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Sample records for clostridium sordellii infection

  1. Foot Infection by Clostridium sordellii: Case Report and Review of 15 Cases in France

    PubMed Central

    Sautereau, Jean; Le Coustumier, Alain; Mory, Francine; Bouchier, Christiane; Popoff, Michel-R.

    2015-01-01

    We report a case of foot infection by Clostridium sordellii and review 15 human infections registered at a Reference Center in France during the period 1998 to 2011. All strains were found nontoxigenic, lacking the lethal toxin gene coding for TcsL. Like Clostridium septicum, several C. sordellii infections were associated with intestinal neoplasms. PMID:25609723

  2. Foot infection by Clostridium sordellii: case report and review of 15 cases in France.

    PubMed

    Bouvet, Philippe; Sautereau, Jean; Le Coustumier, Alain; Mory, Francine; Bouchier, Christiane; Popoff, Michel-R

    2015-04-01

    We report a case of foot infection by Clostridium sordellii and review 15 human infections registered at a Reference Center in France during the period 1998 to 2011. All strains were found nontoxigenic, lacking the lethal toxin gene coding for TcsL. Like Clostridium septicum, several C. sordellii infections were associated with intestinal neoplasms. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Clostridium Sordellii Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.109 Clostridium Sordellii Bacterin-Toxoid. Clostridium Sordellii Bacterin-Toxoid shall be produced from a culture of Clostridium sordellii which has...

  4. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Clostridium Sordellii Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.109 Clostridium Sordellii Bacterin-Toxoid. Clostridium Sordellii Bacterin-Toxoid shall be produced from a culture of Clostridium sordellii which has...

  5. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Clostridium Sordellii Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.109 Clostridium Sordellii Bacterin-Toxoid. Clostridium Sordellii Bacterin-Toxoid shall be produced from a culture of Clostridium sordellii which has...

  6. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Clostridium Sordellii Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.109 Clostridium Sordellii Bacterin-Toxoid. Clostridium Sordellii Bacterin-Toxoid shall be produced from a culture of Clostridium sordellii which has...

  7. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Clostridium Sordellii Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.109 Clostridium Sordellii Bacterin-Toxoid. Clostridium Sordellii Bacterin-Toxoid shall be produced from a culture of Clostridium sordellii which has...

  8. Identification and Characterization of Clostridium sordellii Toxin Gene Regulator

    PubMed Central

    Sirigi Reddy, Apoorva Reddy; Girinathan, Brintha Parasumanna; Zapotocny, Ryan

    2013-01-01

    Toxigenic Clostridium sordellii causes uncommon but highly lethal infections in humans and animals. Recently, an increased incidence of C. sordellii infections has been reported in women undergoing obstetric interventions. Pathogenic strains of C. sordellii produce numerous virulence factors, including sordellilysin, phospholipase, neuraminidase, and two large clostridial glucosylating toxins, TcsL and TcsH. Recent studies have demonstrated that TcsL toxin is an essential virulence factor for the pathogenicity of C. sordellii. In this study, we identified and characterized TcsR as the toxin gene (tcsL) regulator in C. sordellii. High-throughput sequencing of two C. sordellii strains revealed that tcsR lies within a genomic region that encodes TcsL, TcsH, and TcsE, a putative holin. By using ClosTron technology, we inactivated the tcsR gene in strain ATCC 9714. Toxin production and tcsL transcription were decreased in the tcsR mutant strain. However, the complemented tcsR mutant produced large amounts of toxins, similar to the parental strain. Expression of the Clostridium difficile toxin gene regulator tcdR also restored toxin production to the C. sordellii tcsR mutant, showing that these sigma factors are functionally interchangeable. PMID:23873908

  9. Identification and characterization of Clostridium sordellii toxin gene regulator.

    PubMed

    Sirigi Reddy, Apoorva Reddy; Girinathan, Brintha Parasumanna; Zapotocny, Ryan; Govind, Revathi

    2013-09-01

    Toxigenic Clostridium sordellii causes uncommon but highly lethal infections in humans and animals. Recently, an increased incidence of C. sordellii infections has been reported in women undergoing obstetric interventions. Pathogenic strains of C. sordellii produce numerous virulence factors, including sordellilysin, phospholipase, neuraminidase, and two large clostridial glucosylating toxins, TcsL and TcsH. Recent studies have demonstrated that TcsL toxin is an essential virulence factor for the pathogenicity of C. sordellii. In this study, we identified and characterized TcsR as the toxin gene (tcsL) regulator in C. sordellii. High-throughput sequencing of two C. sordellii strains revealed that tcsR lies within a genomic region that encodes TcsL, TcsH, and TcsE, a putative holin. By using ClosTron technology, we inactivated the tcsR gene in strain ATCC 9714. Toxin production and tcsL transcription were decreased in the tcsR mutant strain. However, the complemented tcsR mutant produced large amounts of toxins, similar to the parental strain. Expression of the Clostridium difficile toxin gene regulator tcdR also restored toxin production to the C. sordellii tcsR mutant, showing that these sigma factors are functionally interchangeable.

  10. Clostridium novyi, sordellii, and tetani: mechanisms of disease.

    PubMed

    Aronoff, David M

    2013-12-01

    Clostridia represent a diverse group of spore-forming gram positive anaerobes that include several pathogenic species. In general, diseases caused by clostridia are a result of intoxication of the infected host. Thus, clostridial toxins have been targeted for diagnostic, therapeutic, and preventive strategies against infection. Studying the mechanisms of action of clostridial toxins has not only shed light on the pathogenesis of infection but has provided important new insights into cell biology and immunology. A primary purpose of this manuscript is to provide a succinct review on the mechanisms of disease caused by intoxication by the pathogens Clostridium tetani, Clostridium novyi, and Clostridium sordellii.

  11. Comparative genomic and phenomic analysis of Clostridium difficile and Clostridium sordellii, two related pathogens with differing host tissue preference.

    PubMed

    Scaria, Joy; Suzuki, Haruo; Ptak, Christopher P; Chen, Jenn-Wei; Zhu, Yongzhang; Guo, Xiao-Kui; Chang, Yung-Fu

    2015-06-10

    Clostridium difficile and C. sordellii are two anaerobic, spore forming, gram positive pathogens with a broad host range and the ability to cause lethal infections. Despite strong similarities between the two Clostridial strains, differences in their host tissue preference place C. difficile infections in the gastrointestinal tract and C. sordellii infections in soft tissues. In this study, to improve our understanding of C. sordellii and C. difficile virulence and pathogenesis, we have performed a comparative genomic and phenomic analysis of the two. The global phenomes of C. difficile and C. sordellii were compared using Biolog Phenotype microarrays. When compared to C. difficile, C. sordellii was found to better utilize more complex sources of carbon and nitrogen, including peptides. Phenotype microarray comparison also revealed that C. sordellii was better able to grow in acidic pH conditions. Using next generation sequencing technology, we determined the draft genome of C. sordellii strain 8483 and performed comparative genome analysis with C. difficile and other Clostridial genomes. Comparative genome analysis revealed the presence of several enzymes, including the urease gene cluster, specific to the C. sordellii genome that confer the ability of expanded peptide utilization and survival in acidic pH. The identified phenotypes of C. sordellii might be important in causing wound and vaginal infections respectively. Proteins involved in the metabolic differences between C. sordellii and C. difficile should be targets for further studies aimed at understanding C. difficile and C. sordellii infection site specificity and pathogenesis.

  12. Structural Characterization of Clostridium sordellii Spores of Diverse Human, Animal, and Environmental Origin and Comparison to Clostridium difficile Spores.

    PubMed

    Rabi, Rebecca; Turnbull, Lynne; Whitchurch, Cynthia B; Awad, Milena; Lyras, Dena

    2017-01-01

    Clostridium sordellii is an often-lethal bacterium causing human and animal disease. Crucial to the infectious cycle of C. sordellii is its ability to produce spores, which can germinate into toxin-producing vegetative bacteria under favorable conditions. However, structural details of the C. sordellii spore are lacking. Here, we used a range of electron microscopy techniques together with superresolution optical microscopy to characterize the C. sordellii spore morphology with an emphasis on the exosporium. The C. sordellii spore is made up of multiple layers with the exosporium presenting as a smooth balloon-like structure that is open at the spore poles. Focusing on the outer spore layers, we compared the morphologies of C. sordellii spores derived from different strains and determined that there is some variation between the spores, most notably with spores of some strains having tubular appendages. Since Clostridium difficile is a close relative of C. sordellii, their spores were compared by electron microscopy and their exosporia were found to be distinctly different from each other. This study therefore provides new structural details of the C. sordellii spore and offers insights into the physical structure of the exosporium across clostridial species. IMPORTANCEClostridium sordellii is a significant pathogen with mortality rates approaching 100%. It is the bacterial spore that is critical in initiating infection and disease. An understanding of spore structures as well as spore morphology across a range of strains may lead to a better understanding of C. sordellii infection and disease. However, the structural characteristics of the C. sordellii spores are limited. In this work, we have addressed this lack of detail and characterized the C. sordellii spore morphology. The use of traditional and advanced microscopy techniques has provided detailed new observations of C. sordellii spore structural features, which serve as a reference point for

  13. Vaginal and Rectal Clostridium sordellii and Clostridium perfringens Presence Among Women in the United States.

    PubMed

    Chong, Erica; Winikoff, Beverly; Charles, Dyanna; Agnew, Kathy; Prentice, Jennifer L; Limbago, Brandi M; Platais, Ingrida; Louie, Karmen; Jones, Heidi E; Shannon, Caitlin

    2016-02-01

    To characterize the presence of Clostridium sordellii and Clostridium perfringens in the vagina and rectum, identify correlates of presence, and describe strain diversity and presence of key toxins. We conducted an observational cohort study in which we screened a diverse cohort of reproductive-aged women in the United States up to three times using vaginal and rectal swabs analyzed by molecular and culture methods. We used multivariate regression models to explore predictors of presence. Strains were characterized by pulsed-field gel electrophoresis and tested for known virulence factors by polymerase chain reaction assays. Of 4,152 participants enrolled between 2010 and 2013, 3.4% (95% confidence interval [CI] 2.9-4.0) were positive for C sordellii and 10.4% (95% CI 9.5-11.3) were positive for C perfringens at baseline. Among the 66% with follow-up data, 94.7% (95% CI 88.0-98.3) of those positive for C sordellii and 74.4% (95% CI 69.0-79.3) of those positive for C perfringens at baseline were negative at follow-up. At baseline, recent gynecologic surgery was associated with C sordellii presence, whereas a high body mass index was associated with C perfringens presence in adjusted models. Two of 238 C sordellii isolates contained the lethal toxin gene, and none contained the hemorrhagic toxin gene. Substantial strain diversity was observed in both species with few clusters and no dominant clones identified. The relatively rare and transient nature of C sordellii and C perfringens presence in the vagina and rectum makes it inadvisable to use any screening or prophylactic approach to try to prevent clostridial infection. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01283828.

  14. Lethal toxin is a critical determinant of rapid mortality in rodent models of Clostridium sordellii endometritis.

    PubMed

    Hao, Yibai; Senn, Tennille; Opp, Judy S; Young, Vincent B; Thiele, Teri; Srinivas, Geetha; Huang, Steven K; Aronoff, David M

    2010-04-01

    The toxigenic anaerobe Clostridium sordellii is an uncommon but highly lethal cause of human infection and toxic shock syndrome, yet few studies have addressed its pathogenetic mechanisms. To better characterize the microbial determinants of rapid death from infection both in vitro and in vivo studies were performed to compare a clinical strain of C. sordellii (DA-108), isolated from a patient who survived a disseminated infection unaccompanied by toxic shock syndrome, to a virulent reference strain (ATCC9714). Rodent models of endometrial and peritoneal infection with C. sordellii ATCC9714 were rapidly lethal, while infections with DA-108 were not. Extensive genetic and functional comparisons of virulence factor and toxin expression between these two bacterial strains yielded many similarities, with the noted exception that strain DA-108 lacked the tcsL gene, which encodes the large clostridial glucosyltransferase enzyme lethal toxin (TcsL). The targeted removal by immunoprecipitation of TcsL protected animals from death following injection of crude culture supernatants from strain ATCC9714. Injections of a monoclonal anti-TcsL IgG protected animals from death during C. sordellii ATCC9714 infection, suggesting that such an approach might improve the treatment of patients with C. sordellii-induced toxic shock syndrome. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Necrotic Enteritis in Chickens Associated with Clostridium sordellii.

    PubMed

    Rimoldi, Guillermo; Uzal, Francisco; Chin, R P; Palombo, Enzo A; Awad, Milena; Lyras, Dena; Shivaprasad, H L

    2015-09-01

    Three outbreaks of necrotic enteritis-like disease associated with Clostridium sordelii were diagnosed in commercial broiler chicken flocks with 18,000 to 31,000 birds between 18 and 26 days old. Clinical signs in the affected flocks included high mortality up to 2% a day, depression, and diarrhea. The main gross changes included segmental dilation of the small intestine with watery contents, gas, mucoid exudate, and roughened and uneven mucosa, occasionally covered with a pseudomembrane. Microscopic lesions in the small intestine were characterized by extensive areas of coagulative necrosis of the villi, fibrinous exudate in the lumen, and high numbers of large, Gram-positive rods, occasionally containing subterminal spores, seen in the necrotic tissue and lumen. These rods were identified as C. sordellii by immunohistochemistry. Clostridium sordellii was isolated in an almost pure culture from the intestine of affected birds. A retrospective study of commercial broiler chicken and turkey submissions to the California Animal Health and Food Safety Laboratory System revealed that C. sordellii had been isolated from intestinal lesions in outbreaks of necrotic enteritis-like disease in 8 of 39 cases, 5 times together with Clostridium perfringens and 3 times alone. The latter three cases are reported here.

  16. Outbreak of necrotizing fasciitis due to Clostridium sordellii among black-tar heroin users.

    PubMed

    Kimura, Akiko C; Higa, Jeffrey I; Levin, Robert M; Simpson, Gail; Vargas, Yolanda; Vugia, Duc J

    2004-05-01

    In California, black tar heroin (BTH) use among injection drug users (IDUs) has resulted in an increased number of cases of wound botulism due to Clostridium botulinum, tetanus due to Clostridium tetani, and necrotizing soft-tissue infections due to a variety of clostridia. From December 1999 to April 2000, nine IDUs in Ventura County, California, developed necrotizing fasciitis; 4 died. Cultures of wound specimens from 6 case patients yielded Clostridium sordellii. Some of the patients appeared to have the toxic shock syndrome previously reported to be characteristic of toxin-mediated C. sordellii infection, which is characterized by hypotension, marked leukocytosis, and hemoconcentration. The suspected source of this outbreak was contaminated BTH that was injected subcutaneously or intramuscularly ("skin popped"). This outbreak of C. sordellii infection serves as another example of how BTH can potentially serve as a vehicle for transmitting severe and often deadly clostridial infections, and reinforces the need to educate IDUs and clinicians about the risks associated with skin popping of BTH.

  17. Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci.

    PubMed

    Couchman, Edward C; Browne, Hilary P; Dunn, Matt; Lawley, Trevor D; Songer, J Glenn; Hall, Val; Petrovska, Liljana; Vidor, Callum; Awad, Milena; Lyras, Dena; Fairweather, Neil F

    2015-05-16

    Clostridium sordellii can cause severe infections in animals and humans, the latter associated with trauma, toxic shock and often-fatal gynaecological infections. Strains can produce two large clostridial cytotoxins (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile, Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin production remains uncharacterised. Phylogenetic analysis of the genome sequences of 44 strains isolated from human and animal infections in the UK, US and Australia placed the species into four clades. Although all strains originated from animal or clinical disease, only 5 strains contained LCC genes: 4 strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin-positive strains were found within one clade. Where present, tcsL and tcsH were localised in a pathogenicity locus, similar to but distinct from that present in C. difficile. In contrast to C. difficile, where the LCCs are chromosomally localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our data suggest gain and loss of entire toxigenic plasmids in addition to horizontal transfer of the pathogenicity locus. A high quality, annotated sequence of ATCC9714 reveals many putative virulence factors including neuraminidase, phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are highly conserved between all strains studied. Genome analysis of C. sordellii reveals that the LCCs, the major virulence factors, are localised on plasmids. Many strains do not contain the LCC genes; it is probable that in several of these cases the plasmid has been lost upon laboratory subculture. Our data are consistent with LCCs being the primary virulence factors in the majority of infections, but LCC-negative strains may precipitate certain categories of infection. A high quality genome sequence reveals putative virulence factors whose role in virulence can be investigated.

  18. Ulcerative enteritis-like disease associated with Clostridium sordellii in quail.

    PubMed

    Crespo, Rocio; Franca, Monique; Shivaprasad, H L

    2013-09-01

    A natural outbreak of ulcerative enteritis-like disease associated with Clostridium sordellii was diagnosed in two commercial quail flocks. Clinical signs in the quail included anorexia, weakness, and increased mortality in the flocks. Lesions in the intestine were characterized by ulcers covered with fibrinonecrotic exudate in the small intestine and occasional hemorrhages. There were also multifocal pale areas of necrosis in the liver. Clostridium sordellii was isolated from the intestine and liver. A retrospective study of avian cases submitted to the California Animal Health and Food Safety Laboratories revealed that C. sordellii had been isolated in 45 avian submissions, most commonly in chickens and turkeys. In most of these cases the birds were diagnosed with necrotic enteritis, with or without hepatitis. Clostridium sordellii has occasionally been associated with gangrenous dermatitis in poultry, but this is the first report of enteritis in an avian species.

  19. Detection of Clostridium sordellii strains expressing hemorrhagic toxin (TcsH) and implications for diagnostics and regulation of veterinary vaccines.

    PubMed

    Thiele, Teri L; Stuber, Tod P; Hauer, Paul J

    2013-10-17

    Clostridium sordellii is a Gram positive anaerobic bacterium that causes multiple disease syndromes in both humans and animals. As with many clostridial pathogens, toxins contribute to the virulence of C. sordellii. Two large toxins have been identified: a lethal toxin (TcsL) and a hemorrhagic toxin (TcsH) which are similar in structure and function to Clostridium difficile toxin B (TcdB) and toxin A (TcdA), respectively. While TcdA, TcdB, and TcsL have been extensively studied, relatively little is known about TcsH. This study elucidated the TcsH gene sequence using whole genome sequencing, compared the genotype with toxin expression of 52 C. sordellii strains, and examined the role of TcsH in batch release potency tests required for veterinary vaccines licensed in the United States and other testing utilizing WHO standard antitoxin. Data from this study will assist in future research to clarify the TcsH contribution to the pathogenesis of C. sordellii infections and may aid in the development of improved vaccines.

  20. Inositol hexakisphosphate-dependent processing of Clostridium sordellii lethal toxin and Clostridium novyi alpha-toxin.

    PubMed

    Guttenberg, Gregor; Papatheodorou, Panagiotis; Genisyuerek, Selda; Lü, Wei; Jank, Thomas; Einsle, Oliver; Aktories, Klaus

    2011-04-29

    Clostridium sordellii lethal toxin and Clostridium novyi α-toxin, which are virulence factors involved in the toxic shock and gas gangrene syndromes, are members of the family of clostridial glucosylating toxins. The toxins inactivate Rho/Ras proteins by glucosylation or attachment of GlcNAc (α-toxin). Here, we studied the activation of the autoproteolytic processing of the toxins by inositol hexakisphosphate (InsP(6)) and compared it with the processing of Clostridium difficile toxin B. In the presence of low concentrations of InsP(6) (<1 μM), toxin fragments consisting of the N-terminal glucosyltransferase (or GlcNAc-transferase) domains and the cysteine protease domains (CPDs) of C. sordellii lethal toxin, C. novyi α-toxin, and C. difficile toxin B were autocatalytically processed. The cleavage sites of lethal toxin (Leu-543) and α-toxin (Leu-548) and the catalytic cysteine residues (Cys-698 of lethal toxin and Cys-707 of α-toxin) were identified. Affinity of the CPDs for binding InsP(6) was determined by isothermal titration calorimetry. In contrast to full-length toxin B and α-toxin, autocatalytic cleavage and InsP(6) binding of full-length lethal toxin depended on low pH (pH 5) conditions. The data indicate that C. sordellii lethal toxin and C. novyi α-toxin are InsP(6)-dependently processed. However, full-length lethal toxin, but not its short toxin fragments consisting of the glucosyltransferase domain and the CPD, requires a pH-sensitive conformational change to allow binding of InsP(6) and subsequent processing of the toxin.

  1. Inositol Hexakisphosphate-dependent Processing of Clostridium sordellii Lethal Toxin and Clostridium novyi α-Toxin*

    PubMed Central

    Guttenberg, Gregor; Papatheodorou, Panagiotis; Genisyuerek, Selda; Lü, Wei; Jank, Thomas; Einsle, Oliver; Aktories, Klaus

    2011-01-01

    Clostridium sordellii lethal toxin and Clostridium novyi α-toxin, which are virulence factors involved in the toxic shock and gas gangrene syndromes, are members of the family of clostridial glucosylating toxins. The toxins inactivate Rho/Ras proteins by glucosylation or attachment of GlcNAc (α-toxin). Here, we studied the activation of the autoproteolytic processing of the toxins by inositol hexakisphosphate (InsP6) and compared it with the processing of Clostridium difficile toxin B. In the presence of low concentrations of InsP6 (<1 μm), toxin fragments consisting of the N-terminal glucosyltransferase (or GlcNAc-transferase) domains and the cysteine protease domains (CPDs) of C. sordellii lethal toxin, C. novyi α-toxin, and C. difficile toxin B were autocatalytically processed. The cleavage sites of lethal toxin (Leu-543) and α-toxin (Leu-548) and the catalytic cysteine residues (Cys-698 of lethal toxin and Cys-707 of α-toxin) were identified. Affinity of the CPDs for binding InsP6 was determined by isothermal titration calorimetry. In contrast to full-length toxin B and α-toxin, autocatalytic cleavage and InsP6 binding of full-length lethal toxin depended on low pH (pH 5) conditions. The data indicate that C. sordellii lethal toxin and C. novyi α-toxin are InsP6-dependently processed. However, full-length lethal toxin, but not its short toxin fragments consisting of the glucosyltransferase domain and the CPD, requires a pH-sensitive conformational change to allow binding of InsP6 and subsequent processing of the toxin. PMID:21385871

  2. EP4 and EP2 receptor activation of protein kinase A by prostaglandin E2 impairs macrophage phagocytosis of Clostridium sordellii

    PubMed Central

    Rogers, Lisa M.; Thelen, Tennille; Fordyce, Krystle; Bourdonnay, Emilie; Lewis, Casey; Yu, Han; Zhang, Junyong; Xie, Jingli; Serezani, Carlos H.; Peters-Golden, Marc; Aronoff, David M.

    2013-01-01

    Problem Clostridium sordellii causes endometrial infections but little is known regarding host defenses against this pathogen. Method of Study We tested the hypothesis that the immunoregulatory lipid prostaglandin (PG) E2 suppresses human macrophage clearance of C. sordellii through receptor-induced increases in intracellular cAMP. The THP-1 macrophage cell line was used to quantify C. sordellii phagocytosis. Results PGE2 increased cAMP levels, activated protein kinase A (PKA), and inhibited the class A scavenger receptor-dependent phagocytosis of C. sordellii. Activation of the EP2 and EP4 receptors increased intracellular cAMP and inhibited phagocytosis, with evidence favoring a more important role for EP4 over EP2. This was supported by EP receptor expression data and the use of pharmacological receptor antagonists. In addition, the PKA isoform RI appeared to be more important than RII in mediating the suppression of ingestion of C. sordellii. Conclusions The endogenous lipid mediator PGE2 impairs human innate immune responses against C. sordellii. PMID:23902376

  3. Clostridium sordellii Lethal-Toxin Autoprocessing and Membrane Localization Activities Drive GTPase Glucosylation Profiles in Endothelial Cells

    PubMed Central

    Craven, Ryan

    2015-01-01

    ABSTRACT Clostridium sordellii infections cause gangrene and edema in humans and gastrointestinal infections in livestock. One of the principle virulence factors is TcsL, a large protein toxin which glucosylates host GTPases to cause cytopathic and cytotoxic effects. TcsL has two enzymatic domains, an N-terminal glucosyltransferase domain (GTD) and an autoprocessing domain responsible for release of the GTD within the cell. The GTD can then use its N-terminal membrane localization domain (MLD) for orientation on membranes and modification of GTPases. This study describes the use of conditionally immortalized murine pulmonary microvascular endothelial cells as a model for the study of TcsL functional activities. Point mutations that disrupt the glucosyltransferase, autoprocessing, or membrane localization activities were introduced into a recombinant version of TcsL, and the activities of these mutants were compared to those of wild-type toxin. We observed that all mutants are defective or impaired in cytotoxicity but differ in their modification of Rac1 and Ras. The data suggest a model where differences in GTPase localization dictate cellular responses to intoxication and highlight the importance of autoprocessing in the function of TcsL. IMPORTANCE Clostridium sordellii is a bacterium that can infect humans and cause serious disease and death. The principle virulence factor associated with clinical symptoms is a large protein toxin known as lethal toxin. The mechanism of lethal-toxin intoxication is assumed to be similar to that of the homologous toxins from C. difficile, but very few studies have been done in the context of endothelial cells, a relevant target in C. sordellii infections. This study was designed to test the role of the lethal-toxin enzymatic activities and membrane localization in endothelial cell toxicity and host substrate modification. PMID:27303685

  4. The Sialidase NanS Enhances Non-TcsL Mediated Cytotoxicity of Clostridium sordellii

    PubMed Central

    Awad, Milena M.; Singleton, Julie; Lyras, Dena

    2016-01-01

    The clostridia produce an arsenal of toxins to facilitate their survival within the host environment. TcsL is one of two major toxins produced by Clostridium sordellii, a human and animal pathogen, and is essential for disease pathogenesis of this bacterium. C. sordellii produces many other toxins, but the role that they play in disease is not known, although previous work has suggested that the sialidase enzyme NanS may be involved in the characteristic leukemoid reaction that occurs during severe disease. In this study we investigated the role of NanS in C. sordellii disease pathogenesis. We constructed a nanS mutant and showed that NanS is the only sialidase produced from C. sordellii strain ATCC9714 since sialidase activity could not be detected from the nanS mutant. Complementation with the wild-type gene restored sialidase production to the nanS mutant strain. Cytotoxicity assays using sialidase-enriched culture supernatants applied to gut (Caco2), vaginal (VK2), and cervical cell lines (End1/E6E7 and Ect1/E6E7) showed that NanS was not cytotoxic to these cells. However, the cytotoxic capacity of a toxin-enriched supernatant to the vaginal and cervical cell lines was substantially enhanced in the presence of NanS. TcsL was not the mediator of the observed cytotoxicity since supernatants harvested from a TcsL-deficient strain displayed similar cytotoxicity levels to TcsL-containing supernatants. This study suggests that NanS works synergistically with an unknown toxin or toxins to exacerbate C. sordellii-mediated tissue damage in the host. PMID:27322322

  5. Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B

    PubMed Central

    Genth, Harald; Schelle, Ilona; Just, Ingo

    2016-01-01

    Lethal Toxin from Clostridium sordellii (TcsL) and Toxin B from Clostridium difficile (TcdB) belong to the family of the “Large clostridial glycosylating toxins.” These toxins mono-O-glucosylate low molecular weight GTPases of the Rho and Ras families by exploiting UDP-glucose as a hexose donor. TcsL is casually involved in the toxic shock syndrome and the gas gangrene. TcdB—together with Toxin A (TcdA)—is causative for the pseudomembranous colitis (PMC). Here, we present evidence for the in vitro metal ion activation of the glucosyltransferase and the UDP-glucose hydrolysis activity of TcsL and TcdB. The following rating is found for activation by divalent metal ions: Mn2+ > Co2+ > Mg2+ >> Ca2+, Cu2+, Zn2+. TcsL and TcdB thus require divalent metal ions providing an octahedral coordination sphere. The EC50 values for TcsL were estimated at about 28 µM for Mn2+ and 180 µM for Mg2+. TcsL and TcdB further require co-stimulation by monovalent K+ (not by Na+). Finally, prebound divalent metal ions were dispensible for the cytopathic effects of TcsL and TcdB, leading to the conclusion that TcsL and TcdB recruit intracellular metal ions for activation of the glucosyltransferase activity. With regard to the intracellular metal ion concentrations, TcsL and TcdB are most likely activated by K+ and Mg2+ (rather than Mn2+) in mammalian target cells. PMID:27089365

  6. Experimental identification and computational characterization of a novel extracellular metalloproteinase produced by Clostridium sordellii † †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra27654g Click here for additional data file.

    PubMed Central

    Tao, Aoxiang; Heeney, Dustin D.; McIndoo, Eric R.; French, John M.

    2017-01-01

    Clostridium sordellii is a lethal pathogen for both animals and humans. Severe capillary leakage, toxic shock syndrome, and an extreme leukemoid reaction (LR), are hallmark features of C. sordellii infections and contribute to its high mortality rate. Here we report the discovery of a previously unknown and uncharacterized metalloproteinase of C. sordellii (referred as Mcs1) that cleaves human vascular cell adhesion molecule (VCAM)-1 in vitro, an adhesion molecule critical to hematopoietic precursor retention and leukocyte diapedesis. We successfully identified the open reading frame encoding Mcs1 within the ATCC 9714 genome and developed an Δmcs1 mutant strain using the ClosTron mutagenesis technology. No VCAM-1 proteolysis was observed from exotoxins collected from mutant strain cultures. Using advanced protein structural modeling and molecular dynamics simulation techniques, the 3D molecular structure and conformational features of Mcs1 were also characterized. Our data demonstrates that Mcs1 proteolytic activity is controlled by the electrostatic interactions between Glu113 and Arg227 residues and the gating motions within its cleft region. This pilot interdisciplinary investigation provided crucial experimental evidence of the existence of Mcs1 in C. sordellii and molecular insights into its 3D structure and proteolytic activity. These findings have the potential to help advance new therapeutics and diagnostics against deadly C. sordellii infections. Follow-up in vitro and in vivo work is under way to further characterize Mcs1 enzymatic kinetics and its role in C. sordellii pathogenesis. PMID:28515901

  7. Degeneration and Regeneration of Murine Skeletal Neuromuscular Junctions after Intramuscular Injection with a Sublethal Dose of Clostridium sordellii Lethal Toxin

    PubMed Central

    Barbier, Julien; Popoff, Michel R.; Molgó, Jordi

    2004-01-01

    Clostridium sordellii lethal toxin (LT), a 250-kDa protein which is the bacteria's major virulence factor, belongs to a family of large clostridial cytotoxins which glucosylate small GTP-binding proteins. Here, we report the results of our ex vivo analysis of the structure and function of skeletal neuromuscular tissue obtained from mice at various times after intramuscular injection of a sublethal dose of LT (0.25 ng/g of body wt). The toxin caused, within 24 h, pronounced localized edema, inflammation, myofibril disassembly, and degeneration of skeletal muscle fibers in the injected area, and it glucosylated the muscle tissue's small GTPases. Regeneration of the damaged fibers was evident 6 to 9 days postinjury and was completed by 60 days. The expression of dystrophin, laminin, and fast and neonatal myosin in regenerating fibers, detected by immunofluorescence microscopy, confirmed that LT does not impair the high regenerative capacity of murine skeletal muscle fibers. Functional studies revealed that LT affects muscle contractility and neuromuscular transmission. However, partial recovery of nerve-evoked muscle twitches and tetanic contractions was observed by day 15 postinjection, and extensive remodeling of the neuromuscular junction's nerve terminals and clusters of muscle acetylcholine receptors was still evident 30 days postinjection. In conclusion, to the best of our knowledge, this is the first report to characterize the degeneration and regeneration of skeletal neuromuscular tissue after in vivo exposure to a large clostridial cytotoxin. In addition, our data may provide an explanation for the severe neuromuscular alterations accompanying wound infections caused by C. sordellii. PMID:15155613

  8. Degeneration and regeneration of murine skeletal neuromuscular junctions after intramuscular injection with a sublethal dose of Clostridium sordellii lethal toxin.

    PubMed

    Barbier, Julien; Popoff, Michel R; Molgó, Jordi

    2004-06-01

    Clostridium sordellii lethal toxin (LT), a 250-kDa protein which is the bacteria's major virulence factor, belongs to a family of large clostridial cytotoxins which glucosylate small GTP-binding proteins. Here, we report the results of our ex vivo analysis of the structure and function of skeletal neuromuscular tissue obtained from mice at various times after intramuscular injection of a sublethal dose of LT (0.25 ng/g of body wt). The toxin caused, within 24 h, pronounced localized edema, inflammation, myofibril disassembly, and degeneration of skeletal muscle fibers in the injected area, and it glucosylated the muscle tissue's small GTPases. Regeneration of the damaged fibers was evident 6 to 9 days postinjury and was completed by 60 days. The expression of dystrophin, laminin, and fast and neonatal myosin in regenerating fibers, detected by immunofluorescence microscopy, confirmed that LT does not impair the high regenerative capacity of murine skeletal muscle fibers. Functional studies revealed that LT affects muscle contractility and neuromuscular transmission. However, partial recovery of nerve-evoked muscle twitches and tetanic contractions was observed by day 15 postinjection, and extensive remodeling of the neuromuscular junction's nerve terminals and clusters of muscle acetylcholine receptors was still evident 30 days postinjection. In conclusion, to the best of our knowledge, this is the first report to characterize the degeneration and regeneration of skeletal neuromuscular tissue after in vivo exposure to a large clostridial cytotoxin. In addition, our data may provide an explanation for the severe neuromuscular alterations accompanying wound infections caused by C. sordellii.

  9. Lethal toxin of Clostridium sordellii is associated with fatal equine atypical myopathy.

    PubMed

    Unger-Torroledo, Lucia; Straub, Reto; Lehmann, Andrea D; Graber, Franziska; Stahl, Christina; Frey, Joachim; Gerber, Vinzenz; Hoppeler, Hans; Baum, Oliver

    2010-08-26

    The lethal toxin of Clostridium sordellii (TcsL) evokes severe, mostly fatal disease patterns like toxic shock syndrome in humans and animals. Since this large clostridial toxin-induced severe muscle damaging when injected intramuscularly into mice, we hypothesized that TcsL is also associated with equine atypical myopathy (EAM), a fatal myodystrophy of hitherto unknown etiology. Transmission electron microscopy revealed skeletal and heart muscles of EAM-affected horses to undergo degeneration ultrastructurally similar to the damage found in TcsL-treated mice. Performing immunohistochemistry, myofibers of EAM-affected horses specifically reacted with sera derived from horses with EAM as well as an antibody specific for the N-terminal part of TcsL, while both antibodies failed to bind to the myofibers of either healthy horses or those with other myopathies. The presence of TcsL in myofibers of horses with EAM suggests that it plays a role as trigger or even as lethal factor in this disease. Copyright 2010 Elsevier B.V. All rights reserved.

  10. Clostridium difficile Infection

    MedlinePlus

    ... Schedules Nutrient Shortfall Questionnaire Home Diseases and Conditions Clostridium difficile (C. diff.) Infection Clostridium difficile (C. diff.) Infection Condition Family HealthSeniors Share ...

  11. Paraclostridium benzoelyticum gen. nov. sp. nov., isolated from marine sediment and reclassification of Clostridium bifermentans as Paraclostridium bifermentans comb. nov. Proposal of a new genus Paeniclostridium gen. nov. to accommodate Clostridium sordellii and Clostridium ghonii.

    PubMed

    T S, Sasi Jyothsna; L, Tushar; Ch, Sasikala; Ch V, Ramana

    2016-01-05

    Twenty three rod shaped, endospore forming, Gram-stain-positive, obligately anaerobic bacteria were isolated from different marine sediment samples of Gujarat. All the twenty three strains have 16S rRNA gene sequence similarity of ~100%. Strain JC272T was designated as the type strain and has sequence similarity with Clostridium bifermentans ATCC638T (99.8%), Clostridium ghonii JCM1400T (98.0%), Clostridium sordellii ATCC9714T (97.9%) and other members of the genus Clostridium (<96.4%). C16:0, C18:0, C17:0, C16:1ω9C and iso-C16:0 are the major (>5%) fatty acids. Strain JC272T contains diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and unidentified amino lipids (AL1&AL2). However, genome based analysis of ANI and in silico DDH of strain JC272T with C. bifermentans ATCC 638T yielded values of 94.35% and 58.5+2.8%, respectively. G+C mol% of strain JC272T was 28.3%. Strain JC272T together with C. bifermentans fall outside Clostridium rRNA cluster I considered as Clostridium senso stricto. Based on ANI value, in-silico DDH, distinct morphological and physiological differences from the previously described taxa, we propose strain JC272T as a representative of a new genus and species in the family Clostridiaceae, for which the name Paraclostridium benzoelyticum gen. nov., sp. nov. is proposed. Type strain is JC272T (=KCTC15476T =LMG28745T). It is also proposed to transfer C. bifermentans to this new genus, as Paraclostridium bifermentans comb. nov. (type strain is ATCC638T =DSM14991T =JCM1386T). We also propose the genus Paeniclostridium gen. nov. to accommodate Clostridium sordellii and Clostridium ghonii as Paeniclostridium sordellii comb. nov. (type strain is ATCC9714T =LMG15708T =JCM3814T) and Paeniclostridium ghonii comb. nov. (type strain is ATCC25757T = DSM15049T =JCM1400T).

  12. Inhibition of small G proteins by clostridium sordellii lethal toxin activates cdc2 and MAP kinase in Xenopus oocytes.

    PubMed

    Rime, H; Talbi, N; Popoff, M R; Suziedelis, K; Jessus, C; Ozon, R

    1998-12-15

    The lethal toxin (LT) from Clostridium sordellii is a glucosyltransferase that modifies and inhibits small G proteins of the Ras family, Ras and Rap, as well as Rac proteins. LT induces cdc2 kinase activation and germinal vesicle breakdown (GVBD) when microinjected into full-grown Xenopus oocytes. Toxin B from Clostridium difficile, that glucosylates and inactivates Rac proteins, does not induce cdc2 activation, indicating that proteins of the Ras family, Ras and/or Rap, negatively regulate cdc2 kinase activation in Xenopus oocyte. In oocyte extracts, LT catalyzes the incorporation of [14C]glucose into a group of proteins of 23 kDa and into one protein of 27 kDa. The 23-kDa proteins are recognized by anti-Rap1 and anti-Rap2 antibodies, whereas the 27-kDa protein is recognized by several anti-Ras antibodies and probably corresponds to K-Ras. Microinjection of LT into oocytes together with UDP-[14C]glucose results in a glucosylation pattern similar to the in vitro glucosylation, indicating that the 23- and 27-kDa proteins are in vivo substrates of LT. In vivo time-course analysis reveals that the 27-kDa protein glucosylation is completed within 2 h, well before cdc2 kinase activation, whereas the 23-kDa proteins are partially glucosylated at GVBD. This observation suggests that the 27-kDa Ras protein could be the in vivo target of LT allowing cdc2 kinase activation. Interestingly, inactivation of Ras proteins does not prevent the phosphorylation of c-Raf1 and the activation of MAP kinase that occurs normally around GVBD. Copyright 1998 Academic Press.

  13. Haemorrhagic toxin and lethal toxin from Clostridium sordellii strain vpi9048: molecular characterization and comparative analysis of substrate specificity of the large clostridial glucosylating toxins.

    PubMed

    Genth, Harald; Pauillac, Serge; Schelle, Ilona; Bouvet, Philippe; Bouchier, Christiane; Varela-Chavez, Carolina; Just, Ingo; Popoff, Michel R

    2014-11-01

    Large clostridial glucosylating toxins (LCGTs) are produced by toxigenic strains of Clostridium difficile, Clostridium perfringens, Clostridium novyi and Clostridium sordellii. While most C. sordellii strains solely produce lethal toxin (TcsL), C. sordellii strain VPI9048 co-produces both hemorrhagic toxin (TcsH) and TcsL. Here, the sequences of TcsH-9048 and TcsL-9048 are provided, showing that both toxins retain conserved LCGT features and that TcsL and TcsH are highly related to Toxin A (TcdA) and Toxin B (TcdB) from C. difficile strain VPI10463. The substrate profile of the toxins was investigated with recombinant LCGT transferase domains (rN) and a wide panel of small GTPases. rN-TcsH-9048 and rN-TcdA-10463 glucosylated preferably Rho-GTPases but also Ras-GTPases to some extent. In this respect, rN-TcsH-9048 and rN-TcdA-10463 differ from the respective full-length TcsH-9048 and TcdA-10463, which exclusively glucosylate Rho-GTPases. rN-TcsL-9048 and full length TcsL-9048 glucosylate both Rho- and Ras-GTPases, whereas rN-TcdB-10463 and full length TcdB-10463 exclusively glucosylate Rho-GTPases. Vero cells treated with full length TcsH-9048 or TcdA-10463 also showed glucosylation of Ras, albeit to a lower extent than of Rho-GTPases. Thus, in vitro analysis of substrate spectra using recombinant transferase domains corresponding to the auto-proteolytically cleaved domains, predicts more precisely the in vivo substrates than the full length toxins. Except for TcdB-1470, all LCGTs evoked increased expression of the small GTPase RhoB, which exhibited cytoprotective activity in cells treated with TcsL isoforms, but pro-apoptotic activity in cells treated with TcdA, TcdB, and TcsH. All LCGTs induced a rapid dephosphorylation of pY118-paxillin and of pS144/141-PAK1/2 prior to actin filament depolymerization indicating that disassembly of focal adhesions is an early event leading to the disorganization of the actin cytoskeleton. © 2014 John Wiley & Sons Ltd.

  14. Role of p38alpha/beta MAP Kinase in Cell Susceptibility to Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B

    PubMed Central

    Schelle, Ilona; Bruening, Janina; Buetepage, Mareike; Genth, Harald

    2016-01-01

    Lethal Toxin from Clostridium sordellii (TcsL), which is casually involved in the toxic shock syndrome and in gas gangrene, enters its target cells by receptor-mediated endocytosis. Inside the cell, TcsL mono-O-glucosylates and thereby inactivates Rac/Cdc42 and Ras subtype GTPases, resulting in actin reorganization and an activation of p38 MAP kinase. While a role of p38 MAP kinase in TcsL-induced cell death is well established, data on a role of p38 MAP kinase in TcsL-induced actin reorganization are not available. In this study, TcsL-induced Rac/Cdc42 glucosylation and actin reorganization are differentially analyzed in p38alpha−/− MSCV empty vector MEFs and the corresponding cell line with reconstituted p38alpha expression (p38alpha−/− MSCV p38alpha MEFs). Genetic deletion of p38alpha results in reduced susceptibility of cells to TcsL-induced Rac/Cdc42 glucosylation and actin reorganization. Furthermore, SB203580, a pyridinyl imidazole inhibitor of p38alpha/beta MAP kinase, also protects cells from TcsL-induced effects in both p38−/− MSCV empty vector MEFs and in p38alpha−/− MSCV p38alpha MEFs, suggesting that inhibition of p38beta contributes to the protective effect of SB203580. In contrast, the effects of the related C. difficile Toxin B are responsive neither to SB203580 treatment nor to p38alpha deletion. In conclusion, the protective effects of SB203580 and of p38alpha deletion are likely not based on inhibition of the toxins’ glucosyltransferase activity rather than on inhibited endocytic uptake of specifically TcsL into target cells. PMID:28025502

  15. Clostridium difficile Infection

    PubMed Central

    Heinlen, Latisha; Ballard, Jimmy D.

    2010-01-01

    Clostridium difficile is the leading cause of hospital-acquired diarrhea in Europe and North America and is a serious re-emerging pathogen. Recent outbreaks have led to increasing morbidity and mortality and have been associated with a new strain (BI/NAP1/027) of C. difficile that produces more toxin than historical strains. With the increasing incidence of C. difficile infection, clinicians have also seen a change in the epidemiology with increased infections in previously low-risk populations. This chapter highlights the current knowledge on C. difficile virulence, human disease, epidemic outbreaks, and optimal treatment strategies. PMID:20697257

  16. Transient expression of RhoA, -B, and -C GTPases in HeLa cells potentiates resistance to Clostridium difficile toxins A and B but not to Clostridium sordellii lethal toxin.

    PubMed Central

    Giry, M; Popoff, M R; von Eichel-Streiber, C; Boquet, P

    1995-01-01

    The bacterial pathogen Clostridium difficle synthesizes two high-molecular-weight toxins (A and B), which exhibit toxic effects in vivo and in vitro. Here, we present evidence that the major intracellular targets of these two toxins are the Rho GTPases. Overexpression of RhoA, RhoB, or RhoC GTPases in transfected HeLa cells conferred an increased resistance to toxins A and B, indicating that these toxins cause their cytopathic effects primarily by affecting Rho proteins. In addition, toxin A and B treatment appeared to result in modification of Rho, since Rho isolated from toxin-treated cells had a decreased ability to be ADP-ribosylated by Clostridium botulinum C3 exoenzyme. In contrast, the lethal toxin (LT) of Clostridium sordellii, although structurally and immunologically related to C. difficile toxin B, appeared to induce cytopathic effects independently of the Rho GTPases. Overexpression of RhoA in transfected HeLa cells did not protect them from the effect of LT, and Rho isolated from lysates of LT-treated cells was not resistant to modification by C3. Immunofluorescence studies showed that LT treatment caused a cytopathic effect that was very different from those described for C. difficile toxins A and B, resulting in an increase in cortical F-actin, with a concomitant decrease in the number of stress fibers, and in the formation of numerous microvilli containing the actin-bundling protein fimbrin/plastin. PMID:7558320

  17. 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

  18. Clostridium difficile infection.

    PubMed

    Alcalá Hernández, Luis; Reigadas Ramírez, Elena; Bouza Santiago, Emilio

    2017-05-23

    Clostridium difficile infection (CDI) is the main cause of nosocomial diarrhea in industrialized countries and the source of a growing number of cases of diarrhea in the community. The outbreak of the hypervirulent strain belonging to ribotype 027 has increased the incidence and severity of CDI in some countries. Although CDI usually courses as a mild diarrhea it can lead to severe forms such as toxic megacolon or septic shock. One of every 2 episodes of CDI is not diagnosed in Spanish hospitals due to a lack of clinical suspicion or the use of insensitive diagnostic methods. The diagnostic techniques of choice are algorithms based on the detection of glutamate dehydrogenase and molecular detection of the genes of the toxins with or without the direct detection of the toxins. The recommended treatment for CDI depends on the type of infection and the characteristics of the patient. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  19. The Tip of the Four N-Terminal α-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation.

    PubMed

    Varela Chavez, Carolina; Haustant, Georges Michel; Baron, Bruno; England, Patrick; Chenal, Alexandre; Pauillac, Serge; Blondel, Arnaud; Popoff, Michel-Robert

    2016-03-25

    Clostridium sordellii lethal toxin (TcsL) is a powerful virulence factor responsible for severe toxic shock in man and animals. TcsL belongs to the large clostridial glucosylating toxin (LCGT) family which inactivates small GTPases by glucosylation with uridine-diphosphate (UDP)-glucose as a cofactor. Notably, TcsL modifies Rac and Ras GTPases, leading to drastic alteration of the actin cytoskeleton and cell viability. TcsL enters cells via receptor-mediated endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat) into the cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS)-containing membranes and to increase the glucosylation of Rac anchored to the lipid membrane. We have previously reported that the N-terminal four helical bundle structure (1-93 domain) recognizes a broad range of lipids, but that TcsL-cat specifically binds to PS and phosphatidic acid. Here, we show using mutagenesis that the PS binding site is localized on the tip of the four-helix bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17, and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3, between helices 3 and 4, form a pocket which accommodates L-serine. The functional PS-binding site is required for TcsL-cat binding to the plasma membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high enzymatic activity towards membrane-anchored Ras by about three orders of magnitude as compared to Ras in solution. The PS-binding site is conserved in LCGTs, which likely retain a common mechanism of binding to the membrane for their full activity towards membrane-bound GTPases.

  20. The catalytic domains of Clostridium sordellii lethal toxin and related large clostridial glucosylating toxins specifically recognize the negatively charged phospholipids phosphatidylserine and phosphatidic acid.

    PubMed

    Varela Chavez, Carolina; Hoos, Sylviane; Haustant, Georges Michel; Chenal, Alexandre; England, Patrick; Blondel, Arnaud; Pauillac, Serge; Lacy, D Borden; Popoff, Michel Robert

    2015-10-01

    Clostridium sordellii lethal toxin (TcsL) is a potent virulence factor belonging to the large clostridial glucosylating toxin family. TcsL enters target cells via receptor-mediated endocytosis and delivers the N-terminal catalytic domain (TcsL-cat) into the cytosol upon an autoproteolytic process. TcsL-cat inactivates small GTPases including Rac and Ras by glucosylation with uridine-diphosphate (UDP)-glucose as cofactor leading to drastic changes in cytoskeleton and cell viability. TcsL-cat was found to preferentially bind to phosphatidylserine (PS)-containing membranes and to increase the glucosylation of Rac anchored to lipid membrane. We here report binding affinity measurements of TcsL-cat for brain PS-containing membranes by surface plasmon resonance and enzyme-linked immunosorbent assay (ELISA). In addition, TcsL-cat bound to phosphatidic acid (PA) and, to a lesser extent, to other anionic lipids, but not to neutral lipids, sphingolipids or sterol. We further show that the lipid unsaturation status influenced TcsL-cat binding to phospholipids, PS with unsaturated acyl chains and PA with saturated acyl chains being the preferred bindingsubstrates. Phospholipid binding site is localized at the N-terminal four helical bundle structure (1-93 domain). However, TcsL-1-93 bound to a broad range of substrates, whereas TcsL-cat, which is the active domain physiologically delivered into the cytosol, selectively bound to PS and PA. Similar findings were observed with the other large clostridial glucosylating toxins from C. difficile, C. novyi and C. perfringens. © 2015 John Wiley & Sons Ltd.

  1. The Tip of the Four N-Terminal α-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation

    PubMed Central

    Varela Chavez, Carolina; Haustant, Georges Michel; Baron, Bruno; England, Patrick; Chenal, Alexandre; Pauillac, Serge; Blondel, Arnaud; Popoff, Michel-Robert

    2016-01-01

    Clostridium sordellii lethal toxin (TcsL) is a powerful virulence factor responsible for severe toxic shock in man and animals. TcsL belongs to the large clostridial glucosylating toxin (LCGT) family which inactivates small GTPases by glucosylation with uridine-diphosphate (UDP)-glucose as a cofactor. Notably, TcsL modifies Rac and Ras GTPases, leading to drastic alteration of the actin cytoskeleton and cell viability. TcsL enters cells via receptor-mediated endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat) into the cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS)-containing membranes and to increase the glucosylation of Rac anchored to the lipid membrane. We have previously reported that the N-terminal four helical bundle structure (1–93 domain) recognizes a broad range of lipids, but that TcsL-cat specifically binds to PS and phosphatidic acid. Here, we show using mutagenesis that the PS binding site is localized on the tip of the four-helix bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17, and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3, between helices 3 and 4, form a pocket which accommodates L-serine. The functional PS-binding site is required for TcsL-cat binding to the plasma membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high enzymatic activity towards membrane-anchored Ras by about three orders of magnitude as compared to Ras in solution. The PS-binding site is conserved in LCGTs, which likely retain a common mechanism of binding to the membrane for their full activity towards membrane-bound GTPases. PMID:27023605

  2. Clostridium Difficile Infections

    MedlinePlus

    Clostridium difficile (C. difficile) is a bacterium that causes diarrhea and more serious intestinal conditions such as colitis. Symptoms include Watery ... Nausea Abdominal pain or tenderness You might get C. difficile disease if you have an illness that ...

  3. 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

  4. Management of Clostridium difficile Infection.

    PubMed

    Al-Jashaami, Layth S; DuPont, Herbert L

    2016-10-01

    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.

  5. Fidaxomicin: in Clostridium difficile infection.

    PubMed

    Duggan, Sean T

    2011-12-24

    Fidaxomicin is a first-in-class macrocyclic antibacterial that primarily demonstrates activity against species of clostridia, predominantly Clostridium difficile, while having limited or no activity against normal faecal microflora. Fidaxomicin is minimally absorbed following oral administration and is excreted almost solely in the faeces. Fidaxomicin displayed a high level of antibacterial activity against C. difficile in vitro, with a minimum inhibitory concentration required to inhibit 90% of C. difficile strains of 0.125-0.5 μg/mL, and was ≈2- to 8-fold more active than vancomycin or metronidazole. Fidaxomicin demonstrated a prolonged postantibiotic effect against C. difficile relative to vancomycin and metronidazole. In two randomized, double-blind, phase III trials, oral fidaxomicin 200 mg every 12 hours for 10 days was no less effective than oral vancomycin 125 mg every 6 hours for 10 days in the treatment of C. difficile infection, based on noninferiority analyses of clinical cure rates (primary endpoint). Fidaxomicin therapy was associated with a significantly lower rate of recurrence, as well as a significantly higher rate of global cure (i.e. sustained clinical response; resolution of diarrhoea without recurrence) compared with vancomycin therapy in the two clinical trials. Fidaxomicin was generally well tolerated in patients with C. difficile infection, with a tolerability profile generally similar to that of vancomycin.

  6. 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.

  7. 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.

  8. Prevention of Infection Due to Clostridium difficile.

    PubMed

    Cooper, Christopher C; Jump, Robin L P; Chopra, Teena

    2016-12-01

    Clostridium difficile is one of the foremost nosocomial pathogens. Preventing infection is particularly challenging. Effective prevention efforts typically require a multifaceted bundled approach. A variety of infection control procedures may be advantageous, including strict hand decontamination with soap and water, contact precautions, and using chlorine-containing decontamination agents. Additionally, risk factor reduction can help reduce the burden of disease. The risk factor modification is principally accomplished though antibiotic stewardship programs. Unfortunately, most of the current evidence for prevention is in acute care settings. This review focuses on preventative approaches to reduce the incidence of Clostridium difficile infection in healthcare settings.

  9. Constipation in Clostridium difficile infection.

    PubMed

    Kawsar, Hameem I; Gopal, K V; Shahnewaz, Jamila; Daw, Hamed A

    2012-07-03

    A patient presented to our hospital with worsening shortness of breath, cough and respiratory distress that slowly worsened over 7-10 days. She had a viral-like illness with runny nose and cough for 1 week, which became productive of yellowish sputum. She was treated with antibiotic and steroid with clinical improvement. Her leucocyte count continued to increase despite discontinuation of both antibiotic and steroid. All culture results returned negative. She did not have any abdominal pain or diarrhoea. Her stool was positive for Clostridium difficile toxin assayed by PCR. A CT of abdomen showed distension of cecum and proximal colon. She was treated with intravenous metronidazole, oral and rectal vancomycin and intravenous immunoglobulin. She developed multi-organ failure and died.

  10. Constipation in Clostridium difficile infection

    PubMed Central

    Kawsar, Hameem I; Gopal, K V; Shahnewaz, Jamila; Daw, Hamed A

    2012-01-01

    A patient presented to our hospital with worsening shortness of breath, cough and respiratory distress that slowly worsened over 7–10 days. She had a viral-like illness with runny nose and cough for 1 week, which became productive of yellowish sputum. She was treated with antibiotic and steroid with clinical improvement. Her leucocyte count continued to increase despite discontinuation of both antibiotic and steroid. All culture results returned negative. She did not have any abdominal pain or diarrhoea. Her stool was positive for Clostridium difficile toxin assayed by PCR. A CT of abdomen showed distension of cecum and proximal colon. She was treated with intravenous metronidazole, oral and rectal vancomycin and intravenous immunoglobulin. She developed multi-organ failure and died. PMID:22761206

  11. Immunization strategies for Clostridium difficile infections.

    PubMed

    Rebeaud, Fabien; Bachmann, Martin F

    2012-04-01

    Clostridium difficile infection is a major cause of nosocomial disease in Western countries. The recent emergence of hypervirulent strains resistant to most antibiotics correlates with increasing disease incidence, severity and lethal outcomes. Current treatments rely on metronidazol and vancomycin, but the limited ability of these antibiotics to cure infection and prevent relapse highlights the need for new strategies. A better knowledge of the molecular mechanisms of the disease, the host immune response and identification of key virulence factors of Clostridium difficile now permits the development of new products specifically targeting the pathogen. Immune-based strategies relying on active vaccination or passive administration of antibody products are the focus of intense research and, today, the efficacy of monoclonal antibodies and of two vaccines are evaluated clinically. This review presents recent data, discusses the different strategies and highlights the challenges linked to the development of immunization strategies against this emerging threat.

  12. Alternative strategies for Clostridium difficile infection.

    PubMed

    Bauer, Martijn P; van Dissel, Jaap T

    2009-03-01

    Although antibiotics are generally effective in achieving symptomatic recovery from Clostridium difficile infection, the disease frequently relapses, partly because antibiotics not only kill C. difficile, but also disrupt colonisation resistance of the gut microflora. Non-antibiotic strategies for the prevention and treatment of the infection include probiotics, deliberate colonisation by non-toxigenic C. difficile strains, toxin-binding agents, active immunisation, passive immunotherapy with intravenous immunoglobulin, monoclonal antibodies or bovine anti-C. difficile whey concentrate, and faecal transplantation. None of these alternative therapies has proven benefit in therapy or prevention, and prospective randomised trials are urgently needed.

  13. Clostridium difficile infection and fecal bacteriotherapy.

    PubMed

    Mitchell, Indya; Shropshire, Kasheena; Ruel, Jennifer

    2013-01-01

    Clostridium difficile, also called "C. diff," is a gram-positive bacillus associated with nosocomial infections involving diarrhea, most often seen in developing countries. The severity of C. diff-associated diarrhea varies tremendously from mild and self-limiting to fulminant and life-threatening. C. diff has become an extremely important pathogen in community health but can be minimized with attention to proper hygiene. This article presents a case study regarding the treatment and management options of C. diff infection using a recent update of clinical guidelines for patient management.

  14. Clostridium difficile Infection and Fecal Microbiota Transplant.

    PubMed

    Liubakka, Alyssa; Vaughn, Byron P

    2016-07-01

    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. ©2016 American Association of Critical-Care Nurses.

  15. Clostridium difficile infection in older adults

    PubMed Central

    Jump, Robin LP

    2014-01-01

    Clostridium difficile infection, the most frequent cause of nosocomial diarrhea, disproportionately affects older adults. The two most important risk factors for developing C. difficile infection are antimicrobial exposure and age >65 years old. Risk factors specific to older adults are frequent interactions with healthcare systems and age-related changes in physiology, including immune senescence and changes to the gut microbiome. Metronidazole and oral vancomcyin are the mainstays of conventional treatment for C. difficile infection. Alternative therapies include fidaxomicin, a narrow-spectrum macrocyclic antibiotic, and fectal bacteriotherapy, which offers an excellent therapeutic outcome. Strategies to prevent C. difficile infections include enhanced infection control measures and reducing inappropriate antimicrobial use through stewardship. PMID:24955106

  16. Faecal microbiota transplantation for Clostridium difficile infection.

    PubMed

    Dodin, M; Katz, D E

    2014-03-01

    To review the current clinical literature regarding the use of fecal microbiota transplantation (FMT) for severe and recurrent Clostridium difficile disease (CDAD). Clostridium difficile (C. difficile) is a gram positive, spore forming bacteria, and an important nosocomial pathogen causing healthcare associated diarrhoea in hospitalized patients in developed and developing countries. During the past several years, CDAD has become more frequent, severe, refractory, and more likely to relapse. It has become apparent that C. difficile is no longer just a nosocomial infection, with a rising rate of infection in populations not previously affected. Standard treatment regimens and new medications exist, but recurrence rates are high. Using PubMed, we conducted a Boolean search with the following medical subject headings (MeSH): Clostridium difficile infection and fecal transplantation or recurrent C. difficile infection. We restricted the search to human studies, published in English, between 2011 through June 1, 2013. There were 104 publications identified. Of those related to FMT, there were 20 clinical reviews, 6 case reports, 3 clinical trials (one, a randomized control trial), and 1 meta-analysis. Since 1958 there have been 36 published reports of FMT for C. difficile infection (CDI) representing 583 patients. Success rates were higher when FMT was administered via colonoscopy (representing the majority of patients, 79.2%). The overall success rate for FMT, regardless of administration method, was 80-98%. Fecal microbiota transplantation attempts to restore the normal microbiome of the colon, and has achieved a cure rate reaching more than 90%. Mounting evidence supports the utility of FMT for severe and recurrent cases of CDI. Barriers that will need to be addressed are patient perceptions and fears, standard protocol development, and further clinical trials. © 2013 John Wiley & Sons Ltd.

  17. Clostridium difficile Infection: New Insights Into Management

    PubMed Central

    Khanna, Sahil; Pardi, Darrell S.

    2012-01-01

    Clostridium difficile was first described as a cause of diarrhea in 1978 and is now among the leading 3 hospital-acquired infections in the United States, along with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In the past 2 decades, there has been an increase in the incidence, severity, and recurrence rates of C difficile infection, all of which are associated with poor outcomes. In addition, several novel risk factors and newer treatment methods are emerging, including fidaxomicin therapy, treatment using monoclonal antibodies, and fecal microbiota transplantation, that have shown promise for the treatment of C difficile infection. This review focuses on the changing epidemiology, risk factors, and newer methods for treatment of C difficile infection. PMID:23127735

  18. Vancomycin-resistant Clostridium innocuum bacteremia following oral vancomycin for Clostridium difficile infection.

    PubMed

    Hung, Yuan-Pin; Lin, Hsiao-Ju; Wu, Chi-Jung; Chen, Po-Lin; Lee, Jen-Chieh; Liu, Hsiao-Chieh; Wu, Yi-Hui; Yeh, Fang Hao; Tsai, Pei-Jane; Ko, Wen-Chien

    2014-12-01

    An 85 year-old male initially admitted for septic shock due to urinary tract infection experienced Clostridium difficile-associated diarrhea during hospitalization and was treated by oral vancomycin. His clinical course was complicated by cytomegalovirus colitis and then vancomycin-resistant Clostridium innocuum bacteremia, which was cured by uneventfully parenteral piperacillin-tazobactam therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Antibodies for Treatment of Clostridium difficile Infection

    PubMed Central

    Wilcox, Mark H.

    2014-01-01

    Antibodies for the treatment of Clostridium difficile infection (CDI) have been demonstrated to be effective in the research and clinical environments. Early uncertainties about molecular and treatment modalities now appear to have converged upon the systemic dosing of mixtures of human IgG1. Although multiple examples of high-potency monoclonal antibodies (MAbs) exist, significant difficulties were initially encountered in their discovery. This minireview describes historical and contemporary MAbs and highlights differences between the most potent MAbs, which may offer insight into the pathogenesis and treatment of CDI. PMID:24789799

  20. Diagnosis of Clostridium difficile Infections in Children

    PubMed Central

    Leber, Amy L.

    2016-01-01

    The detection and diagnosis of Clostridium difficile infection in pediatric populations have some unique considerations in comparison to testing in adults. The testing methodologies, including toxigenic culture, cell cytotoxicity, antigen detection, and, more recently, molecular testing, are the same in all age groups. However, limited data exist on the specific performance characteristics in children. In this review, we focus on the challenges of testing in pediatric populations and assess the available data on test performance in these populations. Additionally, a review of the existing guidance for testing is provided. PMID:26912759

  1. Chronic Clostridium botulinum infections in farmers.

    PubMed

    Rodloff, Arne C; Krüger, Monika

    2012-04-01

    Although botulism is usually an acute, often lethal disease that is caused by the ingestion of botulinum neurotoxin, there are also recognized forms like infant botulism, wound botulism, or "botulism of undefined origin" that are characterized by the fact that Clostridium botulinum colonizes the host and produces its toxin in the host. Evidence is presented here that a disease in cattle and in human care takers of diseased animals that has evolved over the past two decades, may be a chronic, visceral form of C. botulinum infection.

  2. Clostridium difficile infection: Updates in management.

    PubMed

    Tariq, Raseen; Khanna, Sahil

    2017-01-01

    Clostridium difficile was first identified in 1978 as a diarrhea-causing bacterium in humans. In the last three decades, C. difficile infection (CDI) has reached an epidemic state, both in health care and community settings worldwide. There has been substantial progress in the field of CDI, including identification of novel risk factors, presence of CDI in individuals not considered at risk previously, and treatment options including new drugs, monoclonal antibodies, and fecal microbiota transplantation. This review discusses epidemiology, novel and traditional risk factors, and updates in management for CDI.

  3. Clostridium difficile infection and intestinal microbiota interactions.

    PubMed

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

    2015-12-01

    Clostridium difficile remains the leading cause of healthcare-associated diarrhoea and outbreaks continue to occur worldwide. Aside from nosocomial C. difficile infection, the bacterium is also increasingly important as a community pathogen. Furthermore, asymptomatic carriage of C. difficile in neonates, adults and animals is also well recognised. The investigation of the gut's microbial communities, in both healthy subjects and patients suffering C. difficile infection (CDI), provides findings and information relevant for developing new successful approaches for its treatment, such as faecal microbiota transplantation, or for the prophylaxis of the infection by modification of the gut microbiota using functional foods and beverages. The analysis of all available data shows new insights into the role of intestinal microbiota in health and disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Investigational new treatments for Clostridium difficile infection.

    PubMed

    Ivarsson, Mattias E; Leroux, Jean-Christophe; Castagner, Bastien

    2015-05-01

    Significant progress has been made by industry and academia in the past two years to address the medical threats posed by Clostridium difficile infection. These developments provide an excellent example of how patient need has driven a surge of innovation in drug discovery. Indeed, only two drugs were approved for the infection in the past 30 years but there are 13 treatment candidates in clinical trials today. What makes the latter number even more remarkable is the diversity in the strategies represented (antibiotics, microbiota supplements, vaccines, antibiotic quenchers and passive immunization). In this review, we provide a snapshot of the current stage of these breakthroughs and argue that there is still room for further innovation in treating C. difficile infection.

  5. Clostridium difficile infection in horses: a review.

    PubMed

    Diab, S S; Songer, G; Uzal, F A

    2013-11-29

    Clostridium difficile is considered one of the most important causes of diarrhea and enterocolitis in horses. Foals and adult horses are equally susceptible to the infection. The highly resistant spore of C. difficile is the infectious unit of transmission, which occurs primarily via the fecal-oral route, with sources of infection including equine feces, contaminated soil, animal hospitals, and feces of other animals. Two major risk factors for the development of C. difficile associated disease (CDAD) in adult horses are hospitalization and antimicrobial treatment, although sporadically, cases of CDAD can occur in horses that have not received antimicrobials or been hospitalized. The most common antibiotics associated with CDAD in horses are erythromycin, trimethoprim/sulfonamides, β-lactam antimicrobials, clindamycin, rifampicin, and gentamicin. Clinical signs and intestinal lesions of CDAD infection are not specific and they cannot be used to distinguish infections by C. difficile from infections by other agents, such as Clostridium perfringens or Salmonella sp. The distribution of lesions throughout the intestinal tract seems to be age-dependent. Small intestine is invariably affected, and colon and cecum may or may not have lesions in foals<1-month old. Naturally acquired disease in older foals and adult horses has a more aboral distribution, affecting colon and sometimes cecum, but rarely the small intestine. Detection of toxin A, toxin B or both in intestinal contents or feces is considered the most reliable diagnostic criterion for CDAD in horses. Isolation of toxigenic strains of C. difficile from horses with intestinal disease is highly suggestive of CDAD. A better understanding of pathogenesis, reservoirs of infection, and vaccines and other methods of control is needed. Also further studies are recommended to investigate other possible predisposing factors and/or etiological agents of enteric diseases of horses.

  6. Tea and Recurrent Clostridium difficile Infection

    PubMed Central

    Starley, Brad; Galagan, Jack Carl; Yabes, Joseph Michael; Evans, Sara

    2016-01-01

    Background and Aims. Studies have shown effects of diet on gut microbiota. We aimed to identify foods associated with recurrent Clostridium difficile infection (CDI). Methods. In this cross-sectional survey, consecutive patients diagnosed with CDI were identified by electronic medical records. Colitis symptoms and positive Clostridium difficile assay were confirmed. Health-care onset-health-care facility associated CDI was excluded. Food surveys were mailed to 411 patients. Survey responses served as the primary outcome measure. Spearman's rank correlation identified risk factors for CDI recurrence. Results. Surveys were returned by 68 patients. Nineteen patients experienced CDI recurrence. Compared to patients without CDI recurrence, patients with CDI recurrence had more antibiotics prescribed preceding their infection (p = 0.003). Greater numbers of the latter also listed tea (p = 0.002), coffee (p = 0.013), and eggs (p = 0.013), on their 24-hour food recall. Logistic regression identified tea as the only food risk factor for CDI recurrence (adjusted OR: 5.71; 95% CI: 1.26–25.89). Conclusion. The present results indicate a possible association between tea and CDI recurrence. Additional studies are needed to characterize and confirm this association. PMID:27651790

  7. [Selected aspects of Clostridium difficile infection].

    PubMed

    Mehlich, Agnieszka; Górska, Sabina; Gamian, Andrzej; Myc, Andrzej

    2015-05-05

    Clostridium difficile pathogen is a cause of the most frequent nosocomial infection, which is antibiotic-associated diarrhea. Antibiotic treatment causes disruption of the microbiome balance, which makes the gut a friendly environment for the pathogen. It leads to pseudomembranous colitis, toxic megacolon and even death. Clostridium difficile infection (CDI) is particularly dangerous to elderly patients, leading to the highest mortality rate. C. difficile is equipped with many virulence factors such as toxin A and B, binary toxin CDT, flagellum, S-layer proteins, Cwp66 and GroEL proteins, protease Cwp84, fibronectin-binding protein and the ability to form biofilm and spores. Problems with anti-CDI therapy prompt researchers and clinicians to seek alternative ways of therapy. Identification of immunological epitopes in outer layer proteins and the use of them as antigens for anti-CDI vaccines would be a rational approach to prevent the disease, but unfortunately such vaccines are not available yet. In this article we review the course of the disease, virulence and risk factors. We summarize briefly epidemiological data and the latest achievements in CDI treatment.

  8. Nonantimicrobial drug targets for Clostridium difficile infections.

    PubMed

    Darkoh, Charles; Deaton, Magdalena; DuPont, Herbert L

    2017-09-01

    Clostridium difficile infection (CDI) is a major public health problem worldwide. Treatment has become complicated due to the emergence of strains with increased toxigenicity and sporulation rate, together with rampant antibiotics use that disrupts colonization resistance of the colonic microbiota. As a result, there is a critical need for nonantibiotic treatments. Therapies based on inhibiting the toxins, bacterial structures responsible for colonization, virulence and restoration of the gut microbiota are the most important nonantibiotic targets to combat CDI. This report outlines these targets and how they could become the focus of future therapeutic agents. Inhibiting colonization and virulence factors during CDI will disrupt pathogen persistence and decrease exposure to the inflammatory toxins, allowing the immune system to clear the infection.

  9. Clostridium difficile infection in hospitalized children in the United States

    PubMed Central

    Nylund, Cade M.; Goudie, Anthony; Garza, Jose M.; Fairbrother, Gerry; Cohen, Mitchell B.

    2015-01-01

    Objective To evaluate the trend, impact, severity and risk factors of Clostridium difficile infections in hospitalized children in the United States. Design A retrospective cohort study utilizing the triennial Healthcare Cost and Utilization Project Kids’ Inpatient Database years: 1997, 2000, 2003, and 2006. Setting Hospitalized children in the United States. Participants 10,495,728 nationally weighted hospital discharges and 21,274 with Clostridium difficile infection. Main Exposure Discharge diagnosis of Clostridium difficile infection. Outcome measures Trend in cases; impact and severity was measured by length of stay, hospital charges, colectomy rate and death rate. Results There was an increasing trend in cases of Clostridium difficile infection from 3,565 in 1997 to 7,779 in 2006 (p<.001). Clostridium difficile infections had an increased risk of death with an adjusted odds ratio (95% confidence interval); 1.20 (1.01–1.43), colectomy; 1.36 (1.04–1.79), longer length of stay; 4.34 (3.97–4.83) and higher charges; 2.12 (1.98–2.26). There was no trend in death, colectomy, length of stay, or charges over the four time periods. The risk of comorbid diagnoses associated with Clostridium difficile infection included inflammatory bowel disease, with an odds ratio of 11.42 (10.16–12.83), and other comorbid diagnoses associated with immunosuppression, or antibiotic administration. Conclusions There is an increasing trend and a significant impact of Clostridium difficile infections on hospitalized children. In contrast to adults, there is no increasing trend in the severity of Clostridium difficile infections in children. Children with medical conditions, including inflammatory bowel disease, immunosuppression, or conditions requiring antibiotic administration are at high risk of Clostridium difficile infection. PMID:21199971

  10. Clostridium difficile infection: monoclonal or polyclonal genesis?

    PubMed

    Hell, M; Permoser, M; Chmelizek, G; Kern, J M; Maass, M; Huhulescu, S; Indra, A; Allerberger, F

    2011-10-01

    Clostridium difficile is considered to be a leading cause of hospital-acquired diarrhea. C. difficile (CDI) infection shows a high rate of recurrence. There would have to be a predominantly monoclonal mechanism of CDI within individual patients in order for molecular epidemiologic tools such as polymerase chain reaction (PCR) ribotyping to be useful in outbreak investigation or differentiation between infection relapse versus re-infection. It was the aim of our study to determine whether CDI is of monoclonal or of polyclonal genesis. Between December 2009 and June 2010, 11 patients with nosocomial CDI were chosen arbitrarily. Five individual colonies of C. difficile were picked from each of the primary culture plates. Of 55 isolates gained, 47 were available for PCR ribotyping (eight isolates failed attempts to re-culture). Among these 47 isolates, eight different PCR ribotypes were identified. Only one of the 11 patients had a stool sample that yielded more than one ribotype (PCR ribotypes 438 and 232); this 67-year-old female cancer patient was already suffering from recurring diarrhea prior to the fatal episode of colitis which was subsequently investigated. We conclude that polyclonal infections may occasionally occur in patients with CDI. Our findings of predominantly monoclonal origin of CDI within patients suggest that molecular epidemiologic investigations can be used reliably for outbreak investigations or discrimination between relapse and re-infection.

  11. Therapeutic approaches for Clostridium difficile infections.

    PubMed

    Marsh, Jane W; Curry, Scott R

    2013-10-02

    Metronidazole and vancomycin remain the front-line therapies for most Clostridium difficile infections (CDI). However, recurrent CDI occurs in ∼ 25% of patients, causing significant morbidity and mortality and healthcare costs. For this population, traditional antibiotic therapies fail and new treatment options are greatly needed. The US Food and Drug Administration recently approved fidaxomicin for CDI treatment. This narrow-spectrum antibiotic preserves the normal gut microbiota and shows promise as a treatment for severe and recurrent CDI. Monoclonal antibodies and vaccines directed against toxin are currently in clinical trials and represent alternative, non-antibiotic therapies. Less traditional therapeutic interventions include bacteriotherapy with non-toxigenic C. difficile and fecal transplant. This commentary will provide an overview of current and forthcoming CDI therapies.

  12. [Laboratory diagnosis of Clostridium difficile infection].

    PubMed

    Alcalá-Hernández, Luis; Mena-Ribas, Ana; Niubó-Bosh, Jordi; Marín-Arriaza, Mercedes

    2016-11-01

    Clostridium difficile is the leading cause of nosocomial diarrhoea in developed countries, and is one of the main aetiologic agents of community diarrhea. The eruption of the hypervirulent strain BI/NAP1/027 has given rise to an increase in the morbidity and mortality of C.difficile infection (CDI). This document aims to review the main clinical pictures of CDI and the laboratory diagnosis, including sampling, transport and storage of specimens, specimen processing, diagnostic procedures, antimicrobial susceptibility testing, and molecular characterisation of the isolates. The main purpose of the article is to develop a practical document that provides answers to the main questions that arise in the laboratory diagnosis of CDI.

  13. Flooding and Clostridium difficile infection: a case-crossover analysis

    EPA Science Inventory

    Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospttalized and/or receiving antibiotics; however, community­ associated infections affecting otherwise healthy individuals have become more ...

  14. Flooding and Clostridium difficile infection: a case-crossover analysis

    EPA Science Inventory

    Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospttalized and/or receiving antibiotics; however, community­ associated infections affecting otherwise healthy individuals have become more ...

  15. Clostridium perfringens infection after transarterial chemoembolization for large hepatocellular carcinoma.

    PubMed

    Li, Jing-Huan; Yao, Rong-Rong; Shen, Hu-Jia; Zhang, Lan; Xie, Xiao-Ying; Chen, Rong-Xin; Wang, Yan-Hong; Ren, Zheng-Gang

    2015-04-14

    We report an unusual case of Clostridium perfringens liver abscess formation after transcatheter arterial chemoembolization (TACE) for large hepatocellular carcinoma. Severe deterioration in liver and renal function accompanied with hemocytolysis was found on the 2(nd) day after TACE. Blood culture found Clostridium perfringens and abdominal computed tomography revealed a gas-containing abscess in the liver. Following antibiotics administration and support care, the infection was controlled and the liver and renal function turned normal. The 2(nd) TACE procedure was performed 1.5 mo later and no recurrent Clostridium perfringens infection was found.

  16. The Changing Epidemiology of Clostridium difficile Infections

    PubMed Central

    Freeman, J.; Bauer, M. P.; Baines, S. D.; Corver, J.; Fawley, W. N.; Goorhuis, B.; Kuijper, E. J.; Wilcox, M. H.

    2010-01-01

    Summary: The epidemiology of Clostridium difficile infection (CDI) has changed dramatically during this millennium. Infection rates have increased markedly in most countries with detailed surveillance data. There have been clear changes in the clinical presentation, response to treatment, and outcome of CDI. These changes have been driven to a major degree by the emergence and epidemic spread of a novel strain, known as PCR ribotype 027 (sometimes referred to as BI/NAP1/027). We review the evidence for the changing epidemiology, clinical virulence and outcome of treatment of CDI, and the similarities and differences between data from various countries and continents. Community-acquired CDI has also emerged, although the evidence for this as a distinct new entity is less clear. There are new data on the etiology of and potential risk factors for CDI; controversial issues include specific antimicrobial agents, gastric acid suppressants, potential animal and food sources of C. difficile, and the effect of the use of alcohol-based hand hygiene agents. PMID:20610822

  17. Fecal microbiota transplantation in the treatment of Clostridium difficile infections.

    PubMed

    Austin, Matthew; Mellow, Mark; Tierney, William M

    2014-06-01

    In recent years, Clostridium difficile infections have become more frequent, more severe, more refractory to standard treatment, and more likely to recur. Current antibiotic treatment regimens for Clostridium difficile infection alter the normal gut flora, which provide colonization resistance against Clostridium difficile. Over the past few years, there has been a marked increase in the knowledge of the gut microbiota and its role in health maintenance and disease causation. This has, fortuitously, coincided with the use of a unique microbial replacement therapy, fecal microbiota transplantation, in the treatment of patients with multiple recurrent Clostridium difficile infections. We briefly review current knowledge of the gut microbiota's functions. We then review the indications for use of fecal microbiota transplantation in Clostridium difficile infection, the techniques employed, and results of treatment. Fecal microbiota transplantation has been shown to be efficacious for patients with multiply recurrent Clostridium difficile infections (reported cure rates of 90%), with an excellent short-term safety profile, and has been included in the American College of Gastroenterology treatment guidelines for this troublesome disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Clostridium novyi type A infection: a sporadic fatal case.

    PubMed

    McGuigan, Christopher; Roworth, Michael

    2002-01-01

    Infection with type A Clostridium novyi is rare. We report the case of a previously healthy 31-y-old woman with no known risk factors who died suddenly with a necrotizing soft tissue infection. We compare this case with a simultaneous outbreak of this infection amongst Scottish IDUs (injecting drug users).

  19. Clostridium novyi infection: a fatal association with injecting drug users.

    PubMed

    Ryan, J M; Paul, J; Curtis, S; Patel, N K

    2001-03-01

    Injecting drug users frequently use accident and emergency (A&E) departments to access emergency care for local and systemic infections. Clostridium novyi type A is a bacterium that has recently been associated with a number of fatalities among drug injecting addicts. The clinical course is described of a patient who attended an A&E department with septicaemia who was found at postmortem examination to have been infected with Clostridium novyi type A. Doctors working in A&E departments should be aware of the existence of this infection and be vigilant when treating injecting drug users with localised infection.

  20. Risk factors for Clostridium difficile infection.

    PubMed

    Bignardi, G E

    1998-09-01

    A systematic review of the literature to identify risk factors associated with Clostridium difficile infection was conducted. Two main outcomes were considered: C. difficile diarrhoea and C. difficile carriage. A qualitative assessment, based on a set of defined and consistently applied criteria, appeared to be the best approach for risk factors other than antibiotic use, as an approach based on meta-analysis would have utilized only the information provided by a minority of the studies. Risk factors for which there was evidence suggestive or consistent with an association with C. difficile diarrhoea were: increasing age (excluding infancy), severity of underlying diseases, non-surgical gastrointestinal procedures, presence of a nasogastric tube, anti-ulcer medications, stay on ITU, duration of hospital stay, duration of antibiotic course, administration of multiple antibiotics. For malignant haematological disorders there was evidence of an association only with C. difficile carriage, but there were no suitable studies to explore a possible association of this risk factor with symptomatic infection. Antibiotic use lent itself to quantitative assessment with meta-analysis using logistic regression. Exposure to an antibiotic was shown to be statistically significantly associated with both C. difficile diarrhoea and C. difficile carriage. The meta-analysis approach enabled the ranking of individual antibiotics in relation to the risk of C. difficile infection, though the 95% confidence intervals were often wide and overlapping. Antibiotics associated with a lower risk of C. difficile diarrhoea should be considered, especially when attempting to control a C. difficile outbreak or when prescribing for a patient with other C. difficile risk factors. This systematic review of the literature enabled the identification of features it would be desirable to consider in future epidemiological studies.

  1. Current Status of Clostridium difficile Infection Epidemiology

    PubMed Central

    Lessa, Fernanda C.; Gould, Carolyn V.; McDonald, L. Clifford

    2012-01-01

    The dramatic changes in the epidemiology of Clostridium difficile infection (CDI) during recent years, with increases in incidence and severity of disease in several countries, have made CDI a global public health challenge. Increases in CDI incidence have been largely attributed to the emergence of a previously rare and more virulent strain, BI/NAP1/027. Increased toxin production and high-level resistance to fluoroquinolones have made this strain a very successful pathogen in healthcare settings. In addition, populations previously thought to be at low risk are now being identified as having severe CDI. Recent genetic analysis suggests that C. difficile has a highly fluid genome with multiple mechanisms to modify its content and functionality, which can make C. difficile adaptable to environmental changes and potentially lead to the emergence of more virulent strains. In the face of these changes in the epidemiology and microbiology of CDI, surveillance systems are necessary to monitor trends and inform public health actions. PMID:22752867

  2. Clostridium difficile infection in an Iranian hospital

    PubMed Central

    2012-01-01

    Background Clostridium difficile infection (CDI) is an important cause of morbidity and mortality internationally, yet there are important regional differences in the epidemiology and microbiology of disease. Most reports have come from North America and Europe, with limited information from other regions, including the Middle East. Given the changes in the epidemiology of CDI in developed countries, particularly associated with the dissemination of hypervirulent epidemic clones, an understanding of the epidemiology and microbiology of CDI in diverse regions is warranted. This study involved collection of stool samples from individuals with diarrhea at the Isfahan University of Medical Sciences Teaching Hospital, Isfahan, Iran, between October 2010 and March 2011. Selective enrichment culture for C. difficile was performed and isolates were characterised using ribotyping, PCR for the detection of tcdA, tcdB and cdtB genes, and tcdC sequence analysis. Findings Clostridium difficile was isolated from 19/89 (21%) stool samples of 17/86 (20%) patients. 13/17 (77%) cases of CDI were hospital-associated. Patients with CDI were significantly older (43 ± 28y) than those with non-CDI diarrhea (24, ± 26y)(P = 0.018). All isolates were toxigenic, and possessed genes encoding for toxins A and B. Six (32%) of 19 isolates also possessed cdtB. Twelve ribotypes were identified. Ribotype 078/toxinotype V was most common, accounting for 4 (21%) of isolates. A single isolate of a different toxinotype V ribotype was identified, as was a toxinotype XXIV isolate. The remaining isolates consisted of 9 different toxinotype 0 ribotypes. Conclusions CDI is an important cause of diarrhea in patients in this hospital. The diversity of ribotypes was striking, and the number of different types suggests the presence of a broad range of strains in the community, the hospital or both. The predominance of toxinotype V strains, which have been associated with community-associated disease and food

  3. Clostridium difficile associated infection, diarrhea and colitis

    PubMed Central

    Hookman, Perry; Barkin, Jamie S

    2009-01-01

    A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods: pulsed-field gel electrophoresis (NAP1), restriction endonuclease analysis (BI) and polymerase chain reaction (027). In 2004 and 2005, the US Centers for Disease Control and Prevention (CDC) emphasized that the risk of C. difficile-associated diarrhea (CDAD) is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors (PPIs) have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. difficile-associated colitis (CDAC), was rare, but its incidence has increased dramatically. Up to two-thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease (IBD). C. difficile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficile-associated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate

  4. [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.

  5. Diagnosis and management of Clostridium difficile infection.

    PubMed

    Dupont, Herbert L

    2013-10-01

    Clostridium difficile infection (CDI) is increasing in frequency and severity in and out of the hospital, with a high probability of recurrence after treatment. The recent literature on CDI was reviewed using PubMed to include recent publications dealing with diagnosis and therapy. Real-time polymerase chain reaction is a sensitive and useful diagnostic test for CDI but there are growing concerns of false-positive test results if the rate of CDI is low in the patient population providing samples and/or if the population being studied commonly includes people with C difficile colonization. Recommended therapy of CDI includes oral metronidazole for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases, each given for 10 days. Colectomy is being performed more frequently in patients with fulminant CDI. For treatment of first recurrences the drug used in the first bout can be used again and for second recurrences longer courses of vancomycin often are given in a tapered dose or intermittently to allow gut flora reconstitution, or other treatments including fidaxomicin may be used. Bacteriotherapy with fecal transplantation is playing an increasing role in therapy of recurrent cases. Metagenomic studies of patients with CDI during successful therapy are needed to determine how best to protect the flora from assaults from antibacterial drugs and to develop optimal therapeutic approaches. Immunotherapy and immunoprophylaxis offer opportunities to prevent CDI, to speed up recovery from CDI, and to eliminate recurrent infection. Humanized monoclonal antitoxin antibodies and active immunization with vaccines against C difficile or its toxins are both in development and appear to be of potential value.

  6. Risk factors for Clostridium difficile infection in a hepatology ward.

    PubMed

    Vanjak, Dominique; Girault, Guillaume; Branger, Catherine; Rufat, Pierre; Valla, Dominique-Charles; Fantin, Bruno

    2007-02-01

    During 2001, Clostridium difficile infection was observed in 23 patients hospitalized in a hepatology ward (attack rate, 0.9%). Since strain typing ruled out a clonal dissemination, we performed a case-control study. In addition to antibiotic use as a risk factor, the C. difficile infection rate was higher among patients with autoimmune hepatitis (P<.01).

  7. Risk factors for Clostridium difficile infection in HIV-infected patients

    PubMed Central

    Imlay, Hannah; Kaul, Daniel; Rao, Krishna

    2016-01-01

    Background: Clostridium difficile infection is a healthcare-associated infection resulting in significant morbidity. Although immunosuppression is associated with Clostridium difficile infection acquisition and adverse outcomes, the epidemiology of Clostridium difficile infection in HIV-infected patients has been little studied in the era of antiretroviral therapy. This study identifies the risk factors for acquisition of Clostridium difficile infection in HIV-infected patients. Methods: A retrospective, propensity score–matched case–control study design was employed, with patients selected from our institution’s outpatient HIV clinic. Clostridium difficile infection cases were defined as having positive stool testing plus an appropriate clinical presentation. The propensity score was generated via multiple logistic regression from year of HIV diagnosis, age at first contact, duration of follow-up, gender, and initial CD4 count. Results: The 46 cases included were matched to a total of 180 controls. Prior antibiotic treatment was a significant predictor of Clostridium difficile infection (odds ratio: 13, 95% confidence interval: 3.49–48.8, p < .001) as was number of hospital admissions in the preceding year (odds ratio: 4.02, confidence interval: 1.81–8.94, p < .001). Having both proton pump inhibitor use and CD4 count <200 cells/µL significantly increased odds of Clostridium difficile infection in the multivariable model (odds ratio: 15.17, confidence interval: 1.31–175.9, p = .021). Conclusion: As in the general population, frequent hospitalizations and exposure to antimicrobials are independent predictors of Clostridium difficile infection acquisition in patients with HIV. Additionally, low CD4 count and proton pump inhibitor use are new potentially modifiable variables that can be targeted for prevention of Clostridium difficile infection in future interventional studies. PMID:28348742

  8. Carbapenem-Resistant Enterobacteriaceae (CRE) Infection

    MedlinePlus

    ... about VAP Diseases and Organisms Acinetobacter Burkholderia cepacia Clostridium difficile Patients Clinicians FAQs about C. difficile for ... Facilities/Settings State Health Departments Tracking C. difficile Clostridium Sordellii Carbapenem-resistant Enterobacteriaceae (CRE) Tracking CRE Interim ...

  9. Frequently Asked Questions about Surgical Site Infections

    MedlinePlus

    ... about VAP Diseases and Organisms Acinetobacter Burkholderia cepacia Clostridium difficile Patients Clinicians FAQs about C. difficile for ... Facilities/Settings State Health Departments Tracking C. difficile Clostridium Sordellii Carbapenem-resistant Enterobacteriaceae (CRE) Tracking CRE Interim ...

  10. Catheter-Associated Urinary Tract Infections

    MedlinePlus

    ... about VAP Diseases and Organisms Acinetobacter Burkholderia cepacia Clostridium difficile Patients Clinicians FAQs about C. difficile for ... Facilities/Settings State Health Departments Tracking C. difficile Clostridium Sordellii Carbapenem-resistant Enterobacteriaceae (CRE) Tracking CRE Interim ...

  11. Types of Healthcare-Associated Infections

    MedlinePlus

    ... about VAP Diseases and Organisms Acinetobacter Burkholderia cepacia Clostridium difficile Patients Clinicians FAQs about C. difficile for ... Facilities/Settings State Health Departments Tracking C. difficile Clostridium Sordellii Carbapenem-resistant Enterobacteriaceae (CRE) Tracking CRE Interim ...

  12. Fecal microbiota transplantation in children with recurrent Clostridium difficile infection.

    PubMed

    Pierog, Anne; Mencin, Ali; Reilly, Norelle Rizkalla

    2014-11-01

    Clostridium difficile eradication using fecal microbiota transplantation (FMT) has been successful in adults but little information is available in pediatrics. We report 6 pediatric patients with refractory C. difficile cured by FMT with no recurrences to date. Our results demonstrate that FMT can be an effective treatment for refractory C. difficile infection in pediatrics. Long-term safety and efficacy need to be studied.

  13. Healthcare-Associated Infections (HAIs) Data and Statistics

    MedlinePlus

    ... about VAP Diseases and Organisms Acinetobacter Burkholderia cepacia Clostridium difficile Patients Clinicians FAQs about C. difficile for ... Facilities/Settings State Health Departments Tracking C. difficile Clostridium Sordellii Carbapenem-resistant Enterobacteriaceae (CRE) Tracking CRE Interim ...

  14. Clostridium difficile Infection: Epidemiology, Pathogenesis, Risk Factors, and Therapeutic Options

    PubMed Central

    Seyedjavadi, Sima Sadat; Goudarzi, Hossein; Mehdizadeh Aghdam, Elnaz; Nazeri, Saeed

    2014-01-01

    The incidence and mortality rate of Clostridium difficile infection have increased remarkably in both hospital and community settings during the last two decades. The growth of infection may be caused by multiple factors including inappropriate antibiotic usage, poor standards of environmental cleanliness, changes in infection control practices, large outbreaks of C. difficile infection in hospitals, alteration of circulating strains of C. difficile, and spread of hypervirulent strains. Detection of high-risk populations could be helpful for prompt diagnosis and consequent treatment of patients suffering from C. difficile infection. Metronidazole and oral vancomycin are recommended antibiotics for the treatment of initial infection. Current treatments for C. difficile infection consist of supportive care, discontinuing the unnecessary antibiotic, and specific antimicrobial therapy. Moreover, novel approaches include fidaxomicin therapy, monoclonal antibodies, and fecal microbiota transplantation mediated therapy. Fecal microbiota transplantation has shown relevant efficacy to overcome C. difficile infection and reduce its recurrence. PMID:24991448

  15. Using expert process to combat Clostridium difficile infections.

    PubMed

    Guerreiro, Isabelle; Achonu, Camille; Volkening, Grace; MacFarlane, Sam; McCreight, Liz; Egan, Cathy; Robertson, Jennifer; Garber, Gary

    2016-12-01

    In 2008, Clostridium difficile rates were increasing in Ontario, Canada, and in response, hospitals were mandated by the Ontario Ministry of Health to publicly report their C difficile infection (CDI) rates. In order to assist hospitals which had ongoing CDI outbreaks, a process of an external infection control resource team (ICRT) was introduced. This article describes the function and process of the ICRT, managed by Public Health Ontario, and reviews the lessons learned over the first 5 years of operation. These lessons may assist other hospitals in managing their own infection prevention and control outbreak.

  16. Models for the study of Clostridium difficile infection

    PubMed Central

    Best, Emma L.; Freeman, Jane; Wilcox, Mark H.

    2012-01-01

    Models of Clostridium difficile infection (C. difficile) have been used extensively for Clostridium difficile (C. difficile) research. The hamster model of C. difficile infection has been most extensively employed for the study of C. difficile and this has been used in many different areas of research, including the induction of C. difficile, the testing of new treatments, population dynamics and characterization of virulence. Investigations using in vitro models for C. difficile introduced the concept of colonization resistance, evaluated the role of antibiotics in C. difficile development, explored population dynamics and have been useful in the evaluation of C. difficile treatments. Experiments using models have major advantages over clinical studies and have been indispensible in furthering C. difficile research. It is important for future study programs to carefully consider the approach to use and therefore be better placed to inform the design and interpretation of clinical studies. PMID:22555466

  17. Fecal microbiota transplantation for the management of Clostridium difficile infection.

    PubMed

    Rao, Krishna; Young, Vincent B

    2015-03-01

    This article discusses the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The disruption of the normal gut microbiota is central to the pathogenesis of CDI, and disruption persists in recurrent disease. The use of FMT for recurrent CDI is characterized by a high response rate and short term safety is excellent, although the long-term effects of FMT are as yet unknown. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Self-Administered Home Series Fecal "Minitransplants" for Recurrent Clostridium difficile Infection on a Rectal Remnant.

    PubMed

    Popa, Daniel; Laszlo, Mihaela; Ciobanu, Lidia; Ucenic, Elena; Mihalache, Manuela; Pascu, Oliviu

    2015-12-01

    A fecal microbiota transplant has proved to be an extremely effective method for patients with recurrent infections with Clostridium difficile. We present the case of a 65-year-old female patient with multiple Clostridium difficile infection (CDI) relapses on the rectal remnant, post-colectomy for a CDI-related toxic megacolon. The patient also evidenced associated symptomatic Clostridium difficile vaginal infection. She was successfully treated with serial fecal "minitransplants" (self-administered at home) and metronidazole ovules.

  19. Clostridium difficile Infection in Pediatric Inflammatory Bowel Disease

    PubMed Central

    Sears, Cynthia L.; Oliva-Hemker, Maria

    2015-01-01

    Abstract: Children with inflammatory bowel disease (IBD) are disproportionately susceptible to Clostridium difficile infection (CDI) and the incidence is increasing. There has also been growing recognition of asymptomatic C. difficile colonization in pediatric IBD, which can sometimes be very difficult to distinguish from symptomatic C. difficile–associated disease in this population. In this study, we discuss the current knowledge of C. difficile infection in children with IBD, reviewing epidemiology, risk factors, and outcomes that often differ from the adult IBD population, and discuss the complexities and dilemmas of diagnosing and treating CDI in pediatric IBD. PMID:26689599

  20. Disease transmission model for community-associated Clostridium difficile infection.

    PubMed

    Otten, A M; Reid-Smith, R J; Fazil, A; Weese, J S

    2010-06-01

    Participating researchers and public health personnel at a Canadian workshop in 2007, noted considerable gaps in current understanding of community-associated Clostridium difficile infection (CA-CDI), specifically infection sources and risk factors. A disease transmission model for CA-CDI was requested as an initial step towards a risk assessment, to analyse infection sources and risk factors, addressing priority research areas. The developed model contains eight infection states (susceptible, gastrointestinal exposure, colonized, diseased, deceased, clinically resolved colonized, relapse diseased, and cleared) and notes directional transfers between the states. Most published research used focused on hospital-associated C. difficile infection (HA-CDI) and further studies are needed to substantiate the use of HA-CDI knowledge in the transmission of CA-CDI. The aim was to provide a consistent framework for researchers, and provide a theoretical basis for future quantitative risk assessment of CA-CDI.

  1. Clostridium difficile infection in the elderly.

    PubMed

    Taslim, Hartono

    2009-07-01

    The aging society and the advanced of supportive treatment means that large numbers of elderly patients with risk factors for C difficile enterocolitis will continue to receive care in intensive care unit. Antibiotic resistance and older, sicker patients means that combination antibiotic therapy will become a trend in clinical setting. Age, several co-morbidities, and gastrointestinal surgery appear to be specific risk factors for C difficile infection. Diarrhea which is the only symptom in hospitalized patient should drive us to rethink about the possibility of C difficile infection especially in the elderly patient. Prudent use of antibiotic, infection control are strategies to prevent C difficile infection in clinical setting. Elderly patients who undergo gastrointestinal surgery have an increased rate of C difficile infection because of commonly used nasogastric tube. Gastrointestinal surgical patients typically have preoperative bowel preparation, receive oral preoperative antibiotics that are poorly absorbed, impaired bowel motility secondary to ileus, receive systemic preoperative antibiotics prophylaxis, and have variable lengths of no oral caloric intake during the preoperative period. The continued imprudent use of prolonged postoperative systemic antibiotics for presumed preventive purposes, particularly among the elderly and patients who have nasogastric tubes or other enteric tubes, appears to be a recipe for preventable infections with C difficile.

  2. Clostridium difficile infection: A critical analysis of the guidance.

    PubMed

    Aziz, Ann-Marie

    A recent report by the Department of Health, Clostridium Difficile Infection: How to deal with the problem - a board to ward approach, is a revised set of guidelines based on best practice and key recommendations for the NHS to ensure the control of Clostridium difficile infection (CDI). It takes into account a national framework for clinical governance which did not previously exist, a framework that gives significant weight to infection control as a matter of patient safety, and highlights that all clinicians have a personal responsibility for infection prevention and control. It puts the onus on Trust management and PCTs to ensure that measures are in place to prevent and manage CDI according to best evidence. However, the report fails to explain how these measures will have an impact on finance and resources on an already burdened system. The author explains how much of the report is comparable with the one published in 1994, and highlights many of its limitations within the busy hospital setting. Reducing CDI is achievable, as many hospitals are showing large reductions in their CDI rates. Healthcare workers must be applauded for their success in reducing CDI, but there is more to be done.

  3. Clostridium difficile infection in the twenty-first century

    PubMed Central

    Ghose, Chandrabali

    2013-01-01

    Clostridium difficile is a spore-forming gram-positive bacillus, and the leading cause of antibiotic-associated nosocomial diarrhea and colitis in the industrialized world. With the emergence of a hypervirulent strain of C. difficile (BI/NAP1/027), the epidemiology of C. difficile infection has rapidly changed in the last decade. C. difficile infection, once thought to be an easy to treat bacterial infection, has evolved into an epidemic that is associated with a high rate of mortality, causing disease in patients thought to be low-risk. In this review, we discuss the changing face of C .difficile infection and the novel treatment and prevention strategies needed to halt this ever growing epidemic. PMID:26038491

  4. Predictors of Clostridium difficile colitis infections in hospitals

    PubMed Central

    RICCIARDI, R.; HARRIMAN, K.; BAXTER, N. N.; HARTMAN, L. K.; TOWN, R. J.; VIRNIG, B. A.

    2008-01-01

    SUMMARY Hospital-level predictors of high rates of ‘Clostridium difficile-associated disease’ (CDAD) were evaluated in over 2300 hospitals across California, Arizona, and Minnesota. American Hospital Association data were used to determine hospital characteristics associated with high rates of CDAD. Significant correlations were found between hospital rates of CDAD, common infections and other identified pathogens. Hospitals in urban areas had higher average rates of CDAD; yet, irrespective of geographic location, hospital rates of CDAD were associated with other infections. In addition, hospitals with ‘high CDAD’ rates had slower turnover of beds and were more likely to offer transplant services. These results reveal large differences in rates of CDAD across regions. Hospitals with high rates of CDAD have high rates of other common infections, suggesting a need for broad infection control policies. PMID:17686193

  5. Clostridium septicum infection of hepatic metastases following alcohol injection: a case report

    PubMed Central

    2009-01-01

    Clostridium septicum infections are generally associated with gastrointestinal or hematologic malignancies. We report the first case of hepatic metastases infection with Clostridium septicum that followed alcohol injection of liver lesion. Clinicians should consider this possibility in patients with underlying malignancy who present with hepatic abscess, as prompt surgical drainage and empiric antibiotics may be life saving. PMID:20072687

  6. Clostridium septicum infection of hepatic metastases following alcohol injection: a case report.

    PubMed

    Saleh, Neam; Sohail, Muhammad R; Hashmey, Rayhan H; Al Kaabi, Mohammed

    2009-12-31

    Clostridium septicum infections are generally associated with gastrointestinal or hematologic malignancies. We report the first case of hepatic metastases infection with Clostridium septicum that followed alcohol injection of liver lesion. Clinicians should consider this possibility in patients with underlying malignancy who present with hepatic abscess, as prompt surgical drainage and empiric antibiotics may be life saving.

  7. Two Serious Cases of Infection with Clostridium celatum after 40 Years in Hiding?

    PubMed Central

    Hoegh, Silje Vermedal; Holt, Hanne Marie; Justesen, Ulrik Stenz

    2015-01-01

    Clostridium celatum [ce.la'tum. L. adj. celatum hidden] has been known since 1974, when it was isolated from human feces. In 40 years, no association with human infection has been reported. In this work, we present two serious cases of infection with the anaerobic Gram-positive rod Clostridium celatum. PMID:26560535

  8. Two Serious Cases of Infection with Clostridium celatum after 40 Years in Hiding?

    PubMed

    Agergaard, Charlotte Nielsen; Hoegh, Silje Vermedal; Holt, Hanne Marie; Justesen, Ulrik Stenz

    2016-01-01

    Clostridium celatum [ce.la'tum. L. adj. celatum hidden] has been known since 1974, when it was isolated from human feces. In 40 years, no association with human infection has been reported. In this work, we present two serious cases of infection with the anaerobic Gram-positive rod Clostridium celatum. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. The prospect for vaccines to prevent Clostridium difficile infection.

    PubMed

    Ghose, Chandrabali; Kelly, Ciarán P

    2015-03-01

    Clostridium difficile is a spore-forming anaerobic gram-positive organism that is the leading cause of antibiotic-associated nosocomial infectious diarrhea in the Western world. This article describes the evolving epidemiology of C difficile infection (CDI) in the twenty-first century, evaluates the importance of vaccines against the disease, and defines the roles of both innate and adaptive host immune responses in CDI. The effects of passive immunotherapy and active vaccination against CDI in both humans and animals are also discussed.

  10. Fecal microbiota transplantation and emerging treatments for Clostridium difficile infection.

    PubMed

    Gens, Krista D; Elshaboury, Ramy H; Holt, Jessica S

    2013-10-01

    Due to the increased incidence and recurrence of Clostridium difficile infection, health care providers are seeking new and alternative treatments to the standard antibiotic therapy. The objective of this article is to present a review on the background, microbiologic efficacy, clinical efficacy, and safety of fecal microbiota transplantation and to provide an overview of emerging treatment options currently under investigation. Emerging treatment options discussed include the use of monoclonal antibodies directed against toxins A and B, C difficile vaccination, and transplantation of nontoxigenic C difficile strains.

  11. [Treating Clostridium difficile infection with faecal transplantation: donor microbiological testing].

    PubMed

    Russello, Giuseppe; Brovarone, Flavia; Bardaro, Marcellino; Carretto, Edoardo

    2014-03-01

    Clostridium difficile associated diseases (CDADs) or C. difficile infections (CDIs) are increasing in incidence, severity and mortality. Among patients with CDIs, those with recurrent disease are less responsive to traditional therapies with commonly used drugs, such as metronidazole and vancomycin. Faecal microbiota transplantation is an old therapeutic procedure that has been recently proposed as a safe and effective treatment for CDI patients non-responsive to antibiotic therapy. In this paper we discuss the microbiological procedures that should be performed on faecal microbiota donors.

  12. [Recurrent Clostridium difficile infection treated with faecal microbiota transplantation].

    PubMed

    Fløe, Andreas; Leutscher, Peter

    2014-02-17

    Treatment of severe Clostridium difficile infection (CDI) poses a clinical challenge. Emerging evidence supports the use of faecal microbiota transplantation (FMT). An 81-year-old man was admitted with a third recurrent episode of CDI within two months. Because of clinical deterioration with development of pancolitis in spite of two weeks of metronidazole and vanco-mycin treatment, FMT was performed using a duodenal tube. The patient recovered completely without further relapse during follow-up. FMT was shown to be an efficient adjuvant treatment of complicated CDI.

  13. 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.

  14. Current concepts in the management of Clostridium tetani infection.

    PubMed

    Brook, Itzhak

    2008-06-01

    This review summarizes the microbiology, management and prevention of tetanus. Tetanus is an acute toxemic illness caused by Clostridium tetani infection at a laceration or break in the skin. It can also occur as a complication of burns, puerperal infections, umbilical stumps (tetanus neonatorum) and surgical-site infection. Tetanus is an intoxication, manifested mostly by neuromuscular dysfunction, caused by tetanal exotoxin (tetanospasmin), a potent exotoxin produced by C. tetani. It starts with tonic spasms of the skeletal muscles and is followed by paroxysmal contractions. The muscle stiffness initially involves the jaw (lockjaw) and neck and later becomes generalized. Treatment goals include interrupting the production of toxin, neutralizating the unbound toxin, controlling muscle spasms, managing dysautonomia and appropriate supportive management. Specific therapy includes intramuscular administration of tetanus immunoglobulin to neutralize circulating toxin before it binds to neuronal cell membranes. The disease can be prevented by immunization with tetanal toxoid and appropriate wound care.

  15. 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

  16. 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.

  17. Flooding and Clostridium difficile Infection: A Case-Crossover Analysis

    PubMed Central

    Lin, Cynthia J.; Wade, Timothy J.; Hilborn, Elizabeth D.

    2015-01-01

    Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospitalized and/or receiving antibiotics; however, community-associated infections affecting otherwise healthy individuals have become more commonly reported. A case-crossover study was used to assess emergency room (ER) and outpatient visits for C. difficile infection following flood events in Massachusetts from 2003 through 2007. Exposure status was based on whether or not a flood occurred prior to the case/control date during the following risk periods: 0–6 days, 7–13 days, 14–20 days, and 21–27 days. Fixed-effects logistic regression was used to estimate the risk of diagnosis with C. difficile infection following a flood. There were 129 flood events and 1575 diagnoses of C. difficile infection. Among working age adults (19–64 years), ER and outpatient visits for C. difficile infection were elevated during the 7–13 days following a flood (Odds Ratio, OR = 1.69; 95% Confidence Interval, CI: 0.84, 3.37). This association was more substantial among males (OR = 3.21; 95% CI: 1.01–10.19). Associations during other risk periods were not observed (p < 0.05). Although we were unable to differentiate community-associated versus nosocomial infections, a potential increase in C. difficile infections should be considered as more flooding is projected due to climate change. PMID:26090609

  18. Conventional and alternative treatment approaches for Clostridium difficile infection

    PubMed Central

    Aljarallah, Khalid M.

    2017-01-01

    Clostridium difficile-associated disease continues to be one of the leading health concerns worldwide. C. difficile is considered as a causative agent of nosocomial diarrhea that causes serious infection, which may result in death. The incidences of C. difficile infection (CDI) in developed countries have become increasingly high which may be attributed to the emergence of newer epidemic strains, extensive use of antibiotics, and limited alternative therapies. The available treatment options against CDI are expensive and promote resistance. Therefore, there is urgent need for new approaches to meet these challenges. This review discusses the current understanding of CDI, the existing clinical treatment strategies and future potential options as antidifficile agents based on the available published works. PMID:28293151

  19. Fecal microbiota transplantation in treating Clostridium difficile infection.

    PubMed

    Brown, William R

    2014-08-01

    Clostridium difficile infection (CDI) is an increasingly common and severe international health problem. Customary treatment of this infection, usually with antibiotics, is often ineffective and its recurrence is common. In recent years the treatment of recurrent or refractory CDI by the transfer of stool from an uninfected person, so called fecal "microbiota transplantation" has become recognized as effective and generally safe. The effectiveness of this novel treatment is incompletely defined but is likely to be due to its correction of the intestinal dysbiosis that characterizes the disease. Practical methods for the administration of the transplantation have been described. This review summarizes the current reported experiences with fecal microbiota transplantation in the treatment for CDI. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  20. 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

  1. Recurrent Clostridium difficile infections: the importance of the intestinal microbiota.

    PubMed

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

    2014-06-21

    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.

  2. ECCMID 2016: addressing the burden of recurrent Clostridium difficile infections.

    PubMed

    Eckmann, Christian; Lyon, Sue

    2016-10-01

    26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), 9-12th April 2016, Amsterdam, The Netherlands The European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) is the annual scientific meeting of the European Society of Clinical Microbiology. ECCMID 2016, held in Amsterdam, The Netherlands, was attended by over 11,600 clinical microbiologists and infectious disease physicians from more than 120 countries. The Congress offered an essential opportunity to learn more about the diagnosis, prevention and treatment of healthcare-associated infections, especially those caused by Clostridium difficile. Recurrent C. difficile infections have an especially serious adverse impact on patients, their families and healthcare systems across Europe and around the world, and continue to be a cause for concern among ECCMID delegates and their colleagues responsible for managing vulnerable patients in acute hospitals and other healthcare facilities.

  3. Clostridium difficile infection: molecular pathogenesis and novel therapeutics

    PubMed Central

    Rineh, Ardeshir; Kelso, Michael J; Vatansever, Fatma; Tegos, George P; Hamblin, Michael R

    2015-01-01

    The Gram-positive anaerobic bacterium Clostridium difficile produces toxins A and B, which can cause a spectrum of diseases from pseudomembranous colitis to C. difficile-associated diarrhea. A limited number of C. difficile strains also produce a binary toxin that exhibits ADP ribosyltransferase activity. Here, the structure and the mechanism of action of these toxins as well as their role in disease are reviewed. Nosocomial C. difficile infection is often contracted in hospital when patients treated with antibiotics suffer a disturbance in normal gut microflora. C. difficile spores can persist on dry, inanimate surface for months. Metronidazole and oral vancomycin are clinically used for treatment of C. difficile infection but clinical failure and concern about promotion of resistance are motivating the search for novel non-antibiotic therapeutics. Methods for controlling both toxins and spores, replacing gut microflora by probiotics or fecal transplant, and killing bacteria in the anaerobic gut by photodynamic therapy are discussed. PMID:24410618

  4. Genome Sequence of Clostridium paraputrificum 373-A1 Isolated in Chile from a Patient Infected with Clostridium difficile.

    PubMed

    Guerrero-Araya, Enzo; Plaza-Garrido, Angela; Díaz-Yañez, Fernando; Pizaro-Guajardo, Marjorie; Valenzuela, Sandro L; Meneses, Claudio; Gil, Fernando; Castro-Nallar, Eduardo; Paredes-Sabja, Daniel

    2016-11-03

    Clostridium paraputrificum is a gut microbiota member reported in several cases of bacteremia and coinfections. So far, only one genome sequence of a C. paraputrificum (AGR2156) isolate is available. Here, we present the draft genome of C. paraputrificum strain 373-A1, isolated from stools from a patient with C. difficile infection.

  5. Genome Sequence of Clostridium paraputrificum 373-A1 Isolated in Chile from a Patient Infected with Clostridium difficile

    PubMed Central

    Guerrero-Araya, Enzo; Plaza-Garrido, Angela; Díaz-Yañez, Fernando; Pizaro-Guajardo, Marjorie; Valenzuela, Sandro L.; Meneses, Claudio; Gil, Fernando

    2016-01-01

    Clostridium paraputrificum is a gut microbiota member reported in several cases of bacteremia and coinfections. So far, only one genome sequence of a C. paraputrificum (AGR2156) isolate is available. Here, we present the draft genome of C. paraputrificum strain 373-A1, isolated from stools from a patient with C. difficile infection. PMID:27811092

  6. Revised nomenclature of Clostridium difficile toxins and associated genes.

    PubMed

    Rupnik, Maja; Dupuy, Bruno; Fairweather, Neil F; Gerding, Dale N; Johnson, Stuart; Just, Ingo; Lyerly, David M; Popoff, Michel R; Rood, Julian I; Sonenshein, Abraham L; Thelestam, Monica; Wren, Brendan W; Wilkins, Tracy D; von Eichel-Streiber, Christoph

    2005-02-01

    Several different nomenclatures have been applied to the Clostridium difficile toxins and their associated genes. This paper summarizes the new nomenclature that has been agreed to by the research groups currently active in the field. The revised nomenclature includes C. difficile toxins and other related large clostridial toxins produced by Clostridium sordellii and Clostridium novyi, and corresponding toxin genes, as well as toxin production types of C. difficile strains.

  7. Fecal microbiota transplantation in relapsing Clostridium difficile infection

    PubMed Central

    Rohlke, Faith

    2012-01-01

    Clostridium difficile infection rates are Climbing in frequency and severity, and the spectrum of susceptible patients is expanding beyond the traditional scope of hospitalized patients receiving antibiotics. Fecal microbiota transplantation is becoming increasingly accepted as an effective and safe intervention in patients with recurrent disease, likely due to the restoration of a disrupted microbiome. Cure rates of > 90% are being consistently reported from multiple centers. Transplantation can be provided through a variety of methodologies, either to the lower proximal, lower distal, or upper gastrointestinal tract. This review summarizes reported results, factors in donor selection, appropriate patient criteria, and the various preparations and mechanisms of fecal microbiota transplant delivery available to clinicians and patients. PMID:23152734

  8. 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

  9. Clostridium difficile: Changing Epidemiology, Treatment and Infection Prevention Measures.

    PubMed

    Cecil, Jane A

    2012-12-01

    Clostridium difficile was first reported as a cause of antibiotic-associated colitis in 1978. In more recent years we have witnessed disturbing trends associated with C. difficile infection (CDI). CDI has become more common, affecting populations previously considered at low risk, more severe with an associated increase in mortality, and more difficult to treat with some patients experiencing multiple relapses and a reduced responsiveness to previously effective antibiotics. These trends have been coincident with the emergence of a new hypervirulent strain responsible for several outbreaks in the last decade. Fortunately, we have also seen promising developments, particularly with regard to testing and treatment. This review discusses recent changes in the epidemiology of CDI and recent developments in the testing, treatment and prevention of CDI.

  10. The potential for emerging therapeutic options for Clostridium difficile infection.

    PubMed

    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.

  11. 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.

  12. Clostridium difficile Infection and Inflammatory Bowel Disease: A Review

    PubMed Central

    Sinh, Preetika; Barrett, Terrence A.; Yun, Laura

    2011-01-01

    The incidence of Clostridium difficile infection (CDI) has significantly increased in the last decade in the United States adding to the health care burden of the country. Patients with inflammatory bowel disease (IBD) have a higher prevalence of CDI and worse outcomes. In the past, the traditional risk factors for CDI were exposure to antibiotics and hospitalizations in elderly people. Today, it is not uncommon to diagnose CDI in a pregnant women or young adult who has no risk factors. C. difficile can be detected at the initial presentation of IBD, during a relapse or in asymptomatic carriers. It is important to keep a high index of suspicion for CDI in IBD patients and initiate prompt treatment to minimize complications. We summarize here the changing epidemiology, pathogenesis, risk factors, clinical features, and treatment of CDI in IBD. PMID:21915178

  13. Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis.

    PubMed

    Chan, Khee-Siang; Lee, Wen-Ying; Yu, Wen-Liang

    2016-12-01

    Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents. However, CMV colitis is increasingly recognized in immunocompetent hosts. Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection. Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV-PCR in blood and/or stool samples while pending histological diagnosis.

  14. The microbiota and immune response during Clostridium difficile infection.

    PubMed

    Buonomo, Erica L; Petri, William A

    2016-10-01

    Clostridium difficile is a gram-positive, spore forming anaerobe that infects the gut when the normal microbiota has been disrupted. C. difficile infection (CDI) is the most common cause of hospital acquired infection in the United States, and the leading cause of death due to gastroenteritis. Patients suffering from CDI have varying symptoms which range from mild diarrhea to pseudomembranous colitis and death. The involvement of the immune response to influence disease severity is just beginning to be investigated. There is evidence that the immune response can facilitate either protective or pathogenic phenotypes, suggesting it plays a multifaceted role during CDI. In addition to the immune response, the microbiota is pivotal in dictating the pathogenesis to CDI. A healthy microbiota effectively inhibits infection by restricting the ability of C. difficile to expand in the colon. Thus, understanding which immune mediators and components of the microbiota play beneficial roles during CDI will be important to future therapeutic developments. This review outlines how the microbiota can modulate specific immune mediators, such as IL-23 and others, to influence disease outcome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The microbiota and immune response during Clostridium difficile infection

    PubMed Central

    Buonomo, Erica L; Petri, William A.

    2016-01-01

    Clostridium difficile is a gram-positive, spore forming anaerobe that infects the gut when the normal microbiota has been disrupted. C. difficile infection (CDI) in the United States is the most common cause of hospital acquired infection, and the leading cause of death due to gastroenteritis. Patients suffering from CDI have varying symptoms which range from mild diarrhea to pseudomembranous colitis and death. The involvement of the immune response to influence disease severity is just beginning to be investigated. There is evidence that the immune response can facilitate either protective or pathogenic phenotypes, suggesting it plays a multifaceted role during CDI. In addition to the immune response, the microbiota is pivotal in dictating the pathogenesis to CDI. A healthy microbiota effectively inhibits infection by restricting the ability of C. difficile to expand in the colon. Thus, understanding which immune mediators and components of the microbiota play beneficial roles during CDI will be important to future therapeutic developments. This review outlines how the microbiota can modulate specific immune mediators, such as IL-23 and others, to influence disease outcome. PMID:27212111

  16. Present and past perspectives on Clostridium difficile infection.

    PubMed

    Álvarez-Hernández, D A; González-Chávez, A M; González-Hermosillo-Cornejo, D; Franyuti-Kelly, G A; Díaz-Girón-Gidi, A; Vázquez-López, R

    2017-07-03

    Clostridium difficile is a Gram-positive bacillus that has become one of the main hospital-acquired human gastrointestinal infections in recent years. Its incidence is on the rise, involving more virulent strains, affecting new and previously uncontemplated groups of patients, and producing changes in clinical presentation and treatment response that influence disease outcome. Early diagnosis and disease stratification based on the severity of C.difficile infection are essential for therapeutic management and the implementation of containment measures. However, the speed at which new strains with greater pathogenicity are developing is surpassing that of the development of new drugs, making it necessary to validate other therapeutic options. The present article is a review of the epidemiologic, pathophysiologic, diagnostic, and therapeutic aspects of C.difficile infection, from its first isolation to the present date, that aims to contribute to the preparation of general physicians and specialists, so that patients with this infection receive opportune and quality medical attention. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  17. 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.

  18. Role of cephalosporins in the era of Clostridium difficile infection

    PubMed Central

    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. PMID:27659735

  19. Clostridium difficile infection worsens the prognosis of ulcerative colitis

    PubMed Central

    Negrón, María E; Barkema, Herman W; Rioux, Kevin; De Buck, Jeroen; Checkley, Sylvia; Proulx, Marie-Claude; Frolkis, Alexandra; Beck, Paul L; Dieleman, Levinus A; Panaccione, Remo; Ghosh, Subrata; Kaplan, Gilaad G

    2014-01-01

    BACKGROUND: The impact of Clostridium difficile infections among ulcerative colitis (UC) patients is well characterized. However, there is little knowledge regarding the association between C difficile infections and postoperative complications among UC patients. OBJECTIVE: To determine whether C difficile infection is associated with undergoing an emergent colectomy and experiencing postoperative complications. METHODS: The present population-based case-control study identified UC patients admitted to Calgary Health Zone hospitals for a flare between 2000 and 2009. C difficile toxin tests ordered in hospital or 90 days before hospital admission were provided by Calgary Laboratory Services (Calgary, Alberta). Hospital records were reviewed to confirm diagnoses and to extract clinical data. Multivariate logistic regression analyses were performed among individuals tested for C difficile to examine the association between C difficile infection and emergent colectomy and diagnosis of any postoperative complications and, secondarily, an infectious postoperative complication. Estimates were presented as adjusted ORs with 95% CIs. RESULTS: C difficile was tested in 278 (58%) UC patients and 6.1% were positive. C difficile infection was associated with an increased risk for emergent colectomy (adjusted OR 3.39 [95% CI 1.02 to 11.23]). Additionally, a preoperative diagnosis of C difficile was significantly associated with the development of postoperative infectious complications (OR 4.76 [95% CI 1.10 to 20.63]). CONCLUSION: C difficile diagnosis worsened the prognosis of UC by increasing the risk of colectomy and postoperative infectious complications following colectomy. Future studies are needed to explore whether early detection and aggressive management of C difficile infection will improve UC outcomes. PMID:25157528

  20. Novel risk factors for recurrent Clostridium difficile infection in children.

    PubMed

    Nicholson, Maribeth R; Thomsen, Isaac P; Slaughter, James C; Creech, C Buddy; Edwards, Kathryn M

    2015-01-01

    Clostridium difficile, a common cause of antibiotic-associated diarrhea, has been reported to recur in high rates in adults. The rates and risk factors for recurrent C difficile infection (rCDI) in children have not been well established. We conducted a retrospective cohort study of 186 pediatric patients seen at a tertiary care referral center for a 5-year period diagnosed as having a primary C difficile infection. Children with recurrent disease, defined as return of symptoms of C difficile infection and positive testing ≤60 days after the completion of therapy, were compared with children who did not experience an episode of recurrence. Of the 186 pediatric patients included in this study, 41 (22%) experienced rCDI. On univariable analysis, factors significantly associated with rCDI included malignancy, recent hospitalization, recent surgery, antibiotic use, number of antibiotic exposures by class, acid blocker use, immunosuppressant use, and hospital-acquired disease. On multivariable analysis, malignancy (odds ratio [OR] 3.39, 95% confidence interval [CI] 1.52-7.85), recent surgery (OR 2.40, 95% CI 1.05-5.52), and the number of antibiotic exposures by class (OR 1.33, 95% CI 1.01-1.75) were significantly associated with recurrent disease in children. The rate of rCDI in children was 22%. Recurrence was significantly associated with the risk factors of malignancy, recent surgery, and the number of antibiotic exposures by class.

  1. 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

  2. Clostridium difficile infection prevention: biotherapeutics, immunologics, and vaccines.

    PubMed

    Gerding, Dale N

    2012-01-01

    We are in the midst of a resurgence of Clostridium difficile infection (CDI) in North America and Europe for which morbidity and mortality are higher than ever seen. C. difficile has risen in frequency to become the most common healthcare-associated infection pathogen, exceeding methicillin-resistant Staphylococcus aureus in many hospitals. Protection against CDI is thought to be mediated first by the normal bacterial microbiota, supplemented by an adaptive immune antibody response directed primarily at C. difficile toxins. Treatment of CDI is with antimicrobials that also further disrupt the protective bacterial microbiota leaving the patient susceptible to recurrent CDI. In addition, patients most susceptible to CDI, the advanced elderly, may already have a limited immune response and fail to increase their adaptive immune response with infection. The importance of both of these protective modalities has been demonstrated by 1) the success of fecal microbiota to restore "colonization resistance" for patients with multiple recurrences of CDI, and 2) the marked reduction in CDI recurrences with the use of intravenous monoclonal antibodies directed against toxin A and toxin B as an adjunct to antimicrobial treatment. Anti-toxin vaccines, passive monoclonal anti-toxin antibodies, and non-toxigenic C. difficile (to restore colonization resistance) are already undergoing patient clinical trials. The opportunity to prevent CDI is compelling and future research should focus on understanding the critical elements of the microbiota needed to restore colonization resistance and on development of novel immunologic strategies that include systemic and mucosal vaccines and passive immune modulators.

  3. Clostridium Difficile Infection and Takotsubo Cardiomyopathy: Is There a Relation?

    PubMed Central

    Virk, Hafeez Ul Hassan; Inayat, Faisal

    2016-01-01

    Context: Takotsubo cardiomyopathy (TCM) mimics acute coronary syndrome and is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery stenosis. It is a transient condition that typically precedes physical or emotional triggers. Case Report: We describe the case of a 65-year-old woman who presented to our institution with symptomatic Clostridium difficile infection. 24 hours after admission, the patient complained of severe, retrosternal chest pain. Electrocardiogram showed diffuse elevation of ST-segment in the chest leads; however, coronary angiography demonstrated normal coronary arteries. Therein, an echocardiography was performed, which revealed apical ballooning and hypercontractile base with global left ventricular hypokinesis. These features were consistent with TCM. The patient was managed conservatively. Repeat echocardiogram 2 weeks later showed resolution of heart failure. Conclusion: To our research, this is the first report of TCM caused by C. difficile infection. Clinicians involved in the care of patients with C. difficile infection must be aware of this complication and should consider TCM in those who develop atypical chest pain. PMID:27583241

  4. First isolation of Clostridium indolis in a patient with chronic osteitis: a case report and literature review of human infections related to Clostridium saccharolyticum group species.

    PubMed

    Lotte, Romain; Lotte, Laurène; Bouvet, Philippe; Degand, Nicolas; Bal, Antonin; Carles, Michel; de Dompsure, Regis Bernard; Popoff, Michel-Robert; Ruimy, Raymond

    2016-12-01

    Clostridium indolis is an anaerobic spore-forming Gram-positive bacillus belonging to the Clostridium saccharolyticum group. Its clinical significance in human remains poorly known. We describe the first case of osteitis related to C. indolis, identified by MALDI-TOF mass spectrometry and provide a literature review of human infections related to C. saccharolyticum group species.

  5. 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

  6. 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.

  7. 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.

  8. Using a Novel Lysin To Help Control Clostridium difficile Infections

    PubMed Central

    Wang, Qiong; Euler, Chad W.; Delaune, Aurelia

    2015-01-01

    As a consequence of excessive antibiotic therapies in hospitalized patients, Clostridium difficile, a Gram-positive anaerobic spore-forming intestinal pathogen, is the leading cause of hospital-acquired diarrhea and colitis. Drug treatments for these diseases are often complicated by antibiotic-resistant strains and a high frequency of treatment failures and relapse; therefore, novel nonantibiotic approaches may prove to be more effective. In this study, we recombinantly expressed a prophage lysin identified from a C. difficile strain, CD630, which we named PlyCD. PlyCD was found to have lytic activity against specific C. difficile strains. However, the recombinantly expressed catalytic domain of this protein, PlyCD1–174, displayed significantly greater lytic activity (>4-log kill) and a broader lytic spectrum against C. difficile strains while still retaining a high degree of specificity toward C. difficile versus commensal clostridia and other bacterial species. Our data also indicated that noneffective doses of vancomycin and PlyCD1–174 when combined in vitro could be significantly more bactericidal against C. difficile. In an ex vivo treatment model of mouse colon infection, we found that PlyCD1–174 functioned in the presence of intestinal contents, significantly decreasing colonizing C. difficile compared to controls. Together, these data suggest that PlyCD1–174 has potential as a novel therapeutic for clinical application against C. difficile infection, either alone or in combination with other preexisting treatments to improve their efficacy. PMID:26392484

  9. Immune-based treatment and prevention of Clostridium difficile infection

    PubMed Central

    Zhao, Song; Ghose-Paul, Chandrabali; Zhang, Keshan; Tzipori, Saul; Sun, Xingmin

    2015-01-01

    Clostridium difficile (C. difficile) causes over 500,000 infections per year in the US, with an estimated 15,000 deaths and an estimated cost of $1–3 billion. Moreover, a continual rise in the incidence of severe C. difficile infection (CDI) has been observed worldwide. Currently, standard treatment for CDI is the administration of antibiotics. While effective, these treatments do not prevent and may contribute to a disease recurrence rate of 15–35%. Prevention of recurrence is one of the most challenging aspects in the field. A better knowledge of the molecular mechanisms of the disease, the host immune response and identification of key virulence factors of C. difficilenow permits the development of immune-based therapies. Antibodies specific for C. difficile toxins have been shown to effectively treat CDI and prevent disease relapse in animal models and in humans. Vaccination has been recognized as the most cost-effective treatment/prevention for CDI. This review will summarize CDI transmission, epidemiology, major virulent factors and highlights the rational and the development of immune-based approaches against this remerging threat. PMID:25668664

  10. Immune-based treatment and prevention of Clostridium difficile infection.

    PubMed

    Zhao, Song; Ghose-Paul, Chandrabali; Zhang, Keshan; Tzipori, Saul; Sun, Xingmin

    2014-01-01

    Clostridium difficile (C. difficile) causes over 500,000 infections per year in the US, with an estimated 15,000 deaths and an estimated cost of $1-3 billion. Moreover, a continual rise in the incidence of severe C. difficile infection (CDI) has been observed worldwide. Currently, standard treatment for CDI is the administration of antibiotics. While effective, these treatments do not prevent and may contribute to a disease recurrence rate of 15-35%. Prevention of recurrence is one of the most challenging aspects in the field. A better knowledge of the molecular mechanisms of the disease, the host immune response and identification of key virulence factors of C. difficilenow permits the development of immune-based therapies. Antibodies specific for C. difficile toxins have been shown to effectively treat CDI and prevent disease relapse in animal models and in humans. Vaccination has been recognized as the most cost-effective treatment/prevention for CDI. This review will summarize CDI transmission, epidemiology, major virulent factors and highlights the rational and the development of immune-based approaches against this remerging threat.

  11. Breakthroughs in the treatment and prevention of Clostridium difficile infection.

    PubMed

    Kociolek, Larry K; Gerding, Dale N

    2016-03-01

    This Review summarizes the latest advances in the treatment and prevention of Clostridium difficile infection (CDI), which is now the most common health-care-associated infection in the USA. As traditional, standard CDI antibiotic therapies (metronidazole and vancomycin) are limited by their broad spectrum and further perturbation of the intestinal microbiota, which result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are needed. Emerging CDI therapies are focused on limiting further perturbation of the intestinal microbiota and/or restoring the microbiota to its pre-morbid state, reducing colonization of the intestinal tract by toxigenic strains of C. difficile and bolstering the host immune response against C. difficile toxins. Fidaxomicin is associated with reduced CDI recurrences, and other emerging narrow-spectrum CDI antibiotic therapies might eventually demonstrate a similar benefit. Prevention of intestinal colonization of toxigenic strains of C. difficile can be achieved through restoration of the intestinal microbiota with faecal microbiota transplantation, as well as by colonizing the gut with nontoxigenic C. difficile strains. Finally, emerging immunological therapies, including monoclonal antibodies and vaccines against C. difficile toxins, might protect against CDI and subsequent CDI recurrences. The available clinical data for these emerging therapies, and their relative advantages and disadvantages, are described.

  12. 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.

  13. Patient Perspectives on Fecal Microbiota Transplantation for Clostridium Difficile Infection.

    PubMed

    Zellmer, Caroline; De Wolfe, Travis J; Van Hoof, Sarah; Blakney, Rebekah; Safdar, Nasia

    2016-06-01

    Clostridium difficile infection (CDI) is a severe and increasingly frequent healthcare-associated infection that develops after disruption of the gut microbiota. Immunocompromised, hospitalized patients have an increased likelihood of acquiring CDI, leading to lengthened hospital stays, increased medical fees, and higher rates of morbidity and mortality. Treatment of CDI is challenging because of limited treatment options and a 19-20% recurrence rate. Thus, there is a need for effective, affordable and safe treatments for CDI. Fecal microbiota transplantation (FMT) is the transplantation of donor stool into the intestine of a CDI patient to restore the structure and function of the gut microbiota and eradicate CDI. Recently, FMT has become an attractive alternative treatment for CDI due to its overwhelming success rate. However, the patient perspective on the effect of CDI and the role of FMT in that context is lacking. We undertook a patient survey to gather qualitative and quantitative data on the short-term social, physical, emotional outcomes for patients with CDI who have undergone FMT. We found in all patients interviewed that the social implications of CDI were generally more severe than the emotional and physical aspects. Future studies should consider evaluating these important patient-centered factors as outcomes. Moreover, patients are willing to undergo FMT as treatment for CDI.

  14. Clostridium difficile infection: a review of current and emerging therapies

    PubMed Central

    Ofosu, Andrew

    2016-01-01

    Clostridium difficile (C. difficile) infection (CDI) is the most common cause of ­healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value. PMID:27065726

  15. 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

  16. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

    PubMed

    Wilcox, Mark H; Gerding, Dale N; Poxton, Ian R; Kelly, Ciaran; Nathan, Richard; Birch, Thomas; Cornely, Oliver A; Rahav, Galia; Bouza, Emilio; Lee, Christine; Jenkin, Grant; Jensen, Werner; Kim, You-Sun; Yoshida, Junichi; Gabryelski, Lori; Pedley, Alison; Eves, Karen; Tipping, Robert; Guris, Dalya; Kartsonis, Nicholas; Dorr, Mary-Beth

    2017-01-26

    Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80

  17. Clostridium difficile infection in the hospitalized pediatric population: increasing trend in disease incidence.

    PubMed

    Deshpande, Abhishek; Pant, Chaitanya; Anderson, Michael P; Donskey, Curtis J; Sferra, Thomas J

    2013-10-01

    To determine whether the incidence of Clostridium difficile infection continues to increase in hospitalized pediatric patients, we evaluated data from a United States national inpatient database. For the period of 2003 to 2009, we found an increasing trend in the incidence of C. difficile infection. These data suggest greater effort be given to prevent and treat this infection in children.

  18. Life-threatening clostridial infections.

    PubMed

    Stevens, Dennis L; Aldape, Michael J; Bryant, Amy E

    2012-04-01

    Life-threatening soft tissue infections caused by Clostridium species have been described in the medical literature for hundreds of years largely because of their fulminant nature, distinctive clinical presentations and complex management issues. The Clostridium species perfringens, septicum and histolyticum are the principal causes of trauma-associated gas gangrene and their incidence increases dramatically in times of war, hurricanes, earthquakes and other mass casualty conditions. Recently, there has also been an increased incidence of spontaneous gas gangrene caused by Clostridium septicum in association with gastrointestinal abnormalities and neutropenia. Similarly, over the last 15 years there has been increased recognition of a toxic shock-like syndrome associated with Clostridium sordellii in individuals skin-popping black tar heroin, in women undergoing childbirth or other gynecologic procedures including medically-induced abortion. Like their cousins Clostridium tetanus and Clostridium botulinum, the pathogenesis of these clostridial infections is largely the consequence of potent exotoxin production. Strategies to inhibit toxin production, neutralize circulating toxins and prevent their interaction with cells of the innate immune response are sorely needed. Recent studies have elucidated novel targets that may hold promise for newer therapeutic modalities.

  19. Fecal microbiota transplant for Clostridium difficile infection in older adults

    PubMed Central

    Tauxe, William M.; Haydek, John P.; Rebolledo, Paulina A.; Neish, Emma; Newman, Kira L.; Ward, Angela; Dhere, Tanvi; Kraft, Colleen S.

    2015-01-01

    Background: The objective of this study was to describe the safety of fecal microbiota transplant (FMT) for Clostridium difficile infection (CDI) among older adults. Methods: We performed a case review of all FMT recipients aged 65 or older treated at Emory University Hospital, a tertiary care and referral center for Georgia and surrounding states. Results: CDI resolved in 27 (87%) of 31 respondents, including three individuals who received multiple FMTs. Among four whose CDI was not resolved at follow up, three respondents did well initially before CDI recurred, and one individual never eradicated his CDI despite repeating FMT. During the study, five deaths and eight serious adverse events requiring hospitalization were reported within the study group during the follow-up period. Fecal transplant was not a causative factor in these events. The most common adverse event reported in 4 (13%) of 31 respondents was subjective worsening of arthritis. Conclusion: FMT is a generally safe and effective treatment option for older adults with CDI. PMID:27134658

  20. Management of inflammatory bowel disease with Clostridium difficile infection

    PubMed Central

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

    2017-01-01

    AIM To address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. METHODS 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. RESULTS 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. CONCLUSION 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. PMID:28785153

  1. 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

  2. Fecal microbiota transplantation for Clostridium difficile infection: benefits and barriers.

    PubMed

    Lo Vecchio, Andrea; Cohen, Mitchell B

    2014-01-01

    The incidence and severity of Clostridium difficile infection (CDI) have increased worldwide in the past two decades. A principal function of the gut microbiota is to protect the intestine against colonization by exogenous pathogens. Increasingly, the gut microbiota have been shown to influence susceptibility to other genetic and environmentally acquired conditions. Transplantation of healthy donor fecal material in patients with CDI may re-establish the normal composition of the gut microbiota and has been shown to be effective in recurrent CDI. We intend to review the most recent data on fecal microbiota transplantation (FMT) and critically discuss potential advantages and handicaps of this new therapeutic approach. Evidence from case series and only one randomized clinical trial suggests that FMT is able to restore the wide diversity of microflora, improve C. difficile-related symptoms and prevent CDI recurrence. FMT is a promising treatment option for serious and recurrent CDI, and current evidence (although weak) demonstrates consistent and excellent efficacy in clinical outcomes. However, many questions should be answered before it may be recommended as routine standard treatment. Mechanisms of action need to be better understood. Long-term follow-up studies are needed to determine long-lasting effects (including the association with autoimmune diseases).

  3. Host response to Clostridium difficile infection: Diagnostics and detection.

    PubMed

    Usacheva, Elena A; Jin, Jian-P; Peterson, Lance R

    2016-12-01

    Clostridium difficile infection (CDI) is a significant healthcare concern worldwide, and C. difficile is recognised as the most frequent aetiological agent of infectious healthcare-associated diarrhoea in hospitalised adult patients. The clinical manifestation of CDI varies from self-limited diarrhoea to life-threatening colitis. Such a broad disease spectrum can be explained by the impact of host factors. Currently, a complex CDI aetiology is widely accepted, acknowledging the interaction between bacteria and the host. C. difficile strains producing clostridial toxins A and B are considered toxigenic and can cause disease; those not producing the toxins are non-pathogenic. A person colonised with a toxigenic strain will not necessarily develop CDI. It is imperative to recognise patients with active disease from those only colonised with this pathogen and to implement appropriate treatment. This can be achieved by diagnostics that rely on host factors specific to CDI. This review will focus on major aspects of CDI pathogenesis and molecular mechanisms, describing host factors in disease progression and assessment of the host response in order to facilitate the development of CDI-specific diagnostics.

  4. 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.

  5. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections.

    PubMed

    Surawicz, Christina M; Brandt, Lawrence J; Binion, David G; Ananthakrishnan, Ashwin N; Curry, Scott R; Gilligan, Peter H; McFarland, Lynne V; Mellow, Mark; Zuckerbraun, Brian S

    2013-04-01

    Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratified depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mild-to-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classification of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI.

  6. 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.

  7. Fidaxomicin--the new drug for Clostridium difficile infection.

    PubMed

    Vaishnavi, Chetana

    2015-04-01

    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.

  8. [Treatment of refractory or recurrent Clostridium difficile infection].

    PubMed

    Kim, Sang Woo

    2012-08-01

    The incidence and severity of Clostridium difficile infection (CDI) has increased over the past decades. It is related to the emergence of hypervirulent strains and increased use of antibiotics. The incidence of refractory CDI to standard therapies and the risk for recurrent CDI are also increasing. Current guidelines recommend the first recurrence to be treated with the same agent used for the initial episode. However, data are lacking to support any particular treatment strategy for severe refractory CDI or cases with multiple recurrence. Treatments currently available for CDI are inadequate to prevent recurrence. Widely used method for managing a subsequent recurrence involves tapering followed by pulsed doses of vancomycin. Other potentially effective strategies for recurrent CDI are use of other antibiotics such as fidaxomicin, nitazoxanide, rifaximin, tigecycline, and teicoplanin. There are efforts to recover gut microflora and to optimize immune response to CDI. These include use of probiotics, fecal microbiota transplantation, intravenous immunoglobulin, monoclonal antibodies directed against C. difficile toxins, and active vaccination. However treatment of patients with refractory CDI and those with multiple CDI recurrences is based on limited clinical evidence, and there is an ongoing need for continued research to improve the outcomes these patients.

  9. Prevalence and molecular epidemiology of Clostridium difficile infection in Indonesia.

    PubMed

    Collins, D A; Gasem, M H; Habibie, T H; Arinton, I G; Hendriyanto, P; Hartana, A P; Riley, T V

    2017-07-01

    Clostridium difficile has not been studied in detail in Asia, particularly Southeast Asia. We thus performed a prevalence study across four hospitals in Central Java province, Indonesia. Stool samples were collected from patients with diarrhoea and tested by enzyme immunoassay for glutamate dehydrogenase (GDH) and toxin A/B (C DIFF QUIK CHEK COMPLETE, TechLab). Specimens were cultured and molecular typing was performed. In total, 340 samples were tested, of which 70 (20.6%) were GDH positive, with toxin detected in 19 (5.6%). Toxigenic C. difficile was isolated from 37 specimens (10.9%), while a further 36 (10.6%) nontoxigenic isolates were identified. The most common strain was ribotype 017 (24.3% of 74 isolates), followed by nontoxigenic types QX 224 (9.5%), and QX 238 and QX 108 (both 8.1%). The high prevalence of C. difficile highlights a need for ongoing surveillance of C. difficile infection in Indonesia.

  10. Thrombocytopenia in hospitalized patients with severe clostridium difficile infection.

    PubMed

    Fountain, Eric M; Moses, Maggie C; Park, Lawrence P; Woods, Christopher W; Arepally, Gowthami M

    2017-01-01

    Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has not been examined. We performed a single-institution retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with CDI during their hospitalization to document the incidence/prevalence of thrombocytopenia and associated outcomes. Severe disease was defined by a composite endpoint of inpatient death, death within 30 days of discharge, presence of septic shock, or need for colectomy during hospitalization. Of the 533 patients diagnosed with CDI, moderate thrombocytopenia (platelet count <100 × 10(9)/L at time of CDI diagnosis) was present in 15 % of the total cohort and incident thrombocytopenia developed in 3 % of patients after admission. Thrombocytopenia was more common in hospital-acquired disease and associated with increased length of stay, but was not associated with treatment failure. Those with moderate thrombocytopenia were more likely to have severe disease, after controlling for white blood cell count, albumin, and creatinine. Moderate thrombocytopenia is associated with poor prognosis and is a potential risk stratification tool for severe CDI.

  11. Clostridium difficile infection in a French university hospital

    PubMed Central

    Khanafer, Nagham; Oltra, Luc; Hulin, Monique; Dauwalder, Olivier; Vandenesch, Francois; Vanhems, Philippe

    2016-01-01

    Abstract The epidemiology of Clostridium difficile infection (CDI) has changed with an increase in incidence and severity. Prospective surveillance was therefore implemented in a French university hospital to monitor the characteristics of patients at risk and to recognize local trends. Between 2007 and 2014, all hospitalized patients (≥18 years) with CDI were included. During the survey, the mean incidence rate of CDI was 2.9 per 10,000 hospital-days. In all, 590 patients were included. Most of the episodes were healthcare-associated (76.1%). The remaining cases were community-acquired (18.1%) and unknown (5.9%). The comparison with healthcare-associated cases showed that the community-acquired group had a lower rate of antimicrobial exposure (P < 0.001), proton pump inhibitor (P < 0.001), and immunosuppressive drugs (P = 0.02). Over the study period, death occurred in 61 patients (10.3%), with 18 (29.5%) being related to CDI according to the physician in charge of the patient. Active surveillance of CDI is required to obtain an accurate picture of the real dimensions of CDI. PMID:27281101

  12. Clostridium celerecrescens, often misidentified as "Clostridium clostridioforme group," is involved in rare human infection cases.

    PubMed

    Bouvet, Philippe; K'Ouas, Guylène; Le Coustumier, Alain; Popoff, Michel R

    2012-11-01

    Misidentification of rare Clostridium species often originated from the environment as clinically relevant species is problematic. A strain isolated from a traumatic leg wound first identified as C. clostridioforme was finally identified as the rare Clostridium celerecrescens. Two similar misidentifications are reported in the literature. In order to help the phenotypic differentiation of C. celerecrescens from the close species of the "C. clostridioforme group", an identification table and differential susceptibilities to 4 selected antibiotics are proposed. Once a clinical isolate is referred to this group, identification should be definitively confirmed by unambiguous methods such as 16s rDNA sequencing.

  13. Human Clostridium difficile infection: altered mucus production and composition

    PubMed Central

    Engevik, Melinda A.; Yacyshyn, Mary Beth; Engevik, Kristen A.; Wang, Jiang; Darien, Benjamin; Hassett, Daniel J.; Yacyshyn, Bruce R.

    2014-01-01

    The majority of antibiotic-induced diarrhea is caused by Clostridium difficile (C. difficile). Hospitalizations for C. difficile infection (CDI) have tripled in the last decade, emphasizing the need to better understand how the organism colonizes the intestine and maintain infection. The mucus provides an interface for bacterial-host interactions and changes in intestinal mucus have been linked host health. To assess mucus production and composition in healthy and CDI patients, the main mucins MUC1 and MUC2 and mucus oligosaccharides were examined. Compared with healthy subjects, CDI patients demonstrated decreased MUC2 with no changes in surface MUC1. Although MUC1 did not change at the level of the epithelia, MUC1 was the primary constituent of secreted mucus in CDI patients. CDI mucus also exhibited decreased N-acetylgalactosamine (GalNAc), increased N-acetylglucosamine (GlcNAc), and increased terminal galactose residues. Increased galactose in CDI specimens is of particular interest since terminal galactose sugars are known as C. difficile toxin A receptor in animals. In vitro, C. difficile is capable of metabolizing fucose, mannose, galactose, GlcNAc, and GalNAc for growth under healthy stool conditions (low Na+ concentration, pH 6.0). Injection of C. difficile into human intestinal organoids (HIOs) demonstrated that C. difficile alone is sufficient to reduce MUC2 production but is not capable of altering host mucus oligosaccharide composition. We also demonstrate that C. difficile binds preferentially to mucus extracted from CDI patients compared with healthy subjects. Our results provide insight into a mechanism of C. difficile colonization and may provide novel target(s) for the development of alternative therapeutic agents. PMID:25552581

  14. Human Clostridium difficile infection: altered mucus production and composition.

    PubMed

    Engevik, Melinda A; Yacyshyn, Mary Beth; Engevik, Kristen A; Wang, Jiang; Darien, Benjamin; Hassett, Daniel J; Yacyshyn, Bruce R; Worrell, Roger T

    2015-03-15

    The majority of antibiotic-induced diarrhea is caused by Clostridium difficile (C. difficile). Hospitalizations for C. difficile infection (CDI) have tripled in the last decade, emphasizing the need to better understand how the organism colonizes the intestine and maintain infection. The mucus provides an interface for bacterial-host interactions and changes in intestinal mucus have been linked host health. To assess mucus production and composition in healthy and CDI patients, the main mucins MUC1 and MUC2 and mucus oligosaccharides were examined. Compared with healthy subjects, CDI patients demonstrated decreased MUC2 with no changes in surface MUC1. Although MUC1 did not change at the level of the epithelia, MUC1 was the primary constituent of secreted mucus in CDI patients. CDI mucus also exhibited decreased N-acetylgalactosamine (GalNAc), increased N-acetylglucosamine (GlcNAc), and increased terminal galactose residues. Increased galactose in CDI specimens is of particular interest since terminal galactose sugars are known as C. difficile toxin A receptor in animals. In vitro, C. difficile is capable of metabolizing fucose, mannose, galactose, GlcNAc, and GalNAc for growth under healthy stool conditions (low Na(+) concentration, pH 6.0). Injection of C. difficile into human intestinal organoids (HIOs) demonstrated that C. difficile alone is sufficient to reduce MUC2 production but is not capable of altering host mucus oligosaccharide composition. We also demonstrate that C. difficile binds preferentially to mucus extracted from CDI patients compared with healthy subjects. Our results provide insight into a mechanism of C. difficile colonization and may provide novel target(s) for the development of alternative therapeutic agents. Copyright © 2015 the American Physiological Society.

  15. 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.

  16. Clostridium difficile infection in children hospitalized due to diarrhea.

    PubMed

    Dulęba, K; Pawłowska, M; Wietlicka-Piszcz, M

    2014-02-01

    The frequency of Clostridium difficile infection (CDI)-related hospitalizations is increasing. The aim of this study was to determine the extent of CDI among children hospitalized with diarrhea, risk factors or predictors for severe CDI, the prevalence of NAP1, and to compare the course of CDI depending on bacteria toxicity profile. A retrospective analysis of case records of 64 children (age range 3 months-16 years, median age 2.12 years) with CDI as defined by diarrheal disease and positive polymerase chain reaction (PCR) test (Xpert C. difficile) was conducted. Modified national adult guidelines were used to assess the severity of CDI. CDIs represented 2.7 % of patients with diarrhea (13.5 cases per 1,000 admissions). Thirty-three CDIs (52 %) were community-associated. Antibacterial use preceded CDI in 61 patients (95 %). Seventeen cases (27 %) were binary toxin-positive (CDT+), 13 of which were NAP1 (20.5 %). Over 75 % of CDIs with NAP1 was hospital-acquired, and more often proceeded with generalized infection (p < 0.05). Risk factors for severe CDI (34 %) included NAP1 [odds ratio (OR), 4.85; 95 % confidence interval (Cl), 1.23, 21.86) and co-morbidities (OR, 4.25; 95 % Cl, 1.34, 14.38). Diarrhea ≥10 stools daily was associated with severe CDI (p = 0.01). Recurrence occurred in three patients (4.5 %). There was no mortality. C. difficile is an important factor of antibiotic-associated diarrhea in children. Co-morbidities and NAP1 predispose to severe CDI.

  17. Fecal Microbiota Transplantation for Clostridium difficile Infection: The Ochsner Experience

    PubMed Central

    Ray, Arnab; Smith, Robert; Breaux, Jacob

    2014-01-01

    Background Clostridium difficile infection (CDI) accounts for 20%-30% of cases of antibiotic-associated diarrhea and is the most commonly recognized cause of infectious diarrhea in healthcare settings. The incidence of CDI is rising, while the effectiveness of antibiotics for treatment decreases with recurrent episodes. The use of fecal microbiota transplantation (FMT) for cure of CDI has been reported since 1958, and the worldwide cure rate is reported to be 93%. We report our experience with FMT for the treatment of CDI. Methods We performed a retrospective chart review of patients undergoing FMT for CDI at Ochsner Clinic Foundation from August 2012 to November 2013. FMT was administered via colonoscopy for patients with recurrent or severe CDI. Stool donors were screened for infections in the majority of cases. Results FMT was performed in 20 CDI patients. The 16 female and 4 male patients ranged in age from 27 to 89 years (mean 62 years). The average duration of illness from diagnosis to treatment was 49.6 weeks, based on available data. Only 3 donors were unscreened for infectious pathogens. Nine donors were related to the recipients by blood; most of the other donors were spouses. The average length of follow-up after FMT was 3 months. No recurrences of CDI after treatment have been documented. Adverse events reported after treatment included abdominal cramping, bloating, flatulence, and nausea that resolved. Conclusion Although the US Food and Drug Administration currently considers FMT an experimental therapy, we demonstrate that FMT is safe, well tolerated, and effective for recurrent and severe CDI. PMID:25598718

  18. A bundle strategy including patient hand hygiene to decrease clostridium difficile infections.

    PubMed

    Pokrywka, Marian; Feigel, Jody; Douglas, Barbara; Grossberger, Susan; Hensler, Amelia; Hensler, Amelia; Weber, David

    2014-01-01

    Prevention strategies for Clostridium difficile infection traditionally have addressed barrier precautions, environmental disinfection, and health care worker hand hygiene. When applied as a bundle, this approach has been used widely as an evidence-based strategy to prevent hospital-acquired C. difficile infection. Expanding the bundle to include patient hand hygiene is a nurse-driven approach to prevent C. difficile transmission.

  19. Myocardial Necrosis Associated with Clostridium novyi Infection in a Bighorn Sheep ( Ovis canadensis ).

    PubMed

    Redford, Tony; Cubberley, J Clint; Hengeveld, Pamela; Zabek, Erin; Britton, Ann P

    2017-07-01

    We describe a case of myocardial emphysema and necrosis in a bighorn sheep ( Ovis canadensis ), associated with infection by Clostridium novyi , diagnosed through necropsy, histopathology, and fluorescent antibody testing. We documented rapid onset of disease in an apparently healthy wild sheep and discuss our findings in the context of reported clostridial infections in humans, domestic animals, and wildlife.

  20. Key Advantages of a Targeted Incident Reporting System for Severe and Critical Clostridium difficile Infection Incidents.

    PubMed

    Mahamed, Hibak; Lemieux, Camille; Hota, Susy

    2017-01-01

    There is little guidance on how to design and implement an incident reporting system (IRS) targeted at one of the most common types of adverse events in hospitals: hospital-associated infections. In this article, we describe an IRS for severe and critical Clostridium difficile infection incidents and highlight its key advantages.

  1. Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice

    PubMed Central

    Kim, Mi Na; Koh, Seong-Joon; Kim, Jung Mogg; Im, Jong Pil; Jung, Hyun Chae; Kim, Joo Sung

    2014-01-01

    AIM: To investigate the effect of Clostridium difficile (C. difficile) infection in an interleukin 10-deficient (IL-10-/-) mouse model of inflammatory bowel disease. METHODS: Bone marrow-derived dendritic cells isolated from wild type (WT) and IL-10-/-mice were stimulated for 4 h with C. difficile toxin A (200 μg/mL), and gene expression of interferon (IFN)-γ, IL-12 and IL-23 was determined by real-time reverse transcription polymerase chain reaction. WT and IL-10-/- mice (n = 20 each) were exposed to an antibiotic cocktail for three days and then were injected with clindamycin (i.p.). Mice (n = 10 WT, 10 IL-10-/-) were then challenged with oral administration of C. difficile (1 × 105 colony forming units of strain VPI 10463). Animals were monitored daily for 7 d for signs of colitis. Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis. RESULTS: C. difficile toxin A treatment induced IFN-γ gene expression to a level that was significantly higher in BDMCs from IL-10-/- compared to those from WT mice (P < 0.05). However, expression of IL-12 and IL-23 was not different among the groups. Following C. difficile administration, mice developed diarrhea and lost weight within 2-3 d. Weight loss was significantly greater in IL-10-/- compared to WT mice (P < 0.05). C. difficile infection induced histopathologic features typical of colitis in both IL-10-/- and WT mice. The histopathologic severity score was significantly higher in the IL-10-/- than in WT mice (mean ± standard error; 5.50 ± 0.53 vs 2.44 ± 0.46; P < 0.05). This was accompanied by a significantly greater increase in IFN-γ gene expression in colonic tissues from IL-10-/- than from WT mice challenged with C. difficile (P < 0.05). CONCLUSION: These results indicate that colitis is more severe after C. difficile infection in IL-10-/-mice, and that IFN-γ expression is involved in this process. PMID:25493020

  2. Role of microbiota and innate immunity in recurrent Clostridium difficile infection.

    PubMed

    Bibbò, Stefano; Lopetuso, Loris Riccardo; Ianiro, Gianluca; Di Rienzo, Teresa; Gasbarrini, Antonio; Cammarota, Giovanni

    2014-01-01

    Recurrent Clostridium difficile infection represents a burdensome clinical issue whose epidemiology is increasing worldwide. The pathogenesis is not yet completely known. Recent observations suggest that the alteration of the intestinal microbiota and impaired innate immunity may play a leading role in the development of recurrent infection. Various factors can cause dysbiosis. The causes most involved in the process are antibiotics, NSAIDs, acid suppressing therapies, and age. Gut microbiota impairment can favor Clostridium difficile infection through several mechanisms, such as the alteration of fermentative metabolism (especially SCFAs), the alteration of bile acid metabolism, and the imbalance of antimicrobial substances production. These factors alter the intestinal homeostasis promoting the development of an ecological niche for Clostridium difficile and of the modulation of immune response. Moreover, the intestinal dysbiosis can promote a proinflammatory environment, whereas Clostridium difficile itself modulates the innate immunity through both toxin-dependent and toxin-independent mechanisms. In this narrative review, we discuss how the intestinal microbiota modifications and the modulation of innate immune response can lead to and exacerbate Clostridium difficile infection.

  3. Role of Microbiota and Innate Immunity in Recurrent Clostridium difficile Infection

    PubMed Central

    Bibbò, Stefano; Lopetuso, Loris Riccardo; Ianiro, Gianluca; Di Rienzo, Teresa; Gasbarrini, Antonio

    2014-01-01

    Recurrent Clostridium difficile infection represents a burdensome clinical issue whose epidemiology is increasing worldwide. The pathogenesis is not yet completely known. Recent observations suggest that the alteration of the intestinal microbiota and impaired innate immunity may play a leading role in the development of recurrent infection. Various factors can cause dysbiosis. The causes most involved in the process are antibiotics, NSAIDs, acid suppressing therapies, and age. Gut microbiota impairment can favor Clostridium difficile infection through several mechanisms, such as the alteration of fermentative metabolism (especially SCFAs), the alteration of bile acid metabolism, and the imbalance of antimicrobial substances production. These factors alter the intestinal homeostasis promoting the development of an ecological niche for Clostridium difficile and of the modulation of immune response. Moreover, the intestinal dysbiosis can promote a proinflammatory environment, whereas Clostridium difficile itself modulates the innate immunity through both toxin-dependent and toxin-independent mechanisms. In this narrative review, we discuss how the intestinal microbiota modifications and the modulation of innate immune response can lead to and exacerbate Clostridium difficile infection. PMID:24995345

  4. Recurrent Clostridium difficile infection among Medicare patients in nursing homes

    PubMed Central

    Zilberberg, Marya D.; Shorr, Andrew F.; Jesdale, William M.; Tjia, Jennifer; Lapane, Kate

    2017-01-01

    Abstract 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. PMID:28272217

  5. Clostridium difficile infection increases mortality risk in lung transplant recipients.

    PubMed

    Lee, Janet T; Kelly, Rosemary F; Hertz, Marshall I; Dunitz, Jordan M; Shumway, Sara J

    2013-10-01

    Clostridium difficile infection (CDI) and associated mortality in solid organ transplant recipients is rising, but data are scarce in lung transplant recipients. We aimed to characterize CDI and its effect on mortality in a large cohort of lung transplant recipients. Lung transplant recipients were identified from our transplant database from 2000 to 2011. Cox proportional hazard models were used to calculate hazard ratios for CDI and death after adjusting for potential confounders identified from bivariate analysis. We identified 388 patients (196 female, 192 male), with a median age of 56 years (range, 8-75 years), during the study period. CDI developed after transplant in 89 (22.9%), with 27 (7.0%) developing CDI during the initial hospitalization at a mean diagnosis of 12.7 ± 11.4 days. Incidence varied widely each year (median, 24%; range, 5%-32%), with the highest rates in 2007 to 2008. Post-operative length of stay was identified as a significant predictor of CDI (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03). Early CDI was an independent significant predictor of death (HR, 1.96; 95% CI, 1.14-3.36) as well as CDI anytime after transplant (HR, 1.61; 95% CI, 1.02-2.52). CDI rates varied widely from 2000 through 2011, with the highest rates in 2007 to 2008. Lung transplant recipients who developed CDI had a higher risk of death, especially when CDI occurred in the first 6 months after transplant. © 2013 International Society for Heart and Lung Transplantation. All rights reserved.

  6. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review.

    PubMed

    Drekonja, Dimitri; Reich, Jon; Gezahegn, Selome; Greer, Nancy; Shaukat, Aasma; MacDonald, Roderick; Rutks, Indy; Wilt, Timothy J

    2015-05-05

    The role of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) is not well-known. To assess the efficacy, comparative effectiveness, and harms of FMT for CDI. MEDLINE (1980 to January 2015), Cochrane Library, and ClinicalTrials.gov, followed by hand-searching references from systematic reviews and identified studies. Any study of FMT to treat adult patients with CDI; case reports were only used to report harms. Data were extracted by 1 author and verified by another; 2 authors independently assessed risk of bias and strength of evidence. Two randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports were included. Two RCTs and 21 case-series studies (516 patients receiving FMT) reported using FMT for patients with recurrent CDI. A high proportion of treated patients had symptom resolution; however, the role of previous antimicrobials is unclear. One RCT comparing FMT with 2 control groups (n = 43) reported resolution of symptoms in 81%, 31%, and 23% of the FMT, vancomycin, or vancomycin-plus-bowel lavage groups, respectively (P < 0.001 for both control groups vs. FMT). An RCT comparing FMT route (n = 20) reported no difference between groups (60% in the nasogastric tube group and 80% in the colonoscopy group; P = 0.63). Across all studies for recurrent CDI, symptom resolution was seen in 85% of cases. In 7 case-series studies of patients with refractory CDI, symptom resolution ranged from 0% to 100%. Among 7 patients treated with FMT for initial CDI, results were mixed. Most studies were uncontrolled case-series studies; only 2 RCTs were available for analysis. Fecal microbiota transplantation may have a substantial effect with few short-term adverse events for recurrent CDI. Evidence is insufficient on FMT for refractory or initial CDI treatment and on whether effects vary by donor, preparation, or delivery method. U.S. Department of Veterans Affairs.

  7. Fecal Microbiota Transplant in Patients With Recurrent Clostridium Difficile Infection.

    PubMed

    Hagel, Stefan; Fischer, Anne; Ehlermann, Philipp; Frank, Thorsten; Tueffers, Kester; Sturm, Andreas; Link, Alexander; Demir, Muenevver; Siebenhaar, Arno; Storr, Martin; Glueck, Thomas; Siegel, Erhard; Solbach, Philip; Goeser, Felix; Koelbel, Christian B.; Lohse, Ansgar; Luebbert, Christoph; Kandzi, Ulrich; Maier, Matthias; Schuerle, Stefanie; Lerch, Markus M.; Tacke, Daniela; Cornely, Oliver A.; Stallmach, Andreas; Vehreschild, Maria

    2016-09-05

    The clinical effectiveness of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridium difficile infections (rCDI) has been demonstrated in randomized controlled trials. To assess the current status of FMT in Germany with respect to active centers, local standards, clinical effectiveness and safety, the MicroTrans Registry (NCT02681068) was established. In a long-term retrospective multicenter observational study by the German Clinical Microbiome Study Group (GCMSG), primary and secondary cure on day 30 and 90, as well as occurrence of treatment-related adverse events were assessed. In addition to patient demographic data, we provide an overview of the FMT procedures and techniques used at different centers. Overall, 133 eligible patients from 33 centers were included, of which 64.7% were female (n = 86). The mean age was 75 years (interquartile range: 59.5-81.5). Administration via the duodenal route (n = 59; 44.4%) was the most frequently applied option, followed by colonic (n = 55; 41.1%), capsule (n = 13; 9.8%), and gastric administration (n = 4; 3.0%). Primary cure on day 30 and 90 was achieved in 84.2% (n = 101/120) and 78.3% (n = 72/92) of patients, respectively. Including re-treatment, secondary response was achieved in 87.5% (d 30; n = 105/120) and 85.9% (d 90; n = 79/92), respectively. Treatment- elated adverse events were documented in 16 patients (12.0%). FMT is a safe and effective treatment option for rCDI. However, FMT is currently available only in few centers in Germany, and treatment options vary from one center to another.

  8. Development of Clostridium septicum gas gangrene as an adverse effect of clindamycin-induced Clostridium difficile infection in a pediatric patient.

    PubMed

    Kiser, Casey J; Urish, Kenneth L; Boateng, Henry A

    2014-09-01

    Clostridium myonecrosis or gas gangrene is a life-threatening infection characterized by either traumatic or atraumatic etiology. It has been widely described in patients with traumatic open wounds and in immunocompromised patients, including malignancy. A third source can result from natural flora in the gastrointestinal tract after bowel ischemia. This is a rare occurrence and is even less commonly described in the pediatric population. We present a pediatric patient who developed Clostridium septicum myonecrosis as an iatrogenic complication from clindamycin-induced Clostridium difficile ischemic colitis.

  9. Clostridium difficile Infections after Blunt Trauma: A Different Patient Population?

    PubMed Central

    Vanzant, Erin L.; Ozrazgat-Baslanti, Tezcan; Liu, Huazhi; Malik, Seemab; Davis, Ruth; Lanz, Jennifer; Miggins, Makesha V.; Gentile, Lori F.; Cuenca, Angela; Cuenca, Alex G.; Lottenberg, Lawrence; Moore, Frederick A.; Ang, Darwin N.; Bihorac, Azra

    2015-01-01

    Abstract Background: The epidemiology of Clostridium difficile-associated infection (CDI) has changed, and it is evident that susceptibility is related not only to exposures and bacterial potency, but host factors as well. Several small studies have suggested that CDI after trauma is associated with a different patient phenotype. The purpose of this study was to examine and describe the epidemiologic factors associated with C. difficile in blunt trauma patients without traumatic brain injury using the Trauma-Related Database as a part of the “Inflammation and Host Response to Injury” (Glue Grant) and the University of Florida Integrated Data Repository. Methods: Previously recorded baseline characteristics, clinical data, and outcomes were compared between groups (67 C. difficile and 384 uncomplicated, 813 intermediate, and 761 complicated non-C. difficile patients) as defined by the Glue Grant on admission and at days seven and 14. Results: The majority of CDI patients experienced complicated or intermediate clinical courses. The mean ages of all cohorts were less than 65 y and CDI patients were significantly older than uncomplicated patients without CDI. The CDI patients had increased days in the hospital and on the ventilator, as well as significantly higher new injury severity scores (NISS), and a greater percentage of patients with NISS >34 points compared with non-CDI patients. They also had greater Marshall and Denver multiple organ dysfunction scores than non-CDI uncomplicated patients, and greater creatinine, alkaline phosphatase, neutrophil count, lactic acid, and PiO2:FiO2 compared with all non-CDI cohorts on admission. In addition, the CDI patients had higher glucose concentrations and base deficit from uncomplicated patients and greater leukocytosis than complicated patients on admission. Several of these changes persisted to days seven and 14. Conclusion: Analysis of severe blunt trauma patients with C. difficile, as compared with non

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

    PubMed

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

    2017-08-11

    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'.

  11. Clostridium perfringens type A netF and netE positive and Clostridium difficile co-infection in two adult dogs.

    PubMed

    Diniz, Amanda Nádia; Silva, Rodrigo Otávio Silveira; Oliveira Junior, Carlos Augusto; Pierezan, Felipe; Lobato, Francisco Carlos Faria

    2016-04-01

    The aim of this study was to report two cases of Clostridium perfringens type A and Clostridium difficile co-infection in adult dogs. Both animals were positive for A/B toxin. Toxigenic C. difficile and C. perfringens type A positive for NetE and NetF-encoding genes were isolated. This report reinforces the necessity of studying a possible synergism of C. difficile and C. perfringens in enteric disorders.

  12. Infection control practices related to Clostridium difficile infection in acute care hospitals in Canada.

    PubMed

    Gravel, Denise; Gardam, Michael; Taylor, Geoffrey; Miller, Mark; Simor, Andrew; McGeer, Allison; Hutchinson, James; Moore, Dorothy; Kelly, Sharon; Mulvey, Michael

    2009-02-01

    We carried out a survey to identify the infection prevention and control practices in place in Canadian hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP). An infection prevention and control practices survey was sent to CNISP hospitals at the beginning of November 2004, the same time that CNISP started a 6-month prospective surveillance for Clostridium difficile infection (CDI) to evaluate their infection prevention and control measures and laboratory methods for C difficile. A total of 33 hospitals completed and returned the survey. Infection control precautions were initiated in 18 hospitals (55%) due to the presence of a symptomatic patient before the C difficile laboratory tests were available. All of the hospitals used gloves and gowns as additional precautions. Twenty-three hospitals (70%) tested liquid stools based on a clinician's order, and 8 (24%) tested all liquid stools submitted whether of not C difficile testing was requested. The hospitals used 1 of 3 different products as a standard hospital-wide disinfectant; 24 (73%) used a quaternary ammonium compound, 8 (24%) used accelerated hydrogen peroxide, and 1 (3%) used a hypochlorite solution (1:10 bleach solution). Although the hospitals used contact precautions quite uniformly, considerable variation was seen among hospitals in terms of testing strategies, cleaning and disinfection protocols and products, and isolation practices. The timing for the initiation of infection control precautions is important to prevent secondary transmission of CDI. Most of the hospitals implemented precautions while waiting for the toxin assay results.

  13. Effect of cobra venom factor on experimental infection of mice against Clostridium chauvoei.

    PubMed

    Tamura, Y; Kijima, M; Suzuki, S; Takahashi, T; Nakamura, M

    1992-10-01

    The effect of cobra venom factor (CoVF) treatment was examined to clarify the mechanism of resistance of mice to Clostridium chauvoei infection. In CoVF-treated mice inoculated with spores of C. chauvoei, no death occurred and the organisms in the infected muscle progressively decreased, similar to that of non-treated control mice. These results indicated that C3 did not play a significant role in the resistance of mice against C. chauvoei infection.

  14. Successful therapy of Clostridium difficile infection with fecal microbiota transplantation.

    PubMed

    Konturek, P C; Koziel, J; Dieterich, W; Haziri, D; Wirtz, S; Glowczyk, I; Konturek, K; Neurath, M F; Zopf, Y

    2016-12-01

    Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea and represents an important burden for healthcare worldwide. Symptoms of severe CDI include watery, foul-smelling diarrhea, peripheral leucocytosis, increased C-reactive protein (CRP), acute renal failure, hypotension and pseudomembranous colitis. Recent studies indicate that the main cause of CDI is dysbiosis, an imbalance in the normal gut microbiota. The restoration of a healthy gut microbiota composition via fecal microbiota transplantation (FMT) recently became more popular. The aim of the present study was to assess the effect of FMT on the healing of CDI and to analyze the changes in the level of pro-inflammatory markers (C-reactive protein, fecal calprotectin) and pro-inflammatory cytokines. Eighteen patients with CDI were included in our study (6 males and 12 females) with recurrent and/or severe CDI. The FMT was performed in 17 patients using colonoscopy, including 16 patients receiving a one-time FMT and 1 patient who needed 2 additional FMTs. One patient was treated with a single round of FMT using push-and-pull enteroscopy. In all CDI patients, before and 3 weeks after FMT, the following parameters were analyzed: C-reactive protein, fecal calprotectin, and plasma interleukin (IL)-6, IL-8 and IL-12, and tumor necrosis factor-alpha (TNF-α). In addition, the plasma level of LL-37, a cathelicidine peptide was assessed by fluorescence-activated cell sorting (FACS) before and 3 months after FMT. Finally, in 7 patients a microbiome analysis was performed by sequencing of 16SrRNA in stool probes obtained before and 3 weeks after FMT. The healing rate of CDI was 94%. In all successfully treated patients no recurrent CDI was observed during follow-up (16 months). The serum level of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8 and IL-12) significantly decreased after FMT. Similarly, CRP and fecal calprotectin normalized after FMT. 3 months after FMT a significant

  15. Diagnosis of Clostridium perfringens intestinal infections in sheep and goats.

    PubMed

    Uzal, F A

    2004-04-01

    Clostridium perfringens produces disease in sheep, goats and other animal species, most of which are generically called enterotoxemias. This micro-organism can be a normal inhabitant of the intestine of most animal species including humans, but when the intestinal environment is altered by sudden changes in diet or other factors, C. perfringens proliferates in large numbers and produces several potent toxins that are absorbed into the general circulation or act locally with usually devastating effects on the host. History, clinical signs and gross post-mortem findings are useful tools for establishing a presumptive diagnosis of enterotoxaemia by C. perfringens in sheep and goats, although no definitive diagnosis of these diseases can be made without laboratory confirmation. Because all types of C. perfringens can be normal inhabitants of the intestine of most animals, culture of this micro-organism from intestinal contents of animals has no diagnostic value unless a colony count is performed and large numbers (usually more than 10(4)-10(7)CFU/g) of C. perfringens are found. The most accepted criterion in establishing a definitive diagnosis of enterotoxaemia by C. perfringens is the detection of its toxins in intestinal contents. However, some of the major toxins of C. perfringens (i.e. epsilon toxin) can also be found, albeit in small amounts, in the small intestine of clinically normal sheep, and this poses a diagnostic challenge. In such cases the histopathology of the brain must be used as an alternative diagnostic tool, since the lesions produced by epsilon toxin in the brains of sheep and goats are unique and pathognomonic for C. perfringens type D enterotoxaemia. Ancillary tests, such as measurement of urine glucose or observation of Gram stained smears of intestinal mucosa can be used and, although they have a presumptive diagnostic value when positive, they cannot be used to rule out a diagnosis of enterotoxaemia if they are negative. In conclusion, the

  16. Severe anaphylaxis caused by orally administered vancomycin to a patient with Clostridium difficile infection.

    PubMed

    Bossé, D; Lemire, C; Ruel, J; Cantin, A M; Ménard, F; Valiquette, L

    2013-04-01

    We report the first case of anaphylaxis to oral vancomycin in a cystic fibrosis patient with severe and relapsing Clostridium difficile infection (CDI) refractory to metronidazole. The patient's colitis has been successfully treated with a combination of intravenous metronidazole and tigecycline.

  17. Clostridium difficile Infection in the Department of Defense (DOD): 2007-2013

    DTIC Science & Technology

    2015-02-01

    Edwards JR, Cohen J, et al. Effect of nucleic acid amplification testing on population-based incidence rates of Clostridium difficile infection. Clin...Comorbidity Burden among CDI Patients............................................................. 14 Previous Antibiotic and Gastric Acid Inhibitor...23 Previous Antibiotic and Gastric Acid Inhibitor Use

  18. Implementing automated surveillance for tracking Clostridium difficile infection at multiple healthcare facilities.

    PubMed

    Dubberke, Erik R; Nyazee, Humaa A; Yokoe, Deborah S; Mayer, Jeanmarie; Stevenson, Kurt B; Mangino, Julie E; Khan, Yosef M; Fraser, Victoria J

    2012-03-01

    Automated surveillance using electronically available data has been found to be accurate and save time. An automated Clostridium difficile infection (CDI) surveillance algorithm was validated at 4 Centers for Disease Control and Prevention Epicenter hospitals. Electronic surveillance was highly sensitive, specific, and showed good to excellent agreement for hospital-onset; community-onset, study facility-associated; indeterminate; and recurrent CDI.

  19. Rapid Identification of Key Pathogens in Wound Infection by Molecular Means

    DTIC Science & Technology

    2006-01-01

    odontolyticus, A. viscosus, A. naeslundii, A. israelii Clostridium perfringens , C. ramosum, C. sordellii, C. novyi C. clostridioforme group: C. bolteae, C...Wise MG, Siragusa GR. Quantitative detection of Clostridium perfringens in the broiler fowl gastrointestinal tract by real-time PCR. Appl Environ...clostridoforme, and Clostridium hathewayi Aerobes Gram-positive cocci: Streptococci: Group A streptococci (Streptococcus pyogenes) Group B

  20. A case of toxic megacolon caused by clostridium difficile infection and treated with fecal microbiota transplantation.

    PubMed

    Gweon, Tae Geun; Lee, Kyung Jin; Kang, Dong Hoon; Park, Sung Soo; Kim, Kyung Hoon; Seong, Hyeon Jin; Ban, Tae Hyun; Moon, Sung Jin; Kim, Jin Su; Kim, Sang Woo

    2015-03-01

    Clostridium difficile infection. The mortality rate of fulminant C. difficile infection is reported to be as high as 50%. Fecal microbiota transplantation is a highly effective treatment in patients with recurrent or refractory C. difficile infection. However, there are few published articles on the use of such transplantation for fulminant C. difficile infection. Here, we report on a patient with toxic megacolon complicated by C. difficile infection who was treated successfully with fecal mi-crobiota transplantation. (Gut Liver, 2015;9:247-250).

  1. Clostridium difficile infection in children with inflammatory bowel disease: current evidence.

    PubMed

    Banaszkiewicz, Aleksandra; Pituch, Hanna

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease of the gastrointestinal tract that develops in genetically susceptible individuals. Questions about the role of infections in the development and exacerbations of inflammatory bowel disease remain unanswered. Among numerous bacteria that have been linked to IBD, the most frequently associated is Clostridium difficile. Clinical symptoms of C. difficile infection and an exacerbation of inflammatory bowel disease are often indistinguishable. In cases of diarrhea in patients with IBD and C. difficile infection, antibiotic treatment is recommended. This review attempts to summarize C. difficile infection's epidemiology and clinical features and describes current evidence on treatment of C. difficile infection in children with IBD.

  2. [Recent epidemiology of Clostridium difficile infection in Japan].

    PubMed

    Yamagishi, Yuka; Mikamo, Hiroshige

    2015-12-01

    Clostridium difficile (C. difficile) is a major pathogen for diarrhea in hospitalized patients and because of outbreak of highly virulent strain in EU and US, increased length of hospital stay and increased numbers of severe patients and deaths have become major challenges. In recent years, transmissions through community-acquired or food-borne infections are reported. National surveillance has been already performed overseas. Guidelines for preventing C. difficile infection (CDI) is available, and education activities are promoted for preventing the infection spread. Meanwhile, in Japan, medical hospitals are reporting individual CDI incidence, however, a large-scale research has not been conducted up to the present date and therefore the entire status of CDI including infection of the highly virulent strain has yet to be revealed. This time, we performed a questionnaire-based survey at 2,537 hospitals nationwide between April 15, 2013 and May 31, 2013 to investigate CDI incidence, diagnosis and treatment. Valid responses were obtained from 321 hospitals. Regarding the annual number of CDI patients at all the hospitals, the highest group of hospitals responding "1 to 5 patients a year" was 17.8%, and the second highest group of hospitals responding "no patients a year" was 13.1%. In contrast, there was a group of hospitals with "more than 101 patients a year", which was 3.1%. This indicates that there was the difference in the CDI incidences among hospitals. According to the questionnaire results, a highest group of hospitals responding "0-20%" for CDI patients with serious complication such as toxic megacolon, gastrointestinal perforation, ileus paralytic, bacteremia, sepsis, crohn's disease, and ulcerative colitis was 62.6%, and for CDI patients with recurrence more than one, a group of hospitals answering "0 to 20%" was 56.4%, which was the highest. This suggested that there was only a small number of serious CDI patients and recurrence CDI patients in Japan

  3. Viral co-infections are common and are associated with higher bacterial burden in children with clostridium difficile infection.

    PubMed

    El Feghaly, Rana E; Stauber, Jennifer L; Tarr, Phillip I; Haslam, David B

    2013-12-01

    Clostridium difficile infections in children are increasing. In this cohort study, we enrolled 62 children with diarrhea and C difficile. We performed polymerase chain reaction assays to detect viral agents of gastroenteritis and quantify C difficile burden. Fifteen (24%) children diagnosed as having C difficile infection had a concomitant viral co-infection. These patients tended to be younger and had a higher C difficile bacterial burden than children with no viral co-infections (median difference = 565,957 cfu/mL; P = 0.011), but were clinically indistinguishable. The contribution of viral co-infection to C difficile disease in children warrants future investigation.

  4. Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection

    NASA Astrophysics Data System (ADS)

    Surawicz, Christina M.

    Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.

  5. Outbreak of Clostridium histolyticum infections in injecting drug users in England and Scotland.

    PubMed

    Brazier, J S; Gal, M; Hall, V; Morris, T E

    2004-09-01

    Clostridial infections in injecting drug users in the United Kingdom are a relatively new phenomenon that came to light in 2000 when cases of serious illness and deaths due to Clostridium novyi were recorded. In the period December 2003 to April 2004, the Anaerobe Reference Laboratory received twelve referrals of an extremely rare isolate, Clostridium histolyticum, from cases of infection in injecting drug users submitted from nine different hospitals in England and Scotland. Molecular typing of these isolates by two different methods of pulsed-field gel electrophoresis and PCR ribotyping revealed they are all indistinguishable, indicating a common source of the infections, most probably a batch of heroin that was recently distributed across the UK.

  6. [Fecal microbiota transplantation, a novel therapy for recurrent Clostridium difficile infection].

    PubMed

    Terveer, E M; van Beurden, Y H; Kuijper, E J; Keller, J J

    2016-09-01

    Clostridium difficile infection is caused by a disturbance of the gut microbiota, often resulting from the use of antibiotics. Among a sub group of patients with this disorder, treatment with antibiotics is not effective. They develop a chronic, recurrent infection. Such patients can be treated with a fecal microbiota transplantation (FMT), or fecal transplantation. The crucial steps for safe application of fecal transplantation are central donor selection and screening. To optimise safety and to guarantee the availability of donor feces for fecal transplantation, the Nederlandse Donor Feces Bank (Dutch Donor Feces Bank) was established. At this facility, ready-to-use, screened donor feces can be ordered for patients with (recurrent) Clostridium difficile infections, who can then be treated at their own hospital.

  7. [Septic shock due to a community acquired Clostridium difficile infection. A case study and a review of the literature].

    PubMed

    Bermejo, C; Maseda, E; Salgado, P; Gabilondo, G; Gilsanz, F

    2014-04-01

    The epidemiology of Clostridium difficile infection has changed in the past decade. The incidence rate of community acquired cases has increased in patients with no typical risk factors. We present a patient who was diagnosed with community-acquired Clostridium difficile infection who presented with acute abdominal pain, and subsequently developed acute renal failure and septic shock. We describe the diagnosis, treatment and outcome and brief review of the literature.

  8. What is the current role of algorithmic approaches for diagnosis of Clostridium difficile infection?

    PubMed

    Wilcox, Mark H; Planche, Tim; Fang, Ferric C; Gilligan, Peter

    2010-12-01

    With the recognition of several serious outbreaks of Clostridium difficile infection in the industrialized world coupled with the development of new testing technologies for detection of this organism, there has been renewed interest in the laboratory diagnosis of C. difficile infection. Two factors seem to have driven much of this interest. First, the recognition that immunoassays for detection of C. difficile toxins A and B, for many years the most widely used tests for C. difficile infection diagnosis, were perhaps not as sensitive as previously believed at a time when attributed deaths to C. difficile infections were showing a remarkable rise. Second, the availability of FDA-approved commercial and laboratory-developed PCR assays which could detect toxigenic strains of C. difficile provided a novel and promising testing approach for diagnosing this infection. In this point-counterpoint on the laboratory diagnosis of C. difficile infection, we have asked two experts in C. difficile infection diagnosis, Ferric Fang, who has recently published two articles in the Journal of Clinical Microbiology advocating the use of PCR as a standalone test (see this author's references 12 and 28), and Mark Wilcox, who played a key role in developing the IDSA/SHEA guidelines on Clostridium difficile infection (see Wilcox and Planche's reference 1), along with his colleague, Tim Planche, to address the following question: what is the current role of algorithmic approaches to the diagnosis of C. difficile infection?

  9. What Is the Current Role of Algorithmic Approaches for Diagnosis of Clostridium difficile Infection?▿

    PubMed Central

    2010-01-01

    With the recognition of several serious outbreaks of Clostridium difficile infection in the industrialized world coupled with the development of new testing technologies for detection of this organism, there has been renewed interest in the laboratory diagnosis of C. difficile infection. Two factors seem to have driven much of this interest. First, the recognition that immunoassays for detection of C. difficile toxins A and B, for many years the most widely used tests for C. difficile infection diagnosis, were perhaps not as sensitive as previously believed at a time when attributed deaths to C. difficile infections were showing a remarkable rise. Second, the availability of FDA-approved commercial and laboratory-developed PCR assays which could detect toxigenic strains of C. difficile provided a novel and promising testing approach for diagnosing this infection. In this point-counterpoint on the laboratory diagnosis of C. difficile infection, we have asked two experts in C. difficile infection diagnosis, Ferric Fang, who has recently published two articles in the Journal of Clinical Microbiology advocating the use of PCR as a standalone test (see this author's references 12 and 28), and Mark Wilcox, who played a key role in developing the IDSA/SHEA guidelines on Clostridium difficile infection (see Wilcox and Planche's reference 1), along with his colleague, Tim Planche, to address the following question: what is the current role of algorithmic approaches to the diagnosis of C. difficile infection? PMID:20980568

  10. Clostridium difficile infection in a patient with Crohn disease.

    PubMed

    Hsu, Chien-Hui; Jeng, Yung-Ming; Ni, Yen-Hsuan

    2012-06-01

    Crohn disease is a chronic inflammatory disorder, which is rare in pediatric patients. The definite etiology and mechanism to induce an acute exacerbation of Crohn disease remains mostly unknown. The authors report on a 14-year-old girl with Crohn disease who has acute gastrointestinal symptoms caused by toxin A-producing Clostridium difficile, which mimicked a flare-up of Crohn disease. There was no preceding antibiotic prescription before the episode. The disease activity did not improve after steroid treatment, which is unusual for Crohn disease. However, all symptoms were dramatically relieved after eradication of C difficile, and led to a symptom-free period for more than 3 years. This case report aims to address the unusual presentation of a usual pathogen, C difficile, in a pediatric patient with Crohn disease. Copyright © 2012. Published by Elsevier B.V.

  11. Evidence-based medicine concerning efficacy of vaccination against Clostridium chauvoei infection in cattle.

    PubMed

    Uzal, Francisco A

    2012-03-01

    Clostridium chauvoei infections occur frequently in cattle and produce disease end lethality. Vaccination is frequently used to prevent occurrence of these infections. Although the literature on blackleg is voluminous, scientific evidence on the efficacy of vaccination against C chauvoei to prevent diseases and lethality in cattle is scant. This study demonstrates that the evidence of efficacy of C chauvoei vaccines to prevent infection by this microorganism in cattle is poor to moderate. A greater participation of practitioners in clinical research and greater access to informational tools such as systematic reviews must be part of the objectives of veterinary medicine.

  12. Clostridium difficile infection in cancer patients and hematopoietic stem cell transplant recipients.

    PubMed

    Chopra, Teena; Alangaden, George J; Chandrasekar, Pranatharthi

    2010-10-01

    Clostridium difficile has become the most common bacterial cause of nosocomial diarrhea. High rates of C. difficile infection (CDI) coupled with increasing morbidity and mortality attributed to CDI have sparked a renewed interest in this disease. Emergence of hypervirulent strains, rising rates of severe and recurrent infection and associated infection control challenges, and diagnostic and therapeutic dilemmas are major issues in the non-oncology population. Scant data on CDI exist in the cancer/transplant population. The purpose of this article is to describe the epidemiology, pathogenesis and management of CDI in patients receiving cancer chemotherapeutic agents, and in hematopoietic stem cell transplant recipients.

  13. Faecal microbiota transplantation for severe Clostridium difficile infection in the intensive care unit.

    PubMed

    Trubiano, Jason A; Gardiner, Bradley; Kwong, Jason C; Ward, Peter; Testro, Adam G; Charles, Patrick G P

    2013-02-01

    We describe a case of faecal microbiota transplantation (FMT) used for severe binary toxin-positive Clostridium difficile infection in an intensive care setting. The patient was admitted to the ICU of a tertiary hospital and failed traditional maximal pharmacological management. Adjunctive therapy with FMT given through gastroscopy resulted in resolution of the C. difficile-related symptoms. Although there is a growing experience with FMT for recurrent C. difficile infection, published evidence in severe disease is very limited. In a landscape of increasingly severe C. difficile infection, adjunctive FMT may be considered a useful early treatment option.

  14. Severe sepsis following wound infection by an unusual organism--Clostridium novyi.

    PubMed

    Majumdar, S; Woodcock, S; Cheesbrough, J

    2004-09-01

    We present a case of post-operative wound infection with Clostridium novyi in a non-intravenous drug user. Clinical features included progressive cellulitis despite being on antibiotics, accompanied by hypotension, marked leucocytosis and oedema but minimal fever. While established infection with this organism is associated with high mortality, our patient survived. The administration of clindamycin and intravenous immunoglobulin in addition to early surgical assessment and aggressive debridement of affected tissue may have contributed to this successful outcome. To our knowledge, this is the only reported post-operative wound infection due to this pathogen.

  15. Fecal transplantation as a treatment for Clostridium difficile infection in patients with ulcerative colitis.

    PubMed

    Izquierdo Romero, Marta; Varela Trastoy, Pilar; Mancebo Mata, Alejo

    2017-09-01

    Clostridium difficile (CD) infection is currently the most frequent etiology of nosocomial diarrhea. Besides, its incidence is progressively increasing in ambulatory patients. Inflammatory bowel disease (IBD) is a risk factor of CD infection itself, but also due to the regular immunosuppressive treatment used in these patients. At the present time, fecal transplantation (FT) is a safe and cost-effective alternative if the previous antibiotic treatments have failed. Similar outcomes between patients with IBD and general population have been reported. We present a case of a patient with ulcerative colitis and recurrent CD infection successfully treated with FT.

  16. Risk Factors and Outcomes for Bloodstream Infections Secondary to Clostridium difficile Infection

    PubMed Central

    Russo, Alessandro; Iraci, Federica; Carfagna, Paolo; Goldoni, Paola; Vullo, Vincenzo; Venditti, Mario

    2015-01-01

    We determined the incidence, risk factors, and outcomes of bloodstream infections (BSI) subsequent to Clostridium difficile infection (CDI). We performed a retrospective study of all patients with definite diagnosis of CDI admitted from January 2014 to December 2014 in two large hospitals in Rome. Two groups of patients were analyzed: those with CDI and subsequent BSI (CDI/BSI+) and those with CDI and no evidence of primary BSI (CDI/BSI−). Data about clinical features, microbiology, treatments, and mortality were obtained. Overall, 393 cases of CDI were included in the final analysis: 72 developed a primary nosocomial BSI, while 321 had CDI without microbiological and clinical evidence of BSI. Etiologic agents of BSI were Candida species (47.3%), Enterobacteriaceae (19.4%), enterococci (13.9%), and mixed infections (19.4%). In multivariate analysis, ribotype 027 status (odds ratio [OR], 6.5), CDI recurrence (OR, 5.5), severe CDI infection (OR, 8.3), and oral vancomycin at >500 mg/day (OR, 3.1) were recognized as factors independently associated with the development of nosocomial BSI. Thirty-day mortality from CDI diagnosis was higher for patients of the CDI/BSI+ group than for the controls (38.9 versus 13.1%; P < 0.001). Among patients of the CDI/BSI+ group, mortality attributable to primary BSI was as high as 57%. Our findings suggest that severe CDI is complicated by the development of nosocomial BSI. Candida species and enteric bacteria appear to be the leading causative pathogens and are associated with poor outcomes. PMID:26482315

  17. Risk Factors and Outcomes for Bloodstream Infections Secondary to Clostridium difficile Infection.

    PubMed

    Falcone, Marco; Russo, Alessandro; Iraci, Federica; Carfagna, Paolo; Goldoni, Paola; Vullo, Vincenzo; Venditti, Mario

    2015-10-19

    We determined the incidence, risk factors, and outcomes of bloodstream infections (BSI) subsequent to Clostridium difficile infection (CDI). We performed a retrospective study of all patients with definite diagnosis of CDI admitted from January 2014 to December 2014 in two large hospitals in Rome. Two groups of patients were analyzed: those with CDI and subsequent BSI (CDI/BSI(+)) and those with CDI and no evidence of primary BSI (CDI/BSI(-)). Data about clinical features, microbiology, treatments, and mortality were obtained. Overall, 393 cases of CDI were included in the final analysis: 72 developed a primary nosocomial BSI, while 321 had CDI without microbiological and clinical evidence of BSI. Etiologic agents of BSI were Candida species (47.3%), Enterobacteriaceae (19.4%), enterococci (13.9%), and mixed infections (19.4%). In multivariate analysis, ribotype 027 status (odds ratio [OR], 6.5), CDI recurrence (OR, 5.5), severe CDI infection (OR, 8.3), and oral vancomycin at >500 mg/day (OR, 3.1) were recognized as factors independently associated with the development of nosocomial BSI. Thirty-day mortality from CDI diagnosis was higher for patients of the CDI/BSI(+) group than for the controls (38.9 versus 13.1%; P < 0.001). Among patients of the CDI/BSI(+) group, mortality attributable to primary BSI was as high as 57%. Our findings suggest that severe CDI is complicated by the development of nosocomial BSI. Candida species and enteric bacteria appear to be the leading causative pathogens and are associated with poor outcomes.

  18. A quality committee's evaluation of surgical intervention for Clostridium difficile infection.

    PubMed

    Vasaly, Fran White; Reines, David

    2009-08-01

    Clostridium difficile (C diff) is an anaerobic bacterium that causes antibiotic-associated colitis, which can progress to a life-threatening illness for some patients. Clostridium difficile is highly transmissible in health care settings and has high morbidity and mortality rates. The increased prevalence of this bacterium and the consequences of infection necessitate an understanding of its transmission and use of stringent infection control practices. A two-year retrospective evaluation was performed to examine the effectiveness of a screening tool for patients requiring surgical intervention for C diff and to determine whether treatment was timely and effective. Early, aggressive surgical intervention appears to bel the single most effective treatment for fulminant C diff colitis.

  19. Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.

    PubMed

    Woodworth, Michael H; Neish, Emma M; Miller, Nancy S; Dhere, Tanvi; Burd, Eileen M; Carpentieri, Cynthia; Sitchenko, Kaitlin L; Kraft, Colleen S

    2017-04-01

    Fecal microbiota transplantation is an efficacious and inexpensive therapy for recurrent Clostridium difficile infection, yet its safety is thought to depend on appropriate fecal donor screening. FDA guidance for regulation of this procedure is in flux, but screening and manufacture of fecal material from asymptomatic donors present many challenges to clinical laboratories. This minireview summarizes FDA regulatory changes, principles of donor selection, and recommended laboratory screening practices for fecal microbiota transplantation.

  20. 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

  1. 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.

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

    DTIC Science & Technology

    2017-06-30

    incidence among all beneficiaries seeking care within the Military Health System (MHS). This report is a calendar year (CY) 2016 update to the CY...Department NMCPHC-EDC-TR-364-2017 Appendix A: Acronym and Abbreviation List Acronym/Abbreviation Definition CHCS  Composite  Health   Care  System CO...Annual Surveillance Summary: Clostridium difficile Infections in the Military Health System (MHS), 2016

  3. Coxofemoral luxation in a border collie as a complication of a Clostridium tetani infection.

    PubMed

    Goldhammer, M A; Chapman, P S; Grierson, J M

    2008-03-01

    A four-month-old male, entire, border collie was presented to the Queen Mother Hospital for Animals with a two day history of muscular spasms and "Risus sardonicus". Tetanus was diagnosed, and the dog was treated with tetanus antitoxin, antibiotics and supportive therapy. Coxofemoral luxation resulted as a complication of the tetanus and was successfully managed by performing a femoral head and neck excision. This is the first report of joint luxation associated with Clostridium tetani infection in a dog.

  4. 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.

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

    PubMed

    Mullish, B H; Marchesi, J R; Thursz, M R; Williams, H R T

    2015-05-01

    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.

  6. Clostridium glycolicum Wound Infections: Case Reports and Review of the Literature▿

    PubMed Central

    Jiang, Wei; Abrar, Sahibzada; Romagnoli, Mark; Carroll, Karen C.

    2009-01-01

    We describe two cases of Clostridium glycolicum wound infections in immunocompetent adults. The bacterium was identified by 16S rRNA gene sequencing. This is the third published report of the recovery of this organism from human clinical material and highlights the importance of the organism as a potential human pathogen. Our report extends the spectrum of the diseases caused by C. glycolicum. PMID:19261780

  7. 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.

  8. Association between bacterial strain type and host biomarkers in Clostridium perfringens infected goats.

    PubMed

    Khan, Mumtaz Ali; Durrani, Aneela Zameer; Khan, Sher Bahadar; Khan, Muhammad Arif; Sheikh, Ali Ahmad; Khan, Naimat Ullah; Prince, Kashif; Ullah, Naimat; Khan, Azmat Ullah

    2017-09-26

    The study project was designed to determine the effects of Clostridium perfringens type D infection on hematological and biochemical parameters in goats. Purposive blood samples were collected from 6 healthy and 12 diseased goats positive for C. perfringens infection. Neither the animals nor their mother were vaccinated against Clostridium perfringens from whom samples were obtained. Study was carried out in two different topographic areas; hilly (district Swat) and plain (district Mardan) of Khyber Pakhtunkhwa, Pakistan but nonsignificant (P > 0.05) statistical difference was recorded between the prevalence of Clostridium perfringens infected goats. Mean erythrocytes count (RBC) and hemoglobin level decreased significantly (P < 0.05) while the white blood cells (WBC) increased significantly (P < 0.05) in diseased animals compared to the healthy animals. However non-significant differences (P > 0.05) were observed in packet cell volume (PCV) and platelets count in healthy and diseased animals. According to biochemical analysis, a significant increase (P < 0.05) in liver enzymes, total bilirubin, serum creatinine, blood urea and glucose was recorded in diseased goats. . The results demonstrated that fluctuation in most of the mean hematological values remained within the normal range however the mean liver enzymes, total bilirubin, serum creatinine, blood urea and glucose levels gone beyond the normal levels which demonstrated severe damages to liver and kidneys. Copyright © 2017. Published by Elsevier Ltd.

  9. Diagnosis of Clostridium perfringens intestinal infections in sheep and goats.

    PubMed

    Uzal, Francisco A; Songer, J Glenn

    2008-05-01

    Clostridium perfringens produces enteric diseases, generically called enterotoxemias, in sheep, goats, and other animals. This microorganism can be a normal inhabitant of the intestine of most animal species, including humans, but when the intestinal environment is altered by sudden changes in diet or other factors, C. perfringens proliferates and produces potent toxins that act locally or are absorbed into the general circulation with usually devastating effects on the host. History, clinical signs, and gross postmortem findings are useful tools for establishing a presumptive diagnosis of clostridial enterotoxemia in sheep and goats. Definitive diagnosis requires laboratory confirmation. Isolation of some types of C. perfringens (e.g., B and C) can be of diagnostic value, but other types (e.g., A) are so commonly found in the intestine of normal animals that isolation is meaningless from a diagnostic point of view. The most accepted criterion in establishing a definitive diagnosis of enterotoxemia is detection of C. perfringens toxins in intestinal contents. Also, histopathological examination of brain is very useful for diagnosis of type D disease, as lesions produced by epsilon toxin in the brains of sheep and goats are pathognomonic for type D enterotoxemia. Ancillary tests, such as measuring urine glucose or observing Gram-stained smears of intestinal mucosa, can be used. However, although such tests have a presumptive diagnostic value when positive, they cannot be used to rule out a diagnosis of enterotoxemia when negative.

  10. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review.

    PubMed

    Cammarota, Giovanni; Ianiro, Gianluca; Gasbarrini, Antonio

    2014-09-01

    By systematic review, we assessed the impact of fecal microbiota transplantation (FMT) for the treatment of Clostridium difficile (CD)-associated diarrhea. Fecal microbiota microbiota transplantation from a healthy donor into an individual with CD infection (CDI) can resolve symptoms. We conducted systematic searches in PubMed, SCOPUS, Web of Science, and Cochrane Library. The last search was run on February 8, 2013. The following Medical Subject Headings terms and keywords were used alone or in combination: Clostridium difficile; Clostridium infection; pseudomembranous colitis; feces; stools; fecal suspension; fecal transplantation; fecal transfer; fecal infusion; microbiota; bacteriotherapy; enema; nasogastric tube; colonoscopy; gastroscopy; fecal donation; donor. A critical appraisal of the clinical research evidence on the effectiveness and safety of FMT for the treatment of patients with CD-associated diarrhea was made. Twenty full-text case series, 15 case reports, and 1 randomized controlled study were included for the final analysis. Almost all patients treated with donors' fecal infusion experienced recurrent episodes of CD-associated diarrhea despite standard antibiotic treatment. Of a total of 536 patients treated, 467 (87%) experienced resolution of diarrhea. Diarrhea resolution rates varied according to the site of infusion: 81% in the stomach; 86% in the duodenum/jejunum; 93% in the cecum/ascending colon; and 84% in the distal colon. No severe adverse events were reported with the procedure. FMT seems efficacious and safe for the treatment of recurrent CDI. Hospitals should encourage the development of fecal transplantation programs to improve therapy of local patients.

  11. Fecal microbiota transplantation via nasogastric tube for recurrent clostridium difficile infection in pediatric patients.

    PubMed

    Kronman, Matthew P; Nielson, Heather J; Adler, Amanda L; Giefer, Matthew J; Wahbeh, Ghassan; Singh, Namita; Zerr, Danielle M; Suskind, David L

    2015-01-01

    Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.

  12. Epidemiology and Risk Factors for Community-Associated Clostridium difficile Infection: A Narrative Review.

    PubMed

    Bloomfield, Lauren E; Riley, Thomas V

    2016-09-01

    Clostridium difficile infection (CDI) was once considered a primarily nosocomial concern. Emerging evidence from the last 20 years has highlighted a drastic shift in the known epidemiology of CDI, with disease outside of hospitals apparently occurring more frequently and causing severe disease in populations that were thought to be at low risk. This narrative review summarises potential pathways for infection outside of the hospital environment and highlights likely routes of transmission. Further, evidence is presented on potential risk factors for development of disease. Understanding the epidemiology of CDI outside of hospitals is essential to the ability to prevent and control disease in vulnerable populations.

  13. [Treatment of a severe Clostridium difficile infection with colonic lavages. Report of one case].

    PubMed

    Quezada, Felipe; Castillo, Richard; Villalón, Constanza; Zúñiga, José Miguel; Manterola, Carla; Molina, María Elena; Bellolio, Felipe; Urrejola, Gonzalo

    2015-05-01

    A loop ileostomy with intraoperative anterograde colonic lavage has been described as an alternative to colectomy in the management of cases of Clostridium difficile infection refractory to medical treatment. We report a 69 years old diabetic women admitted with a septic shock. An abdominal CAT scan showed a pan-colitis that seemed to be infectious. A polymerase chain reaction was positive for Clostridium Difficile. Due to the failure to improve after full medical treatment, a derivative loop ileostomy and intra-operatory colonic lavage were performed, leaving a Foley catheter in the proximal colon. In the postoperative period, anterograde colonic instillations of Vancomycin flushes through the catheter were performed every 6 hours. Forty eight hours after surgery, the patient improved. A colonoscopy prior to discharge showed resolution of the pseudomembranous colitis.

  14. Pathway to Prevention of Nosocomial Clostridium difficile Infection.

    PubMed

    Goldstein, Ellie J C; Johnson, Stuart; Maziade, Pierre-Jean; McFarland, Lynne V; Trick, William; Dresser, Linda; Millette, Mathieu; Mazloum, Hadi; Low, Donald E

    2015-05-15

    To address the significant morbidity and mortality rates associated with nosocomial Clostridium difficile-associated diarrhea (CDAD), a series of recommendations and a pathway to prevention were developed. An expert panel of infectious disease (ID) specialists participated in a modified Delphi process with specific objectives: (1) conduct a review for CDAD and prevention; (2) develop statements based upon panel members' opinions; (3) hold a panel meeting during the 2012 IDWeek; and (4) review the final recommendations and prevention pathway prior to submission for publication. The panel voted on (1) antibiotic stewardship (7 of 8 panelists); (2) reduction of other potentially modifiable risk factors (variable); (3) utilization of specific probiotics to prevent C. difficile overgrowth (8/8); (4) staff education regarding CDAD preventive measures (8/8); (5) appropriate hand hygiene for everyone (7/8); (6) environmental cleaning (8/8); (7) medical equipment disinfection (7/8); (8) early detection of CDAD in symptomatic patients (7/8); (9) usage of protective clothing/gloves (8/8); (10) proper measures during outbreak (8/8); and (11) surveillance to monitor efficacy data of preventive measures (8/8). The panel members agreed with 11 of 17 recommendations presented. The additional recommendations by the panel were proton pump inhibitor use as a risk factor and the use of adjunctive therapy with specific probiotic, as it was approved by Health Canada for the risk reduction of CDAD in hospitalized patients. © 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.

  15. Fecal Microbiota Transplant for Clostridium difficile Infection in a Pregnant Patient.

    PubMed

    Saeedi, Bejan J; Morison, Doree Gardner; Kraft, Colleen S; Dhere, Tanvi

    2017-03-01

    Clostridium difficile infection has been associated with negative outcomes in the general population and in pregnant patients. Fecal microbiota transplant has become the standard for treatment of recurrent as well as refractory C difficile infection. We present a case of a 28-year-old pregnant woman who presented with recurrent C difficile infection despite treatment with vancomycin and fidaxomicin and underwent a successful fecal microbiota transplant through colonoscopy at 18 weeks of gestation. She no longer required antibiotics for the remainder of her pregnancy to treat C difficile and had a term vaginal delivery at 39 weeks of gestation. Our pregnant patient tolerated and responded to a fecal microbiota transplant for treatment of recurrent C difficile infection. Future large-scale studies are needed to determine the efficacy, safety, and long-term effects of manipulating the microbiome in pregnant patients and the neonates.

  16. BACTERIOCIN E1073 PRODUCED BY ENTEROCOCCUS FAECIUM LWP1073 IS EFFECTIVE FOR TREATING COMMENSAL CLOSTRIDIUM PERFRINGENS INFECTION IN BROILERS

    USDA-ARS?s Scientific Manuscript database

    Enterotoxin-producing Clostridium perfringens type A bacteria occupy a significant place in the etiological structure of food-borne infections in humans. One potential approach to minimize infections associated with food-borne pathogens is to control the carriage of C. perfringens in broilers. For ...

  17. Treatment of Clostridium difficile infection: a national survey of clinician recommendations and the use of faecal microbiota transplantation.

    PubMed

    Prior, A R; Kevans, D; McDowell, L; Cudmore, S; Fitzpatrick, F

    2017-04-01

    Adherence to Clostridium difficile infection treatment guidelines is associated with lower recurrence rates and mortality as well as cost savings. This survey of Irish clinicians indicates that patients are managed using a variety of approaches. Faecal microbiota transplantation is potentially underused despite its recommendation in national and European guidelines. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  18. Immunization of hamsters against Clostridium difficile infection using the Cwp84 protease as an antigen.

    PubMed

    Péchiné, Séverine; Denève, Cécile; Le Monnier, Alban; Hoys, Sandra; Janoir, Claire; Collignon, Anne

    2011-10-01

    Clostridium difficile is a pathogen responsible for diarrhoea and colitis, particularly after antibiotic treatment. We evaluated the C. difficile protease Cwp84, found to be associated with the S-layer proteins, as a vaccine antigen to limit the C. difficile intestinal colonization and therefore the development of the infection in a clindamycin-treated hamster model. First, we evaluated the immune response and the animal protection against death induced by several immunization routes: rectal, intragastric and subcutaneous. Antibody production was variable according to the immunization routes. In addition, serum Cwp84 antibody titres did not always correlate with animal protection after challenge with a toxigenic C. difficile strain. The best survival rate was observed with the rectal route of immunization. Then, in a second assay, we selected this immunization route to perform a larger immunization assay including a Cwp84 immunized group and a control group. Clostridium difficile intestinal colonization and survival rate, as well as the immune response were examined. Clostridium difficile hamster challenge resulted in a 26% weaker and slower C. difficile intestinal colonization in the immunized group. Furthermore, hamster survival in the Cwp84 immunized group was 33% greater than that of the control group, with a significant statistical difference.

  19. A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections.

    PubMed

    Henderson, Mackenzie; Bragg, Amanda; Fahim, Germin; Shah, Monica; Hermes-DeSantis, Evelyn R

    2017-09-02

    This review aims to evaluate the literature on the safety and efficacy of novel toxoid vaccines for the prophylaxis of Clostridium difficile infections (CDI) in healthy adults. Literature searches for clinical trials were performed through MEDLINE, ClinicalTrials.gov, and Web of Science using the keywords bacterial vaccines, Clostridium difficile, and vaccine. English-language clinical trials evaluating the efficacy and/or safety of Clostridium difficile toxoid vaccines that were completed and had results posted on ClinicalTrials.gov or in a published journal article were included. Six clinical trials were included. The vaccines were associated with mild self-reported adverse reactions, most commonly injection site reactions and flu-like symptoms, and minimal serious adverse events. Five clinical trials found marked increases in antibody production in vaccinated participants following each dose of the vaccine. Clinical trials evaluating C. difficile toxoid vaccines have shown them to be well tolerated and relatively safe. Surrogate markers of efficacy (seroconversion and geometric mean antibody levels) have shown significant immune responses to a vaccination series in healthy adults, indicating that they have the potential to be used as prophylaxis for CDI. However, more research is needed to determine the clinical benefits of the vaccines.

  20. Structural and functional changes in the gut microbiota associated to Clostridium difficile infection

    PubMed Central

    Pérez-Cobas, Ana E.; Artacho, Alejandro; Ott, Stephan J.; Moya, Andrés; Gosalbes, María J.; Latorre, Amparo

    2014-01-01

    Antibiotic therapy is a causative agent of severe disturbances in microbial communities. In healthy individuals, the gut microbiota prevents infection by harmful microorganisms through direct inhibition (releasing antimicrobial compounds), competition, or stimulation of the host's immune defenses. However, widespread antibiotic use has resulted in short- and long-term shifts in the gut microbiota structure, leading to a loss in colonization resistance in some cases. Consequently, some patients develop Clostridium difficile infection (CDI) after taking an antibiotic (AB) and, at present, this opportunistic pathogen is one of the main causes of antibiotic-associated diarrhea in hospitalized patients. Here, we analyze the composition and functional differences in the gut microbiota of C. difficile infected (CDI) vs. non-infected patients, both patient groups having been treated with AB therapy. To do so we used 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. Samples were taken before, during and after AB treatment and were checked for the presence of the pathogen. We performed different analyses and comparisons between infected (CD+) vs. non-infected (CD−) samples, allowing proposing putative candidate taxa and functions that might protect against C. difficile colonization. Most of these potentially protective taxa belonged to the Firmicutes phylum, mainly to the order Clostridiales, while some candidate protective functions were related to aromatic amino acid biosynthesis and stress response mechanisms. We also found that CDI patients showed, in general, lower diversity and richness than non-infected, as well as an overrepresentation of members of the families Bacteroidaceae, Enterococcaceae, Lactobacillaceae and Clostridium clusters XI and XIVa. Regarding metabolic functions, we detected higher abundance of genes involved in the transport and binding of carbohydrates, ions, and others compounds as a response to an antibiotic environment. PMID

  1. Reduction in Clostridium difficile infection associated with the introduction of hydrogen peroxide vapour automated room disinfection.

    PubMed

    McCord, J; Prewitt, M; Dyakova, E; Mookerjee, S; Otter, J A

    2016-10-01

    The clinical impact of implementing hydrogen peroxide vapour (HPV) disinfection of rooms vacated by patients with Clostridium difficile infection (CDI) was evaluated. Breakpoint time series analysis indicated a significant reduction (P<0.001) in the CDI rate at the time when HPV disinfection was implemented, resulting in a reduction in the CDI rate from 1.0 to 0.4 cases per 1000 patient-days in the 24 months before HPV usage compared with the first 24 months of HPV usage. HPV should be considered to augment the terminal disinfection of rooms vacated by patients with CDI. Copyright © 2016. Published by Elsevier Ltd.

  2. Antibiotic overuse and Clostridium difficile infections: the Indian paradox and the possible role of dietary practices.

    PubMed

    Ramakrishnan, N; Sriram, K

    2015-01-01

    Antibiotic abuse is rampant in India, such that one may expect to see an increase of Clostridium difficile infections (CDI). However, we found that the incidence of CDI in India (1.67%) is no different from that reported in USA (1.6%) using similar techniques of detection (polymerase chain reaction test). We offer a possible explanation for this paradox. It is likely that a diet rich in fiber, yogurt, and possibly turmeric may have a protective role in decreasing the incidence of CDIs in India. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. IgG antibody response to toxins A and B in patients with Clostridium difficile infection.

    PubMed

    Wullt, M; Norén, T; Ljungh, A; Åkerlund, T

    2012-09-01

    IgG antibodies against Clostridium difficile toxins A and B were followed in controls and in patients with an initial C. difficile infection (CDI). Of the 50 CDI patients, 38 were cured and 12 developed recurrence. Compared to controls, patients had significantly lower anti-toxin A and B IgGs at inclusion, but the subsequent levels rose slightly regardless of clinical outcome. The results imply that the general serum reactivity against toxins A and B in the population reduces the risk of CDI, which suggests implications for vaccine strategies.

  4. Concurrent swine erysipelas and Clostridium novyi infections associated with sow mortality in outdoor sows in Kenya.

    PubMed

    Friendship, C R; Bilkei, G

    2007-05-01

    A sudden increase in sow mortality was reported from a large outdoor pig-breeding unit in Kenya. The sows showed pyrexia and diamond shaped to confluent skin lesions ante-mortem. Gross pathological examination of the carcases was performed and organ samples (heart, liver, kidney, spleen, mandible lymph nodes) were sent for further diagnostic investigation. Based upon the clinical, gross- and microscopic-pathological signs, bacteriological findings and toxin testing, concurrent infection with Erysipelothrix rhusiopathiae and Clostridium novyi was diagnosed as the cause of the sow mortality.

  5. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient.

    PubMed

    Neemann, K; Eichele, D D; Smith, P W; Bociek, R; Akhtari, M; Freifeld, A

    2012-12-01

    We present a case of severe Clostridium difficile infection (CDI) in a non-neutropenic allogeneic hematopoietic stem cell transplant recipient who was treated successfully with fecal microbiota therapy after standard pharmacologic therapy had failed. Following naso-jejunal instillation of donor stool, the patient's symptoms resolved within 48 h. Bowel resection was averted. This is the first case in the literature, to our knowledge, to describe fecal microbiota therapy in a profoundly immunocompromised host with severe CDI. We propose that fecal microbiota therapy be considered as a therapeutic option in immunosuppressed patients with refractory severe CDI. © 2012 John Wiley & Sons A/S.

  6. Evolution of Testing Algorithms at a University Hospital for Detection of Clostridium difficile Infections

    PubMed Central

    Culbreath, Karissa; Ager, Edward; Nemeyer, Ronald J.; Kerr, Alan

    2012-01-01

    We present the evolution of testing algorithms at our institution in which the C. Diff Quik Chek Complete immunochromatographic cartridge assay determines the presence of both glutamate dehydrogenase and Clostridium difficile toxins A and B as a primary screen for C. difficile infection and indeterminate results (glutamate dehydrogenase positive, toxin A and B negative) are confirmed by the GeneXpert C. difficile PCR assay. This two-step algorithm is a cost-effective method for highly sensitive detection of toxigenic C. difficile. PMID:22718938

  7. Clostridium Perfringens Infection in a Febrile Patient with Severe Hemolytic Anemia

    PubMed Central

    Hashiba, Masamitsu; Tomino, Atsutoshi; Takenaka, Nobuyoshi; Hattori, Tomonori; Kano, Hideki; Tsuda, Masanobu; Takeyama, Naoshi

    2016-01-01

    Patient: Male, 82 Final Diagnosis: Clostridium perfringens infection Symptoms: Anemia • fever • shock Medication: — Clinical Procedure: Antimicrobial chemotherapy Specialty: Infectious Diseases Objective: Rare disease Background: Clostridium perfringens (C. perfringens) can cause various infections, including gas gangrene, crepitant cellulitis, and fasciitis. While C. perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin of this bacterium induces massive intravascular hemolysis by disrupting red blood cell membranes. Case Report: We present the case of a male patient with diabetes who developed a fatal liver abscess with massive intravascular hemolysis and septic shock caused by toxigenic C. perfringens. The peripheral blood smear showed loss of central pallor, with numerous spherocytes. Multiplex PCR only detected expression of the cpa gene, indicating that the pathogen was C. perfringens type A. Conclusions: C. perfringens infection should be considered in a febrile patient who has severe hemolytic anemia with a very low MCV, hemolyzed blood sample, and negative Coombs test. The characteristic peripheral blood smear findings may facilitate rapid diagnosis. PMID:27049736

  8. Analysis of nosocomial acquired Clostridium difficile infection in an Italian research and teaching hospital.

    PubMed

    Bertizzolo, L; Domeniconi, G; Fabio, G; Jacchetti, G; Serafino, S; Formica, S; Nobile, M; Castaldi, S

    2013-01-01

    Clostridium difficile (Cd) infection is a nosocomial plague which is correlated with several clinical and medical factors such as antibiotics intake. It is known that prevention is possible through infection control measures both clinical and epidemiological. We examined the data from a study about Cd infection in four internal medicine wards in a teaching and research hospital in the north part of Italy in a two years period. The wards are only slightly different in size, plan, structures, nursing staff and patient's characteristics but have a different room' organization, lay out and different level of continuous education programs for nursing personnel. We reported a high incidence of the infection and a non-significant difference between wards also looking to the different possibility-capacity of taking preventive measures and the different level of nursing staff continuous educational performance. The analysis of the data we obtained was the basis to write a protocol and to start a training course for the medical and nursing personnel of the four wards on the managing of patients infected with Cd infection. On March 2011 we started a one year longitudinal study about the Cd infections in the same wards with the purpose of evaluating the adherence to the protocol, monitoring the incidence of infection and studying the risk factors of the infected patients related to the proper use of the protocol on Cd.

  9. Toxic megacolon from fulminant Clostridium difficile infection induced by topical silver sulphadiazine.

    PubMed

    Tan, Christopher B; Rajan, Dhyan; Shah, Mitanshu; Ahmed, Shadab; Freedman, Lester; Rizvon, Kaleem; Mustacchia, Paul

    2012-08-08

    Pseudomembranous colitis and toxic megacolon (TM) are well-known complications of Clostridium difficile infections. Systemic antibiotic is considered as the major risk factor for the development of C difficile colitis. However, topical antibiotics are rarely associated with the infection. As previously thought, the use of topical antibiotic is capable of systemic absorption in damaged and denuded skin; sufficient enough to suppress the normal bowel flora. Here, we present an unusual case of TM from C difficile infection induced by topical silver sulphadiazine in a 60-year-old man with immune-bullous pemphigus vulgaris. The diagnosis is further complicated by the absence of diarrhoea as the initial presentation. Despite adequate medical and surgical intervention, the patient had an unfavourable outcome.

  10. Fecal microbiota transplantation - methods of treatment of recurrent Clostridium difficile infections and other diseases.

    PubMed

    Juszczuk, Klaudia; Grudlewska, Katarzyna; Mikucka, Agnieszka; Gospodarek, Eugenia

    2017-03-27

    Clostridium difficile is a serious epidemiological problem and particularly dangerous microorganism causing hospital infections. Currently, the treatment of C. difficile infections is the use of metronidazole or vancomycin. However, in some patients, recurrent infection difficult to treat occurs. Fecal microbiota transplantation (FMT) is a new method used to treat the recurrent CDI. FMT consists in the infusion of the fecal suspension from a healthy donor into the gastrointestinal tract of a patient with CDI to restore the natural intestinal microflora. FMT is safe and effective treatment of recurrent CDI. FMT is extensively described around the world, but to date only two randomized studies confirming the effectiveness of FMT have been conducted. This method was also applied in the treatment of diseases such as pseudomembranous colitis, ulcerative colitis, Crohn's disease and irritable bowel syndrome. The review describes the procedure for FMT and the current state of knowledge about the effectiveness of FMT in the treatment of recurrent CDI.

  11. Clostridium difficile Infection: A Model for Disruption of the Gut Microbiota Equilibrium.

    PubMed

    Blanchi, Julie; Goret, Julien; Mégraud, Francis

    2016-01-01

    The gut microbiota is a complex ecosystem defined by the combination of microorganisms living in the gastrointestinal tract. Its equilibrium is intimately involved in several aspects of vital process for human physiology and nutrition. Its composition changes depending on both exogenous and endogenous factors. The disruption of the gut microbiota by antibiotics often leads to an opportunistic infection by Clostridium difficile. The unbalanced intestinal microbiota promotes spore germination, growth of vegetative forms and toxin production leading to C. difficile infection, which is characterized by diarrhea and possibly pseudomembranous colitis. This nosocomial infection is a good model to understand the role of the gut microbiota in preventing the development of pathogens. © 2016 S. Karger AG, Basel.

  12. THE POWER OF POOP: FECAL MICROBIOTA TRANSPLANTATION FOR CLOSTRIDIUM DIFFICILE INFECTION.

    PubMed

    Edmond, Michael B

    2016-01-01

    The human gut is colonized with 200 to 1,000 bacterial species. Administration of antibiotics reduces the diversity of the intestinal microbiota, reduces colonization resistance, and can lead to infection with Clostridium difficile. These infections have become more prevalent and increasingly patients are experiencing multiple recurrences that are incurable with standard treatment. Although fecal microbiota transplantation (FMT) has been used for centuries in human and veterinary medicine, only recently has it be shown to be highly effective for recurrent C. difficile infection. The goal of FMT is to re-introduce a complete, stable community of gut microorganisms to repair or replace the disrupted native microbiota. FMT can be delivered via nasoenteric tube, colonoscopy, or enema. Despite a cure rate approximating 90%, many barriers to FMT have limited its availability to patients. The recent development of a not-for-profit stool bank has helped to make this therapy more accessible. Additional indications for FMT are currently under investigation.

  13. Clostridium difficile infection in inflammatory bowel disease: challenges in diagnosis and treatment.

    PubMed

    Tang, Ying M; Stone, Christian D

    2017-04-01

    The problem of Clostridium difficile infection (CDI) has reached epidemic proportions, particularly in industrialized nations. The pathophysiology, disease course and the potential complications are well appreciated in the general hospitalized patient. However, when CDI occurs in the setting of inflammatory bowel disease (IBD), a number of distinct differences in the diagnosis and clinical management of the infection in this population should be appreciated by gastroenterologists, hospitalists and other care providers. This review highlights the unique aspects of CDI when it occurs in IBD patients with an emphasis on the challenge of distinguishing persistent infection from exacerbation of underlying chronic colitis. An understanding of how CDI may differ in presentation and how management should be altered can prevent serious and life-threatening complications.

  14. Editorial: Making Fecal Microbiota Transplantation Easier to Swallow: Freeze-Dried Preparation for Recurrent Clostridium difficile Infections.

    PubMed

    Youngster, Ilan; Gerding, Dale N

    2017-06-01

    Fecal microbiota transplant (FMT) has emerged as an effective and increasingly popular therapy for recurrent Clostridium difficile infections in patients that have failed standard antimicrobial treatment. Patient access to FMT is hampered by the logistics of manufacturing, storing, and delivering the inocula. An observational study describes the development and clinical efficacy of freeze-dried FMT capsules for oral administration. While awaiting the emergence of defined bacterial therapeutics for Clostridium difficile infections, this refinement of FMT is an encouraging step toward simplifying FMT treatment. Randomized controlled trials are required to further establish the efficacy and safety of lyophilized FMT.

  15. Management of candidemia in patients with Clostridium difficile infection.

    PubMed

    Falcone, Marco; Venditti, Mario; Sanguinetti, Maurizio; Posteraro, Brunella

    2016-07-01

    Patients with C. difficile infection (CDI) experience intestinal microflora changes that can promote the overgrowth and subsequent translocation of gut resident pathogens into the blood. Consistently, CDI due to PCR-ribotype 027 strain, severe or relapsing CDI, and treatment with high-dosage vancomycin are independent risk factors for candidemia. We review the role played by the gut microbiota during CDI and its treatment, as well as the clinical profile of CDI patients who are at risk of developing candidemia. Also, we discuss the management of these patients by focusing on pre-emptive strategies aimed at reducing the risk of candidemia, and on innovative anti-C. difficile therapies that may mitigate CDI-related effects such as the altered gut microbiota composition and prolonged intestinal mucosa damage. Expert commentary: A closer clinical and diagnostic monitoring of patients with CDI should help to limit the CDI-associated long-term consequences, including Candida infections, which worsen the outcome of hospitalized patients.

  16. A Review of Clostridium difficile Infection at the University Hospital of the West Indies, Jamaica

    PubMed Central

    Clare-Pascoe, N; Lee, MG; Murphy, T; Nicholson, A; Ferguson, TS

    2015-01-01

    ABSTRACT Objectives: This study examined the frequency of Clostridium difficile infection (CDI) among hospital admission and diarrhoeal stool samples over a six-year period. Methods: A review of all suspected cases of C difficile positive patients from 2007 to 2012 at the University Hospital of the West Indies (UHWI), Jamaica, was performed. Clostridium difficile infection was confirmed by clinical features and a positive enzyme-linked immunosorbent assay (ELISA) stool test for Clostridium Toxins A and B. The demographics, clinical features, risk factors, treatment and outcomes were also collated. Results: There were 56 patients reviewed. The most commonly affected age group was 40–59 years of age. The proportion of CDI cases per total stool samples increased from 0.5% in 2007 to 5.9% in 2010 then fell to 2.2% in 2011 but increased again to 4.3% in 2012. The proportion of cases per total UHWI admissions also increased from 0.12 cases per 1000 admissions in 2007 to 1.16 in 2010 and 1.36 in 2012 (p < 0.001). Most CDI cases were nosocomial (76% males, 48.6% females). Co-morbidities included hypertension and end-stage renal disease. Ceftazidime was the most common antibiotic associated with the development of CDI. Resolution occurred in 62.5% of patients. Duration of hospital stay was longer in males than females (≥ 21 versus < 7 days) and males had more adverse outcomes, with death in 23.8% versus 11.4%. Conclusion: There has been an increase in the frequency of CDI at UHWI with a greater than expected frequency of community acquired CDI. Increased awareness is needed of the increasing risk for CDI and measures must be taken to prevent the disease, especially in hospitalized patients. PMID:26624597

  17. Therapeutic Success of Rifaximin for Clostridium difficile Infection Refractory to Metronidazole and Vancomycin

    PubMed Central

    Tannous, George; Neff, Guy; Kemmer, Nyingi

    2010-01-01

    We report the case of a 46-year-old white male with confirmed Clostridium difficile infection for >4 weeks after fluoroquinolone therapy. The patient received two courses of metronidazole 500 mg three times daily (t.i.d.) during which time diarrhea resolved; however, symptoms recurred 14–15 days after treatment termination. He received a 2-week course of vancomycin 125 mg four times daily, with symptoms recurring 10 days after treatment conclusion. The patient then received a pulsed tapering schedule of vancomycin with adjunctive Saccharomyces boulardii. Diarrhea recurred 12 days after treatment completion. He received rifaximin 400 mg t.i.d. while hospitalized for diarrhea-associated complications. Symptoms resolved within 24 h. The patient received a 4-week regimen of rifaximin 400 mg orally t.i.d. after discharge. No further episodes of diarrhea were reported within 6 months after treatment termination. The present case supports the potential benefit of rifaximin for the treatment of recurrent Clostridium difficile infection. PMID:21060709

  18. Hydralazine-Induced ANCA Vasculitis in the Setting of Acute Clostridium Difficile Infection.

    PubMed

    Rasla, Somwail; El Meligy, Amr; Cucu, Dragos F

    2016-11-01

    We report a rare case of Hydralazine-induced ANCA associated glomerulonephritis with alveolar hemorrhage in the setting of acute Clostridium Difficile Infection. A 71-year-old Caucasian woman with hypertension, who was being treated with hydralazine 25 mg twice a day for six years, presented to the hospital with diarrhea, nausea, vomiting and anemia. She had acute kidney injury and urinalysis showed proteinuria, dysmorphic RBCs, and rare RBC cast. She was found to have Clostridium difficile colitis which was successfully treated. She became hypoxemic; CT scan findings showed bilateral pulmonary infiltrates. Broncho-alveolar lavage was consistent with pulmonary hemorrhage. Kidney biopsy revealed focal segmental necrotizing and diffuse crescentic glomerulonephritis, pauci-immune type (ANCA-associated). Hydralazine was discontinued and the patient was treated with corticosteroids, intravenous cyclophosphamide and plasmapheresis. To our knowledge, hydralazine-associated low complement in the setting of C-diff infection has not been previously reported. This is considered a potentially life-threatening condition requiring immediate discontinuation of the offending medication and expedited lifesaving measures. [Full article available at http://rimed.org/rimedicaljournal-2016-11.asp].

  19. Development and Evaluation of an Ovine Antibody-Based Platform for Treatment of Clostridium difficile Infection

    PubMed Central

    Roberts, April; McGlashan, Joanna; Al-Abdulla, Ibrahim; Ling, Roger; Denton, Harriet; Green, Steve; Coxon, Ruth; Landon, John

    2012-01-01

    Treatment of Clostridium difficile is a major problem as a hospital-associated infection which can cause severe, recurrent diarrhea. The currently available antibiotics are not effective in all cases and alternative treatments are required. In the present study, an ovine antibody-based platform for passive immunotherapy of C. difficile infection is described. Antibodies with high toxin-neutralizing titers were generated against C. difficile toxins A and B and were shown to neutralize three sequence variants of these toxins (toxinotypes) which are prevalent in human C. difficile infection. Passive immunization of hamsters with a mixture of toxin A and B antibodies protected them from a challenge with C. difficile spores in a dose-dependent manner. Antibodies to both toxins A and B were required for protection. The administration of toxin A and B antibodies up to 24 h postchallenge was found to reduce significantly the onset of C. difficile infection compared to nonimmunized controls. Protection from infection was also demonstrated with key disease isolates (ribotypes 027 and 078), which are members of the hypervirulent C. difficile clade. The ribotype 027 and 078 strains also have the capacity to produce an active binary toxin and these data suggest that neutralization of this toxin is unnecessary for the management of infection induced by these strains. In summary, the data suggest that ovine toxin A and B antibodies may be effective in the treatment of C. difficile infection; their potential use for the management of severe, fulminant cases is discussed. PMID:22144483

  20. Community-acquired Clostridium difficile infection: an increasing public health threat

    PubMed Central

    Gupta, Arjun; Khanna, Sahil

    2014-01-01

    There has been a startling shift in the epidemiology of Clostridium difficile infection over the last decade worldwide, and it is now increasingly recognized as a cause of diarrhea in the community. Classically considered a hospital-acquired infection, it has now emerged in populations previously considered to be low-risk and lacking the traditional risk factors for C. difficile infection, such as increased age, hospitalization, and antibiotic exposure. Recent studies have demonstrated great genetic diversity for C. difficile, pointing toward diverse sources and a fluid genome. Environmental sources like food, water, and animals may play an important role in these infections, apart from the role symptomatic patients and asymptomatic carriers play in spore dispersal. Prospective strain typing using highly discriminatory techniques is a possible way to explore the suspected diverse sources of C. difficile infection in the community. Patients with community-acquired C. difficile infection do not necessarily have a good outcome and clinicians should be aware of factors that predict worse outcomes in order to prevent them. This article summarizes the emerging epidemiology, risk factors, and outcomes for community-acquired C. difficile infection. PMID:24669194

  1. 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.

  2. The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease?

    PubMed Central

    Bien, Justyna; Palagani, Vindhya

    2013-01-01

    Gut microbiota is a compilation of microorganisms dwelling in the entire mammalian gastrointestinal tract. They display a symbiotic relationship with the host contributing to its intestinal health and disease. Even a slight fluctuation in this equipoise may be deleterious to the host, leading to many pathological conditions like Clostridium difficile infection or inflammatory bowel disease (IBD). In this review, we focus on the role of microbial dysbiosis in initiation of C. difficile infection and IBD, and we also touch upon the role of specific pathogens, particularly C. difficile, as causative agents of IBD. We also discuss the molecular mechanisms activated by C. difficile that contribute to the development and exacerbation of gastrointestinal disorders. PMID:23320050

  3. An update on antibody-based immunotherapies for Clostridium difficile infection

    PubMed Central

    Hussack, Greg; Tanha, Jamshid

    2016-01-01

    Clostridium difficile continues to be one of the most prevalent hospital-acquired bacterial infections in the developed world, despite the recent introduction of a novel and effective antibiotic agent (fidaxomicin). Alternative approaches under investigation to combat the anaerobic Gram-positive bacteria include fecal transplantation therapy, vaccines, and antibody-based immunotherapies. In this review, we catalog the recent advances in antibody-based approaches under development and in the clinic for the treatment of C. difficile infection. By and large, inhibitory antibodies that recognize the primary C. difficile virulence factors, toxin A and toxin B, are the most popular passive immunotherapies under investigation. We provide a detailed summary of the toxin epitopes recognized by various antitoxin antibodies and discuss general trends on toxin inhibition efficacy. In addition, antibodies to other C. difficile targets, such as surface-layer proteins, binary toxin, motility factors, and adherence and colonization factors, are introduced in this review. PMID:27536153

  4. Clostridium Perfringens Infection in a Febrile Patient with Severe Hemolytic Anemia.

    PubMed

    Hashiba, Masamitsu; Tomino, Atsutoshi; Takenaka, Nobuyoshi; Hattori, Tomonori; Kano, Hideki; Tsuda, Masanobu; Takeyama, Naoshi

    2016-04-06

    Clostridium perfringens (C. perfringens) can cause various infections, including gas gangrene, crepitant cellulitis, and fasciitis. While C. perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin of this bacterium induces massive intravascular hemolysis by disrupting red blood cell membranes. We present the case of a male patient with diabetes who developed a fatal liver abscess with massive intravascular hemolysis and septic shock caused by toxigenic C. perfringens. The peripheral blood smear showed loss of central pallor, with numerous spherocytes. Multiplex PCR only detected expression of the cpa gene, indicating that the pathogen was C. perfringens type A. C. perfringens infection should be considered in a febrile patient who has severe hemolytic anemia with a very low MCV, hemolyzed blood sample, and negative Coombs test. The characteristic peripheral blood smear findings may facilitate rapid diagnosis.

  5. Clostridium difficile Infection and Proton Pump Inhibitor Use in Hospitalized Pediatric Cystic Fibrosis Patients.

    PubMed

    Pohl, John F; Patel, Raza; Zobell, Jeffery T; Lin, Ellen; Korgenski, E Kent; Crowell, Kody; Mackay, Mark W; Richman, Aleesha; Larsen, Christian; Chatfield, Barbara A

    2011-01-01

    Children with cystic fibrosis (CF) often take proton pump inhibitors (PPIs), which helps improve efficacy of fat absorption with pancreatic enzyme replacement therapy. However, PPI use is known to be associated with Clostridium difficile-(C. diff-) associated diarrhea (CDAD). We retrospectively evaluated the incidence of C. diff infection from all pediatric hospital admissions over a 5-year period at a single tertiary children's hospital. We found significantly more C. diff-positive stool tests in hospitalized patients with CF compared to patients with no diagnosis of CF. However, use of a PPI was not associated with an increased risk of CDAD in hospitalized CF patients. In summary, C. diff infection is more common in hospitalized pediatric CF patients although PPI use may not be a risk factor for CDAD development in this patient population.

  6. 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

  7. Complicated fecal microbiota transplantation in a tetraplegic patient with severe Clostridium difficile infection.

    PubMed

    Brechmann, Thorsten; Swol, Justyna; Knop-Hammad, Veronika; Willert, Jörg; Aach, Mirko; Cruciger, Oliver; Schmiegel, Wolff; Schildhauer, Thomas A; Hamsen, Uwe

    2015-03-28

    A 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent Clostridium difficile (C. difficile) infection subsequent to antibiotic treatment for pneumonia. After a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. Four days subsequent to the procedure, the patient showed a systemic inflammation response syndrome. Without detecting an infectious cause, the patient received antimicrobial treatment, including tigecycline, metronidazole, vancomycin via polyethylene glycol and an additional enema for a period of seven days, leading to a prompt recovery and no reported C. difficile infection relapse during a 12 wk follow up.

  8. The potential beneficial role of faecal microbiota transplantation in diseases other than Clostridium difficile infection.

    PubMed

    Singh, R; Nieuwdorp, M; ten Berge, I J M; Bemelman, F J; Geerlings, S E

    2014-11-01

    This review gives an outline of the indications for faecal microbiota transplantation (FMT) for diseases other than Clostridium difficile (C. difficile) infection. The remarkable efficacy of FMT against C. difficile infection has already been demonstrated. The use of FMT for other diseases, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and metabolic syndrome, is now being evaluated. The currently available data suggest that FMT might be beneficial for IBD (including ulcerative colitis and, to some extent, Crohn's disease), IBS, and insulin resistance. Several randomized clinical trials are currently being performed, and data are eagerly awaited. A new field of research for the implementation of FMT is the eradication of pathogenic and multiresistant enteric microorganisms. A few animal studies have been performed within this field, but hardly any research data from human studies are available at present.

  9. Use of probiotics in prevention and treatment of patients with Clostridium difficile infection.

    PubMed

    Ollech, Jacob E; Shen, Nicole T; Crawford, Carl V; Ringel, Yehuda

    2016-02-01

    Clostridium difficile is an anaerobic, gram positive, sporulating, toxin-producing bacillus which causes a spectrum of clinical disease ranging from an asymptomatic carrier state to toxic megacolon and fulminant disease. Infection with C. difficile is an expensive and pervasive health care burden. The current theory regarding the development of C. difficile infection (CDI) suggests that disruption of the structure and/or function of an individual's normal intestinal microbiota enables colonization by C. difficile, and in the absence of an effective immune response, the bacteria causes illness. In this article we discuss the role of the colonic microbiota in the development of CDI and the potential role of probiotics in preventing and treating CDI. We review the evidence from in vitro laboratory and pre-clinical studies, as well as evidence from clinical studies and discuss the current recommendations for the use of probiotics for CDI in clinical practice. Copyright © 2016. Published by Elsevier Ltd.

  10. Molecular basis of early stages of Clostridium difficile infection: germination and colonization.

    PubMed

    Sarker, Mahfuzur R; Paredes-Sabja, Daniel

    2012-08-01

    Clostridium difficile infections (CDIs) occur when antibiotic therapy disrupts the gastrointestinal flora, favoring infected C. difficile spores to germinate, outgrow, colonize and produce toxins. During CDI, C. difficile vegetative cells initiate the process of sporulation allowing a fraction of the spores to remain adhered to the intestinal surfaces. These spores, which are unaffected by antibiotic therapy commonly used for CDIs, then germinate, outgrow and recolonize the host's GI tract causing relapse of CDI. Consequently, the germination and colonization processes can be considered as the earliest and most essential steps for the development as well as relapse of CDI. The aim of this review is to provide an overview on the molecular basis involved in C. difficile spore germination and colonization.

  11. The effect of pharmacy restriction of clindamycin on Clostridium difficile infection rates in an orthopedics ward.

    PubMed

    Cruz-Rodríguez, Nora Cecilia; Hernández-García, Raúl; Salinas-Caballero, Ana Gabriela; Pérez-Rodríguez, Edelmiro; Garza-González, Elvira; Camacho-Ortiz, Adrián

    2014-06-01

    A high consumption of clindamycin was noted in an orthopedics ward with high rates of Clostridium difficile infection (CDI). We restricted clindamycin for the entire ward. A reduction of 88% in CDI (1.07 to 0.12 × 1,000 patients-days, P = .056) and 84% for all-cause diarrhea (2.40 to 0.38 × 1,000 patients-days, P = .021) was achieved. Clindamycin was reduced 92.61% without an increase in other antibiotics. We identified high consumption of clindamycin as a risk factor for CDI. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  12. Lack of Clostridium difficile infection in patients treated with rifaximin for hepatic encephalopathy: a retrospective analysis.

    PubMed

    Neff, Guy W; Jones, Michael; Jonas, Mark; Ravinuthala, Ravi; Novick, David; Kaiser, Tiffany E; Kemmer, Nyingi

    2013-02-01

    The purpose of this study was to assess the incidence of Clostridium difficile infection in patients who received rifaximin for the treatment of hepatic encephalopathy (HE). Medical charts of patients who received rifaximin for the treatment of HE were reviewed. The number of patients who developed diarrhea during treatment with rifaximin and results of latex agglutination assays to detect C. difficile in stool samples were analyzed. A total of 211 patients received rifaximin for HE. Of these, 152 were treated in a university practice and 59 were treated in community practices. The mean dose of rifaximin was 1055 mg/d (range, 600 to 1600 mg/d) for a mean duration of 250 days (range, 180 to 385 d). Eighteen patients developed diarrhea during rifaximin treatment. None of these patients tested positive for C. difficile. This study demonstrates that treatment of HE with the safe, nonsystemic, gut-selective antibiotic rifaximin was not associated with the development of C. difficile infection.

  13. 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

  14. Saccharomyces boulardii for the prevention of hospital onset Clostridium difficile infection.

    PubMed

    Flatley, Elizabeth A; Wilde, Ashley M; Nailor, Michael D

    2015-03-01

    Probiotics, including Saccharomyces boulardii, have been advocated for the prevention of Clostridium difficile infection. The aim of this project was to evaluate the effects of the removal of S. boulardii from an automatic antibiotic order set and hospital formulary on hospital onset C. difficile infection rates. A retrospective chart review was performed on all patients with hospital onset C. difficile infection during the 13 months prior (control group) and the 13 months after (study group) removal of an automatic order set linking S. boulardii capsules to certain broad spectrum antibiotics. A large 800+ bed tertiary hospital. Among all hospitalized patients, the rate of hospital onset C. difficile infection was 0.99 per 1000 patient days while the S. boulardii protocol was active compared with 1.04 per 1000 patient days (p=0.10) after S. boulardii was removed from the formulary. No difference in the rate of hospital onset C. difficile infection was detected in patients receiving the linked broad spectrum antibiotics during and after the removal of the protocol (1.25% vs. 1.51%, respectively; p=0.70). Removal of S. boulardii administration to patients receiving broad spectrum antibiotics and the hospital formulary did not impact the rate of hospital onset C. difficile infection in either the hospital population or patients receiving broad spectrum antibiotics.

  15. The role of immunoglobulin for the treatment of Clostridium difficile infection: a systematic review.

    PubMed

    O'Horo, John; Safdar, Nasia

    2009-11-01

    Clostridium difficile is the most common infectious cause of nosocomial healthcare-associated diarrhea. The increasing prevalence of C difficile, spread in the community, virulence and frequent relapse has created an urgent need to identify new effective treatments for C. difficile infection. Among these, intravenous immunoglobulin (IVIG) is used for cases of severe C. difficile infection. We undertook a systematic review to examine the published literature pertaining to the use of immunoglobulin for C. difficile infection. Four retrospective studies and five case reports that addressed the use of IVIG for the treatment of C. difficile infection were identified. One study on the use of oral immunoglobulin was identified. Although overall there appear to be benefits to using IVIG in recurrent severe disease, the small sample sizes and lack of control groups in three of the four studies do not allow recommendations to be made regarding the use of immunoglobulin in C. difficile infection. Further research is urgently needed to clarify the role of immunoglobulin--intravenous or oral--for the treatment of C. difficile infection.

  16. Draft Genome Sequences of Five Enterococcus Species Isolated from the Gut of Patients with Suspected Clostridium difficile Infection.

    PubMed

    Castro-Nallar, Eduardo; Valenzuela, Sandro L; Baquedano, Sebastián; Sánchez, Carolina; Fernández, Fabiola; Trombert, Annette N

    2017-05-18

    We present draft genome sequences of five Enterococcus species from patients suspected of Clostridium difficile infection. Genome completeness was confirmed by presence of bacterial orthologs (97%). Gene searches using Hidden-Markov models revealed that the isolates harbor between seven and 11 genes involved in antibiotic resistance to tetracyclines, beta-lactams, and vancomycin. Copyright © 2017 Castro-Nallar et al.

  17. An enhanced DNA fingerprinting service to investigate potential Clostridium difficile infection case clusters sharing the same PCR ribotype.

    PubMed

    Fawley, Warren N; Wilcox, Mark H

    2011-12-01

    Of 53 potential Clostridium difficile infection (CDI) case clusters/outbreaks, affecting 2 to 41 patients in 27 institutions, 19% comprised unrelated isolates and 34% had highly related and distinct isolates as shown by multilocus variable-number tandem-repeat analysis, despite sharing a common ribotype. These findings emphasize the value of enhanced fingerprinting to confirm or refute suspected CDI case clusters.

  18. Clinical predictors of recurrent Clostridium difficile infection in out-patients.

    PubMed

    Shivashankar, R; Khanna, S; Kammer, P P; Scott Harmsen, W; Zinsmeister, A R; Baddour, L M; Pardi, D S

    2014-09-01

    Clostridium difficile infection (CDI) recurs in 20-30% of patients. To describe the predictors of recurrence in out-patients with CDI. Out-patient cases of CDI in Olmsted County, MN residents diagnosed between 28 June 2007 and 25 June 2010 were identified. Recurrent CDI was defined as recurrence of diarrhoea with a positive C. difficile PCR test from 15 to 56 days after the initial diagnosis with interim resolution of symptoms. Patients who had two positive tests within 14 days were excluded. Cox proportional hazard models were used to assess the association of clinical variables with time to recurrence of CDI. The cohort included 520 out-patients; 104 had recurrent CDI (cumulative incidence of 17.5% by 30 days). Univariate analysis identified increasing age and antibiotic use to be associated with recurrent CDI. Severe CDI, peripheral leucocyte count and change in serum creatinine >1.5-fold were not. In a multiple variable model, concomitant antibiotic use was associated with risk of recurrent CDI (HR = 5.4, 95% CI 1.6-17.5, P = 0.005), while age (HR per 10 year increase = 1.1, 95% CI 0.9-1.3, P = 0.22); peripheral leucocyte count >15 × 10(9) /L (HR = 1.0, 95% CI 0.5-2.1, P = 0.92); and change in serum creatinine greater than 1.5-fold (HR = 0.8, 95% CI 0.4-1.5, P = 0.44) were not. Antibiotic use was independently associated with a dramatic risk of recurrent Clostridium difficile infection in an out-patient cohort. It is important to avoid unnecessary systemic antibiotics in patients with Clostridium difficile infection, and patients with ongoing antibiotic use should be monitored closely for recurrent infection. © 2014 John Wiley & Sons Ltd.

  19. Clostridium Difficile Infection Worsen Outcome of Hospitalized Patients with Inflammatory Bowel Disease

    PubMed Central

    Zhang, Ting; Lin, Qian-Yun; Fei, Jia-Xi; Zhang, Yan; Lin, Min-Yi; Jiang, Shuang-Hong; Wang, Pu; Chen, Ye

    2016-01-01

    The prevalence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD) has increased rapidly over the past several decades in North America and Europe. However, the exact global epidemiology remains unclear because of insufficient data from developing countries. A total of 646 hospitalized adult IBD patients were enrolled; and their fresh stool specimens were obtained and used for Clostridium difficile detection. The incidence of CDI in Crohn’s disease (CD) patients (12.7%) was significantly lower than that in Ulcerative disease (UC) patients (19.3%). Among the toxin types, A+B+ strain was the most common. Length of stay, hospitalization frequency and bowel surgery rate were significantly higher in the CDI than in the non-CDI group in CD or UC patients. More patients in CDI-CD group were still in active and even clinical moderate or severe CD stage than non-CDI-CD group after 2 years of following-up. Fistula, antibiotics and infliximab usage likely increased the CDI rate in CD patients, Infliximab treatment was considered a risk factor in UC patients. CDI is an exacerbating public health issue that may influence IBD course, increase expenditures, and delay the remission of IBD patients. IBD patients with CDI require urgent attention. PMID:27417996

  20. Hospital-Onset Clostridium difficile Infection among Solid Organ Transplant Recipients

    PubMed Central

    Donnelly, John P.; Wang, Henry E.; Locke, Jayme E.; Mannon, Roslyn B.; Safford, Monika M.; Baddley, John W.

    2017-01-01

    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 impact graft as well as patient survival. However, little is known about the impact of CDI on health services utilization post-transplant. We examined hospital-onset CDI from 2012-2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the US. Infection was five times more common among transplant recipients compared to general 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 three-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 and 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; $198,728,368 vs. $154,020,528 costs). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted. PMID:26484839

  1. Discovery of LFF571: An Investigational Agent for Clostridium difficile Infection

    SciTech Connect

    LaMarche, Matthew J.; Leeds, Jennifer A.; Amaral, Adam; Brewer, Jason T.; Bushell, Simon M.; Deng, Gejing; Dewhurst, Janetta M.; Ding, Jian; Dzink-Fox, JoAnne; Gamber, Gabriel; Jain, Akash; Lee, Kwangho; Lee, Lac; Lister, Troy; McKenney, David; Mullin, Steve; Osborne, Colin; Palestrant, Deborah; Patane, Michael A.; Rann, Elin M.; Sachdeva, Meena; Shao, Jian; Tiamfook, Stacey; Trzasko, Anna; Whitehead, Lewis; Yifru, Aregahegn; Yu, Donghui; Yan, Wanlin; Zhu, Qingming

    2012-11-09

    Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection.

  2. Hospital Transfer Network Structure as a Risk Factor for Clostridium difficile Infection.

    PubMed

    Simmering, Jacob E; Polgreen, Linnea A; Campbell, David R; Cavanaugh, Joseph E; Polgreen, Philip M

    2015-09-01

    To determine the effect of interhospital patient sharing via transfers on the rate of Clostridium difficile infections in a hospital. Retrospective cohort. Using data from the Healthcare Cost and Utilization Project California State Inpatient Database, 2005-2011, we identified 2,752,639 transfers. We then constructed a series of networks detailing the connections formed by hospitals. We computed 2 measures of connectivity, indegree and weighted indegree, measuring the number of hospitals from which transfers into a hospital arrive, and the total number of incoming transfers, respectively. Next, we estimated a multivariate model of C. difficile infection cases using the log-transformed network measures as well as covariates for hospital fixed effects, log median length of stay, log fraction of patients aged 65 or older, and quarter and year indicators as predictors. We found an increase of 1 in the log indegree was associated with a 4.8% increase in incidence of C. difficile infection (95% CI, 2.3%-7.4%) and an increase of 1 in log weighted indegree was associated with a 3.3% increase in C. difficile infection incidence (1.5%-5.2%). Moreover, including measures of connectivity in our models greatly improved their fit. Our results suggest infection control is not under the exclusive control of a given hospital but is also influenced by the connections and number of connections that hospitals have with other hospitals.

  3. Efficacy of a diagnostic and therapeutic algorithm for Clostridium difficile infection.

    PubMed

    Marukawa, Yohei; Komura, Takuya; Kagaya, Takashi; Ohta, Hajime; Unoura, Masashi

    2016-08-01

    In July 2012, metronidazole was approved for the treatment of Clostridium difficile infection (CDI). To clarify the selection criteria for the drug in terms of CDI severity, we established a diagnostic and therapeutic algorithm with reference to the SHEA-IDSA Clinical Practice Guidelines. We compared patients whose treatments were guided by the algorithm (29 cases, October 2012-September 2013) with patients treated prior to the development of the algorithm (37 cases, October 2011-September 2012). All cases treated with reference to the algorithm were diagnosed using enzyme immunoassay of C. difficile toxins A and B and glutamate dehydrogenase;an appropriate drug was prescribed in 93.1% of the cases. We found no significant between-group differences in the cure, recurrence, or complication rates. However, drug costs in cases wherein treatments were guided by the algorithm were markedly reduced. We have, thus, shown that algorithm-guided treatment is efficacious and cost-effective.

  4. Clinical differences in Clostridium difficile infection based on age: a multicenter study.

    PubMed

    Kim, Hyung Hun; Kim, You Sun; Han, Dong Soo; Kim, Young-Ho; Kim, Won Ho; Kim, Joo Sung; Kim, Hyunsoo; Kim, Hyun-Soo; Park, Young-Sook; Song, Hyun Joo; Shin, Sung Jae; Yang, Suk-Kyun; Ye, Byong Duk; Eun, Chang Soo; Lee, Kang-Moon; Lee, Sang Heon; Jang, Byung-Ik; Jung, Sung-Ae; Cheon, Jae Hee; Choi, Chang Hwan; Huh, Kyuchan

    2014-01-01

    Advancing age is a well-known risk factor for Clostridium difficile infection (CDI). However, age-specific clinical differences in CDI are uncertain. A retrospective comparative analysis was performed based on age in 1367 patients with CDI in Korea. Most clinical features were similar in the two age groups studied, however malignancy was more common in the older group (age ≥ 65 y) (p < 0.001), while chemotherapy and transplantation were more common in the younger group (age < 65 y) (p < 0.001). Endoscopic examinations were more commonly performed in the older group (p = 0.010), which had a high positive predictive value (88.3%). More patients recovered from CDI without specific antibiotic treatment in the younger group than in the older group (p < 0.001). Although advancing age is an important risk factor for CDI, the clinical features of younger patients are similar to those of the older patient population.

  5. Clostridium difficile infection in cystic fibrosis: an uncommon but life-threatening complication.

    PubMed

    Piccolo, Francesco; Tai, Anna Sze; Ee, Hooi; Mulrennan, Siobhain; Bell, Scott; Ryan, Gerard

    2017-01-01

    Adults with cystic fibrosis (CF) have significant rates of asymptomatic Clostridium difficile carriage and are frequently exposed to risk factors for C. difficile infection (CDI). Despite this, the rate of reported CDI in CF is low. We describe three cases of near fatal CDI in adults with CF and review the literature regarding presentation, management, and recurrence prevention. Early recognition is important as the clinical presentation may be atypical and the illness can be severe and even life-threatening. Management can be complicated by respiratory and nutritional failure. CF-related gastrointestinal dysfunction may alter the typical host-pathogen interaction between patient and C. difficile, potentially explaining the low rates of CDI and atypical presentation.

  6. Fecal Microbiota-based Therapeutics for Recurrent Clostridium difficile Infection, Ulcerative Colitis and Obesity.

    PubMed

    Carlucci, Christian; Petrof, Elaine O; Allen-Vercoe, Emma

    2016-11-01

    The human gut microbiome is a complex ecosystem of fundamental importance to human health. Our increased understanding of gut microbial composition and functional interactions in health and disease states has spurred research efforts examining the gut microbiome as a valuable target for therapeutic intervention. This review provides updated insight into the state of the gut microbiome in recurrent Clostridium difficile infection (CDI), ulcerative colitis (UC), and obesity while addressing the rationale for the modulation of the gut microbiome using fecal microbiota transplant (FMT)-based therapies. Current microbiome-based therapeutics in pre-clinical or clinical development are discussed. We end by putting this within the context of the current regulatory framework surrounding FMT and related therapies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Fecal Microbiota Transplant: Treatment Options for Clostridium difficile Infection in the Intensive Care Unit.

    PubMed

    Han, Samuel; Shannahan, Sarah; Pellish, Randall

    2016-10-01

    Clostridium difficile infection (CDI) has steadily increased in incidence since the 1990s, with an associated increase in recurrence and severity, which has in turn lead to more intensive care unit (ICU) admissions. The development of recurrent CDI, in particular, has been associated with increasing patient morbidity and mortality as well as an immense financial burden on the health care system. Recently, fecal microbiota transplantation (FMT) has received much publicity as an effective means of treatment for recurrent CDI. The goal of this review is to provide evidence-based recommendations for the diagnosis and management of CDI, with a particular focus on FMT and its utilization in the ICU. © The Author(s) 2015.

  8. Establishing a Fecal Microbiota Transplant Service for the Treatment of Clostridium difficile Infection.

    PubMed

    Costello, Samuel P; Tucker, Emily C; La Brooy, Justin; Schoeman, Mark N; Andrews, Jane M

    2016-04-01

    Recurrent or refractory Clostridium difficile infection (CDI) has become an increasing problem in the past decade. Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent CDI; however, a number of technical, logistical, and regulatory issues have hampered the development of an FMT capability at many hospitals. The development of a frozen stool bank of screened donor stool is an important step in the standardization of the procedure. This gives clinicians rapid access to thoroughly screened donor stool when needed, without the ethical and logistical problems associated with patient-selected donors. We describe the practicalities of establishing such a service using a stool bank of prescreened donor stool including detail regarding donor recruitment and screening, stool preparation, and delivery of the FMT. © 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.

  9. Fecal microbiota transplantation (FMT) for Clostridium difficile infection: focus on immunocompromised patients.

    PubMed

    Di Bella, Stefano; Gouliouris, Theodore; Petrosillo, Nicola

    2015-04-01

    Clostridium difficile infection (CDI) is an emerging problem worldwide associated with significant morbidity, mortality, recurrence rates and healthcare costs. Immunosuppressed patients, including HIV-seropositive individuals, solid organ transplant recipients, patients with malignancies, hematopoietic stem cell transplant recipients, and patients with inflammatory bowel disease are increasingly recognized as being at higher risk of developing CDI where it may be associated with significant complications, recurrence, and mortality. Fecal microbiota transplantation (FMT) has proven to be an effective and safe procedure for the treatment of recurrent or refractory CDI in immunocompetent patients by restoring the gut microbiota and resistance to further recurrences. During the last two years the first data on FMT in immunocompromised patients began to appear in the medical literature. Herein we summarize the use of FMT for the treatment of CDI with a focus on immunocompromised patients. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Specificities of the intestinal microbiota in patients with inflammatory bowel disease and Clostridium difficile infection.

    PubMed

    Sokol, Harry; Jegou, Sarah; McQuitty, Claire; Straub, Marjolene; Leducq, Valentin; Landman, Cecilia; Kirchgesner, Julien; Le Gall, Guillaume; Bourrier, Anne; Nion-Larmurier, Isabelle; Cosnes, Jacques; Seksik, Philippe; Richard, Mathias L; Beaugerie, Laurent

    2017-08-08

    Clostridium difficile infection (CDI) is a common complication in inflammatory bowel disease (IBD) and has been associated with poor IBD outcome. Intestinal microbiota composition in IBD patients with CDI has not been specifically evaluated to date. The fecal microbiota of 56 IBD patients, including 8 in flare with concomitant CDI, 24 in flare without CDI, and 24 in remission, as well as 24 healthy subjects, was studied using 16S sequencing. Analysis was performed using the Qiime pipeline. Compared to IBD patients without CDI, IBD patients with CDI had more pronounced dysbiosis with higher levels of Ruminococcus gnavus and Enterococcus operational taxonomic units (OTUs) and lower levels of Blautia and Dorea OTUs. Correlation network analysis suggested a disrupted ecosystem in IBD patients in flare, particularly in those with CDI. In patients with IBD, CDI is associated with a more pronounced intestinal dysbiosis with specific alterations in intestinal microorganisms.

  11. Synthetic Lipoteichoic Acid Glycans Are Potential Vaccine Candidates to Protect from Clostridium difficile Infections.

    PubMed

    Broecker, Felix; Martin, Christopher E; Wegner, Erik; Mattner, Jochen; Baek, Ju Yuel; Pereira, Claney L; Anish, Chakkumkal; Seeberger, Peter H

    2016-08-18

    Infections with Clostridium difficile increasingly cause morbidity and mortality worldwide. Bacterial surface glycans including lipoteichoic acid (LTA) were identified as auspicious vaccine antigens to prevent colonization. Here, we report on the potential of synthetic LTA glycans as vaccine candidates. We identified LTA-specific antibodies in the blood of C. difficile patients. Therefore, we evaluated the immunogenicity of a semi-synthetic LTA-CRM197 glycoconjugate. The conjugate elicited LTA-specific antibodies in mice that recognized natural LTA epitopes on the surface of C. difficile bacteria and inhibited intestinal colonization of C. difficile in mice in vivo. Our findings underscore the promise of synthetic LTA glycans as C. difficile vaccine candidates.

  12. Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection.

    PubMed

    Dutta, Sudhir K; Girotra, Mohit; Garg, Shashank; Dutta, Anand; von Rosenvinge, Erik C; Maddox, Cynthia; Song, Yang; Bartlett, John G; Vinayek, Rakesh; Fricke, W Florian

    2014-09-01

    The prevalence of recurrent Clostridium difficile infection (RCDI) is increasing; fecal microbiota transplantation (FMT) is an effective therapy. However, there have been no studies of the efficacy of a single session of combined enteral and colonic FMT or characterizations of changes in the microbiota between donors and recipients. We performed a study of 27 patients with RCDI who were given a fixed volume of processed fecal filtrate via enteroscopy and colonoscopy in a single session. Patients were closely monitored, and fecal samples were collected from 2 patient-donor pairs for 16S rRNA analysis. All patients had reduced stool frequency, abdominal pain, white blood cell counts, and elimination of fecal C difficile toxin (P < .05). FMT increased microbial diversity, increasing proportions of Lachnospiraceae (phylum Firmicutes) and reducing proportions of Enterobacteriaceae. FMT was associated with marked changes in the composition of fecal microbiota in 2 patients with RCDI.

  13. Serum markers for severe Clostridium difficile infection in immunosuppressed hospitalized patients.

    PubMed

    Pant, Chaitanya; Sferra, Thomas J; Ondrade, Christina; Bass, Pat F; Deshpande, Abhishek; Burton, Cary V

    2011-01-01

    Clostridium difficile infection (CDI) has emerged as the leading cause of nosocomial diarrhea in the developed world. The prompt recognition of severe CDI is essential in providing early aggressive therapy. Though previous studies have identified leukocytosis, azotemia, and hypoalbuminemia as markers to differentiate severe from non-severe CDI in the general patient population, there is little data in immunosuppressed patients. We conducted a retrospective chart review of immunosuppressed patients with CDI to identify serum markers associated with severe CDI. Twenty-nine immunosuppressed patients with CDI (nine with severe disease) were identified. Those with severe disease were older and had evidence of renal dysfunction. The white blood cell count, platelet, and albumin levels were the same in the severe and non-severe immunosuppressed CDI patients. Therefore, recognized serum markers of severe CDI are not universally useful in immunosuppressed patients. Moreover, the clinician must be aware that immunosuppressed patients can develop severe CDI while remaining leukopenic.

  14. Successful use of nitazoxanide in the treatment of recurrent Clostridium difficile infection

    PubMed Central

    Rafiullah, Fnu; Kanwal, Sunil; Majeed, Usman M; Korsten, Mark A; Cheema, Faisal H; Luthra, Munish; Sohail, Muhammad Rizwan

    2011-01-01

    A 78-year-old, retired Caucasian male presented in emergency room with 3 days history of progressive watery diarrhoea. Two weeks earlier, he received intravenous levofloxacin for community acquired pneumonia. The patient was diagnosed as severe Clostridium difficile infection based on clinical presentation, labs and imaging studies. The patient was initially treated with intravenous metronidazole and oral vancomycin. While awaiting subacute rehabilitation placement, the patient relapsed twice. After first recurrence the patient was treated with 2 weeks of oral nitazoxanide. After second recurrence, the patient was treated 2 weeks of nitazoxanide followed by tapering dose of vancomycin. The patient was followed and no relapse was reported at 1 year follow-up visit. PMID:22674696

  15. Gut solutions to a gut problem: bacteriocins, probiotics and bacteriophage for control of Clostridium difficile infection.

    PubMed

    Rea, Mary C; Alemayehu, Debebe; Ross, R Paul; Hill, Colin

    2013-09-01

    Clostridium difficile infection (CDI) is a major cause of morbidity and mortality among hospitalized patients and imposes a considerable financial burden on health service providers in both Europe and the USA. The incidence of CDI has dramatically increased in recent years, partly due to the emergence of a number of hypervirulent strains. The most commonly documented risk factors associated with CDIs are antibiotic usage leading to alterations of the gut microbiota, age >65 years and long-term hospital stay. Since standard therapies for antibiotic-associated diarrhoea and CDI have limited efficacy, there is now an urgent need for alternative therapeutics. In this review, we outline the current state of play with regard to the potential of gut-derived bacteriocins, probiotics and phage to act as antimicrobial agents against CDI in the human gut.

  16. Clostridium difficile

    MedlinePlus

    ... 18-21yrs. Healthy Living Healthy Living Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Sleep Safety & ... Head Neck & Nervous System Heart Infections Learning Disabilities Obesity Orthopedic Prevention ... Children > Health Issues > Conditions > Abdominal > Clostridium difficile Health Issues ...

  17. Does Alkaline Colonic pH Predispose to Clostridium difficile Infection?

    PubMed

    Gupta, Purba; Yakubov, Stanley; Tin, Kevin; Zea, Diego; Garankina, Olga; Ghitan, Monica; Chapnick, Edward K; Homel, Peter; Lin, Yu Shia; Koegel, Michael M

    2016-02-01

    Clostridium difficile caused nearly 500,000 infections and was associated with approximately 29,000 deaths in 2011, according to data from the Centers for Disease Control and Prevention. C. difficile is a bacterium that causes diarrhea and, often, severe illness in healthcare facilities, as well as the community. Our objective was to determine whether alkaline colonic pH predisposes to colonization and infection with C. difficile. A total of 228 patients with diarrhea and/or abdominal pain, leukocytosis, and fever were included. Stool pH was measured, and C. difficile antigen and toxin in stool were detected. Of 228 patients, 30 (13.2%) tested positive for C. difficile (antigen+/toxin+) and 171 (75%) were C. difficile negative (antigen-/toxin-). Of 171 patients who tested negative, 93 (54.4%) had stool pH >7.0 and 78 (45.6%) had pH ≤7.0. Among the 30 patients who tested positive, 26 (86.7%) had stool pH >7.0 (P = 0.002). Among the 27 colonized patients (antigen+/toxin-), 12 (44.4%) had stool pH >7.0 (P = 0.34). For all patients with stool pH ≤7.0, 96% tested negative for C. difficile infection (P = 0.002). A strong association between C. difficile infection and alkaline stool pH was found.

  18. How do Clostridium difficile infections affect nurses' everyday hospital work: A qualitative study.

    PubMed

    Guillemin, Isabelle; Marrel, Alexia; Beriot-Mathiot, Axelle; Doucet, Carole; Kazoglou, Odysseas; Luxemburger, Christine; Reygrobellet, Camille; Arnould, Benoit

    2015-05-01

    This qualitative study explored the impact of Clostridium difficile infections on nurses' everyday work in the hospital. Twelve nurses (six in France and six in the United States) were interviewed in depth using a semi-structured interview guide. Thematic analysis of the interviews was performed. Managing diarrhoea and taking precautionary measures for infection control were the two most inconvenient aspects nurses reported with C. difficile patient management. Precautions included contact isolation, hand hygiene and reorganization/coordination of nursing care and ward. Precautions were time consuming and significantly increased nurses' workload when combined with caring for patients with uncontrollable, frequent bouts of diarrhoea. Management of C. difficile infection is extremely burdensome for nurses in their everyday work and disruptive to hospital organizations as a whole. Prevention of C. difficile infections, together with coordinated team work and communication, would therefore contribute to decreasing nurses' workload and the burden to health-care facilities associated with caring for these patients. © 2015 Wiley Publishing Asia Pty Ltd.

  19. Use of Rifamycin Drugs and Development of Infection by Rifamycin-Resistant Strains of Clostridium difficile

    PubMed Central

    Huang, Jamie S.; Jiang, Zhi-Dong; Garey, Kevin W.; Lasco, Todd

    2013-01-01

    The relationship between rifamycin drug use and the development of resistant strains of Clostridium difficile was studied at a large university hospital in Houston, TX, between May 2007 and September 2011. In 49 of 283 (17.3%) patients with C. difficile infection (CDI), a rifamycin-resistant strain of C. difficile was identified that compares to a rate of 8% using the same definitions in 2006-2007 (P = 0.59). The 49 patients infected by a resistant organism were matched by date of admission to 98 control patients with CDI from whom a rifamycin-susceptible C. difficile strain was isolated. Cases and controls did not differ according to demographic and clinical characteristics and showed similar but low rates of prior rifamycin use. Similar rates of rifamycin resistance were seen in cases of hospital-acquired CDI (38/112 [34%]) versus community-acquired CDI (7/20 [35%]). At a university hospital in which rifaximin was commonly used, infection by rifamycin-resistant strains of C. difficile was not shown to relate to prior use of a rifamycin drug or to acquiring the infection in the hospital, although the rate of overall resistance appeared to be rising. PMID:23545528

  20. [Clinical and demographic profile and risk factors for Clostridium difficile infection].

    PubMed

    Carvajal, Carlos; Pacheco, Carlos; Jaimes, Fabián

    2017-01-24

    Clostridium difficile infection is the leading cause of nosocomial infectious diarrhea. The increasing incidence added to a lower rate of response to the initial treatment and higher rates of relapse has generated a higher burden of the disease. To determine the clinical characteristics of hospitalized patients with C. difficile infection. We made a nested case-cohort study. We reviewed medical records of the patients with nosocomial diarrhea for whom an assay for toxin A-B of C. difficile had been requested from February, 2010, to February, 2012. We defined case as a patient with diarrhea and a positive assay for the toxin, and control as those patients with a negative assay for the toxin. We collected data on demographic and clinical characteristics, risk factors, hospital length of stay, treatment, and complications. We collected data from 123 patients during the follow-up period, 30 of whom were positive for the toxin. Mean age in the study population was 49 years and 60% were men. The main symptoms were abdominal pain (35%) and fever (34%). The principal complications were electrolytic alteration and severe sepsis with secondary acute kidney injury. Mortality was 13% and independent factors associated to the appearance of the infection were the use of proton pump inhibitors and previous gastrointestinal tract surgery. The use of proton pump inhibitors and previous gastrointestinal tract surgery were factors associated to C. difficile infection.

  1. 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.

  2. Uterine Perforation with Intra-Abdominal Clostridium perfringens Gas Gangrene: A Rare and Fatal Infection.

    PubMed

    Kashan, David; Muthu, Nagarajan; Chaucer, Benjamin; Davalos, Fidencio; Bernstein, Michael; Chendrasekhar, Akella

    2016-06-01

    Background:Clostridium perfringens gas gangrene is an extremely rare and fatal infection. Necrosis of the myometrium is rarely seen and has only been recorded in 18 cases to date. Of these 18 reported cases, only 5 have occurred in nonpregnant women. This article presents the 6th case of myometrium necrosis from C. perfringens.Case: A 72-year-old woman, gravida 2, para 2, presented with abdominal pain and vaginal bleeding. After examinations, laboratory testing, and several surgical interventions, she was found to have C. perfringens infection and advanced high-grade serous adenocarcinoma of the endometrium with >50% invasion into the myometrium. Results: Despite the surgical interventions and use of several antibiotics, this patient did not improve. She was weaned from treatment per her advance directive and died after weaning. Conclusions: Awareness of the many etiologies for peritonitis is of great importance when a fatal infection may be the cause of the condition. Correct diagnosis and proper treatment is essential for the survival of patients infected with C. perfringens. (J GYNECOL SURG 32:182).

  3. Uterine Perforation with Intra-Abdominal Clostridium perfringens Gas Gangrene: A Rare and Fatal Infection

    PubMed Central

    Kashan, David; Muthu, Nagarajan; Davalos, Fidencio; Bernstein, Michael; Chendrasekhar, Akella

    2016-01-01

    Abstract Background: Clostridium perfringens gas gangrene is an extremely rare and fatal infection. Necrosis of the myometrium is rarely seen and has only been recorded in 18 cases to date. Of these 18 reported cases, only 5 have occurred in nonpregnant women. This article presents the 6th case of myometrium necrosis from C. perfringens. Case: A 72-year-old woman, gravida 2, para 2, presented with abdominal pain and vaginal bleeding. After examinations, laboratory testing, and several surgical interventions, she was found to have C. perfringens infection and advanced high-grade serous adenocarcinoma of the endometrium with >50% invasion into the myometrium. Results: Despite the surgical interventions and use of several antibiotics, this patient did not improve. She was weaned from treatment per her advance directive and died after weaning. Conclusions: Awareness of the many etiologies for peritonitis is of great importance when a fatal infection may be the cause of the condition. Correct diagnosis and proper treatment is essential for the survival of patients infected with C. perfringens. (J GYNECOL SURG 32:182) PMID:27274183

  4. The Ecology and Pathobiology of Clostridium difficile Infections: An Interdisciplinary Challenge

    PubMed Central

    Dubberke, Erik R.; Haslam, David B.; Lanzas, Cristina; Bobo, Linda D.; Burnham, Carey-Ann D.; Gröhn, Yrjö T.; Tarr, Phillip I.

    2013-01-01

    Summary Clostridium difficile is a well recognized pathogen of humans and animals. Although C. difficile was first identified over 70 years ago, much remains unknown in regards to the primary source of human acquisition and its pathobiology. These deficits in our knowledge have been intensified by dramatic increases in both the frequency and severity of disease in humans over the last decade. The changes in C. difficile epidemiology might be due to the emergence of a hypervirulent stain of C. difficile, aging of the population, altered risk of developing infection with newer medications, and/or increased exposure to C. difficile outside of hospitals. In recent years there have been numerous reports documenting C. difficile contamination of various foods, and reports of similarities between strains that infect animals and strains that infect humans as well. The purposes of this review are to highlight the many challenges to diagnosing, treating, and preventing C. difficile infection in humans, and to stress that collaboration between human and veterinary researchers is needed to control this pathogen. PMID:21223531

  5. [Identifying gaps between guidelines and clinical practice in Clostridium difficile infection].

    PubMed

    Rodríguez-Martín, C; Serrano-Morte, A; Sánchez-Muñoz, L A; de Santos-Castro, P A; Bratos-Pérez, M A; Ortiz de Lejarazu-Leonardo, R

    2016-01-01

    The first aim was to determine whether patients are being treated in accordance with the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America (IDSA/SHEA) Clostridium difficile guidelines and whether adherence impacts patient outcomes. The second aim was to identify specific action items in the guidelines that are not being translated into clinical practice, for their subsequent implementation. A retrospective, descriptive study was conducted over a 36 month period, on patients with compatible clinical symptoms and positive test for C. difficile toxins A and/or B in stool samples, in an internal medicine department of a tertiary medical centre. Patient demographic and clinical data (outcomes, comorbidity, risk factors) and compliance with guidelines, were examined A total of 77 patients with C. difficile infection were identified (87 episodes). Stratified by disease severity criteria, 49.3% of patients were mild-moderate, 35.1% severe, and 15.6% severe-complicated. Full adherence with the guidelines was observed in only 40.2% of patients, and was significantly better for mild-moderate (71.0%), than in severe (7.4%) or severe-complicated patients (16.6%) (P<.003). Adherence was significantly associated with clinical cure (57% vs 42%), fewer recurrences (22.2% vs 77.7%), and mortality (25% vs 75%) (P<.01). The stratification of severity of the episode, and the adequacy of antibiotic to clinical severity, need improvement. Overall adherence with the guidelines for management of Clostridium difficile infection was poor, especially in severe and severe-complicated patients, being associated with worse clinical outcomes. Educational interventions aimed at improving guideline adherence are warranted. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  6. Clostridium difficile Infection Among US Emergency Department Patients With Diarrhea and No Vomiting.

    PubMed

    Abrahamian, Fredrick M; Talan, David A; Krishnadasan, Anusha; Citron, Diane M; Paulick, Ashley L; Anderson, Lydia J; Goldstein, Ellie J C; Moran, Gregory J

    2017-07-01

    The incidence of Clostridium difficile infection has increased and has been observed among persons from the community who have not been exposed to antibiotics or health care settings. Our aims are to determine prevalence of C difficile infection among emergency department (ED) patients with diarrhea and the prevalence among patients without traditional risk factors. We conducted a prospective observational study of patients aged 2 years or older with diarrhea (≥3 episodes/24 hours) and no vomiting in 10 US EDs (2010 to 2013). We confirmed C difficile infection by positive stool culture result and toxin assay. C difficile infection risk factors were antibiotic use or overnight health care stay in the previous 3 months or previous C difficile infection. We typed strains with pulsed-field gel electrophoresis. Of 422 participants, median age was 46 years (range 2 to 94 years), with median illness duration of 3.0 days and 43.4% having greater than or equal to 10 episodes of diarrhea during the previous 24 hours. At least one risk factor for C difficile infection was present in 40.8% of participants; 25.9% were receiving antibiotics, 26.9% had health care stay within the previous 3 months, and 3.3% had previous C difficile infection. Forty-three participants (10.2%) had C difficile infection; among these, 24 (55.8%) received antibiotics and 19 (44.2%) had health care exposure; 17 of 43 (39.5%) lacked any risk factor. Among participants without risk factors, C difficile infection prevalence was 6.9%. The most commonly identified North American pulsed-field gel electrophoresis (NAP) strains were NAP type 1 (23.3%) and NAP type 4 (16.3%). Among mostly adults presenting to US EDs with diarrhea and no vomiting, C difficile infection accounted for approximately 10%. More than one third of patients with C difficile infection lacked traditional risk factors for the disease. Among participants without traditional risk factors, prevalence of C difficile infection was

  7. 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.

  8. Older Is Not Wiser, Immunologically Speaking: Effect of Aging on Host Response to Clostridium difficile Infections.

    PubMed

    Shin, Jae Hyun; High, Kevin P; Warren, Cirle A

    2016-07-01

    Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and a significant burden on the health care system. Aging has been identified in the literature as a risk factor for CDI as well as adverse outcome from CDI. Although this effect of advanced age on CDI could be partially explained by clinical factors associated with aging, biologic factors are important. Innate immune system, responsible for immediate response to acute infections, plays a major role in CDI pathogenesis. Impairment in function of innate immunity with aging, demonstrated in other infection models, may lead to worse outcome with CDI. C. difficile toxin-specific antibody response protects the host against initial and recurrent infections as shown in observational studies and clinical trial. Effect of aging on antibody response to CDI has not been demonstrated, but the results from vaccine studies in other infections suggest a negative effect on humoral immunity from aging. Although intestinal microbiota from healthy people confers resistance to CDI by preventing C. difficile colonization, changes in composition of microbiota with aging may affect that resistance and increase risk for CDI. There are also age-associated changes in physiology, especially of the gastrointestinal tract, that may play a role in CDI risk and outcomes. In this review, we will first discuss the epidemiology of CDI in the elderly people, then the alteration in innate immunity, humoral response, and microbiota that increases susceptibility to CDI and severe disease and lastly, the physiological and functional changes that may modify outcomes of infection. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Genome-Based Infection Tracking Reveals Dynamics of Clostridium difficile Transmission and Disease Recurrence

    PubMed Central

    Kumar, Nitin; Miyajima, Fabio; He, Miao; Roberts, Paul; Swale, Andrew; Ellison, Louise; Pickard, Derek; Smith, Godfrey; Molyneux, Rebecca; Dougan, Gordon; Parkhill, Julian; Wren, Brendan W.; Parry, Christopher M.; Pirmohamed, Munir; Lawley, Trevor D.

    2016-01-01

    Background. Accurate tracking of Clostridium difficile transmission within healthcare settings is key to its containment but is hindered by the lack of discriminatory power of standard genotyping methods. We describe a whole-genome phylogenetic-based method to track the transmission of individual clones in infected hospital patients from the epidemic C. difficile 027/ST1 lineage, and to distinguish between the 2 causes of recurrent disease, relapse (same strain), or reinfection (different strain). Methods. We monitored patients with C. difficile infection in a UK hospital over a 2-year period. We performed whole-genome sequencing and phylogenetic analysis of 108 strains isolated from symptomatic patients. High-resolution phylogeny was integrated with in-hospital transfers and contact data to create an infection network linking individual patients and specific hospital wards. Results. Epidemic C. difficile 027/ST1 caused the majority of infections during our sampling period. Integration of whole-genome single nucleotide polymorphism (SNP) phylogenetic analysis, which accurately discriminated between 27 distinct SNP genotypes, with patient movement and contact data identified 32 plausible transmission events, including ward-based contamination (66%) or direct donor–recipient contact (34%). Highly contagious donors were identified who contributed to the persistence of clones within distinct hospital wards and the spread of clones between wards, especially in areas of intense turnover. Recurrent cases were identified between 4 and 26 weeks, highlighting the limitation of the standard <8-week cutoff used for patient diagnosis and management. Conclusions. Genome-based infection tracking to monitor the persistence and spread of C. difficile within healthcare facilities could inform infection control and patient management. PMID:26683317

  10. Faecal microbiota transplantation for Clostridium difficile infection in the United Kingdom.

    PubMed

    Porter, R J; Fogg, C

    2015-06-01

    Faecal microbiota transplantation (FMT) has been shown to be highly effective in treating recurrent Clostridium difficile infection, but to date there have been no data from the United Kingdom. An electronic survey was developed at Portsmouth Hospitals' National Health Service (NHS) Trust and sent out to UK hospital specialists utilizing the contact databases of the British Infection Association and the Royal College of Gastroenterologists. A total of 162 responses were received, representing nearly one in every seven of the United Kingdom's infection specialists and a response from one in every two UK NHS acute trusts or boards. Ninety-six per cent believe that the evidence base supports the use of FMT, and 94% reported consulting on at least one patient a year in whom they would recommend FMT. However, only 22% reported FMT use in their institution in the last 10 years, and 6% reported performing more than ten FMTs in the last 10 years. Concerns with patient acceptance, donor selection, availability of screened faecal solution, feasibility of procedure and availability of local expertise were reported as inhibiting the use of FMT. More than 90% of respondents would like access to regional guidelines, prescreened faecal solution and expert advice to facilitate implementation, and more than two thirds of respondents would support a regional FMT referral centre. A large gap exists in the United Kingdom between physicians desire to use FMT and the ability and facilities to provide it as a therapy at the bedside. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  11. Fecal microbiota transplantation for Clostridium difficile infection: back to the future.

    PubMed

    Borgia, Guglielmo; Maraolo, Alberto Enrico; Foggia, Maria; Buonomo, Antonio Riccardo; Gentile, Ivan

    2015-07-01

    Clostridium difficile infection (CDI) is a leading cause of diarrhea in the industrialized world. The estimated costs of this infection are impressive: over 3.2 billion dollars annually in the US. The introduction of fecal microbiota transplantation (FMT) to clinical practice can be considered a Copernican Revolution. The rationale of this approach consists of correcting the imbalance of the organisms dwelling in the gut by reintroducing a normal flora. This review focuses on the indication for FMT in CDI; it examines in-depth the most relevant aspects of the techniques used, and the safety and efficacy of this new 'old' therapy. Authoritative guidelines about the management of CDI strongly recommend FMT for multiple recurrent episodes of infection by C. difficile unresponsive to repeated antibiotic treatment. The cure rates are about 90%, with no serious adverse events having been reported. The main concerns are the long-term outcomes, lack of a standardized procedure for the delivery of donor material, and a cultural barrier to the transplantation of fecal microbiota. A promising solution to some of these problems could be the use of a more acceptable administration route of fecal material, namely, oral capsules.

  12. Clostridium difficile Infections amongst Patients with Haematological Malignancies: A Data Linkage Study

    PubMed Central

    Slimings, Claudia; Joske, David J. L.; Riley, Thomas V.

    2016-01-01

    Objectives Identify risk factors for Clostridium difficile infection (CDI) and assess CDI outcomes among Australian patients with a haematological malignancy. Methods A retrospective cohort study involving all patients admitted to hospitals in Western Australia with a haematological malignancy from July 2011 to June 2012. Hospital admission data were linked with all hospital investigated CDI case data. Potential risk factors were assessed by logistic regression. The risk of death within 60 and 90 days of CDI was assessed by Cox Proportional Hazards regression. Results There were 2085 patients of whom 65 had at least one CDI. Twenty percent of CDI cases were either community-acquired, indeterminate source or had only single-day admissions in the 28 days prior to CDI. Using logistic regression, having acute lymphocytic leukaemia, neutropenia and having had bacterial pneumonia or another bacterial infection were associated with CDI. CDI was associated with an increased risk of death within 60 and 90 days post CDI, but only two deaths had CDI recorded as an antecedent factor. Ribotyping information was available for 33 of the 65 CDIs. There were 19 different ribotypes identified. Conclusions Neutropenia was strongly associated with CDI. While having CDI is a risk factor for death, in many cases it may not be a direct contributor to death but may reflect patients having higher morbidity. A wide variety of C. difficile ribotypes were found and community-acquired infection may be under-estimated in these patients. PMID:27314498

  13. 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

  14. 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.

  15. 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.

  16. Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection.

    PubMed

    Fuentes, Susana; van Nood, Els; Tims, Sebastian; Heikamp-de Jong, Ineke; ter Braak, Cajo J F; Keller, Josbert J; Zoetendal, Erwin G; de Vos, Willem M

    2014-08-01

    Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.

  17. Clinical Characteristics and Treatment Outcomes of Clostridium difficile Infections by PCR Ribotype 017 and 018 Strains

    PubMed Central

    Kim, Yeonjae; Pai, Hyunjoo

    2016-01-01

    The objective of this study was to identify the clinical characteristics of Clostridium difficile infections (CDIs) caused by toxin A-negative/toxin B-positive (A-B+) PCR ribotype 017 (R017) and A+B+ ribotype 018 (R018) strains, prevalent in Asian countries. From February 2010 through January 2013, all CDI patients in our hospital were enrolled; their medical records were retrospectively reviewed, and the isolates were characterized by toxigenic culture and PCR ribotyping. Based on the ribotypes, a total of 510 cases were categorized as R017 (139, 27.3%), R018 (157, 30.8%) and other ribotypes groups (214, 42.0%), and clinical variables were compared between R017 and other ribotypes, R018 and other ribotypes and R018 and R017 groups. The patients with R017 infections had a higher mean Charlson’s comorbidity index (OR 1.1, 1–1.21, p = 0.05), lower serum albumin (OR 0.47, 0.31–0.73, p = 0.001) and lower CRP levels (OR 0.96, 0.92–0.99, p = 0.022) than those with other ribotypes. R018 infections caused more azotemia (OR 4.06, 1.28–12.91, p = 0.018) and more frequent severe CDI (OR 1.87, 1.12–3.13, p = 0.016) than the other ribotypes infections. R017 and R018 infections were more often associated with toxin positive stools (OR 2.94, 1.65–4.09, p<0.001; OR 4.55, 2.82–7.33, p<0.001). In terms of treatment outcomes, R017 infections caused a marginally higher 30-day mortality than other ribotypes infection. In a final multiple logistic regression model, 30-day mortality was associated with leukocytosis (OR 2.45, 1.0–6.01, p = 0.05) and hypoalbuminemia (OR 4.57, 1.83–11.39, p = 0.001), but only marginally with R017 infection (OR 2.14, 0.88–5.22, p = 0.094). In conclusion, infections by C. difficile R018 strains tend to cause more severe disease, while there was a trend for higher mortality with R017 infections. PMID:28002482

  18. High Variability in Nosocomial Clostridium difficile Infection Rates Across Hospitals After Colorectal Resection.

    PubMed

    Aquina, Christopher T; Probst, Christian P; Becerra, Adan Z; Hensley, Bradley J; Iannuzzi, James C; Noyes, Katia; Monson, John R T; Fleming, Fergal J

    2016-04-01

    Hospital-acquired Clostridium difficile infection is associated with adverse patient outcomes and high medical costs. The incidence and severity of C. difficile has been rising in both medical and surgical patients. Our aim was to assess risk factors and variation associated with the development of nosocomial C. difficile colitis among patients undergoing colorectal resection. This was a retrospective cohort study. The study included segmental colectomy and proctectomy cases in New York State from 2005 to 2013. The study cohort included 150,878 colorectal resections. Patients with a documented previous history of C. difficile infection or residence outside of New York State were excluded. A diagnosis of C. difficile colitis either during the index hospital stay or on readmission within 30 days was the main measure. C. difficile colitis occurred in 3323 patients (2.2%). Unadjusted C. difficile colitis rates ranged from 0% to 11.3% among surgeons and 0% to 6.8% among hospitals. After controlling for patient, surgeon, and hospital characteristics using mixed-effects multivariable analysis, significant unexplained variation in C. difficile rates remained present across hospitals but not surgeons. Patient factors explained only 24% of the total hospital-level variation, and known surgeon and hospital-level characteristics explained an additional 8% of the total hospital-level variation. Therefore, ≈70% of the hospital variation in C. difficile infection rates remained unexplained by captured patient, surgeon, and hospital factors. Furthermore, there was an ≈5-fold difference in adjusted C. difficile rates across hospitals. A limited set of hospital and surgeon characteristics was available. Colorectal surgery patients appear to be at high risk for C. difficile infection, and alarming variation in nosocomial C. difficile infection rates currently exists among hospitals after colorectal resection. Given the high morbidity and cost associated with C. difficile colitis

  19. Pharmacokinetics of LFF571 and Vancomycin in Patients with Moderate Clostridium difficile Infections

    PubMed Central

    Bhansali, Suraj G.; Mullane, Kathleen; Ting, Lillian S. L.; Leeds, Jennifer A.; Dabovic, Kristina; Praestgaard, Jens

    2014-01-01

    Clostridium difficile infection causes diarrheal disease with potentially fatal complications. Although treatments are available, including vancomycin, metronidazole, and fidaxomicin, the recurrence of disease after therapy remains a problem. LFF571 is a novel thiopeptide antibacterial that shows in vitro potency against C. difficile that is comparable to or greater than that of other clinically used antibiotics. Here, we compare the pharmacokinetics (PK) of LFF571 and vancomycin in patients with C. difficile infection as part of an early efficacy study. This multicenter, randomized, evaluator-blind, and active-controlled study evaluated the safety, efficacy, and pharmacokinetics of LFF571 in adults with primary episodes or first relapses of moderate C. difficile infections. Patients were randomized to receive 200 mg of LFF571 or 125 mg of vancomycin four times daily for 10 days. The PK parameters were calculated from drug concentrations measured in serum and fecal samples. The systemic exposure following oral administration of 200 mg of LFF571 four times per day for 10 days in patients with C. difficile infection was limited. The highest LFF571 serum concentration observed was 41.7 ng/ml, whereas the levels in feces at the end of treatment were between 107 and 12,900 μg/g. In comparison, the peak vancomycin level observed in serum was considerably higher, at 2.73 μg/ml; the levels of vancomycin in feces were not measured. Similar to healthy volunteers, patients with C. difficile infections exhibited high fecal concentrations and low serum levels of LFF571. These results are consistent with the retention of LFF571 in the lumen of the gastrointestinal tract. (This study has been registered at ClinicalTrials.gov under registration no. NCT01232595.) PMID:25534724

  20. A Simulation-Based Assessment of Strategies to Control Clostridium Difficile Transmission and Infection

    PubMed Central

    Rubin, Michael A.; Jones, Makoto; Leecaster, Molly; Khader, Karim; Ray, Willy; Huttner, Angela; Huttner, Benedikt; Toth, Damon; Sablay, Theodore; Borotkanics, Robert J.; Gerding, Dale N.; Samore, Matthew H.

    2013-01-01

    Background Clostridium difficile is one of the most common and important nosocomial pathogens, causing severe gastrointestinal disease in hospitalized patients. Although "bundled" interventions have been proposed and promoted, optimal control strategies remain unknown. Methods We designed an agent-based computer simulation of nosocomial C. difficile transmission and infection, which included components such as: patients and health care workers, and their interactions; room contamination via C. difficile shedding; C. difficile hand carriage and removal via hand hygiene; patient acquisition of C. difficile via contact with contaminated rooms or health care workers; and patient antimicrobial use. We then introduced six interventions, alone and "bundled" together: aggressive C. difficile testing; empiric isolation and treatment of symptomatic patients; improved adherence to hand hygiene and contact precautions; improved use of soap and water for hand hygiene; and improved environmental cleaning. All interventions were tested using values representing base-case, typical intervention, and optimal intervention scenarios. Findings In the base-case scenario, C. difficile infection rates ranged from 8–21 cases/10,000 patient-days, with a case detection fraction between 32%–50%. Implementing the "bundle" at typical intervention levels had a large impact on C. difficile acquisition and infection rates, although intensifying the intervention to optimal levels had much less additional impact. Most of the impact came from improved hand hygiene and empiric isolation and treatment of suspected C. difficile cases. Conclusion A "bundled" intervention is likely to reduce nosocomial C. difficile infection rates, even under typical implementation conditions. Real-world implementation of the "bundle" should focus on those components of the intervention that are likely to produce the greatest impact on C. difficile infection rates, such as hand hygiene and empiric isolation and

  1. A Genomic Analysis of Clostridium difficile Infections in Blunt Trauma Patients

    PubMed Central

    Efron, Philip Alexander; Liu, Huazhi; Lottenberg, Lawrence; Cuenca, Alex Gervacio; Gentile, Lori Filichia; Miggins, Makesha Vernee; Bihorac, Azra; Baker, Henry V.; Moore, Frederick Alan; Moldawer, Lyle Linc; Ang, Darwin N

    2013-01-01

    Background Evidence demonstrates that susceptibility to Clostridium difficile infection (C. diff. ) is related as much to host risk factors as bacterial potency. Using blood leukocyte genome-wide expression patterns of severe blunt trauma patients obtained by the NIGMS sponsored Glue Grant “Inflammation and the Host Response to Injury” we examined C. diff. patients’ leukocyte genomic profiles to determine pre- and post-infection gene expression changes. Methods The genomic responses of 21 severe trauma patients were analyzed (5 C. diff. 16 controls matched for age and severity of injury). After elimination of probe sets whose expression was below baseline or were unchanged, remaining probe sets underwent hierarchical clustering and principal component analysis. Molecular pathways were generated through Ingenuity Pathways Analysis ®. Results Supervised analysis demonstrated 118 genes whose expression in C. diff. patients varied before and after their infection. Supervised analysis comparing C. diff. to matched non-C. diff. patients prior to infection suggested that the expression of 501 genes were different in the two groups with up to 87% class prediction (p<0.05). Many of these genes are related to cell-mediated immune responses, signaling and interaction. Conclusions Genomic analysis of severe blunt trauma patients reveals a distinct leukocyte expression profile of C. diff. both prior to and after infection. We conclude that an association may exist between a severe trauma patient’s leukocyte genomic expression profile and subsequent susceptibility to C. diff. Further prospective expression analysis of this C. diff. population may reveal potential therapeutic interventions and allow early identification of C. diff. susceptible patients. Level of Evidence Level III prognostic/diagnostic study. PMID:23271108

  2. Effect of continuous sub-culturing on infectivity of Clostridium perfringens ATCC13124 in mouse gas gangrene model.

    PubMed

    Kumar, Ravi Bhushan; Alam, Syed Imteyaz

    2017-07-01

    Clostridium perfringens is a Validated Biological Agent and a pathogen of medical, veterinary, and military significance. Gas gangrene is the most destructive of all the clostridial diseases and is caused by C. perfringens type A strains wherein the infection spreads quickly (several inches per hour) with production of gas. Influence of repeated in vitro cultivation on the infectivity of C. perfringens was investigated by comparing the surface proteins of laboratory strain and repository strains of the bacterium using 2DE-MS approach. In order to optimize host-pathogen interaction during experimental gas gangrene infection, we also explored the role of particulate matrix on ability of C. perfringens to cause gas gangrene.

  3. Active and Secretory IgA-Coated Bacterial Fractions Elucidate Dysbiosis in Clostridium difficile Infection

    PubMed Central

    Moya, Andrés; Vázquez-Castellanos, Jorge F.; Artacho, Alejandro; Chen, Xinhua; Kelly, Ciaran

    2016-01-01

    ABSTRACT The onset of Clostridium difficile infection (CDI) has been associated with treatment with wide-spectrum antibiotics. Antibiotic treatment alters the activity of gut commensals and may result in modified patterns of immune responses to pathogens. To study these mechanisms during CDI, we separated bacteria with high cellular RNA content (the active bacteria) and their inactive counterparts by fluorescence-activated cell sorting (FACS) of the fecal bacterial suspension. The gut dysbiosis due to the antibiotic treatment may result in modification of immune recognition of intestinal bacteria. The immune recognition patterns were assessed by FACS of bacterial fractions either coated or not with intestinal secretory immunoglobulin A (SIgA). We described the taxonomic distributions of these four bacterial fractions (active versus inactive and SIgA coated versus non-SIgA coated) by massive 16S rRNA gene amplicon sequencing and quantified the proportion of C. difficile toxin genes in the samples. The overall gut microbiome composition was more robustly influenced by antibiotics than by the C. difficile toxins. Bayesian networks revealed that the C. difficile cluster was preferentially SIgA coated during CDI. In contrast, in the CDI-negative group Fusobacterium was the characteristic genus of the SIgA-opsonized fraction. Lactobacillales and Clostridium cluster IV were mostly inactive in CDI-positive patients. In conclusion, although the proportion of C. difficile in the gut is very low, it is able to initiate infection during the gut dysbiosis caused by environmental stress (antibiotic treatment) as a consequence of decreased activity of the protective bacteria. IMPORTANCE C. difficile is a major enteric pathogen with worldwide distribution. Its expansion is associated with broad-spectrum antibiotics which disturb the normal gut microbiome. In this study, the DNA sequencing of highly active bacteria and bacteria opsonized by intestinal secretory immunoglobulin

  4. Non-invasive fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient presenting with hypertensive disorder post interventionem.

    PubMed

    Goeser, F; Schlabe, S; Ruiner, C E; Kramer, L; Strassburg, C P; Spengler, U

    2016-10-01

    Fecal microbiota transplantation has gathered much attention due to its high efficacy in resolving recurrent Clostridium difficile infection. Until today, it is recognized as a safe procedure without any severe side effects. Patients with impaired conscious states suffering from recurrent episodes of aspiration are at increased risk by endoscopic interventions needed during standard approaches for fecal microbiota transplantation application.Here, we illustrate the case of a tetraplegic patient undergoing fecal microbiota transplantation due to his fifth recurrent episode of Clostridium difficile infection using a self-advancing nasal jejunal feeding tube as effective minimal-invasive option of fecal microbiota transplantation application. Persistent aggravation of arterial hypertension, which developed post-intervention in this patient, could be interpreted as a hitherto unknown side effect of fecal microbiota transplantation in this setting. Moreover, this is a further hint for a link between the intestinal microbiome and arterial hypertension in general. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation.

    PubMed

    Sokol, Harry; Galperine, Tatiana; Kapel, Nathalie; Bourlioux, Pierre; Seksik, Philippe; Barbut, Frederic; Scanzi, Julien; Chast, François; Batista, Rui; Joly, Francisca; Joly, Anne-Christine; Collignon, Anne; Guery, Benoit; Beaugerie, Laurent

    2016-03-01

    Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  6. Risk of Clostridium difficile infection in intensive care unit patients with sepsis exposed to metronidazole.

    PubMed

    Sabbah, Mohamad A; Schorr, Christa; Czosnowski, Quinn A; Hunter, Krystal; Torjman, Marc C; Fraimow, Henry S; Zanotti, Sergio; Tsigrelis, Constantine

    2015-04-01

    Antimicrobial agents used to treat Clostridium difficile infection (CDI), such as metronidazole and vancomycin, have been used during antibiotic treatment of other infections to try to prevent the development of CDI. We evaluated the hypothesis that intensive care unit (ICU) patients who receive metronidazole as part of an antibiotic treatment regimen for sepsis have a lower risk of subsequently developing CDI. This was a nested case-control study in a cohort of ICU patients who received antibiotic therapy for sepsis. A total of 10 012 patients aged ≥ 18 years were admitted to the Cooper University Hospital medical/surgical ICU from 1/1/2003 to 12/31/2008. After applying inclusion criteria including having received antibiotic therapy for sepsis and subsequently having developed CDI, 67 cases were identified. The cases were matched for age, gender, date of ICU admission, and hospital length of stay to 67 controls that also received antibiotic therapy for sepsis but did not subsequently develop CDI. In the multivariate analysis, there was no association between metronidazole exposure and the risk of CDI (odds ratio (OR) = 0.57; p = 0.23). The only significant associations on multivariate analysis were antifungal therapy (OR = 0.30; p = 0.02) and aminoglycoside and/or colistin therapy (OR = 0.17; p = 0.02). No association was found between metronidazole use and subsequent CDI in ICU patients who received antibiotic therapy for sepsis.

  7. Animal models to study the pathogenesis of human and animal Clostridium perfringens infections

    PubMed Central

    Uzal, Francisco A.; McClane, Bruce A.; Cheung, Jackie K.; Theoret, James; Garcia, Jorge P.; Moore, Robert J.; Rood, Julian I.

    2016-01-01

    The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats. PMID:25770894

  8. [Experience with fecal transplantation in the treatment of Clostridium difficile infection].

    PubMed

    Vigvári, Szabolcs; Nemes, Zsuzsanna; Vincze, Aron; Solt, Jenő; Sipos, Dávid; Feiszt, Zsófia; Kappéter, Agnes; Kovács, Beáta; Péterfi, Zoltán

    2014-11-02

    During the past years a dramatic change has been observed in the epidemiology of Clostridium difficile infections. The aim of the authors was to investigate the possibility of the fecal microbiota transplantation and study differences, if any, in the success rate of the two different upper gastrointestinal tract method. 100 ml of fecal microbiota solution was instilled via a nasoduodenal tube in 15 cases and a nasogastric tube in 15 cases. The authors defined the primary cure rate as the percentage of cases in which the symptoms disappeared without recurrence within 6 weeks after the first fecal microbiota transplantation, while secondary cure rate was calculated as the percentage of cases in which the symptoms resolved after the second fecal microbiota transplantation. It was found that fecal microbiota transplantation applied via the nasoduodenal tube resulted in a 100% primary cure rate. With the use of the nasogastric tube, the primary and secondary cure rate were 80% and 93.3%, respectively. Fecal microbiota transplantation via the upper gastrointestinal tract was found to have an overall primary cure rate of 90.0% and a secondary cure rate of 96.7%. Fecal microbiota transplantation proved to be very effective, particularly in recurrent infections and cases where conventional treatment failed.

  9. 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

  10. Fecal microbiota transplant for recurrent Clostridium difficile infection: Mayo Clinic in Arizona experience.

    PubMed

    Patel, Neal C; Griesbach, Cheryl L; DiBaise, John K; Orenstein, Robert

    2013-08-01

    To report the initial experience of treating recurrent Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) at Mayo Clinic in Arizona. The study retrospectively reviewed FMTs performed at Mayo Clinic in Arizona between January 1, 2011, and January 31, 2013. All the recipients had multiple recurrent CDIs unresponsive to traditional antibiotic drug therapy. A standardized protocol was developed to identify patients, screen donors, perform FMT, and determine outcomes via telephone surveys. Thirty-one patients (mean ± SD age, 61.26±19.34 years) underwent FMT. Median time from index infection to FMT was 340 days. Ninety-seven percent (29 of 30) of patients reported substantial improvement or resolution of diarrhea (median time to improvement, 3 days), 74% (17 of 23) reported improvement or resolution of abdominal pain (median time to improvement, 3 days), and 55% (16 of 29) had improvement or resolution of fatigue (median time to improvement, 6 days). Three patients underwent repeated FMT owing to persistent symptoms; 2 reported improvement in diarrhea with the second therapy. No serious adverse events directly related to FMT were reported. A standardized regimen of FMT for recurrent CDI is safe, is highly effective, and can be provided using a relatively simple protocol. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  11. Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection

    PubMed Central

    Ross, Caná L.; Spinler, Jennifer K.; Savidge, Tor C.

    2016-01-01

    Alteration of the gut microbial community structure and function through antibiotic use increases susceptibility to colonization by Clostridium difficile and other enteric pathogens. However, the mechanisms that mediate colonization resistance remain elusive. As the leading definable cause of infectious diarrhea, toxigenic C. difficile represents a burden for patients and health care systems, underscoring the need for better diagnostics and treatment strategies. Next-generation sequence data has increased our understanding of how the gut microbiota is influenced by many factors including diet, disease, aging and drugs. However, a microbial-based biomarker differentiating C. difficile infection from antibiotic-associated diarrhea remains elusive. Metabolomics profiling, which is highly responsive to changes in physiological conditions, have shown promise in differentiating subtle disease phenotypes that exhibit a nearly identical microbiome community structure, suggesting metabolite-based biomarkers may be an ideal diagnostic for identifying patients with CDI. This review focuses on the current understanding of structural and functional changes to the gut microbiota during C. difficile infection obtained from studies assessing the microbiome and metabolome of samples from patients and murine models. PMID:27180006

  12. Probiotics and Fecal Microbiota Transplant for Primary and Secondary Prevention of Clostridium difficile Infection.

    PubMed

    Crow, Jessica R; Davis, Stephanie L; Chaykosky, Darlene M; Smith, Tiffeny T; Smith, Janessa M

    2015-11-01

    Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea and is associated with an increased risk of mortality. The use of probiotics and fecal microbiota transplantation (FMT) has been studied to reduce the incidence and severity of this infection, but variable efficacy and safety data have been reported. Probiotics are hypothesized to be effective in the management of CDI through a number of mechanisms that include maintenance of normal gastrointestinal flora, antimicrobial and antitoxin properties, and immunomodulatory effects. Despite promising results in small trials and meta-analyses, prospective, randomized, controlled trials have not demonstrated probiotics to be effective in the primary prevention of C. difficile-associated diarrhea (CDAD). Probiotics may be effective for secondary prevention in patients with recurrent CDI, but guidelines acknowledge the lack of compelling evidence. Trials are limited by the use of varying types of strains, numbers of strains, and doses of probiotics, as well the definitions of CDI and CDAD. FMT has been proposed as a method for restoring gut microbiota and has been shown to significantly increase the rate of cure in patients with recurrent CDI. Current studies have demonstrated minimal adverse effects, with no reports of transmission of infectious diseases; however, the optimal delivery method, sample preparation, and donor selection remain unclear. In this review, findings from recent literature are highlighted, and guideline recommendations for the use of these agents in the primary and secondary prevention of CDI are summarized. © 2015 Pharmacotherapy Publications, Inc.

  13. [Fecal microbiota transplantation in recurrent Clostridium difficile infections. Framework and pharmaceutical preparation aspects].

    PubMed

    Batista, R; Kapel, N; Megerlin, F; Chaumeil, J-C; Barbut, F; Bourlioux, P; Chast, F

    2015-09-01

    The fecal microbiota transplantation consists in introducing a preparation constituted by a dilution of stools of a healthy donor in the digestive tract of a patient recipient, to restore his intestinal physiological balance. This therapeutic approach was the subject of numerous studies showing its efficiency in the treatment of the recurrent infections with Clostridium difficile. The fecal microbiota transplantation has now a high level of clinical evidence, which explains that it appears in various international recommendations. In France, the fecal microbiota transplantation responds to the definition of a medication and can be executed as a pharmaceutical preparation or as an experimental drug for clinical trials under the responsibility of a hospital pharmacy. The objective of this paper is to propose a definition of a framework and to describe the methods of preparation of the fecal microbiota transplantation in the treatment of the recurrent infections with C. difficile and the interactions to consider for hospital pharmacies that do not have technical means to operate this technique. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. 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.

  15. Hospital Transfer Network Structure as a Risk Factor for Clostridium difficile Infection

    PubMed Central

    Simmering, Jacob E.; Polgreen, Linnea A.; Campbell, David R.; Cavanaugh, Joseph E.; Polgreen, Philip M.

    2016-01-01

    Objective To determine the effect on inter-hospital patient sharing via transfers on the rate of Clostridium difficile infections (CDI) in a hospital. Design Retrospective cohort Methods Using data from the Healthcare Cost and Utilization Project California State Inpatient Database, 2005–2011, we identified 2,752,639 transfers. We then constructed a series of networks detailing the connections formed by hospitals. We computed two measures of connectivity, indegree and weighted indegree, measuring the number of hospitals from which transfers into a hospital arrive, and the total number of incoming transfers, respectively. We estimated a multivariate model of CDI cases using the log-transformed network measures as well as covariates for hospital fixed effects, log median length of stay, log fraction of patients aged 65 or older, quarter and year indicators as predictors. Results We found an increase of one in the log indegree was associated with a 4.8% increase in incidence of CDI (95% CI: 2.3–7.4) and an increase of one in log weighted indegree was associated with a 3.3% increase in CDI incidence (95% CI: 1.5–5.2). Moreover, including measures of connectivity in the models greatly improved their fit. Conclusions Our results suggest infection control is not under the exclusive control of a given hospital but is also influenced by the connections and number of connections that hospitals have with other hospitals. PMID:26072907

  16. Clostridium difficile infection in the "oldest" old: clinical outcomes in patients aged 80 and older.

    PubMed

    Cober, Eric D; Malani, Preeti N

    2009-04-01

    Clostridium difficile infection (CDI) represents a cause of substantial morbidity, particularly for older adults. Although older age is a risk factor for CDI, few studies have specifically focused on clinical outcomes in older adults, particularly the "oldest" old. Retrospective review. University of Michigan Health System. All patients aged 80 and older with a positive cytotoxin assay for C. difficile and a clinical course consistent with CDI during 2006. Clinical data were recorded, including comorbid conditions and treatment regimens, as well as outcomes, including treatment failure, infection relapse, and 90-day mortality. Seventy patients aged 80 and older (mean 84.0+/-4.1) with CDI were identified. Metronidazole was given as initial therapy in 65 (92.8%); 18 of these 65 (27.7%) experienced treatment failure, requiring subsequent use of oral vancomycin. Serious adverse events included three episodes of toxic megacolon, two requiring colectomy. One death was directly attributable to CDI. All-cause mortality was 8.6% at 30 days and 17.1% at 90 days. Higher white blood cell (WBC) counts were independently associated with treatment failure (P=.02) and coronary artery disease with 90-day mortality (P=.02). In older adults with CDI, treatment failure on metronidazole occurred frequently and was associated with higher WBC count. Larger prospective studies are needed to determine risk factors for treatment failure and relapse in order to develop better paradigms for CDI treatment in older adults. Initial therapy with vancomycin may be appropriate for elderly patients, especially those with elevated WBC counts.

  17. Design and Purification of Subunit Vaccines for Prevention of Clostridium difficile Infection.

    PubMed

    Karczewski, Jerzy; Bodmer, Jean-Luc; Cook, James C; Xoconostle, Rachel F; Nahas, Debbie D; Joyce, Joseph G; Heinrichs, Jon H; Secore, Susan

    2016-01-01

    Clostridium difficile is a gram-positive bacterium responsible for a large proportion of nosocomial infections in the developed world. C. difficile secretes toxins A and B (TcdA and TcdB) and both toxins act synergistically to induce a spectrum of pathological responses in infected individuals ranging from pseudomembranous colitis to C. difficile-associated diarrhea. Toxins A and B have been actively investigated as components of prophylactic vaccine as well as targets for therapeutic intervention with antibodies. Expression of such toxins by recombinant technology is often difficult and may require special handling and adherence to strict safety regulations during the manufacturing process due to the inherent toxicity of the proteins. Both toxins are large proteins (308 kDa and 270 kDa, respectively) and contain distinct domains mediating cell attachment, cellular translocation, and enzymatic (glucosidase) activity. Here we describe methods to produce fragments of Toxin B for their subsequent evaluation as components of experimental C. difficile vaccines. Methods presented include selection of fragments encompassing distinct functional regions of Toxin B, purification methods to yield high quality proteins, and analytical evaluation techniques. The approach presented focuses on Toxin B but could be applied to the other component, Toxin A, and/or to any difficult to express or toxic protein.

  18. Faecal transplantation for the treatment of Clostridium difficile infection: a review.

    PubMed

    McCune, V L; Struthers, J K; Hawkey, P M

    2014-03-01

    Clostridium difficile infection (CDI) remains a major healthcare burden despite recent global falls in its prevalence. The risk of recurrence is high when using antibiotics such as vancomycin, particularly in already recurrent disease. In light of this, new therapy options are being perused, including novel antibiotics such as fidaxomicin, probiotics, intravenous immunoglobulin and faecal transplantation. Faecal transplantation, referred to here as human probiotic infusion (HPI), is attracting an increasing amount of interest from physicians and patients. Its use has been documented in ca. 500 cases for the treatment of CDI, with overall efficacy rates reported to be ca. 91%. The first randomised controlled trial (RCT) demonstrated that HPI was superior to a 14-day course of vancomycin (89% vs. 31%; P<0.001) and reported no deaths or serious adverse events. Safety and patient acceptability are often cited as limitations to the widespread use of this technique. However, data suggest that the short-term safety profile is encouraging, and concerns over patient acceptability are not warranted in the majority of cases. It seems appropriate to treat an infection which is caused by a major disturbance in the gut microbiota with a treatment that reverses this disturbance, rather than antibiotics that may exacerbate the problem. However, to fully understand the role of HPI in the management of CDI, further RCTs are needed with comparator antibiotics such as fidaxomicin and to establish the most efficacious HPI protocol for administration and preparation.

  19. Probiotics as adjunctive therapy for preventing Clostridium difficile infection – What are we waiting for?

    PubMed Central

    Spinler, Jennifer K.; Ross, Caná L.; Savidge, Tor C.

    2016-01-01

    With the end of the golden era of antibiotic discovery, the emergence of a new post-antibiotic age threatens to thrust global health and modern medicine back to the pre-antibiotic era. Antibiotic overuse has resulted in the natural evolution and selection of multi-drug resistant bacteria. One major public health threat, Clostridium difficile, is now the single leading cause of hospital-acquired bacterial infections and is by far the most deadly enteric pathogen for the U.S. population. Due to the high morbidity and mortality and increasing incidence that coincides with antibiotic use, non-traditional therapeutics are ideal alternatives to current treatment methods and also provide an avenue towards prevention. Despite the need for alternative therapies to antibiotics and the safety of most probiotics on the market, researchers are inundated with regulatory issues that hinder the translational science required to push these therapies forward. This review discusses the regulatory challenges of probiotic research, expert opinion regarding the application of probiotics to C. difficile infection and the efficacy of probiotics in preventing this disease. PMID:27180657

  20. Risk factors for and estimated incidence of community-associated Clostridium difficile infection, North Carolina, USA.

    PubMed

    Kutty, Preeta K; Woods, Christopher W; Sena, Arlene C; Benoit, Stephen R; Naggie, Susanna; Frederick, Joyce; Evans, Sharon; Engel, Jeffery; McDonald, L Clifford

    2010-02-01

    We determined estimated incidence of and risk factors for community-associated Clostridium difficile infection (CA-CDI) among patients treated at 6 North Carolina hospitals. CA-CDI case-patients were defined as adults (>18 years of age) with a positive stool test result for C. difficile toxin and no hospitalization within the prior 8 weeks. CA-CDI incidence was 21 and 46 per 100,000 person-years in Veterans Affairs (VA) outpatients and Durham County populations, respectively. VA case-patients were more likely than controls to have received antimicrobial drugs (adjusted odds ratio [aOR] 17.8, 95% confidence interval [CI] 6.6-48] and to have had a recent outpatient visit (aOR 5.1, 95% CI 1.5-17.9). County case-patients were more likely than controls to have received antimicrobial drugs (aOR 9.1, 95% CI 2.9-28.9), to have gastroesophageal reflux disease (aOR 11.2, 95% CI 1.9-64.2), and to have cardiac failure (aOR 3.8, 95% CI 1.1-13.7). Risk factors for CA-CDI overlap with those for healthcare-associated infection.

  1. Dietary Zinc Alters the Microbiota and Decreases Resistance to Clostridium difficile Infection

    PubMed Central

    Zackular, Joseph P.; Moore, Jessica L.; Jordan, Ashley T.; Juttukonda, Lillian J.; Noto, Michael J.; Nicholson, Maribeth R.; Crews, Jonathan D.; Semler, Matthew W.; Zhang, Yaofang; Ware, Lorraine B.; Washington, M. Kay; Chazin, Walter J.; Caprioli, Richard M.; Skaar, Eric P.

    2016-01-01

    Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide1. Over the past decade, incidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically2. CDI is most commonly initiated by antibiotic-mediated disruption of the gut microbiota; however, non-antibiotic associated CDI cases are well documented and on the rise3,4. This suggests that unexplored environmental, nutrient, and host factors likely influence CDI. Here we show that excess dietary zinc (Zn) significantly alters the gut microbiota and in turn reduces the threshold of antibiotics needed to confer susceptibility to C. difficile infection. In mice colonized with C. difficile, excess dietary Zn severely exacerbates C. difficile-associated disease by increasing toxin activity and altering the host immune response. In addition, we show that the Zn binding S100 protein calprotectin is antimicrobial against C. difficile and an essential component of the innate immune response to CDI. Together, these data suggest that nutrient Zn levels play a key role in determining susceptibility to CDI and severity of disease, and that calprotectin-mediated metal limitation is an important factor in the host immune response to C. difficile. PMID:27668938

  2. Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients.

    PubMed

    Mani, S; Rybicki, L; Jagadeesh, D; Mossad, S B

    2016-05-01

    Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of preparative regimen and GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P=0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI.

  3. Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection.

    PubMed

    Ross, Caná L; Spinler, Jennifer K; Savidge, Tor C

    2016-10-01

    Alteration of the gut microbial community structure and function through antibiotic use increases susceptibility to colonization by Clostridium difficile and other enteric pathogens. However, the mechanisms that mediate colonization resistance remain elusive. As the leading definable cause of infectious diarrhea, toxigenic C. difficile represents a burden for patients and health care systems, underscoring the need for better diagnostics and treatment strategies. Next-generation sequence data has increased our understanding of how the gut microbiota is influenced by many factors including diet, disease, aging and drugs. However, a microbial-based biomarker differentiating C. difficile infection from antibiotic-associated diarrhea has not been identified. Metabolomics profiling, which is highly responsive to changes in physiological conditions, have shown promise in differentiating subtle disease phenotypes that exhibit a nearly identical microbiome community structure, suggesting metabolite-based biomarkers may be an ideal diagnostic for identifying patients with CDI. This review focuses on the current understanding of structural and functional changes to the gut microbiota during C. difficile infection obtained from studies assessing the microbiome and metabolome of samples from patients and murine models.

  4. Increasing rates in Clostridium difficile infection (CDI) among hospitalised patients, Spain 1999-2007.

    PubMed

    Asensio, A; Vaque-Rafart, J; Calbo-Torrecillas, F; Gestal-Otero, J J; López-Fernández, F; Trilla-Garcia, A; Canton, R

    2008-07-31

    Limited information is available on the burden and epidemiology of Clostridium difficile infection (CDI) in Spain. The present report communicates the secular trends in prevalence of CDI among hospitalised patients in Spain from 1999 through 2007. Data were obtained through the EPINE study (Estudio de prevalencia de las infecciones nosocomiales en los hospitales españoles), a point prevalence study series of nosocomial infections among patients admitted to hospital in Spain. A total of 378 cases with CDI were identified. Median age was 74 years. Prevalence rates of CDI increased from 3.9 to 12.2 cases per 10,000 hospitalised patients and showed a significantly increasing secular trend from 1999 through 2007 (prevalence rate ratio per each year increment 1.09; 95% CI 1.05 - 1.14). Percentage of hospitalised patients receiving antimicrobials increased linearly from 36.0% in 1999 to 40.7% in 2007 (p <0.001) and was strongly correlated to CDI prevalence (R square = 0.73; regression coefficient =1.194, 95% CI= 1.192 - 1.196).

  5. Lactic acid production by Streptococcus thermophilus alters Clostridium difficile infection and in vitro Toxin A production

    PubMed Central

    Kolling, Glynis L.; Wu, Martin; Warren, Cirle A.; Durmaz, Evelyn; Klaenhammer, Todd R.; Guerrant, Richard L.

    2012-01-01

    Antibiotic treatment to treat specific infections has the potential to effectively target the offending microbe as well as other microbes that colonize sites within a host. Antibiotic-associated diarrhea (AAD) is a classic example resulting from disruption of host microbial communities; 20% of patients with AAD are likely to become colonized with Clostridium difficile. Restoration of a “normal” microbial community within the host using probiotic bacteria is one approach to circumvent AAD and C. difficile infection. The goals of this study were to assess the interactions between Streptococcus thermophilus, a potential probiotic organism and C. difficile using both in vitro and in vivo systems. Exposure of C. difficile to filtered supernatants from S. thermophilus showed a dose-dependent, bactericidal effect due to lactic acid. Additional studies show that levels of lactic acid (10 mM) that did not inhibit bacterial growth had the potential to decrease tcdA expression and TcdA release into the extracellular milieu. In vivo, treatment with viable S. thermophilus significantly increased luminal levels of lactate in the cecum compared with UV-irradiated S. thermophilus. In the context of infection with C. difficile, mice treated with viable S. thermophilus exhibited 46% less weight loss compared with untreated controls; moreover, less pathology, diarrhea, and lower detectable toxin levels in cecal contents were evident more often in S. thermophillus treated mice. A significant, inverse correlation (Spearman r = -0.942, p = 0.017) between the levels of luminal lactate and abundance of C. difficile were noted suggesting that lactate produced by S. thermophilus is a factor impacting the progression of C. difficile infection in the murine system. PMID:22895082

  6. National European guidelines for the prevention of Clostridium difficile infection: a systematic qualitative review.

    PubMed

    Martin, M; Zingg, W; Knoll, E; Wilson, C; Dettenkofer, M

    2014-08-01

    Clostridium difficile is the most frequent infectious cause of nosocomial diarrhoea and a major topic in infection prevention. To overview current national European guidelines for C. difficile infection (CDI) prevention and review the recommendations in respect of their evidence base and conformity to each other and the European Centre for Disease Control and Prevention (ECDC) guidance. In 34 European countries, the ECDC healthcare-associated infection (HCAI) surveillance National Contact Points and other HCAI experts (NCPs) were invited to complete an online questionnaire and to supply their guidelines. Guidelines not available in English, French or German were translated into English. For the qualitative analysis, a matrix with key measures based on the 2008 ECDC guidance was established. The review process was conducted independently by two reviewers. All 34 NCPs responded to the questionnaire and supplied 15 guidelines in total. Six of 34 (18%) countries reported having used the ECDC guidance as a basis for the development or revision of their national guideline. There was wide variation in the scope and detailing. Only six of the documents and the ECDC guidance supplied a rating for the strength of recommendations. The rating systems varied in how the categories were defined. Furthermore, the stated strength for similar measures varied across different guidelines. The ECDC guidance has not yet had a strong influence on the development or revision of national CDI prevention guidelines. One possible explanation for the variations is the necessity to adapt recommendations to national conditions. The use of internationally recognized instruments for the development of guidelines could help to improve their quality. Recommendations about monitoring or auditing the implementation would make them more useful. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  7. Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID).

    PubMed

    Davies, Kerrie A; Longshaw, Christopher M; Davis, Georgina L; Bouza, Emilio; Barbut, Frédéric; Barna, Zsuzsanna; Delmée, Michel; Fitzpatrick, Fidelma; Ivanova, Kate; Kuijper, Ed; Macovei, Ioana S; Mentula, Silja; Mastrantonio, Paola; von Müller, Lutz; Oleastro, Mónica; Petinaki, Efthymia; Pituch, Hanna; Norén, Torbjörn; Nováková, Elena; Nyč, Otakar; Rupnik, Maja; Schmid, Daniela; Wilcox, Mark H

    2014-12-01

    Variations in testing for Clostridium difficile infection can hinder patients' care, increase the risk of transmission, and skew epidemiological data. We aimed to measure the underdiagnosis of C difficile infection across Europe. We did a questionnaire-based study at 482 participating hospitals across 20 European countries. Hospitals were questioned about their methods and testing policy for C difficile infection during the periods September, 2011, to August, 2012, and September, 2012, to August, 2013. On one day in winter, 2012-13 (December, 2012, or January, 2013), and summer, 2013 (July or August), every hospital sent all diarrhoeal samples submitted to their microbiology laboratory to a national coordinating laboratory for standardised testing of C difficile infection. Our primary outcome measures were the rates of testing for and cases of C difficile infection per 10 000 patient bed-days. Results of local and national C difficile infection testing were compared with each other. If the result was positive at the national laboratory but negative at the local hospital, the result was classified as undiagnosed C difficile infection. We compared differences in proportions with the Mann-Whitney test, or McNemar's test if data were matched. During the study period, participating hospitals reported a mean of 65·8 tests (country range 4·6-223·3) for C difficile infection per 10 000 patient-bed days and a mean of 7·0 cases (country range 0·7-28·7) of C difficile infection per 10 000 patient-bed days. Only two-fifths of hospitals reported using optimum methods for testing of C difficile infection (defined by European guidelines), although the number of participating hospitals using optimum methods increased during the study period, from 152 (32%) of 468 in 2011-12 to 205 (48%) of 428 in 2012-13. Across all 482 European hospitals on the two sampling days, 148 (23%) of 641 samples positive for C difficile infection (as determined by the national laboratory

  8. Contribution of Adenosine A2B Receptors in Clostridium difficile Intoxication and Infection

    PubMed Central

    Li, Yuesheng; Calabrese, Gina M.; Freire, Rosemayre S.; Zaja-Milatovic, Snjezana; van Opstal, Edward; Figler, Robert A.; Linden, Joel; Guerrant, Richard L.

    2012-01-01

    Clostridium difficile toxins A (TcdA) and B (TcdB) induce a pronounced systemic and intestinal inflammatory response. A2B adenosine receptors (A2BARs) are the predominant adenosine receptors in the intestinal epithelium. We investigated whether A2BARs are upregulated in human intestinal cells by TcdA or TcdB and whether blockade of A2BARs can ameliorate C. difficile TcdA-induced enteritis and alter the outcome of C. difficile infection (CDI). Adenosine receptor subtype (A1, A2A, A2B, and A3) mRNAs were assayed in HCT-8 cells. Ileal loops from wild-type rabbits and mice and A2BAR−/− mice were treated with TcdA, with or without the selective A2BAR antagonist ATL692 or PSB1115. A murine model of CDI was used to determine the effect of A2BAR deletion or blockade with the orally available agent ATL801, on clinical outcome, histopathology and intestinal interleukin-6 (IL-6) expression from infection. TcdA and TcdB upregulated A2BAR gene expression in HCT-8 cells. ATL692 decreased TcdA-induced secretion and epithelial injury in rabbit ileum. Deletion of A2BARs reduced secretion and histopathology in TcdA-challenged mouse ileum. Deletion or blockade of A2BARs reduced histopathology, IL-6 expression, weight loss, diarrhea, and mortality in C. difficile-infected mice. A2BARs mediate C. difficile toxin-induced enteritis and disease. Inhibition of A2BAR activation may be a potential strategy to limit morbidity and mortality from CDI. PMID:23045479

  9. Toxin-positive Clostridium difficile latently infect mouse colonies and protect against highly pathogenic C. difficile.

    PubMed

    Etienne-Mesmin, Lucie; Chassaing, Benoit; Adekunle, Oluwaseyi; Mattei, Lisa M; Bushman, Frederic D; Gewirtz, Andrew T

    2017-02-20

    Clostridium difficile is a toxin-producing bacterium and a leading cause of antibiotic-associated disease. The ability of C. difficile to form spores and infect antibiotic-treated persons at low multiplicity of infection (MOI) underlies its large disease burden. However, C. difficile-induced disease might also result from long-harboured C. difficile that blooms in individuals administered antibiotics. Mice purchased from multiple vendors and repeatedly testing negative for this pathogen by quantitative PCR bloomed C. difficile following antibiotic treatment. This endogenous C. difficile strain, herein termed LEM1, which formed spores and produced toxin, was compared with highly pathogenic C. difficile strain VPI10463. Whole-genome sequencing revealed that LEM1 and VPI10463 shared 95% of their genes, including all known virulence genes. In contrast to VPI10463, LEM1 did not induce overt disease when administered to antibiotic-treated or germ-free mice, even at high doses. Rather, blooms of LEM1 correlated with survival following VPI10463 inoculation, and exogenous administration of LEM1 before or shortly following VPI10463 inoculation prevented C. difficile-induced death. Accordingly, despite similar growth properties in vitro, LEM1 strongly outcompeted VPI10463 in mice even at 100-fold lower inocula. These results highlight the difficulty of determining whether individual cases of C. difficile infection resulted from a bloom of endogenous C. difficile or a new exposure to this pathogen. In addition to impacting the design of studies using mouse models of C. difficile-induced disease, this study identified, isolated and characterised an endogenous murine spore-forming C. difficile strain able to decrease colonisation, associated disease and death induced by a pathogenic C. difficile strain. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Clostridium difficile infection, a descriptive analysis of solid organ transplant recipients at a single center.

    PubMed

    Tsapepas, Demetra S; Martin, Spencer T; Miao, Jennifer; Shah, Shreya A; Scheffert, Jenna; Fester, Keith; Ma, Karlene; Lat, Asma; Egan, Ron; McKeen, Jaclyn T

    2015-04-01

    Clostridium difficile is a bacterial enteric pathogen, which causes clinical disease among solid organ transplant (SOT) recipients. This large, single-center, retrospective study describes incidence, demographics, and impact of C. difficile infection (CDI) among adult SOT recipients, cardiac (n=5), lung (n=14), liver (n=9), renal (n=26), and multiorgan (n=9) patients transplanted and diagnosed with CDI (geneB PCR) between 9/2009 and 12/2012. The overall incidence of CDI in our population during the 40-month period of study was 4%. CDI incidence among cardiac, lung, liver, and renal transplant recipients was 1.9%, 7%, 2.7%, and 3.2%, respectively (P=0.03 between organ-types). Median time from transplant to CDI for all was 51 (14-249) days, with liver recipients having the shortest time to infection, median 36 (15-101) days, and lung recipients having a longer time to infection, median 136 (29-611) days. Antibiotic exposure within 3 months of CDI was evident in 45 of the 63 (71%) patients in this study, 80%, 79%, 100%, 58%, and 67% of cardiac, lung, liver, renal, and multiorgan transplant recipients, respectively. Most patients (83%) were hospitalized within the 3 months preceding CDI. Recipients were followed for a median time of 23 (16-31) months; at the time of last follow-up, 83% of allografts were functioning, and 86% of patients were alive. One death and 1 graft failure were causally related to CDI. CDI had an overall incidence of 4%; clinicians should have heightened awareness for CDI, especially among patients receiving antibiotics, with increased monitoring and aggressive management of CDI.

  11. 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.

  12. 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

  13. Outcomes of Clostridium difficile infection in recipients of solid abdominal organ transplants.

    PubMed

    Hsu, Jennifer L; Enser, James J; McKown, Trevor; Leverson, Glen E; Pirsch, John D; Hess, Timothy M; Safdar, Nasia

    2014-02-01

    Knowledge of outcomes of Clostridium difficile infection (CDI) in solid organ transplant (SOT) recipients is limited. To evaluate this population, we undertook a retrospective cohort study of all recipients of kidney and liver transplants diagnosed with CDI at a single center over 14 yr. Data pertaining to all episodes of CDI were collected. Multivariate analysis using logistic regression was performed to determine independent predictors of clinical cure. Overall, 170 patients developed 215 episodes of CDI. Among these patients, 162 episodes (75%) were cured, and in 103 episodes (48%), patients were cured within 14 d. In a multivariate analysis, lack of clinical cure at 14 d was predicted by recurrent episode (0.21, 95% CI 0.06-0.72, p = 0.0128), treatment with vancomycin (OR 0.27, 95% CI 0.1-0.74, p = 0.011), vasopressor support (OR 0.23, 95% CI 0.07-0.76, p = 0.0161), and CDI before the year 2004 (OR 0.44, 95% CI 0.2-0.98, p = 0.0446). The latter three factors are likely markers for severity of illness. In this cohort, 13 patients (8%) died during hospitalization, and 49 patients (29%) died within one yr. No deaths were attributed to CDI. Recurrent episode was a major predictor of treatment failure, suggesting that research into development of therapeutic options for recurrent disease is needed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Quantifying sources of bias in National Healthcare Safety Network laboratory-identified Clostridium difficile infection rates.

    PubMed

    Haley, Valerie B; DiRienzo, A Gregory; Lutterloh, Emily C; Stricof, Rachel L

    2014-01-01

    To assess the effect of multiple sources of bias on state- and hospital-specific National Healthcare Safety Network (NHSN) laboratory-identified Clostridium difficile infection (CDI) rates. Sensitivity analysis. A total of 124 New York hospitals in 2010. New York NHSN CDI events from audited hospitals were matched to New York hospital discharge billing records to obtain additional information on patient age, length of stay, and previous hospital discharges. "Corrected" hospital-onset (HO) CDI rates were calculated after (1) correcting inaccurate case reporting found during audits, (2) incorporating knowledge of laboratory results from outside hospitals, (3) excluding days when patients were not at risk from the denominator of the rates, and (4) adjusting for patient age. Data sets were simulated with each of these sources of bias reintroduced individually and combined. The simulated rates were compared with the corrected rates. Performance (ie, better, worse, or average compared with the state average) was categorized, and misclassification compared with the corrected data set was measured. Counting days patients were not at risk in the denominator reduced the state HO rate by 45% and resulted in 8% misclassification. Age adjustment and reporting errors also shifted rates (7% and 6% misclassification, respectively). Changing the NHSN protocol to require reporting of age-stratified patient-days and adjusting for patient-days at risk would improve comparability of rates across hospitals. Further research is needed to validate the risk-adjustment model before these data should be used as hospital performance measures.

  15. Fecal microbiota transplantation in the treatment of refractory Clostridium difficile infection in children: an update.

    PubMed

    Walia, Ritu; Kunde, Sachin; Mahajan, Lori

    2014-10-01

    The use of transplanted fecal material for the treatment of diarrheal illness dates back to the fourth-century China. While fecal microbiota transplant has gained increasing popularity over the past 50 years for the treatment of refractory Clostridium difficile infections (RCDIs) in adults, it has only been recently utilized in children. The purpose of this article is to review the use of fecal microbiota transplant (FMT) in the treatment of pediatric RCDIs. Minimal pediatric data, including few case reports and series, document the successful use of FMT for treatment of RCDI in the past 2 years. Patients in these reports included otherwise healthy children, those with inflammatory bowel disease as well as significantly immunocompromised children. Donor fecal infusion via nasogastric tube, gastroscope or colonoscope in children aged 16 months and older demonstrated a high rate of symptom resolution and organism eradication. No complications to date have been reported in children who have undergone FMT. FMT is emerging as a well-tolerated and effective treatment for RCDI in not only adults but also children.

  16. Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection.

    PubMed

    Zackular, Joseph P; Moore, Jessica L; Jordan, Ashley T; Juttukonda, Lillian J; Noto, Michael J; Nicholson, Maribeth R; Crews, Jonathan D; Semler, Matthew W; Zhang, Yaofang; Ware, Lorraine B; Washington, M Kay; Chazin, Walter J; Caprioli, Richard M; Skaar, Eric P

    2016-11-01

    Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide. Over the past decade, incidence, severity and costs associated with C. difficile infection (CDI) have increased dramatically. CDI is most commonly initiated by antibiotic-mediated disruption of the gut microbiota; however, non-antibiotic-associated CDI cases are well documented and on the rise. This suggests that unexplored environmental, nutrient and host factors probably influence CDI. Here we show that excess dietary zinc (Zn) substantially alters the gut microbiota and, in turn, reduces the minimum amount of antibiotics needed to confer susceptibility to CDI. In mice colonized with C. difficile, excess dietary Zn severely exacerbated C. difficile-associated disease by increasing toxin activity and altering the host immune response. In addition, we show that the Zn-binding S100 protein calprotectin has antimicrobial effects against C. difficile and is an essential component of the innate immune response to CDI. Taken together, these data suggest that nutrient Zn levels have a key role in determining susceptibility to CDI and severity of disease, and that calprotectin-mediated metal limitation is an important factor in the host immune response to C. difficile.

  17. Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection.

    PubMed

    Hirsch, Bruce E; Saraiya, Nimit; Poeth, Kaitlin; Schwartz, Rebecca M; Epstein, Marcia E; Honig, Gerard

    2015-04-17

    Clostridium difficile infection (CDI), a complication of antibiotic-induced injury to the gut microbiome, is a prevalent and dangerous cause of infectious diarrhea. Antimicrobial therapy for CDI is typically effective for acute symptoms, but up to one third of patients later experience recurrent CDI. Fecal-derived microbiota transplantation (FMT) can ameliorate the underlying dysbiosis and is highly effective for recurrent CDI. Traditional methods of FMT are limited by patient discomfort, risk and inefficient procedures. Many individuals with recurrent CDI have extensive comorbidities and advanced age. Widespread use of FMT requires strategies that are non-invasive, scalable and applicable across healthcare settings. A method to facilitate microbiota transfer was developed. Fecal samples were collected and screened for potential pathogens. Bacteria were purified, concentrated, cryopreserved and formulated into multi-layered capsules. Capsules were administered to patients with recurrent CDI, who were then monitored for 90 days. Thirteen women and six men with recurrent CDI were provided with microbiota transfer with orally administered capsules. The procedure was well tolerated. Thirteen individuals responded to a single course. Four patients were cured after a second course. There were 2 failures. The cumulative clinical cure rate of 89% is similar to the rates achieved with reported fecal-derived transplantation procedures. Recurrent CDI represents a profound dysbiosis and a debilitating chronic disease. Stable cure can be achieved by restoring the gut microbiome with an effective, well-tolerated oral capsule treatment. This strategy of microbiota transfer can be widely applied and is particularly appropriate for frail patients.

  18. Impacts of infection with different toxigenic Clostridium difficile strains on faecal microbiota in children.

    PubMed

    Ling, Zongxin; Liu, Xia; Jia, Xiaoyun; Cheng, Yiwen; Luo, Yueqiu; Yuan, Li; Wang, Yuezhu; Zhao, Chunna; Guo, Shu; Li, Lanjuan; Xu, Xiwei; Xiang, Charlie

    2014-12-15

    Increasing evidence suggests that altered intestinal microbial composition and function result in an increased risk of Clostridium difficile-associated diarrhoea (CDAD); however, the specific changes of intestinal microbiota in children suffering from CDAD and their associations with C. difficile strain toxigenicity are poorly understood. High-throughput pyrosequencing showed that reduced faecal bacterial diversity and dramatic shifts of microbial composition were found in children with CDAD. The Firmicutes/Bacteroidetes ratio was increased significantly in patients with CDAD, which indicated that dysbiosis of faecal microbiota was closely associated with CDAD. C. difficile infection resulted in an increase in lactate-producing phylotypes, with a corresponding decrease in butyrate-producing bacteria. The decrease in butyrate and lactate buildup impaired intestinal colonisation resistance, which increased the susceptibility to C. difficile colonisation. Strains of C. difficile which were positive for both toxin A and toxin B reduced faecal bacterial diversity to a greater degree than strains that were only toxin B-positive, and were associated with unusually abundant Enterococcus, which implies that the C. difficile toxins have different impacts on the faecal microbiota of children. Greater understanding of the relationships between disruption of the normal faecal microbiota and colonisation with C. difficile that produces different toxins might lead to improved treatment.

  19. Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization.

    PubMed

    Zhang, Lihua; Dong, Danfeng; Jiang, Cen; Li, Zhen; Wang, Xuefeng; Peng, Yibing

    2015-08-01

    Clostridium difficile is well recognized as the common pathogen of nosocomial diarrhea, meanwhile, asymptomatic colonization with C. difficile in part of the population has also drawn public attention. Although gut microbiota is known to play an important role in the pathogenesis of C. difficile infection (CDI), whether there is any alteration of gut microbial composition in asymptomatic C. difficile carriers hasn't been clearly described. The purpose of this study was to explore the differences in gut microbiome among CDI patients, asymptomatic C. difficile carriers and healthy individuals. We performed fecal microbiota analysis on the samples of eight CDI patients, eight asymptomatic C. difficile carriers and nine healthy subjects using 16S rRNA gene pyrosequencing. CDI patients and asymptomatic carriers showed reduced microbial richness and diversity compared with healthy subjects, accompanied with a paucity of phylum Bacteroidetes and Firmicutes as well as an overabundance of Proteobacteria. Some normally commensal bacteria, especially butyrate producers, were significantly depleted in CDI patients and asymptomatic carriers. Furthermore, the differences observed in microbial community structure between CDI patients and asymptomatic carriers suggested that the gut microbiota may be a potential factor of disease state for CDI. Our study demonstrates the characterization and diversity of gut microbiota in CDI and asymptomatic C. difficile colonization, which will provide new ideas for surveillance of the disease state and development of microbiota-targeted agents for CDI prevention and treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. 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.

  1. 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.

  2. Clostridium difficile infection in the Lao People's Democratic Republic: first isolation and review of the literature.

    PubMed

    Cheong, Elaine; Roberts, Tamalee; Rattanavong, Sayaphet; Riley, Thomas V; Newton, Paul N; Dance, David A B

    2017-09-21

    Current knowledge of the epidemiology of Clostridium difficile infection in Asia, and in particular the Greater Mekong Subregion, is very limited. Only a few studies from Thailand and Vietnam have been reported from the region with variable testing methods and results, and no studies from Lao People's Democratic Republic (PDR). Therefore we investigated the presence of C. difficile in a single centre in the Lao PDR and determined the ribotypes present. Seventy unformed stool samples from hospital inpatients at Mahosot Hospital, Vientiane, were tested for the presence of C. difficile using selective differential agar and confirmed by latex agglutination. C. difficile isolates were further characterised by ribotyping and toxin gene detection. C. difficile was isolated from five of the 70 patients, and five different ribotypes were identified (014, 017, 020, QX 107 and QX 574). This is the first isolation of C. difficile from human stool samples in the Lao PDR. These results will add to the limited amount of data on C. difficile in the region. In addition, we hope this information will alert clinicians to the presence of C. difficile in the country and will help inform future investigations into the epidemiology and diagnosis of C. difficile in Lao PDR.

  3. 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

  4. Clostridium difficile infections: do we know the real dimensions of the problem?

    PubMed

    Tattevin, Pierre; Buffet-Bataillon, Sylvie; Donnio, Pierre-Yves; Revest, Matthieu; Michelet, Christian

    2013-06-01

    Clostridium difficile infection (CDI) is the primary cause of nosocomial diarrhoea in industrialised countries, usually occurring as a complication of antibiotic therapy in elderly patients. Landmark events contributed to boosting interest in CDI over the last 10 years, including the emergence of unusually severe and recurrent CDI due to the NAP1/BI/027 strain, as well as reports suggesting that CDI is also significantly encountered in patients previously considered at no risk, such as community-acquired CDI in patients with no recent antibiotic use, or CDI during pregnancy. Despite this growing interest from the medical community, we do not know the real dimensions of the disease for the following reasons: (i) despite comprehensive guidelines published in Europe and in the USA, most laboratories still use diagnostic tests with suboptimal sensitivity as a 'rule-out' test, hence a significant proportion of CDIs remain undiagnosed; (ii) use of PCR as a stand-alone test by others will probably overestimate the real incidence of CDI and jeopardise any comparison between institutions with different diagnostic procedures; and (iii) transversal studies, with optimum design and diagnostic tests, are rapidly outdated due to the dramatic changes in CDI epidemiology that may occur from one year to another. To get an accurate picture of the real dimensions of the CDI issue, we need more systematic use of an adequate and homogeneous diagnostic strategy in the field as well as the implementation of continuous monitoring of CDI incidence through surveillance programmes.

  5. Serum 25-Hydroxyvitamin D Levels are not Associated with Adverse Outcomes in Clostridium Difficile Infection

    PubMed Central

    Micic, Dejan; Rao, Krishna; Trindade, Bruno Caetano; Walk, Seth T.; Chenoweth, Elizabeth; Jain, Ruchika; Trivedi, Itishree; Santhosh, Kavitha; Young, Vincent B.; Aronoff, David M.

    2015-01-01

    Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI. PMID:26500740

  6. 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.

  7. Prediction of recurrent clostridium difficile infection at the bedside: the GEIH-CDI score.

    PubMed

    Cobo, Javier; Merino, Esperanza; Martínez, Cristina; Cózar-Llistó, Alberto; Shaw, Evelyn; Marrodán, Teresa; Calbo, Esther; Bereciartúa, Elena; Sánchez-Muñoz, Luis A; Salavert, Miguel; Pérez-Rodríguez, M Teresa; García-Rosado, Dácil; Bravo-Ferrer, J María; Gálvez-Acebal, Juan; Henríquez-Camacho, César; Cuquet, Jordi; Pino-Calm, Berta; Torres, Luis; Sánchez-Porto, Antonio; Fernández-Félix, Borja M

    2017-09-19

    Recurrence of Clostridium difficile infection (CDI) has major consequences for both patients and the health system. The ability to predict which patients are at an increased risk of recurrent CDI makes it possible to select candidates for therapy with new drugs and therapies (including fecal microbiota transplantation) that have proven to reduce the incidence of recurrence of CDI. Our objective was to develop a clinical prediction tool, the GEIH-CDI score, to determine the risk of recurrence of CDI. Predictors of recurrence of CDI were investigated using logistic regression in a prospective cohort of 274 patients diagnosed with CDI. The model was calibrated using the Hosmer-Lemeshow test. The tool comprises 4 factors: age (70-79 years and ≥80 years), history of CDI during the previous year, direct detection of toxin in stool, and persistence of diarrhea on the fifth day of treatment. The functioning of the GEIH-CDI score was validated in a prospective cohort of 183 patients. The area under the ROC curve was 0.72 (0.65 - 0.79). Application of the tool makes it possible to select patients at high risk (>50%) of recurrence and patients with low risk (<10%) of recurrence. GEIH-CDI score may be useful for clinicians treating patients with CDI. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  8. 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.

  9. 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

  10. Development and application of an oral challenge mouse model for studying Clostridium perfringens type D infection.

    PubMed

    Fernandez-Miyakawa, Mariano E; Sayeed, Sameera; Fisher, Derek J; Poon, Rachael; Adams, Vicki; Rood, Julian I; McClane, Bruce A; Saputo, Julian; Uzal, Francisco A

    2007-09-01

    Clostridium perfringens type D isolates cause enterotoxemia in sheep, goats, and probably cattle. While the major disease signs and lesions of type D animal disease are usually attributed to epsilon toxin, a class B select agent, these bacteria typically produce several lethal toxins. Understanding of disease pathogenesis and development of improved vaccines are hindered by the lack of a small-animal model mimicking natural disease caused by type D isolates. Addressing this need, we developed an oral challenge mouse model of C. perfringens type D enterotoxemia. When BALB/c mice with a sealed anus were inoculated by intragastric gavage with type D isolates, 7 of 10 type D isolates were lethal, as defined by spontaneous death or severe clinical signs necessitating euthanasia. The lethalities of the seven type D isolates varied between 14 and 100%. Clinical signs in the lethally challenged mice included seizures, convulsions, hyperexcitability, and/or depression. Mild intestinal gas distention and brain edema were observed at necropsy in a few mice, while histology showed multifocal acute tubular necrosis of the kidney and edema in the lungs of most challenged mice that developed a clinical response. When the lethality of type D isolates in this model was compared with in vitro toxin production, only a limited correlation was observed. However, mice could be protected against lethality by intravenous passive immunization with an epsilon toxin antibody prior to oral challenge. This study provides an economical new model for studying the pathogenesis of C. perfringens type D infections.

  11. Predictors of severe outcomes in patients with Clostridium difficile infection from a Hispanic population.

    PubMed

    Paláu-Dávila, Laura; Garza-González, Elvira; Gutiérrez-Delgado, Eva María; Camacho-Ortiz, Adrián

    2017-01-01

    Factors associated with complicated Clostridium difficile infection (CDI) may vary among populations, and predictors of severe outcomes in CDI have not been studied in Hispanic patients. The aim of this study was to identify factors associated with a higher risk of colectomy, all-cause mortality, and CDI-associated mortality in a Hispanic population. We performed a retrospective study of all hospitalized patients with a diagnosis of CDI between January 1, 2011 and September 30, 2015 in a 450-bed teaching hospital in Monterrey, northeast Mexico. Three main outcomes were defined: fulminant colitis with subsequent colectomy, all-cause mortality within 30 days of diagnosis, and CDI-attributable mortality. Of 261 patients with diarrhea, 176 were diagnosed with CDI. For colectomy, Charlson comorbidity index, ICU stay and mechanical ventilation prior to CDI diagnosis, days with diarrhea prior to treatment, total days of hospital stay and days after CDI diagnosis, elevated ATLAS score, days of diarrhea post CDI treatment, and treatment failure significantly predicted the necessity of surgical treatment with colectomy. Treatment failure, persistent diarrhea, and a high ATLAS score were identified as risk factors for severe outcomes of CDI. A low albumin concentration and high creatinine were associated with higher overall mortality.

  12. A prospective study of community-associated Clostridium difficile infection in Kuwait: Epidemiology and ribotypes.

    PubMed

    Jamal, Wafaa; Pauline, Eunice; Rotimi, Vincent

    2015-10-01

    Clostridium difficile infection (CDI) is increasingly recognized as a significant community acquired pathogen that causes disease in the community. The aim of the study was to investigate prospectively the incidence of community-acquired-CDI (CA-CDI) in Kuwait. Of the 2584 patients with diarrhea, 16 (0.62%) were confirmed cases of CA-CDI. The other notable pathogens were Salmonella spp. (0.39%) and Campylobacter spp. (0.23%). The mean age was 39 years and the CDI was mild. Exposure to antibiotics in the previous 12 weeks, contact with infant aged <2 years and history of foreign travel was significantly associated with CA-CDI (P < 0.001; P < 0.0001; P < 0.002, respectively). Detected PCR ribotypes were 139 (n = 4) and 014, 056, 070, 097 and 179 (each n = 2). CA-CDI in Kuwait is more likely to occur in younger age and associated with ribotype 139. CA-CDI is not a common problem in Kuwait however extra vigilance must be maintained to detect it in the community even without traditional predisposing factors.

  13. Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond

    PubMed Central

    Borody, Thomas J.; Peattie, Debra; Mitchell, Scott W.

    2015-01-01

    Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases. PMID:27025624

  14. Cadazolid: A new hope in the treatment of Clostridium difficile infection.

    PubMed

    Kali, Arunava; Charles, Marie Victor Pravin; Srirangaraj, Srirangaraj

    2015-01-01

    Clostridium difficile infection (CDI) is a potential life-threatening consequence of antibiotic therapy. Although the risk increases with duration of treatment, it can also occur after a short treatment course. In addition to broad-spectrum antibiotics, anti-neoplastic agents, proton pump inhibitors, H(2) blockers, and several other drugs have been reported to induce intestinal dysbiosis, which is central to the pathogenesis of CDI. There is an increase in incidence and mortality attributed to CDI globally. Moreover, the epidemiology of C. difficile-associated diseases has changed significantly with an increasing occurrence of community-acquired CDI. Metronidazole and oral vancomycin are the first-line antibiotics used to treat CDI. However, metronidazole has limited effectiveness in severe cases and vancomycin use is associated with increasing risk of vancomycin resistance among Enterococcus spp. Cadazolid, a novel oxazolidinone antibiotic, has recently shown potent antimicrobial activity against C. difficile and has a lower propensity to induce resistance. The implications of its use in treating CDI have been reviewed based on current evidence.

  15. Clinical approach to severe Clostridium difficile infection: update for the hospital practitioner.

    PubMed

    Pant, Chaitanya; Sferra, Thomas J; Deshpande, Abhishek; Minocha, Anil

    2011-12-01

    The rising incidence of Clostridium difficile (C. difficile) infection or CDI is now a problem of pandemic proportions. The NAP1 hypervirulent strain of C. difficile is responsible for a majority of recent epidemics and the widespread use of fluoroquinolone antibiotics may have facilitated the selective proliferation of this strain. The NAP1 strain also is more likely to cause severe and fulminant colitis characterized by marked leukocytosis, renal failure, hemodynamic instability, and toxic megacolon. No single test suffices to diagnose severe CDI, instead; the clinician must rely on a combination of clinical acumen, laboratory testing, and radiologic and endoscopic modalities. Although oral vancomycin and metronidazole are considered standard therapies in the medical management of CDI, recently it has been demonstrated that vancomycin is the more effective antibiotic in cases of severe disease. Moreover, early surgical consultation is necessary in patients who do not respond to medical therapy or who demonstrate rising white blood cell counts or hemodynamic instability indicative of fulminant colitis. Subtotal colectomy with end ileostomy is the procedure of choice for fulminant colitis. When applied to select patients in a judicious and timely fashion, surgery can be a life-saving intervention. In addition to these therapeutic approaches, several investigational treatments including novel antibiotics, fecal bacteriotherapy and immunotherapy have shown promise in the care of patients with severe CDI.

  16. Impacts of infection with different toxigenic Clostridium difficile strains on faecal microbiota in children

    PubMed Central

    Ling, Zongxin; Liu, Xia; Jia, Xiaoyun; Cheng, Yiwen; Luo, Yueqiu; Yuan, Li; Wang, Yuezhu; Zhao, Chunna; Guo, Shu; Li, Lanjuan; Xu, Xiwei; Xiang, Charlie

    2014-01-01

    Increasing evidence suggests that altered intestinal microbial composition and function result in an increased risk of Clostridium difficile-associated diarrhoea (CDAD); however, the specific changes of intestinal microbiota in children suffering from CDAD and their associations with C. difficile strain toxigenicity are poorly understood. High-throughput pyrosequencing showed that reduced faecal bacterial diversity and dramatic shifts of microbial composition were found in children with CDAD. The Firmicutes/Bacteroidetes ratio was increased significantly in patients with CDAD, which indicated that dysbiosis of faecal microbiota was closely associated with CDAD. C. difficile infection resulted in an increase in lactate-producing phylotypes, with a corresponding decrease in butyrate-producing bacteria. The decrease in butyrate and lactate buildup impaired intestinal colonisation resistance, which increased the susceptibility to C. difficile colonisation. Strains of C. difficile which were positive for both toxin A and toxin B reduced faecal bacterial diversity to a greater degree than strains that were only toxin B-positive, and were associated with unusually abundant Enterococcus, which implies that the C. difficile toxins have different impacts on the faecal microbiota of children. Greater understanding of the relationships between disruption of the normal faecal microbiota and colonisation with C. difficile that produces different toxins might lead to improved treatment. PMID:25501371

  17. Gut microbiota composition and Clostridium difficile infection in hospitalized elderly individuals: a metagenomic study

    PubMed Central

    Milani, Christian; Ticinesi, Andrea; Gerritsen, Jacoline; Nouvenne, Antonio; Lugli, Gabriele Andrea; Mancabelli, Leonardo; Turroni, Francesca; Duranti, Sabrina; Mangifesta, Marta; Viappiani, Alice; Ferrario, Chiara; Maggio, Marcello; Lauretani, Fulvio; De Vos, Willem; van Sinderen, Douwe; Meschi, Tiziana; Ventura, Marco

    2016-01-01

    The gut microbiota composition of elderly hospitalized patients with Clostridium difficile infection (CDI) exposed to previous antibiotic treatment is still poorly investigated. The aim of this study was to compare the microbiota composition by means of 16S rRNA microbial profiling among three groups of hospitalized elderly patients (age ≥ 65) under standard diet including 25 CDI-positive (CDI group), 29 CDI-negative exposed to antibiotic treatment (AB+ group) and 30 CDI-negative subjects not on antibiotic treatment (AB− group). The functional properties of the gut microbiomes of CDI-positive vs CDI-negative subjects were also assessed by shotgun metagenomics. A significantly lower microbial diversity was detected in CDI samples, whose microbiomes clustered separately from CDI-negative specimens. CDI was associated with a significant under-representation of gut commensals with putative protective functionalities, including Bacteroides, Alistipes, Lachnospira and Barnesiella, and over-representation of opportunistic pathogens. These findings were confirmed by functional shotgun metagenomics analyses, including an in-depth profiling of the Peptostreptococcaceae family. In CDI-negative patients, antibiotic treatment was associated with significant depletion of few commensals like Alistipes, but not with a reduction in species richness. A better understanding of the correlations between CDI and the microbiota in high-risk elderly subjects may contribute to identify therapeutic targets for CDI. PMID:27166072

  18. DNA detection of Clostridium difficile infection based on real-time resistance measurement.

    PubMed

    Liu, C; Jiang, D N; Xiang, G M; Luo, F K; Liu, L L; Yu, J C; Pu, X Y

    2013-09-03

    We used a newly developed electrochemical method, real-time resistance measurement, based on loop-mediated isothermal amplification (LAMP), with real-time resistance monitoring and derivative analysis. DNA extracted from specimens was amplified through LAMP reaction. The 2 products of LAMP, DNA and pyrophosphate, both are negative ions; they combine with positive dye (crystal violet) and positive ions (Mg(2+)), which leads to an increase in the resistivity of the reaction liquid. The changes of resistivity were measured in real-time with a specially designed resistance electrode, to detect Clostridium difficile DNA. We found that electrochemical detection of C. difficile could be completed in 0.5-1 h, with a detection limit of 10(2) CFU/mL, with high accuracy (95.0%), sensitivity (91.1%), and specificity (97.3%) compared to PCR methods. C. difficile is commonly associated with antibiotic-induced diarrhea. Due to the difficulty in performing anaerobic culture and cytotoxicity neutralization assays, a simple, rapid, sensitive, and accurate method is preferred. We conclude that real-time resistance measurement is a rapid, sensitive, and stable method for the diagnosis of C. difficile infection that could be applied to gene chips and pocket instruments.

  19. 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.

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

    PubMed

    Fang, Ferric C; Polage, Christopher R; Wilcox, Mark H

    2017-03-01

    INTRODUCTIONIn 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. Copyright © 2017 American Society for Microbiology.

  1. 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

  2. Accuracy of ICD-9 coding for Clostridium difficile infections: a retrospective cohort.

    PubMed

    Scheurer, D B; Hicks, L S; Cook, E F; Schnipper, J L

    2007-08-01

    Clostridium difficile (C. diff) is a major nosocomial problem. Epidemiological surveillance of the disease can be accomplished by microbiological or administrative data. Microbiological tracking is problematic since it does not always translate into clinical disease, and it is not always available. Tracking by administrative data is attractive, but ICD-9 code accuracy for C. diff is unknown. By using a large administrative database of hospitalized patients with C. diff (by ICD-9 code or cytotoxic assay), this study found that the sensitivity, specificity, positive, and negative predictive values of ICD-9 coding were 71%, 99%, 87%, and 96% respectively (using micro data as the gold standard). When only using symptomatic patients the sensitivity increased to 82% and when only using symptomatic patients whose test results were available at discharge, the sensitivity increased to 88%. C. diff ICD-9 codes closely approximate true C. diff infection, especially in symptomatic patients whose test results are available at the time of discharge, and can therefore be used as a reasonable alternative to microbiological data for tracking purposes.

  3. Impacts of infection with different toxigenic Clostridium difficile strains on faecal microbiota in children

    NASA Astrophysics Data System (ADS)

    Ling, Zongxin; Liu, Xia; Jia, Xiaoyun; Cheng, Yiwen; Luo, Yueqiu; Yuan, Li; Wang, Yuezhu; Zhao, Chunna; Guo, Shu; Li, Lanjuan; Xu, Xiwei; Xiang, Charlie

    2014-12-01

    Increasing evidence suggests that altered intestinal microbial composition and function result in an increased risk of Clostridium difficile-associated diarrhoea (CDAD); however, the specific changes of intestinal microbiota in children suffering from CDAD and their associations with C. difficile strain toxigenicity are poorly understood. High-throughput pyrosequencing showed that reduced faecal bacterial diversity and dramatic shifts of microbial composition were found in children with CDAD. The Firmicutes/Bacteroidetes ratio was increased significantly in patients with CDAD, which indicated that dysbiosis of faecal microbiota was closely associated with CDAD. C. difficile infection resulted in an increase in lactate-producing phylotypes, with a corresponding decrease in butyrate-producing bacteria. The decrease in butyrate and lactate buildup impaired intestinal colonisation resistance, which increased the susceptibility to C. difficile colonisation. Strains of C. difficile which were positive for both toxin A and toxin B reduced faecal bacterial diversity to a greater degree than strains that were only toxin B-positive, and were associated with unusually abundant Enterococcus, which implies that the C. difficile toxins have different impacts on the faecal microbiota of children. Greater understanding of the relationships between disruption of the normal faecal microbiota and colonisation with C. difficile that produces different toxins might lead to improved treatment.

  4. 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.

  5. Biofilms of Clostridium species.

    PubMed

    Pantaléon, Véronique; Bouttier, Sylvie; Soavelomandroso, Anna Philibertine; Janoir, Claire; Candela, Thomas

    2014-12-01

    The biofilm is a microbial community embedded in a synthesized matrix and is the main bacterial way of life. A biofilm adheres on surfaces or is found on interfaces. It protects bacteria from the environment, toxic molecules and may have a role in virulence. Clostridium species are spread throughout both environments and hosts, but their biofilms have not been extensively described in comparison with other bacterial species. In this review we describe all biofilms formed by Clostridium species during both industrial processes and in mammals where biofilms may be formed either during infections or associated to microbiota in the gut. We have specifically focussed on Clostridium difficile and Clostridium perfringens biofilms, which have been studied in vitro. Regulatory processes including sporulation and germination highlight how these Clostridium species live in biofilms. Furthermore, biofilms may have a role in the survival and spreading of Clostridium species.

  6. Microbiota Dynamics in Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

    PubMed Central

    Song, Yang; Garg, Shashank; Girotra, Mohit; Maddox, Cynthia; von Rosenvinge, Erik C.; Dutta, Anand; Dutta, Sudhir; Fricke, W. Florian

    2013-01-01

    Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. To shed light on microbial events associated with RCDI and treatment by FMT, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient and healthy donor samples collected up to one year after FMT were studied longitudinally, including one post-FMT patient with antibiotic-associated relapse three months after FMT. This analysis allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or Enterobacteriaceae were significantly increased and putative butyrate producers, such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples from RCDI patients before FMT as compared to post-FMT patient and healthy donor samples. RCDI patient samples showed more case-specific variations than post-FMT patient and healthy donor samples. However, none of the bacterial groups were invariably associated with RCDI or successful treatment by FMT. Overall microbiota compositions in post-FMT patients, specifically abundances of the above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT, suggesting that full microbiota

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

    PubMed Central

    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.

    2017-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:28405601

  8. Animal models to study the pathogenesis of human and animal Clostridium perfringens infections.

    PubMed

    Uzal, Francisco A; McClane, Bruce A; Cheung, Jackie K; Theoret, James; Garcia, Jorge P; Moore, Robert J; Rood, Julian I

    2015-08-31

    The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Predictors of Clostridium difficile infection-related mortality among older adults.

    PubMed

    Chopra, Teena; Awali, Reda A; Biedron, Caitlin; Vallin, Eileen; Bheemreddy, Suchitha; Saddler, Christopher M; Mullins, Keith; Echaiz, Jose F; Bernabela, Luigino; Severson, Richard; Marchaim, Dror; Lephart, Paul; Johnson, Laura; Thyagarajan, Rama; Kaye, Keith S; Alangaden, George

    2016-11-01

    Over 90% of annual deaths caused by Clostridium difficile infection (CDI) occur in persons aged ≥65 years. However, no large-scale studies have been conducted to investigate predictors of CDI-related mortality among older adults. This case-control study included 540 CDI patients aged ≥60 years admitted to a tertiary care hospital in Detroit, Michigan, between January 2005 and December 2012. Cases were CDI patients who died within 30 days of CDI date. Controls were CDI patients who survived >30 days after CDI date. Cases were matched to controls on a 1:3 ratio based on age and hospital acquisition of CDI. One-hundred and thirty cases (25%) were compared with 405 controls (75%). Independent predictors of CDI-related mortality included admission from another acute hospital (odds ratio [OR], 8.25; P = .001) or a long-term care facility (OR, 13.12; P = .012), McCabe score ≥2 (OR, 12.19; P < .001), and high serum creatinine (≥1.7 mg/dL) (OR, 3.43; P = .021). The regression model was adjusted for the confounding effect of limited activity of daily living score, total number of antibiotic days prior to CDI, ileus on abdominal radiograph, low albumin (≤2.5 g/dL), elevated white blood cell count (>15 × 1,000/mm(3)), and admission to intensive care unit because of CDI. Predictors of CDI-related mortality reported in this study could be applied to the development of a bedside scoring system for older adults with CDI. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients.

    PubMed

    Webb, B J; Brunner, A; Ford, C D; Gazdik, M A; Petersen, F B; Hoda, D

    2016-08-01

    Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor-derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25-75 interquartile range [IQR] 38-791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long-term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso-jejunal route in 6 of the 7 patients. Mean follow-up was 265 days (IQR 51-288). Minor post-FMT adverse effects included self-limited bloating and urgency. One patient was suspected of having post-FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all-cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft-versus-host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects. © 2016 John Wiley

  12. Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.

    PubMed

    Song, Yang; Garg, Shashank; Girotra, Mohit; Maddox, Cynthia; von Rosenvinge, Erik C; Dutta, Anand; Dutta, Sudhir; Fricke, W Florian

    2013-01-01

    Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. To shed light on microbial events associated with RCDI and treatment by FMT, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient and healthy donor samples collected up to one year after FMT were studied longitudinally, including one post-FMT patient with antibiotic-associated relapse three months after FMT. This analysis allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or Enterobacteriaceae were significantly increased and putative butyrate producers, such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples from RCDI patients before FMT as compared to post-FMT patient and healthy donor samples. RCDI patient samples showed more case-specific variations than post-FMT patient and healthy donor samples. However, none of the bacterial groups were invariably associated with RCDI or successful treatment by FMT. Overall microbiota compositions in post-FMT patients, specifically abundances of the above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT, suggesting that full microbiota

  13. Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.

    PubMed

    Khoruts, Alexander; Rank, Kevin M; Newman, Krista M; Viskocil, Kimberly; Vaughn, Byron P; Hamilton, Matthew J; Sadowsky, Michael J

    2016-10-01

    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. 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. 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. 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. Copyright

  14. Delirium and other clinical factors with Clostridium difficile infection that predict mortality in hospitalized patients.

    PubMed

    Archbald-Pannone, Laurie R; McMurry, Timothy L; Guerrant, Richard L; Warren, Cirle A

    2015-07-01

    Clostridium difficile infection (CDI) severity has increased, especially among hospitalized older adults. We evaluated clinical factors to predict mortality after CDI. We collected data from inpatients diagnosed with CDI at a U.S. academic medical center (HSR-IRB#13630). We evaluated age, Charlson comorbidity index (CCI), whether patients were admitted from a long-term care facility, whether patients were in an intensive care unit (ICU) at the time of diagnosis, white blood cell count (WBC), blood urea nitrogen (BUN), low body mass index, and delirium as possible predictors. A parsimonious predictive model was chosen using the Akaike information criterion (AIC) and a best subsets model selection algorithm. The area under the receiver operating characteristic curve was used to assess the model's comparative, with the AIC as the selection criterion for all subsets to measure fit and control for overfitting. From the 362 subjects, the selected model included CCI, WBC, BUN, ICU, and delirium. The logistic regression coefficients were converted to a points scale and calibrated so that each unit on the CCI contributed 2 points, ICU admission contributed 5 points, each unit of WBC (natural log scale) contributed 3 points, each unit of BUN contributed 5 points, and delirium contributed 11 points.Our model shows substantial ability to predict short-term mortality in patients hospitalized with CDI. Patients who were diagnosed in the ICU and developed delirium are at the highest risk for dying within 30 days of CDI diagnosis. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Role of the leukocyte response in normal and immunocompromised host after Clostridium difficile infection.

    PubMed

    Vargas, Edwin; Apewokin, Senu; Madan, Rajat

    2017-02-20

    Clostridium difficile is the leading cause of healthcare-associated infections in the United States. Clinically, C. difficile-associated disease can present as asymptomatic colonization, self-limited diarrheal illness or severe colitis (that may result in death). This variability in disease course and outcomes suggests that host factors play an important role as key determinants of disease severity. Currently, there are several scoring indices to estimate severity of C. difficile-associated disease. Leukocytosis and renal failure are considered to be the most important predictors of C. difficile disease severity in hosts with a normal immune system. The degree of leukocytosis which is considered significant for severe disease and how it is scored vary amongst scoring indices. None of the scores have been prospectively validated, and while total WBC count is useful to estimate the magnitude of the host response in most patient populations, in immune-compromised patients like those receiving chemotherapy, solid organ transplant patients or hematopoietic stem cell transplants the WBC response can be variable or even absent making this marker of severity difficult to interpret. Other cellular subsets like neutrophils, eosinophils and lymphocytes provide important information about the host immune status and play an important role in the immune response against C. difficile infection. However, under the current scoring systems the role of these cellular subsets have been underestimated and only total white blood cell counts are taken into account. In this review we highlight the role of host leukocyte response to C. difficile challenge in the normal and immunocompromised host, and propose possible ways that would allow for a better representation of the different immune cell subsets (neutrophils, lymphocytes and eosinophils) in the current scoring indices.

  16. 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

  17. High resolution melt analysis to track infections due to ribotype 027 Clostridium difficile.

    PubMed

    Grando, Danilla; Said, Mohamed M; Mayall, Barrie C; Gurtler, Volker

    2012-05-01

    The increased prevalence of hypervirulent ribotype 027 Clostridium difficile requires rapid identification of isolates in order to implement timely infection control strategies. High resolution melt (HRM) analysis of PCR products can identify strain variation amongst genera of bacteria. The intergenic (16S-23S rDNA) spacer region contains sequence regions conserved within genera and other sequence region variables between species within genera. We wished to investigate whether HRM analysis of PCR ribotyping products could identify ribotype 027 C. difficile. Ribotyping was performed on 93 clinical isolates and five control strains and band patterns were analysed using GelCompar II (Applied Maths, USA). Real-time PCR using ribotyping primers was performed and normalised melt curves were generated. The HRM data was then imported into ScreenClust software (QIAGEN) to generate principal component analysis graphs depicting clustered relationships of strains. Ribotyping produced clear PCR bands for 88/98 isolates tested. Dendrograms generated by GelCompar showed a diversity of ribotype patterns amongst these 88 isolates with 18 groups identified with 70% homology. One clinical isolate showed 100% homology with the control 027 strains. ScreenClust analysis of the same 88 HRM results showed clustering of isolates, with 027 strains identifiable as a unique cluster. HRM analysis correctly identified the control 027 stains and the clinical isolate shown to be 027. HRM combined with ScreenClust analysis of real-time PCR products of the 16S-23S rDNA spacer region successfully identified ribotype 027 strains. For infection control purposes this was achieved within 2-3 h of colony isolation.

  18. Humoral immune response as predictor of recurrence in Clostridium difficile infection.

    PubMed

    Bauer, M P; Nibbering, P H; Poxton, I R; Kuijper, E J; van Dissel, J T

    2014-12-01

    Low serum concentrations of antibodies directed against the toxins TcdA and TcdB have been associated with a higher risk of recurrence of Clostridium difficile infection (CDI) after successful antibiotic treatment. However, there are conflicting reports. Herein, we compared serum levels of antibodies of patients with a single episode of CDI with those of patients who subsequently suffered a recurrence. We used a serum bank from patients who received an experimental whey protein product following successful antibiotic treatment for CDI. We determined levels of IgA and IgG directed against TcdA, TcdB and non-toxin cell surface antigens in serum collected directly and 3 weeks after completing a 10-day course of antibiotic treatment for CDI. We also developed an objective flow cytometry-based assay to determine the proportion of cells exhibiting cytopathic effect after exposure to TcdB. Using this method, we measured the TcdB-neutralizing capacity of sera. We compared the results for patients without a subsequent recurrence with those of patients who suffered a recurrence within 60 days after completing the antibiotic treatment. Advanced age, comorbidity other than immunocompromised state and low serum levels of anti-TcdA and anti-TcdB antibodies were associated with recurrence, whereas serum levels of antibodies directed against cell surface antigens were not. Serum TcdB-neutralizing capacity, which correlated only weakly with serum IgG anti-TcdB, was not significantly associated with recurrence. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  19. Antibiotics for Treatment of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease.

    PubMed

    Horton, Henry A; Dezfoli, Seper; Berel, Dror; Hirsch, Julianna; Ippoliti, Andrew; McGovern, Dermot; Kaur, Manreet; Shih, David; Dubinsky, Marla; Targan, Stephan R; Fleshner, Phillip; Vasiliauskas, Eric A; Grein, Jonathan; Murthy, Rekha; Melmed, Gil Y

    2014-09-01

    Patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD), have worse outcomes with Clostridium difficile infection (CDI), including increased readmissions, colectomy, and death. Oral vancomycin is recommended for the treatment of severe CDI, while metronidazole is the standard of care for nonsevere infection. We aimed to assess treatment outcomes of CDI in IBD. We conducted a retrospective observational study of inpatients with CDI and IBD from January 2006 through December 2010. CDI severity was assessed using published criteria. Outcomes included readmission for CDI within 30 days and 12 weeks, length of stay, colectomy, and death. A total of 114 patients met inclusion criteria (UC, 62; CD, 52). Thirty-day readmissions were more common among UC than CD patients (24.2% versus 9.6%; P=0.04). Same-admission colectomy occurred in 27.4% of UC patients and 0% of CD patients (P<0.01). Severe CDI was more common among UC than CD patients (32.2% versus 19.4%; P=0.12) but not statistically significant. Two patients died from CDI-associated complications (UC, 1; CD, 1). Patients with UC and nonsevere CDI had fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen compared to those treated with metronidazole (30-day readmissions, 31.0% versus 0% [P=0.04]; length of stay, 13.62 days versus 6.38 days [P=0.02]). Patients with UC and nonsevere CDI have fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen relative to those treated with metronidazole alone. Patients with ulcerative colitis and CDI should be treated with vancomycin.

  20. Patients' experience and perception of hospital-treated Clostridium difficile infections: a qualitative study.

    PubMed

    Guillemin, Isabelle; Marrel, Alexia; Lambert, Jérémy; Beriot-Mathiot, Axelle; Doucet, Carole; Kazoglou, Odysseas; Luxemburger, Christine; Reygrobellet, Camille; Arnould, Benoit

    2014-01-01

    Clostridium difficile is the leading cause of antibiotic-associated diarrhea and an important source of nosocomial infection. Clinical manifestations can range from mild diarrhea to lethal pseudomembranous colitis. Little is known about the burden of C. difficile infections (CDI) in patients. This qualitative study explored the impact of hospital-treated CDI on patients' lives from the first occurrence of CDI symptoms, through their hospital stay, and after discharge. Semi-structured interviews with 12 US and 12 French patients who had experienced CDI were conducted using an interview guide that was developed on the basis of a thorough literature review. Transcripts from these interviews were analyzed to identify concepts related to the research question. CDI affected numerous aspects of patients' lives. Patients reported that the continuous, watery, and uncontrollable diarrhea characteristic of CDI had the most impact on their daily lives. Diarrhea prevented them from participating in usual daily activities; this caused the collapse of their social lives. Patients felt humiliated and embarrassed. Patients' emotional distress worsened once hospitalized; they reported feelings of loneliness and worry when placed in isolation. From discharge to the time of the interview, patients reported both psychological and physical improvement. However, despite continuing improvement, most patients reported persistent worry and fear of recurrent episodes, and they were thus more careful about their diet and hygiene. As one patient in this study explained, CDI is "the worst of everything that I've had." The emotional distress and extreme physical exhaustion associated with CDI result in a traumatic and frightening experience for patients. This trauma persists after recovery and includes lingering fears of a recurrent episode.

  1. 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

  2. Risk Factors for Recurrence, Complications and Mortality in Clostridium difficile Infection: A Systematic Review

    PubMed Central

    Abou Chakra, Claire Nour; Pepin, Jacques; Sirard, Stephanie; Valiquette, Louis

    2014-01-01

    Background Clostridium difficile infection (CDI) can lead to complications, recurrence, and death. Numerous studies have assessed risk factors for these unfavourable outcomes, but systematic reviews or meta-analyses published so far were limited in scope or in quality. Methods A systematic review was completed according to PRISMA guidelines. An electronic search in five databases was performed. Studies published until October 2013 were included if risk factors for at least one CDI outcome were assessed with multivariate analyses. Results 68 studies were included: 24 assessed risk factors for recurrence, 18 for complicated CDI, 8 for treatment failure, and 30 for mortality. Most studies accounted for mortality in the definition of complicated CDI. Important variables were inconsistently reported, such as previous episodes and use of antibiotics. Substantial heterogeneity and methodological limitations were noted, mainly in the sample size, the definition of the outcomes and periods of follow-up, precluding a meta-analysis. Older age, use of antibiotics after diagnosis, use of proton pump inhibitors, and strain type were the most frequent risk factors for recurrence. Older age, leucocytosis, renal failure and co-morbidities were frequent risk factors for complicated CDI. When considered alone, mortality was associated with age, co-morbidities, hypo-albuminemia, leucocytosis, acute renal failure, and infection with ribotype 027. Conclusion Laboratory parameters currently used in European and American guidelines to define patients at risk of a complicated CDI are adequate. Strategies for the management of CDI should be tailored according to the age of the patient, biological markers of severity, and underlying co-morbidities. PMID:24897375

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

    PubMed

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

    2016-03-21

    Antibiotic-associated diarrhea (AAD) and Clostridium 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.

  4. 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.

  5. Bed occupancy rates and hospital-acquired Clostridium difficile infection: a cohort study.

    PubMed

    Ahyow, Lauren C; Lambert, Paul C; Jenkins, David R; Neal, Keith R; Tobin, Martin

    2013-10-01

    An emergent strain (ribotype 027) of Clostridium difficile infection (CDI) has been implicated in epidemics worldwide. Organizational factors such as bed occupancy have been associated with an increased incidence of CDI; however, the data are sparse, and the association has not been widely demonstrated. We investigated the association of bed occupancy and CDI within a large hospital organization in the United Kingdom. To establish whether bed occupancy rates are a significant risk factor for CDI in the general ward setting. A retrospective cohort study was carried out on data from 2006 to 2008. Univariate and multivariate Cox regression modeling was used to examine the strength and significance of the associations. Variables included patient characteristics, antibiotic policy exposure, case mix, and bed occupancy rates. A total of 1,589 cases of hospital-acquired CDI were diagnosed (1.7% of admissions), with an overall infection rate of 2.16 per 1,000 patient-days. Median bed occupancy was 93.3% (interquartile range, 83.3%-100%) Univariate and multivariate analyses showed positive and statistically significant associations. In the adjusted model, patients on wards with occupancy rates of 80%-89.9% had rates of CDI that were 56% higher (hazard ratio, 1.56 [95% confidence interval, 1.18-2.04]; P < .001) compared with baseline (0%-69.9% occupancy). CDI rates were 55% higher for patients on wards with maximal bed occupancy (100%). There is strong evidence of an association between high bed occupancy and CDI. Without effective interventions at high levels of bed occupancy, the economic benefits sought from reducing bed numbers may be negated by the increased risk of CDI.

  6. 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.

  7. Perceptions of fecal microbiota transplantation for Clostridium difficile infection: factors that predict acceptance

    PubMed Central

    Park, Leslie; Mone, Anjali; Price, Jennifer C.; Tzimas, Demetrios; Hirsh, Jacqueline; Poles, Michael A.; Malter, Lisa; Chen, Lea Ann

    2017-01-01

    Background Despite the effectiveness of fecal microbiota transplantation (FMT) for treating recurrent Clostridium difficile (C. difficile) infection, some patients are reluctant to accept this therapy. Our study examined attitudes towards FMT and factors that contribute to patients’ acceptance of this treatment. Methods We distributed patient surveys at a Veterans Affairs hospital, a public hospital, and an academic faculty practice. Multivariable logistic regression was performed, adjusting for factors associated with FMT acceptance on univariate analysis and prior experience with C. difficile infection. Results Of 267 patients, only 12% knew of FMT prior to the survey, but 77% would undergo the procedure if medically indicated. On multivariable analysis, those with children and with college degrees or higher were more likely to agree to FMT (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.02-4.35; OR 2.27, 95% CI 1.11-4.60 respectively). Sixty-five respondents (71%) chose colonoscopy as the preferred vehicle for FMT, while nasogastric tube was least preferred. Disease transmission was the most common concern (30%, n=242), and FMT success rate was the least selected concern (9.1%). Conclusions Most patients in a diverse sample of gastroenterology clinics had no prior knowledge of FMT, but were receptive to the procedure. Having children and higher education levels were predictors for FMT acceptance. Our findings suggest that barriers to FMT utilization may be overcome with counseling about safety concerns. More data on the risk of transmitting diseases or clinical characteristics, such as obesity, through FMT are needed and will be important for the acceptance of this procedure. PMID:28042242

  8. Clostridium difficile infection diagnosis in a paediatric population: comparison of methodologies.

    PubMed

    Hart, J; Putsathit, P; Knight, D R; Sammels, L; Riley, T V; Keil, A

    2014-09-01

    The increasing incidence of Clostridium difficile infection (CDI) in paediatric hospitalised populations, combined with the emergence of hypervirulent strains, community-acquired CDI and the need for prompt treatment and infection control, makes the rapid, accurate diagnosis of CDI crucial. We validated commonly used C. difficile diagnostic tests in a paediatric hospital population. From October 2011 to January 2012, 150 consecutive stools were collected from 75 patients at a tertiary paediatric hospital in Perth, Western Australia. Stools were tested using: C. Diff Quik Chek Complete, Illumigene C. difficile, GeneOhm Cdiff, cycloserine cefoxitin fructose agar (CCFA) culture, and cell culture cytotoxin neutralisation assay (CCNA). The reference standard was growth on CCFA or Cdiff Chromagar and PCR on isolates to detect tcdA, tcdB, cdtA, and cdtB. Isolates were PCR ribotyped. The prevalence of CDI was high (43 % of patients). Quik Chek Complete glutamate dehydrogenase (GDH) demonstrated a low negative predictive value (NPV) (93 %). Both CCNA and Quik Chek Complete toxin A/B had poor sensitivity (33 % and 29 % respectively). Molecular methods both had 89 % sensitivity. Algorithms using GDH + Illumigene or GeneOhm reduced the sensitivity to 85 % and 83 % respectively. Ribotype UK014/20 predominated. GDH NPV and GeneOhm and Illumigene sensitivities were reduced compared with adult studies. Quik Chek Complete and CCNA cannot reliably detect toxigenic CDI. A GDH first algorithm showed reduced sensitivity. In a high prevalence paediatric population, molecular methods alone are recommended over the use of GDH algorithm or culture and CCNA, as they demonstrate the best test performance characteristics.

  9. Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection.

    PubMed

    Shaughnessy, Megan K; Bobr, Aleh; Kuskowski, Michael A; Johnston, Brian D; Sadowsky, Michael J; Khoruts, Alexander; Johnson, James R

    2016-05-01

    Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficilespores 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 ofC. 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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. 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

  11. Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection

    PubMed Central

    Dial, Sandra; Kezouh, Abbas; Dascal, Andre; Barkun, Alan; Suissa, Samy

    2008-01-01

    Background Previous observations have indicated that infection with Clostridium difficile occurs almost exclusively after exposure to antibiotics, but more recent observations have suggested that prior antibiotic exposure may be less frequent among cases of community-acquired disease. Methods We used 2 linked health databases to perform a matched, nested case–control study of elderly patients admitted to hospital with community-acquired C. difficile infection. For each of 836 cases among people 65 years of age or older, we selected 10 controls. We determined the proportion of cases that occurred without prior antibiotic exposure and estimated the risk related to exposure to different antibiotics and the duration of increased risk. Results Of the 836 cases, 442 (52.9%) had no exposure to antibiotics in the 45-day period before the index date, and 382 (45.7%) had no exposure in the 90-day period before the index date. Antibiotic exposure was associated with a rate ratio (RR) of 10.6 (95% confidence interval [CI] 8.9–12.8). Clindamycin (RR 31.8, 95% CI 17.6–57.6), cephalosporins (RR 14.9, 95% CI 10.9–20.3) and gatifloxacin (RR 16.7, 95% CI 8.3–33.6) were associated with the highest risk. The RR for C. difficile infection associated with antibiotic exposure declined from 15.4 (95% CI 12.2–19.3) by about 20 days after exposure to 3.2 (95% CI 2.0–5.0) after 45 days. Use of a proton pump inhibitor was associated with increased risk (RR 1.6, 95% CI 1.3–2.0), as were concurrent diagnoses of inflammatory bowel disease (RR 4.1, 95% CI 2.6–6.6), irritable bowel syndrome (RR 3.4, 95% CI 2.3–5.0) and renal failure (RR 1.7, 95% CI 1.2–2.2). Interpretation Community-acquired C. difficile infection occurred in a substantial proportion of individuals with no recent exposure to antibiotics. Among patients who had been exposed to antibiotics, the risk declined markedly by 45 days after discontinuation of use. PMID:18838451

  12. Performance management of Clostridium difficile infection in hospitals - The carrot or stick approach?

    PubMed

    Fitzpatrick, Fidelma; Riordan, Mary O

    2016-02-01

    Public and political pressure for healthcare quality indicator monitoring, specifically healthcare-associated infection (HAI) has intensified the debate regarding the merits of public reporting and target setting as policy approaches. This paper reviews the evidence for these approaches with a focus on HAI, including Clostridium difficile infection (CDI). Healthcare key performance indicators (KPIs) and associated targets have been used widely with little evaluation. While targets are associated with some HAI reductions including CDI, as their control is multi-factorial, it is likely that reductions are due to numerous, concurrent control measures. Targets may help tackle organizational-wide issues that require high level management engagement and have contributed to the increased access and influence of infection control teams. HAI public reporting has also gained traction and is mandatory in many countries despite little scientific evaluation. CDI is one of the KPIs used but there is little consensus as to the best KPI for public reporting. Countries without public reporting have also seen improvements. Using indicator-based strategies rather than evidence-based ones risk improving the KPI but not necessarily quality of care. 'Bottom-up' approaches focussing on quality improvement and innovation generated by front line staff are seen as a lever for sustainable change. Positive deviance, where the resourcefulness and problem solving abilities of staff is harnessed, enables 'bottom-up' changes with process and outcome improvements. As implementation of best practice in healthcare is dependent on behavioural and cultural change, it is most likely that a combination of 'top-down' and 'bottom-up' approaches are required for sustainable improvement. This combined approach was used to improve staff influenza vaccination rates. Regulation may initially direct the spot-light onto infection control needs but true sustainable HAI reduction will only be fostered with

  13. Interleukin-22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice.

    PubMed

    Sadighi Akha, Amir A; McDermott, Andrew J; Theriot, Casey M; Carlson, Paul E; Frank, Charles R; McDonald, Roderick A; Falkowski, Nicole R; Bergin, Ingrid L; Young, Vincent B; Huffnagle, Gary B

    2015-04-01

    Our previous work has shown the significant up-regulation of Il22 and increased phosphorylation of signal transducer and activator of transcription 3 (STAT3) as part of the mucosal inflammatory response to Clostridium difficile infection in mice. Others have shown that phosphorylation of STAT3 at mucosal surfaces includes interleukin-22 (IL-22) and CD160-mediated components. The current study sought to determine the potential role(s) of IL-22 and/or CD160 in the mucosal response to C. difficile infection. Clostridium difficile-infected mice treated with anti-IL-22, anti-CD160 or a combination of the two showed significantly reduced STAT3 phosphorylation in comparison to C. difficile-infected mice that had not received either antibody. In addition, C. difficile-infected mice treated with anti-IL-22/CD160 induced a smaller set of genes, and at significantly lower levels than the untreated C. difficile-infected mice. The affected genes included pro-inflammatory chemokines and cytokines, and anti-microbial peptides. Furthermore, histopathological and flow cytometric assessments both showed a significantly reduced influx of neutrophils in C. difficile-infected mice treated with anti-IL-22/CD160. These data demonstrate that IL-22 and CD160 are together responsible for a significant fraction of the colonic STAT3 phosphorylation in C. difficile infection. They also underscore the additive effects of IL-22 and CD160 in mediating both the pro-inflammatory and pro-survival aspects of the host mucosal response in this infection.

  14. View from the front lines: an emergency medicine perspective on clostridial infections in injection drug users.

    PubMed

    Gonzales y Tucker, Richard Diego; Frazee, Bradley

    2014-12-01

    Injection drug use (IDU), specifically non-intravenous "skin-popping" of heroin, seems to provide optimal conditions for Clostridial infection and toxin production. IDU is therefore a major risk factor for wound botulism and Clostridial necrotizing soft tissue infections (NSTI) and continues to be linked to cases of tetanus. Case clusters of all 3 diseases have occurred among IDUs in Western U.S. and Europe. Medical personnel who care for the IDU population must be thoroughly familiar with the clinical presentation and management of these diseases. Wound botulism presents with bulbar symptoms and signs that are easily overlooked; rapid acquisition and administration of antitoxin can prevent neuromuscular respiratory failure. In addition to Clostridium perfringens, IDU-related NSTIs can be caused by Clostridium sordellii and Clostridium novyi, which may share a distinct clinical presentation. Early definitive NSTI management, which decreases mortality, requires a low index of suspicion on the part of emergency physicians and low threshold for surgical exploration and debridement on the part of the surgeon. Tetanus should be preventable in the IDU population through careful attention to vaccination status.

  15. Risk of Clostridium difficile infection in hospitalized patients receiving metronidazole for a non-C difficile infection.

    PubMed

    Rodriguez, Sandra; Hernandez, Marlow B; Tarchini, Giorgio; Zaleski, Megan; Vatanchi, Marjon; Cardona, Lyssette; Castro-Pavia, Fernando; Schneider, Alison

    2014-11-01

    Antibiotics often are given to prevent infections but also constitute a risk factor for Clostridium difficile infection (CDI). Metronidazole is an effective treatment for CDI. We investigated whether prophylactic administration of metronidazole to patients before they receive other antibiotics reduces the risk of CDI. We performed a retrospective cohort analysis of data collected from 12,026 high-risk patients admitted to Cleveland Clinic Foundation Hospitals from 2008 through 2012. High-risk patients were defined as age 55 or older who received a broad-spectrum antibiotic (piperacillin-tazobactam or ciprofloxacin) and a gastric acid suppressant (a proton pump inhibitor or a histamine-2 receptor blocker) during their hospitalization. Development of CDI was compared between patients who received metronidazole for non-CDI indications before broad-spectrum antibiotics (n = 811) and those who did not (n = 11,215). Logistic regression was used to control for patient demographics and comorbidities. The rate of CDI was 1.4% (n = 11) among the patients who received metronidazole for non-CDI indications and 6.5% (n = 728) among those who did not. This was observed to be an 80% reduction in CDI among patients who received metronidazole (odds ratio, 0.21; 95% confidence interval, 0.11-0.38; P < .001), adjusted for age, sex, and comorbidities. Based on a retrospective analysis, metronidazole might be used to prevent CDI in certain high-risk patients. Prospective controlled trials are necessary before making further recommendations. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Non-inferiority of pulsed xenon UV light versus bleach for reducing environmental Clostridium difficile contamination on high-touch surfaces in Clostridium difficile infection isolation rooms

    PubMed Central

    Ghantoji, Shashank S.; Stibich, Mark; Stachowiak, Julie; Cantu, Sherry; Adachi, Javier A.; Raad, Issam I.

    2015-01-01

    The standard for Clostridium difficile surface decontamination is bleach solution at a concentration of 10 % of sodium hypochlorite. Pulsed xenon UV light (PX-UV) is a means of quickly producing germicidal UV that has been shown to be effective in reducing environmental contamination by C. difficile spores. The purpose of this study was to investigate whether PX-UV was equivalent to bleach for decontamination of surfaces in C. difficile infection isolation rooms. High-touch surfaces in rooms previously occupied by C. difficile infected patients were sampled after discharge but before and after cleaning using either bleach or non-bleach cleaning followed by 15 min of PX-UV treatment. A total of 298 samples were collected by using a moistened wipe specifically designed for the removal of spores. Prior to disinfection, the mean contamination level was 2.39 c.f.u. for bleach rooms and 22.97 for UV rooms. After disinfection, the mean level of contamination for bleach was 0.71 c.f.u. (P = 0.1380), and 1.19 c.f.u. (P = 0.0017) for PX-UV disinfected rooms. The difference in final contamination levels between the two cleaning protocols was not significantly different (P = 0.9838). PX-UV disinfection appears to be at least equivalent to bleach in the ability to decrease environmental contamination with C. difficile spores. Larger studies are needed to validate this conclusion. PMID:25627208

  17. Non-inferiority of pulsed xenon UV light versus bleach for reducing environmental Clostridium difficile contamination on high-touch surfaces in Clostridium difficile infection isolation rooms.

    PubMed

    Ghantoji, Shashank S; Stibich, Mark; Stachowiak, Julie; Cantu, Sherry; Adachi, Javier A; Raad, Issam I; Chemaly, Roy F

    2015-02-01

    The standard for Clostridium difficile surface decontamination is bleach solution at a concentration of 10 % of sodium hypochlorite. Pulsed xenon UV light (PX-UV) is a means of quickly producing germicidal UV that has been shown to be effective in reducing environmental contamination by C. difficile spores. The purpose of this study was to investigate whether PX-UV was equivalent to bleach for decontamination of surfaces in C. difficile infection isolation rooms. High-touch surfaces in rooms previously occupied by C. difficile infected patients were sampled after discharge but before and after cleaning using either bleach or non-bleach cleaning followed by 15 min of PX-UV treatment. A total of 298 samples were collected by using a moistened wipe specifically designed for the removal of spores. Prior to disinfection, the mean contamination level was 2.39 c.f.u. for bleach rooms and 22.97 for UV rooms. After disinfection, the mean level of contamination for bleach was 0.71 c.f.u. (P = 0.1380), and 1.19 c.f.u. (P = 0.0017) for PX-UV disinfected rooms. The difference in final contamination levels between the two cleaning protocols was not significantly different (P = 0.9838). PX-UV disinfection appears to be at least equivalent to bleach in the ability to decrease environmental contamination with C. difficile spores. Larger studies are needed to validate this conclusion.

  18. 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

  19. Process and Outcome of Fecal Microbiota Transplants in Patients With Recurrent Clostridium difficile Infection: A Prospective Study.

    PubMed

    Walton, Janice; Burns, Denise; Gaehle, Kay E

    The incidence of Clostridium difficile infection is on the rise worldwide, causing high mortality rates and costing patients, hospitals, and insurance companies millions of dollars annually. Fecal microbiota transplants successfully treat recurrent C. difficile infections unresponsive to standard pharmacologic treatment such as flagyl, vancomycin, or rifaximin. Evidence in the literature provided the foundation for the development and refinement of this fecal microbiota transplant protocol. During the initial phase of the project, the protocol included patient selection criteria, donor screening/selection, infection control, fecal processing and delivery, and patient pre and postprocedure education. This article highlights the second phase of prospective testing of a nurse-driven protocol to implement fecal microbiota transplantation in patients with recurrent C. difficile infection. All stages of the protocol are explained as well as rationale for component parts to achieve successful patient outcomes when the protocol is carefully followed.

  20. Decreased Cure and Increased Recurrence Rates for Clostridium difficile Infection Caused by the Epidemic C. difficile BI Strain

    PubMed Central

    Petrella, Laurica A.; Sambol, Susan P.; Cheknis, Adam; Nagaro, Kristin; Kean, Yin; Sears, Pamela S.; Babakhani, Farah; Johnson, Stuart; Gerding, Dale N.

    2012-01-01

    Background. An epidemic strain of Clostridium difficile designated by restriction endonuclease analysis (REA) as group BI has caused multiple outbreaks of severe C. difficile infection (CDI). The treatment response of patients infected with this strain is uncertain. Methods. Clostridium difficile isolates were collected from 2 phase 3 clinical trials comparing fidaxomicin to vancomycin and typed using REA. Clinical cure and recurrence outcomes were analyzed by strain type of the infecting organism, BI and non-BI, using both univariate and multivariate analyses. Results. From 999 patients, 719 isolates were available for typing (356 fidaxomicin treated and 363 vancomycin treated). BI was the most common REA group (34% of isolates). Patients infected with BI had lower cure rates (86.6%; 214 of 247) than those infected with non-BI strains (94.3%; 445 of 472) (P < .001). The cure rate difference between the BI and non-BI patients was significant for both vancomycin (P = .02) and fidaxomicin (P = .007). BI patients had a recurrence rate of 27.4% (51 of 186), compared with a recurrence rate of 16.6% (66 of 397) in non-BI patients (P = .002). By multivariate analysis, BI infection was statistically significant as a risk factor for reduced cure (odds ratio [OR], 0.48; 95% confidence interval [CI], .27–.85; P = .030) and for increased recurrence (OR, 1.57; 95% CI, 1.01–2.45; P = .046). Conclusions. The clinical cure rate of patients infected with the epidemic BI C. difficile strain is lower than the cure rate of those infected with non-BI strains whether treated with fidaxomicin or vancomycin. Similarly, the CDI recurrence rate is increased in patients with the BI strain compared with patients with other C. difficile strains. PMID:22523271

  1. 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

  2. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection.

    PubMed

    Stevens, Vanessa; Dumyati, Ghinwa; Fine, Lynn S; Fisher, Susan G; van Wijngaarden, Edwin

    2011-07-01

    Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is most commonly associated with changes in normal intestinal flora caused by administration of antibiotics. Few studies have examined the risk of CDI associated with total dose, duration, or number of antibiotics while taking into account the complex changes in exposures over time. A retrospective cohort study conducted from 1 January to 31 December 2005 among hospitalized patients 18 years or older receiving 2 or more days of antibiotics. The study identified 10,154 hospitalizations for 7,792 unique patients and 241 cases of CDI, defined as the detection of C. difficile toxin in a diarrheal stool sample within 60 days of discharge. We observed dose-dependent increases in the risk of CDI associated with increasing cumulative dose, number of antibiotics, and days of antibiotic exposure. Compared to patients who received only 1 antibiotic, the adjusted hazard ratios (HRs) for those who received 2, 3 or 4, or 5 or more antibiotics were 2.5 (95% confidence interval [CI] 1.6-4.0), 3.3 (CI 2.2-5.2), and 9.6 (CI 6.1-15.1), respectively. The receipt of fluoroquinolones was associated with an increased risk of CDI, while metronidazole was associated with reduced risk. Cumulative antibiotic exposures appear to be associated with the risk of CDI. Antimicrobial stewardship programs that focus on the overall reduction of total dose as well as number and days of antibiotic exposure and the substitution of high-risk antibiotic classes for lower-risk alternatives may reduce the incidence of hospital-acquired CDI. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

  3. Effect of Lactobacillus acidophilus & epidermal growth factor on experimentally induced Clostridium difficile infection

    PubMed Central

    Kaur, Sukhminderjit; Vaishnavi, Chetana; Prasad, Kaushal Kishor; Ray, Pallab; Kochhar, Rakesh

    2011-01-01

    Background & objectives: Clostridium difficile-associated disease (CDAD) remains an important nosocomial ailment. Antimicrobial therapy used for CDAD gives inconsistent results. This experimental study was planned to investigate the beneficial effects of Lactobacillus acidophilus and epidermal growth factor (EGF) for CDAD management. Methods: Among 10 groups of BALB/c mice (6 in each), group 1 served as controls receiving no inoculum. Animals in groups 2-10 received C. difficile, those in groups 3, 6 and 9 received L. acidophilus and those in groups 4, 7 and 10 received EGF after C. difficile inoculation. Animals in groups 5-7 were pre-treated with ampicillin and those in groups 8-10 with lansoprazole prior to C. difficile. The animals were killed and investigated for colonisation by C. difficile and toxin production, myeloperoxidase (MPO) activity and histopathology. Results: Colonisation by C. difficile was found to be significantly different (P<0.001) in the various groups. C. difficile toxin titres and MPO activity were significantly lower in animals given L. acidophilus and EGF after ampicillin (groups 6 and 7) and lansoprazole (groups 9 and 10). The severity of acute inflammation was also significantly less (P<0.05) in caecal and colonic segments of animals in groups 6 and 7 compared to those in group 5. Although the severity of acute inflammation was less in the caecal and colonic segment of animals in groups 9 and 10, the reduction was not significant compared to group 8. Interpretation & conclusions: Our findings showed that the administration of L. acidophilus and EGF reduced the severity of C. difficile infection in the experimental animals. PMID:21537099

  4. Toxin-Mediated Paracellular Transport of Antitoxin Antibodies Facilitates Protection against Clostridium difficile Infection

    PubMed Central

    Zhang, Z.; Chen, X.; Hernandez, L. D.; Lipari, P.; Flattery, A.; Chen, S.-C.; Kramer, S.; Polishook, J. D.; Racine, F.; Cape, H.; Kelly, C. P.

    2014-01-01

    The exotoxins TcdA and TcdB are the major virulence factors of Clostridium difficile. Circulating neutralizing antitoxin antibodies are protective in C. difficile infection (CDI), as demonstrated, in part, by the protective effects of actoxumab and bezlotoxumab, which bind to and neutralize TcdA and TcdB, respectively. The question of how systemic IgG antibodies neutralize toxins in the gut lumen remains unresolved, although it has been suggested that the Fc receptor FcRn may be involved in active antibody transport across the gut epithelium. In this study, we demonstrated that genetic ablation of FcRn and excess irrelevant human IgG have no impact on actoxumab-bezlotoxumab-mediated protection in murine and hamster models of CDI, suggesting that Fc-dependent transport of antibodies across the gut wall is not required for efficacy. Tissue distribution studies in hamsters suggest, rather, that the transport of antibodies depends on toxin-induced damage to the gut lining. In an in vitro two-dimensional culture system that mimics the architecture of the intestinal mucosal epithelium, toxins on the apical side of epithelial cell monolayers are neutralized by basolateral antibodies, and antibody transport across the cell layer is dramatically increased upon addition of toxin to the apical side. Similar data were obtained with F(ab′)2 fragments, which lack an Fc domain, consistent with FcRn-independent paracellular, rather than transcellular, transport of antibodies. Kinetic studies show that initial damage caused by apical toxin is required for efficient neutralization by basolateral antibodies. These data may represent a general mechanism of humoral response-mediated protection against enteric pathogens. PMID:25385797

  5. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials.

    PubMed

    Johnson, Stuart; Louie, Thomas J; Gerding, Dale N; Cornely, Oliver A; Chasan-Taber, Scott; Fitts, David; Gelone, Steven P; Broom, Colin; Davidson, David M

    2014-08-01

    Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is treated with antibiotics, contributing to ongoing disruption of the colonic microbiota and CDI recurrence. Two multinational trials were conducted to compare the efficacy of tolevamer, a nonantibiotic, toxin-binding polymer, with vancomycin and metronidazole. Patients with CDI were randomly assigned in a 2:1:1 ratio to oral tolevamer 9 g (loading dose) followed by 3 g every 8 hours for 14 days, vancomycin 125 mg every 6 hours for 10 days, or metronidazole 375 mg every 6 hours for 10 days. The primary endpoint was clinical success, defined as resolution of diarrhea and absence of severe abdominal discomfort for more than 2 consecutive days including day 10. In a pooled analysis, 563 patients received tolevamer, 289 received metronidazole, and 266 received vancomycin. Clinical success of tolevamer was inferior to both metronidazole and vancomycin (P < .001), and metronidazole was inferior to vancomycin (P = .02; 44.2% [n = 534], 72.7% [n = 278], and 81.1% [n = 259], respectively). Clinical success in patients with severe CDI who received metronidazole was 66.3% compared with vancomycin, which was 78.5%. (P = .059). A post-hoc multivariate analysis that excluded tolevamer found 3 factors that were strongly associated with clinical success: vancomycin treatment, treatment-naive status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups. Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole.

    PubMed

    Pham, Vy P; Luce, Andrea M; Ruppelt, Sara C; Wei, Wenjing; Aitken, Samuel L; Musick, William L; Roux, Ryan K; Garey, Kevin W

    2015-10-01

    Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection

    PubMed Central

    Chilton, C. H.; Crowther, G. S.; Śpiewak, K.; Brindell, M.; Singh, G.; Wilcox, M. H.; Monaghan, T. M.

    2016-01-01

    Objectives Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe3+ saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe3+ saturated) bovine holo-lactoferrin (holo-bLf) in a human in vitro gut model that simulates CDI. Methods Two parallel triple-stage chemostat gut models were inoculated with pooled human faeces and spiked with C. difficile spores (strain 027 210, PCR ribotype 027). Holo- or apo-bLf was instilled (5 mg/mL, once daily) for 35 days. After 7 days, clindamycin was instilled (33.9 mg/L, four times daily) to induce simulated CDI. Indigenous microflora populations, C. difficile total counts and spores, cytotoxin titres, short chain fatty acid concentrations, biometal concentrations, lactoferrin concentration and iron content of lactoferrin were monitored daily. Results In the apo-bLf model, germination of C. difficile spores occurred 6 days post instillation of clindamycin, followed by rapid vegetative cell proliferation and detectable toxin production. By contrast, in the holo-bLf model, only a modest vegetative cell population was observed until 16 days post antibiotic administration. Notably, no toxin was detected in this model. In separate batch culture experiments, holo-bLf prevented C. difficile vegetative cell growth and toxin production, whereas apo-bLf and iron alone did not. Conclusions Holo-bLf, but not apo-bLf, delayed C. difficile growth and prevented toxin production in a human gut model of CDI. This inhibitory effect may be iron independent. These observations suggest that bLf in its iron-saturated state could be used as a novel preventative or treatment strategy for CDI. PMID:26759363

  8. 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.

  9. Evaluation of a bedside scoring system for predicting clinical cure and recurrence of Clostridium difficile infections.

    PubMed

    Jacobson, Shauna M; Slain, Douglas

    2015-11-01

    The accuracy of a bedside scoring system, ATLAS, for predicting clinical cure and recurrence of Clostridium difficile infections (CDIs) was evaluated. A single-center retrospective medical record review was performed for symptomatic adult patients with stool assay-diagnosed CDI treated with metronidazole or vancomycin or both. Multiple logistic regression analysis was performed to assess the potential association of the ATLAS score and other potential factors on achieving cure and 90-day CDI recurrence. ATLAS scores were calculated, and risk factors for severe CDI, severe-complicated CDI, decreased cure rates, and recurrence were recorded. Data from 245 adult patients were assessed. ATLAS scores showed a significant inverse association with the cure rate (p = 0.009) but not with the 90-day recurrence rate (p = 0.901). The only ATLAS component to be independently associated (inversely) with cure was the concomitant use of antibiotics (p = 0.022). Metronidazole was initiated in 97% of patients, with 32% switching to oral vancomycin. Longer courses of vancomycin were associated with a higher cure rate (p = 0.0009) but not with recurrence (p = 0.170). Complicated cases were less likely to be cured (p = 0.027) and more likely to recur within 90 days (p = 0.002). Antibiotics continued after CDI treatment was associated with recurrence (p = 0.055). A low ATLAS score was found to correlate with higher cure rates in patients with CDI receiving metronidazole, oral vancomycin, or both. However, the score could not predict CDI recurrence. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  10. Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile

    PubMed Central

    Engevik, Melinda A.; Engevik, Kristen A.; Yacyshyn, Mary Beth; Wang, Jiang; Hassett, Daniel J.; Darien, Benjamin; Yacyshyn, Bruce R.

    2014-01-01

    Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets. In cell lines, C. difficile toxin B has been shown to inhibit Na+/H+ exchanger 3 (NHE3) and loss of NHE3 in mice results in an altered intestinal environment coupled with a transformed gut microbiota composition. However, this has yet to be established in vivo in humans. We hypothesize that C. difficile toxin inhibits NHE3, resulting in alteration of the intestinal environment and gut microbiota. Our results demonstrate that CDI patient biopsy specimens have decreased NHE3 expression and CDI stool has elevated Na+ and is more alkaline compared with stool from healthy individuals. CDI stool microbiota have increased Bacteroidetes and Proteobacteria and decreased Firmicutes phyla compared with healthy subjects. In vitro, C. difficile grows optimally in the presence of elevated Na+ and alkaline pH, conditions that correlate to changes observed in CDI patients. To confirm that inhibition of NHE3 was specific to C. difficile, human intestinal organoids (HIOs) were injected with C. difficile or healthy and CDI stool supernatant. Injection of C. difficile and CDI stool decreased NHE3 mRNA and protein expression compared with healthy stool and control HIOs. Together these data demonstrate that C. difficile inhibits NHE3 in vivo, which creates an altered environment favored by C. difficile. PMID:25552580

  11. 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.

  12. Alteration of the murine gastrointestinal microbiota by tigecycline leads to increased susceptibility to Clostridium difficile infection.

    PubMed

    Bassis, Christine M; Theriot, Casey M; Young, Vincent B

    2014-05-01

    Antibiotics can play dual roles in Clostridium difficile infection (CDI); antibiotic treatment increases the risk of CDI, and antibiotics are used to treat CDI. The glycylcycline antibiotic tigecycline has broad antimicrobial activity, yet it is rarely associated with the development of CDI, presumably due to its activity against C. difficile. In this study, we investigated how tigecycline treatment affects the structure of the gut microbiota and susceptibility to CDI by treating mice with tigecycline (n = 20) or saline (n = 8) for 10 days. A sequence analysis of the bacterial 16S rRNA gene amplicons was used to monitor changes in the fecal microbiota. A subset of the mice was followed for 5 weeks after the end of treatment. The remaining mice were challenged with C. difficile strain VPI 10463 spores 2 days after the tigecycline treatment ended. Tigecycline treatment resulted in major shifts in the gut microbiota, including large decreases in Bacteroidetes levels and large increases in Proteobacteria levels. Mice with tigecycline-altered microbial communities were susceptible to challenge with C. difficile spores and developed clinical signs of severe CDI. Five weeks after the cessation of tigecycline treatment, the recovery of the bacterial community was incomplete and diversity was lower than in the untreated controls. Antibiotics with intrinsic activity against C. difficile can still alter the microbiota in a way that leads to susceptibility to CDI after discontinuation of the drug. These results indicate that microbiotic dynamics are key in the development of CDI, and a better understanding of these dynamics may lead to better strategies to prevent and treat this disease.

  13. 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.

  14. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection.

    PubMed

    Hu, Mary Y; Katchar, Kianoosh; Kyne, Lorraine; Maroo, Seema; Tummala, Sanjeev; Dreisbach, Valley; Xu, Hua; Leffler, Daniel A; Kelly, Ciarán P

    2009-04-01

    Prevention of recurrent Clostridium difficile infection (CDI) is a substantial therapeutic challenge. A previous prospective study of 63 patients with CDI identified risk factors associated with recurrence. This study aimed to develop a prediction rule for recurrent CDI using the above derivation cohort and prospectively evaluate the performance of this rule in an independent validation cohort. The clinical prediction rule was developed by multivariate logistic regression analysis and included the following variables: age>65 years, severe or fulminant illness (by the Horn index), and additional antibiotic use after CDI therapy. A second rule combined data on serum concentrations of immunoglobulin G (IgG) against toxin A with the clinical predictors. Both rules were then evaluated prospectively in an independent cohort of 89 patients with CDI. The clinical prediction rule discriminated between patients with and without recurrent CDI, with an area under the curve of the receiver-operating-characteristic curve of 0.83 (95% confidence interval [CI]: 0.70-0.95) in the derivation cohort and 0.80 (95% CI: 0.67-0.92) in the validation cohort. The rule correctly classified 77.3% (95% CI: 62.2%-88.5%) and 71.9% (95% CI: 59.2%-82.4%) of patients in the derivation and validation cohorts, respectively. The combined rule performed well in the derivation cohort but not in the validation cohort (area under the curve of the receiver-operating-characteristic curve, 0.89 vs 0.62; diagnostic accuracy, 93.8% vs 69.2%, respectively). We prospectively derived and validated a clinical prediction rule for recurrent CDI that is simple, reliable, and accurate and can be used to identify high-risk patients most likely to benefit from measures to prevent recurrence.

  15. The undiagnosed cases of Clostridium difficile infection in a whole nation: where is the problem?

    PubMed

    Alcalá, L; Martín, A; Marín, M; Sánchez-Somolinos, M; Catalán, P; Peláez, T; Bouza, E

    2012-07-01

    Underdiagnosis of Clostridium difficile infection (CDI) because of lack of clinical suspicion or the use of non-sensitive diagnostic techniques is a known problem whose real magnitude has not yet been quantified. In order to estimate the extent of this underdiagnosis, we performed C. difficile cultures on all unformed stool specimens sent-irrespective of the type of request-to a series of laboratories in Spain on a single day. The specimens were cultured, and isolates were characterized at a central reference laboratory. A total of 807 specimens from 730 patients aged ≥ 2 years were selected from 118 laboratories covering 75.4% of the Spanish population. The estimated rate of hospital-acquired CDI was 2.4 episodes per 1000 admissions or 3.8 episodes per 10,000 patient-days. Only half of the episodes occurred in patients hospitalized for >2 days. Two of every three episodes went undiagnosed or were misdiagnosed, owing to non-sensitive diagnostic tests (19.0%) or lack of clinical suspicion and request (47.6%; mostly young people or non-hospitalized patients). The main ribotypes were 014/020 (20.5%), 001 (18.2%), and 126/078 (18.2%). No ribotype 027 strains were detected. Strains were fully susceptible to metronidazole and vancomycin. CDI was underdiagnosed in diarrhoeic stools in a high proportion of episodes, owing to the use of non-sensitive techniques or lack of clinical suspicion, particularly in people aged <65 years or patients with community-acquired diarrhoea. C. difficile toxins should be routinely sought in unformed stools of any origin sent for microbiological diagnosis. The ribotype 027 clone has not yet disseminated in Spain.

  16. Persistence of Clostridium difficile RT 237 infection in a Western Australian piggery.

    PubMed

    Moono, Peter; Putsathit, Papanin; Knight, Daniel R; Squire, Michele M; Hampson, David J; Foster, Niki F; Riley, Thomas V

    2016-02-01

    Clostridium difficile is commonly associated with healthcare-related infections in humans, and is an emerging pathogen in food animal species. There is potential for transmission of C. difficile from animals or animal products to humans. This study aimed to determine if C. difficile RT 237 had persisted in a Western Australian piggery or if there had been a temporal change in C. difficile diversity. C. difficile carriage in litters with and without diarrhea was investigated, as was the acquisition of C. difficile over time using cohort surveys. Rectal swabs were obtained from piglets aged 1-10 days to determine prevalence of C. difficile carriage and samples were obtained from 20 piglets on days 1, 7, 13, 20, and 42 of life to determine duration of shedding. Isolation of C. difficile from feces was achieved by selective enrichment culture. All isolates were characterized by standard molecular typing. Antimicrobial susceptibility testing was performed on selected isolates (n = 29). Diarrheic piglets were more likely to shed C. difficile than the non-diseased (p = 0.0124, χ2). In the cohort study, C. difficile was isolated from 40% samples on day 1, 50% on day 7, 20% on day 13, and 0% on days 20 and 42. All isolates were RT 237 and no antimicrobial resistance was detected. The decline of shedding of C. difficile to zero has public health implications because slaughter age pigs have a low likelihood of spreading C. difficile to consumers via pig meat.

  17. Elevated Fecal Calprotectin Associates with Adverse Outcomes from Clostridium difficile Infection in Older Adults

    PubMed Central

    Rao, Krishna; Santhosh, Kavitha; Mogle, Jill A.; Higgins, Peter D. R.; Young, Vincent B.

    2016-01-01

    Background Clostridium difficile infection (CDI) causes a mild to moderate colitis in most patients, but some, especially older adults, develop severe, adverse outcomes. Biomarkers predicting outcomes are needed to optimize treatments. This study tested whether fecal calprotectin associated with a composite primary outcome of complicated CDI (intensive care unit admission, colectomy, or death due to CDI within 30 days of diagnosis) and/or 8-week recurrence. Methods Stool was collected in Cary-Blair media at the time of diagnosis from inpatients of age >60 years that tested positive for C. difficile (enzyme immunoassay [EIA] for toxin A/B or polymerase chain reaction for the tcdB gene). Fecal calprotectin was measured and normalized to solid stool weight. Analysis was performed using logistic regression. Variables were selected for the final model using likelihood ratio tests. Results Fifty patients were included with a mean age 72.8 (± 7.5), and 13 (26%) developed the primary outcome. Clinical variables such as age, gender, and comorbid disease did not associate with complicated CDI/recurrence, nor did traditional biomarkers such as serum albumin or white blood cell count. A high normalized fecal calprotectin (>2000 µg/g) associated with the primary outcome in the final model after adjustment for gender and detectable fecal toxin(s) by EIA (OR 24.9, 95% CI 2.4–257.9, P=.007) with a specificity of 91.9%. Conclusion This study provides evidence that fecal calprotectin level associates with complications from CDI in older adults. Further studies are required to validate these findings in larger cohorts and incorporate them into clinical prediction algorithms. PMID:27206404

  18. Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole

    PubMed Central

    Pham, Vy P.; Luce, Andrea M.; Ruppelt, Sara C.; Wei, Wenjing; Aitken, Samuel L.; Musick, William L.; Roux, Ryan K.

    2015-01-01

    Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole. PMID:26195522

  19. 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

  20. A chimeric toxin vaccine protects against primary and recurrent Clostridium difficile infection.

    PubMed

    Wang, Haiying; Sun, Xingmin; Zhang, Yongrong; Li, Shan; Chen, Kevin; Shi, Lianfa; Nie, Weijia; Kumar, Raj; Tzipori, Saul; Wang, Jufang; Savidge, Tor; Feng, Hanping

    2012-08-01

    The global emergence of Clostridium difficile infection (CDI) has contributed to the recent surge in severe antibiotic-associated diarrhea and colonic inflammation. C. difficile produces two homologous glucosylating exotoxins, TcdA and TcdB, both of which are pathogenic and require neutralization to prevent disease occurrence. However, because of their large size and complex multifunctional domain structures, it has been a challenge to produce native recombinant toxins that may serve as vaccine candidates. Here, we describe a novel chimeric toxin vaccine that retains major neutralizing epitopes from both toxins and confers complete protection against primary and recurrent CDI in mice. Using a nonpathogenic Bacillus megaterium expression system, we generated glucosyltransferase-deficient holotoxins and demonstrated their loss of toxicity. The atoxic holotoxins induced potent antitoxin neutralizing antibodies showing little cross-immunogenicity or protection between TcdA and TcdB. To facilitate simultaneous protection against both toxins, we generated an active clostridial toxin chimera by switching the receptor binding domain of TcdB with that of TcdA. The toxin chimera was fully cytotoxic and showed potent proinflammatory activities. This toxicity was essentially abolished in a glucosyltransferase-deficient toxin chimera, cTxAB. Parenteral immunization of mice or hamsters with cTxAB induced rapid and potent neutralizing antibodies against both toxins. Complete and long-lasting disease protection was conferred by cTxAB vaccinations against both laboratory and hypervirulent C. difficile strains. Finally, prophylactic cTxAB vaccination prevented spore-induced disease relapse, which constitutes one of the most significant clinical issues in CDI. Thus, the rational design of recombinant chimeric toxins provides a novel approach for protecting individuals at high risk of developing CDI.

  1. 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.

  2. First recurrence of Clostridium difficile infection: clinical relevance, risk factors, and prognosis.

    PubMed

    Larrainzar-Coghen, T; Rodriguez-Pardo, D; Puig-Asensio, M; Rodríguez, V; Ferrer, C; Bartolomé, R; Pigrau, C; Fernández-Hidalgo, N; Pumarola, T; Almirante, B

    2016-03-01

    Therapy for recurrent Clostridium difficile-associated diarrhea (CDAD) is challenging. We evaluated the frequency, associated risk factors, and prognosis of first CDAD recurrences. Prospective cohort study of all consecutive cases of primary CDAD diagnosed in a university hospital from January 2006 to June 2013. Recurrent infection was defined as reappearance of symptoms within 8 weeks of the primary diagnosis, provided that CDAD symptoms had previously resolved and a new toxin test was positive. Predictors of a first episode of recurrent CDAD were determined by logistic regression analysis. In total, 502 patients (51.6 % men) with a mean age of 62.3 years (SD 18.5) had CDAD; 379 (76 %) were cured, 61 (12 %) had a first recurrence, 52 (10 %) died within 30 days of the CDAD diagnosis, nine (2 %) required colectomy, and one was lost to follow-up. Among the 61 patients with a first recurrence, 36 (59.3 %) were cured, 15 (23.7 %) had a second recurrence, nine (15.3 %) died, and one (1.7 %) required colectomy. On multivariate analysis, age older than 65 years (OR 2.04; 95 % CI, 1.14-3.68; P < 0.02) and enteral nutrition (OR, 3.62; 95%CI, 1.66-7.87; P < 0.01) were predictors of a first recurrence. A risk score was developed for first CDAD recurrence using the predictive factors and selected biological variables. In our CDAD cohort, 12 % of patients had a first recurrence of this disease, in which the prognosis was less favorable than that of the primary episode, as it heralded a higher risk of additional recurrences. Patient age and enteral nutrition were predictors of a first recurrence.

  3. Impact of vancomycin faecal concentrations on clinical and microbiological outcomes in Clostridium difficile infection.

    PubMed

    Thabit, Abrar K; Nicolau, David P

    2015-08-01

    To assess the impact of faecal vancomycin concentrations on clinical and microbiological outcomes in patients with Clostridium difficile infection (CDI) and whether these concentrations vary with stool consistency and frequency, faecal concentrations of vancomycin were measured in stools collected at various times from patients initiated on 125mg every 6h (q6h) for 10 days. Stool consistency and frequency were determined over the course of therapy. Clinical and microbiological outcomes were assessed during therapy, at the end of therapy (EOT) and during a 19-38-day follow-up visit. Faecal vancomycin concentrations in 55 stool samples from 15 patients ranged from 175-6299μg/g at Days 3-5 of therapy (midpoint), 17-5277μg/g at EOT and 0-70μg/g at follow-up. Clinical cure or failure at EOT and at follow-up was not dependent on vancomycin concentrations measured at the midpoint (P=0.72) or at EOT (P=0.76). Likewise, concentrations at EOT and at follow-up did not predict colonisation at follow-up (P=0.85 and 0.71, respectively). Faecal vancomycin concentrations during the course of therapy (Days 3-5) did not differ with either stool consistency or frequency (P=0.94 and 0.16, respectively). However, after completion of therapy, patients with more frequent stools showed higher concentrations than patients with less frequent stools (P=0.04). Oral vancomycin 125mg q6h led to faecal concentrations that did not predict clinical outcomes of CDI in terms of cure or gut colonisation and did not vary with stool consistency and frequency.

  4. Alteration of the Murine Gastrointestinal Microbiota by Tigecycline Leads to Increased Susceptibility to Clostridium difficile Infection

    PubMed Central

    Bassis, Christine M.; Young, Vincent B.

    2014-01-01

    Antibiotics can play dual roles in Clostridium difficile infection (CDI); antibiotic treatment increases the risk of CDI, and antibiotics are used to treat CDI. The glycylcycline antibiotic tigecycline has broad antimicrobial activity, yet it is rarely associated with the development of CDI, presumably due to its activity against C. difficile. In this study, we investigated how tigecycline treatment affects the structure of the gut microbiota and susceptibility to CDI by treating mice with tigecycline (n = 20) or saline (n = 8) for 10 days. A sequence analysis of the bacterial 16S rRNA gene amplicons was used to monitor changes in the fecal microbiota. A subset of the mice was followed for 5 weeks after the end of treatment. The remaining mice were challenged with C. difficile strain VPI 10463 spores 2 days after the tigecycline treatment ended. Tigecycline treatment resulted in major shifts in the gut microbiota, including large decreases in Bacteroidetes levels and large increases in Proteobacteria levels. Mice with tigecycline-altered microbial communities were susceptible to challenge with C. difficile spores and developed clinical signs of severe CDI. Five weeks after the cessation of tigecycline treatment, the recovery of the bacterial community was incomplete and diversity was lower than in the untreated controls. Antibiotics with intrinsic activity against C. difficile can still alter the microbiota in a way that leads to susceptibility to CDI after discontinuation of the drug. These results indicate that microbiotic dynamics are key in the development of CDI, and a better understanding of these dynamics may lead to better strategies to prevent and treat this disease. PMID:24590475

  5. Clostridium difficile colonization and/or infection during infancy and the risk of childhood allergic diseases.

    PubMed

    Lee, Sun Hwa; Gong, Yun Na; Ryoo, Eell

    2017-05-01

    The gut microbiota can influence several diseases through immune modulation; however, the exact role of microbes such as Clostridium difficileand the relationship between microbiota colonization and allergic diseases are not well known. This study aimed to determine the relationship between C. difficilecolonization and/or infection (CDCI) during infancy and allergic diseases during early childhood. Infants 1-12 months of age presenting changes in bowel habits for more than 2 weeks were enrolled in this study. After dividing them into 2 groups according to the presence and absence of C. difficile, the risk of allergic disease development during childhood was identified and compared. Sixty-five patients were included in this study; 22 (33.8%) were diagnosed with CDCI. No significant differences were observed in baseline characteristics between the C. difficile-positive and -negative groups except for antibiotic exposure (22.7% vs. 60.5%, P=0.004). Compared to the C. difficile-negative group, the risk of developing at least one allergic disease was higher in the C. difficile-positive group after adjusting other variables (adjusted odds ratios, 5.61; 95% confidence interval, 1.52-20.74; P=0.007). Furthermore, food allergies were more prevalent in the C. difficile-positive group (P=0.03). CDCI during infancy were associated with a higher risk of developing allergic diseases during early childhood. These results suggest that CDCI during infancy might reflect the reduced diversity of the intestinal microbiota, which is associated with an increased risk of allergic sensitization. To identify the underlying mechanism, further investigation and a larger cohort study will be needed.

  6. 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.

  7. 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.

  8. Effect of Clostridium difficile Prevalence in Hospitals and Nursing Homes on Risk of Infection.

    PubMed

    Joyce, Nina R; Mylonakis, Eleftherios; Mor, Vincent

    2017-07-01

    To assess the effect of facility Clostridium difficile infection (CDI) prevalence on risk of healthcare facility (HFC) acquired CDI. Retrospective cohort study. Medicare fee-for-service (FFS) claims and skilled nursing facility (SNF) Minimum Data Set 3.0 assessments. Medicare beneficiaries with 90 days or more of no contact with a HCF before a hospital admission without a CDI diagnosis. Participants were separated into two cohorts: discharged to the community and discharged to a SNF. Risk of HCF-acquired CDI associated with CDI prevalence at the index facility measured according to 30-day rehospitalization with a discharge diagnosis of CDI or diagnosis in the SNF after admission. Hospital and SNF CDI prevalence were categorized into three groups: 0% and above and below the median value for facilities with greater than 0% prevalence. Of 817,900 eligible individuals, there were 553,423 admissions in the first cohort (discharged to the community) and 315,109 in the second (discharged to a SNF). In the first cohort, the risk of HCF-acquired CDI was higher for individuals admitted to hospitals with CDI prevalence less than the median (relative risk (RR) = 1.58, 95% confidence interval (CI) = 1.18-2.12) and greater than the median (RR = 2.56, 95% CI = 1.91-3.45) than for those with no CDI. In the second cohort, the risk of HCF-acquired CDI was greater for individuals admitted to a hospital (RR = 1.89, 95% CI = 1.49-2.39) and a SNF (RR = 1.48, 95% CI = 1.31-1.67) with CDI prevalence greater than the median. The risk of HCF-acquired CDI is greater for noninfected individuals admitted to hospitals and SNFs with a high prevalence of CDI. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  9. The effect of polydextrose and probiotic lactobacilli in a Clostridium difficile–infected human colonic model

    PubMed Central

    Forssten, Sofia D.; Röytiö, Henna; Hibberd, Ashley A.; Ouwehand, Arthur C.

    2015-01-01

    Background Clostridium difficile is a natural resident of the intestinal microbiota; however, it becomes harmful when the normal intestinal microbiota is disrupted, and overgrowth and toxin production occurs. The toxins can cause bloating and diarrhoea, which may cause severe disease and have the potential to cause outbreaks in hospitals and other healthcare settings. Normally, antibiotic agents are used for treatment, although for some of the patients, these treatments provide only a temporary relief with a recurrence of C. difficile–associated diarrhoea. Objective The effects of polydextrose (PDX), Lactobacillus acidophilus NCFM, and L. paracasei Lpc-37 on the growth of C. difficile were investigated in an in vitro model of infected human large intestine. Design The semi-continuous colonic model is composed of four connected vessels inoculated with human faecal microbes and spiked with pathogenic C. difficile (DSM 1296). PDX in two concentrations (2 and 4%), NCFM, and Lpc-37 were fed to the system during the 2-day simulation, and the growth of C. difficile and several other microbial groups were monitored using quantitative polymerase chain reaction (qPCR) and 16S rDNA sequencing. Results The microbial community structure of the simulation samples was closely grouped according to treatment, and the largest shifts in the microbial composition were seen with PDX. The microbial diversity decreased significantly with 4% PDX, and the OTU containing C. difficile was significantly (p<0.01) decreased when compared to control and lactobacilli treatments. The mean numbers of C. difficile also decreased as detected by qPCR, although the reduction did not reach statistical significance. Conclusions The treatments influenced the colonic microbiota, and a trend for reduced numbers of C. difficile as well as alterations of several microbial groups could be detected. This suggests that PDX may be able to modulate the composition and/or function of the colonic microbiota in

  10. Impact of Targeted Educational Interventions on Clostridium difficile Infection Treatment in Critically Ill Adults.

    PubMed

    Hammond, Drayton A; Hughes, Catherine A; Painter, Jacob T; Pennick, Rose E; Chatterjee, Kshitij; Boye, Bradley; Meena, Nikhil

    2016-12-01

    Background: Clostridium difficile infection (CDI) is a growing clinical and economic burden throughout the world. Pharmacists often are members of the primary care team in the intensive care unit (ICU) setting; however, the impact of pharmacists educating other health care providers on appropriateness of CDI treatment has not been previously examined. Objective: This study was performed to determine the impact of structured educational interventions on CDI treatment on appropriateness of CDI treatment and clinical outcomes. Methods: This was a single-center, retrospective, cohort study of patients with CDI in the medical ICU at an academic medical center between January and June 2014 (pre-period) and 2015 (post-period). All patients were evaluated for appropriate CDI treatment before and after implementing pharmacist-provided educational interventions on CDI treatment. Results: Patients in the post-period were prescribed appropriate CDI treatment more frequently than patients in the pre-period (91.7% vs 41.7%; p = .03) and received fewer inappropriate doses of a CDI treatment agent (14 doses vs 30 doses). Patients in the pre-period had a shorter ICU length of stay [1.5 days (range, 1-19) vs 3.5 days (range, 2-36); p = .01] and a similar hospital length of stay [9.5 days (range, 4-24) vs 11.5 days (range, 3-56); p = .30]. Total time spent providing interventions was 4 hours. Conclusion: Patients had appropriate CDI treatment initiated more frequently in the post-period. This low-cost intervention strategy should be easy to implement in institutions where pharmacists interact with physicians during clinical rounds and should be evaluated in institutions where interactions between pharmacists and physicians occur more frequently in non-rounding situations.

  11. Comprehensive evaluation of chemiluminescent immunoassays for the laboratory diagnosis of Clostridium difficile infection.

    PubMed

    Makristathis, A; Zeller, I; Mitteregger, D; Kundi, M; Hirschl, A M

    2017-07-01

    For the microbiological diagnosis of a Clostridium (C.) difficile infection (CDI), a two-test algorithm consisting of a C. difficile glutamate dehydrogenase (GDH)-immunoassay followed by a toxin-immunoassay in positive cases is widely used. In this study, two chemiluminescent immunoassays (CLIAs), one for GDH and the other for the toxins A and B, have been evaluated systematically using appropriate reference methods. Three-hundred diarrhoeal stool specimens submitted for CDI diagnosis were analysed by the LIAISON CLIAs (DiaSorin). Toxigenic culture (TC) and cell cytotoxicity assay (CCTA) were used as "gold standard" reference methods. In addition, GDH and toxin A and B enzyme immunoassays (EIAs), C. diff Chek-60 and toxin A/B II (TechLab), and the Cepheid Xpert C. difficile polymerase chain reaction (PCR) were performed. C. difficile was grown in 42 (14%), TC was positive in 35 (11.7%) and CCTA in 25 (8.3%) cases. CLIAs were more sensitive but less specific than the respective EIAs. Using culture as reference, the sensitivity of the GDH CLIA was 100%. In comparison to CCTA sensitivity, specificity, positive predictive value and negative predictive value of the two-test algorithm were 88, 99.3, 91.7 and 98.9% by CLIAs and 72, 99.6, 94.7 and 97.5% by EIAs. Discrepant results by CLIAs were more frequent than that by EIAs (9% vs. 6.3%); in those cases, PCR allowed for the accurate detection of toxigenic strains. Due to performance characteristics and testing comfort, CLIAs in combination with PCR represent a favourable option for the rapid laboratory C. difficile diagnostics.

  12. Clostridium difficile infection in acute flares of inflammatory bowel disease: A prospective study.

    PubMed

    Sokol, Harry; Lalande, Valérie; Landman, Cecilia; Bourrier, Anne; Nion-Larmurier, Isabelle; Rajca, Sylvie; Kirchgesner, Julien; Seksik, Philippe; Cosnes, Jacques; Barbut, Frédéric; Beaugerie, Laurent

    2017-06-01

    Clostridium difficile infection (CDI) is a common complication in inflammatory bowel disease (IBD) and has been associated with poor IBD outcome. The aims of our study were to look for predictive factors of CDI in patients hospitalized for IBD flare and to evaluate a rapid testing strategy in this population. Consecutive patients hospitalized for IBD flare in Saint-Antoine Hospital (Paris, France) were prospectively tested for CDI with a defined strategy involving rapid testing and reference methods. Risk factors for CDI were investigated and performances of diagnostic tests were evaluated. C. difficile testing was performed at admission in 461 hospitalizations for IBD flare. CDI was diagnosed in 35 cases (7.6%) and non-toxigenic C. difficile was identified in 10 cases (2.2%). In multivariate analysis, UC phenotype was associated with CDI (OR 2.2, 95% CI 1.03-4.6, p=0.047). Glutamate dehydrogenase (GDH) test had a 97.1% sensitivity and a 100% negative predictive value for CDI diagnosis but a positive predictive value of 79.1%. Enzyme immunoassay (EIA)-based toxin detection (C. Diff Quik Chek complete(®), Alere) had a poor sensitivity and diagnosis was rescued by toxin PCR in 100% of cases. CDI is frequent in patients hospitalized for IBD flare. Clinical parameters do not help for the diagnosis and rapid testing should be performed in all patients. Currently, a negative result of an EIA-based toxin search associated with a positive GDH test cannot rule out a CDI and should not delay initiation of specific treatment in case of severe symptoms or high presumption. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile.

    PubMed

    Engevik, Melinda A; Engevik, Kristen A; Yacyshyn, Mary Beth; Wang, Jiang; Hassett, Daniel J; Darien, Benjamin; Yacyshyn, Bruce R; Worrell, Roger T

    2015-03-15

    Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets. In cell lines, C. difficile toxin B has been shown to inhibit Na(+)/H(+) exchanger 3 (NHE3) and loss of NHE3 in mice results in an altered intestinal environment coupled with a transformed gut microbiota composition. However, this has yet to be established in vivo in humans. We hypothesize that C. difficile toxin inhibits NHE3, resulting in alteration of the intestinal environment and gut microbiota. Our results demonstrate that CDI patient biopsy specimens have decreased NHE3 expression and CDI stool has elevated Na(+) and is more alkaline compared with stool from healthy individuals. CDI stool microbiota have increased Bacteroidetes and Proteobacteria and decreased Firmicutes phyla compared with healthy subjects. In vitro, C. difficile grows optimally in the presence of elevated Na(+) and alkaline pH, conditions that correlate to changes observed in CDI patients. To confirm that inhibition of NHE3 was specific to C. difficile, human intestinal organoids (HIOs) were injected with C. difficile or healthy and CDI stool supernatant. Injection of C. difficile and CDI stool decreased NHE3 mRNA and protein expression compared with healthy stool and control HIOs. Together these data demonstrate that C. difficile inhibits NHE3 in vivo, which creates an altered environment favored by C. difficile.

  14. A Detrimental Role of Immunosuppressive Drug, Dexamethasone, During Clostridium difficile Infection in Association with a Gastrointestinal Microbial Shift

    PubMed Central

    Kim, Hyeun Bum; Wang, Yuankai; Sun, Xingmin

    2016-01-01

    We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota. PMID:26809802

  15. 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.

  16. A Detrimental Role of Immunosuppressive Drug, Dexamethasone, During Clostridium difficile Infection in Association with a Gastrointestinal Microbial Shift.

    PubMed

    Kim, Hyeun Bum; Wang, Yuankai; Sun, Xingmin

    2016-03-01

    We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota.

  17. Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment.

    PubMed

    2016-01-01

    Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians' perception of patients' lived experience, and a modified grounded theory method to analyze information from the survey. For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85-5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14-3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46-212.44; abdominal cramping, relative risk 14.81, 95% CI 2.07-105.97) (GRADE: low). For

  18. Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). Methods We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians’ perception of patients’ lived experience, and a modified grounded theory method to analyze information from the survey. Results For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85–5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14–3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46–212.44; abdominal cramping, relative risk 14

  19. A Tetraspecific VHH-Based Neutralizing Antibody Modifies Disease Outcome in Three Animal Models of Clostridium difficile Infection

    PubMed Central

    Beamer, Gillian; Tremblay, Jacqueline M.; Steele, Jennifer A.; Kim, Hyeun Bum; Wang, Yaunkai; Debatis, Michele; Sun, Xingmin; Kashentseva, Elena A.; Dmitriev, Igor P.; Curiel, David T.; Shoemaker, Charles B.

    2016-01-01

    Clostridium difficile infection (CDI), a leading cause of nosocomial infection, is a serious disease in North America, Europe, and Asia. CDI varies greatly from asymptomatic carriage to life-threatening diarrhea, toxic megacolon, and toxemia. The incidence of community-acquired infection has increased due to the emergence of hypervirulent antibiotic-resistant strains. These new strains contribute to the frequent occurrence of disease relapse, complicating treatment, increasing hospital stays, and increasing morbidity and mortality among patients. Therefore, it is critical to develop new therapeutic approaches that bypass the development of antimicrobial resistance and avoid disruption of gut microflora. Here, we describe the construction of a single heteromultimeric VHH-based neutralizing agent (VNA) that targets the two primary virulence factors of Clostridium difficile, toxins A (TcdA) and B (TcdB). Designated VNA2-Tcd, this agent has subnanomolar toxin neutralization potencies for both C. difficile toxins in cell assays. When given systemically by parenteral administration, VNA2-Tcd protected against CDI in gnotobiotic piglets and mice and to a lesser extent in hamsters. Protection from CDI was also observed in gnotobiotic piglets treated by gene therapy with an adenovirus that promoted the expression of VNA2-Tcd. PMID:27413067

  20. Effects of a predictive preventive model for prevention of Clostridium difficile infection in patients in intensive care units.

    PubMed

    Cruz-Betancourt, Alba; Cooper, Christopher D; Sposato, Kathleen; Milton, Hermanda; Louzon, Patricia; Pepe, Julie; Girgis, Ramy; Patel, Seema V; Ibrahim, Dina; Van Horn, Sandra; Hsu, Vincent

    2016-04-01

    Health care-acquired Clostridium difficile infection (HACDI) is associated with adverse outcomes at both the organization and patient level. Factors that increase risk for development of HACDI have been identified. Objectives of this study were to develop a predictive screening tool to identify patients at risk for HACDI and implement a bundle of mitigation interventions. A predictive screening tool was developed based on risk factors identified in the literature and validated by retrospective analysis of all HACDI cases occurring in critically ill patients during 2013. The tool was used to screen all patients admitted to an intensive care unit. Evidence-based interventions (bundle) were implemented for patients identified as being at high risk for HACDI. Effectiveness of the model was measured by reduction of HACDI rate during the intervention period compared with the preintervention period. During the 12-month intervention period 217 high-risk patients were identified as infected with Clostridium difficile. Sixty-two of these met exclusion criteria, resulting in a study population of 157 patients. During the preintervention phase, 10 cases of HACDI occurred (overall incidence rate, 14.7). During the 12-month study period, 2 cases of HACDI were identified (incidence rate, 3.12). The reduction was statistically significant. A strategy for identifying patients at increased risk and implementation of multidisciplinary risk-mitigation strategies is effective in reducing incidence of HACDI. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  1. 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

  2. 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

  3. Increasing Incidence of Multiply Recurrent Clostridium difficile Infection in the United States: A Cohort Study.

    PubMed

    Ma, Gene K; Brensinger, Colleen M; Wu, Qufei; Lewis, James D

    2017-08-01

    Clostridium difficile infection (CDI), the most common health care-associated infection, often recurs. Fecal microbiota transplantation is increasingly used to treat multiply recurrent CDI (mrCDI). To determine whether the incidence of mrCDI is increasing in proportion to CDI and to identify risk factors for mrCDI. Retrospective cohort study. United States. 38 911 718 commercially insured patients in the OptumInsight Clinformatics Database, of whom 45 341 developed CDI. Age- and sex-standardized incidence rates for CDI and mrCDI. From 2001 to 2012, the annual incidence of CDI and mrCDI per 1000 person-years increased by 42.7% (from 0.4408 to 0.6289 case) and 188.8% (from 0.0107 to 0.0309 case), respectively. The increase in mrCDI incidence was independent of known risk factors for CDI. Those who developed mrCDI were older (median age, 56.0 vs. 49.0 years; adjusted odds ratio [aOR] per 10-year increase in age, 1.25 [95% CI, 1.21 to 1.29]) and were more likely to be female (63.8% vs. 58.7%; aOR, 1.24 [CI, 1.11 to 1.38]) and to have used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [CI, 1.59 to 2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [CI, 1.01 to 1.29]), or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1.00 to 1.32]) within 90 days of CDI diagnosis. Chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [CI, 1.24 to 1.80]) and diagnosis in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [CI, 1.34 to 2.93]) were also associated with increased risk for mrCDI. The primary analyses included only commercially insured patients in the United States. Relative to CDI, mrCDI incidence has disproportionately increased, indicating a rising demand for mrCDI therapies. National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases.

  4. Co-infection with Toxoplasma gondii and Clostridium perfringens in a postpartum woman with uterine gas gangrene: a case report.

    PubMed

    Alsammani, Mohamed Alkhatim; Ahmed, Salah Roshdy; Alsheeha, Muneera A; Saadia, Zaheera; Khairi, Somia A

    2012-07-01

    Toxoplasmosis is a protozoan infection caused by Toxoplasma gondii. We report a case of Toxoplasma gondii and Clostridium perfringens co-infection complicating uterine gas gangrene following a term pregnancy. The histological examination of the necrotic uterine tissues and uterine swab cultures obtained at laparotomy revealed T. gondii and C. perfringens, respectively. Treatment was administered with bactericidal activity against both pathogens and the patient had an uneventful post-operative recovery. Although there have been some cases that have documented an association between toxoplasmosis and non-uterine C. perfringens infection, such a relationship has not been established. It is of interest to determine if the presence of both organisms can explain the severe myonecrosis that occurs in some cases of uterine gas gangrene.

  5. Understanding the current state of infection prevention to prevent Clostridium difficile infection: a human factors and systems engineering approach.

    PubMed

    Yanke, Eric; Zellmer, Caroline; Van Hoof, Sarah; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

    2015-03-01

    Achieving and sustaining high levels of health care worker (HCW) compliance with contact isolation precautions is challenging. The aim of this study was to determine HCW work system barriers to and facilitators of adherence to contact isolation for patients with suspected or confirmed Clostridium difficile infection (CDI) using a human factors and systems engineering approach. This prospective cohort study took place between September 2013 and November 2013 at a large academic medical center (hospital A) and an affiliated Veterans Administration hospital (hospital B). A human factors engineering (HFE) model for patient safety, the Systems Engineering Initiative for Patient Safety model, was used to guide work system analysis and direct observation data collection. There were 288 observations conducted. HCWs and visitors were assessed for compliance with all components of contact isolation precautions (hand hygiene, gowning, and gloving) before and after patient contact. Time required to complete contact isolation precautions was measured, and adequacy of contact isolation supplies was assessed. Full compliance with contact isolation precautions was low at both hospitals A (7%) and B (22%). Lack of appropriate hand hygiene prior to room entry (compliance for hospital A: 18%; compliance for hospital B: 29%) was the most common reason for lack of full compliance. More time was required for full compliance compared with compliance with no components of contact isolation precautions before patient room entry, inside patient room, and after patient room exit (59.9 vs 3.2 seconds, P < .001; 507.3 vs 149.7 seconds, P = .006; 15.2 vs 1.3 seconds, P < .001, respectively). Compliance was lower when contact isolation supplies were inadequate (4% vs 16%, P = .005). Adherence to contact isolation precautions for CDI is a complex, time-consuming process. HFE analysis indicates that multiple work system components serve as barriers and facilitators to full compliance with contact

  6. Understanding the Current State of Infection Prevention to Prevent Clostridium difficile Infection: A Human Factors and Systems Engineering Approach

    PubMed Central

    Yanke, Eric; Zellmer, Caroline; Van Hoof, Sarah; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

    2015-01-01

    Background Achieving and sustaining high levels of healthcare worker (HCW) compliance with contact isolation precautions is challenging. The aim of this study was to determine HCW work system barriers to, and facilitators of, adherence to contact isolation for patients with suspected or confirmed Clostridium difficile infection (CDI) using a human factors and systems engineering approach. Methods Prospective cohort study from September 2013 to November 2013 at a large academic medical center (hospital A) and an affiliated Veterans Administration (VA) hospital (hospital B). A human factors engineering (HFE) model for patient safety – the Systems Engineering Initiative for Patient Safety (SEIPS) model – was used to guide work system analysis and direct observation data collection. 288 observations were conducted. HCWs and visitors were assessed for compliance with all components of contact isolation precautions (hand hygiene, gowning, and gloving) before and after patient contact. Time required to complete contact isolation precautions was measured and adequacy of contact isolation supplies was assessed. Results Full compliance with contact isolation precautions was low at both hospitals: hospital A, 7%; hospital B, 22%. Lack of appropriate hand hygiene prior to room entry (Compliance: hospital A, 18%; hospital B, 29%) was the most common reason for lack of full compliance. More time was required for full compliance as compared to compliance with no components of contact isolation precautions before patient room entry, inside patient room, and after patient room exit (59.9 sec vs. 3.2 sec; P < .001; 507.3 sec vs. 149.7 sec; P = .006; 15.2 sec vs. 1.3 sec; P < .001). Compliance was lower when contact isolation supplies were inadequate (4% vs. 16%; P = .005). Conclusions Adherence to contact isolation precautions for CDI is a complex, time-consuming process. HFE analysis indicates multiple work system components serve as barriers and facilitators to full compliance

  7. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.

    PubMed

    Youngster, Ilan; Russell, George H; Pindar, Christina; Ziv-Baran, Tomer; Sauk, Jenny; Hohmann, Elizabeth L

    2014-11-05

    Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use. To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C. difficile infection. Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C. difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C. difficile infection requiring hospitalization were enrolled. Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80°C (-112°F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months. The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements. No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P = .001) and 1 (IQR, 1-2) at 8 weeks (P < .001). Self-ranked health scores improved significantly on a scale of 1 to 10 from a median of 5 (IQR

  8. 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

  9. Functional Intestinal Bile Acid 7α-Dehydroxylation by Clostridium scindens Associated with Protection from Clostridium difficile Infection in a Gnotobiotic Mouse Model.

    PubMed

    Studer, Nicolas; Desharnais, Lyne; Beutler, Markus; Brugiroux, Sandrine; Terrazos, Miguel A; Menin, Laure; Schürch, Christian M; McCoy, Kathy D; Kuehne, Sarah A; Minton, Nigel P; Stecher, Bärbel; Bernier-Latmani, Rizlan; Hapfelmeier, Siegfried

    2016-01-01

    Bile acids, important mediators of lipid absorption, also act as hormone-like regulators and as antimicrobial molecules. In all these functions their potency is modulated by a variety of chemical modifications catalyzed by bacteria of the healthy gut microbiota, generating a complex variety of secondary bile acids. Intestinal commensal organisms are well-adapted to normal concentrations of bile acids in the gut. In contrast, physiological concentrations of the various intestinal bile acid species play an important role in the resistance to intestinal colonization by pathogens such as Clostridium difficile. Antibiotic therapy can perturb the gut microbiota and thereby impair the production of protective secondary bile acids. The most important bile acid transformation is 7α-dehydroxylation, producing deoxycholic acid (DCA) and lithocholic acid (LCA). The enzymatic pathway carrying out 7α-dehydroxylation is restricted to a narrow phylogenetic group of commensal bacteria, the best-characterized of which is Clostridium scindens. Like many other intestinal commensal species, 7-dehydroxylating bacteria are understudied in vivo. Conventional animals contain variable and uncharacterized indigenous 7α-dehydroxylating organisms that cannot be selectively removed, making controlled colonization with a specific strain in the context of an undisturbed microbiota unfeasible. In the present study, we used a recently established, standardized gnotobiotic mouse model that is stably associated with a simplified murine 12-species "oligo-mouse microbiota" (Oligo-MM(12)). It is representative of the major murine intestinal bacterial phyla, but is deficient for 7α-dehydroxylation. We find that the Oligo-MM(12) consortium carries out bile acid deconjugation, a prerequisite for 7α-dehydroxylation, and confers no resistance to C. difficile infection (CDI). Amendment of Oligo-MM(12) with C. scindens normalized the large intestinal bile acid composition by reconstituting 7

  10. Functional Intestinal Bile Acid 7α-Dehydroxylation by Clostridium scindens Associated with Protection from Clostridium difficile Infection in a Gnotobiotic Mouse Model

    PubMed Central

    Studer, Nicolas; Desharnais, Lyne; Beutler, Markus; Brugiroux, Sandrine; Terrazos, Miguel A.; Menin, Laure; Schürch, Christian M.; McCoy, Kathy D.; Kuehne, Sarah A.; Minton, Nigel P.; Stecher, Bärbel; Bernier-Latmani, Rizlan; Hapfelmeier, Siegfried

    2016-01-01

    Bile acids, important mediators of lipid absorption, also act as hormone-like regulators and as antimicrobial molecules. In all these functions their potency is modulated by a variety of chemical modifications catalyzed by bacteria of the healthy gut microbiota, generating a complex variety of secondary bile acids. Intestinal commensal organisms are well-adapted to normal concentrations of bile acids in the gut. In contrast, physiological concentrations of the various intestinal bile acid species play an important role in the resistance to intestinal colonization by pathogens such as Clostridium difficile. Antibiotic therapy can perturb the gut microbiota and thereby impair the production of protective secondary bile acids. The most important bile acid transformation is 7α-dehydroxylation, producing deoxycholic acid (DCA) and lithocholic acid (LCA). The enzymatic pathway carrying out 7α-dehydroxylation is restricted to a narrow phylogenetic group of commensal bacteria, the best-characterized of which is Clostridium scindens. Like many other intestinal commensal species, 7-dehydroxylating bacteria are understudied in vivo. Conventional animals contain variable and uncharacterized indigenous 7α-dehydroxylating organisms that cannot be selectively removed, making controlled colonization with a specific strain in the context of an undisturbed microbiota unfeasible. In the present study, we used a recently established, standardized gnotobiotic mouse model that is stably associated with a simplified murine 12-species “oligo-mouse microbiota” (Oligo-MM12). It is representative of the major murine intestinal bacterial phyla, but is deficient for 7α-dehydroxylation. We find that the Oligo-MM12 consortium carries out bile acid deconjugation, a prerequisite for 7α-dehydroxylation, and confers no resistance to C. difficile infection (CDI). Amendment of Oligo-MM12 with C. scindens normalized the large intestinal bile acid composition by reconstituting 7

  11. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients.

    PubMed

    Kelly, Colleen R; Ihunnah, Chioma; Fischer, Monika; Khoruts, Alexander; Surawicz, Christina; Afzali, Anita; Aroniadis, Olga; Barto, Amy; Borody, Thomas; Giovanelli, Andrea; Gordon, Shelley; Gluck, Michael; Hohmann, Elizabeth L; Kao, Dina; Kao, John Y; McQuillen, Daniel P; Mellow, Mark; Rank, Kevin M; Rao, Krishna; Ray, Arnab; Schwartz, Margot A; Singh, Namita; Stollman, Neil; Suskind, David L; Vindigni, Stephen M; Youngster, Ilan; Brandt, Lawrence

    2014-07-01

    Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients. A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT. Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3-46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during

  12. Dissemination of Clostridium difficile in food and the environment: Significant sources of C. difficile community-acquired infection?

    PubMed

    Warriner, K; Xu, C; Habash, M; Sultan, S; Weese, S J

    2017-03-01

    Clostridium difficile is a significant pathogen with over 300 000 cases reported in North America annually. Previously, it was thought that C. difficile was primarily a clinically associated infection. However, through the use of whole genome sequencing it has been revealed that the majority of cases are community acquired. The source of community-acquired C. difficile infections (CDI) is open to debate with foodborne being one route considered. Clostridium difficile fits the criteria of a foodborne pathogen with respect to being commonly encountered in a diverse range of foods that includes meat, seafood and fresh produce. However, no foodborne illness outbreaks have been directly linked to C. difficile there is also no conclusive evidence that its spores can germinate in food matrices. This does not exclude food as a potential vehicle but it is likely that the pathogen is also acquired through zoonosis and the environment. The most significant factor that defines susceptibility to CDI is the host microbiome and functioning immune system. In this respect, effective control can be exercised by reducing the environmental burden of C. difficile along with boosting the host defences against the virulent enteric pathogen. © 2016 The Society for Applied Microbiology.

  13. [Successful treatment of life-threatening, treatment resistant Clostridium difficile infection associated pseudomembranous colitis with faecal transplantation].

    PubMed

    Nagy, Gergely György; Várvölgyi, Csaba; Paragh, György

    2012-12-30

    Due to world-wide spread of hypervirulent and antibiotic resistant Clostridium difficile strains, the incidence of these infections are dramatically increasing in Hungary with appalling mortality and recurrence rates. Authors present a case of a 59-year-old patient who developed a severe, relapsing pseudomembranous colitis after antibiotic treatment. Life-threatening symptoms of fulminant colitis were successfully treated with prolonged administration of metronidazole and vancomycin, careful supportive therapy and weeks of intensive care. However, a well-documented, severe relapse developed within a week and this time faecal bacteriotherapy was performed. This treatment resulted in a complete cure without any further antibiotic treatment. In relation to this life-saving faecal transplantation, methodology and indications are briefly discussed. In addition, microbiological issues, epidemiological data and threats associated with antibiotic treatment of Clostridium difficile infections are also covered. Finally, relevant professional societies are urged to prepare a national protocol for faecal transplantation, which could allow introduction of this valuable, cost-effective procedure into the routine clinical practice.

  14. Understanding factors that impact on public and patient's risk perceptions and responses toward Clostridium difficile and other health care-associated infections: a structured literature review.

    PubMed

    Burnett, Emma; Johnston, Bridget; Kearney, Nora; Corlett, Joanne; MacGillivray, Stephen

    2013-06-01

    Clostridium difficile is the most common health care-associated infection and a major cause of death and increased morbidity. It is vital that patients and the public are provided with the right information and communication to assist them to understand their role in preventative measures. Successful implementation of communication and management strategies hinges on individuals' risk perceptions. We performed a structured literature review to examine the evidence regarding public and patients' risk perceptions and responses toward Clostridium difficile and other health care-associated infections. Fourteen studies were included. Only 1 study was specific to Clostridium difficile, and 7 were related to other health care-associated infections. Many reported limited understanding of the technical issues of the infection, concerns of transmission to family and friends, inadequate information available, and distrust. The media were one of the main sources of information. Both emotional and physical responses highlighted the level of confusion, fear, anxiety, and anger. Empirical research of risk perceptions toward Clostridium difficile is limited. Without well-researched studies examining risk perceptions and responses, there is a danger of developing and implementing communication and management strategies that do not meet the needs of our patients or the public. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  15. Flooding and Health Care Visits for Clostridium Difficile Infection: A Case-Crossover Analysis

    EPA Science Inventory

    Floods can contaminate potable water and other resources, thus increasing the potential for fecal-oral transmission of pathogens. Clostridium difficile is a bacterium that can spread by water and cause acute gastrointestinal illness. It often affects older adults who are hospital...

  16. Flooding and Health Care Visits for Clostridium Difficile Infection: A Case-Crossover Analysis

    EPA Science Inventory

    Floods can contaminate potable water and other resources, thus increasing the potential for fecal-oral transmission of pathogens. Clostridium difficile is a bacterium that can spread by water and cause acute gastrointestinal illness. It often affects older adults who are hospital...

  17. Detection of mixed infection from bacterial whole genome sequence data allows assessment of its role in Clostridium difficile transmission.

    PubMed

    Eyre, David W; Cule, Madeleine L; Griffiths, David; Crook, Derrick W; Peto, Tim E A; Walker, A Sarah; Wilson, Daniel J

    2013-01-01

    Bacterial whole genome sequencing offers the prospect of rapid and high precision investigation of infectious disease outbreaks. Close genetic relationships between microorganisms isolated from different infected cases suggest transmission is a strong possibility, whereas transmission between cases with genetically distinct bacterial isolates can be excluded. However, undetected mixed infections-infection with ≥2 unrelated strains of the same species where only one is sequenced-potentially impairs exclusion of transmission with certainty, and may therefore limit the utility of this technique. We investigated the problem by developing a computationally efficient method for detecting mixed infection without the need for resource-intensive independent sequencing of multiple bacterial colonies. Given the relatively low density of single nucleotide polymorphisms within bacterial sequence data, direct reconstruction of mixed infection haplotypes from current short-read sequence data is not consistently possible. We therefore use a two-step maximum likelihood-based approach, assuming each sample contains up to two infecting strains. We jointly estimate the proportion of the infection arising from the dominant and minor strains, and the sequence divergence between these strains. In cases where mixed infection is confirmed, the dominant and minor haplotypes are then matched to a database of previously sequenced local isolates. We demonstrate the performance of our algorithm with in silico and in vitro mixed infection experiments, and apply it to transmission of an important healthcare-associated pathogen, Clostridium difficile. Using hospital ward movement data in a previously described stochastic transmission model, 15 pairs of cases enriched for likely transmission events associated with mixed infection were selected. Our method identified four previously undetected mixed infections, and a previously undetected transmission event, but no direct transmission between the

  18. Identification of risk factors for the development of clostridium difficile-associated diarrhea following treatment of polymicrobial surgical infections.

    PubMed

    Metzger, Rosemarie; Swenson, Brian R; Bonatti, Hugo; Hedrick, Traci L; Hranjec, Tjasa; Popovsky, Kimberley A; Pruett, Timothy L; Sawyer, Robert G

    2010-04-01

    To identify risk factors for Clostridium difficile-associated diarrhea (CDAD) in surgical patients following treatment of polymicrobial infections. Infections among surgical patients are frequently anaerobic or mixed aerobic-anaerobic infections and are therefore subject to polymicrobial antibiotic coverage, including metronidazole. While multiple antibiotics are known to contribute to the development of CDAD, the role of preventive antibiotics is unproven. An 11-year dataset of consecutive infections treated in surgical patients at a single hospital was reviewed. All intra-abdominal, surgical site, or skin/skin structure infections were identified. Each infection was evaluated for antibiotic coverage and subsequent CDAD. Antibiotic usage was assessed using chi analysis. A multiple logistic regression was used to identify independent predictors of CDAD. A total of 4178 intra-abdominal, surgical site, or skin/skin structure infections were identified. Of these infections, 98 were followed by CDAD. Only carbapenem use affected the incidence of CDAD: 3.5% of infections treated with a carbapenem were followed by CDAD, whereas only 2.1% of infections treated without carbapenems were followed by CDAD (P = 0.04). Metronidazole had no association with future CDAD. Only age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independently associated with CDAD by multiple logistic regression analysis. Older patients with a high severity of illness are at greatest risk for developing CDAD following treatment of polymicrobial infections. No specific antibiotic class, including fluoroquinolones, is associated with an increased incidence of CDAD in this population. Although use of metronidazole in the treatment of polymicrobial infections is appropriate for anaerobic coverage, it does not reduce the risk of future CDAD.

  19. Identification of Risk Factors for the Development of Clostridium difficile-Associated Diarrhea Followi