ≥65 years. The mean age of CDI patients was 71.5. Nursing home care, recent hospitalization, antibiotics exposure (adjusted OR 3.0, 95% CI 1.3-7.1) and proton-pump inhibitors use (adjusted OR 2.2, 95% CI 1.2-3.9) were risk factors. Severe CDI occurred in 41.7%. Overall mortality was 16.5% (among severe CDI, 26.5%). The commonest ribotypes were 002 (22.8%), 014 (14.1%), 012 and 046; ribotype 027 was absent. Ribotype 002 was associated with fluoroquinolone resistance and higher mortality (47.6% vs. 12.7%; adjusted HR 2.8, 95% CI 1.1-7.0). Our findings show high morbidity and mortality of CDI in the older adults, and identify ribotype 002 as a possible virulent strain causing serious infections in this cohort. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients.

PubMed

Cusini, A; Béguelin, C; Stampf, S; Boggian, K; Garzoni, C; Koller, M; Manuel, O; Meylan, P; Mueller, N J; Hirsch, H H; Weisser, M; Berger, C; van Delden, C

2018-01-19

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Risk factors associated with Clostridium difficile infection in kidney transplant recipients.

PubMed

Spinner, M L; Stephany, B R; Cerrato, P M; Lam, S W; Neuner, E A; Patel, K S

2018-05-24

Solid organ transplant recipients are especially vulnerable to Clostridium difficile infection (CDI) due to cumulative risk factors including increased exposure to healthcare settings, persistent immunosuppression, and higher rates of antimicrobial exposure. We aimed to identify risk factors associated with CDI development in kidney transplant recipients including implications of immunosuppressive therapies and acid-suppressing agents. This was a single-center, non-interventional, retrospective case-control study of adult subjects between June 1, 2009 and June 30, 2013. During this time, 728 patients underwent kidney transplantation. Overall, 22 developed CDI (cases) and were matched 1:3 with 66 controls. Cases and controls were also matched for induction agent, kidney allograft type (living or deceased), and time from transplant to CDI result (±60 days). The majority of subjects received a deceased donor kidney (77.3%) and basiliximab induction therapy (86.4%). The overall CDI incidence was 3%. Factors independently associated with CDI were average tacrolimus trough (AOR = 1.25, 95% CI = 1.00-1.56, P = .048) and antibiotic exposure for urinary tract infections (UTI) (AOR = 4.17, 95% CI = 1.12-15.54, P = .034). Proton pump inhibitor use was not associated with CDI (OR = 0.81, 95% CI = 0.29-2.29, P = .691). Maintaining a clinically appropriate tacrolimus trough and judicious antibiotic use and selection for UTI treatment could potentially reduce CDI in the kidney transplant population. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inflammatory bowel disease and Clostridium difficile infection: contrasting views of international clinical professionals.

PubMed

Stallmach, Andreas; Anttila, Veli-Jukka; Hell, Markus; Gwynn, Simon; Merino-Amador, Paloma; Petrosillo, Nicola; Ráčil, Zdenek; Warren, Tim; Wenisch, Christoph; Wilcox, Mark

2018-02-09

 In patients with inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) is a risk factor for both morbidity and mortality. Currently, appropriate management is unclear. Guidance on best practice in the diagnosis and treatment of CDI in IBD patients is therefore needed.  A multidisciplinary group of clinicians involved in the treatment of patients with IBD and CDI developed 27 consensus statements. Respondents were asked to rate their agreement with each statement using a 4-point Likert scale. A modified Delphi methodology was used to review responses of 442 physicians from different specialties (including infectious disease specialists [n = 104], microbiologists [n = 95], and gastroenterologists [n = 73]). A threshold of 75 % agreement was predefined as consensus.  Consensus was achieved for 17 of the 27 statements. Unprompted recognition of risk factors for CDI was low. Intensification of immunosuppressive therapy in the absence of clinical improvement was controversial. Clear definitions of treatment failure of antibiotic therapy in CDI and recurrence of CDI in IBD are needed. Respondents require further clarity regarding the place of fecal microbiota transplantation in CDI patients with IBD. Differences were observed between the perceptions of microbiologists and gastroenterologists, as well as between countries.  Different perceptions both between specialties and geographical locations complicate the development of an internationally accepted algorithm for the diagnosis and treatment of CDI in patients with IBD. This study highlights the need for future studies in this area. © Georg Thieme Verlag KG Stuttgart · New York.

Comparing the economic and health benefits of different approaches to diagnosing Clostridium difficile infection.

PubMed

Bartsch, Sarah M; Umscheid, Craig A; Nachamkin, Irving; Hamilton, Keith; Lee, Bruce Y

2015-01-01

Accurate diagnosis of Clostridium difficile infection (CDI) is essential to effectively managing patients and preventing transmission. Despite the availability of several diagnostic tests, the optimal strategy is debatable and their economic values are unknown. We modified our previously existing C. difficile simulation model to determine the economic value of different CDI diagnostic approaches from the hospital perspective. We evaluated four diagnostic methods for a patient suspected of having CDI: 1) toxin A/B enzyme immunoassay, 2) glutamate dehydrogenase (GDH) antigen/toxin AB combined in one test, 3) nucleic acid amplification test (NAAT), and 4) GDH antigen/toxin AB combination test with NAAT confirmation of indeterminate results. Sensitivity analysis varied the proportion of those tested with clinically significant diarrhoea, the probability of CDI, NAAT cost and CDI treatment delay resulting from a false-negative test, length of stay and diagnostic sensitivity and specificity. The GDH/toxin AB plus NAAT approach leads to the timeliest treatment with the fewest unnecessary treatments given, resulted in the best bed management and generated the lowest cost. The NAAT-alone approach also leads to timely treatment. The GDH/toxin AB diagnostic (without NAAT confirmation) approach resulted in a large number of delayed treatments, but results in the fewest secondary colonisations. Results were robust to the sensitivity analysis. Choosing the right diagnostic approach is a matter of cost and test accuracy. GDH/toxin AB plus NAAT diagnosis led to the timeliest treatment and was the least costly. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Impact of clinical awareness and diagnostic tests on the underdiagnosis of Clostridium difficile infection.

PubMed

Alcalá, L; Reigadas, E; Marín, M; Martín, A; Catalán, P; Bouza, E

2015-08-01

A multicenter study of Clostridium difficile infection (CDI) performed during 2008 in Spain revealed that two of every three episodes went undiagnosed or were misdiagnosed owing to nonsensitive diagnostic tests or lack of clinical suspicion and request. Since then, efforts have been made to improve the diagnostic tests used by laboratories and to increase the awareness of this disease among both clinicians and microbiologists. Our objective was to evaluate the impact of these efforts by assessing the current magnitude of underdiagnosis of CDI in Spain using two point-prevalence studies performed on one day each in January and July of 2013. A total of 111 Spanish laboratories selected all unformed stool specimens received for microbiological diagnosis on these days, and toxigenic culture was performed at a central reference laboratory. Toxigenic isolates were characterized both pheno- and genotypically. The reference laboratory detected 103 episodes of CDI in patients aged 2 years or more. Half (50.5 %) of the episodes were not diagnosed in the participating laboratories, owing to insensitive diagnostic tests (15.5 %) or the lack of clinical suspicion and request (35.0 %). The main ribotypes were 014, 078/126, 001/072, and 106. Ribotype 027 caused 2.9 % of all cases. Despite all the interventions undertaken, CDI remains a highly neglected disease because of the lack of sensitive diagnostic tests in some institutions and, especially, the absence of clinical suspicion, mainly in patients with community-associated CDI. Toxigenic C. difficile should be routinely sought in unformed stools sent for microbiological diagnosis, regardless of their origin.

Epidemiology and healthcare costs of incident Clostridium difficile infections identified in the outpatient healthcare setting.

PubMed

Kuntz, Jennifer L; Johnson, Eric S; Raebel, Marsha A; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Spindel, Steven J; Neil, Nancy; Smith, David H

2012-10-01

To describe the epidemiology and healthcare costs of Clostridium difficile infection (CDI) identified in the outpatient setting. Population-based, retrospective cohort study. Kaiser Permanente Colorado and Kaiser Permanente Northwest members between June 1, 2005, and September 30, 2008. We identified persons with incident CDI and classified CDI by whether it was identified in the outpatient or inpatient healthcare setting. We collected information about baseline variables and follow-up healthcare utilization, costs, and outcomes among patients with CDI. We compared characteristics of patients with CDI identified in the outpatient versus inpatient setting. We identified 3,067 incident CDIs; 56% were identified in the outpatient setting. Few strong, independent predictors of diagnostic setting were identified, although a previous stay in a nonacute healthcare institution (odds ratio [OR], 1.45 [95% confidence interval (CI), 1.13-1.86]) was statistically associated with outpatient-identified CDI, as was age from 50 to 59 years (OR, 1.64 [95% CI, 1.18-2.29]), 60 to 69 years (OR, 1.37 [95% CI, 1.03-1.82]), and 70 to 79 years (OR, 1.36 [95% CI, 1.06-1.74]), when compared with persons aged 80-89 years. We found that more than one-half of incident CDIs in this population were identified in the outpatient setting. Patients with outpatient-identified CDI were younger with fewer comorbidities, although they frequently had previous exposure to healthcare. These data suggest that practitioners should be aware of CDI and obtain appropriate diagnostic testing on outpatients with CDI symptoms.

Awareness about clostridium difficile infection among internal medicine residents in the United States.

PubMed

Navaneethan, U; Schauer, D; Giannella, R

2011-09-01

Clostridium difficile infection (CDI) is the leading infective cause of antibiotic associated diarrhea. The principal objective of this study was to assess the knowledge and awareness of internal medicine (IM) residents regarding the epidemiology, clinical recognition, diagnosis and management of CDI. A 20-question survey was distributed to 90 IM residents in all three years of their post graduate training in a university-based program. The survey instrument assessed the resident's knowledge of the current epidemiological trend, clinical recognition and presentation, diagnosis and management of CDI. Forty two out of 90 (48%) residents completed the questionnaire. Only 10/42 (23.8%) of the residents recommended the gold standard investigation for diagnosing CDI. The majority of residents 29/42 (69%) were not aware of the existence of CDI in the outpatient setting and would not test for CDI. Only 50% of the residents were aware of the worse outcome of CDI in inflammatory bowel disease patients and only 12/42 (28.6%) would appropriately risk stratify and treat patients. Almost all of the residents (97.6%) knew about the appropriate time to consult surgery. There was no significant difference in the awareness with respect to the year of training (interns vs. residents), their career choices (primary care vs. fellowship) nor did the knowledge correlate with the United States medical licensing examination (USMLE) scores. IM residents had suboptimal knowledge of many aspects of the common problem of CDI. Educational efforts should be directed at IM residents, many of whom plan careers as primary care/hospitalists, who will encounter patients with CDI.

Evaluation of a Clostridium difficile infection management policy with clinical pharmacy and medical microbiology involvement at a major Canadian teaching hospital.

PubMed

Yeung, S S T; Yeung, J K; Lau, T T Y; Forrester, L A; Steiner, T S; Bowie, W R; Bryce, E A

2015-12-01

Clostridium difficile infection (CDI) represents a spectrum of disease and is a significant concern for healthcare institutions. Our study objective was to assess whether implementation of a regional CDI management policy with Clinical Pharmacy and Medical Microbiology and Infection Control involvement would lead to an improvement in concordance in prescribing practices to an evidence-based CDI disease severity assessment and pharmacological treatment algorithm. Conducted at a tertiary care teaching hospital, this two-phase quality assurance study consisted of a baseline retrospective healthcare record review of patients with CDI prior to the implementation of a regional CDI management policy followed by a prospective evaluation post-implementation. One hundred and forty-one CDI episodes in the pre-implementation group were compared to 283 episodes post-implementation. Overall treatment concordance to the CDI treatment algorithm was achieved in 48 of 141 cases (34%) pre-implementation compared with 136 of 283 cases (48·1%) post-implementation (P = 0·01). The median time to treatment with vancomycin was reduced from five days to one day (P < 0·01), with median length of hospital stay decreasing from 30 days to 21 days (P = 0·01) post-implementation. There was no difference in 30-day all-cause mortality. A comprehensive approach with appropriate stakeholder involvement in the development of clinical pathways, education to healthcare workers and prospective audit with intervention and feedback can ensure patients diagnosed with CDI are optimally managed and prescribed the most appropriate therapy based on CDI disease severity. © 2015 John Wiley & Sons Ltd.

Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection

PubMed Central

Cherian, Philip T.; Wu, Xiaoqian; Yang, Lei; Scarborough, Jerrod S.; Singh, Aman P.; Alam, Zahidul A.; Lee, Richard E.; Hurdle, Julian G.

2015-01-01

Objectives Metronidazole, a mainstay treatment for Clostridium difficile infection (CDI), is often ineffective for severe CDI. Whilst this is thought to arise from suboptimal levels of metronidazole in the colon due to rapid absorption, empirical validation is lacking. In contrast, reutericyclin, an antibacterial tetramic acid from Lactobacillus reuteri, concentrates in the gastrointestinal tract. In this study, we modified metronidazole with reutericyclin's tetramic acid motif to obtain non-absorbed compounds, enabling assessment of the impact of pharmacokinetics on treatment outcomes. Methods A series of metronidazole-bearing tetramic acid substituents were synthesized and evaluated in terms of anti-C. difficile activities, gastric permeability, in vivo pharmacokinetics, efficacy in the hamster model of CDI and mode of action. Results Most compounds were absorbed less than metronidazole in cell-based Caco-2 permeability assays. In hamsters, lead compounds compartmentalized in the colon rather than the bloodstream with negligible levels detected in the blood, in direct contrast with metronidazole, which was rapidly absorbed into the blood and was undetectable in caecum. Accordingly, four leads were more efficacious (P < 0.05) than metronidazole in C. difficile-infected animals. Improved efficacy was not due to an alternative mode of action, as the leads retained the mode of action of metronidazole. Conclusions This study provides the clearest empirical evidence that the high absorption of metronidazole lowers treatment outcomes for CDI and suggests a role for the tetramic acid motif for colon-specific drug delivery. This approach also has the potential to lower systemic toxicity and drug interactions of nitroheterocyclic drugs for treating gastrointestine-specific diseases. PMID:26286574

Clostridium difficile Infection in the Department of Defense (DOD): 2007-2013

DTIC Science & Technology

2015-02-01

Comorbidity Burden among CDI Patients............................................................. 14 Previous Antibiotic and Gastric Acid Inhibitor...23 Previous Antibiotic and Gastric Acid Inhibitor Use...risk factors for CDI have been antibiotic use, advanced age (i.e., 65 years of age or older), comorbidity, use of gastric acid suppressants, and

Fidaxomicin: the newest addition to the armamentarium against Clostridium difficile infections.

PubMed

Lancaster, Jason W; Matthews, S James

2012-01-01

Fidaxomicin, a macrolide antibiotic, was the first medication for the management of Clostridium difficile infections (CDI) to be approved by the US Food and Drug Administration in more than 20 years. This article reviews published literature on fidaxomicin for management of CDI, including its chemistry, spectrum of activity, pharmacokinetic properties, pharmacodynamics, therapeutic efficacy, adverse events, dosing, administration, and pharmacoeconomic considerations. Pertinent English-language literature was reviewed through searches of MEDLINE, EMBASE, and BIOSIS from 1975 through September 2011. Reference lists of identified publications and published abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy meetings were also reviewed. Search terms included, but were not limited to, fidaxomicin, difimicin, lipiarmycin, tiacumicin B, OPT-80, Clostridium spp, and diarrhea. A total of 79 publications were identified and 10 were excluded; 6 review articles and 4 abstracts that were later published as articles. Fidaxomicin's in vitro profile is favorable compared with oral metronidazole and vancomycin, with minimum inhibitory concentrations against C difficile that are 2 dilutions lower. From the 2 published Phase III trials, fidaxomicin was deemed to be noninferior in the treatment of mild to moderate CDI compared with oral vancomycin. Recurrence rates for all strains of CDI were lower with fidaxomicin than vancomycin. Adverse events associated with fidaxomicin were similar to placebo, with nausea and vomiting being the most common. Although no pharmacoeconomic studies have compared fidaxomicin with metronidazole or vancomycin, the current price exceeds $2500 (US) per treatment course. Reports suggest that fidaxomicin is noninferior to oral vancomycin in the treatment of mild or moderate CDI, although no published comparisons with metronidazole exist to date. Additionally, fidaxomicin improved outcomes compared with oral vancomycin in terms of rates of relapse and recurrent CDI, and in patients who might require concomitant antibiotics. Prospective, randomized studies comparing fidaxomicin with metronidazole in the treatment of mild or moderate CDI, as well as against vancomycin for severe CDI, should be undertaken to clarify the exact role of fidaxomicin in clinical practice. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Clinical and Healthcare Burden of Multiple Recurrences of Clostridium difficile Infection.

PubMed

Sheitoyan-Pesant, Caroline; Abou Chakra, Claire Nour; Pépin, Jacques; Marcil-Héguy, Anaïs; Nault, Vincent; Valiquette, Louis

2016-03-01

Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI. This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998-2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14-60 days after the previous episode. We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences. This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Recurrent Clostridium difficile infection among Medicare patients in nursing homes: A population-based cohort study.

PubMed

Zilberberg, Marya D; Shorr, Andrew F; Jesdale, William M; Tjia, Jennifer; Lapane, Kate

2017-03-01

We explored the epidemiology and outcomes of Clostridium difficile infection (CDI) recurrence among Medicare patients in a nursing home (NH) whose CDI originated in acute care hospitals.We conducted a retrospective, population-based matched cohort combining Medicare claims with Minimum Data Set 3.0, including all hospitalized patients age ≥65 years transferred to an NH after hospitalization with CDI 1/2011-11/2012. Incident CDI was defined as ICD-9-CM code 008.45 with no others in prior 60 days. CDI recurrence was defined as (within 60 days of last day of CDI treatment): oral metronidazole, oral vancomycin, or fidaxomicin for ≥3 days in part D file; or an ICD-9-CM code for CDI (008.45) during a rehospitalization. Cox proportional hazards and linear models, adjusted for age, gender, race, and comorbidities, examined mortality within 60 days and excess hospital days and costs, in patients with recurrent CDI compared to those without.Among 14,472 survivors of index CDI hospitalization discharged to an NH, 4775 suffered a recurrence. Demographics and clinical characteristics at baseline were similar, as was the risk of death (24.2% with vs 24.4% without). Median number of hospitalizations was 2 (IQR 1-3) among those with and 0 (IQR 0-1) among those without recurrence. Adjusted excess hospital days per patient were 20.3 (95% CI 19.1-21.4) and Medicare reimbursements $12,043 (95% CI $11,469-$12,617) in the group with a recurrence.Although recurrent CDI did not increase the risk of death, it was associated with a far higher risk of rehospitalization, excess hospital days, and costs to Medicare.

Hospital cost of Clostridium difficile infection including the contribution of recurrences in French acute-care hospitals.

PubMed

Le Monnier, A; Duburcq, A; Zahar, J-R; Corvec, S; Guillard, T; Cattoir, V; Woerther, P-L; Fihman, V; Lalande, V; Jacquier, H; Mizrahi, A; Farfour, E; Morand, P; Marcadé, G; Coulomb, S; Torreton, E; Fagnani, F; Barbut, F

2015-10-01

The impact of Clostridium difficile infection (CDI) on healthcare costs is significant due to the extra costs of associated inpatient care. However, the specific contribution of recurrences has rarely been studied. The aim of this study was to estimate the hospital costs of CDI and the fraction attributable to recurrences in French acute-care hospitals. A retrospective study was performed for 2011 on a sample of 12 large acute-care hospitals. CDI costs were estimated from both hospital and public insurance perspectives. For each stay, CDI additional costs were estimated by comparison to controls without CDI extracted from the national DRG (diagnosis-related group) database and matched on DRG, age and sex. When CDI was the primary diagnosis, the full cost of stay was used. A total of 1067 bacteriological cases of CDI were identified corresponding to 979 stays involving 906 different patients. Recurrence(s) were identified in 118 (12%) of these stays with 51.7% of them having occurred within the same stay as the index episode. Their mean length of stay was 63.8 days compared to 25.1 days for stays with an index case only. The mean extra cost per stay with CDI was estimated at €9,575 (median: €7,514). The extra cost of CDI in public acute-care hospitals was extrapolated to €163.1 million at the national level, of which 12.5% was attributable to recurrences. The economic burden of CDI is substantial and directly impacts healthcare systems in France. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Health care burden of Clostridium difficile infection in hospitalized children with inflammatory bowel disease.

PubMed

Pant, Chaitanya; Anderson, Michael P; Deshpande, Abhishek; Altaf, Muhammad A; Grunow, John E; Atreja, Ashish; Sferra, Thomas J

2013-04-01

Children with inflammatory bowel disease (IBD), similar to adults, are at increased risk of acquiring a Clostridium difficile infection (CDI). Our objective was to characterize the health care burden associated with CDI in hospitalized pediatric patients with IBD. We extracted and analyzed cases with a discharge diagnosis of IBD or CDI from the U.S. Healthcare Cost and Utilization Project Kids' Inpatient Database. In our primary analysis, we evaluated pediatric cases with a principal diagnosis of IBD or CDI. For the year 2009, we identified 12,610 weighted cases with IBD of which 3.5% had CDI. In children with IBD, CDI was independently associated with lengthier hospital stays (8.0 versus 6.0 days; adjusted regression coefficient, 2.1 days; 95% confidence interval [CI], 1.4-2.8), higher charges ($45,126 versus $34,703; adjusted regression coefficient, $11,506; 95% CI, 6192-16,820), and greater need for parenteral nutrition (15.9% versus 12.1%; adjusted odds ratio, 1.5; 95% CI, 1.1-2.0) and blood transfusion (17.7% versus 9.8%; adjusted odds ratio, 1.8; 95% CI, 1.4-2.4). There were no deaths. We made similar observations in a subanalysis of cases with principal or secondary diagnoses of IBD or CDI. The incidence of CDI in patients with IBD increased between 2000 and 2009 from 21.7 to 28.0 cases per 1000 IBD cases per year (P < 0.001). There was a significant increase in CDI complicating ulcerative colitis (28.1 versus 42.2, P < 0.001) but not for Crohn's disease (18.3 versus 20.3). CDI represents a significant health care burden in hospitalized children with IBD.

Incidence of Clostridium difficile infection in patients receiving high-risk antibiotics with or without a proton pump inhibitor.

PubMed

Gordon, D; Young, L R; Reddy, S; Bergman, C; Young, J D

2016-02-01

Considering the incidence and severity of Clostridium difficile infection (CDI), risk reduction strategies are crucial. Prior studies suggest that proton pump inhibitor (PPI) use can increase the risk of CDI over antibiotics alone; however, data and guidelines have been conflicting. The aim was to compare CDI incidence in patients receiving high-risk antibiotics, comparing rates in those prescribed a PPI versus those without overlapping PPI exposure. This retrospective cohort study assessed the incidence of CDI in veterans receiving high-risk antibiotics over an approximately three-year period. High-risk antibiotics were defined as: ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, ceftriaxone, cefotaxime, ceftazidime, or cefixime. We identified subjects who were prescribed any high-risk antibiotic, finding 3513 on a concomitant PPI and 6149 not taking a PPI. Of these subjects, 111 were diagnosed with CDI and met inclusion criteria. Baseline characteristics, CDI severity, length of hospitalization and antibiotic therapy prior to infection were similar in both groups. The incidence of CDI was significantly higher in patients prescribed a PPI (odds ratio: 2.2; 95% confidence interval: 1.52-3.23; P=0.0001). A strong association was found between concurrent PPI use with fluoroquinolones (P=0.005) and clindamycin (P=0.045). The use of PPIs together with high-risk antibiotics was associated with a significantly higher incidence of CDI. Our study provides further support for the CDI prevention strategy of judicious PPI use, especially in patients receiving high-risk antibiotics. Prudent avoidance of PPIs may reduce the incidence of CDI, a major cause of morbidity and mortality worldwide. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Prevalence of Clostridium difficile colonization among healthcare workers

PubMed Central

2013-01-01

Background Clostridium difficile infection (CDI) has increased to epidemic proportions in recent years. The carriage of C. difficile among healthy adults and hospital inpatients has been established. We sought to determine whether C. difficile colonization exists among healthcare workers (HCWs) in our setting. Methods A point prevalence study of stool colonization with C. difficile among doctors, nurses and allied health staff at a large regional teaching hospital in Geelong, Victoria. All participants completed a short questionnaire and all stool specimens were tested by Techlab® C.diff Quik Check enzyme immunoassay followed by enrichment culture. Results Among 128 healthcare workers, 77% were female, of mean age 43 years, and the majority were nursing staff (73%). Nineteen HCWs (15%) reported diarrhoea, and 12 (9%) had taken antibiotics in the previous six weeks. Over 40% of participants reported having contact with a patient with known or suspected CDI in the 6 weeks before the stool was collected. C. difficile was not isolated from the stool of any participants. Conclusion Although HCWs are at risk of asymptomatic carriage and could act as a reservoir for transmission in the hospital environment, with the use of a screening test and culture we were unable to identify C. difficile in the stool of our participants in a non-outbreak setting. This may reflect potential colonization resistance of the gut microbiota, or the success of infection prevention strategies at our institution. PMID:24090343

Point-Counterpoint: Active surveillance for carriers of toxigenic Clostridium difficile should be performed to guide prevention efforts.

PubMed

McDonald, L Clifford; Diekema, Daniel J

2018-05-16

In 2017, we published a point-counterpoint on laboratory diagnosis of C. difficile infection (CDI). At that time, Drs Ferric Fang, Christopher Polage, and Mark Wilcox discussed the strategies for diagnosing Clostridium difficile colitis in symptomatic patients. Since that manuscript new guidelines from the Infectious Diseases Society of American and the Society for Health Care Epidemiology have been published (1) and healthcare systems have begun to explore screening asymptomatic patients for C. difficile colonization. The theory behind screening selected patient populations for C. difficile colonization is that these patients represent a substantial reservoir of the bacteria and can transfer the bacteria to other patients. Hospital administrators are taking note of institutional CDI rates because they are publicly reported. They have become an important metric impacting hospital safety ratings and value-based purchasing where hospitals may have millions of dollars of reimbursement at risk. In this point-counterpoint, Cliff McDonald, of the U.S. Centers for Disease Control and Prevention, will discuss the value of asymptomatic C. difficile screening, while Dan Diekema, of the University of Iowa, will discuss why caution should be used. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Prevalence and Clinical Outcomes of Clostridium difficile Infection in the Intensive Care Unit: A Systematic Review and Meta-Analysis

PubMed Central

Karanika, Styliani; Paudel, Suresh; Zervou, Fainareti N.; Grigoras, Christos; Zacharioudakis, Ioannis M.; Mylonakis, Eleftherios

2016-01-01

Background. Intensive care unit (ICU) patients are at higher risk for Clostridium difficile infection (CDI). Methods. We performed a systematic review and meta-analysis of published studies from 1983 to 2015 using the PubMed, EMBASE, and Google Scholar databases to study the prevalence and outcomes of CDI in this patient population. Among the 9146 articles retrieved from the studies, 22 articles, which included a total of 80 835 ICU patients, were included in our final analysis. Results. The prevalence of CDI among ICU patients was 2% (95% confidence interval [CI], 1%–2%), and among diarrheic ICU patients the prevalence was 11% (95% CI, 6%–17%). Among CDI patients, 25% (95% CI, 5%–51%) were diagnosed with pseudomembranous colitis, and the estimated length of ICU stay before CDI acquisition was 10.74 days (95% CI, 5%–51%). The overall hospital mortality among ICU patients with CDI was 32% (95% CI, 26%–39%), compared with 24% (95% CI, 14%–36%) among those without CDI presenting a statistically significant difference in mortality risk (P = .030). It is worth noting that the length of ICU and hospital stay among CDI patients was significantly longer, compared with non-CDI patients (standardized mean of difference [SMD] = 0.49, 95% CI, .39%–.6%, P = .00 and SMD = 1.15, 95% CI, .44%–1.91%, P = .003, respectively). It is noteworthy that the morbidity score at ICU admission (Acute Physiology and Chronic Health Evaluation II [APACHE II]) was not statistically different between the 2 groups (P = .911), implying that the differences in outcomes can be attributed to CDI. Conclusions. The ICU setting is associated with higher prevalence of CDI. In this setting, CDI is associated with increased hospital mortality and prolonged ICU and overall hospital stay. These findings highlight the need for additional prevention and treatment studies in this setting. PMID:26788544

Effects of Clostridium difficile infection in patients with alcoholic hepatitis.

PubMed

Sundaram, Vinay; May, Folasade P; Manne, Vignan; Saab, Sammy

2014-10-01

Infection increases mortality in patients with alcoholic hepatitis (AH). Little is known about the association between Clostridium difficile infection (CDI) and AH. We examined the prevalence and effects of CDI in patients with AH, compared with those of other infections. We performed a cross-sectional analysis using data collected from the Nationwide Inpatient Sample, from 2008 through 2011. International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with AH. We used multivariable logistic regression to determine risk factors that affect mortality, negative binomial regression to evaluate the effects of CDI on predicted length of stay (LOS), and Poisson regression to determine the effects of CDI on predicted hospital charges. Chi-square and Wilcoxon rank-sum analyses were used to compare mortality, LOS, and hospital charges associated with CDI with those associated with urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP). Of 10,939 patients with AH, 177 had CDI (1.62%). Patients with AH and CDI had increased odds of inpatient mortality (adjusted odds ratio, 1.75; P = .04), a longer predicted LOS (10.63 vs 5.75 d; P < .001), and greater predicted hospital charges ($36,924.30 vs $29,136.58; P < .001), compared with those without CDI. Compared with UTI, CDI was associated with similar mortality but greater LOS (9 vs 6 d; P < .001) and hospital charges ($45,607 vs $32,087; P < .001). SBP was associated with higher mortality than CDI (17.3% vs 10.1%; P = .045), but similar LOS and hospital charges. In patients with AH, CDI is associated with greater mortality and health care use. These effects appear similar to those for UTI and SBP. We propose further studies to determine the cost effectiveness of screening for CDI among patients with AH. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Clostridium difficile Infections among Hospitalized Children, United States, 1997–2006

PubMed Central

Tillotson, Glenn S.; McDonald, L. Clifford

2010-01-01

We evaluated the annual rate (cases/10,000 hospitalizations) of pediatric hospitalizations with Clostridium difficile infection (CDI; International Classification of Diseases, 9th revision, clinical modification code 008.45) in the United States. We performed a time-series analysis of data from the Kids’ Inpatient Database within the Health Care Cost and Utilization Project during 1997–2006 and a cross-sectional analysis within the National Hospital Discharge Survey during 2006. The rate of pediatric CDI-related hospitalizations increased from 7.24 to 12.80 from 1997 through 2006; the lowest rate was for children <1 year of age. Although incidence was lowest for newborns (0.5), incidence for children <1 year of age who were not newborns (32.01) was similar to that for children 5–9 years of age (35.27), which in turn was second only to incidence for children 1–4 years of age (44.87). Pediatric CDI-related hospitalizations are increasing. A better understanding of the epidemiology and outcomes of CDI is urgently needed. PMID:20350373

Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications: A case series.

PubMed

Lahtinen, Perttu; Mattila, Eero; Anttila, Veli-Jukka; Tillonen, Jyrki; Teittinen, Matti; Nevalainen, Pasi; Salminen, Seppo; Satokari, Reetta; Arkkila, Perttu

2017-10-21

Fecal microbiota transplantation (FMT) is effective in recurrent Clostridium difficile infection (rCDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides rCDI. Among our FMT-treated rCDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than rCDI: Salmonella carriage (two patients), trimethylaminuria (two patients), small intestinal bacterial overgrowth (SIBO; one patient), and lymphocytic colitis (one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli ( E. coli ) carriage. Of the thirteen rCDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with rCDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.

Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis.

PubMed

Konijeti, Gauree G; Sauk, Jenny; Shrime, Mark G; Gupta, Meera; Ananthakrishnan, Ashwin N

2014-06-01

Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.

Clinical and economic consequences of vancomycin and fidaxomicin for the treatment of Clostridium difficile infection in Canada.

PubMed

Wagner, Monika; Lavoie, Louis; Goetghebeur, Mireille

2014-03-01

Clostridium difficile infection (CDI) represents a public health problem with increasing incidence and severity. To evaluate the clinical and economic consequences of vancomycin compared with fidaxomicin in the treatment of CDI from the Canadian health care system perspective. A decision-tree model was developed to compare vancomycin and fidaxomicin for the treatment of severe CDI. The model assumed identical initial cure rates and included first recurrent episodes of CDI (base case). Treatment of patients presenting with recurrent CDI was examined as an alternative analysis. Costs included were for study medication, physician services and hospitalization. Cost effectiveness was measured as incremental cost per recurrence avoided. Sensitivity analyses of key input parameters were performed. In a cohort of 1000 patients with an initial episode of severe CDI, treatment with fidaxomicin led to 137 fewer recurrences at an incremental cost of $1.81 million, resulting in an incremental cost of $13,202 per recurrence avoided. Among 1000 patients with recurrent CDI, 113 second recurrences were avoided at an incremental cost of $18,190 per second recurrence avoided. Incremental costs per recurrence avoided increased with increasing proportion of cases caused by the NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and treatment duration but were robust to variations in other parameters. The use of fidaxomicin is associated with a cost increase for the Canadian health care system. Clinical benefits of fidaxomicin compared with vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in patients with severe CDI.

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

PubMed

Dubberke, E R; Reske, K A; Olsen, M A; Bommarito, K; Cleveland, A A; Silveira, F P; Schuster, M G; Kauffman, C A; Avery, R K; Pappas, P G; Chiller, T M

2018-04-01

Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CLOSTRIDIUM DIFFICILE INFECTION IN ACUTE CARE HOSPITALS: SYSTEMATIC REVIEW AND BEST PRACTICES FOR PREVENTION

PubMed Central

Louh, Irene K.; Greendyke, William G.; Hermann, Emilia A.; Davidson, Karina W.; Falzon, Louise; Vawdrey, David K.; Shaffer, Jonathan A.; Calfee, David P.; Furuya, E. Yoko; Ting, Henry H.

2017-01-01

Objective Prevention of Clostridium difficile infection (CDI) in acute care hospitals is a priority for hospitals and clinicians. We performed a qualitative systematic review to update the evidence on interventions to prevent CDI published since 2009. Design We searched Ovid, MEDLINE, EMBASE, The Cochrane Library, CINAHL, ISI Web of Knowledge, and grey literature databases from January 1, 2009 to August 1, 2015. Setting We included studies performed in acute care hospitals. Patients or participants We included studies conducted on hospitalized patients that investigated the impact of specific interventions on CDI rates. Interventions We used the QI-Minimum Quality Criteria Set (QI-MQCS) to assess the quality of included studies. Interventions were grouped thematically: environmental disinfection, antimicrobial stewardship, hand hygiene, chlorhexidine bathing, probiotics, bundled approaches, and others. A meta-analysis was performed when possible. Results Of 3236 articles screened, 261 met the criteria for full-text review and 46 studies were ultimately included. The average quality rating was 82% on the QI-MQCS. The most effective interventions, resulting in a 45% to 85% reduction in CDI, included daily to twice daily disinfection of high-touch surfaces (including bed rails) and terminal cleaning of patient rooms with chlorine-based products. Bundled interventions and antimicrobial stewardship showed promise for reducing CDI rates. Chlorhexidine bathing and intensified hand hygiene practices were not effective for reducing CDI rates. Conclusions Daily and terminal cleaning of patient rooms using chlorine-based products were most effective in reducing CDI rates in hospitals. Further studies are needed to identify the components of bundled interventions that reduce CDI rates. PMID:28300019

Successful treatment of simulated Clostridium difficile infection in a human gut model by fidaxomicin first line and after vancomycin or metronidazole failure.

PubMed

Chilton, C H; Crowther, G S; Freeman, J; Todhunter, S L; Nicholson, S; Longshaw, C M; Wilcox, M H

2014-02-01

Fidaxomicin reduces the risk of recurrent Clostridium difficile infection (CDI) compared with vancomycin. We investigated fidaxomicin primary or secondary treatment efficacy using a gut model. Four triple-stage chemostat gut models were inoculated with faeces. After clindamycin induction of CDI, fidaxomicin (200 mg/L twice daily), vancomycin (125 mg/L four times daily) or metronidazole (9.3 mg/L three times daily) was administered for 7 days. Following failure/CDI recurrence, fidaxomicin (200 mg/L twice daily, 7 days) was instilled. C. difficile (CD) total viable counts (TVC), spore counts (SP), toxin titres (CYT), gut bacteria counts and antimicrobial concentrations were measured throughout. Fidaxomicin instillation reduced CD TVC/SP and CYT below the limit of detection (LOD) after 2 and 4 days, respectively, with no CDI recurrence. Metronidazole instillation failed to decrease CD TVC or CYT. Vancomycin instillation reduced CD TVC and CYT to LOD by day 4, but SP persisted. Recurrence occurred 13 days after vancomycin instillation; subsequent fidaxomicin instillation reduced CD TVC/SP/CYT below the LOD from day 2. CD was isolated sporadically, with no evidence of spore recrudescence or toxin production. Fidaxomicin had a minimal effect on the microflora, except for bifidobacteria. Fidaxomicin was detected for at least 21 days post-instillation, whereas other antimicrobials were undetectable beyond ∼4 days. Fidaxomicin successfully treated simulated primary and recurrent CDI. Fidaxomicin was superior to metronidazole in reducing CD TVC and SP, and superior to vancomycin in reducing SP without recurrence of vegetative cell growth. Fidaxomicin, but not vancomycin or metronidazole, persisted in the gut model for >20 days after instillation.

Impact of the NAP-1 strain on disease severity, mortality, and recurrence of healthcare-associated Clostridium difficile infection.

PubMed

Bauer, Karri A; Johnston, Jessica E W; Wenzler, Eric; Goff, Debra A; Cook, Charles H; Balada-Llasat, Joan-Miquel; Pancholi, Preeti; Mangino, Julie E

2017-12-01

Studies are conflicting regarding the association of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) and outcomes. We evaluated the association of NAP1 with healthcare-associated CDI disease severity, mortality, and recurrence at our academic medical center. Healthcare-associated CDI cases were identified from November 1, 2011 through January 31, 2013. Multivariable regression models were used to evaluate the associations of NAP1 with severe disease (based on the Hines VA severity score index), mortality, and recurrence. Among 5424 stool specimens submitted to the Clinical Microbiology Laboratory, 292 (5.4%) were positive for C. difficile by polymerase chain reaction (PCR) on or after hospital day 4; 70 (24%) of these specimens also tested positive for NAP1. During the study period, 247 (85%) patients had non-severe disease and 45 (15%) patients had severe disease. Among patients with non-severe disease, 65 (26%) had NAP1 and among patients with severe disease, 5 (11%) had NAP1. After controlling for potential confounders, NAP1 was not associated with an increased likelihood of severe disease (adjusted odds ratio [aOR] = 0.35; 95% confidence interval [CI], 0.13-0.93), in-hospital mortality (aOR = 1.02; 95% CI, 0.53-1.96), or recurrence (aOR = 1.16, 95% CI, 0.36-3.77). The NAP1 strain did not increase disease severity, mortality, or recurrence in this study, although the incidence of NAP1-positive healthcare associated-CDI was low. The role of strain typing in outcomes and treatment selection in patients with healthcare-associated CDI remains uncertain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two-step glutamate dehydrogenase antigen real-time polymerase chain reaction assay for detection of toxigenic Clostridium difficile.

PubMed

Goldenberg, S D; Cliff, P R; Smith, S; Milner, M; French, G L

2010-01-01

Current diagnosis of Clostridium difficile infection (CDI) relies upon detection of toxins A/B in stool by enzyme immunoassay [EIA(A/B)]. This strategy is unsatisfactory because it has a low sensitivity resulting in significant false negatives. We investigated the performance of a two-step algorithm for diagnosis of CDI using detection of glutamate dehydrogenase (GDH). GDH-positive samples were tested for C. difficile toxin B gene (tcdB) by polymerase chain reaction (PCR). The performance of the two-step protocol was compared with toxin detection by the Meridian Premier EIA kit in 500 consecutive stool samples from patients with suspected CDI. The reference standard among samples that were positive by either EIA(A/B) or GDH testing was culture cytotoxin neutralisation (culture/CTN). Thirty-six (7%) of 500 samples were identified as true positives by culture/CTN. EIA(A/B) identified 14 of the positive specimens with 22 false negatives and two false positives. The two-step protocol identified 34 of the positive samples with two false positives and two false negatives. EIA(A/B) had a sensitivity of 39%, specificity of 99%, positive predictive value of 88% and negative predictive value of 95%. The two-step algorithm performed better, with corresponding values of 94%, 99%, 94% and 99% respectively. Screening for GDH before confirmation of positives by PCR is cheaper than screening all specimens by PCR and is an effective method for routine use. Current EIA(A/B) tests for CDI are of inadequate sensitivity and should be replaced; however, this may result in apparent changes in CDI rates that would need to be explained in national surveillance statistics. Copyright 2009 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

A Decade of Experience in Primary Prevention of Clostridium difficile Infection at a Community Hospital Using the Probiotic Combination Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+).

PubMed

Maziade, Pierre-Jean; Pereira, Pascale; Goldstein, Ellie J C

2015-05-15

In August 2003, the 284-bed community hospital Pierre-Le Gardeur (PLGH) in Quebec experienced a major outbreak associated with the Clostridium difficile NAP1/027/BI strain. Augmented standard preventive measures (SPMs) were not able to control this outbreak. It was decided in February 2004 to give to every adult inpatient on antibiotics, without any exclusion, a probiotic (Bio-K+: Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2) within 12 hours of the antibiotic prescription. Augmented SPMs were continued. The use of the probiotic in addition to SPMs was associated with a marked reduction of C. difficile infection (CDI). During the 10 years of observation, 44 835 inpatients received Bio-K+, and the CDI rate at PLGH declined from 18.0 cases per 10,000 patient-days and remained at low mean levels of 2.3 cases per 10,000 patient-days. Additionally, 10-year data collected by the Ministry of Health in Quebec comparing the CDI rate between Quebec hospitals showed that CDI rates at PLGH were consistently and continuously lower compared with those at similar hospitals. Blood cultures were monitored at PLGH for Lactobacillus bacteremia through the 10 years' experience, and no Lactobacillus bacteremias were detected. Despite the limitation of an observational study, we concluded that the probiotic Bio-K+ was safe and effective in decreasing our primary CDI rate. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Clostridium difficile the hospital plague.

PubMed

Czepiel, J; Kozicki, M; Panasiuk, P; Birczyńska, M; Garlicki, A; Wesełucha-Birczyńska, A

2015-04-07

Clostridium difficile infection (CDI) has become one of the major public health threats in the last two decades. An increase has been observed not only in the rate of CDI, but also in its severity and mortality. Symptoms caused by this pathogen are accompanied by intense local and systemic inflammation. We confirmed that Raman microspectroscopy can help us in understanding CDI pathogenesis. A single erythrocyte of patients with CDI shows a difference, approximately 10 times, in the intensity of the Raman spectra at the beginning of hospitalization and after one week of treatment. The intensity level is an indicator of the spread of the inflammation within the cell, confirmed by standard laboratory tests. Many of the observed bands with enormously enhanced intensity, e.g. 1587, 1344, 1253, 1118 and 664 cm(-1), come from the symmetric vibration of the pyrrole ring. Heme variation of recovered cells in the acute CDI state between the first and the seventh day of treatment seems to show increased levels of oxygenated hemoglobin. Intense inflammation alters the conformation of the protein which is reflected in the significant changes in the amide I, II and III bands. There is an observed shift and a significant intensity increase of 1253 and 970 cm(-1) amide III and skeletal protein backbone CC stretching vibration bands, respectively. Principal Component Analysis (PCA) was used to find the variance in the data collected on the first and seventh day. PC2 loading in the 1645-1500 cm(-1) range shows an increase of heme, Tyr, Trp, or Phe vibrations because of changes in the protein microenvironment due to their exposure. Positive maxima at 1621, 1563 and 1550 in the PC2 loading originated from the ring vibrations. These observations indicate that Clostridium difficile toxins induce cytopathogenicity by altering cellular proteins.

The use of fidaxomicin for treatment of relapsed Clostridium difficile infections in patients with cancer.

PubMed

Esmaily-Fard, Amin; Tverdek, Frank P; Crowther, David M; Ghantoji, Shashank S; Adachi, Javier A; Chemaly, Roy F

2014-11-01

To report our experience with the use of fidaxomicin (FDX), an oral macrocyclic antibiotic, in cancer patients with Clostridium difficile infection (CDI). A single-center retrospective case series was conducted at The University of Texas MD Anderson Cancer Center. Patients with CDI treated with FDX from May 2011 to January 2013 were identified via the pharmacy database. Clinical response and recurrence after FDX initiation were evaluated. Twenty-two patients were included, most of whom were male (55%) with a mean age of 58 years (range: 20-83 yrs). The most common underlying malignancies were nine patients with lymphoma (41%), seven with leukemia (32%), and six with solid tumors (27%). Indications for FDX included recurrent CDI in 16 patients (72%) and failure of both metronidazole and oral vancomycin in 6 patients (28%). Nineteen patients (86%) were on concomitant antimicrobials during CDI treatment. Clinical response to FDX was 91%, and overall sustained clinical response was 82%. FDX was well tolerated with no major adverse events that were FDX related or discontinuations due to drug-related adverse events. In cancer patients, FDX is effective treatment for the first episode of CDI after failure of standard therapies and treatment of recurrent CDI. This was interesting given the large number of high-risk patients who continued to receive concomitant antimicrobial therapy, which is common in this immunocompromised patient population. © 2014 Pharmacotherapy Publications, Inc.

Hospital-acquired Clostridium difficile infection: determinants for severe disease.

PubMed

Wenisch, J M; Schmid, D; Kuo, H-W; Simons, E; Allerberger, F; Michl, V; Tesik, P; Tucek, G; Wenisch, C

2012-08-01

Risk factors of severity (need for surgical intervention, intensive care or fatal outcome) were analysed in hospital-acquired Clostridium difficile infection (CDI) in a 777-bed community hospital. In a prospective analytical cross-sectional study, age (≥ 65 years), sex, CDI characteristics, underlying diseases, severity of comorbidity and PCR ribotypes were tested for associations with severe CDI. In total, 133 cases of hospital-acquired CDI (mean age 74.4 years) were identified, resulting in an incidence rate of 5.7/10,000 hospital-days. A recurrent episode of diarrhoea occurred in 25 cases (18.8%) and complications including toxic megacolon, dehydration and septicaemia in 69 cases (51.9%). Four cases (3.0%) required ICU admission, one case (0.8%) surgical intervention and 22 cases (16.5%) died within the 30-day follow-up period. Variables identified to be independently associated with severe CDI were severe diarrhoea (odds ratio [OR] 3.64, 95% confidence interval [CI] 1.19-11.11, p=0.02), chronic pulmonary disease (OR 3.0, 95% CI 1.08-8.40, p=0.04), chronic renal disease (OR 2.9, 95% CI 1.07-7.81, p=0.04) and diabetes mellitus (OR 4.30, 95% CI 1.57-11.76, p=0.004). The case fatality of 16.5% underlines the importance of increased efforts in CDI prevention, in particular for patients with underlying diseases.

Highlighting clinical needs in Clostridium difficile infection: the views of European healthcare professionals at the front line.

PubMed

Aguado, J M; Anttila, V J; Galperine, T; Goldenberg, S D; Gwynn, S; Jenkins, D; Norén, T; Petrosillo, N; Seifert, H; Stallmach, A; Warren, T; Wenisch, C

2015-06-01

Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea in Europe. Despite increased focus, its incidence and severity are increasing in many European countries. We developed a series of consensus statements to identify unmet clinical needs in the recognition and management of CDI. A consortium of European experts prepared a series of 29 statements representing their collective views on the diagnosis and management of CDI in Europe. The statements were grouped into the following six broad themes: diagnosis; definitions of severity; treatment failure, recurrence and its consequences; infection prevention and control interventions; education and antimicrobial stewardship; and National CDI clinical guidance and policy. These statements were reviewed using questionnaires by 1047 clinicians involved in managing CDI, who indicated their level of agreement with each statement. Levels of agreement exceeded the 66% threshold for consensus for 27 out of 29 statements (93.1%), indicating strong support. Variance between countries and specialties was analysed and showed strong alignment with the overall consensus scores. Based on the consensus scores of the respondent group, recommendations are suggested for the further development of CDI services in order to reduce transmission and recurrence and to ensure that appropriate diagnosis and treatment strategies are applied across all healthcare settings. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fidaxomicin Versus Vancomycin for Clostridium difficile Infection: Meta-analysis of Pivotal Randomized Controlled Trials

PubMed Central

Crook, Derrick W.; Walker, A. Sarah; Kean, Yin; Weiss, Karl; Cornely, Oliver A.; Miller, Mark A.; Esposito, Roberto; Louie, Thomas J.; Stoesser, Nicole E.; Young, Bernadette C.; Angus, Brian J.; Gorbach, Sherwood L.; Peto, Timothy E. A.

2012-01-01

Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%–51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%–60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13–40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI. PMID:22752871

Hospital-based Clostridium difficile infection surveillance reveals high proportions of PCR ribotypes 027 and 176 in different areas of Poland, 2011 to 2013.

PubMed

Pituch, Hanna; Obuch-Woszczatyński, Piotr; Lachowicz, Dominika; Wultańska, Dorota; Karpiński, Paweł; Młynarczyk, Grażyna; van Dorp, Sofie M; Kuijper, Ed J

2015-01-01

As part of the European Clostridium difficile infections (CDI) surveillance Network (ECDIS-Net), which aims to build capacity for CDI surveillance in Europe, we constructed a new network of hospital-based laboratories in Poland. We performed a survey in 13 randomly selected hospital-laboratories in different sites of the country to determine their annual CDI incidence rates from 2011 to 2013. Information on C. difficile laboratory diagnostic testing and indications for testing was also collected. Moreover, for 2012 and 2013 respectively, participating hospital-laboratories sent all consecutive isolates from CDI patients between February and March to the Anaerobe Laboratory in Warsaw for further molecular characterisation, including the detection of toxin-encoding genes and polymerase chain reaction (PCR)-ribotyping. Within the network, the mean annual hospital CDI incidence rates were 6.1, 8.6 and 9.6 CDI per 10,000 patient-days in 2011, 2012, and 2013 respectively. Six of the 13 laboratories tested specimens only on the request of a physician, five tested samples of antibiotic-associated diarrhoea or samples from patients who developed diarrhoea more than two days after admission (nosocomial diarrhoea), while two tested all submitted diarrhoeal faecal samples. Most laboratories (9/13) used tests to detect glutamate dehydrogenase and toxin A/B either separately or in combination. In the two periods of molecular surveillance, a total of 166 strains were characterised. Of these, 159 were toxigenic and the majority belonged to two PCR-ribotypes: 027 (n=99; 62%) and the closely related ribotype 176 (n=22; 14%). The annual frequency of PCR-ribotype 027 was not significantly different during the surveillance periods (62.9% in 2012; 61.8% in 2013). Our results indicate that CDIs caused by PCR-ribotype 027 predominate in Polish hospitals participating in the surveillance, with the closely related 176 ribotype being the second most common agent of infection.

Rheological properties of erythrocytes in patients infected with Clostridium difficile.

PubMed

Czepiel, Jacek; Jurczyszyn, Artur; Biesiada, Grażyna; Sobczyk-Krupiarz, Iwona; Jałowiecka, Izabela; Świstek, Magdalena; Perucki, William; Teległów, Aneta; Marchewka, Jakub; Dąbrowski, Zbigniew; Mach, Tomasz; Garlicki, Aleksander

2014-12-04

Clostridium difficile infection (CDI) is a bacterial infection of the digestive tract. Acute infections are accompanied by increased risk for venous thromboembolism (VTE). To date, there have been no studies of the rheological properties of blood during the course of digestive tract infections. The aim of our study was to examine the effects of CDI on red blood cell (RBC) rheology, specifically RBC deformability, RBC aggregation, and plasma viscosity. In addition, the activity of glucose 6 phosphate dehydrogenase (G6PD) and acetylcholinesterase (AChE) in RBC was studied. Our study group included 20 patients with CDI, 20 healthy persons comprised the control group. We examined the effects of CDI on the rheology of RBCs, their deformability and aggregation, using a Laser-assisted Optical Rotational Cell Analyzer (LORCA). Plasma viscosity was determined using a capillary tube plasma viscosymeter. Moreover, we estimated the activity of AChE and G6PD in RBC using spectrophotometric method. A statistically significant increase was found in the aggregation index, viscosity and activity of G6PD whereas the amount of time to reach half of maximum aggregation (t½) and the amplitude of aggregation (AMP) both showed statistically significantly decreases among patients with CDI compared to the control group. We also observed that the Elongation Index (EI) was decreased when shear stress values were low, between 0.3 Pa and 0.58 Pa, whereas EI was increased for shear stress in the range of 1.13-59.97 Pa. These observations were statistically significant. We report for the first time that acute infection of the gastrointestinal tract with Clostridium difficile is associated with abnormalities in rheological properties of blood, increased serum viscosity as well as increased aggregation of RBCs, which correlated with severity of inflammation. These abnormalities may be an additional mechanism causing increased incidence of VTE in CDI.

Development of a Novel Vaccine Containing Binary Toxin for the Prevention of Clostridium difficile Disease with Enhanced Efficacy against NAP1 Strains.

PubMed

Secore, Susan; Wang, Su; Doughtry, Julie; Xie, Jinfu; Miezeiewski, Matt; Rustandi, Richard R; Horton, Melanie; Xoconostle, Rachel; Wang, Bei; Lancaster, Catherine; Kristopeit, Adam; Wang, Sheng-Ching; Christanti, Sianny; Vitelli, Salvatore; Gentile, Marie-Pierre; Goerke, Aaron; Skinner, Julie; Strable, Erica; Thiriot, David S; Bodmer, Jean-Luc; Heinrichs, Jon H

2017-01-01

Clostridium difficile infections (CDI) are a leading cause of nosocomial diarrhea in the developed world. The main virulence factors of the bacterium are the large clostridial toxins (LCTs), TcdA and TcdB, which are largely responsible for the symptoms of the disease. Recent outbreaks of CDI have been associated with the emergence of hypervirulent strains, such as NAP1/BI/027, many strains of which also produce a third toxin, binary toxin (CDTa and CDTb). These hypervirulent strains have been associated with increased morbidity and higher mortality. Here we present pre-clinical data describing a novel tetravalent vaccine composed of attenuated forms of TcdA, TcdB and binary toxin components CDTa and CDTb. We demonstrate, using the Syrian golden hamster model of CDI, that the inclusion of binary toxin components CDTa and CDTb significantly improves the efficacy of the vaccine against challenge with NAP1 strains in comparison to vaccines containing only TcdA and TcdB antigens, while providing comparable efficacy against challenge with the prototypic, non-epidemic strain VPI10463. This combination vaccine elicits high neutralizing antibody titers against TcdA, TcdB and binary toxin in both hamsters and rhesus macaques. Finally we present data that binary toxin alone can act as a virulence factor in animal models. Taken together, these data strongly support the inclusion of binary toxin in a vaccine against CDI to provide enhanced protection from epidemic strains of C. difficile.

Development of a Novel Vaccine Containing Binary Toxin for the Prevention of Clostridium difficile Disease with Enhanced Efficacy against NAP1 Strains

PubMed Central

Wang, Su; Doughtry, Julie; Xie, Jinfu; Miezeiewski, Matt; Rustandi, Richard R.; Horton, Melanie; Xoconostle, Rachel; Wang, Bei; Lancaster, Catherine; Kristopeit, Adam; Wang, Sheng-Ching; Christanti, Sianny; Vitelli, Salvatore; Gentile, Marie-Pierre; Goerke, Aaron; Skinner, Julie; Strable, Erica; Thiriot, David S.; Bodmer, Jean-Luc; Heinrichs, Jon H.

2017-01-01

Clostridium difficile infections (CDI) are a leading cause of nosocomial diarrhea in the developed world. The main virulence factors of the bacterium are the large clostridial toxins (LCTs), TcdA and TcdB, which are largely responsible for the symptoms of the disease. Recent outbreaks of CDI have been associated with the emergence of hypervirulent strains, such as NAP1/BI/027, many strains of which also produce a third toxin, binary toxin (CDTa and CDTb). These hypervirulent strains have been associated with increased morbidity and higher mortality. Here we present pre-clinical data describing a novel tetravalent vaccine composed of attenuated forms of TcdA, TcdB and binary toxin components CDTa and CDTb. We demonstrate, using the Syrian golden hamster model of CDI, that the inclusion of binary toxin components CDTa and CDTb significantly improves the efficacy of the vaccine against challenge with NAP1 strains in comparison to vaccines containing only TcdA and TcdB antigens, while providing comparable efficacy against challenge with the prototypic, non-epidemic strain VPI10463. This combination vaccine elicits high neutralizing antibody titers against TcdA, TcdB and binary toxin in both hamsters and rhesus macaques. Finally we present data that binary toxin alone can act as a virulence factor in animal models. Taken together, these data strongly support the inclusion of binary toxin in a vaccine against CDI to provide enhanced protection from epidemic strains of C. difficile. PMID:28125650

Development of a recombinant toxin fragment vaccine for Clostridium difficile infection.

PubMed

Karczewski, Jerzy; Zorman, Julie; Wang, Su; Miezeiewski, Matthew; Xie, Jinfu; Soring, Keri; Petrescu, Ioan; Rogers, Irene; Thiriot, David S; Cook, James C; Chamberlin, Mihaela; Xoconostle, Rachel F; Nahas, Debbie D; Joyce, Joseph G; Bodmer, Jean-Luc; Heinrichs, Jon H; Secore, Susan

2014-05-19

Clostridium difficile infection (CDI) is the major cause of antibiotic-associated diarrhea and pseudomembranous colitis, a disease associated with significant morbidity and mortality. The disease is mostly of nosocomial origin, with elderly patients undergoing anti-microbial therapy being particularly at risk. C. difficile produces two large toxins: Toxin A (TcdA) and Toxin B (TcdB). The two toxins act synergistically to damage and impair the colonic epithelium, and are primarily responsible for the pathogenesis associated with CDI. The feasibility of toxin-based vaccination against C. difficile is being vigorously investigated. A vaccine based on formaldehyde-inactivated Toxin A and Toxin B (toxoids) was reported to be safe and immunogenic in healthy volunteers and is now undergoing evaluation in clinical efficacy trials. In order to eliminate cytotoxic effects, a chemical inactivation step must be included in the manufacturing process of this toxin-based vaccine. In addition, the large-scale production of highly toxic antigens could be a challenging and costly process. Vaccines based on non-toxic fragments of genetically engineered versions of the toxins alleviate most of these limitations. We have evaluated a vaccine assembled from two recombinant fragments of TcdB and explored their potential as components of a novel experimental vaccine against CDI. Golden Syrian hamsters vaccinated with recombinant fragments of TcdB combined with full length TcdA (Toxoid A) developed high titer IgG responses and potent neutralizing antibody titers. We also show here that the recombinant vaccine protected animals against lethal challenge with C. difficile spores, with efficacy equivalent to the toxoid vaccine. The development of a two-segment recombinant vaccine could provide several advantages over toxoid TcdA/TcdB such as improvements in manufacturability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Screening for Asymptomatic Clostridium difficile Among Bone Marrow Transplant Patients: A Mixed-Methods Study of Intervention Effectiveness and Feasibility.

PubMed

Barker, Anna K; Krasity, Benjamin; Musuuza, Jackson; Safdar, Nasia

2018-02-01

OBJECTIVE To identify facilitators and barriers to implementation of a Clostridium difficile screening intervention among bone marrow transplant (BMT) patients and to evaluate the clinical effectiveness of the intervention on the rate of hospital-onset C. difficile infection (HO-CDI). DESIGN Before-and-after trial SETTING A 505-bed tertiary-care medical center PARTICIPANTS All 5,357 patients admitted to the BMT and general medicine wards from January 2014 to February 2017 were included in the study. Interview participants included 3 physicians, 4 nurses, and 4 administrators. INTERVENTION All BMT patients were screened within 48 hours of admission. Colonized patients, as defined by a C. difficile-positive polymerase chain reaction (PCR) stool result, were placed under contact precautions for the duration of their hospital stay. METHODS Interview responses were coded according to the Systems Engineering Initiative for Patient Safety conceptual framework. We compared pre- and postintervention HO-CDI rates on BMT and general internal medicine units using time-series analysis. RESULTS Stakeholder engagement, at both the person and organizational level, facilitates standardization and optimization of intervention protocols. While the screening intervention was generally well received, tools and technology were sources of concern. The mean incidence of HO-CDI decreased on the BMT service postintervention (P<.0001). However, the effect of the change in the trend postintervention was not significantly different on BMT compared to the control wards (P=.93). CONCLUSIONS We report the first mixed-methods study to evaluate a C. difficile screening intervention among the BMT population. The positive nature by which the intervention was received by front-line clinical staff, laboratory staff, and administrators is promising for future implementation studies. Infect Control Hosp Epidemiol 2018;39:177-185.

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology.

PubMed

Elliott, Briony; Androga, Grace O; Knight, Daniel R; Riley, Thomas V

2017-04-01

Over the recent decades, Clostridium difficile infection (CDI) has emerged as a global public health threat. Despite growing attention, C. difficile remains a poorly understood pathogen, however, the exquisite sensitivity offered by next generation sequencing (NGS) technology has enabled analysis of the genome of C. difficile, giving us access to massive genomic data on factors such as virulence, evolution, and genetic relatedness within C. difficile groups. NGS has also demonstrated excellence in investigations of outbreaks and disease transmission, in both small and large-scale applications. This review summarizes the molecular epidemiology, evolution, and phylogeny of C. difficile, one of the most important pathogens worldwide in the current antibiotic resistance era. Copyright © 2016 Elsevier B.V. All rights reserved.

The burden of clostridium difficile infection: estimates of the incidence of CDI from U.S. Administrative databases.

PubMed

Olsen, Margaret A; Young-Xu, Yinong; Stwalley, Dustin; Kelly, Ciarán P; Gerding, Dale N; Saeed, Mohammed J; Mahé, Cedric; Dubberke, Erik R

2016-04-22

Many administrative data sources are available to study the epidemiology of infectious diseases, including Clostridium difficile infection (CDI), but few publications have compared CDI event rates across databases using similar methodology. We used comparable methods with multiple administrative databases to compare the incidence of CDI in older and younger persons in the United States. We performed a retrospective study using three longitudinal data sources (Medicare, OptumInsight LabRx, and Healthcare Cost and Utilization Project State Inpatient Database (SID)), and two hospital encounter-level data sources (Nationwide Inpatient Sample (NIS) and Premier Perspective database) to identify CDI in adults aged 18 and older with calculation of CDI incidence rates/100,000 person-years of observation (pyo) and CDI categorization (onset and association). The incidence of CDI ranged from 66/100,000 in persons under 65 years (LabRx), 383/100,000 in elderly persons (SID), and 677/100,000 in elderly persons (Medicare). Ninety percent of CDI episodes in the LabRx population were characterized as community-onset compared to 41 % in the Medicare population. The majority of CDI episodes in the Medicare and LabRx databases were identified based on only a CDI diagnosis, whereas almost ¾ of encounters coded for CDI in the Premier hospital data were confirmed with a positive test result plus treatment with metronidazole or oral vancomycin. Using only the Medicare inpatient data to calculate encounter-level CDI events resulted in 553 CDI events/100,000 persons, virtually the same as the encounter proportion calculated using the NIS (544/100,000 persons). We found that the incidence of CDI was 35 % higher in the Medicare data and fewer episodes were attributed to hospital acquisition when all medical claims were used to identify CDI, compared to only inpatient data lacking information on diagnosis and treatment in the outpatient setting. The incidence of CDI was 10-fold lower and the proportion of community-onset CDI was much higher in the privately insured younger LabRx population compared to the elderly Medicare population. The methods we developed to identify incident CDI can be used by other investigators to study the incidence of other infectious diseases and adverse events using large generalizable administrative datasets.

Evaluation of bloodstream infections, Clostridium difficile infections, and gut microbiota in pediatric oncology patients.

PubMed

Nycz, Bryan T; Dominguez, Samuel R; Friedman, Deborah; Hilden, Joanne M; Ir, Diana; Robertson, Charles E; Frank, Daniel N

2018-01-01

Bloodstream infections (BSI) and Clostridium difficile infections (CDI) in pediatric oncology/hematology/bone marrow transplant (BMT) populations are associated with significant morbidity and mortality. The objective of this study was to explore possible associations between altered microbiome composition and the occurrence of BSI and CDI in a cohort of pediatric oncology patients. Stool samples were collected from all patients admitted to the pediatric oncology floor from Oct.-Dec. 2012. Bacterial profiles from patient stools were determined by bacterial 16S rRNA gene profiling. Differences in overall microbiome composition were assessed by a permutation-based multivariate analysis of variance test, while differences in the relative abundances of specific taxa were assessed by Kruskal-Wallis tests. At admission, 9 of 42 patients (21%) were colonized with C. difficile, while 6 of 42 (14%) subsequently developed a CDI. Furthermore, 3 patients (7%) previously had a BSI and 6 patients (14%) subsequently developed a BSI. Differences in overall microbiome composition were significantly associated with disease type (p = 0.0086), chemotherapy treatment (p = 0.018), BSI following admission from any cause (p < 0.0001) or suspected gastrointestinal organisms (p = 0.00043). No differences in baseline microbiota were observed between individuals who did or did not subsequently develop C. difficile infection. Additionally, multiple bacterial groups varied significantly between subjects with post-admission BSI compared with no BSI. Our results suggest that differences in gut microbiota not only are associated with type of cancer and chemotherapy, but may also be predictive of subsequent bloodstream infection.

The Monoclonal Antitoxin Antibodies (Actoxumab-Bezlotoxumab) Treatment Facilitates Normalization of the Gut Microbiota of Mice with Clostridium difficile Infection.

PubMed

Džunková, Mária; D'Auria, Giuseppe; Xu, Hua; Huang, Jun; Duan, Yinghua; Moya, Andrés; Kelly, Ciarán P; Chen, Xinhua

2016-01-01

Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab-bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials. Although the main mechanism of protection is through direct neutralization of the toxins, the impact of MK-3415A on gut microbiota and its restoration has not been examined. Using a CDI murine model, we compared the bacterial diversity of the gut microbiome of mice under different treatments including MK-3415A, vancomycin, or vancomycin combined with MK-3415A, sampled longitudinally. Here, we showed that C. difficile infection resulted in the prevalence of Enterobacter species. Sixty percent of mice in the vehicle group died after 2 days and their microbiome was almost exclusively formed by Enterobacter . MK-3415A treatment resulted in lower Enterobacter levels and restoration of Blautia, Akkermansia , and Lactobacillus which were the core components of the original microbiota. Vancomycin treatment led to significantly lower survival rate than the combo treatment of MK-3415A and vancomycin. Vancomycin treatment decreased bacterial diversity with predominant Enterobacter and Akkermansia , while Staphylococcus expanded after vancomycin treatment was terminated. In contrast, mice treated by vancomycin combined with MK-3415A also experienced decreased bacterial diversity during vancomycin treatment. However, these animals were able to recover their initial Blautia and Lactobacillus proportions, even though episodes of Staphylococcus overgrowth were detected by the end of the experiments. In conclusion, MK-3415A (actoxumab-bezlotoxumab) treatment facilitates normalization of the gut microbiota in CDI mice. It remains to be examined whether or not the prevention of recurrent CDI by the antitoxin antibodies observed in clinical trials occurs through modulation of microbiota.

Evaluation of fixed and variable hospital costs due to Clostridium difficile infection: institutional incentives and directions for future research.

PubMed

Ryan, P; Skally, M; Duffy, F; Farrelly, M; Gaughan, L; Flood, P; McFadden, E; Fitzpatrick, F

2017-04-01

Economic analysis of Clostridium difficile infection (CDI) should consider the incentives facing institutional decision-makers. To avoid overstating the financial benefits of infection prevention, fixed and variable costs should be distinguished. To quantify CDI fixed and variable costs in a tertiary referral hospital during August 2015. A micro-costing analysis estimated CDI costs per patient, including the additional costs of a CDI outbreak. Resource use was quantified after review of patient charts, pharmacy data, administrative resource input, and records of salary and cleaning/decontamination expenditure. The incremental cost of CDI was €75,680 (mean: €5,820 per patient) with key cost drivers being cleaning, pharmaceuticals, and length of stay (LOS). Additional LOS ranged from 1.75 to 22.55 days. For seven patients involved in a CDI outbreak, excluding the value of the 58 lost bed-days (€34,585); costs were 30% higher (€7,589 per patient). Therefore, total spending on CDI was €88,062 (mean: €6,773 across all patients). Potential savings from variable costs were €1,026 (17%) or €1,768 (26%) if outbreak costs were included. Investment in an antimicrobial pharmacist would require 47 CDI cases to be prevented annually. Prevention of 5%, 10% and 20% CDI would reduce attributable costs by €4,403, €8,806 and €17,612. Increasing the incremental LOS attributable to CDI to seven days per patient would have increased costs to €7,478 or €8,431 (if outbreak costs were included). As much CDI costs are fixed, potential savings from infection prevention are limited. Future analysis must consider more effectively this distinction and its impact on institutional decision-making. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Comparative epidemiology of Clostridium difficile infection: England and the USA.

PubMed

King, Alice; Mullish, Benjamin H; Williams, Horace R T; Aylin, Paul

2017-10-01

To examine whether there is an epidemiological difference between Clostridium difficile infection (CDI) inpatient populations in England and the United States. A cross-sectional study. National administrative inpatient discharge data from England (Hospital Episode Statistics) and the USA (National Inpatient Sample) in 2012. De-identifiable non-obstetric inpatient discharges from the national datasets were used to estimate national CDI incidence in the United States and England using ICD9-CM(008.45) and ICD10(A04.7) respectively. The rate of CDI was calculated per 100 000 population using national population estimates. Rate per 100 000 inpatient discharges was also calculated separated by primary and secondary diagnosis of CDI. Age, sex and Elixhauser comorbidities profiles were examined. The USA had a higher rate of CDI compared to England: 115.1/100 000 vs. 19.3/100 000 population (P < 0.001). CDI age profiles differed between the countries (P < 0.001): in England, patients ≥75 years constitute a larger proportion of CDI cases, whilst those aged 25-70 constitute more cases in the US (P < 0.001). Overall adjusted odds of CDI in females compared to males was elevated in both England (odds ratios (OR) 1.26 95% CI [1.21,1.31] P < 0.001) and the USA (OR 1.20 95% CI [1.18,1.22] P < 0.001). The proportion of CDI patients with comorbidities was greater in the USA compared to England apart from dementia, which was greater in England (9.63% vs. 1.25%, P < 0.0001). The 2012 inpatient CDI rate within the USA was much higher than in England. Age and comorbidity profiles also differed between CDI patients in both countries. The reasons for this are likely multi-factorial but may reflect national infection control policy. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Fecal Microbiota Therapy With a Focus on Clostridium difficile Infection.

PubMed

Brandt, Lawrence J

2017-10-01

There has been a paradigm shift in our view of bacteria away from their role as just pathogens. We now have a deepening appreciation of their critical influences in our health maintenance, including energy harvest, metabolism, intestinal development, cell proliferation, nervous system and immune function, as well as their role to protect against intestinal and other infections. A perturbed intestinal microbiome has been associated with an increasing number of gastrointestinal and nongastrointestinal diseases but particularly with Clostridium difficile infection (CDI). Although such association does not imply causation, it has been shown that fecal microbiota transplantation (FMT) can correct the dysbiosis that characterizes chronic and recurring CDI and that FMT can effect a seemingly safe and rapidly effective cure for most patients with CDI so treated. FMT has been used to treat a wide range of other diseases, although conclusions about efficacy in any disease other than CDI must await appropriate well-designed trials. More work needs to be conducted with FMT, especially to evaluate and ensure its long-term safety. Future studies are likely to narrow the spectrum of organisms that needs to be given to patients to cure CDI, and perhaps other diseases, and to elucidate the mechanisms whereby such therapeutic benefit occurs. FMT is but the first step in this journey.

[New methodological advances: algorithm proposal for management of Clostridium difficile infection].

PubMed

González-Abad, María José; Alonso-Sanz, Mercedes

2015-06-01

Clostridium difficile infection (CDI) is considered the most common cause of health care-associated diarrhea and also is an etiologic agent of community diarrhea. The aim of this study was to assess the potential benefit of a test that detects glutamate dehydrogenase (GDH) antigen and C. difficile toxin A/B, simultaneously, followed by detection of C. difficile toxin B (tcdB) gene by PCR as confirmatory assay on discrepant samples, and to propose an algorithm more efficient. From June 2012 to January 2013 at Hospital Infantil Universitario Niño Jesús, Madrid, the stool samples were studied for the simultaneous detection of GDH and toxin A/B, and also for detection of toxin A/B alone. When results between GDH and toxin A/B were discordant, a single sample for patient was selected for detection of C. difficile toxin B (tcdB) gene. A total of 116 samples (52 patients) were tested. Four were positive and 75 negative for toxigenic C. difficile (Toxin A/B, alone or combined with GDH). C. difficile was detected in the remaining 37 samples but not toxin A/B, regardless of the method used, except one. Twenty of the 37 specimens were further tested for C. difficile toxin B (tcdB) gene and 7 were positive. The simultaneous detection of GDH and toxin A/B combined with PCR recovered undiagnosed cases of CDI. In accordance with our data, we propose a two-step algorithm: detection of GDH and PCR (in samples GDH positive). This algorithm could provide a superior cost-benefit ratio in our population.

Clostridium difficile infection: New insights into therapeutic options.

PubMed

Kachrimanidou, Melina; Sarmourli, Theopisti; Skoura, Lemonia; Metallidis, Symeon; Malisiovas, Nikolaos

2016-09-01

Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings and represents a major social and economic burden. The major virulence determinants are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), encoded within the pathogenicity locus. Traditional therapies, such as metronidazole and vancomycin, frequently lead to a vicious circle of recurrences due to their action against normal human microbiome. New disease management strategies together with the development of novel therapeutic and containment approaches are needed in order to better control outbreaks and treat patients. This article provides an overview of currently available CDI treatment options and discusses the most promising therapies under development.

Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013.

PubMed

Davies, Kerrie A; Ashwin, Helen; Longshaw, Christopher M; Burns, David A; Davis, Georgina L; Wilcox, Mark H

2016-07-21

Clostridium difficile infection (CDI) is the major cause of infective diarrhoea in healthcare environments. As part of the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), the largest C. difficile epidemiological study of its type, PCR ribotype distribution of C. difficile isolates in Europe was investigated. PCR ribotyping was performed on 1,196 C. difficile isolates from diarrhoeal samples sent to the European coordinating laboratory in 2012-13 and 2013 (from two sampling days) by 482 participating hospitals from 19 European countries. A total of 125 ribotypes were identified, of which ribotypes 027 (19%, n =222), 001/072 (11%, n = 134) and 014/020 (10%, n = 119) were the most prevalent. Distinct regional patterns of ribotype distribution were noted. Of 596 isolates from patients with toxin-positive stools (CDI cases), ribotype 027 accounted for 22% (32/144) of infections in cases aged from 18 to less than 65 years, but the prevalence decreased in those aged ≥ 65 years (14% (59/412)) and further decreased in those aged ≥ 81 years (9% (18/195)). The prevalence of ribotype 027 and 176, but not other epidemic strains, was inversely proportional to overall ribotype diversity (R(2) = 0.717). This study highlights an increased diversity of C. difficile ribotypes across Europe compared with previous studies, with considerable intercountry variation in ribotype distribution. Continuous surveillance programmes are necessary to monitor the changing epidemiology of C. difficile. This article is copyright of The Authors, 2016.

The zoonotic potential of Clostridium difficile from small companion animals and their owners.

PubMed

Rabold, Denise; Espelage, Werner; Abu Sin, Muna; Eckmanns, Tim; Schneeberg, Alexander; Neubauer, Heinrich; Möbius, Nadine; Hille, Katja; Wieler, Lothar H; Seyboldt, Christian; Lübke-Becker, Antina

2018-01-01

Clostridium difficile infections (CDI) in humans range from asymptomatic carriage to life-threatening intestinal disease. Findings on C. difficile in various animal species and an overlap in ribotypes (RTs) suggest potential zoonotic transmission. However, the impact of animals for human CDI remains unclear. In a large-scale survey we collected 1,447 fecal samples to determine the occurrence of C. difficile in small companion animals (dogs and cats) and their owners and to assess potential epidemiological links within the community. The Germany-wide survey was conducted from July 2012-August 2013. PCR ribotyping, Multilocus VNTR Analysis (MLVA) and PCR detection of toxin genes were used to characterize isolated C. difficile strains. A database was defined and logistic regression used to identify putative factors associated with fecal shedding of C. difficile. In total, 1,418 samples met the inclusion criteria. The isolation rates for small companion animals and their owners within the community were similarly low with 3.0% (25/840) and 2.9% (17/578), respectively. PCR ribotyping revealed eight and twelve different RTs in animals and humans, respectively, whereas three RTs were isolated in both, humans and animals. RT 014/0, a well-known human hospital-associated lineage, was predominantly detected in animal samples. Moreover, the potentially highly pathogenic RTs 027 and 078 were isolated from dogs. Even though, C. difficile did not occur simultaneously in animals and humans sharing the same household. The results of the epidemiological analysis of factors associated with fecal shedding of C. difficile support the hypothesis of a zoonotic potential. Molecular characterization and epidemiological analysis revealed that the zoonotic risk for C. difficile associated with dogs and cats within the community is low but cannot be excluded.

Implementation of Global Strategies to Prevent Hospital-Onset Clostridium difficile Infection: Targeting Proton Pump Inhibitors and Probiotics.

PubMed

Lewis, Paul O; Lundberg, Timothy S; Tharp, Jennifer L; Runnels, Clay W

2017-10-01

Proton pump inhibitors (PPIs) have been identified as a significant risk factor for the development of Clostridium difficile infection (CDI). Probiotics given concurrently with antibiotics have been shown to have a moderate impact on preventing CDI. To evaluate the effectiveness of hospital-wide interventions designed to reduce PPI use and increase probiotics and whether these interventions were associated with a change in the incidence of hospital onset (HO)-CDI. This retrospective cohort study compared 2 fiscal years: July 2013 to June 2014 (FY14) and July 2014 to June 2015 (FY15). In July of FY15, global educational initiatives were launched targeting PPIs. Additionally, a HO-CDI prevention bundle was added to antibiotic-containing order sets targeting probiotics. Overall PPI use, probiotic use, and incidence of HO-CDI were recorded and compared for each cohort. Charts were also reviewed for patients who developed HO-CDI for the presence and appropriateness of a PPI and presence of probiotics. The interventions resulted in a decrease in PPI use by 14% or 96 doses/1000 patient days (TPD; P = 0.0002) and a reduction in IV PPI use by 31% or 71 doses/TPD ( P = 0.0008). Probiotic use increased by 130% or 126 doses/TPD ( P = 0.0006). The incidence of HO-CDI decreased by 20% or 0.1 cases/TPD ( P = 0.04). A collaborative, multifaceted educational initiative directed at highlighting the risks associated with PPI use was effective in reducing PPI prescribing. The implementation of a probiotic bundle added to antibiotic order sets was effective in increasing probiotic use. These interventions were associated with a decrease in incidence of HO-CDI.

Cost-effectiveness of Competing Strategies for Management of Recurrent Clostridium difficile Infection: A Decision Analysis

PubMed Central

Konijeti, Gauree G.; Sauk, Jenny; Shrime, Mark G.; Gupta, Meera; Ananthakrishnan, Ashwin N.

2014-01-01

Background. Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. Methods. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. Results. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. Conclusions. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI. PMID:24692533

Clinical and economic burden of Clostridium difficile infection in Europe: a systematic review of healthcare-facility-acquired infection.

PubMed

Wiegand, P N; Nathwani, D; Wilcox, M H; Stephens, J; Shelbaya, A; Haider, S

2012-05-01

PubMed, EMBASE and conference abstracts were reviewed systematically to determine the clinical and economic burden associated with Clostridium difficile infection (CDI) acquired and treated in European healthcare facilities. Inclusion criteria were: published in the English language between 2000 and 2010, and study population of at least 20 patients with documented CDI acquired/treated in European healthcare facilities. Data collection was completed by three unblinded reviewers using the Cochrane Handbook and PRISMA statement. The primary outcomes were mortality, recurrence, length of hospital stay (LOS) and cost related to CDI. In total, 1138 primary articles and conference abstracts were identified, and this was narrowed to 39 and 30 studies, respectively. Data were available from 14 countries, with 47% of studies from UK institutions. CDI mortality at 30 days ranged from 2% (France) to 42% (UK). Mortality rates more than doubled from 1999 to 2004, and continued to rise until 2007 when reductions were noted in the UK. Recurrent CDI varied from 1% (France) to 36% (Ireland); however, recurrence definitions varied between studies. Median LOS ranged from eight days (Belgium) to 27 days (UK). The incremental cost of CDI was £4577 in Ireland and £8843 in Germany, after standardization to 2010 prices. Country-specific estimates, weighted by sample size, ranged from 2.8% to 29.8% for 30-day mortality and from 16 to 37 days for LOS. CDI burden in Europe was most commonly described using 30-day mortality, recurrence, LOS and cost data. The continued spread of CDI and resultant healthcare burden underscores the need for judicious use of antibiotics. Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Economic evaluation of laboratory testing strategies for hospital-associated Clostridium difficile infection.

PubMed

Schroeder, Lee F; Robilotti, Elizabeth; Peterson, Lance R; Banaei, Niaz; Dowdy, David W

2014-02-01

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and <2 transmissions, if lateral-flow GDH diagnostic sensitivity was >93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI.

Increased hospital length of stay attributable to Clostridium difficile infection in patients with four co-morbidities: an analysis of hospital episode statistics in four European countries.

PubMed

Eckmann, Christian; Wasserman, Matthew; Latif, Faisal; Roberts, Graeme; Beriot-Mathiot, Axelle

2013-10-01

Hospital-onset Clostridium difficile infection (CDI) places a significant burden on health care systems throughout Europe, estimated at around €3 billion per annum. This burden is shared between national payers and hospitals that support additional bed days for patients diagnosed with CDI while in hospital or patients re-admitted from a previous hospitalisation. This study was performed to quantify additional hospital stay attributable to CDI in four countries, England, Germany, Spain, and The Netherlands, by analysing nationwide hospital-episode data. We focused upon patients at increased risk of CDI: with chronic obstructive pulmonary disease, heart failure, diabetes, or chronic kidney disease, and aged 50 years or over. Multivariate regression and propensity score matching models were developed to investigate the impact of CDI on additional length of hospital stay, controlling for confounding factors such as underlying disease severity. Patients in England had the longest additional hospital stay attributable to CDI at 16.09 days, followed by Germany at 15.47 days, Spain at 13.56 days, and The Netherlands at 12.58 days, derived using regression analysis. Propensity score matching indicated a higher attributable length of stay of 32.42 days in England, 15.31 days in Spain, and 18.64 days in The Netherlands. Outputs from this study consistently demonstrate that in European countries, for patients whose hospitalisation is complicated by CDI, the infection causes a statistically significant increase in hospital length of stay. This has implications for optimising resource allocation and budget setting at both the national and hospital level to ensure that levels of CDI-complicated hospitalisations are minimised.

Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection

PubMed Central

Nathwani, Dilip; Cornely, Oliver A.; Van Engen, Anke K.; Odufowora-Sita, Olatunji; Retsa, Peny; Odeyemi, Isaac A. O.

2014-01-01

Objectives Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. Methods A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20 000/QALY and £30 000/QALY. One-way and probabilistic sensitivity analyses were performed. Results Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14 515 and £14 344, respectively) and in patients with a first recurrence (£16 535 and £16 926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16 529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30 000/QALY was 60% for severe CDI and 68% in a first recurrence. Conclusions Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin. PMID:25096079

A Systematic Literature Review of Economic Evaluations of Antibiotic Treatments for Clostridium difficile Infection.

PubMed

Burton, Hannah E; Mitchell, Stephen A; Watt, Maureen

2017-11-01

Clostridium difficile infection (CDI) is associated with high management costs, particularly in recurrent cases. Fidaxomicin treatment results in lower recurrence rates than vancomycin and metronidazole, but has higher acquisition costs in Europe and the USA. This systematic literature review summarises economic evaluations (EEs) of fidaxomicin, vancomycin and metronidazole for treatment of CDI. Electronic databases (MEDLINE ® , Embase, Cochrane Library) and conference proceedings (ISPOR, ECCMID, ICAAC and IDWeek) were searched for publications reporting EEs of fidaxomicin, vancomycin and/or metronidazole in the treatment of CDI. Reference bibliographies of identified manuscripts were also reviewed. Cost-effectiveness was evaluated according to the overall population of patients with CDI, as well as in subgroups with severe CDI or recurrent CDI, or those at higher risk of recurrence or mortality. Overall, 27 relevant EEs, conducted from the perspective of 12 different countries, were identified. Fidaxomicin was cost-effective versus vancomycin and/or metronidazole in 14 of 24 EEs (58.3%), vancomycin was cost-effective versus fidaxomicin and/or metronidazole in five of 27 EEs (18.5%) and metronidazole was cost-effective versus fidaxomicin and/or vancomycin in two of 13 EEs (15.4%). Fidaxomicin was cost-effective versus vancomycin in most of the EEs evaluating specific patient subgroups. Key cost-effectiveness drivers were cure rate, recurrence rate, time horizon, drug costs and length and cost of hospitalisation. In most EEs, fidaxomicin was demonstrated to be cost-effective versus metronidazole and vancomycin in patients with CDI. These results have relevance to clinical practice, given the high budgetary impact of managing CDI and increasing restrictions on healthcare budgets. This analysis was initiated and funded by Astellas Pharma Inc.

A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation.

PubMed

Schechner, Vered; Carmeli, Yehuda; Leshno, Moshe

2017-01-01

Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics. We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy. Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving. CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics.

Economic burden of Clostridium difficile in five hospitals of the Florence health care system in Italy.

PubMed

Poli, Anna; Di Matteo, Sergio; Bruno, Giacomo M; Fornai, Enrica; Valentino, Maria Chiara; Colombo, Giorgio L

2015-01-01

Despite the awareness about the increasing rates of Clostridium difficile infection (CDI) and the economic burden arising from its management (prolonged hospitalization, laboratory tests, visits, surgical treatment, environmental sanitation), few studies are available in Italy on the economic costs directly attributable to the CDI. The Florence health care system has designed a study with the aim of describing the costs attributable to the CDI and defines the incremental economic burden associated with the management of this complication. We conducted a retrospective study in five hospitals of the Florence health care system. The enrolled population included all patients who were hospitalized during the year 2013 with a diagnosis of CDI. Of the 187 total cases reported in 2013, 69 patients were enrolled, for whom the main cause of hospitalization was directly attributable to CDI. We enrolled 69 patients (19 males and 50 females), with a mean age of 82.16 years (minimum 46 to maximum 98). The total number of hospitalization days observed was 886 (12.8 per patient on average). The data from this study show that the mean total incremental cost for a patient with CDI was €3,270.52 per year. The hospital stay length is the most significant cost parameter, having the largest influence on the overall costs, with an impact of 87% on the total cost. The results confirm the costs for the management of CDI in five hospitals of the Florence health care system are in line with data from the international literature. The economic impact of CDI is most evident in the extension of the duration of hospitalization and emergency recurrences requiring new therapeutic options with the need to develop and implement new diagnostic and therapeutic algorithms in clinical practice.

Clinical and economic benefits of fidaxomicin compared to vancomycin for Clostridium difficile infection.

PubMed

Gallagher, Jason C; Reilly, Joseph P; Navalkele, Bhagyashri; Downham, Gemma; Haynes, Kevin; Trivedi, Manish

2015-11-01

We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P = 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Economic burden of Clostridium difficile in five hospitals of the Florence health care system in Italy

PubMed Central

Poli, Anna; Di Matteo, Sergio; Bruno, Giacomo M; Fornai, Enrica; Valentino, Maria Chiara; Colombo, Giorgio L

2015-01-01

Introduction Despite the awareness about the increasing rates of Clostridium difficile infection (CDI) and the economic burden arising from its management (prolonged hospitalization, laboratory tests, visits, surgical treatment, environmental sanitation), few studies are available in Italy on the economic costs directly attributable to the CDI. The Florence health care system has designed a study with the aim of describing the costs attributable to the CDI and defines the incremental economic burden associated with the management of this complication. Methods We conducted a retrospective study in five hospitals of the Florence health care system. The enrolled population included all patients who were hospitalized during the year 2013 with a diagnosis of CDI. Of the 187 total cases reported in 2013, 69 patients were enrolled, for whom the main cause of hospitalization was directly attributable to CDI. Results We enrolled 69 patients (19 males and 50 females), with a mean age of 82.16 years (minimum 46 to maximum 98). The total number of hospitalization days observed was 886 (12.8 per patient on average). The data from this study show that the mean total incremental cost for a patient with CDI was €3,270.52 per year. The hospital stay length is the most significant cost parameter, having the largest influence on the overall costs, with an impact of 87% on the total cost. The results confirm the costs for the management of CDI in five hospitals of the Florence health care system are in line with data from the international literature. Conclusion The economic impact of CDI is most evident in the extension of the duration of hospitalization and emergency recurrences requiring new therapeutic options with the need to develop and implement new diagnostic and therapeutic algorithms in clinical practice. PMID:26604846

A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation

PubMed Central

Carmeli, Yehuda; Leshno, Moshe

2017-01-01

Background Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics. Methods We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy. Results Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving. Conclusions CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics. PMID:28187144

Economic Evaluation of Laboratory Testing Strategies for Hospital-Associated Clostridium difficile Infection

PubMed Central

Robilotti, Elizabeth; Peterson, Lance R.; Banaei, Niaz; Dowdy, David W.

2014-01-01

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and <2 transmissions, if lateral-flow GDH diagnostic sensitivity was >93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI. PMID:24478478

European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection.

PubMed

Debast, S B; Bauer, M P; Kuijper, E J

2014-03-01

In 2009 the first European Society of Clinical Microbiology and Infection (ESCMID) treatment guidance document for Clostridium difficile infection (CDI) was published. The guideline has been applied widely in clinical practice. In this document an update and review on the comparative effectiveness of the currently available treatment modalities of CDI is given, thereby providing evidence-based recommendations on this issue. A computerized literature search was carried out to investigate randomized and non-randomized trials investigating the effect of an intervention on the clinical outcome of CDI. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The ESCMID and an international team of experts from 11 European countries supported the process. To improve clinical guidance in the treatment of CDI, recommendations are specified for various patient groups, e.g. initial non-severe disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences and treatment of CDI when oral administration is not possible. Treatment options that are reviewed include: antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and faecal or bacterial intestinal transplantation. Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised. The main antibiotics that are recommended are metronidazole, vancomycin and fidaxomicin. Faecal transplantation is strongly recommended for multiple recurrent CDI. In case of perforation of the colon and/or systemic inflammation and deteriorating clinical condition despite antibiotic therapy, total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Clostridium Difficile Infection in Acute Care Hospitals: Systematic Review and Best Practices for Prevention.

PubMed

Louh, Irene K; Greendyke, William G; Hermann, Emilia A; Davidson, Karina W; Falzon, Louise; Vawdrey, David K; Shaffer, Jonathan A; Calfee, David P; Furuya, E Yoko; Ting, Henry H

2017-04-01

OBJECTIVE Prevention of Clostridium difficile infection (CDI) in acute-care hospitals is a priority for hospitals and clinicians. We performed a qualitative systematic review to update the evidence on interventions to prevent CDI published since 2009. DESIGN We searched Ovid, MEDLINE, EMBASE, The Cochrane Library, CINAHL, the ISI Web of Knowledge, and grey literature databases from January 1, 2009 to August 1, 2015. SETTING We included studies performed in acute-care hospitals. PATIENTS OR PARTICIPANTS We included studies conducted on hospitalized patients that investigated the impact of specific interventions on CDI rates. INTERVENTIONS We used the QI-Minimum Quality Criteria Set (QI-MQCS) to assess the quality of included studies. Interventions were grouped thematically: environmental disinfection, antimicrobial stewardship, hand hygiene, chlorhexidine bathing, probiotics, bundled approaches, and others. A meta-analysis was performed when possible. RESULTS Of 3,236 articles screened, 261 met the criteria for full-text review and 46 studies were ultimately included. The average quality rating was 82% according to the QI-MQCS. The most effective interventions, resulting in a 45% to 85% reduction in CDI, included daily to twice daily disinfection of high-touch surfaces (including bed rails) and terminal cleaning of patient rooms with chlorine-based products. Bundled interventions and antimicrobial stewardship showed promise for reducing CDI rates. Chlorhexidine bathing and intensified hand-hygiene practices were not effective for reducing CDI rates. CONCLUSIONS Daily and terminal cleaning of patient rooms using chlorine-based products were most effective in reducing CDI rates in hospitals. Further studies are needed to identify the components of bundled interventions that reduce CDI rates. Infect Control Hosp Epidemiol 2017;38:476-482.

Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment.

PubMed

Lv, Zhi; Peng, Guoli; Liu, Weihua; Xu, Hufeng; Su, JianRong

2015-07-01

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model

PubMed Central

Nale, Janet Y.; Redgwell, Tamsin A.; Millard, Andrew; Clokie, Martha R. J.

2018-01-01

Clostridium difficile infection (CDI) is a major cause of infectious diarrhea. Conventional antibiotics are not universally effective for all ribotypes, and can trigger dysbiosis, resistance and recurrent infection. Thus, novel therapeutics are needed to replace and/or supplement the current antibiotics. Here, we describe the activity of an optimised 4-phage cocktail to clear cultures of a clinical ribotype 014/020 strain in fermentation vessels spiked with combined fecal slurries from four healthy volunteers. After 5 h, we observed ~6-log reductions in C. difficile abundance in the prophylaxis regimen and complete C. difficile eradication after 24 h following prophylactic or remedial regimens. Viability assays revealed that commensal enterococci, bifidobacteria, lactobacilli, total anaerobes, and enterobacteria were not affected by either regimens, but a ~2-log increase in the enterobacteria, lactobacilli, and total anaerobe abundance was seen in the phage-only-treated vessel compared to other treatments. The impact of the phage treatments on components of the microbiota was further assayed using metagenomic analysis. Together, our data supports the therapeutic application of our optimised phage cocktail to treat CDI. Also, the increase in specific commensals observed in the phage-treated control could prevent further colonisation of C. difficile, and thus provide protection from infection being able to establish. PMID:29438355

Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis.

PubMed

Negm, Ola H; Hamed, Mohamed R; Dilnot, Elizabeth M; Shone, Clifford C; Marszalowska, Izabela; Lynch, Mark; Loscher, Christine E; Edwards, Laura J; Tighe, Patrick J; Wilcox, Mark H; Monaghan, Tanya M

2015-09-01

Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis

PubMed Central

Negm, Ola H.; Hamed, Mohamed R.; Dilnot, Elizabeth M.; Shone, Clifford C.; Marszalowska, Izabela; Lynch, Mark; Loscher, Christine E.; Edwards, Laura J.; Tighe, Patrick J.; Wilcox, Mark H.

2015-01-01

Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost. PMID:26178385

An antimicrobial stewardship program's real-world experience with fidaxomicin for treatment of Clostridium difficile infection: a case series.

PubMed

Vargo, Craig A; Bauer, Karri A; Mangino, Julie E; Johnston, Jessica E W; Goff, Debra A

2014-09-01

To evaluate real-world clinical and economic outcomes in patients with Clostridium difficile infection (CDI) treated with fidaxomicin. Retrospective case series. Academic medical center. A total of 61 patients with CDI who were treated with fidaxomicin monotherapy or combination therapy from September 2011 to December 2012. Data on demographics, infection characteristics, and clinical and economic outcomes were evaluated. Clinical cure was defined as resolution of diarrhea (less than or equal to three unformed stools for at least 2 consecutive days) maintained for the duration of therapy with no further requirement for CDI therapy and was achieved in 44 (72.1%) patients. Clinical cure was significantly higher for patients receiving fidaxomicin monotherapy compared with fidaxomicin combination therapy (25/29 [86.2%] patients vs 19/32 [59.4%] patients, p=0.04). Clinical cure was similar in patients with a first or prior CDI episode (65.5% vs 78.1%, p=0.27) and in patients with severe versus nonsevere disease (68.4% vs 73.8%, p=0.66). Recurrence occurred in 6 (13.6%) of the 44 patients who achieved clinical cure. Mortality attributable to CDI was 11.5%, and 30-day readmission rate was 4.9%. Median cost accrued during CDI was $19,483/patient. Our real-world experience with fidaxomicin significantly differs from the findings of phase III clinical trials. Fidaxomicin is also associated with substantial costs. Multicenter studies are needed to determine the optimal role of fidaxomicin in the treatment of CDI. © 2014 Pharmacotherapy Publications, Inc.

Factors Associated With Health Care Utilization of Recurrent Clostridium difficile Infection in New York State.

PubMed

Mathews, Steven N; Lamm, Ryan; Yang, Jie; Park, Jihye; Tzimas, Demetrios; Buscaglia, Jonathan M; Pryor, Aurora; Talamini, Mark; Telem, Dana; Bucobo, Juan C

2018-03-21

The incidence of infection due to Clostridium difficile infection (CDI) and subsequent economic burden are substantial. The impact of changing practice patterns on demographics at risk and utilization of health care resources for recurrence of CDI remains unclear. A total of 291,163 patients hospitalized for CDI were identified from 1995 to 2014 from the New York SPARCS database. The χ test, the Welch t test, and multivariable logistic regression analysis were performed to evaluate factors related to readmission. Hospital admissions and readmissions for CDI peaked in 2008 at 20,487 and 13,795, respectively, and have since decreased (linear trend, 0.9706 and 0.9464, respectively; P<0.0001). In total, 60,077 (21%) patients required ≥2 admissions. Risk factors for readmission included: age 55 to 74, government insurance, hypertension, diabetes, anemia, hypothyroidism, chronic pulmonary disease, rheumatoid arthritis, renal failure, peripheral vascular disease, and depression (all P<0.05). Trends in surgery showed a similar peak in 2008 at 165 and have since decreased (linear trend, 0.8660; P<0.0001). A total of 1830 (0.63%) patients with CDI underwent surgery, with emergent being more common than elective (71% vs. 29%). Hospital admissions and readmissions for CDI peaked in 2008 and have since been steadily declining. These trends may be secondary to improved diagnostic capabilities and evolving antibiotic regimens. More than 1 in 5 hospitalized patients had at least 1 readmission. Numerous risk factors for these patients have been identified. Although <1% of all patients with CDI undergo surgery, these rates have also been declining.

Cost-effectiveness analysis on the use of fidaxomicin and vancomycin to treat Clostridium difficile infection in France.

PubMed

Watt, Maureen; Dinh, Aurélien; Le Monnier, Alban; Tilleul, Patrick

2017-07-01

Fidaxomicin is a macrocyclic antibiotic with proven efficacy against Clostridium difficile infection (CDI) in adults. It was licensed in France in 2012, but, due to higher acquisition costs compared with existing treatments, healthcare providers require information on its cost/benefit profile. To compare healthcare costs and health outcomes of fidaxomicin and vancomycin, as reference treatment for CDI. A Markov model was used to simulate the treatment pathway, over 1 year, of adult patients with CDI receiving fidaxomicin or vancomycin. Several patient sub-groups (severe CDI; recurrent CDI; concomitant antibiotics; cancer; renal failure; elderly) were evaluated. Cost-effectiveness was analyzed based on cure and recurrence rates derived from published randomized clinical trials comparing fidaxomicin and vancomycin, and costs calculated from the payer perspective using French hospitalization data and drug cost databases. Model outputs included costs in euros (reference year 2014) and health outcomes (recurrence; sustained cure rates). Alternative scenario and sensitivity analyses were performed using data from other clinical trials in CDI, including one conducted in real-life clinical practice in France. Drug acquisition costs were €1,692 higher in fidaxomicin-treated patients, but this was offset by the lower hospitalization costs with fidaxomicin, which were reduced by €1,722. The reduction in the cost of hospitalization was driven by the significantly lower number of recurrences in fidaxomicin-treated patients, offsetting the acquisition cost of fidaxomicin in all sub-groups except recurrent CDI and concomitant antibiotics. This study demonstrated that, despite higher acquisition costs, the lower recurrence rate with fidaxomicin resulted in cost savings or low incremental costs compared with vancomycin.

Trend, Risk Factors, and Costs of Clostridium difficile Infections in Vascular Surgery.

PubMed

Egorova, Natalia N; Siracuse, Jeffrey J; McKinsey, James F; Nowygrod, Roman

2015-01-01

Starting in December 2013, the Hospital Inpatient Quality Reporting Program included Clostridium difficile infection (CDI) rates as a new publically reported quality measure. Our goal was to review the trend, hospital variability in CDI rates, and associated risk factors and costs in vascular surgery. The rates of CDI after major vascular procedures including aortic abdominal aneurysm (AAA) repair, carotid endarterectomy or stenting, lower extremity revascularization (LER), and LE amputation were identified using Nationwide Inpatient Sample database for 2000-2011. Risk factors associated with CDI were analyzed with hierarchical multivariate logistic regression. Extra costs, length of stay (LOS), and mortality were assessed for propensity-matched hospitalizations with and without CDI. During the study period, the rates of CDI after vascular procedures had increased by 74% from 0.6 in 2000 to 1.05% in 2011, whereas the case fatality rate was stable at 9-11%. In 2011, the highest rates were after ruptured aortic abdominal aneurysm (rAAA) repair (3.3%), followed by lower extremity amputations (2.3%) and elective open AAA (1.3%). The rates of CDI increased after all vascular procedures during the 12 years. The highest increase was after endovascular LER (151.8%) and open rAAA repair (135.7%). In 2011, patients who had experienced CDI had median LOS of 15 days (interquartile range, 9-25 days) compared with 8.3 days for matched patients without CDI, in-hospital mortality 9.1% (compared with 5.0%), and $13,471 extra cost per hospitalization. The estimated cost associated with CDI in vascular surgery in the United States was ∼$98 million in 2011. Hospital rates of CDI varied from 0 to 50% with 3.5% of hospitals having infection rates ≥5%. Factors associated with CDI included multiple chronic conditions, female gender, surgery type, emergent and weekend hospitalizations, hospital transfers, and urban locations. Despite potential reduction of infection rates as evidenced by the experience of hospitals with effective interventions, CDI is increasing among vascular surgery patients. It is associated with prolonged LOS, increased mortality, and higher costs. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease.

PubMed

Khanna, Sahil; Vazquez-Baeza, Yoshiki; González, Antonio; Weiss, Sophie; Schmidt, Bradley; Muñiz-Pedrogo, David A; Rainey, John F; Kammer, Patricia; Nelson, Heidi; Sadowsky, Michael; Khoruts, Alexander; Farrugia, Stefan L; Knight, Rob; Pardi, Darrell S; Kashyap, Purna C

2017-05-15

Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD. There was a significant change in gut microbial composition towards the donor microbiota and an overall increase in microbial diversity consistent with previous studies after FMT. FMT was successful in treating CDI using a diverse set of donors, and varying degrees of donor stool engraftment suggesting that donor type and degree of engraftment are not drivers of a successful FMT treatment of CDI. However, patients with underlying IBD experienced an increased number of CDI relapses (during a 24-month follow-up) and a decreased growth of new taxa, as compared to the subjects without IBD. Moreover, the need for IBD therapy did not change following FMT. These results underscore the importance of the existing gut microbial landscape as a decisive factor to successfully treat CDI and potentially for improvement of the underlying pathophysiology in IBD. FMT leads to a significant change in microbial diversity in patients with recurrent CDI and complete resolution of symptoms. Stool donor type (related or unrelated) and degree of engraftment are not the key for successful treatment of CDI by FMT. However, CDI patients with IBD have higher proportion of the original community after FMT and lack of improvement of their IBD symptoms and increased episodes of CDI on long-term follow-up.

National epidemiology of initial and recurrent Clostridium difficile infection in the Veterans Health Administration from 2003 to 2014.

PubMed

Reveles, Kelly R; Lawson, Kenneth A; Mortensen, Eric M; Pugh, Mary Jo V; Koeller, Jim M; Argamany, Jacqueline R; Frei, Christopher R

2017-01-01

Prior studies demonstrated marked increases in Clostridium difficile infection (CDI) in the United States (U.S.) in recent years. The objective of this study was to describe the epidemiology of initial and recurrent CDI in a national Veterans Health Administration (VHA) cohort over a 12-year period. This was a retrospective cohort study of all adult VHA beneficiaries with CDI (ICD-9-CM code 008.45) plus a positive CDI stool test between October 1, 2002 and September 30, 2014. Data were obtained from the VA Informatics and Computing Infrastructure. Recurrence was defined as a second ICD-9-CM code plus a new course of CDI therapy following a minimum three-day gap after the initial therapy was completed. CDI incidence and outcomes were presented descriptively and longitudinally. Overall, 30,326 patients met study inclusion criteria. CDI incidence increased from FY 2003 (1.6 per 10,000) to FY 2013 (5.1 per 10,000). Thereafter, CDI incidence decreased through FY 2014 (4.6 per 10,000). A total of 5,011 patients (17%) experienced a first recurrence and, of those, 1,713 (34%) experienced a second recurrence. Recurrence incidence increased 10-fold over the study period, from (0.1 per 10,000) in FY 2003, to (1.0 per 10,000) in FY 2014. Overall, 30-day mortality and median hospital length of stay (LOS) decreased among initial episodes over the study period. Mortality was higher for initial episodes (21%) compared to first recurrences (11%) and second recurrences (7%). Median hospital LOS was longer for first episodes (13 days) compared to first (9 days) and second recurrences (8 days). Initial and recurrent CDI episodes increased among veterans over a 12-year period. Outcomes, such as mortality and hospital LOS improved in recent years; both of these outcomes are worse for initial CDI episodes than recurrent episodes.

Prevalence, genetic relatedness and antibiotic resistance of hospital-acquired clostridium difficile PCR ribotype 018 strains.

PubMed

Seo, Mi-Ran; Kim, Jieun; Lee, Yangsoon; Lim, Dong-Gyun; Pai, Hyunjoo

2018-05-01

Clostridium difficile infection (CDI) is a major healthcare-associated infection. The aim of this study was to investigate the genetic relatedness of the endemic C. difficile PCR ribotype 018 strains in an institution and changes to their characteristics during a five-year period. A total of 207 isolates from inpatients at Hanyang University Hospital from 2009 to 2013 were analysed using multilocus variable-number tandem-repeat analysis (MLVA). Minimum inhibitory concentrations (MICs) of several antibiotics were determined. In total, 204 (98.6%) were genetically related, with a summed tandem-repeat distance (STRD) ≤ 10. Minimum-spanning-tree analysis identified 78 MLVA types, categorized into six clonal complexes (CCs). The largest cluster, CC-I, included 51 MLVA types from 148 isolates (71.5%) and the second largest cluster, CC-II, included 10 MLVA types from 36 isolates (17.4%). Resistance rates for antibiotics were: clindamycin (CLI), 97.6%; moxifloxacin (MXF), 98.6%; vancomycin (VAN), 1.4%; and rifaximin (RFX), 8.2%. All isolates were susceptible to piperacillin/tazobactam (TZP) and metronidazole (MTZ). Comparing the MICs of antibiotics for the isolates each year from 2009 to 2013, MICs of antibiotics that promote CDI, such as CLI, MXF, TZP and RFX, increased over the five-year period (P-value by Kruskal-Wallis test: < 0.0001, <0.0001, <0.0001, and <0.0001 respectively); however, MICs of VAN or MTZ, antibiotics for treatment of CDI, did not increase or decreased over the same time period (P-value by Kruskal-Wallis test: 0.166, <0.0001). C. difficile RT018 isolates in a tertiary hospital over a five-year period presented a close clonal relationship. MICs of antibiotics promoting CDI increased with this clonal expansion. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

PubMed

Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

2016-10-01

Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Infection prevention and control of Clostridium difficile: a global review of guidelines, strategies, and recommendations.

PubMed

Balsells, Evelyn; Filipescu, Teodora; Kyaw, Moe H; Wiuff, Camilla; Campbell, Harry; Nair, Harish

2016-12-01

Clostridium difficile is the leading cause of health care-associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance. We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI-targeted IPC recommendations and describe the assessment of evidence in available guidelines. We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long-term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported "strong" recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality. Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations.

The Spore Coat Protein CotE Facilitates Host Colonization by Clostridium difficile

PubMed Central

Hong, Huynh A; Ferreira, William T; Hosseini, Siamand; Anwar, Saba; Hitri, Krisztina; Wilkinson, Anthony J; Vahjen, Wilfried; Zentek, Jürgen; Soloviev, Mikhail; Cutting, Simon M

2017-01-01

Abstract Clostridium difficile infection (CDI) is an important hospital-acquired infection resulting from the germination of spores in the intestine as a consequence of antibiotic-mediated dysbiosis of the gut microbiota. Key to this is CotE, a protein displayed on the spore surface and carrying 2 functional elements, an N-terminal peroxiredoxin and a C-terminal chitinase domain. Using isogenic mutants, we show in vitro and ex vivo that CotE enables binding of spores to mucus by direct interaction with mucin and contributes to its degradation. In animal models of CDI, we show that when CotE is absent, both colonization and virulence were markedly reduced. We demonstrate here that the attachment of spores to the intestine is essential in the development of CDI. Spores are usually regarded as biochemically dormant, but our findings demonstrate that rather than being simply agents of transmission and dissemination, spores directly contribute to the establishment and promotion of disease. PMID:28968845

Outcomes in children with Clostridium difficile infection: results from a nationwide survey.

PubMed

Gupta, Arjun; Pardi, Darrell S; Baddour, Larry M; Khanna, Sahil

2016-11-01

Hospital- and population-based studies demonstrate an increasing incidence of Clostridium difficile infection (CDI) in adults and children; although pediatric CDI outcomes are incompletely understood. We analysed United States National Hospital Discharge Survey (NHDS) data to study CDI in hospitalized children. NHDS data for 2005-2009 (demographics, diagnoses and discharge status) were obtained; cases and comorbidities were identified using ICD-9 codes. Weighted univariate and multivariate analyses were performed to ascertain incidence of CDI; associations between CDI and outcomes [length of stay (LOS), colectomy, all-cause in-hospital mortality and discharge to a care facility (DTCF)]. Of an estimated 13.8 million pediatric inpatients; 46 176 had CDI; median age was 3 years; overall incidence was 33.5/10 000 hospitalizations. The annual frequency of CDI did not vary from 2005 to 2009 (0.24-0.43%; P = 0.64). On univariate analyses, children with CDI had a longer median LOS (6 vs 2 days), higher rates of colectomy [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.7-2.4], mortality (OR 2.5; 95% CI 2.3-2.7), and DTCF (OR 1.6; 95% CI 1.6-1.7) (all P < 0.0001). After adjusting for age, sex and comorbidities, CDI was an independent and the strongest predictor of increased LOS (adjusted mean difference, 6.4 days; 95% CI 5.4-7.4), higher rates of colectomy (OR 2.1; 95% CI 1.8-2.5), mortality (OR 2.3; 95% CI 2.2-2.5), and DTCF (OR 1.7; 95% CI 1.6-1.8) (all P < 0.0001). On excluding infants from the analysis, children with CDI had higher rates of mortality, DTCF and longer LOS than children without CDI. Despite increased awareness and advancements in management, CDI remains a significant problem and is associated with increased LOS, colectomy, in-hospital mortality and DTCF in hospitalized children. © The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University.

Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe.

PubMed

Kurti, Zsuzsanna; Lovasz, Barbara D; Mandel, Michael D; Csima, Zoltan; Golovics, Petra A; Csako, Bence D; Mohas, Anna; Gönczi, Lorant; Gecse, Krisztina B; Kiss, Lajos S; Szathmari, Miklos; Lakatos, Peter L

2015-06-07

To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI). A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed. Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ. CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI.

Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe

PubMed Central

Kurti, Zsuzsanna; Lovasz, Barbara D; Mandel, Michael D; Csima, Zoltan; Golovics, Petra A; Csako, Bence D; Mohas, Anna; Gönczi, Lorant; Gecse, Krisztina B; Kiss, Lajos S; Szathmari, Miklos; Lakatos, Peter L

2015-01-01

AIM: To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI). METHODS: A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed. RESULTS: Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ. CONCLUSION: CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI. PMID:26074711

Fidaxomicin in Clostridium difficile infection: latest evidence and clinical guidance

PubMed Central

2014-01-01

The incidence of Clostridium difficile infection (CDI) has risen 400% in the last decade. It currently ranks as the third most common nosocomial infection. CDI has now crossed over as a community-acquired infection. The major failing of current therapeutic options for the management of CDI is recurrence of disease after the completion of treatment. Fidaxomicin has been proven to be superior to vancomycin in successful sustained clinical response to therapy. Improved outcomes may be due to reduced collateral damage to the gut microflora by fidaxomicin, bactericidal activity, inhibition of Clostridial toxin formation and inhibition of new sporulation. This superiority is maintained in groups previously reported as being at high risk for CDI recurrence including those: with relapsed infection after a single treatment course; on concomitant antibiotic therapy; aged >65 years; with cancer; and with chronic renal insufficiency. Because the acquisition cost of fidaxomicin far exceeds that of metronidazole or vancomycin, in order to rationally utilize this agent, it should be targeted to those populations who are at high risk for relapse and in whom the drug has demonstrated superiority. In this manuscript is reviewed the changing epidemiology of CDI, current treatment options for this infection, proposed benefits of fidaxomicin over currently available antimicrobial options, available analysis of cost effectiveness of the drug, and is given recommendations for judicious use of the drug based upon the available published literature. PMID:24587892

Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach

PubMed Central

Fischer, Monika; Phelps, Emmalee; Rogers, Nicholas; Sagi, Sashidhar; Bohm, Matthew; Xu, Huiping; Kassam, Zain

2017-01-01

ABSTRACT Severe and severe-complicated Clostridium difficile infection (CDI) is associated with high morbidity and mortality. Colectomy is standard of care; however, post-surgical mortality rates approach 50%. Case reports suggest fecal microbiota transplant (FMT) is a promising treatment of severe and severe-complicated disease but there is a paucity of data. Here, we present a single center experience with a novel sequential FMT protocol for patients refractory to maximal medical therapy. This approach consists of at least one FMT delivered via colonoscopy with criteria for repeat FMT and continued vancomycin therapy based on clinical response and pseudomembranes. Our cohort included 57 consecutive inpatients diagnosed with severe or severe-complicated CDI and treated with FMT. Overall, 91% (52/57) experienced clinical cure at 1 month with a 100% cure rate among severe CDI (n = 19) patients and an 87% cure rate for severe-complicated CDI (n = 33) patients. For the cohort, the survival rate was 94.7% at 1 month and 78.6% at 3 months. There were no serious adverse events related to FMT including no procedure-related complications or perforation. There was no difference in outcome between fresh or frozen fecal material. Sequential FMT for inpatients with severe or severe-complicated CDI is promising and may be preferred over colectomy in certain patients. PMID:28001467

Fidaxomicin in Clostridium difficile infection: latest evidence and clinical guidance.

PubMed

Mullane, Kathleen

2014-03-01

The incidence of Clostridium difficile infection (CDI) has risen 400% in the last decade. It currently ranks as the third most common nosocomial infection. CDI has now crossed over as a community-acquired infection. The major failing of current therapeutic options for the management of CDI is recurrence of disease after the completion of treatment. Fidaxomicin has been proven to be superior to vancomycin in successful sustained clinical response to therapy. Improved outcomes may be due to reduced collateral damage to the gut microflora by fidaxomicin, bactericidal activity, inhibition of Clostridial toxin formation and inhibition of new sporulation. This superiority is maintained in groups previously reported as being at high risk for CDI recurrence including those: with relapsed infection after a single treatment course; on concomitant antibiotic therapy; aged >65 years; with cancer; and with chronic renal insufficiency. Because the acquisition cost of fidaxomicin far exceeds that of metronidazole or vancomycin, in order to rationally utilize this agent, it should be targeted to those populations who are at high risk for relapse and in whom the drug has demonstrated superiority. In this manuscript is reviewed the changing epidemiology of CDI, current treatment options for this infection, proposed benefits of fidaxomicin over currently available antimicrobial options, available analysis of cost effectiveness of the drug, and is given recommendations for judicious use of the drug based upon the available published literature.

Dynamics and establishment of Clostridium difficile infection in the murine gastrointestinal tract.

PubMed

Koenigsknecht, Mark J; Theriot, Casey M; Bergin, Ingrid L; Schumacher, Cassie A; Schloss, Patrick D; Young, Vincent B

2015-03-01

Clostridium difficile infection (CDI) following antibiotic therapy is a major public health threat. While antibiotic disruption of the indigenous microbiota underlies the majority of cases of CDI, the early dynamics of infection in the disturbed intestinal ecosystem are poorly characterized. This study defines the dynamics of infection with C. difficile strain VPI 10463 throughout the gastrointestinal (GI) tract using a murine model of infection. After inducing susceptibility to C. difficile colonization via antibiotic administration, we followed the dynamics of spore germination, colonization, sporulation, toxin activity, and disease progression throughout the GI tract. C. difficile spores were able to germinate within 6 h postchallenge, resulting in the establishment of vegetative bacteria in the distal GI tract. Spores and cytotoxin activity were detected by 24 h postchallenge, and histopathologic colitis developed by 30 h. Within 36 h, all infected mice succumbed to infection. We correlated the establishment of infection with changes in the microbiota and bile acid profile of the small and large intestines. Antibiotic administration resulted in significant changes to the microbiota in the small and large intestines, as well as a significant shift in the abundance of primary and secondary bile acids. Ex vivo analysis suggested the small intestine as the site of spore germination. This study provides an integrated understanding of the timing and location of the events surrounding C. difficile colonization and identifies potential targets for the development of new therapeutic strategies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile Infection: A Systematic Review.

PubMed

Le, Phuc; Nghiem, Van T; Mullen, Patricia Dolan; Deshpande, Abhishek

2018-04-01

BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider. METHODS We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs. RESULTS We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies. CONCLUSIONS The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment. Infect Control Hosp Epidemiol 2018;39:412-424.

Clostridium difficile Infection in Older Adults: Systematic Review of Efforts to Reduce Occurrence and Improve Outcomes.

PubMed

Marshall, Leisa L; Peasah, Samuel; Stevens, Gregg A

2017-01-01

Provide a systematic review of the primary literature on efforts to reduce Clostridium difficile infection (CDI) occurrence and improve outcomes in older adults. PubMed and CINAHL databases were searched for research studies using search terms CDI, CDI prevention, reduction, control, management, geriatric, elderly, adults 65 years of age and older. The MeSH categories Aged and Aged, 80 and older, were used. A second search of PubMed, CINAHL, National Guideline Clearinghouse, and TRIP databases was conducted for primary, secondary, and tertiary literature for CDI epidemiology, burden, and management in adults of all ages, and prevention and management guidelines. Of the 2,263 articles located, 105 were selected for full review: 55 primary and 50 secondary, tertiary. Primary literature selected for full review included studies of interventions to prevent, reduce occurrence, control, manage, or improve outcomes in adults 65 years of age and older. Patient settings included the community, assisted living, nursing facility, subacute care, or hospital. The main outcome measures for research studies were whether the studied intervention prevented, reduced occurrence, controlled, managed, or improved outcomes. Studies were conducted in acute or long-term hospitals, with a few in nursing facilities. Interventions that prevented or reduced CDI included antibiotic policy changes, education, procedure changes, infection control, and multi-intervention approaches. There were few management studies for adults 65 years of age and older or for all adults with results stratified by age. Treatments studied included efficacy of fidaxomicin, metronidazole, vancomycin, and fecal microbiota transplant. Though clinical outcomes were slightly less robust in those 65 years of age and older, age was not an independent predictor of success or failure. The current prevention and management guidelines for adults of all ages, as well as special considerations in skilled nursing facilities, extracted from the secondary/tertiary literature selected, are summarized. There are a limited number of studies designed for older adults. Our findings suggest that guideline recommendations for adults are adequate and appropriate for older adults. Exposure to antibiotics and Clostridium difficile remain the two major risk factors for CDI, reinforcing the importance of antibiotic stewardship and infection control.

Economic assessment of fidaxomicin for the treatment of Clostridium difficile infection (CDI) in special populations (patients with cancer, concomitant antibiotic treatment or renal impairment) in Spain.

PubMed

Rubio-Terrés, C; Cobo Reinoso, J; Grau Cerrato, S; Mensa Pueyo, J; Salavert Lletí, M; Toledo, A; Anguita, P; Rubio-Rodríguez, D; Watt, M; Gani, R

2015-11-01

The objective of this paper was to assess the cost-utility of fidaxomicin versus vancomycin in the treatment of Clostridium difficile infection (CDI) in three specific CDI patient subgroups: those with cancer, treated with concomitant antibiotic therapy or with renal impairment. A Markov model with six health states was developed to assess the cost-utility of fidaxomicin versus vancomycin in the patient subgroups over a period of 1 year from initial infection. Cost and outcome data used to parameterise the model were taken from Spanish sources and published literature. The costs were from the Spanish hospital perspective, in Euros (€) and for 2013. For CDI patients with cancer, fidaxomicin was dominant versus vancomycin [gain of 0.016 quality-adjusted life-years (QALYs) and savings of €2,397 per patient]. At a cost-effectiveness threshold of €30,000 per QALY gained, the probability that fidaxomicin was cost-effective was 96 %. For CDI patients treated with concomitant antibiotic therapy, fidaxomicin was the dominant treatment versus vancomycin (gain of 0.014 QALYs and savings of €1,452 per patient), with a probability that fidaxomicin was cost-effective of 94 %. For CDI patients with renal impairment, fidaxomicin was also dominant versus vancomycin (gain of 0.013 QALYs and savings of €1,432 per patient), with a probability that fidaxomicin was cost-effective of 96 %. Over a 1-year time horizon, when fidaxomicin is compared to vancomycin in CDI patients with cancer, treated with concomitant antibiotic therapy or with renal impairment, the use of fidaxomicin would be expected to result in increased QALYs for patients and reduced overall costs.

Risks factors and outcomes of Clostridium difficile infection in patients with cancer: a matched case-control study.

PubMed

Hebbard, Andrew I T; Slavin, Monica A; Reed, Caroline; Trubiano, Jason A; Teh, Benjamin W; Haeusler, Gabrielle M; Thursky, Karin A; Worth, Leon J

2017-06-01

Clostridium difficile infection (CDI) is the leading cause of diarrhoea in hospitalised patients. Cancer populations are at high-risk for infection, but comprehensive evaluation in the current era of cancer care has not been performed. The objective of this study was to describe characteristics, risk factors, and outcomes of CDI in cancer patients. Fifty consecutive patients with CDI at a large Australian cancer centre (2013-2015) were identified from the hospital pathology database. Each case was matched by ward and hospital admission date to three controls without toxigenic CDI. Treatment and outcomes of infection were evaluated and potential risk factors were analysed using conditional logistic regression. Patients with CDI had a mean age of 59.7 years and 74% had an underlying solid tumour. Healthcare-associated infection comprised 80% of cases. Recurrence occurred in 10, and 12% of cases were admitted to ICU within 30 days. Severe or severe-complicated infection was observed in 32%. Independent risk factors for infection included chemotherapy (odds ratio (OR) 3.82, 95% CI 1.67-8.75; p = 0.002), gastro-intestinal/abdominal surgery (OR 4.64, 95% CI 1.20-17.91; p = 0.03), proton pump inhibitor (PPI) therapy (OR 2.47, 95% CI 1.05-5.80; p = 0.04), and days of antibiotic therapy (OR 1.04, 95% CI 1.01-1.08; p = 0.02). Severe or complicated infections are frequent in patients with cancer who develop CDI. Receipt of chemotherapy, gastro-intestinal/abdominal surgery, PPI therapy, and antibiotic exposure contribute to infection risk. More effective CDI therapy for cancer patients is required and dedicated antibiotic stewardship programs in high-risk cancer populations are needed to ameliorate infection risk.

Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection.

PubMed

Brown, Kevin A; Khanafer, Nagham; Daneman, Nick; Fisman, David N

2013-05-01

The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

Risk of Clostridium difficile Infection in Patients With Celiac Disease: A Population-Based Study.

PubMed

Lebwohl, Benjamin; Nobel, Yael R; Green, Peter H R; Blaser, Martin J; Ludvigsson, Jonas F

2017-12-01

Patients with celiac disease are at increased risk for infections such as tuberculosis, influenza, and pneumococcal pneumonia. However, little is known about the incidence of Clostridium difficile infection (CDI) in patients with celiac disease. We identified patients with celiac disease based on intestinal biopsies submitted to all pathology departments in Sweden over a 39-year period (from July 1969 through February 2008). We compared risk of CDI (based on stratified Cox proportional hazards models) among patients with celiac disease vs. without celiac disease (controls) matched by age, sex, and calendar period. We identified 28,339 patients with celiac disease and 141,588 controls; neither group had a history of CDI. The incidence of CDI was 56/100,000 person-years among patients with celiac disease and 26/100,000 person-years among controls, yielding an overall hazard ratio (HR) of 2.01 (95% confidence interval (CI), 1.64-2.47; P<0.0001). The risk of CDI was highest in the first 12 months after diagnosis of celiac disease (HR, 5.20; 95% CI, 2.81-9.62; P<0.0001), but remained high, compared to that of controls, 1-5 years after diagnosis (HR, 1.85; 95% CI, 1.22-2.81; P=0.004). Among 493 patients with CDI, antibiotic data were available for 251; there were no significant differences in prior exposures to antibiotics between patients with celiac disease and controls. In a large population-based cohort study, patients with celiac disease had significantly higher incidence of CDI than controls. This finding is consistent with prior findings of higher rates of other infections in patients with celiac disease, and suggests the possibility of altered gut immunity and/or microbial composition in patients with celiac disease.

Impact of end stage kidney disease on costs and outcomes of Clostridium difficile infection.

PubMed

Goyal, Abhinav; Chatterjee, Kshitij; Yadlapati, Sujani; Rangaswami, Janani

2017-09-01

To assess the impact of end stage kidney disease (ESKD) on the outcomes of Clostridium difficile infection (CDI), including complications of infection, length of hospital stay, overall mortality, and healthcare burden. The National Inpatient Sample (NIS) database created by the Agency of Healthcare Research and Quality (AHRQ) was used, covering the years 2009 through 2013. Manufacturer-provided sampling weights were used to produce national estimates. All-cause unadjusted in-hospital mortality was significantly higher for patients with CDI and ESKD than for patients without ESKD (11.6% vs. 7.7%, p<0.001). The in-hospital mortality remained higher even after adjusting for age, sex, race, and Charlson index group using multivariate logistic regression (odds ratio 1.47, confidence interval 1.41-1.53). The median length of stay was found to be longer by 2days in the ESKD group (9 vs. 7 days, p<0.001). The average cost of hospitalization for patients with CDI and ESKD was also significantly higher compared to the non-ESKD group (USD $35 588 vs. $23 505, in terms of the 2013 value of the USD, p<0.001). The presence of end stage kidney disease in hospitalized patients with Clostridium difficile infection is associated with higher mortality, a longer length of stay, and a higher cost of hospitalization. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

[Epidemiology of Clostridium difficile infection in Spain].

PubMed

Asensio, Angel; Monge, Diana

2012-06-01

There has been increasing interest in Clostridium difficile infection (CDI) due its association with healthcare and its impact on morbidity and mortality in the elderly. During the last few years there has been a growing increase in the number of published studies on the incidence, changes on the clinical presentation and on the epidemiology, with the description of new risk factors. The frequency of CDI in Spain is not sufficiently characterised. The available data indicates that incidence is within the range of that of surrounding countries but increasing. Furthermore, the high and growing use of broad spectrum antibiotics, both in our hospitals and in the community setting, are factors that favour the increase of the disease. The hyper-virulent ribotype 027 has not spread in our hospitals. We need to know with enhanced validity and accuracy the incidence of CDI, both community and healthcare-associated, the information on outbreaks, the incidence on certain population groups, the characterisation of circulating ribotypes and the impact of the disease in terms of mortality and health costs. We need to implement programs for the improvement of antibiotic therapy in the hospital, as well as in the community. Furthermore, the knowledge and the performance of standard precautions need to be improved, particularly hand hygiene, and the specific measures to limit the transmission of C. difficile among the healthcare institutions. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Oral Teicoplanin as an Alternative First-Line Regimen in Clostridium difficile Infection in Elderly Patients: A Case Series.

PubMed

Davido, Benjamin; Leplay, Céline; Bouchand, Frédérique; Dinh, Aurélien; Villart, Maryvonne; Le Quintrec, Jean-Laurent; Teillet, Laurent; Salomon, Jérôme; Michelon, Hugues

2017-07-01

Elderly patients are more susceptible to Clostridium difficile infections (CDIs). Despite existing guidelines, there is no specific treatment for CDI in geriatrics. Vancomycin is commonly used in the treatment of CDI. Teicoplanin is an alternative glycopeptide which recently received marketing authorization approval for CDI in Europe. Evaluate the potential interest of oral teicoplanin and assess whether such treatment could potentially become an alternative treatment in mild to severe CDIs in elderly patients. A prospective monocentric study was conducted over 10 months (from December 2015 to October 2016) in a geriatric unit (Sainte Périne, AP-HP, Paris, France). According to the remote infectious disease specialist, some hospitalized patients suffering from CDI and aged over 65 years received oral teicoplanin 200 mg twice a day (highest dose recommended). The clinical response to teicoplanin and relapses after treatment were evaluated. Patients were monitored up to 90 days after teicoplanin administration, and analyzed in non-responder imputation analysis. Eleven patients received teicoplanin among 19 CDIs during the study time period. In non-responder imputation analysis, 90.9% (n = 10) successfully responded to oral teicoplanin. The rate of relapse observed after a 90-day follow-up was 36.4%. Patients reported no drug-related adverse effects. Oral teicoplanin is a glycopeptide that could be proposed as an alternative to other recommended drugs for CDI. In our case series, teicoplanin seems to be an effective therapy as a first-line regimen for CDI in geriatrics. Such treatment has good acceptability in geriatrics, considering it can be taken orally twice a day.

Harnessing the glucosyltransferase activities of Clostridium difficile for functional studies of toxins A and B.

PubMed

Darkoh, Charles; Kaplan, Heidi B; Dupont, Herbert L

2011-08-01

The incidence of Clostridium difficile infection (CDI) has been increasing within the last decade. Pathogenic strains of C. difficile produce toxin A and/or toxin B, which are important virulence factors in the pathogenesis of this bacterium. Current methods for diagnosing CDI are mostly qualitative tests that detect either the bacterium or the toxins. We have developed an assay (Cdifftox activity assay) to detect C. difficile toxin A and B activities that is quantitative and cost-efficient and utilizes a substrate that is stereochemically similar to the native substrate of the toxins (UDP-glucose). To characterize toxin activity, toxins A and B were purified from culture supernatants by ammonium sulfate precipitation and chromatography through DEAE-Sepharose and gel filtration columns. The activities of the final fractions were quantitated using the Cdifftox activity assay and compared to the results of a toxin A- and B-specific enzyme-linked immunosorbent assay (ELISA). The affinity for the substrate was >4-fold higher for toxin B than for toxin A. Moreover, the rate of cleavage of the substrate was 4.3-fold higher for toxin B than for toxin A. The optimum temperature for both toxins ranged from 35 to 40°C at pH 8. Culture supernatants from clinical isolates obtained from the stools of patients suspected to be suffering from CDI were tested using the Cdifftox activity assay, and the results were compared to those of ELISA and PCR amplification of the toxin genes. Our results demonstrate that this new assay is comparable to the current commercial ELISA for detecting the toxins in the samples tested and has the added advantage of quantitating toxin activity.

Clostridium difficile Testing in the Clinical Laboratory by Use of Multiple Testing Algorithms ▿

PubMed Central

Novak-Weekley, Susan M.; Marlowe, Elizabeth M.; Miller, John M.; Cumpio, Joven; Nomura, Jim H.; Vance, Paula H.; Weissfeld, Alice

2010-01-01

The incidence of Clostridium difficile infection (CDI) has risen almost 3-fold in the United States over the past decade, emphasizing the need for rapid and accurate tests for CDI. The Cepheid Xpert C. difficile assay is an integrated, closed, nucleic acid amplification system that automates sample preparation and real-time PCR detection of the toxin B gene (tcdB). A total of 432 stool specimens from symptomatic patients were tested by a glutamate dehydrogenase (GDH) assay, a toxin A and B enzyme immunoassay (EIA), the Xpert C. difficile assay, and a cell culture cytotoxicity neutralization assay (CCCN). The results of these methods, used individually and in combination, were compared to those of toxigenic culture. Results for the Xpert C. difficile assay alone showed a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 94.4, 96.3, 84.0, and 98.8%, while the EIA alone gave corresponding values of 58.3, 94.7, 68.9, and 91.9%, respectively. An algorithm using the GDH assay and the EIA (plus the CCCN if the EIA was negative) showed corresponding values of 83.1, 96.7, 83.1, and 96.1%. The Xpert C. difficile assay was statistically superior to the EIA (P, <0.001 by Fisher's exact test) and to the GDH-EIA-CCCN algorithm (P, 0.0363). Combining the GDH and Xpert C. difficile assays lowered both the sensitivity and the NPV of the Xpert assay. The GDH-EIA-CCCN procedure required, on average, 2 days to complete testing on GDH-positive results, while testing by the Xpert C. difficile assay was completed, on average, in less than 1 h. Xpert C. difficile testing yielded the highest sensitivity and NPV, in the least amount of time, of the individual- and multiple-test algorithms evaluated in this study. PMID:20071552

Impact of Oral Fidaxomicin Administration on the Intestinal Microbiota and Susceptibility to Clostridium difficile Colonization in Mice.

PubMed

Ajami, N J; Cope, J L; Wong, M C; Petrosino, J F; Chesnel, L

2018-05-01

Clostridium difficile infection (CDI), a common cause of hospital-acquired infections, typically occurs after disruption of the normal gut microbiome by broad-spectrum antibiotics. Fidaxomicin is a narrow-spectrum antibiotic that demonstrates a reduced impact on the normal gut microbiota and is approved for the treatment of CDI. To further explore the benefits of this property, we used a murine model to examine the effects of fidaxomicin versus vancomycin on gut microbiota and susceptibility to C. difficile colonization while tracking microbiota recovery over time. Mice were exposed to fidaxomicin or vancomycin by oral gavage for 3 days and subsequently challenged with C. difficile spores at predetermined time points up to 21 days postexposure to antibiotics. Fecal samples were subsequently collected for analysis. Twenty-four hours postchallenge, mice were euthanized and the colon contents harvested. The microbiota was characterized using 16S rRNA gene sequencing. All fidaxomicin-exposed mice (except for one at day 8) were resistant to C. difficile colonization. However, 9 of 15 vancomycin-exposed mice were susceptible to C. difficile colonization until day 12. All vancomycin-exposed mice recovered colonization resistance by day 16. Bacterial diversity was similar prior to antibiotic exposure in both arms and decreased substantially after exposure. A shift in taxonomic structure and composition occurred after both exposures; however, the shift was greater in vancomycin-exposed than in fidaxomicin-exposed mice. In summary, compared with vancomycin, fidaxomicin exposure had less impact on microbiota composition, promoted faster microbial recovery, and had less impact on the loss of C. difficile colonization resistance. Copyright © 2018 American Society for Microbiology.

The Phosphotransfer Protein CD1492 Represses Sporulation Initiation in Clostridium difficile.

PubMed

Childress, Kevin O; Edwards, Adrianne N; Nawrocki, Kathryn L; Anderson, Sarah E; Woods, Emily C; McBride, Shonna M

2016-12-01

The formation of spores is critical for the survival of Clostridium difficile outside the host gastrointestinal tract. Persistence of C. difficile spores greatly contributes to the spread of C. difficile infection (CDI), and the resistance of spores to antimicrobials facilitates the relapse of infection. Despite the importance of sporulation to C. difficile pathogenesis, the molecular mechanisms controlling spore formation are not well understood. The initiation of sporulation is known to be regulated through activation of the conserved transcription factor Spo0A. Multiple regulators influence Spo0A activation in other species; however, many of these factors are not conserved in C. difficile and few novel factors have been identified. Here, we investigated the function of a protein, CD1492, that is annotated as a kinase and was originally proposed to promote sporulation by directly phosphorylating Spo0A. We found that deletion of CD1492 resulted in increased sporulation, indicating that CD1492 is a negative regulator of sporulation. Accordingly, we observed increased transcription of Spo0A-dependent genes in the CD1492 mutant. Deletion of CD1492 also resulted in decreased toxin production in vitro and in decreased virulence in the hamster model of CDI. Further, the CD1492 mutant demonstrated effects on gene expression that are not associated with Spo0A activation, including lower sigD and rstA transcription, suggesting that this protein interacts with factors other than Spo0A. Altogether, the data indicate that CD1492 negatively affects sporulation and positively influences motility and virulence. These results provide further evidence that C. difficile sporulation is regulated differently from that of other endospore-forming species. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Phosphotransfer Protein CD1492 Represses Sporulation Initiation in Clostridium difficile

PubMed Central

Childress, Kevin O.; Edwards, Adrianne N.; Nawrocki, Kathryn L.; Anderson, Sarah E.; Woods, Emily C.

2016-01-01

The formation of spores is critical for the survival of Clostridium difficile outside the host gastrointestinal tract. Persistence of C. difficile spores greatly contributes to the spread of C. difficile infection (CDI), and the resistance of spores to antimicrobials facilitates the relapse of infection. Despite the importance of sporulation to C. difficile pathogenesis, the molecular mechanisms controlling spore formation are not well understood. The initiation of sporulation is known to be regulated through activation of the conserved transcription factor Spo0A. Multiple regulators influence Spo0A activation in other species; however, many of these factors are not conserved in C. difficile and few novel factors have been identified. Here, we investigated the function of a protein, CD1492, that is annotated as a kinase and was originally proposed to promote sporulation by directly phosphorylating Spo0A. We found that deletion of CD1492 resulted in increased sporulation, indicating that CD1492 is a negative regulator of sporulation. Accordingly, we observed increased transcription of Spo0A-dependent genes in the CD1492 mutant. Deletion of CD1492 also resulted in decreased toxin production in vitro and in decreased virulence in the hamster model of CDI. Further, the CD1492 mutant demonstrated effects on gene expression that are not associated with Spo0A activation, including lower sigD and rstA transcription, suggesting that this protein interacts with factors other than Spo0A. Altogether, the data indicate that CD1492 negatively affects sporulation and positively influences motility and virulence. These results provide further evidence that C. difficile sporulation is regulated differently from that of other endospore-forming species. PMID:27647869

Acute kidney injury impact on inpatient mortality in Clostridium difficile infection: A national propensity-matched study.

PubMed

Charilaou, Paris; Devani, Kalpit; John, Febin; Kanna, Sowjanya; Ahlawat, Sushil; Young, Mark; Khanna, Sahil; Reddy, Chakradhar

2018-06-01

Acute kidney injury (AKI) is used as a marker of severity in Clostridium difficile infection (CDI) patients. We estimated the true effect of AKI in inpatient mortality of CDI patients, as there are no large-scale, population-based, propensity-matched studies evaluating AKI's effect in this patient cohort. A retrospective observational study utilizing the National Inpatient Sample from years 2003 to 2012, including all adults with CDI, excluding cases missing data on age, inpatient mortality or gender. Trends and CDI-related complications as mortality predictors were assessed using survey-weighted multivariable regression. We estimated AKI's independent effect by propensity-matching, post-stratifying by chronic kidney disease status, allowing for multiple comorbidity adjustment. A total of 2 859 599 patients with CDI were included, of which 896 122 (31.3%) had principal diagnosis of CDI. AKI prevalence was 22%. Mortality rate was 8.4%, while among AKI patients was higher (18.2%). In multivariable regression, AKI was associated with higher mortality (odds ratio [OR] = 3.16, 95% confidence interval [CI]: 3.02-3.30; P < 0.001), while after propensity matching, AKI increased mortality by 86% (OR = 1.86, 95% CI: 1.79-1.94; P < 0.001). CDI incidence increased by 1.8, together with the rate of AKI (12.6% in 2003 to 28.8% in 2012, P-trend < 0.001). Despite increasing hospitalizations, mortality over the study period decreased to 7.2% (2012) from 9.0% (2003); P-trend < 0.001. Hospital admissions of patients with CDI and concomitant AKI are increasing, but their inpatient mortality has improved over the study period. AKI is a significant contributor to mortality, independently of other comorbidities, complications, and hospital characteristics, emphasizing the need for early diagnosis and aggressive management in such patients. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Clinical and economic impact of the introduction of a nucleic acid amplification assay for Clostridium difficile.

PubMed

Guinta, Margaret M; Bunnell, Kristen; Harrington, Amanda; Bleasdale, Susan; Danziger, Larry; Wenzler, Eric

2017-12-04

The clinical outcomes and cost implications of a diagnostic shift from an EIA- to PCR-based assay for Clostridium difficile infection (CDI) have not been completely described in the literature. The impact of the PCR-based assay on the incidence and duration of CDI therapy was compared to the EIA assay for patients with a negative CDI diagnostic result. Secondary clinical and economic outcomes were also evaluated. Independent predictors of receipt of antibiotic therapy were assessed via logistic regression. 141 EIA and 140 PCR patients were included. Significantly more patients were started or continued on anti-CDI antibiotic therapy after a known negative assay result in the EIA group (26 patients vs. 8 patients, P = 0.002). Duration of antibiotic therapy after a known negative result was significantly shorter in the PCR group (1 vs. 4 days, P = 0.029) and a 23% reduction in the number of tests obtained per patient was observed (1.41 ± 0.86 vs. 1.82 ± 1.35, P = 0.007). The over fourfold difference in per-test cost of the EIA assay ($8.33 vs. $42.86, P < 0.0001) was offset by the overall medication costs required for the increased treatment in the EIA group ($546.60 vs. $188.96, P = 0.191). Utilization of the EIA-based CDI assay was associated with increased odds of CDI treatment after a negative test (aOR 4.71, 95% CI 1.93-11.46, P = 0.001). The transition from an EIA to PCR-based assay for diagnosing CDI resulted in a significant decrease in the number of patients treated and the duration of treatment in response to a negative test result. This significant decrease in treatment resulted in decreased costs offsetting the utilization of a more expensive molecular test for patients with a negative CDI diagnostic result.

Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection.

PubMed

Nathwani, Dilip; Cornely, Oliver A; Van Engen, Anke K; Odufowora-Sita, Olatunji; Retsa, Peny; Odeyemi, Isaac A O

2014-11-01

Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20,000/QALY and £30,000/QALY. One-way and probabilistic sensitivity analyses were performed. Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14,515 and £14,344, respectively) and in patients with a first recurrence (£16,535 and £16,926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16,529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30,000/QALY was 60% for severe CDI and 68% in a first recurrence. Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

PubMed Central

Khoruts, Alexander; Rank, Kevin M.; Newman, Krista M.; Viskocil, Kimberly; Vaughn, Byron P.; Hamilton, Matthew J.; Sadowsky, Michael J.

2017-01-01

BACKGROUND & AIMS A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure. METHODS We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients’ right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT. RESULTS Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P = .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI. CONCLUSIONS Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure. PMID:26905904

Statin use and the risk of Clostridium difficile infection: a systematic review with meta-analysis.

PubMed

Tariq, Raseen; Mukhija, Dhruvika; Gupta, Arjun; Singh, Siddharth; Pardi, Darrell S; Khanna, Sahil

2018-01-01

Statins have pleiotropic effects beyond cholesterol lowering by immune modulation. The association of statins with primary Clostridium difficile infection (CDI) is unclear as studies have reported conflicting findings. We performed a systematic review and meta-analysis to evaluate the association between statin use and CDI. We searched MEDLINE, Embase, and Web of Science from January 1978 to December 2016 for studies assessing the association between statin use and CDI. The Newcastle-Ottawa Scale was used to assess the methodologic quality of included studies. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Eight studies (6 case-control and 2 cohort) were included in the meta-analysis, which comprised 156,722 patients exposed to statins and 356,185 controls, with 34,849 total cases of CDI available in 7 studies. The rate of CDI in patients with statin use was 4.3%, compared with 7.8% in patients without statin use. An overall meta-analysis of 8 studies using the random-effects model demonstrated that statins may be associated with a decreased risk of CDI (maximally adjusted odds ratio [OR], 0.80; 95% CI, 0.66-0.97; P =0.02). There was significant heterogeneity among the studies, with an I 2 of 79%. No publication bias was seen. Meta-analysis of studies that adjusted for confounders revealed no protective effect of statins (adjusted OR, 0.84; 95% CI, 0.70-1.01; P =0.06, I 2 =75%). However, a meta-analysis of only full-text studies using the random-effects model demonstrated a decreased risk of CDI with the use of statins (OR 0.77; 95% CI, 0.61-0.99; P =0.04, I 2 =85%). Meta-analyses of existing studies suggest that patients prescribed a statin may be at decreased risk for CDI. The results must be interpreted with caution given the significant heterogeneity and lack of benefit on analysis of studies that adjusted for confounders.

Clinical and microbiological characterization of Clostridium difficile infection in a tertiary care hospital in Shanghai, China.

PubMed

Dong, Danfeng; Peng, Yibing; Zhang, Lihua; Jiang, Cen; Wang, Xuefeng; Mao, Enqiang

2014-01-01

Over the last decade, Clostridium difficile infection (CDI) has emerged as a significant nosocomial infection, yet little has been reported from China. This study aimed to characterize the clinical and microbiological features of CDI from a hospital in Shanghai. Patients with CDI seen between December 2010 and March 2013 were included in this study, of which clinical data were retrospectively collected. The microbiological features of corresponding isolates were analyzed including genotype by multi-locus sequence typing (MLST), antimicrobial susceptibility, toxin production, sporulation capacity, biofilm formation, and motility. Ninety-four cases of CDI were included during this study period, 12 of whom were severe cases. By reviewing the clinical data, all patients were treated empirically with proton pump inhibitor or antibiotics or both, and they were distributed widely across various wards, most frequently to the digestive ward (28/94, 29.79%). Comparing the severe with mild cases, no significant differences were found in the basic epidemiological data or the microbiological features. Among the 94 isolates, 31 were toxin A-negative toxin B-positive all genotyped as ST37. They generated fewer toxins and spores, as well as similar amounts of biofilm and motility percentages, but exhibited highest drug resistance to cephalosporins, quinolones, macrolide-lincosamide and streptogramin (MLSB), and tetracycline. No specific clinical genotype or microbiological features were found in severe cases; antimicrobial resistance could be the primary reason for epidemic strains leading to the dissemination and persistence of CDI.

Cost-Effectiveness Analysis of Probiotic Use to Prevent Clostridium difficile Infection in Hospitalized Adults Receiving Antibiotics.

PubMed

Shen, Nicole T; Leff, Jared A; Schneider, Yecheskel; Crawford, Carl V; Maw, Anna; Bosworth, Brian; Simon, Matthew S

2017-01-01

Systematic reviews with meta-analyses and meta-regression suggest that timely probiotic use can prevent Clostridium difficile infection (CDI) in hospitalized adults receiving antibiotics, but the cost effectiveness is unknown. We sought to evaluate the cost effectiveness of probiotic use for prevention of CDI versus no probiotic use in the United States. We programmed a decision analytic model using published literature and national databases with a 1-year time horizon. The base case was modeled as a hypothetical cohort of hospitalized adults (mean age 68) receiving antibiotics with and without concurrent probiotic administration. Projected outcomes included quality-adjusted life-years (QALYs), costs (2013 US dollars), incremental cost-effectiveness ratios (ICERs; $/QALY), and cost per infection avoided. One-way, two-way, and probabilistic sensitivity analyses were conducted, and scenarios of different age cohorts were considered. The ICERs less than $100000 per QALY were considered cost effective. Probiotic use dominated (more effective and less costly) no probiotic use. Results were sensitive to probiotic efficacy (relative risk <0.73), the baseline risk of CDI (>1.6%), the risk of probiotic-associated bactermia/fungemia (<0.26%), probiotic cost (<$130), and age (>65). In probabilistic sensitivity analysis, at a willingness-to-pay threshold of $100000/QALY, probiotics were the optimal strategy in 69.4% of simulations. Our findings suggest that probiotic use may be a cost-effective strategy to prevent CDI in hospitalized adults receiving antibiotics age 65 or older or when the baseline risk of CDI exceeds 1.6%.

Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile.

PubMed

Bakker, Guido J; Nieuwdorp, Max

2017-08-01

The human intestinal tract contains trillions of bacteria, collectively called the gut microbiota. Recent insights have linked the gut microbiota to a plethora of diseases, including Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), and metabolic diseases such as obesity, type 2 diabetes (T2D), and nonalcoholic steatohepatitis (NASH). Fecal microbiota transplantation (FMT) is currently tested as a therapeutic option in various diseases and can also help to dissect association from causality with respect to gut microbiota and disease. In CDI, FMT has been shown to be superior to antibiotic treatment. For IBD, T2D, and NASH, several placebo-controlled randomized controlled trials are under way. Moreover, techniques and standardization are developing. With the extension of FMT as a treatment modality in diseases other than CDI, a whole new treatment option may be emerging. Moreover, correlating alterations in specific strains to disease outcome may prove pivotal in finding new bacterial targets. Thus, although causality of the gut microbiota in various diseases still needs to be proven, FMT may prove to be a powerful tool providing us with diagnostic and therapeutic leads.

Derivation and Validation of a Clostridium difficile Infection Recurrence Prediction Rule in a National Cohort of Veterans.

PubMed

Reveles, Kelly R; Mortensen, Eric M; Koeller, Jim M; Lawson, Kenneth A; Pugh, Mary Jo V; Rumbellow, Sarah A; Argamany, Jacqueline R; Frei, Christopher R

2018-03-01

Prior studies have identified risk factors for recurrent Clostridium difficile infection (CDI), but few studies have integrated these factors into a clinical prediction rule that can aid clinical decision-making. The objectives of this study were to derive and validate a CDI recurrence prediction rule to identify patients at risk for first recurrence in a national cohort of veterans. Retrospective cohort study. Veterans Affairs Informatics and Computing Infrastructure. A total of 22,615 adult Veterans Health Administration beneficiaries with first-episode CDI between October 1, 2002, and September 30, 2014; of these patients, 7538 were assigned to the derivation cohort and 15,077 to the validation cohort. A 60-day CDI recurrence prediction rule was created in a derivation cohort using backward logistic regression. Those variables significant at p<0.01 were assigned an integer score proportional to the regression coefficient. The model was then validated in the derivation cohort and a separate validation cohort. Patients were then split into three risk categories, and rates of recurrence were described for each category. The CDI recurrence prediction rule included the following predictor variables with their respective point values: prior third- and fourth-generation cephalosporins (1 point), prior proton pump inhibitors (1 point), prior antidiarrheals (1 point), nonsevere CDI (2 points), and community-onset CDI (3 points). In the derivation cohort, the 60-day CDI recurrence risk for each score ranged from 7.5% (0 points) to 57.9% (8 points). The risk score was strongly correlated with recurrence (R 2  = 0.94). Patients were split into low-risk (0-2 points), medium-risk (3-5 points), and high-risk (6-8 points) classes and had the following recurrence rates: 8.9%, 20.2%, and 35.0%, respectively. Findings were similar in the validation cohort. Several CDI and patient-specific factors were independently associated with 60-day CDI recurrence risk. When integrated into a clinical prediction rule, higher risk scores and risk classes were strongly correlated with CDI recurrence. This clinical prediction rule can be used by providers to identify patients at high risk for CDI recurrence and help guide preventive strategy decisions, while accounting for clinical judgment. © 2018 Pharmacotherapy Publications, Inc.

Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+): Characterization, Manufacture, Mechanisms of Action, and Quality Control of a Specific Probiotic Combination for Primary Prevention of Clostridium difficile Infection.

PubMed

Auclair, Julie; Frappier, Martin; Millette, Mathieu

2015-05-15

A specific probiotic formulation composed of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+) has been marketed in North America since 1996. The strains and the commercial products have been evaluated for safety, identity, gastrointestinal survival, and stability throughout shelf life. The capacity of both the fermented beverages and the capsules to reduce incidences of antibiotic-associated diarrhea and Clostridium difficile infection (CDI) has been demonstrated in human clinical trials. Individual strains and the finished products have shown antimicrobial activity against C. difficile and toxin A/B neutralization capacity in vitro. The use of this specific probiotic formulation as part of a bundle of preventive measures to control CDI in healthcare settings is discussed. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Toward an Understanding of Changes in Diversity Associated with Fecal Microbiome Transplantation Based on 16S rRNA Gene Deep Sequencing

PubMed Central

Shahinas, Dea; Silverman, Michael; Sittler, Taylor; Chiu, Charles; Kim, Peter; Allen-Vercoe, Emma; Weese, Scott; Wong, Andrew; Low, Donald E.; Pillai, Dylan R.

2012-01-01

ABSTRACT Fecal microbiome transplantation by low-volume enema is an effective, safe, and inexpensive alternative to antibiotic therapy for patients with chronic relapsing Clostridium difficile infection (CDI). We explored the microbial diversity of pre- and posttransplant stool specimens from CDI patients (n = 6) using deep sequencing of the 16S rRNA gene. While interindividual variability in microbiota change occurs with fecal transplantation and vancomycin exposure, in this pilot study we note that clinical cure of CDI is associated with an increase in diversity and richness. Genus- and species-level analysis may reveal a cocktail of microorganisms or products thereof that will ultimately be used as a probiotic to treat CDI. PMID:23093385

Comparative Effectiveness of Vancomycin and Metronidazole for the Prevention of Recurrence and Death in Patients With Clostridium difficile Infection.

PubMed

Stevens, Vanessa W; Nelson, Richard E; Schwab-Daugherty, Elyse M; Khader, Karim; Jones, Makoto M; Brown, Kevin A; Greene, Tom; Croft, Lindsay D; Neuhauser, Melinda; Glassman, Peter; Goetz, Matthew Bidwell; Samore, Matthew H; Rubin, Michael A

2017-04-01

Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied. To evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI. This retrospective, propensity-matched cohort study evaluated patients treated for CDI, defined as a positive laboratory test result for the presence of C difficile toxins or toxin genes in a stool sample, in the US Department of Veterans Affairs health care system from January 1, 2005, through December 31, 2012. Data analysis was performed from February 7, 2015, through November 22, 2016. Treatment with vancomycin or metronidazole. The outcomes of interest in this study were CDI recurrence and all-cause 30-day mortality. Recurrence was defined as a second positive laboratory test result within 8 weeks of the initial CDI diagnosis. All-cause 30-day mortality was defined as death from any cause within 30 days of the initial CDI diagnosis. A total of 47 471 patients (mean [SD] age, 68.8 [13.3] years; 1947 women [4.1%] and 45 524 men [95.9%]) developed CDI, were treated with vancomycin or metronidazole, and met criteria for entry into the study. Of 47 147 eligible first treatment episodes, 2068 (4.4%) were with vancomycin. Those 2068 patients were matched to 8069 patients in the metronidazole group for a total of 10 137 included patients. Subcohorts were constructed that comprised 5452 patients with mild to moderate disease and 3130 patients with severe disease. There were no differences in the risk of recurrence between patients treated with vancomycin vs those treated with metronidazole in any of the disease severity cohorts. Among patients in the any severity cohort, those who were treated with vancomycin were less likely to die (adjusted relative risk, 0.86; 95% CI, 0.74 to 0.98; adjusted risk difference, -0.02; 95% CI, -0.03 to -0.01). No significant difference was found in the risk of mortality between treatment groups among patients with mild to moderate CDI, but vancomycin significantly reduced the risk of all-cause 30-day mortality among patients with severe CDI (adjusted relative risk, 0.79; 95% CI, 0.65 to 0.97; adjusted risk difference, -0.04; 95% CI, -0.07 to -0.01). Recurrence rates were similar among patients treated with vancomycin and metronidazole. However, the risk of 30-day mortality was significantly reduced among patients who received vancomycin. Our findings may further justify the use of vancomycin as initial therapy for severe CDI.

A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany.

PubMed

Watt, Maureen; McCrea, Charles; Johal, Sukhvinder; Posnett, John; Nazir, Jameel

2016-10-01

Clostridium difficile infection (CDI) represents a significant economic healthcare burden, especially the cost of recurrent disease. Fidaxomicin produced significantly lower recurrence rates and higher sustained cure rates in clinical trials. We evaluated the cost-effectiveness and budget impact of fidaxomicin compared with vancomycin in Germany in the first-line treatment of patient subgroups with CDI at increased risk of recurrence. A semi-Markov model was used to compare the cost-effectiveness and budget impact of fidaxomicin vs. vancomycin from a payer perspective in Germany. The model cycle length was 10 days. The time horizon was 1 year. Model inputs were probability of clinical cure, 30-day probability of recurrence, and 30-day attributable mortality based on evidence from two randomized controlled trials comparing fidaxomicin and vancomycin in patients with CDI. Cost-effectiveness outcomes were cost per quality-adjusted life year gained, cost per bed-day saved, and cost per recurrence avoided. Despite higher drug acquisition costs, fidaxomicin was dominant in the cancer subgroup (less costly and more effective) and cost-effective in the other subgroups, with incremental cost-effectiveness ratios vs. vancomycin ranging from €26,900 to €44,500. Hospitalization costs of the first-line treatment of CDI with fidaxomicin vs. vancomycin were lower in every patient subgroup, resulting in budget impacts ranging from -€1325 (in patients ≥65 years) to -€2438 (in cancer patients). Reductions in the cost of treating recurrence with fidaxomicin ranged from -€574.32 per patient in those receiving concomitant antibiotics to -€1500.68 per patient in renally impaired patients. In patient subgroups with CDI at increased recurrence risk, fidaxomicin was cost-effective vs. vancomycin, and less costly and more effective in patients with cancer.

The cost-benefit of federal investment in preventing Clostridium difficile infections through the use of a multifaceted infection control and antimicrobial stewardship program.

PubMed

Slayton, Rachel B; Scott, R Douglas; Baggs, James; Lessa, Fernanda C; McDonald, L Clifford; Jernigan, John A

2015-06-01

To determine the potential epidemiologic and economic value of the implementation of a multifaceted Clostridium difficile infection (CDI) control program at US acute care hospitals Markov model with a 5-year time horizon Patients whose data were used in our simulations were limited to hospitalized Medicare beneficiaries ≥65 years old. CDI is an important public health problem with substantial associated morbidity, mortality, and cost. Multifaceted national prevention efforts in the United Kingdom, including antimicrobial stewardship, patient isolation, hand hygiene, environmental cleaning and disinfection, and audit, resulted in a 59% reduction in CDI cases reported from 2008 to 2012. Our analysis was conducted from the federal perspective. The intervention we modeled included the following components: antimicrobial stewardship utilizing the Antimicrobial Use and Resistance module of the National Healthcare Safety Network (NHSN), use of contact precautions, and enhanced environmental cleaning. We parameterized our model using data from CDC surveillance systems, the AHRQ Healthcare Cost and Utilization Project, and literature reviews. To address uncertainty in our parameter estimates, we conducted sensitivity analyses for intervention effectiveness and cost, expenditures by other federal partners, and discount rate. Each simulation represented a cohort of 1,000 hospitalized patients over 1,000 trials. RESULTS In our base case scenario with 50% intervention effectiveness, we estimated that 509,000 CDI cases and 82,000 CDI-attributable deaths would be prevented over a 5-year time horizon. Nationally, the cost savings across all hospitalizations would be $2.5 billion (95% credible interval: $1.2 billion to $4.0 billion). The potential benefits of a multifaceted national CDI prevention program are sizeable from the federal perspective.

A prospective study of risk factors and historical trends in metronidazole failure for Clostridium difficile infection

PubMed Central

Hu, Mary Y.; Maroo, Seema; Kyne, Lorraine; Cloud, Jeffrey; Tummala, Sanjeev; Katchar, Kianoosh; Dreisbach, Valley; Noddin, Laura; Kelly, Ciarán P.

2009-01-01

Background & Aims Recent studies of C. difficile infection (CDI) indicate a dramatic increase in metronidazole failure. The aims of this study were to compare current and historical rates of metronidazole failure and identify risk factors for metronidazole failure. Methods 89 patients with CDI in 2004–2006 were followed for 60 days. Data were compared to a historical cohort of 63 CDI patients studied prospectively in 1998. Metronidazole failure was defined as persistent diarrhea after 10 days of therapy or a change of therapy to vancomycin. Stool samples were analyzed for the presence of NAP-1 strain. Results Metronidazole failure rates were 35% in both the 1998 and 2004–2006 cohorts. There was no difference in the median time to resolution of diarrhea (8 vs. 5 days, p = 0.52) or the proportion with more than 10 days of diarrhea (35% vs. 29%, p = 0.51). Risk factors for metronidazole failure included recent cephalosporin use (OR 32, 95% CI 5–219), CDI on admission (OR 23, 95% CI 3–156), and transfer from another hospital (OR 11, 95% CI 2–72). The frequency of NAP-1 infection in patients with and without metronidazole failure was similar (26% vs. 21%, p = 0.67). Conclusions We found no difference in metronidazole failure rates in 1998 and 2004–2006. Patients with recent cephalosporin use, CDI on admission, and transfer from another hospital were more likely to fail metronidazole and may benefit from early aggressive therapy. Infection with the epidemic NAP-1 strain was not associated with metronidazole failure in endemic CDI. PMID:19081526

Evaluation of the US Food and Drug Administration sentinel analysis tools in confirming previously observed drug-outcome associations: The case of clindamycin and Clostridium difficile infection.

PubMed

Carnahan, Ryan M; Kuntz, Jennifer L; Wang, Shirley V; Fuller, Candace; Gagne, Joshua J; Leonard, Charles E; Hennessy, Sean; Meyer, Tamra; Archdeacon, Patrick; Chen, Chih-Ying; Panozzo, Catherine A; Toh, Sengwee; Katcoff, Hannah; Woodworth, Tiffany; Iyer, Aarthi; Axtman, Sophia; Chrischilles, Elizabeth A

2018-03-13

The Food and Drug Administration's Sentinel System developed parameterized, reusable analytic programs for evaluation of medical product safety. Research on outpatient antibiotic exposures, and Clostridium difficile infection (CDI) with non-user reference groups led us to expect a higher rate of CDI among outpatient clindamycin users vs penicillin users. We evaluated the ability of the Cohort Identification and Descriptive Analysis and Propensity Score Matching tools to identify a higher rate of CDI among clindamycin users. We matched new users of outpatient dispensings of oral clindamycin or penicillin from 13 Data Partners 1:1 on propensity score and followed them for up to 60 days for development of CDI. We used Cox proportional hazards regression stratified by Data Partner and matched pair to compare CDI incidence. Propensity score models at 3 Data Partners had convergence warnings and a limited range of predicted values. We excluded these Data Partners despite adequate covariate balance after matching. From the 10 Data Partners where these models converged without warnings, we identified 807 919 new clindamycin users and 8 815 441 new penicillin users eligible for the analysis. The stratified analysis of 807 769 matched pairs included 840 events among clindamycin users and 290 among penicillin users (hazard ratio 2.90, 95% confidence interval 2.53, 3.31). This evaluation produced an expected result and identified several potential enhancements to the Propensity Score Matching tool. This study has important limitations. CDI risk may have been related to factors other than the inherent properties of the drugs, such as duration of use or subsequent exposures. Copyright © 2018 John Wiley & Sons, Ltd.

"The Invisible Staff": A Qualitative Analysis of Environmental Service Workers' Perceptions of the VA Clostridium difficile Prevention Bundle Using a Human Factors Engineering Approach.

PubMed

Yanke, Eric; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

2018-06-11

Using a novel human factors engineering approach, the Systems Engineering Initiative for Patient Safety model, we evaluated environmental service workers' (ESWs) perceptions of barriers and facilitators influencing adherence to the nationally mandated Department of Veterans Affairs Clostridium difficile infection (CDI) prevention bundle. A focus group of ESWs was conducted. Qualitative analysis was performed employing a visual matrix display to identify barrier/facilitator themes related to Department of Veterans Affairs CDI bundle adherence using the Systems Engineering Initiative for Patient Safety work system as a framework. Environmental service workers reported adequate cleaning supplies/equipment and displayed excellent knowledge of CDI hand hygiene requirements. Environmental service workers described current supervisory practices as providing an acceptable amount of time to clean CDI rooms, although other healthcare workers often pressured ESWs to clean rooms more quickly. Environmental service workers reported significant concern for CDI patients' family members as well as suggesting uncertainty regarding the need for family members to follow infection prevention practices. Small and cluttered patient rooms made cleaning tasks more difficult, and ESW cleaning tasks were often interrupted by other healthcare workers. Environmental service workers did not feel comfortable asking physicians for more time to finish cleaning a room nor did ESWs feel comfortable pointing out lapses in physician hand hygiene. Multiple work system components serve as barriers to and facilitators of ESW adherence to the nationally mandated Department of Veterans Affairs CDI bundle. Environmental service workers may represent an underappreciated resource for hospital infection prevention, and further efforts should be made to engage ESWs as members of the health care team.

Discordance of SHEA/IDSA Clostridium difficile Disease Severity Scale in Solid Organ Transplant Patients

PubMed Central

Lee, Tiffany; McCoy, Christopher; Alonso, Carolyn D; Snyder, Graham M; Rogers, Christin; Richards, Katelyn; Hirsch, Elizabeth B; Mahoney, Monica V

2017-01-01

Abstract Background Solid organ transplant (SOT) patients are at high risk for Clostridium difficile infections (CDI) due to chronic immunosuppression and a propensity to receive antimicrobials. Management of CDI in SOT patients poses unique challenges as this population has disease-altered clinical and laboratory parameters. The objective of this study was to assess concordance between various CDI severity scales and the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) guidelines. Methods This retrospective study included all SOT recipients with a first CDI episode following transplant and time-matched (2:1) to non-SOT patients experiencing first CDI episodes between 2008 and 2016. The primary endpoint was concordance rates of CDI episodes considered mild-moderate or severe/severe-complicated in published CDI scales compared with the SHEA/IDSA guidelines. We also sought to compare the distribution of CDI severity across all scales between SOT and non-SOT patients. Results Overall, 32 SOT patients and 64 non-SOT patients were included. The SOT group had significantly higher leukopenia rates at CDI diagnosis; however, the magnitude of serum creatinine change did not differ between groups. According to the SHEA/IDSA scale, CDI episodes in SOT recipients were categorized as mild-moderate and severe/severe-complicated in 23 (72%) and 9 (28%) patients, respectively. Overall concordance rates among SHEA/IDSA guidelines and other scales ranged from 28% to 72%. Concordance rates were highest for mild-moderate CDI with Belmares and for severe/severe-complicated CDI with ESCMID (Table 1). No scale evenly categorized SOT and non-SOT patients across all severities (Figure 1). Conclusion Severity scales with heavy emphasis on white blood cell counts may not adequately categorize SOT patients. Immunocompromised status may need to be considered on its own when categorizing CDI severity and prescribing therapy. Table 1 Number (%) of Severity Classification-Concordant CDI Episodes, in Comparison to SHEA/IDSA Guidelines Overall n = 32 Mild/Moderate n = 23 Severe or Severe-Complicated n = 9 AST 23 (71.9) 18 (78.3) 5 (55.6) ESCMID 9 (28.1) 0 9 (100) Zar 20 (62.5) 13 (56.5) 7 (77.8) Belmares 22 (68.8) 22 (95.7) 0 Disclosures C. D. Alonso, Merck: Grant Investigator and Scientific Advisor, Research grant sanofi pasteur: Investigator and Scientific Advisor, Research support GSK: Investigator, Research support; E. B. Hirsch, Merck: Grant Investigator, Grant recipient The Medicines Company: Speaker’s Bureau, Speaker honorarium

Recurrent Clostridium difficile Infection: From Colonization to Cure

PubMed Central

Shields, Kelsey; Araujo-Castillo, Roger V.; Theethira, Thimmaiah G.; Alonso, Carolyn D.; Kelly, Ciaran

2015-01-01

Clostridium difficile infection (CDI) is increasingly prevalent, dangerous and challenging to prevent and manage. Despite intense national and international attention the incidence of primary and of recurrent CDI (PCDI and RCDI, respectively) have risen rapidly throughout the past decade. Of major concern is the increase in cases of RCDI resulting in substantial morbidity, morality and economic burden. RCDI management remains challenging as there is no uniformly effective therapy, no firm consensus on optimal treatment, and reliable data regarding RCDI-specific treatment options is scant. Novel therapeutic strategies are critically needed to rapidly, accurately, and effectively identify and treat patients with, or at-risk for, RCDI. In this review we consider the factors implicated in the epidemiology, pathogenesis and clinical presentation of RCDI, evaluate current management options for RCDI and explore novel and emerging therapies. PMID:25930686

The role of single-shot metronidazole in the prevention of Clostridium difficile infection following ileostomy reversal surgery.

PubMed

Fernandes, Roland; Robinson, Paul; Rangarajan, Karan; Scott, Sophie; Angco, Laura

2017-05-01

Symptomatic infection with Clostridium difficile is strongly linked to antibiotic use and rates are higher for colorectal surgery. In February 2015, trust policy for antibiotic prophylaxis of ileostomy reversal surgery was changed from three doses of metronidazole plus cefuroxime to single-dose metronidazole, in a bid to reduce rates of Clostridium difficile infection. A retrospective cohort study was conducted at a single, large hospital trust between February 2014 and February 2016, before and after change in antimicrobial policy. Theatre data, clinical notes and pathology results were all reviewed. Outcome data, patient age, gender, length of operation and hospital stay were extracted. One hundred three patients underwent ileostomy reversal surgery between February 2014 and February 2015. All received cefuroxime together with metronidazole at induction of anaesthesia followed by two further post-operative doses as operative prophylaxis. Ninety-six patients underwent ileostomy reversal surgery between February 2015 and February 2016. All received single-dose metronidazole at induction as prophylaxis. Post-operative diarrhoea was significantly reduced in patients given single-dose metronidazole compared with patients managed with multiple dose, dual antibiotic therapy (32 vs 12.5%, P 0.001). Rates of CDI were also significantly reduced in patients given single-dose metronidazole (6.8 vs 1%, P 0.038). Single-dose, pre-operative metronidazole is effective at reducing post-operative diarrhoea and CDI in ileostomy reversal surgery compared with multiple-dose cefuroxime plus metronidazole. Metronidazole may be effective as a prophylactic antibiotic against CDI in colonic surgery.

Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis

PubMed Central

Auchtung, Jennifer; Brown, Aaron; Boonma, Prapaporn; Oezguen, Numan; Ross, Caná L.; Luna, Ruth Ann; Runge, Jessica; Versalovic, James; Peniche, Alex; Dann, Sara M.; Britton, Robert A.; Haag, Anthony; Savidge, Tor C.

2017-01-01

ABSTRACT Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials. PMID:28760934

Rifaximin-resistant Clostridium difficile strains isolated from symptomatic patients.

PubMed

Reigadas, E; Muñoz-Pacheco, P; Vázquez-Cuesta, S; Alcalá, L; Marín, M; Martin, A; Bouza, E

2017-12-01

Rifaximin has been proposed as an alternative treatment for specific cases of Clostridium difficile infection (CDI) and intestinal decontamination. Rifaximin-resistant C. difficile has occasionally been reported. Antibiotic susceptibility testing relies on anaerobic agar dilution (reference method), which is cumbersome and not routinely used. There is no commercial test for detection of resistance to rifaximin. To assess resistance to rifaximin by C. difficile and to evaluate the correlation between the results of the rifampicin E-test and susceptibility to rifaximin. We compared the in vitro susceptibility of clinical CDI isolates to rifaximin over a 6-month period using the agar dilution method with susceptibility to rifampicin using the E-test. All isolates were characterized using PCR-ribotyping. Clinical data were recorded prospectively. We recovered 276 consecutive C. difficile isolates and found that 32.2% of episodes were caused by rifaximin-resistant strains. The MICs for rifaximin ranged from <0.0009-256 mg/L, with a geometric mean (GM) of 0.256 mg/L, an MIC 50/90 of 0.015/>256 mg/L. Rifaximin and rifampicin MICs were comparable, and all strains classed as resistant by agar dilution were correctly classified as resistant by E-test. The most common ribotypes were 001 (37.2%), 078/126 (14.3%), and 014 (12.0%). Ribotype 001 exhibited the highest MICs for rifaximin. Resistance to rifaximin was common; resistance rates were higher in ribotype 001 strains. Susceptibility to rifaximin determined by agar dilution correlated with susceptibility to rifampicin determined using the E-test, including rifaximin-resistant strains. Our results suggest that the rifampicin E-test is a valid method for the prediction of rifaximin-resistant C. difficile. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low sensitivity of fecal toxin A/B enzyme immunoassay for diagnosis of Clostridium difficile infection in immunocompromised patients.

PubMed

Erb, S; Frei, R; Strandén, A M; Dangel, M; Tschudin-Sutter, S; Widmer, A F

2015-11-01

The optimal approach in laboratory diagnosis of Clostridium difficile infection (CDI) is still not well defined. Toxigenic culture (TC) or alternatively fecal toxin assay by cell cytotoxicity neutralization assay are considered to be the reference standard, but these methods are time-consuming and labor intensive. In many medical centers, diagnosis of CDI is therefore still based on fecal toxin A/B enzyme immunoassay (EIA) directly from stool alone, balancing cost and speed against limited diagnostic sensitivity. The aim of the study was to assess in which patient population the additional workload of TC is justified. All consecutive stool specimens submitted for diagnosis of suspected CDI between 2004 and 2011 at a tertiary-care center were examined by toxin EIA and TC. Clinical data of patients with established diagnosis of CDI were collected in a standardized case-report form. From 12,481 stool specimens submitted to the microbiologic laboratory, 480 (3.8%) fulfilled CDI criteria; 274 (57.1%) were diagnosed by toxin EIA; and an additional 206 (42.9%) were diagnosed by TC when toxin EIA was negative. Independent predictors for negative toxin EIA but positive TC were high-dose corticosteroids (odds ratio (OR) 2.97, 95% confidence interval (CI) 1.50-5.90, p 0.002), leukocytopenia <1000/μL (OR 2.52, 95% CI 1.22-5.23, p 0.013) and nonsevere CDI (OR 2.21, 95% CI 1.39-3.50, p 0.001). There was no difference in outcomes such as in-hospital mortality and recurrence between both groups. In conclusion, negative toxin EIA does not rule out CDI in immunocompromised patients in the setting of relevant clinical symptoms. Methods with improved sensitivity such as TC or PCR should be used, particularly in this patient population. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Vancomycin for the treatment of Clostridium difficile Infection: for whom is this expensive bullet really magic?

PubMed

Pepin, Jacques

2008-05-15

The epidemiology, clinical severity, and case-fatality ratio of Clostridium difficile infection (CDI) changed dramatically with the emergence of a toxin hyperproducing strain (BI/NAP1/027) in North America and Europe in 2000. For the treatment of CDI, metronidazole and vancomycin remain the 2 most commonly used drugs. The 3 randomized controlled trials published thus far, as well as the upcoming tolevamer trial, use intermediate outcomes, rather than the outcomes that now preoccupy clinicians: the frequency of complications or recurrence. The major advantage of metronidazole is its low price. The major advantage of orally administered vancomycin is its more favorable pharmacokinetics. Facilitating vancomycin-resistant enterococci colonization and/or infection is a potential drawback of both drugs. Pending the development of a prospectively validated scoring system, members of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America expert committee will define severe CDI as present in any patient with a leukocyte count > or =15,000 cells/mm(3) or a creatinine level increased by > or =50% from baseline. For patients with mild-to-moderate CDI (defined by a leukocyte count <15000 cells/mm(3) and a creatinine level <1.5 times the baseline value), there is no evidence that treatment with vancomycin is superior to treatment with metronidazole (even for intermediate outcomes), and metronidazole therapy should be preferred. For patients with severe CDI who are not infected with BI/NAP1/027, there is reasonable evidence that the better pharmacokinetics of vancomycin translate into a lower probability of complications. For those patients who are infected with BI/NAP1/027, the superiority of vancomycin therapy remains to be proven. In practice, because it is not yet possible to rapidly type the strains, all patients with severe CDI should be treated with vancomycin. Future trials should use complicated CDI and recurrences as their primary outcomes.

Cost-Effectiveness Analysis of Probiotic Use to Prevent Clostridium difficile Infection in Hospitalized Adults Receiving Antibiotics

PubMed Central

Leff, Jared A; Schneider, Yecheskel; Crawford, Carl V; Maw, Anna; Bosworth, Brian; Simon, Matthew S

2017-01-01

Abstract Background Systematic reviews with meta-analyses and meta-regression suggest that timely probiotic use can prevent Clostridium difficile infection (CDI) in hospitalized adults receiving antibiotics, but the cost effectiveness is unknown. We sought to evaluate the cost effectiveness of probiotic use for prevention of CDI versus no probiotic use in the United States. Methods We programmed a decision analytic model using published literature and national databases with a 1-year time horizon. The base case was modeled as a hypothetical cohort of hospitalized adults (mean age 68) receiving antibiotics with and without concurrent probiotic administration. Projected outcomes included quality-adjusted life-years (QALYs), costs (2013 US dollars), incremental cost-effectiveness ratios (ICERs; $/QALY), and cost per infection avoided. One-way, two-way, and probabilistic sensitivity analyses were conducted, and scenarios of different age cohorts were considered. The ICERs less than $100000 per QALY were considered cost effective. Results Probiotic use dominated (more effective and less costly) no probiotic use. Results were sensitive to probiotic efficacy (relative risk <0.73), the baseline risk of CDI (>1.6%), the risk of probiotic-associated bactermia/fungemia (<0.26%), probiotic cost (<$130), and age (>65). In probabilistic sensitivity analysis, at a willingness-to-pay threshold of $100000/QALY, probiotics were the optimal strategy in 69.4% of simulations. Conclusions Our findings suggest that probiotic use may be a cost-effective strategy to prevent CDI in hospitalized adults receiving antibiotics age 65 or older or when the baseline risk of CDI exceeds 1.6%. PMID:29230429

A qualitative, interprofessional analysis of barriers to and facilitators of implementation of the Department of Veterans Affairs' Clostridium difficile prevention bundle using a human factors engineering approach.

PubMed

Yanke, Eric; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

2018-03-01

Clostridium difficile infection (CDI) is increasingly prevalent, severe, and costly. Adherence to infection prevention practices remains suboptimal. More effective strategies to implement guidelines and evidence are needed. Interprofessional focus groups consisting of physicians, resident physicians, nurses, and health technicians were conducted for a quality improvement project evaluating adherence to the Department of Veterans Affairs' (VA) nationally mandated C difficile prevention bundle. Qualitative analysis with a visual matrix display identified barrier and facilitator themes guided by the Systems Engineering Initiative for Patient Safety model, a human factors engineering approach. Several themes, encompassing both barriers and facilitators to bundle adherence, emerged. Rapid turnaround time of C difficile polymerase chain reaction testing was a facilitator of timely diagnosis. Too few, poorly located, and cluttered sinks were barriers to appropriate hand hygiene. Patient care workload and the time-consuming process of contact isolation precautions were also barriers to adherence. Multiple work system components serve as barriers to and facilitators of adherence to the VA CDI prevention bundle among an interprofessional group of health care workers. Organizational factors appear to significantly influence bundle adherence. Interprofessional perspectives are needed to identify barriers to and facilitators of bundle implementation, which is a necessary first step to address adherence to bundled infection prevention practices. Published by Elsevier Inc.

Rethinking Strategies to Select Antibiotic Therapy in Clostridium difficile infection.

PubMed

Chopra, Teena; Goldstein, Ellie J C; Gorbach, Sherwood L

2016-12-01

In recent years, Clostridium difficile infection (CDI) has become a global public health threat associated with increased morbidity, mortality, and economic burden, all of which are exacerbated with disease recurrence. Current guidelines informing treatment decisions are largely based on definitions of disease severity at diagnosis, with subjective components not well delineated across treatment algorithms and clinical trials. Furthermore, there is little evidence linking severity at onset to outcome. However, reducing the risk of recurrence may offer both a better outcome for the individual and decreased downstream economic impact. The authors present data supporting the opinion that patients deemed at low risk for recurrence should receive vancomycin (or metronidazole when cost is an issue), while those at higher risk of recurrence would benefit from fidaxomicin treatment. Although further prospective studies are needed, choosing treatment with the goal of preventing recurrent CDI may offer a better guide than disease severity. © 2016 Pharmacotherapy Publications, Inc.

Genomic study of the Type IVC secretion system in Clostridium difficile: understanding C. difficile evolution via horizontal gene transfer.

PubMed

Zhang, Wen; Cheng, Ying; Du, Pengcheng; Zhang, Yuanyuan; Jia, Hongbing; Li, Xianping; Wang, Jing; Han, Na; Qiang, Yujun; Chen, Chen; Lu, Jinxing

2017-01-01

Clostridium difficile, the etiological agent of Clostridium difficile infection (CDI), is a gram-positive, spore-forming bacillus that is responsible for ∼20% of antibiotic-related cases of diarrhea and nearly all cases of pseudomembranous colitis. Previous data have shown that a substantial proportion (11%) of the C. difficile genome consists of mobile genetic elements, including seven conjugative transposons. However, the mechanism underlying the formation of a mosaic genome in C. difficile is unknown. The type-IV secretion system (T4SS) is the only secretion system known to transfer DNA segments among bacteria. We searched genome databases to identify a candidate T4SS in C. difficile that could transfer DNA among different C. difficile strains. All T4SS gene clusters in C. difficile are located within genomic islands (GIs), which have variable lengths and structures and are all conjugative transposons. During the horizontal-transfer process of T4SS GIs within the C. difficile population, the excision sites were altered, resulting in different short-tandem repeat sequences among the T4SS GIs, as well as different chromosomal insertion sites and additional regions in the GIs.

An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

PubMed

Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P

2016-01-01

Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

Efficacy of surotomycin in an in vitro gut model of Clostridium difficile infection.

PubMed

Chilton, C H; Crowther, G S; Todhunter, S L; Nicholson, S; Freeman, J; Chesnel, L; Wilcox, M H

2014-09-01

We investigated the efficacy of the cyclic lipopeptide surotomycin in treating clindamycin-induced Clostridium difficile infection (CDI) using an in vitro gut model. Two three-stage chemostat gut models were inoculated with human faeces, spiked with C. difficile spores (∼10(7) cfu/mL, PCR ribotype 027 or 001). Clindamycin (33.9 mg/L, four times daily for 7 days) was dosed to induce CDI. Following high-level toxin production, surotomycin (250 mg/L, twice daily for 7 days) was instilled. Microflora populations, C. difficile vegetative cells and spores, cytotoxin titres and antimicrobial levels (LC-MS/MS and bioassay) were determined. The emergence of C. difficile and enterococci with reduced susceptibility to surotomycin was monitored on breakpoint agar (4 × MIC). Counts of viable C. difficile were reduced to near the limit of detection on Days 1 and 3 of surotomycin instillation, and cytotoxin was undetectable on Days 3 and 4 of surotomycin instillation in the 027 and 001 models, respectively. Recurrence of vegetative growth and toxin production occurred 11 days (001 model) and 15 days (027 model) after surotomycin instillation had ceased, and remained for the duration of the experiment. Surotomycin instillation decreased populations of bifidobacteria, clostridia, enterococci and lactobacilli, but was sparing of Bacteroides fragilis group populations. All enumerated organisms had recovered to steady-state levels by 3 weeks post-surotomycin instillation. No evidence of the emergence of reduced susceptibility to surotomycin was observed. Surotomycin successfully reduced C. difficile vegetative cell counts and toxin levels in the gut model and was sparing of B. fragilis group populations. There was no evidence of decreased susceptibility to surotomycin during exposure or post-exposure. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Novel Strategies for Enhanced Removal of Persistent Bacillus anthracis Surrogates and Clostridium difficile Spores from Skin

PubMed Central

Nerandzic, Michelle M.; Rackaityte, Elze; Jury, Lucy A.; Eckart, Kevin; Donskey, Curtis J.

2013-01-01

Background Removing spores of Clostridium difficile and Bacillus anthracis from skin is challenging because they are resistant to commonly used antimicrobials and soap and water washing provides only modest efficacy. We hypothesized that hygiene interventions incorporating a sporicidal electrochemically generated hypochlorous acid solution (Vashe®) would reduce the burden of spores on skin. Methods Hands of volunteers were inoculated with non-toxigenic C. difficile spores or B. anthracis spore surrogates to assess the effectiveness of Vashe solution for reducing spores on skin. Reduction in spores was compared for Vashe hygiene interventions versus soap and water (control). To determine the effectiveness of Vashe solution for removal of C. difficile spores from the skin of patients with C. difficile infection (CDI), reductions in levels of spores on skin were compared for soap and water versus Vashe bed baths. Results Spore removal from hands was enhanced with Vashe soak (>2.5 log10 reduction) versus soap and water wash or soak (~2.0 log10 reduction; P <0.05) and Vashe wipes versus alcohol wipes (P <0.01). A combined approach of soap and water wash followed by soaking in Vashe removed >3.5 log10 spores from hands (P <0.01 compared to washing or soaking alone). Bed baths using soap and water (N =26 patients) did not reduce the percentage of positive skin cultures for CDI patients (64% before versus 57% after bathing; P =0.5), whereas bathing with Vashe solution (N =21 patients) significantly reduced skin contamination (54% before versus 8% after bathing; P =0.0001). Vashe was well-tolerated with no evidence of adverse effects on skin. Conclusions Vashe was safe and effective for reducing the burden of B. anthracis surrogates and C. difficile spores on hands. Bed baths with Vashe were effective for reducing C. difficile on skin. These findings suggest a novel strategy to reduce the burden of spores on skin. PMID:23844234

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis.

PubMed

Shen, Nicole T; Maw, Anna; Tmanova, Lyubov L; Pino, Alejandro; Ancy, Kayley; Crawford, Carl V; Simon, Matthew S; Evans, Arthur T

2017-06-01

Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice. We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality. We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I 2  = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I 2  = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I 2  = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high. In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories

PubMed Central

Carroll, Karen C.

2013-01-01

SUMMARY Clostridium difficile is a formidable nosocomial and community-acquired pathogen, causing clinical presentations ranging from asymptomatic colonization to self-limiting diarrhea to toxic megacolon and fulminant colitis. Since the early 2000s, the incidence of C. difficile disease has increased dramatically, and this is thought to be due to the emergence of new strain types. For many years, the mainstay of C. difficile disease diagnosis was enzyme immunoassays for detection of the C. difficile toxin(s), although it is now generally accepted that these assays lack sensitivity. A number of molecular assays are commercially available for the detection of C. difficile. This review covers the history and biology of C. difficile and provides an in-depth discussion of the laboratory methods used for the diagnosis of C. difficile infection (CDI). In addition, strain typing methods for C. difficile and the evolving epidemiology of colonization and infection with this organism are discussed. Finally, considerations for diagnosing C. difficile disease in special patient populations, such as children, oncology patients, transplant patients, and patients with inflammatory bowel disease, are described. As detection of C. difficile in clinical specimens does not always equate with disease, the diagnosis of C. difficile infection continues to be a challenge for both laboratories and clinicians. PMID:23824374

In silico analysis of antibiotic-induced Clostridium difficile infection: Remediation techniques and biological adaptations

PubMed Central

Carlson, Jean M.

2018-01-01

In this paper we study antibiotic-induced C. difficile infection (CDI), caused by the toxin-producing C. difficile (CD), and implement clinically-inspired simulated treatments in a computational framework that synthesizes a generalized Lotka-Volterra (gLV) model with SIR modeling techniques. The gLV model uses parameters derived from an experimental mouse model, in which the mice are administered antibiotics and subsequently dosed with CD. We numerically identify which of the experimentally measured initial conditions are vulnerable to CD colonization, then formalize the notion of CD susceptibility analytically. We simulate fecal transplantation, a clinically successful treatment for CDI, and discover that both the transplant timing and transplant donor are relevant to the the efficacy of the treatment, a result which has clinical implications. We incorporate two nongeneric yet dangerous attributes of CD into the gLV model, sporulation and antibiotic-resistant mutation, and for each identify relevant SIR techniques that describe the desired attribute. Finally, we rely on the results of our framework to analyze an experimental study of fecal transplants in mice, and are able to explain observed experimental results, validate our simulated results, and suggest model-motivated experiments. PMID:29451873

In silico analysis of antibiotic-induced Clostridium difficile infection: Remediation techniques and biological adaptations.

PubMed

Jones, Eric W; Carlson, Jean M

2018-02-01

In this paper we study antibiotic-induced C. difficile infection (CDI), caused by the toxin-producing C. difficile (CD), and implement clinically-inspired simulated treatments in a computational framework that synthesizes a generalized Lotka-Volterra (gLV) model with SIR modeling techniques. The gLV model uses parameters derived from an experimental mouse model, in which the mice are administered antibiotics and subsequently dosed with CD. We numerically identify which of the experimentally measured initial conditions are vulnerable to CD colonization, then formalize the notion of CD susceptibility analytically. We simulate fecal transplantation, a clinically successful treatment for CDI, and discover that both the transplant timing and transplant donor are relevant to the the efficacy of the treatment, a result which has clinical implications. We incorporate two nongeneric yet dangerous attributes of CD into the gLV model, sporulation and antibiotic-resistant mutation, and for each identify relevant SIR techniques that describe the desired attribute. Finally, we rely on the results of our framework to analyze an experimental study of fecal transplants in mice, and are able to explain observed experimental results, validate our simulated results, and suggest model-motivated experiments.

Infection prevention and control of Clostridium difficile: a global review of guidelines, strategies, and recommendations

PubMed Central

Balsells, Evelyn; Filipescu, Teodora; Kyaw, Moe H.; Wiuff, Camilla; Campbell, Harry; Nair, Harish

2016-01-01

Background Clostridium difficile is the leading cause of health care–associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance. Methods We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI–targeted IPC recommendations and describe the assessment of evidence in available guidelines. Results We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long–term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported “strong” recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality. Conclusion Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations. PMID:28028434

A two-stage algorithm for Clostridium difficile including PCR: can we replace the toxin EIA?

PubMed

Orendi, J M; Monnery, D J; Manzoor, S; Hawkey, P M

2012-01-01

A two step, three-test algorithm for Clostridium difficile infection (CDI) was reviewed. Stool samples were tested by enzyme immunoassays for C. difficile common antigen glutamate dehydrogenase (G) and toxin A/B (T). Samples with discordant results were tested by polymerase chain reaction detecting the toxin B gene (P). The algorithm quickly identified patients with detectable toxin A/B, whereas a large group of patients excreting toxigenic C. difficile but with toxin A/B production below detection level (G(+)T(-)P(+)) was identified separately. The average white blood cell count in patients with a G(+)T(+) result was higher than in those with a G(+)T(-)P(+) result. Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

European Practice for CDI Treatment.

PubMed

Fitzpatrick, Fidelma; Skally, Mairead; Brady, Melissa; Burns, Karen; Rooney, Christopher; Wilcox, Mark H

2018-01-01

Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e.g., metronidazole, vancomycin), the role of newer anti-CDI agents (e.g., fidaxomicin), indications for surgical intervention and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). A 2017 survey of 20 European countries found that while the majority (n = 14) have national CDI guidelines that provide a variety of recommendations for CDI treatment, only five have audited guideline implementation. A variety of restrictions are in place in 13 (65%) countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. Novel anti-CDI agents are being evaluated in Phase III trials; it is not yet clear what will be the roles of these agents. Prophylaxis is an optimum approach to reduce the impact of CDI especially in high-risk populations; monoclonal antibodies, antibiotic blocking approaches and multiple vaccines are currently in advanced clinical trials. The treatment of recurrent CDI is particularly troublesome, and several different live bio therapeutics are being developed, in addition to FMT.

The Economic Burden of Hospital-Acquired Clostridium difficile Infection: A Population-Based Matched Cohort Study.

PubMed

Nanwa, Natasha; Kwong, Jeffrey C; Krahn, Murray; Daneman, Nick; Lu, Hong; Austin, Peter C; Govindarajan, Anand; Rosella, Laura C; Cadarette, Suzanne M; Sander, Beate

2016-09-01

BACKGROUND High-quality cost estimates for hospital-acquired Clostridium difficile infection (CDI) are vital evidence for healthcare policy and decision-making. OBJECTIVE To evaluate the costs attributable to hospital-acquired CDI from the healthcare payer perspective. METHODS We conducted a population-based propensity-score matched cohort study of incident hospitalized subjects diagnosed with CDI (those with the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada code A04.7) from January 1, 2003, through December 31, 2010, in Ontario, Canada. Infected subjects were matched to uninfected subjects (those without the code A04.7) on age, sex, comorbidities, geography, and other variables, and followed up through December 31, 2011. We stratified results by elective and nonelective admissions. The main study outcomes were up-to-3-year costs, which were evaluated in 2014 Canadian dollars. RESULTS We identified 28,308 infected subjects (mean annual incidence, 27.9 per 100,000 population, 3.3 per 1,000 admissions), with a mean age of 71.5 years (range, 0-107 years), 54.0% female, and 8.0% elective admissions. For elective admission subjects, cumulative mean attributable 1-, 2-, and 3-year costs adjusted for survival (undiscounted) were $32,151 (95% CI, $28,192-$36,005), $34,843 ($29,298-$40,027), and $37,171 ($30,364-$43,415), respectively. For nonelective admission subjects, the corresponding costs were $21,909 ($21,221-$22,609), $26,074 ($25,180-$27,014), and $29,944 ($28,873-$31,086), respectively. CONCLUSIONS Hospital-acquired CDI is associated with substantial healthcare costs. To the best of our knowledge, this study is the first CDI costing study to present longitudinal costs. New strategies may be warranted to mitigate this costly infectious disease. Infect Control Hosp Epidemiol 2016;37:1068-1078.

Management and Prevention of Recurrent Clostridium Difficile Infection in Patients After Total Joint Arthroplasty

PubMed Central

Stein, Benjamin E.; Greenough, William B.; Mears, Simon C.

2012-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea in elderly patients, accounting for 15% to 25% of all cases of antibiotic-induced diarrhea in those patients. Virulent forms of this organism have developed, increasing the associated morbidity, mortality, and complication rates. The average patient undergoing total joint arthroplasty is at particular risk of CDI because of advanced age, the use of prophylactic antibiotic coverage in the perioperative period, multiple comorbid conditions, and length of hospital stay. In addition, patients who have had one CDI are at risk of another; the rate of recurrent CDI (RCDI) is 15% to 30%. To review the available information on RCDI, we conducted an extensive literature search, focusing on its epidemiology and the management strategies for its treatment and prevention. We found the management of RCDI is a controversial topic, with as yet no consensus regarding specific treatment guidelines. Several experienced clinicians have published suggested treatment algorithms, but they are based on anecdotal experience. With regard to the prevention of RCDI, the literature is scarce, and currently, the only effective strategies remain judicious use of perioperative antibiotics and appropriate implementation of infection control procedures. There are several vaccination medications that are currently being studied but are not yet ready for clinical use. We agree with the approach to management of RCDI that has been proposed in several articles, that is, on confirmation of a first recurrence of CDI by a stool toxin assay and clinical symptoms, a 14-day course of metronidazole or vancomycin; for a second recurrence, a tapered-pulsed course of vancomycin; and, for 3 or more recurrences, a repeat course of the tapered-pulsed vancomycin and adjunctive Saccharomyces boulardii or cholestyramine. PMID:23569710

Prevalence of and Factors Associated with Clostridium difficile Co-infection Among Patients with Candidemia, United States, 2014–2016

PubMed Central

Tsay, Sharon; Benedict, Kaitlin; Beldavs, Zintars G; Farley, Monica M; Harrison, Lee H; Schaffner, William; Gerth, Taryn; Chiller, Tom; Vallabhaneni, Snigdha

2017-01-01

Abstract Background Candidemia and Clostridium difficile infection (CDI) are two common healthcare-associated infections (HAIs) and share risk factors such as antibiotic use and prolonged hospitalization. CDI and CDI treatment disrupt gut microbial diversity, allowing Candida overgrowth and translocation to the bloodstream. We describe CDI co-infection among patients with candidemia. Methods Population-based surveillance for candidemia was conducted through CDC’s Emerging Infections Program during 2014–2016. A case of candidemia was defined as a blood culture positive for Candida species collected from a surveillance area resident. Demographic and medical information, including occurrence of CDI was collected. We defined co-infection as CDI within 90 days of candidemia and performed bivariable analysis to assess factors associated with co-infection. Results Among 2129 cases of candidemia, 190 (9%) had CDI co-infection; 116 (5%) had CDI in the 90 days before candidemia (median: 10 days) and 60 (3%) had CDI following candidemia (median: 8 days). The median age of those with CDI-candidemia co-infection was 61 years and 100 (53%) were male. Compared with candidemia alone, the odds of CDI-candidemia co-infection was significantly greater for patients of black race (OR 1.41, 95% CI 1.05–1.90), those with diabetes (OR 1.68, 1.24–2.27), pancreatitis (OR 1.91, 1.01–3.61), or solid organ transplant (OR 4.15, 2.09–8.22). Those with co-infection had higher odds of certain healthcare exposures: hemodialysis (OR 2.27, 1.57–3.28), hospital stay in the past 90 days (OR 1.9, 1.37–2.64), ICU admission in the past 14 days (OR 1.78, 1.20–2.66), and central venous catheter (CVC) at the time of candidemia (OR 1.71, 1.19–2.46). There were no significant differences in 30-day mortality or in type of Candida species, although C. parapsilosis was less common in the co-infection group (8% vs. 13%). Conclusion Nearly one in ten patients with candidemia also had CDI co-infection. Black race, certain underlying conditions, hemodialysis, previous hospitalization, ICU stay, and the presence of a CVC were associated with co-infection. Clinicians should be vigilant for coinfection of CDI and candidemia, particularly in situations with associated risk factors. Disclosures W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee

Saccharomyces cerevisiae colonization associated with fecal microbiota treatment failure

USDA-ARS?s Scientific Manuscript database

Background: Fecal microbiota therapy (FMT) has emerged as the gold standard for treatment of persistent, symptomatic Clostridium difficile infection (CDI) that does not respond to conventional antimicrobial treatment. Probiotics are commonly recommended in addition to antimicrobial treatment for CD...

Clostridium difficile infection

PubMed Central

Vedantam, Gayatri; Clark, Andrew; Chu, Michele; McQuade, Rebecca; Mallozzi, Michael; Viswanathan, V. K.

2012-01-01

Clostridium difficile infection is the leading cause of antibiotic- and healthcare-associated diarrhea, and its containment and treatment imposes a significant financial burden, estimated to be over $3 billion in the USA alone. Since the year 2000, CDI epidemics/outbreaks have occurred in North America, Europe and Asia. These outbreaks have been variously associated with, or attributed to, the emergence of Clostridium difficile strains with increased virulence, an increase in resistance to commonly used antimicrobials such as the fluoroquinolones, or host susceptibilities, including the use of gastric acid suppressants, to name a few. Efforts to elucidate C. difficile pathogenic mechanisms have been hampered by a lack of molecular tools, manipulatable animal models, and genetic intractability of clinical C. difficile isolates. However, in the past 5 y, painstaking efforts have resulted in the unraveling of multiple C. difficile virulence-associated pathways and mechanisms. We have recently reviewed the disease, its associated risk factors, transmission and interventions (Viswanathan, Gut Microbes 2010). This article summarizes genetics, non-toxin virulence factors, and host-cell biology associated with C. difficile pathogenesis as of 2011, and highlights those findings/factors that may be of interest as future intervention targets. PMID:22555464

Differences in the rate of carbapenem-resistant Enterobacteriaceae colonisation or Clostridium difficile infection following frontline treatment with tigecycline vs. meropenem for intra-abdominal infections.

PubMed

Bartoletti, Michele; Tedeschi, Sara; Pascale, Renato; Raumer, Luigi; Maraolo, Alberto Enrico; Palmiero, Giulia; Tumietto, Fabio; Cristini, Francesco; Ambretti, Simone; Giannella, Maddalena; Lewis, Russell Edward; Viale, Pierluigi

2018-03-01

We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra-abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen. We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves. We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002-0.72, P = 0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68-2.78, P = 0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03-0.71, P = 0.02), but not CRE (HR 1.12, 95% CI 0.45-2.83, P = 0.80). All-cause 30-day mortality was similar in the two groups (P = 0.46). TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Comparison of Control of Clostridium difficile Infection in Six English Hospitals Using Whole-Genome Sequencing.

PubMed

Eyre, David W; Fawley, Warren N; Rajgopal, Anu; Settle, Christopher; Mortimer, Kalani; Goldenberg, Simon D; Dawson, Susan; Crook, Derrick W; Peto, Tim E A; Walker, A Sarah; Wilcox, Mark H

2017-08-01

Variation in Clostridium difficile infection (CDI) rates between healthcare institutions suggests overall incidence could be reduced if the lowest rates could be achieved more widely. We used whole-genome sequencing (WGS) of consecutive C. difficile isolates from 6 English hospitals over 1 year (2013-14) to compare infection control performance. Fecal samples with a positive initial screen for C. difficile were sequenced. Within each hospital, we estimated the proportion of cases plausibly acquired from previous cases. Overall, 851/971 (87.6%) sequenced samples contained toxin genes, and 451 (46.4%) were fecal-toxin-positive. Of 652 potentially toxigenic isolates >90-days after the study started, 128 (20%, 95% confidence interval [CI] 17-23%) were genetically linked (within ≤2 single nucleotide polymorphisms) to a prior patient's isolate from the previous 90 days. Hospital 2 had the fewest linked isolates, 7/105 (7%, 3-13%), hospital 1, 9/70 (13%, 6-23%), and hospitals 3-6 had similar proportions of linked isolates (22-26%) (P ≤ .002 comparing hospital-2 vs 3-6). Results were similar adjusting for locally circulating ribotypes. Adjusting for hospital, ribotype-027 had the highest proportion of linked isolates (57%, 95% CI 29-81%). Fecal-toxin-positive and toxin-negative patients were similarly likely to be a potential transmission donor, OR = 1.01 (0.68-1.49). There was no association between the estimated proportion of linked cases and testing rates. WGS can be used as a novel surveillance tool to identify varying rates of C. difficile transmission between institutions and therefore to allow targeted efforts to reduce CDI incidence. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Polyethylene glycol intestinal lavage in addition to usual antibiotic treatment for severe Clostridium difficile colitis: a randomised controlled pilot study.

PubMed

McCreery, Greig; Jones, Philip M; Kidane, Biniam; DeMelo, Vanessa; Mele, Tina

2017-07-31

Clostridium difficile infections (CDI) are common, costly and potentially life threatening. Most CDI will respond to antibiotic therapy, but 3%-10% of all patients with CDI will progress to a severe, life-threatening course. Complete removal of the large bowel is indicated for severe CDI. However, the 30-day mortality following surgical intervention for severe CDI ranges from 20% to 70%. A less invasive approach using surgical faecal diversion and direct colonic lavage with polyethylene glycol (PEG) and vancomycin has demonstrated a relative mortality reduction of approximately 50%. As an alternative to these operative approaches, we propose to treat patients with bedside intestinal lavage with PEG and vancomycin instillation via nasojejunal tube, in addition to usual antibiotic management. Preliminary data collected by our research group are encouraging. We will conduct a 1-year, single-centre, pilot randomised controlled trial to study this new treatment strategy for patients with severe CDI and additional risk factors for fulminant or complicated infection. After informed consent, patients with severe-complicated CDI without immediate indication for surgery will be randomised to either usual antibiotic treatment or usual antibiotic treatment with the addition of 8 L of PEG lavage via nasojejunal tube. This pilot trial will evaluate our eligibility and enrolment rate, protocol compliance and adverse event rates and provide further data to inform a more robust sample size calculation and protocol modifications for a definitive multicentre trial design. Based on historical data, we anticipate enrolling approximately 24 patients during the 1-year pilot study period.As a pilot study, data will be reported in aggregate. Between-group differences will be assessed in a blinded fashion for evidence of harm, and to further refine our sample size calculation. This study protocol has been reviewed and approved by our local institutional review board. Results of the pilot trial and subsequent main trial will be submitted for publication in a peer-reviewed journal. NCT02466698; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Polyethylene glycol intestinal lavage in addition to usual antibiotic treatment for severe Clostridium difficile colitis: a randomised controlled pilot study

PubMed Central

McCreery, Greig; Jones, Philip M; Kidane, Biniam; DeMelo, Vanessa

2017-01-01

Introduction Clostridium difficile infections (CDI) are common, costly and potentially life threatening. Most CDI will respond to antibiotic therapy, but 3%–10% of all patients with CDI will progress to a severe, life-threatening course. Complete removal of the large bowel is indicated for severe CDI. However, the 30-day mortality following surgical intervention for severe CDI ranges from 20% to 70%. A less invasive approach using surgical faecal diversion and direct colonic lavage with polyethylene glycol (PEG) and vancomycin has demonstrated a relative mortality reduction of approximately 50%. As an alternative to these operative approaches, we propose to treat patients with bedside intestinal lavage with PEG and vancomycin instillation via nasojejunal tube, in addition to usual antibiotic management. Preliminary data collected by our research group are encouraging. Methods and analysis We will conduct a 1-year, single-centre, pilot randomised controlled trial to study this new treatment strategy for patients with severe CDI and additional risk factors for fulminant or complicated infection. After informed consent, patients with severe-complicated CDI without immediate indication for surgery will be randomised to either usual antibiotic treatment or usual antibiotic treatment with the addition of 8 L of PEG lavage via nasojejunal tube. This pilot trial will evaluate our eligibility and enrolment rate, protocol compliance and adverse event rates and provide further data to inform a more robust sample size calculation and protocol modifications for a definitive multicentre trial design. Based on historical data, we anticipate enrolling approximately 24 patients during the 1-year pilot study period. As a pilot study, data will be reported in aggregate. Between-group differences will be assessed in a blinded fashion for evidence of harm, and to further refine our sample size calculation. Ethics and dissemination This study protocol has been reviewed and approved by our local institutional review board. Results of the pilot trial and subsequent main trial will be submitted for publication in a peer-reviewed journal. Trial registration number NCT02466698; Pre-results. PMID:28760801

Economic evaluation of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection in Australia.

PubMed

Merlo, Gregory; Graves, Nicholas; Brain, David; Connelly, Luke B

2016-12-01

Clostridium difficile is the most common cause of hospital-acquired diarrhea in Australia. In 2013, a randomized controlled trial demonstrated the effectiveness of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The aim of this study is to evaluate the cost-effectiveness of fecal microbiota transplantation-via either nasoduodenal or colorectal delivery-compared with vancomycin for the treatment of recurrent CDI in Australia. A Markov model was developed to compare the cost-effectiveness of fecal microbiota transplantation compared with standard antibiotic therapy. A literature review of clinical evidence informed the structure of the model and the choice of parameter values. Clinical effectiveness was measured in terms of quality-adjusted life years. Uncertainty in the model was explored using probabilistic sensitivity analysis. Both nasoduodenal and colorectal FMT resulted in improved quality of life and reduced cost compared with vancomycin. The incremental effectiveness of either FMT delivery compared with vancomycin was 1.2 (95% CI: 0.1, 2.3) quality-adjusted life years, or 1.4 (95% CI: 0.4, 2.4) life years saved. Treatment with vancomycin resulted in an increased cost of AU$4094 (95% CI: AU$26, AU$8161) compared with nasoduodenal delivery of FMT and AU$4045 (95% CI: -AU$33, AU$8124) compared with colorectal delivery. The mean difference in cost between colorectal and nasoduodenal FMT was not significant. If FMT, rather than vancomycin, became standard care for recurrent CDI in Australia, the estimated national healthcare savings would be over AU$4000 per treated person, with a substantial increase in quality of life. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Novel Riboswitch-Binding Flavin Analog That Protects Mice against Clostridium difficile Infection without Inhibiting Cecal Flora

PubMed Central

Megyola, Cynthia; Plummer, Mark; Osterman, David; O'Connell, Tim; Aristoff, Paul; Quinn, Cheryl; Chrusciel, R. Alan; Poel, Toni J.; Schostarez, Heinrich J.; Stewart, Catherine A.; Walker, Daniel P.; Wuts, Peter G. M.

2015-01-01

Novel mechanisms of action and new chemical scaffolds are needed to rejuvenate antibacterial drug discovery, and riboswitch regulators of bacterial gene expression are a promising class of targets for the discovery of new leads. Herein, we report the characterization of 5-(3-(4-fluorophenyl)butyl)-7,8-dimethylpyrido[3,4-b]quinoxaline-1,3(2H,5H)-dione (5FDQD)—an analog of riboflavin that was designed to bind riboswitches that naturally recognize the essential coenzyme flavin mononucleotide (FMN) and regulate FMN and riboflavin homeostasis. In vitro, 5FDQD and FMN bind to and trigger the function of an FMN riboswitch with equipotent activity. MIC and time-kill studies demonstrated that 5FDQD has potent and rapidly bactericidal activity against Clostridium difficile. In C57BL/6 mice, 5FDQD completely prevented the onset of lethal antibiotic-induced C. difficile infection (CDI). Against a panel of bacteria representative of healthy bowel flora, the antibacterial selectivity of 5FDQD was superior to currently marketed CDI therapeutics, with very little activity against representative strains from the Bacteroides, Lactobacillus, Bifidobacterium, Actinomyces, and Prevotella genera. Accordingly, a single oral dose of 5FDQD caused less alteration of culturable cecal flora in mice than the comparators. Collectively, these data suggest that 5FDQD or closely related analogs could potentially provide a high rate of CDI cure with a low likelihood of infection recurrence. Future studies will seek to assess the role of FMN riboswitch binding to the mechanism of 5FDQD antibacterial action. In aggregate, our results indicate that riboswitch-binding antibacterial compounds can be discovered and optimized to exhibit activity profiles that merit preclinical and clinical development as potential antibacterial therapeutic agents. PMID:26169403

Antimicrobial Susceptibility Patterns of Clostridium difficile Isolates from Family Dairy Farms.

PubMed

Bandelj, P; Golob, M; Ocepek, M; Zdovc, I; Vengust, M

2017-05-01

A significant risk factor for developing Clostridium difficile infection (CDI) in humans and animals is associated with the antimicrobial use. It has often been hypothesized that farm animals could be the source for human infection with Clostridium difficile (CD). In the European Union, family-run dairy farms are the predominant farming model, which are more interlinked within the community compared to large-scale intensive dairy or beef farms. Therefore, it is important to investigate antimicrobial susceptibility patterns of CD in such environment. A total of 159 CD isolates from 20 family dairy farms were tested with a customized broth microdilution plate for their antimicrobial resistance. Seventeen antimicrobials were selected (amoxicillin, ceftriaxone, clindamycin, daptomycin, erythromycin, fusidic acid, imipenem, levofloxacin, linezolid, metronidazole, moxifloxacin, oxacillin, rifampicin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole and vancomycin), which are commonly used for treatment of CDI in veterinary and human medicine, or were previously applied in CD epidemiological studies. Antimicrobials, which are used for treatment of CDI in humans (metronidazole, vancomycin, fusidic acid, tigecycline, linezolid) inhibited CD growth in vitro. Most CD isolates were resistant to erythromycin (93.1%), daptomycin (69.2%) and clindamycin (46.5%). High multiple-resistance was found in CD ribotype 012 (n = 5, 100%), some CD SLO 060 (n = 4, 25%) and one CD 033 (n = 1, 1.1%). High multiple-resistance in this study was linked with CD ribotypes and not with the origin of CD. The low prevalence of these ribotypes (6.3%; 10/159) indicates that family-run dairy farms are an unlikely source of CD with multiple-resistance to antimicrobials. © 2016 Blackwell Verlag GmbH.

Treatment of recurrent Clostridium difficile infection: a systematic review

PubMed Central

O'Horo, J. C.; Jindai, K.; Kunzer, B.; Safdar, N.

2014-01-01

Background Clostridium difficile infection (CDI) recurs in nearly one-third of patients who develop an initial infection. Recurrent CDI (RCDI) is associated with considerable morbidity, mortality, and cost. Treatment for RCDI has not been not well examined. Methods A systematic review. Results Sixty-four articles were identified evaluating eight different treatment approaches: metronidazole, vancomycin, fidaxomicin, nitazoxanide, rifampin, immunoglobulins, probiotics, and fecal bacteriotherapy. The meta-analysis found vancomycin to have a similar efficacy to metronidazole, although studies used varying doses and durations of therapy. Fidaxomicin was slightly more efficacious than vancomycin, though the number of studies was small. Good evidence for probiotics was limited. Fecal bacteriotherapy was found to be highly efficacious in a single randomized trial. Conclusion Metronidazole and vancomycin have good evidence for use in RCDI but heterogeneity in treatment duration and dose precludes robust conclusions. Fidaxomicin may have a role in treatment, but evidence is limited to subgroup analyses. Fecal bacteriotherapy was the most efficacious. Saccharomyces boulardii may have a role as adjunctive treatment. PMID:23839210

The Need for European Surveillance of CDI.

PubMed

Wiuff, Camilla; Banks, A-Lan; Fitzpatrick, Fidelma; Cottom, Laura

2018-01-01

Since the turn of the millennium, the epidemiology of Clostridium difficile infection (CDI) has continued to challenge. Over the last decade there has been a growing awareness that improvements to surveillance are needed. The increasing rate of CDI and emergence of ribotype 027 precipitated the implementation of mandatory national surveillance of CDI in the UK. Changes in clinical presentation, severity of disease, descriptions of new risk factors and the occurrence of outbreaks all emphasised the importance of early diagnosis and surveillance.However a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has lead to the underestimation of CDI and impeded comparison between countries. These inconsistencies have prevented the true burden of disease from being appreciated.Acceptance that a multi-country surveillance programme and optimised diagnostic strategies are required not only to detect and control CDI in Europe, but for a better understanding of the epidemiology, has built the foundations for a more robust, unified surveillance. The concerted efforts of the European Centre for Disease Prevention and Control (ECDC) CDI networks, has lead to the development of an over-arching long-term CDI surveillance strategy for 2014-2020. Fulfilment of the ECDC priorities and targets will no doubt be challenging and will require significant investment however the hope is that both a national and Europe-wide picture of CDI will finally be realised.

Efficacy of fecal microbiota transplantation in 2 children with recurrent Clostridium difficile infection and its impact on their growth and gut microbiome.

PubMed

Walia, Ritu; Garg, Shashank; Song, Yang; Girotra, Mohit; Cuffari, Carmen; Fricke, Wolfgang Florian; Dutta, Sudhir K

2014-11-01

Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (<3 years old) who failed available therapeutics for RCDI, but responded remarkably well to FMT. Besides resolution of clinical features of C difficile infection (CDI), FMT administration led to marked improvement in their growth, along with increased microbiota diversity, especially proportion of Bacteroides. Our 2 cases illustrate the efficacy of FMT in children with RCDI and its positive effect on their growth and gut microbiota.

The role of local and systemic cytokines in patients infected with Clostridium difficile.

PubMed

Czepiel, J; Biesiada, G; Brzozowski, T; Ptak-Belowska, A; Perucki, W; Birczynska, M; Jurczyszyn, A; Strzalka, M; Targosz, A; Garlicki, A

2014-10-01

It is widely accepted that the pathogenesis of Clostridium difficile infection (CDI) is multifactorial, dependent on pathogen virulence factors produced by the organism as well as disorders of the gastrointestinal tract, the alteration in intestinal flora and the immune response of the host. In particular, the immune response in the course of CDI and the involvement of cytokines in the pathogenesis of CDI is not fully understood. The aim of our study was to evaluate the relationship between proinflammatory and anti-inflammatory cytokines and the course of CDI in vivo. We prospectively studied 80 patients. Our study group included 40 patients aged 30-87 years (mean age 66.9 years) with CDI hospitalized at Infectious Diseases Department and Gastroenterology and Hepatology Clinic, University Hospital in Cracow, and 40 healthy volunteers aged 24-62 years (mean age 51.1 years). The serum concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and prostaglandin E2 (PGE2) were measured using ELISA assays. Additionally, the routine biochemical parameters were assessed including the following: white blood cells with differential leukocyte count, platelets counts, and blood plasma levels of creatinine, alanine transaminase, and C-reactive protein were determined. We noted a significant increase in the concentration of the following cytokines in the CDI group when compared to the control group: IL-1b (4.7 vs. 3.6 pg/ml), IL-6 (21.0 vs. 0.04 pg/ml), IL-10 (8.5 vs. 0.5 pg/ml), TNF-α (7.1 vs. 0.09 pg/ml). In addition the serum concentration of MPO (1056.0 vs. 498.0 pg/ml), and PGE2 (2036.7 vs. 1492.0 pg/ml) showed a significant increase in CDI patients as compared with control subjects. Most CDI patients did not show any increase in the concentration of IL-8. We did observe a direct relationship between TNF-α and creatinine. The course of CDI is characterized by an initial local inflammatory process followed by a systemic inflammatory response, which manifests clinically as fever, and includes leukocytosis, an increase in the level of neutrophils in the blood, and an increase in the serum concentrations of TNF-α, IL-1β, IL-6, IL-10, MPO and PGE2. Despite the leading role of IL-8 in the local inflammatory process, we postulate TNF-α and IL-6 play a key role in the systemic inflammatory response in CDI, and the plasma TNF-α level seems to act as a major factor of poor prognosis in patients with CDI.

Factors predictive of severe Clostridium difficile infection depend on the definition used.

PubMed

Khanafer, Nagham; Barbut, Frédéric; Eckert, Catherine; Perraud, Michel; Demont, Clarisse; Luxemburger, Christine; Vanhems, Philippe

2016-02-01

Clostridium difficile infection (CDI) produces a variety of clinical presentations ranging from mild diarrhea to severe infection with fulminant colitis, septic shock, and death. Over the past decade, the emergence of the BI/NAP1/027 strain has been linked to higher prevalence and severity of CDI. The guidelines to treat patients with CDI are currently based on severity factors identified in the literature and on expert opinion and have not been systematically evaluated. The objective of this study was to identify factors associated with severe CDI defined according to four different severity definitions (Def): the 2010 SHEA/IDSA guidelines (Def1), the 2014 ESCMID guidelines (Def2), complicated CDI at the end of diarrhea (Def3), and our hospital-specific guidelines (white blood cell (WBC) count ≥15 × 10(9)/L, serum creatinine concentration >50% above baseline, pseudomembranous colitis, megacolon, intestinal perforation, or septic shock requiring intensive care unit admission. A three-year cohort study was conducted in a university hospital in Lyon, France. All hospitalized (≥48 h) patients ≥18 years old, suffering from CDI, and agreeing to participate were included. Patients were followed-up for 60 days after CDI diagnosis. After bivariate regression analyses, factors associated with severe CDI during the course of disease were identified by a multivariate logistic regression. Statistical significance was reached with a two-sided p-value <0.05. 233 CDI patients diagnosed between 2011 and 2014 were included for a mean incidence rate of 2.15 cases/1000 hospitalized patients or 3.16 cases/10,000 patient days. Mean age was 65.3 years and 52.5% were men. Death occurred in 37 patients (15.9%) within 60 days of diagnosis. Death was related to CDI in 15 patients (40.5%). Frequency of severe CDI ranges from 11.6% to 59.2% depending on the case-definition. Factors independently associated with severe CDI were: age ≥68 years, male gender, renal disease, and serum albumin <30 g/L according to Def1 (n = 106, 45.5%); exposure to antivirals in the previous 4 weeks, renal disease, and blood neutrophils >7,5 × 10(9)/L in patients with Def2 (n = 138, 59.2%); abdominal pain, serum albumin <30 g/L, and WBC >10 × 10(9)/L according to Def3 (n = 27, 11.6%); age ≥68 years, renal disease, serum albumin <30 g/L, serum lactate dehydrogenase >248 IU/L, and blood neutrophils >7,5 × 10(9)/L were associated with severe CDI in patients with Def4 (n = 113, 48.5%). Our results indicate that appropriate case definition is needed for characterizing patients at risk of developing severe CDI. Our study suggest that serum albumin and the presence of renal disease, associated with severe CDI in three definitions, may be useful for identifying patients at risk of a poor outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults.

PubMed

Nelson, Richard L; Suda, Katie J; Evans, Charlesnika T

2017-03-03

Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhoea and colitis. This review is an update of a previously published Cochrane review. The aim of this review is to investigate the efficacy and safety of antibiotic therapy for C. difficile-associated diarrhoea (CDAD), or C. difficile infection (CDI), being synonymous terms. We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD Group Specialized Trials Register from inception to 26 January 2017. We also searched clinicaltrials.gov and clinicaltrialsregister.eu for ongoing trials. Only randomised controlled trials assessing antibiotic treatment for CDI were included in the review. Three authors independently assessed abstracts and full text articles for inclusion and extracted data. The risk of bias was independently rated by two authors. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We pooled data using a fixed-effect model, except where significant heterogeneity was detected, at which time a random-effects model was used. The following outcomes were sought: sustained symptomatic cure (defined as initial symptomatic response and no recurrence of CDI), sustained bacteriologic cure, adverse reactions to the intervention, death and cost. Twenty-two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy-two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy-one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly-seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo-controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co-morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co-morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest.

Laboratory and Clinical features of EIA Toxin-positive and EIA Toxin-negative Community-acquired Clostridium difficile Infection.

PubMed

Patel, Hiren; Randhawa, Jeewanjot; Nanavati, Sushant; Marton, L Randy; Baddoura, Walid J; DeBari, Vincent A

2015-01-01

Studies have described the clinical course of patients with Clostridium difficile infection (CDI) with positive enzyme immunoassay (EIA) for toxins A and B. Limited information is available for the patients with negative EIA but positive for the toxin B gene (TcdB) by the PCR. The aim of our study is to determine if there are any differences that exist among the clinical and laboratory parameters in the patients tested to be positive by EIA for toxin and those who were negative. This is a retrospective cohort study conducted in a 700-bed teaching hospital. We reviewed charts of the patients with presumptive CDI between January 2006 and July 2013. We divided these patients into two groups, EIA-positive and EIA-negative, based on result of EIA for toxins A and B and the requirement for a positive PCR analysis of the TcdB gene. The EIA-positive group had significantly higher white blood cell counts (p<0.001), with a significantly greater percentage of bands (p<0.0001). Albumin and total protein both exhibit significantly (p<0.0001, both comparisons) lower values in the EIA-positive group. Among clinical findings, the EIA-positive group had significantly longer length of hospital stay (p=0.010). These data suggest that an infection with an EIA-negative strain of C. difficile presents laboratory markers closer to those of healthy subjects and clinical features suggesting considerably less severe than infection with EIA-positive C. difficile. © 2015 by the Association of Clinical Scientists, Inc.

A Mixture of Functionally Oligoclonal Humanized Monoclonal Antibodies That Neutralize Clostridium difficile TcdA and TcdB with High Levels of In Vitro Potency Shows In Vivo Protection in a Hamster Infection Model

PubMed Central

Davies, Nicola L.; Compson, Joanne E.; MacKenzie, Brendon; O'Dowd, Victoria L.; Oxbrow, Amanda K. F.; Heads, James T.; Turner, Alison; Sarkar, Kaushik; Dugdale, Sarah L.; Jairaj, Mark; Christodoulou, Louis; Knight, David E. O.; Cross, Amanda S.; Hervé, Karine J. M.; Tyson, Kerry L.; Hailu, Hanna; Doyle, Carl B.; Ellis, Mark; Kriek, Marco; Cox, Matthew; Page, Matthew J. T.; Moore, Adrian R.; Lightwood, Daniel J.

2013-01-01

Clostridium difficile infections are a major cause of antibiotic-associated diarrhea in hospital and care facility patients. In spite of the availability of effective antibiotic treatments, C. difficile infection (CDI) is still a major cause of patient suffering, death, and substantial health care costs. Clostridium difficile exerts its major pathological effects through the actions of two protein exotoxins, TcdA and TcdB, which bind to and disrupt gut tissue. Antibiotics target the infecting bacteria but not the exotoxins. Administering neutralizing antibodies against TcdA and TcdB to patients receiving antibiotic treatment might modulate the effects of the exotoxins directly. We have developed a mixture of three humanized IgG1 monoclonal antibodies (MAbs) which neutralize TcdA and TcdB to address three clinical needs: reduction of the severity and duration of diarrhea, reduction of death rates, and reduction of the rate of recurrence. The UCB MAb mixture showed higher potency in a variety of in vitro binding and neutralization assays (∼10-fold improvements), higher levels of protection in a hamster model of CDI (82% versus 18% at 28 days), and higher valencies of toxin binding (12 versus 2 for TcdA and 3 versus 2 for TcdB) than other agents in clinical development. Comparisons of the MAb properties also offered some insight into the potential relative importance of TcdA and TcdB in the disease process. PMID:23324518

Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in a Pediatric Heart Transplant Patient.

PubMed

Flannigan, Kyle L; Rajbar, Taylor; Moffat, Andrew; McKenzie, Leanna S; Dicke, Frank; Rioux, Kevin; Workentine, Matthew L; Louie, Thomas J; Hirota, Simon A; Greenway, Steven C

2017-01-01

The microbiome is increasingly recognized as an important influence on human health and many of the comorbidities that affect patients after solid organ transplantation (SOT) have been shown to involve changes in gut bacterial populations. Thus, microbiome changes in an individual patient may have important health implications after SOT but this area remains understudied. We describe changes in the composition of the fecal microbiome from a pediatric heart transplant recipient before and >2.5 years after he underwent repeated fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI). With both documented episodes of CDI, there was marked loss of bacterial diversity with overgrowth of Proteobacteria (>98.9% of phyla identified) associated with symptomatic colitis that was corrected after FMT. We hypothesize that a second CDI occurring after FMT was related to incomplete restoration of normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae . Following the second FMT, there was a gradual shift in gut bacterial composition coincident with the recipient developing lymphonodular hyperplasia of the colon and painless hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF). This case documents dynamic changes in the bacterial microbiome after FMT and suggests that MMF may influence the gut microbiome with consequences for the patient.

Microbial taxonomic and metabolic alterations during faecal microbiota transplantation to treat Clostridium difficile infection.

PubMed

Kellingray, Lee; Gall, Gwénaëlle Le; Defernez, Marianne; Beales, Ian L P; Franslem-Elumogo, Ngozi; Narbad, Arjan

2018-05-07

This study aimed to examine changes to the microbiota composition and metabolic profiles of seven patients with recurrent Clostridium difficile infection (rCDI), following treatment with faecal microbiota transplant (FMT). 16S rDNA sequencing and 1 H NMR were performed on faecal samples from the patients (pre-, post-FMT, and follow-up) and the associated donor samples. Sparse partial-least-square analysis was used to identify correlations between the two datasets. The patients' microbiota post-FMT tended to shift towards the donor microbiota, specifically through proportional increases of Bacteroides, Blautia, and Ruminococcus, and proportional decreases of Enterococcus, Escherichia, and Klebsiella. However, although cured of infection, one patient, who suffers from chronic alcohol abuse, retained the compositional characteristics of the pre-FMT microbiota. Following FMT, increased levels of short-chain fatty acids, particularly butyrate and acetate, were observed in all patients. Sparse partial-least-square analysis confirmed a positive correlation between butyrate and Bacteroides, Blautia, and Ruminococcus, with a negative correlation between butyrate and Klebsiella and Enterococcus. Clear differences were observed in the microbiota composition and metabolic profiles between donors and rCDI patients, which were largely resolved in patients following FMT. Increased levels of butyrate appear to be a factor associated with resolution of rCDI. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection.

PubMed

Shea, Katherine M; Hobbs, Athena L V; Jaso, Theresa C; Bissett, Jack D; Cruz, Christopher M; Douglass, Elizabeth T; Garey, Kevin W

2017-06-01

Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P < 0.0001) were associated with decreased utilization. In addition, the CDI rates decreased significantly ( P = 0.044) from preintervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean monthly CDI cases/10,000 PD decreased from 4.0 (SD = 2.1) preintervention to 2.2 (SD = 1.35) postrestriction. A significant increase in appropriate respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P < 0.001), as well as in those receiving two or more doses (47/65 [72%] versus 67/191 [35%]; P < 0.001). A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system. Copyright © 2017 American Society for Microbiology.

Identification of patients at high risk for Clostridium difficile infection: development and validation of a risk prediction model in hospitalized patients treated with antibiotics.

PubMed

van Werkhoven, C H; van der Tempel, J; Jajou, R; Thijsen, S F T; Diepersloot, R J A; Bonten, M J M; Postma, D F; Oosterheert, J J

2015-08-01

To develop and validate a prediction model for Clostridium difficile infection (CDI) in hospitalized patients treated with systemic antibiotics, we performed a case-cohort study in a tertiary (derivation) and secondary care hospital (validation). Cases had a positive Clostridium test and were treated with systemic antibiotics before suspicion of CDI. Controls were randomly selected from hospitalized patients treated with systemic antibiotics. Potential predictors were selected from the literature. Logistic regression was used to derive the model. Discrimination and calibration of the model were tested in internal and external validation. A total of 180 cases and 330 controls were included for derivation. Age >65 years, recent hospitalization, CDI history, malignancy, chronic renal failure, use of immunosuppressants, receipt of antibiotics before admission, nonsurgical admission, admission to the intensive care unit, gastric tube feeding, treatment with cephalosporins and presence of an underlying infection were independent predictors of CDI. The area under the receiver operating characteristic curve of the model in the derivation cohort was 0.84 (95% confidence interval 0.80-0.87), and was reduced to 0.81 after internal validation. In external validation, consisting of 97 cases and 417 controls, the model area under the curve was 0.81 (95% confidence interval 0.77-0.85) and model calibration was adequate (Brier score 0.004). A simplified risk score was derived. Using a cutoff of 7 points, the positive predictive value, sensitivity and specificity were 1.0%, 72% and 73%, respectively. In conclusion, a risk prediction model was developed and validated, with good discrimination and calibration, that can be used to target preventive interventions in patients with increased risk of CDI. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Analysis of Clostridium difficile infections after cardiac surgery: epidemiologic and economic implications from national data.

PubMed

Flagg, Andrew; Koch, Colleen G; Schiltz, Nicholas; Chandran Pillai, Aiswarya; Gordon, Steven M; Pettersson, Gösta B; Soltesz, Edward G

2014-11-01

Clostridium difficile infections (CDIs) have increased during the past 2 decades, especially among cardiac surgical patients, who share many of the comorbidity risk factors for CDI. Our objectives were to use a large national database to identify the regional-, hospital-, patient-, and procedure-level risk factors for CDI; and determine mortality, resource usage, and cost of CDIs in cardiac surgery. Using the Nationwide Inpatient Sample database, we identified 349,122 patients who had undergone coronary artery bypass, valve, or thoracic-aortic surgery from 2004 to 2008. Of these, 2581 (0.75%) had been diagnosed with CDI. Multivariable regression analysis and the propensity method were used for risk adjustment. Compared with the West, CDIs were more likely to occur in the Northeast (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47) and Midwest (OR, 1.27, 95% CI, 1.11-1.46) and less likely in the South (OR, 0.80; 95% CI, 0.70-0.90). Medium-size hospitals (OR, 0.88; 95% CI, 0.78-0.99) had a lower risk of CDI than did large hospitals. Older age (>75 years; OR, 2.59; 95% CI, 1.93-3.49), longer preoperative length of stay (OR, 1.51; 95% CI, 1.43-1.60), Medicare (OR, 1.21; 95% CI, 1.05-1.39) and Medicaid (OR, 1.60; 95% CI, 1.31-1.96) coverage, and more comorbidities were associated with CDI. Among the matched pairs, patients with CDIs had greater mortality (302 [12%] vs 187 [7.2%], P<.001), a longer median length of stay (21 vs 11 days, P<.001), and greater median hospital charges ($193,330 vs $112,245, P<.001). The cumulative incremental cost of CDIs was an estimated $212 million annually. Our results have shown that CDI is associated with increased morbidity and resource usage. Additional work is needed to better understand the complex interplay among regional-, hospital-, and patient-level factors. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Enhanced Cleaning and Education to Prevent Transmission of Clostridium difficile in Pediatrics

PubMed Central

Aslam, Anoshé; Melendez, Giselle; Wang, Min; Stell, Frederic; Kelly, Paulette; Killinger, James; Dannaoui, Aimee; Riedman, Scott; Lopez, Ruben; Ackerman, Jill; Chou, Alexander; Wexler, Leonard; Smith, David; Sanchez, Stacy; Robilotti, Elizabeth; Kamboj, Mini; Eagan, Janet

2017-01-01

Abstract Background Transmission of healthcare-associated Clostridium difficile infection (HA-CDI) has been shown to occur directly or indirectly through a contaminated environment. At a tertiary-care cancer center, HA-CDI rates were higher for pediatric units than for other general oncology units. To address the problem, a multidisciplinary team, including Infection Control, Nursing, and Environmental Services (EVS), was convened and identified refusals and room clutter as barriers to proper cleaning of rooms on the unit. Aim: The aim of this study seeks to reduce HA-CDI in the inpatient pediatrics setting through environmental and educational interventions. Methods In the first phase of the study from February to April 2016, a baseline assessment of prevalent environmental disinfection practices was made among Nursing, EVS, Physicians, and Patient Representatives. Based on this feedback, the following were implemented during Phase 2, from June through October 2016: 1) Unit-wide disinfection with bleach twice a day including common and high traffic areas; 2) Initiation of a “preferred time for cleaning” program to engage families; 3) Enhanced visitor and family education on PPE use; 4) Creation of a communication plan in case of refusal to clean rooms; and 5) Dedicated use of diaper scales. Results During the first phase of the study, the following barriers to cleaning were identified: 1) High refusal rate as cleaning was perceived as inconvenient by families due to timing; 2) Common perception among EVS staff that multiple requests for cleaning the room may appear intrusive to the families; 3) Excessive clutter in the room; 4) Lack of education regarding PPE use; and 5) Shared equipment for diapers. To overcome these barriers, several interventions as outlined in methods were implemented. In Phase 2, there were 0 cases of HA-CDI identified in pediatric patients starting in July through October, 2016. Conclusion Control of CDI on pediatric units poses unique challenges. Engagement of key stakeholders is essential to identify and meet these challenges and to devise effective strategies that will ultimately lead to reduced hospital-based transmission of CDI. Disclosures All authors: No reported disclosures.