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Sample records for albicans bloodstream infections

  1. Elimination of Bloodstream Infections Associated with Candida albicans Biofilm in Intravascular Catheters

    PubMed Central

    Akbari, Freshta; Kjellerup, Birthe Veno

    2015-01-01

    Intravascular catheters are among the most commonly inserted medical devices and they are known to cause a large number of catheter related bloodstream infections (BSIs). Biofilms are associated with many chronic infections due to the aggregation of microorganisms. One of these organisms is the fungus Candida albicans. It has shown to be one of the leading causes of catheter-related BSIs. The presence of biofilm on intravascular catheters provide increased tolerance against antimicrobial treatments, thus alternative treatment strategies are sought. Traditionally, many strategies, such as application of combined antimicrobials, addition of antifungals, and removal of catheters, have been practiced, but they were not successful in eradicating BSIs. Since these fungal infections can result in significant morbidity, mortality, and increased healthcare cost, other promising preventive strategies, including antimicrobial lock therapy, chelating agents, alcohol, and biofilm disruptors, have been applied. In this review, current success and failure of these new approaches, and a comparison with the previous strategies are discussed in order to understand which preventative treatment is the most effective in controlling the catheter-related BSIs. PMID:26131615

  2. Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012-2013.

    PubMed

    Rajendran, R; Sherry, L; Nile, C J; Sherriff, A; Johnson, E M; Hanson, M F; Williams, C; Munro, C A; Jones, B J; Ramage, G

    2016-01-01

    Bloodstream infections caused by Candida species remain a significant cause of morbidity and mortality in hospitalized patients. Biofilm formation by Candida species is an important virulence factor for disease pathogenesis. A prospective analysis of patients with Candida bloodstream infection (n = 217) in Scotland (2012-2013) was performed to assess the risk factors associated with patient mortality, in particular the impact of biofilm formation. Candida bloodstream isolates (n = 280) and clinical records for 157 patients were collected through 11 different health boards across Scotland. Biofilm formation by clinical isolates was assessed in vitro with standard biomass assays. The role of biofilm phenotype on treatment efficacy was also evaluated in vitro by treating preformed biofilms with fixed concentrations of different classes of antifungal. Available mortality data for 134 patients showed that the 30-day candidaemia case mortality rate was 41%, with predisposing factors including patient age and catheter removal. Multivariate Cox regression survival analysis for 42 patients showed a significantly higher mortality rate for Candida albicans infection than for Candida glabrata infection. Biofilm-forming ability was significantly associated with C. albicans mortality (34 patients). Finally, in vitro antifungal sensitivity testing showed that low biofilm formers and high biofilm formers were differentially affected by azoles and echinocandins, but not by polyenes. This study provides further evidence that the biofilm phenotype represents a significant clinical entity, and that isolates with this phenotype differentially respond to antifungal therapy in vitro. Collectively, these findings show that greater clinical understanding is required with respect to Candida biofilm infections, and the implications of isolate heterogeneity. PMID:26432192

  3. Klebsiella pneumoniae Bloodstream Infection

    PubMed Central

    Girometti, Nicolò; Lewis, Russell E.; Giannella, Maddalena; Ambretti, Simone; Bartoletti, Michele; Tedeschi, Sara; Tumietto, Fabio; Cristini, Francesco; Trapani, Filippo; Gaibani, Paolo; Viale, Pierluigi

    2014-01-01

    Abstract Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniae bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42%) KPC-positive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo-beta-lactamase-positive isolates. Adequate empirical therapy was administered in 74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23% of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment outcomes, we compared several different models comprised of non-antibiotic treatment-related factors predictive of patients’ 30-day survival status. Acute Physiology and Chronic Health Evaluation (APACHE) II score determined at the time of positive blood culture was superior to other investigated models, correctly predicting survival status in 83% of the study cohort. In multivariate analysis accounting for APACHE II, receipt of inadequate empirical therapy was associated with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95% confidence interval 1.1–3.4; p = 0.02). Multidrug-resistant K. pneumoniae accounted for two-thirds of all K. pneumoniae BSIs, high rates of inappropriate empirical therapy, and twofold higher rates of patient death irrespective of underlying illness. PMID:25398065

  4. Catheter-related bloodstream infection.

    PubMed

    Goede, Matthew R; Coopersmith, Craig M

    2009-04-01

    Catheter-related bloodstream infections (CR-BSIs) are a common, frequently preventable complication of central venous catheterization. CR-BSIs can be prevented by strict attention to insertion and maintenance of central venous catheters and removing unneeded catheters as soon as possible. Antiseptic- or antibiotic-impregnated catheters are also an effective tool to prevent infections. The diagnosis of CR-BSI is made largely based on culture results. CR-BSIs should always be treated with antibiotics, and except in rare circumstances the infected catheter needs to be removed. PMID:19281894

  5. Candida Infection of the Bloodstream - Candidemia

    MedlinePlus

    Candida Infection of the Bloodstream– Candidemia Fungal Disease Series #4 Candida is the single most important cause of fungal infections worldwide. In the U.S., Candida is the 4th most common cause of bloodstream ...

  6. Diagnosis of Bloodstream Infections in Children.

    PubMed

    Dien Bard, Jennifer; McElvania TeKippe, Erin

    2016-06-01

    Identification of bloodstream infections is among the most critical tasks performed by the clinical microbiology laboratory. While the criteria for achieving an adequate blood culture specimen in adults have been well described, there is much more ambiguity in pediatric populations. This minireview focuses on the available pediatric literature pertaining to the collection of an optimal blood culture specimen, including timing, volume, and bottle selection, as well as rapid diagnostic approaches and their role in the management of pediatric bloodstream infections. PMID:26818669

  7. Hospital Specificity, Region Specificity, and Fluconazole Resistance of Candida albicans Bloodstream Isolates

    PubMed Central

    Pfaller, M. A.; Lockhart, S. R.; Pujol, C.; Swails-Wenger, J. A.; Messer, S. A.; Edmond, M. B.; Jones, R. N.; Wenzel, R. P.; Soll, D. R.

    1998-01-01

    In a survey of bloodstream infection (BSI) isolates across the continental United States, 162 Candida albicans isolates were fingerprinted with the species-specific probe Ca3 and the patterns were analyzed for relatedness with a computer-assisted system. The results demonstrate that particular BSI strains are more highly concentrated in particular geographic locales and that established BSI strains are endemic in some, but not all, hospitals in the study and undergo microevolution in hospital settings. The results, however, indicate no close genetic relationship among fluconazole-resistant BSI isolates in the collection, either from the same geographic locale or the same hospital. This study represents the first of three fingerprinting studies designed to analyze the origin, genetic relatedness, and drug resistance of Candida isolates responsible for BSI. PMID:9620370

  8. Bloodstream infections in the Intensive Care Unit.

    PubMed

    Bassetti, Matteo; Righi, Elda; Carnelutti, Alessia

    2016-04-01

    Bloodstream infections (BSIs) represent a common complication among critically ill patients and a leading cause of morbidity and mortality. The prompt initiation of an effective antibiotic therapy is necessary in order to reduce mortality and to improve clinical outcomes. However, the choice of the empiric antibiotic regimen is often challenging, due to the worldwide spread of multi-drug resistant (MDR) organisms with reduced susceptibility to the available broad-spectrum antimicrobials. New therapeutic strategies are 5 to improve the effectiveness of antibiotic treatment while minimizing the risk of resistance selection. PMID:26760527

  9. Bloodstream infections after solid-organ transplantation.

    PubMed

    Kritikos, Antonios; Manuel, Oriol

    2016-04-01

    Solid-organ transplantation (SOT) has become the preferred strategy to treat a number of end-stage organ disease, because a continuous improvement in survival and quality of life. While preventive strategies has decreased the risk for classical opportunistic infections (such as viral, fungal and parasite infections), bacterial infections, and particularly bloodstream infections (BSIs) remain the most common and life-threatening complications in SOT recipients. The source of BSI after transplant depends on the type of transplantation, being urinary tract infection, pneumonia, and intraabdominal infections the most common infections occurring after kidney, lung and liver transplantation, respectively. The risk for candidemia is higher in abdominal-organ than in thoracic-organ transplantation. Currently, the increasing prevalence of multi-drug resistant (MDR) Gram-negative pathogens, such as extended-spectrum betalactamase-producing Enterobacteriaciae and carbapenem-resistant Klebsiella pneumoniae, is causing particular concerns in SOT recipients, a population which presents several risk factors for developing infections due to MDR organisms. The application of strict preventive policies to reduce the incidence of post transplant BSIs and to control the spread of MDR organisms, including the implementation of specific stewardship programs to avoid the overuse of antibiotics and antifungal drugs, are essential steps to reduce the impact of post transplant infections on allograft and patient outcomes. PMID:26766415

  10. Candida Associated Bloodstream Infections in Pediatric Hematology Patients: A Single Center Experience

    PubMed Central

    Gokcebay, Dilek Gurlek; Yarali, Nese; Isik, Pamir; Bayram, Cengiz; Ozkaya-Parlakay, Aslinur; Kara, Abdurrahman; Tunc, Bahattin

    2016-01-01

    Background and Objectives Candida-associated bloodstream infections are frequent and potentially life-threatening conditions in hematology patients. The aim of this study is to evaluate the characteristics, risk factors, and outcome of Candida-associated bloodstream infections in children with hematological diseases. Methods The medical records of the patients with hematological diseases and hematopoietic stem cell transplantation (HSCT) recipients who were diagnosed as Candida-associated bloodstream infection between February 2010 and February 2014 were reviewed retrospectively. Results Thirty episodes of candidemia involving 26 patients (38% female, and 62% male) with a median age of 7-year (range; 1 to 17) were noted. The incidence of candidemia in our study was 5.2 per 1000 hospital admissions. Infections with non-albicans Candida spp. occurred more frequently (63%) and C. krusei was the predominant microorganism among non-albicans Candida spp. (37%). Candida albicans was isolated from 11 of the 30 episodes (37%). Twenty-six of the episodes (88%) patients had a central venous catheter (CVC) prior to candidemia, and they were removed in 16 (62%). Thirty-day mortality rate was 20%. Isolated Candida spp, underlying disease and its status, presence of mucositis, neutropenia, using of broad spectrum antibiotics, corticosteroids or total parenteral nutrition were not identified as predictors of outcome. Multivariate analysis revealed that CVCs kept in place was the only significant factor associated with mortality (OR, 0.07; 95% CI, 0.006–0.716). Conclusions Candida-associated bloodstream infections were common in children with hematological diseases and HSCT recipients, particularly in patients with CVCs. In addition to appropriate antifungal therapy, CVC removal improves the outcome of candidemia in children with hematological disease. PMID:26977277

  11. New antibiotic agents for bloodstream infections.

    PubMed

    Vergidis, Paschalis I; Falagas, Matthew E

    2008-11-01

    Infections due to multidrug-resistant pathogens have shown a dramatic worldwide increase in prevalence. Bloodstream infections (BSIs) represent an important cause of morbidity and mortality in hospitalised patients. Research in the field led to the introduction of several novel antibiotic agents in the fight against bacterial pathogens. New antibiotics used against Gram-positive bacteria, mainly meticillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, include daptomycin, linezolid, quinupristin/dalfopristin and semisynthetic lipoglycopeptides. Among the Gram-negative bacteria, extended-spectrum beta-lactamase-producing Enterobacteriaceae as well as highly resistant Pseudomonas and Acinetobacter isolates are of particular concern. Doripenem is a recently approved carbapenem. Polymyxins are reconsidered as valuable therapeutic options for Gram-negative infections. Tigecycline, a glycylcycline, and ceftobiprole, a novel cephalosporin under investigation, have activity both against Gram-positive and Gram-negative organisms. In addition to the above agents, alternative treatment approaches that require further investigation have also been introduced into clinical practice. These include antibiotic lock therapy and continuous intravenous administration of antibiotics. In this article, we review the above treatment options for BSIs based on current clinical evidence. Comparative trials specifically focusing on patients with bacteraemia were generally not performed; however, a proportion of patients from the reported studies did have bacteraemia. PMID:18723329

  12. Comparison of serum procalcitonin in respiratory infections and bloodstream infections

    PubMed Central

    Zhu, Yanhui; Yuan, Yulin; Huang, Huayi

    2015-01-01

    Purpose: This study observed the relationship between procalcitonin (PCT) and results of sputum culture, the relationship between PCT and results of blood culture to evaluate and compare the value of PCT in respiratory and bloodstream infections. Methods: We analyzed 1616 patients in which PCT and sputum culture were concurrently ordered and analyzed, and 1096 patients in which PCT and blood culture were concurrently ordered and analyzed from January 2014 to May 2015. PCT concentrations were measured by on a Roche Cobas E601 ECL analyzer. Results: The average values of PCT from patients with sputum culture positive and negative were 0.42 (0.17-2.16) and 0.12 (0.06-0.57) ng/ml respectively, and the average values of PCT from patients with blood culture positive and negative were 9.54 (2.10-48.47) and 0.28 (0.10-1.23) ng/ml respectively. In sputum culture, positive rate of PCT in cases with growth of pathogens was 47.1%. In blood culture, positive rate of PCT in cases with growth of pathogens was 89.2%. Conclusions: PCT is useful in early diagnosis of respiratory infections and bloodstream infections, but the specificity of PCT in diagnosing respiratory infections is not as high as it is in bloodstream infections. PMID:26885109

  13. Antimicrobial therapy of Staphylococcus aureus bloodstream infection.

    PubMed

    Tacconelli, Evelina; Cataldo, Maria A

    2007-10-01

    Staphylococcus aureus bloodstream infection (BSI) contributes significantly to the morbidity and mortality of in-patients. The optimal therapy for methicillin-susceptible S. aureus BSI consists of penicillins. The efficacy of these drugs is well documented from several published data and supported from a long clinical experience. Methicillin-resistant S. aureus (MRSA) strains are responsible for the majority of nosocomial BSI and are recovered with increasing frequency at hospital admission. Although glycopeptides still represent the drugs of choice, there are several concerns on the treatment of MRSA BSI: reports of clinical failure with vancomycin treatment, regardless of the in vitro susceptibility; increasing reports of MRSA strains with reduced vancomycin susceptibility; difficulty in therapeutic dosage monitoring of teicoplanin; lack of evidence on the efficacy of combination therapy. Recently, new drugs have been introduced in the therapeutic arsenal for MRSA infections, but their clinical use is not yet clearly established for BSI. The review summarises evidence on present therapeutic options for the treatment of S. aureus BSI. PMID:17931086

  14. Bloodstream Infections in Patients With Solid Tumors

    PubMed Central

    Marín, Mar; Gudiol, Carlota; Garcia-Vidal, Carol; Ardanuy, Carmen; Carratalà, Jordi

    2014-01-01

    Abstract Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/μL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum β-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate

  15. Candida Bloodstream Infections in Italy: Changing Epidemiology during 16 Years of Surveillance.

    PubMed

    Caggiano, Giuseppina; Coretti, Caterina; Bartolomeo, Nicola; Lovero, Grazia; De Giglio, Osvalda; Montagna, Maria Teresa

    2015-01-01

    Although considerable progress has been made in the management of patients with invasive fungal infections, Candida bloodstream infections are still widespread in hospital settings. Incidence rates vary geographically, often because of different patient populations. The aim of the present study was to describe the epidemiology of candidemia, to analyze the trend of species distribution, and to measure the in vitro susceptibility to antifungal drugs in a university Italian hospital from 1998 to 2013. The antifungal susceptibility for all Candida isolates was evaluated by broth microdilution assay (CLSI M27-A3 document). Of 394 episodes of candidemia, the average incidence was 3.06/10,000 admissions. C. albicans and non-albicans Candida species caused 44.2% and 55.8% of the episodes, respectively. C. parapsilosis (62.2%) was the most common non-albicans.  C. albicans predominated in almost all departments whereas C. parapsilosis was found in adult and paediatric oncohaematology units (34.8% and 77.6%, resp.). Overall, mortality occurred in 111 (28.2%) patients. Death occurred most often in intensive care units (47.1%) and specialist surgeries (43.7%). Most of the isolates were susceptible to antifungal drugs, but there was an upward trend for azole (P < 0.05). In conclusion, this study emphasizes the importance of monitoring local epidemiologic data and the diversity of patient groups affected. PMID:26064890

  16. Comparison of Total Hospital-Acquired Bloodstream Infections to Central Line-Associated Bloodstream Infections and Implications for Outcome Measures in Infection Control

    PubMed Central

    Leekha, Surbhi; Li, Shanshan; Thom, Kerri A.; Anne Preas, Michael; Caffo, Brian S.; Morgan, Daniel J.; Harris, Anthony D.

    2014-01-01

    Validity of the central line-associated bloodstream infection (CLABSI) measure is compromised by subjectivity. We observed significant decreases in both CLABSI and total hospital-acquired bloodstream infection (BSI) following a CLABSI prevention intervention in adult intensive care units. Total hospital-acquired BSI could be explored as an adjunct, objective CLABSI measure. PMID:23917916

  17. In vitro activities of voriconazole (UK-109, 496), fluconazole, itraconazole and amphotericin B against 132 non-albicans bloodstream yeast isolates (CANARI study).

    PubMed

    Swinne, D; Watelle, M; Van der Flaes, M; Nolard, N

    2004-06-01

    The aim was to evaluate the in vitro activity of voriconazole compared with those of amphotericin B, itraconazole and fluconazole against 132 bloodstream isolates of Candida non-albicans and Saccharomyces cerevisiae species. The minimal inhibitory concentrations (MICs) were determined by an adapted National Committee for Clinical Laboratory Standards (NCCLS) M27-A method using RPMI 1640 as test medium supplemented with 2% glucose. MIC end-points were determined with a spectrophotometer after incubation for 48 h at 35 degrees C. Optical density data were used for the calculation of the MIC end-points. For amphotericin B, the end-point was defined as the minimal antifungal concentration that exerts 90% inhibition compared with the control well growth. For the azoles, the end-points were determined at 50% inhibition of growth. Amphotericin B is highly active with 97% of isolates inhibited by < or =1 microg ml(-1). Decreased susceptibility or resistance to fluconazole was the rule among C. krusei, which is intrinsically resistant to fluconazole. For C. glabrata isolates, resistance to fluconazole and itraconazole was measured in 13% and 17% of the isolates respectively. Voriconazole was quite active in vitro against all the isolates with a MIC90% of < or =1 microg ml(-1) and we conclude that it may be useful in the treatment of non-albicans bloodstream infections. PMID:15189180

  18. Urinary tract infections and Candida albicans

    PubMed Central

    Behzadi, Payam; Behzadi, Elham

    2015-01-01

    Introduction Urinary tract candidiasis is known as the most frequent nosocomial fungal infection worldwide. Candida albicans is the most common cause of nosocomial fungal urinary tract infections; however, a rapid change in the distribution of Candida species is undergoing. Simultaneously, the increase of urinary tract candidiasis has led to the appearance of antifungal resistant Candida species. In this review, we have an in depth look into Candida albicans uropathogenesis and distribution of the three most frequent Candida species contributing to urinary tract candidiasis in different countries around the world. Material and methods For writing this review, Google Scholar –a scholarly search engine– (http://scholar.google.com/) and PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) were used. The most recently published original articles and reviews of literature relating to the first three Candida species causing urinary tract infections in different countries and the pathogenicity of Candida albicans were selected and studied. Results Although some studies show rapid changes in the uropathogenesis of Candida species causing urinary tract infections in some countries, Candida albicans is still the most important cause of candidal urinary tract infections. Conclusions Despite the ranking of Candida albicans as the dominant species for urinary tract candidiasis, specific changes have occurred in some countries. At this time, it is important to continue the surveillance related to Candida species causing urinary tract infections to prevent, control and treat urinary tract candidiasis in future. PMID:25914847

  19. Prosthetic Valve Endocarditis and Bloodstream Infection Due to Mycobacterium chimaera

    PubMed Central

    Achermann, Yvonne; Rössle, Matthias; Hoffmann, Matthias; Deggim, Vanessa; Kuster, Stefan; Zimmermann, Dieter R.; Hombach, Michael; Hasse, Barbara

    2013-01-01

    Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly growing NTM, however, are lacking. We present here one case of PVE and one case of bloodstream infection caused by Mycobacterium chimaera. Randomly amplified polymorphic DNA (RAPD)-PCR indicated a relatedness of the two M. chimaera strains. Both patients had heart surgery 2 years apart from each other. A nosocomial link was not detected. PMID:23536407

  20. Acinetobacter baumannii Genes Required for Bacterial Survival during Bloodstream Infection

    PubMed Central

    Subashchandrabose, Sargurunathan; Smith, Sara; DeOrnellas, Valerie; Crepin, Sebastien; Kole, Monica; Zahdeh, Carina

    2015-01-01

    ABSTRACT Acinetobacter baumannii is emerging as a leading global multiple-antibiotic-resistant nosocomial pathogen. The identity of genes essential for pathogenesis in a mammalian host remains largely unknown. Using transposon-directed insertion-site sequencing (TraDIS), we identified A. baumannii genes involved in bacterial survival in a leukopenic mouse model of bloodstream infection. Mice were inoculated with a pooled transposon mutant library derived from 109,000 mutants, and TraDIS was used to map transposon insertion sites in the genomes of bacteria in the inoculum and of bacteria recovered from mouse spleens. Unique transposon insertion sites were mapped and used to calculate a fitness factor for every insertion site based on its relative abundance in the inoculum and postinfection libraries. Eighty-nine transposon insertion mutants that were underrepresented after experimental infection in mice compared to their presence in the inocula were delineated as candidates for further evaluation. Genetically defined mutants lacking feoB (ferrous iron import), ddc (d-ala-d-ala-carboxypeptidase), and pntB (pyridine nucleotide transhydrogenase subunit) exhibited a fitness defect during systemic infection resulting from bacteremia. In vitro, these mutants, as well as a fepA (ferric enterobactin receptor) mutant, are defective in survival in human serum and within macrophages and are hypersensitive to killing by antimicrobial peptides compared to the survival of the parental strain under these conditions. Our data demonstrate that FepA is involved in the uptake of exogenous enterobactin in A. baumannii. Genetic complementation rescues the phenotypes of mutants in assays that emulate conditions encountered during infection. In summary, we have determined novel A. baumannii fitness genes involved in the pathogenesis of mammalian infection. IMPORTANCE A. baumannii is a significant cause of bacterial bloodstream infection in humans. Since multiple antibiotic resistance

  1. Biofilm-based central line-associated bloodstream infections.

    PubMed

    Yousif, Ammar; Jamal, Mohamed A; Raad, Issam

    2015-01-01

    Different types of central venous catheters (CVCs) have been used in clinical practice to improve the quality of life of chronically and critically ill patients. Unfortunately, indwelling devices are usually associated with microbial biofilms and eventually lead to catheter-related bloodstream infections (CLABSIs).An estimated 250,000-400,000 CLABSIs occur every year in the United States, at a rate of 1.5 per 1,000 CVC days and a mortality rate of 12-25 %. The annual cost of caring for patients with CLABSIs ranges from 296 million to 2.3 billion dollars.Biofilm formation occurs on biotic and abiotic surfaces in the clinical setting. Extensive studies have been conducted to understand biofilm formation, including different biofilm developmental stages, biofilm matrix compositions, quorum-sensing regulated biofilm formation, biofilm dispersal (and its clinical implications), and multi-species biofilms that are relevant to polymicrobial infections.When microbes form a matured biofilm within human hosts through medical devices such as CVCs, the infection becomes resistant to antibiotic treatment and can develop into a chronic condition. For that reason, many techniques have been used to prevent the formation of biofilm by targeting different stages of biofilm maturation. Other methods have been used to diagnose and treat established cases of CLABSI.Catheter removal is the conventional management of catheter associated bacteremia; however, the procedure itself carries a relatively high risk of mechanical complications. Salvaging the catheter can help to minimize these complications.In this article, we provide an overview of microbial biofilm formation; describe the involvement of various genetic determinants, adhesion proteins, organelles, mechanism(s) of biofilm formation, polymicrobial infections, and biofilm-associated infections on indwelling intravascular catheters; and describe the diagnosis, management, and prevention of catheter-related bloodstream infections

  2. Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections.

    PubMed

    Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves; Felden, Brice

    2016-09-01

    Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections. PMID:27224202

  3. Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections

    PubMed Central

    Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves

    2016-01-01

    Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections. PMID:27224202

  4. Bloodstream infections in patients with hematological malignancies: which is more fatal – cancer or resistant pathogens?

    PubMed Central

    Gedik, Habip; Şimşek, Funda; Kantürk, Arzu; Yildirmak, Taner; Arica, Deniz; Aydin, Demet; Demirel, Naciye; Yokuş, Osman

    2014-01-01

    Background The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies. Methods In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward. Results During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in the second study year. In 13 of 18 cases (72%) with bloodstream yeast infections, previous azole exposure was recorded. Candida parapsilosis, C. glabrata, and C. albicans isolates were resistant to voriconazole and fluconazole. Conclusion BSIs that occur during febrile neutropenic episodes in hematology patients due to Gram-negative bacteria should be treated initially with non-carbapenem-based antipseudomonal therapy taking into consideration antimicrobial stewardship. Non-azole antifungal drugs, including caspofungin and liposomal amphotericin B, should be preferred as empirical antifungal therapy in the events of possible

  5. Bloodstream infections due to Peptoniphilus spp.: report of 15 cases

    PubMed Central

    Brown, K; Church, D; Lynch, T; Gregson, D

    2014-01-01

    Peptoniphilus spp. are Gram-positive anaerobic cocci (GPAC) that were formerly classified in the genus Peptostreptococcus. This study describes 15 cases of Peptoniphilus spp. bloodstream infection (BSI) diagnosed from 2007 to 2011 using 16S rDNA sequencing in patients with pneumonia, pre-term delivery, soft tissue infection or colon or bladder disease. Seven out of 15 (47%) of these cases had polymicrobial BSIs. One of the isolates was closely related to P. duerdenii (EU526290), while the other 14 isolates were most closely related to a Peptoniphilus sp. reference strain (ATCC 29743) and P. hareii (Y07839). Peptoniphilus is a rare but important cause of BSI. PMID:24773457

  6. Reducing bloodstream infection with a chlorhexidine gel IV dressing.

    PubMed

    Jeanes, Annette; Bitmead, James

    The use of vascular access devices (VAD) is common in healthcare provision but there is a significant risk of acquiring an infection. Central venous catheters (CVC) are associated with the highest risk of intravenous catheter-related bloodstream infection (CRBSI). 3M™ Tegaderm™ CHG IV dressing is a semi-permeable transparent adhesive dressing with an integrated gel pad containing chlorhexidine gluconate 2%. This product was reviewed by the National Institute for Health and Care Excellence (NICE) in 2015, recommending that Tegaderm CHG could be used for CVC and arterial line dressings in high-dependency and intensive-care settings. This article discusses issues around CRBSI, interventions to reduce the risk of CRBSI, and the use of Tegaderm CHG dressing. PMID:26496869

  7. Cefotaxime resistance and outcome of Klebsiella spp bloodstream infection.

    PubMed

    Ortega, M; Marco, F; Soriano, A; Almela, M; Martínez, J A; López, J; Pitart, C; Mensa, J

    2011-12-01

    We attempt to describe the epidemiology and outcome associated with cefotaxime-resistant (CTX-R) Klebsiella spp bacteraemia. Klebsiella spp bloodstream infection episodes prospectively collected through a blood culture surveillance programme from January 1991 to December 2008 in a single institution were analysed. A total of 910 monomicrobial episodes of Klebsiella spp bacteraemia were identified during the study period. The most important sources were from urinary tract infection, unknown sources, billiary focus and catheter related infection. There were 112 (12%) CTX-R isolates. Out of 112 isolates, 98 were CTX-R by Extended-Spectrum β-Lactamase production. Shock on presentation and mortality were significantly more frequent in CTX-R than in CTX susceptible isolates. Inappropriate empirical therapy was received in 50 (45%) cases in the CTX-R Klebsiella spp group (13 cases of death, 26%). Predictive factors associated with CTX-R Klebsiella spp isolate were: previous β-lactam therapy (OR = 4.16), nosocomial acquired bacteraemia (OR = 1.93), solid organ trasplantation (OR = 2.09) and shock (OR = 1.90). Independent risk factors associated with mortality in Klebsiella spp bacteraemia were: age (OR = 1.03), liver cirrhosis (OR = 2.63), ultimately or rapidly fatal prognosis of underlying disease (OR = 2.44), shock (OR = 8.60), pneumonia (OR = 4.96) or intraabdominal (OR = 3.85) source of bacteraemia and CTX-R isolate (OR = 4.63). Klebsiella spp is an important cause of bloodstream infection. CTX-R isolates have been increasing since 2000. CTX-R is an independent factor associated with mortality in Klebsiella spp bacteraemia. PMID:21509474

  8. Diagnosis of Bacterial Bloodstream Infections: A 16S Metagenomics Approach

    PubMed Central

    Van Puyvelde, Sandra; De Block, Tessa; Maltha, Jessica; Palpouguini, Lompo; Tahita, Marc; Tinto, Halidou; Jacobs, Jan; Deborggraeve, Stijn

    2016-01-01

    Background Bacterial bloodstream infection (bBSI) is one of the leading causes of death in critically ill patients and accurate diagnosis is therefore crucial. We here report a 16S metagenomics approach for diagnosing and understanding bBSI. Methodology/Principal Findings The proof-of-concept was delivered in 75 children (median age 15 months) with severe febrile illness in Burkina Faso. Standard blood culture and malaria testing were conducted at the time of hospital admission. 16S metagenomics testing was done retrospectively and in duplicate on the blood of all patients. Total DNA was extracted from the blood and the V3–V4 regions of the bacterial 16S rRNA genes were amplified by PCR and deep sequenced on an Illumina MiSeq sequencer. Paired reads were curated, taxonomically labeled, and filtered. Blood culture diagnosed bBSI in 12 patients, but this number increased to 22 patients when combining blood culture and 16S metagenomics results. In addition to superior sensitivity compared to standard blood culture, 16S metagenomics revealed important novel insights into the nature of bBSI. Patients with acute malaria or recovering from malaria had a 7-fold higher risk of presenting polymicrobial bloodstream infections compared to patients with no recent malaria diagnosis (p-value = 0.046). Malaria is known to affect epithelial gut function and may thus facilitate bacterial translocation from the intestinal lumen to the blood. Importantly, patients with such polymicrobial blood infections showed a 9-fold higher risk factor for not surviving their febrile illness (p-value = 0.030). Conclusions/Significance Our data demonstrate that 16S metagenomics is a powerful approach for the diagnosis and understanding of bBSI. This proof-of-concept study also showed that appropriate control samples are crucial to detect background signals due to environmental contamination. PMID:26927306

  9. Emerging commercial molecular tests for the diagnosis of bloodstream infection.

    PubMed

    Mwaigwisya, Solomon; Assiri, Rasha Assad M; O'Grady, Justin

    2015-05-01

    Bloodstream infection (BSI) by microorganisms can lead to sepsis. This condition has a high mortality rate, which rises significantly with delays in initiation of appropriate antimicrobial treatment. Current culture methods for diagnosing BSI have long turnaround times and poor clinical sensitivity. While clinicians wait for culture diagnosis, patients are treated empirically, which can result in inappropriate treatment, undesirable side effects and contribute to drug resistance development. Molecular diagnostics assays that target pathogen DNA can identify pathogens and resistance markers within hours. Early diagnosis improves antibiotic stewardship and is associated with favorable clinical outcomes. Nonetheless, limitations of current molecular diagnostic methods are substantial. This article reviews recent commercially available molecular methods that use pathogen DNA to diagnose BSI, either by testing positive blood cultures or directly testing patient blood. We critically assess these tests and their application in clinical microbiology. A view of future directions in BSI diagnosis is also provided. PMID:25866124

  10. Molecular tracking of Candida albicans in a neonatal intensive care unit: long-term colonizations versus catheter-related infections.

    PubMed Central

    Ruiz-Diez, B; Martinez, V; Alvarez, M; Rodriguez-Tudela, J L; Martinez-Suarez, J V

    1997-01-01

    Nosocomial neonatal candidiasis is a major problem in infants requiring intensive therapy. The subjects of this retrospective study were nine preterm infants admitted to the neonatal intensive care unit of the Hospital Central de Asturias between March 1993 and August 1994. The infants were infected with or colonized by Candida albicans. Five patients developed C. albicans bloodstream infections. A total of 36 isolates (including isolates from catheters and parenteral nutrition) were examined for molecular relatedness by PCR fingerprinting and restriction fragment length polymorphism (RFLP) analysis. The core sequence of phage M13 was used as a single primer in the PCR-based fingerprinting procedure, and RFLP analysis was performed with C. albicans-specific DNA probe 27A. Both techniques were evaluated with a panel of eight C. albicans reference strains, and each technique showed eight different patterns. With the 36 isolates from neonates, each technique enabled us to identify by PCR and RFLP analysis seven and six different patterns, respectively. The combination of these two methods (composite DNA type) identified eight different profiles. A strain with one of these profiles was present in three patients and in their respective catheters. Patients infected with or colonized by this isolate profile were clustered in time. Among the other patients, each patient was infected over time and at multiple anatomic sites with a C. albicans strain with a distinct DNA type. We conclude that C. albicans was most commonly producing long-term colonizations, although horizontal transmission probably due to catheters also occurred. PMID:9399489

  11. Infectious Complications and Morbidities After Neonatal Bloodstream Infections

    PubMed Central

    Tsai, Ming-Horng; Lee, Chiang-Wen; Chu, Shih-Ming; Lee, I-Ta; Lien, Reyin; Huang, Hsuan-Rong; Chiang, Ming-Chou; Fu, Ren-Huei; Hsu, Jen-Fu; Huang, Yhu-Chering

    2016-01-01

    Abstract Few data are available on the clinical characteristics of complications and morbidities after neonatal bloodstream infections (BSIs), understood as any newly infectious focus or organ dysfunction directly related to BSIs but not occur concurrently. However, these bloodstream-associated infectious complications (BSICs) contribute significantly to increased hospital stay, cost, and final mortality. We performed an observational cohort study of unselected neonatal intensive care unit (NICU) patients based on records in a large clinical database. All neonates hospitalized in our NICU with BSI between 2006 and 2013 were reviewed, and those who developed BSICs were analyzed to identify the clinical characteristics and outcomes. Multivariate logistic regression was used to identify independent risk factors for BSICs. Of 975 episodes of neonatal BSI, 101 (10.4%) BSICs occurred in 93 neonates with a median interval of 3 days (range, 0–17 days) after onset of BSI and included newly infectious focuses in 40 episodes (39.6%), major organ dysfunctions after septic shock in 36 episodes (35.6%), and neurological complications after meningitis or septic shock in 34 episodes (33.7%). All patients with BSICs encountered various morbidities, which subsequently resulted in in-hospital death in 30 (32.3%) neonates, critical discharge in 4 (4.3%), and persistent sequelae in 17 (18.3%). After multivariate logistic regression analysis, independent risk factors for BSICs included initial inappropriate antibiotics (odds ratio [OR], 5.54; 95% confidence interval [CI], 3.40–9.01), BSI with septic shock (OR, 5.75; 95% CI, 3.51–9.40), and BSI concurrent with meningitis (OR, 9.20; 95% CI, 4.33–19.56). It is worth noting that a percentage of neonates with BSI encountered subsequent sequelae or died of infections complications, which were significantly associated with initial inappropriate antibiotic therapy, septic shock, and the occurrence of meningitis. Further investigation is

  12. Bloodstream Infection Due to Brachyspira pilosicoli in a Patient with Multiorgan Failure▿

    PubMed Central

    Prim, Núria; Pericas, Roser; Español, Montse; Rivera, Alba; Mirelis, Beatriz; Coll, Pere

    2011-01-01

    Brachyspira pilosicoli is an etiological agent of human intestinal spirochetosis. Bloodstream infection due to this microorganism is rare. We report a case of B. pilosicoli bacteremia in a 70-year-old patient who presented with multiorgan failure. PMID:21832021

  13. In vitro antifungal susceptibility of Malassezia furfur from bloodstream infections.

    PubMed

    Iatta, Roberta; Figueredo, Luciana A; Montagna, Maria Teresa; Otranto, Domenico; Cafarchia, Claudia

    2014-11-01

    Fungaemia caused by Malassezia spp. in hospitalized patients requires prompt and appropriate therapy, but standard methods for the definition of the in vitro antifungal susceptibility have not been established yet. In this study, the in vitro susceptibility of Malassezia furfur from bloodstream infections (BSIs) to amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), posaconazole (POS) and voriconazole (VRC) was assessed using the broth microdilution (BMD) method of the Clinical and Laboratory Standards Institute (CLSI) with different media such as modified Sabouraud dextrose broth (SDB), RPMI and Christensen's urea broth (CUB). Optimal broth media that allow sufficient growth of M. furfur, and produce reliable and reproducible MICs using the CLSI BMD protocol were assessed. Thirty-six M. furfur isolates collected from BSIs of patients before and during AMB therapy, and receiving FLC prophylaxis, were tested. A good growth of M. furfur was observed in RPMI, CUB and SDB at 32 °C for 48 and 72 h. No statistically significant differences were detected between the MIC values registered after 48 and 72 h incubation. ITC, POS and VRC displayed lower MICs than FLC and AMB. These last two antifungal drugs showed higher and lower MICs, respectively, when the isolates were tested in SDB. SDB is the only medium in which it is possible to detect isolates with high FLC MICs in patients receiving FLC prophylaxis. A large number of isolates showed high AMB MIC values regardless of the media used. In conclusion, SDB might be suitable to determine triazole susceptibility. However, the media, the drug formulation or the breakpoints herein applied might not be useful for assessing the AMB susceptibility of M. furfur from BSIs. PMID:25168965

  14. Surveillance of Candida spp Bloodstream Infections: Epidemiological Trends and Risk Factors of Death in Two Mexican Tertiary Care Hospitals

    PubMed Central

    Corzo-Leon, Dora E.; Alvarado-Matute, Tito; Colombo, Arnaldo L.; Cornejo-Juarez, Patricia; Cortes, Jorge; Echevarria, Juan I.; Guzman-Blanco, Manuel; Macias, Alejandro E.; Nucci, Marcio; Ostrosky-Zeichner, Luis; Ponce-de-Leon, Alfredo; Queiroz-Telles, Flavio; Santolaya, Maria E.; Thompson-Moya, Luis; Tiraboschi, Iris N.; Zurita, Jeannete; Sifuentes-Osornio, Jose

    2014-01-01

    Introduction Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI). Objective To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City. Design Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010. Methods All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis. Results CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥16 (OR = 6.94, CI95% = 2.34–20.58, p<0.0001), and liver disease (OR = 186.11, CI95% = 7.61–4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed. Conclusions The cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI. PMID:24830654

  15. Non-albicans Candida Infection: An Emerging Threat

    PubMed Central

    Deorukhkar, Sachin C.; Saini, Santosh

    2014-01-01

    The very nature of infectious diseases has undergone profound changes in the past few decades. Fungi once considered as nonpathogenic or less virulent are now recognized as a primary cause of morbidity and mortality in immunocompromised and severely ill patients. Candida spp. are among the most common fungal pathogens. Candida albicans was the predominant cause of candidiasis. However, a shift toward non-albicans Candida species has been recently observed. These non-albicans Candida species demonstrate reduced susceptibility to commonly used antifungal drugs. In the present study, we investigated the prevalence of non-albicans Candida spp. among Candida isolates from various clinical specimens and analysed their virulence factors and antifungal susceptibility profile. A total of 523 Candida spp. were isolated from various clinical specimens. Non-albicans Candida species were the predominant pathogens isolated. Non-albicans Candida species also demonstrated the production of virulence factors once attributed to Candida albicans. Non-albicans Candida demonstrated high resistance to azole group of antifungal agents. Therefore, it can be concluded that non-albicans Candida species have emerged as an important cause of infections. Their isolation from clinical specimen can no longer be ignored as a nonpathogenic isolate nor can it be dismissed as a contaminant. PMID:25404942

  16. Enterobacteriaceae Bloodstream Infections: Presence of Integrons, Risk Factors, and Outcome▿

    PubMed Central

    Daikos, George L.; Kosmidis, Chris; Tassios, Panayotis T.; Petrikkos, George; Vasilakopoulou, Alexandra; Psychogiou, Mina; Stefanou, Ioanna; Avlami, Athina; Katsilambros, Nikolaos

    2007-01-01

    A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum β-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-β-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of ≥4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic

  17. Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella

    PubMed Central

    2013-01-01

    Background Candida spp. are recognized as a primary agent of severe fungal infection in immunocompromised patients, and are the fourth most common cause of bloodstream infections. Our study explores treatment with photodynamic therapy (PDT) as an innovative antimicrobial technology that employs a nontoxic dye, termed a photosensitizer (PS), followed by irradiation with harmless visible light. After photoactivation, the PS produces either singlet oxygen or other reactive oxygen species (ROS) that primarily react with the pathogen cell wall, promoting permeabilization of the membrane and cell death. The emergence of antifungal-resistant Candida strains has motivated the study of antimicrobial PDT (aPDT) as an alternative treatment of these infections. We employed the invertebrate wax moth Galleria mellonella as an in vivo model to study the effects of aPDT against C. albicans infection. The effects of aPDT combined with conventional antifungal drugs were also evaluated in G. mellonella. Results We verified that methylene blue-mediated aPDT prolonged the survival of C. albicans infected G. mellonella larvae. The fungal burden of G. mellonella hemolymph was reduced after aPDT in infected larvae. A fluconazole-resistant C. albicans strain was used to test the combination of aPDT and fluconazole. Administration of fluconazole either before or after exposing the larvae to aPDT significantly prolonged the survival of the larvae compared to either treatment alone. Conclusions G. mellonella is a useful in vivo model to evaluate aPDT as a treatment regimen for Candida infections. The data suggests that combined aPDT and antifungal therapy could be an alternative approach to antifungal-resistant Candida strains. PMID:24083556

  18. Catheter salvage in home infusion patients with central line-associated bloodstream infection.

    PubMed

    Caroff, Daniel A; Norris, Anne H; Keller, Sara; Vinnard, Christopher; Zeitler, Kristen E; Lukaszewicz, Jennifer; Zborowski, Kristine A; Linkin, Darren R

    2014-12-01

    In a retrospective study of home infusion patients with central line-associated bloodstream infection, use of a central venous port, cancer diagnosis, and absence of systemic inflammatory response syndrome were associated with use of catheter salvage. Relapse of infection was uncommon. PMID:25465266

  19. A case of catheter-related bloodstream infection caused by Mycobacterium phocaicum.

    PubMed

    Simkins, Jacques; Rosenblatt, Joseph D

    2013-05-01

    We present a patient with double hit Burkitt's like lymphoma who developed a catheter-related bloodstream infection due to Mycobacterium phocaicum that was identified by rpoB gene sequencing. His infection resolved with 7 weeks of antibiotics and port-a-cath removal. PMID:23537787

  20. Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity

    PubMed Central

    2014-01-01

    Background Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation. Results Biofilm formation was shown to be heterogeneous; with isolates being defined as either high or low biofilm formers (LBF and HBF) based on different biomass quantification. These categories could also be differentiated using a cell surface hydrophobicity assay with 24 h biofilms. HBF isolates were more resistance to amphotericin B (AMB) treatment than LBF, but not voriconazole (VRZ). In a Galleria mellonella model of infection HBF mortality was significantly increased in comparison to LBF. Histological analysis of the HBF showed hyphal elements intertwined indicative of the biofilm phenotype. Transcriptional analysis of 23 genes implicated in biofilm formation showed no significant differential expression profiles between LBF and HBF, except for Cdr1 at 4 and 24 h. Cluster analysis showed similar patterns of expression for different functional classes of genes, though correlation analysis of the 4 h biofilms with overall biomass at 24 h showed that 7 genes were correlated with high levels of biofilm, including Als3, Eap1, Cph1, Sap5, Plb1, Cdr1 and Zap1. Conclusions Our findings show that biofilm formation is variable amongst C. albicans isolates, and categorising isolates depending on this can be used to predict how pathogenic the isolate will behave clinically. We have shown that looking at individual genes in less informative than looking at multiple genes when trying to categorise isolates at LBF or HBF. These findings are important when developing biofilm-specific diagnostics as these could be

  1. Innate immune cell response upon Candida albicans infection.

    PubMed

    Qin, Yulin; Zhang, Lulu; Xu, Zheng; Zhang, Jinyu; Jiang, Yuan-Ying; Cao, Yongbing; Yan, Tianhua

    2016-07-01

    Candida albicans is a polymorphic fungus which is the predominant cause of superficial and deep tissue fungal infections. This microorganism has developed efficient strategies to invade the host and evade host defense systems. However, the host immune system will be prepared for defense against the microbe by recognition of receptors, activation of signal transduction pathways and cooperation of immune cells. As a consequence, C. albicans could either be eliminated by immune cells rapidly or disseminate hematogenously, leading to life-threatening systemic infections. The interplay between Candida albicans and the host is complex, requiring recognition of the invaded pathogens, activation of intricate pathways and collaboration of various immune cells. In this review, we will focus on the effects of innate immunity that emphasize the first line protection of host defense against invaded C. albicans including the basis of receptor-mediated recognition and the mechanisms of cell-mediated immunity. PMID:27078171

  2. Draft Genome Sequences of Two Multidrug-Resistant Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae Strains Causing Bloodstream Infections.

    PubMed

    Carasso, Eran; Salmon-Divon, Mali; Carmeli, Yehuda; Banin, Ehud; Navon-Venezia, Shiri

    2016-01-01

    Multidrug-resistant (MDR) Klebsiella pneumoniae has become a major contributor to nosocomial bloodstream infections. Here, we report the draft genome sequences of two MDR extended-spectrum-β-lactamase-producing strains causing bloodstream infections. These sequenced genomes display a wide-spectrum virulence arsenal and will help us understand the genomic basis of K. pneumoniae virulence. PMID:26798092

  3. Use of heparin-coated central venous lines to prevent catheter-related bloodstream infection.

    PubMed

    Abdelkefi, Abderrahman; Achour, Wafa; Ben Othman, Tarek; Ladeb, Saloua; Torjman, Lamia; Lakhal, Amel; Ben Hassen, Assia; Hsairi, Mohamed; Ben Abdeladhim, Abdeladhim

    2007-06-01

    Bloodstream infections related to the use of central venous catheters are an important cause of patient morbidity, mortality, and increased health care costs. Catheter-related infection may be due to fibrin deposition associated with catheters. Interventions designed to decrease fibrin deposition have the potential to reduce catheter-related infections. This study was a randomized, controlled trial in which 246 patients with nontunneled central venous catheters were randomly assigned to receive a heparin-coated catheter with 50 mL/d of normal saline solution as a continuous infusion (heparin-coated group) or a noncoated catheter with a continuous infusion of low-dose unfractionated heparin (control group: continuous infusion of 100 U/kg/d). Catheter-related bloodstream infection occurred in 2.5% (3/120 catheters) in the heparin-coated group (0.9 events per 1,000 days) and in 9.1% (11/120 catheters) in the control group (3.5 events per 1,000 days; P = 0.027). No other risk factors were found for the development of catheter-related bloodstream infection. Six and seven patients experienced severe bleeding in the heparin-coated and control groups, respectively (P = 1.00). We did not observe heparin-induced thrombocytopenia. The use of heparin-coated catheters can be a safe and effective approach to the prevention of catheter-related bloodstream infection in patients with hematooncologic disease. PMID:17624052

  4. Prevention of bloodstream infections by photodynamic inactivation of multiresistant Pseudomonas aeruginosa in burn wounds

    NASA Astrophysics Data System (ADS)

    Hashimoto, M. C. E.; Prates, R. A.; Toffoli, D. J.; Courrol, L. C.; Ribeiro, M. S.

    2010-02-01

    Bloodstream infections are potentially life-threatening diseases. They can cause serious secondary infections, and may result in endocarditis, severe sepsis or toxic-shock syndrome. Pseudomonas aeruginosa is an opportunistic pathogen and one of the most important etiological factors responsible for nosocomial infections, mainly in immuno-compromissed hosts, characteristic of patients with severe burns. Its multiresistance to antibiotics produces many therapeutic problems, and for this reason, the development of an alternative method to antibiotic therapy is needed. Photodynamic inactivation (PDI) may be an effective and alternative therapeutic option to prevent bloodstream infections in patients with severe burns. In this study we report the use of PDI to prevent bloodstream infections in mice with third-degree burns. Burns were produced on the back of the animals and they were infected with 109 cfu/mL of multi-resistant (MR) P. aeruginosa. Fifteen animals were divided into 3 groups: control, PDT blue and PDT red. PDT was performed thirty minutes after bacterial inoculation using 10μM HB:La+3 and a light-emitting diode (LED) emitting at λ=460nm+/-20nm and a LED emitting at λ=645 nm+/-10nm for 120s. Blood of mice were colected at 7h, 10h, 15h, 18h and 22h pos-infection (p.i.) for bacterial counting. Control group presented 1×104 cfu/mL in bloodstream at 7h p.i. increasing to 1×106 at 22h, while mice PDT-treated did not present any bacteria at 7h; only at 22h p.i. they presented 1×104cfu/mL. These results suggest that HB:La+3 associated to blue LED or red LED is effective to delay and diminish MR P.aeruginosa bloodstream invasion in third-degree-burned mice.

  5. Tsukamurella pulmonis Bloodstream Infection Identified by secA1 Gene Sequencing

    PubMed Central

    Cano, María E.; García de la Fuente, Celia; Martínez-Martínez, Luis; López, Mónica; Fernández-Mazarrasa, Carlos

    2014-01-01

    Recurrent bloodstream infections caused by a Gram-positive bacterium affected an immunocompromised child. Tsukamurella pulmonis was the microorganism identified by secA1 gene sequencing. Antibiotic treatment in combination with removal of the subcutaneous port healed the patient. PMID:25520439

  6. Deltamethrin Increases Candida albicans infection susceptibility in mice.

    PubMed

    Rehman, H; Mohan, A; Tabassum, H; Ahmad, F; Rahman, S; Parvez, S; Raisuddin, S

    2011-05-01

    Deltamethrin, an alpha-cyano type II synthetic pyrethroid insecticide, is used to control a wide range of insects on a variety of crops and vectors of diseases. Deltamethrin has been previously reported for its immunotoxic effects and therefore its exposure may affect the host resistance to infection and tumour challenge. Effect of exposure of deltamethrin on host resistance to Candida albicans infection was examined in Swiss albino mice. The objective of this study was to investigate the modulatory action of deltamethrin in C. albicans infected mice. The dose of deltamethrin was initially tested and selected from our previous study (18 mg/kg). Percentage of infection in deltamethrin treated animals increased faster when compared to that of the controls. Deltamethrin exposure along with C. albicans infection caused alteration of humoral immune response. The number of colony forming unit in liver and spleen were also found to be significantly increased in the treated group. The results from our present study suggest that deltamethrin exhibits an immunosuppressive effect and has a negative impact on host resistance to C. albicans infection. PMID:21272049

  7. Challenges in anti-infective development in the era of bad bugs, no drugs: a regulatory perspective using the example of bloodstream infection as an indication.

    PubMed

    Boucher, Helen W

    2010-01-01

    Bloodstream infections present many challenges to clinicians. The number of hospitalized patients with bloodstream infection continues to increase, and the number of newly available antimicrobial agents to treat these particularly lethal infections and many other serious infections continues to decrease. Drug-development programs for bloodstream infection that have adhered to existing regulatory guidelines have not been significantly successful. This article examines the regulatory history of the bloodstream infection indication as an example of the challenges faced by individuals and sponsors developing drugs for treatment of the current spectrum of antimicrobial-resistant infections, with the goal of providing insight into development pathways for agents targeting drug-resistant bacterial pathogens. Disease-specific and pathogen-specific indications are discussed, and recent regulatory approvals for bloodstream infection caused by vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus are reviewed. PMID:20067391

  8. Prevention of catheter-related bloodstream infections in patients on hemodialysis: challenges and management strategies

    PubMed Central

    Soi, Vivek; Moore, Carol L; Kumbar, Lalathakasha; Yee, Jerry

    2016-01-01

    Catheter-related bloodstream infections are a significant source of morbidity and mortality in the end-stage renal disease population. Although alternative accesses to undergoing renal replacement therapy exist, many patients begin hemodialysis with a dialysis catheter due to logistic and physiologic factors involved in arteriovenous fistula creation and maturation. Colonization of catheters via skin flora leads to the production of biofilm, which acts as a reservoir for virulent bacteria. Preventative therapies center on appropriate catheter maintenance, infection control measures, and early removal of devices as patients transition to other access. Despite best efforts, when conservative measures fail to prevent infections in a high-risk population, antimicrobial lock therapy should be considered as an option to combat catheter-related bloodstream infections. PMID:27143948

  9. Severe Community-Acquired Bloodstream Infection with Acinetobacter ursingii in Person who Injects Drugs

    PubMed Central

    Salzer, Helmut J.F.; Rolling, Thierry; Schmiedel, Stefan; Klupp, Eva-Maria; Lange, Christoph

    2016-01-01

    We report a community-acquired bloodstream infection with Acinteobacter ursingii in an HIV-negative woman who injected drugs. The infection was successfully treated with meropenem. Species identification was performed by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Improved identification of Acinetobacter spp. by using this method will help identify clinical effects of this underdiagnosed pathogen. PMID:26689082

  10. The Impact of Infectious Disease Specialist Consultation for Staphylococcus aureus Bloodstream Infections: A Systematic Review.

    PubMed

    Paulsen, Julie; Solligård, Erik; Damås, Jan Kristian; DeWan, Andrew; Åsvold, Bjørn Olav; Bracken, Michael B

    2016-03-01

    Staphylococcus aureus is a common cause of severe bloodstream infection. We performed a systematic review to assess whether consultation with infectious disease specialists decreased all-cause mortality or rate of complications of S aureus bloodstream infections. The review also assessed parameters associated with the quality of management of the infection. We searched for eligible studies in PubMed, Embase, Scopus, and clinical trials.gov as well as the references of included studies. We identified 22 observational studies and 1 study protocol for a randomized trial. A meta-analysis was not performed because of the high risk of bias in the included studies. The outcomes are reported in a narrative review. Most included studies reported survival benefit, in the adjusted analysis. Recommended management strategies were carried out significantly more often among patients seen by an infectious disease specialist. Trials, such as cluster-randomized controlled trials, can more validly assess the studies at low risk of bias. PMID:27047985

  11. The Impact of Infectious Disease Specialist Consultation for Staphylococcus aureus Bloodstream Infections: A Systematic Review

    PubMed Central

    Paulsen, Julie; Solligård, Erik; Damås, Jan Kristian; DeWan, Andrew; Åsvold, Bjørn Olav; Bracken, Michael B.

    2016-01-01

    Staphylococcus aureus is a common cause of severe bloodstream infection. We performed a systematic review to assess whether consultation with infectious disease specialists decreased all-cause mortality or rate of complications of S aureus bloodstream infections. The review also assessed parameters associated with the quality of management of the infection. We searched for eligible studies in PubMed, Embase, Scopus, and clinical trials.gov as well as the references of included studies. We identified 22 observational studies and 1 study protocol for a randomized trial. A meta-analysis was not performed because of the high risk of bias in the included studies. The outcomes are reported in a narrative review. Most included studies reported survival benefit, in the adjusted analysis. Recommended management strategies were carried out significantly more often among patients seen by an infectious disease specialist. Trials, such as cluster-randomized controlled trials, can more validly assess the studies at low risk of bias. PMID:27047985

  12. Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine prospects.

    PubMed

    Cassone, A

    2015-05-01

    Although a number of fungal species belonging to the genus Candida can cause acute vulvovaginal infection (VVC), Candida albicans is by far the most prevalent etiological agent, particularly for the most severe chronic condition known as recurrent vulvovaginal candidiasis (RVVC). This review focuses on recent advances in pathogenic mechanisms and host immune responses to C. albicans and on the utilisation of this information in the development of a vaccine to prevent and/or treat vaginal candidiasis. Currently, two vaccines with main or sole RVVC as clinical indication have completed a phase 1 clinical trial, and one of them has entered a phase 2 trial. PMID:25052208

  13. Two unlike cousins: Candida albicans and C. glabrata infection strategies

    PubMed Central

    Brunke, Sascha; Hube, Bernhard

    2013-01-01

    Candida albicans and C. glabrata are the two most common pathogenic yeasts of humans, yet they are phylogenetically, genetically and phenotypically very different. In this review, we compare and contrast the strategies of C. albicans and C. glabrata to attach to and invade into the host, obtain nutrients and evade the host immune response. Although their strategies share some basic concepts, they differ greatly in their outcome. While C. albicans follows an aggressive strategy to subvert the host response and to obtain nutrients for its survival, C. glabrata seems to have evolved a strategy which is based on stealth, evasion and persistence, without causing severe damage in murine models. However, both fungi are successful as commensals and as pathogens of humans. Understanding these strategies will help in finding novel ways to fight Candida, and fungal infections in general. PMID:23253282

  14. Second-Generation central venous catheter in the prevention of bloodstream infection: a systematic review 1

    PubMed Central

    Stocco, Janislei Gislei Dorociaki; Hoers, Hellen; Pott, Franciele Soares; Crozeta, Karla; Barbosa, Dulce Aparecida; Meier, Marineli Joaquim

    2016-01-01

    Abstract Objective: to evaluate the effectiveness and safety in the use of second-generation central venous catheters impregnated in clorhexidine and silver sulfadiazine when compared with other catheters, being them impregnated or not, in order to prevent the bloodstream infection prevention. Method: systematic review with meta-analysis. Databases searched: MEDLINE, EMBASE, CINAHL, LILACS/SciELO, Cochrane CENTRAL; search in Congress Proceedings and records from Clinical Trials. Results: 1.235 studies were identified, 97 were pre-selected and 4 were included. In catheter-related bloodstream infection, there was no statistical significance between second-generation impregnated catheter compared with the non-impregnated ones, absolute relative risk 1,5% confidence interval 95% (3%-1%), relative risk 0,68 (confidence interval 95%, 0,40-1,15) and number needed to treat 66. In the sensitivity analysis, there was less bloodstream infection in impregnated catheters (relative risk 0,50, confidence interval 95%, 0,26-0,96). Lower colonization, absolute relative risk 9,6% (confidence interval 95%, 10% to 4%), relative risk 0,51 (confidence interval 95% from 0,38-0,85) and number needed to treat 5. Conclusion: the use of second-generation catheters was effective in reducing the catheter colonization and infection when a sensitivity analysis is performed. Future clinical trials are suggested to evaluate sepsis rates, mortality and adverse effects. PMID:27508901

  15. Activity of daptomycin against staphylococci collected from bloodstream infections in Spanish medical centers.

    PubMed

    Picazo, Juan J; Betriu, Carmen; Culebras, Esther; Rodríguez-Avial, Iciar; Gómez, María; López, Fátima

    2009-08-01

    We used the broth microdilution method to determine the MICs of daptomycin and 13 comparator agents against 319 methicillin-susceptible Staphylococcus aureus isolates, 201 methicillin-resistant S. aureus (MRSA) isolates, and 183 coagulase-negative staphylococci (CoNS). Isolates were consecutively collected from bloodstream infections in 39 Spanish medical centers during a 3-month period (March through May 2008). Among MRSA, 1 isolate with intermediate susceptibility to vancomycin and 6 isolates resistant to linezolid were found. Nonsusceptibility to teicoplanin was detected in 3.9% of CoNS. Daptomycin was highly active against the staphylococcal blood isolates tested-all were inhibited at the daptomycin susceptibility breakpoint of < or = 1 microg/mL. Daptomycin retained its activity against the isolates that were resistant to teicoplanin or linezolid, or that had reduced susceptibility to vancomycin. These data suggest that daptomycin could be useful for the treatment of bloodstream infections caused by staphylococci. PMID:19631100

  16. Rapid and Selective Detection of Pathogenic Bacteria in Bloodstream Infections with Aptamer-Based Recognition.

    PubMed

    Shen, Haijing; Wang, Jie; Liu, Haoyang; Li, Zhihao; Jiang, Fenglei; Wang, Fu-Bing; Yuan, Quan

    2016-08-01

    Sepsis and bacteremia are life-threatening clinical syndromes associated with significant patient morbidity and mortality. Rapid and sensitive detection of pathogenic bacteria is the key to improve patient survival rates. Herein, we have rationally constructed a simple aptamer-based capture platform to shorten the time needed for confirmation of bacterial bloodstream infection in clinical blood samples. This capture platform is made of a mesoporous TiO2-coated magnetic nanoparticle and is modified with target aptamer. It features excellent bacterial enrichment efficiency of about 80% even at low bacterial concentrations (10-2000 CFU mL(-1)). More importantly, the bacteria can be enriched within 2 h, and the time for bacterial identification is effectively shortened in comparison to the "gold standard" in clinical diagnosis of bloodstream infection. The aptamer-based capture platform may pave a way for the detection of biomarkers and find potential applications in disease diagnosis. PMID:27411775

  17. Local Probiotic Therapy for Vaginal Candida albicans Infections.

    PubMed

    Kovachev, Stefan Miladinov; Vatcheva-Dobrevska, Rossitza Stefanova

    2015-03-01

    The high rate of vaginal Candida albicans recurrence is attributed to azole resistance rates as high as 15%. The aim of this study was to determine the clinical and microbiological efficacy of standard azole therapy for treatment of vaginal C. albicans infection alone and in combination with local probiotic as well as the effects on vaginal microbiota. This study included 436 women with vaginal candidiasis randomly assigned to two treatment groups. The first group, with 207 patients (12 dropouts), was administered 150 mg fluconazole and a single vaginal globule of fenticonazole (600 mg) on the same day. The second group of 209 patients (8 dropouts) followed the same treatment schedule; however, ten applications of a vaginal probiotic containing Lactobacillus acidophilus, L. rhamnosus, Streptococcus thermophilus, and L. delbrueckii subsp. bulgaricus were also administered beginning the fifth day after azole treatment. Microbiological analysis of the therapy efficacy in the first treatment group showed C. albicans resistance in over 30% of patients. Clinical complaints persisted after treatment administration in 79.7% (n = 165) of women in this group. Clinical complaints in the second group decreased to 31.1% (n = 65) and microbiological efficacy also improved among investigated parameters, from 93.7% (n = 193) to 95.2% (n = 198). The local application of probiotics after administration of combined azoles for treatment of vaginal C. albicans infections increases therapy efficacy and could prevent relapse. PMID:25362524

  18. Independent influence of negative blood cultures and bloodstream infections on in-hospital mortality

    PubMed Central

    2014-01-01

    Background The independent influence of blood culture testing and bloodstream infection (BSI) on hospital mortality is unclear. Methods We included all adults treated in non-psychiatric services at our hospital between 2004 and 2011. We identified all blood cultures and their results to determine the independent association of blood culture testing and BSI on death in hospital using proportional hazards modeling that adjusted for important covariates. Results Of 297 070 hospitalizations, 48 423 had negative blood cultures and 5274 had BSI. 12 529 (4.2%) died in hospital. Compared to those without blood cultures, culture-negative patients and those with BSI were sicker. Culture-negative patients had a significantly increased risk of death in hospital (adjusted hazard ratio [HR] ranging between 3.1 and 4.4 depending on admission urgency, extent of comorbidities, and whether the blood culture was taken in the intensive care unit). Patients with BSI had a significantly increased risk of death (adj-HR ranging between 3.8 and 24.3] that was significantly higher when BSI was: diagnosed within the first hospital day; polymicrobial; in patients who were exposed to immunosuppressants or were neutropenic; or due to Clostridial and Candidal organisms. Death risk in culture negative and bloodstream infection patients decreased significantly with time. Conclusions Risk of death in hospital is independently increased both in patients with negative blood cultures and further in those with bloodstream infection. Death risk associated with bloodstream infections varied by the patient’s immune status and the causative microorganism. PMID:24444097

  19. Persistent Bloodstream Infection with Kocuria rhizophila Related to a Damaged Central Catheter

    PubMed Central

    Becker, Karsten; Mérens, Audrey; Ferroni, Agnès; Dubern, Béatrice; Vu-Thien, Hoang

    2012-01-01

    A case of persistent bloodstream infection with Kocuria rhizophila related to a damaged central venous catheter in a 3-year-old girl with Hirschsprung's disease is reported. The strain was identified as K. rhizophila by 16S rRNA gene sequencing and matrix-assisted laser desorption ionization–time of flight mass spectrometry. Arbitrarily primed PCR analysis showed a clonal strain. The repeated septic episodes were resolved with the catheter repair. PMID:22259211

  20. Catheter-Related Bloodstream Infections (CR-BSI) in Geriatric Patients in Intensive Care Units.

    PubMed

    Chernecky, Cynthia; Macklin, Denise; Blackburn, Paul

    2015-01-01

    Catheter-related bloodstream infections (CR-BSIs) are bloodstream infections that, through specific laboratory testing, identify the intravascular catheter as the source of the bloodstream infection. By 2015, the rate of elderly patients 80 years of age and older admitted to the intensive care unit (ICU) will represent 1 in 4 admissions. Approximately 80 000 CR-BSIs occur in ICUs annually, potentially resulting in as many as 56 000 CR-BSIs occurring in the geriatric ICU patient, with 20% of these cases resulting in death. To minimize the occurrence of CR-BSIs in these patients, specific knowledge about the geriatric patient will have to be factored into the ICU health care professional's practice, including the development of a vascular access plan, which includes selection of the correct device and proper insertion of that device along with an evidence-based care and maintenance program. Intensive care unit health care professionals may be at a loss when it comes to navigating the vast array of vascular access medical devices available today. The Healthcare and Technology Synergy framework can assist the ICU health care professional to logically review each vascular access device and select those devices that best meet patient needs. PMID:26039650

  1. Cost-Effectiveness of Surveillance for Bloodstream Infections for Sepsis Management in Low-Resource Settings.

    PubMed

    Penno, Erin C; Baird, Sarah J; Crump, John A

    2015-10-01

    Bacterial sepsis is a leading cause of mortality among febrile patients in low- and middle-income countries, but blood culture services are not widely available. Consequently, empiric antimicrobial management of suspected bloodstream infection is based on generic guidelines that are rarely informed by local data on etiology and patterns of antimicrobial resistance. To evaluate the cost-effectiveness of surveillance for bloodstream infections to inform empiric management of suspected sepsis in low-resource areas, we compared costs and outcomes of generic antimicrobial management with management informed by local data on etiology and patterns of antimicrobial resistance. We applied a decision tree model to a hypothetical population of febrile patients presenting at the district hospital level in Africa. We found that the evidence-based regimen saved 534 more lives per 100,000 patients at an additional cost of $25.35 per patient, resulting in an incremental cost-effectiveness ratio of $4,739. This ratio compares favorably to standard cost-effectiveness thresholds, but should ultimately be compared with other policy-relevant alternatives to determine whether routine surveillance for bloodstream infections is a cost-effective strategy in the African context. PMID:26175032

  2. Significance of yeasts in bloodstream infection: Epidemiology and predisposing factors of Candidaemia in adult patients at a university hospital (2010-2014).

    PubMed

    Pongrácz, Júlia; Juhász, Emese; Iván, Miklós; Kristóf, Katalin

    2015-09-01

    The incidence of Candida bloodstream infection (BSI) has increased during the past decades. Species distribution is changing worldwide, and non-albicans Candida spp. are becoming more prevalent. Acquired resistance to antifungal agents has been documented in several reports. The aim of our study was to assess the epidemiology and antifungal susceptibility of Candida isolates from BSI at our institute. The incidence of Candida BSI increased during the first four years of our investigation, from 1.7 to 3.5 episodes / 10 000 admissions, then dropped to 2.66 episodes / 10 000 admissions in the last year. The most frequently isolated species was C. albicans (63%), followed by C. glabrata (13%), C. parapsilosis (10.2%), C. tropicalis (9.3%), and C. krusei (3.7%). One isolate each of C. kefyr, C. fabianii and C. inconspicua were detected. The percentage of C. albicans remained stable throughout the study period. The most frequent risk factors of Candida BSI in our patient population were intensive care treatment (60.4%), abdominal surgery (52.5%), and solid malignancy (30.7%). All isolates were wild-type organisms, no acquired antifungal resistance was detected. PMID:26551574

  3. Reactivity of (1→3)-β-d-glucan assay in bacterial bloodstream infections.

    PubMed

    Albert, O; Toubas, D; Strady, C; Cousson, J; Delmas, C; Vernet, V; Villena, I

    2011-11-01

    To diagnose invasive fungal infections, the detection of (1 → 3)-β-d-glucan in serum has shown variable specificity, depending on the targeted population. Several circumstances for false-positive results of beta-glucan tests have been identified, among which are severe bacterial infections. In this study, we measured (1 → 3)-β-d-glucan by the Fungitell test in the serum of 62 patients (one serum sample tested per patient) for whom invasive fungal infection was not suspected: 19 control subjects and 43 patients with bacteraemia. The test was interpretable for 58 sera: all 19 control subjects had negative beta-glucan test; among the 39 bacteraemic patients, we report 16 false-positive results. For the 22 patients undergoing bacteraemia due to Gram-negative bacilli, we observed 13 false-positive results (59%). Among the 17 patients with bloodstream infection involving Gram-positive cocci, three false-positive tests were recorded, but none in the eight cases of Streptococcus pneumoniae bacteraemia. Statistical analysis showed that beta-glucan levels were significantly higher in patients with Gram-negative bacilli bloodstream infection in comparison to those with bacteraemia due to Gram-positive cocci. These results were independent from other previously described causes for false-positive beta-glucan tests. These data might help physicians to interpret positive beta-glucan detection when an invasive fungal infection is suspected, especially for patients with bacterial infections. PMID:21479838

  4. Zebrafish Egg Infection Model for Studying Candida albicans Adhesion Factors.

    PubMed

    Chen, Yin-Zhi; Yang, Yun-Liang; Chu, Wen-Li; You, May-Su; Lo, Hsiu-Jung

    2015-01-01

    Disseminated candidiasis is associated with 30-40% mortality in severely immunocompromised patients. Among the causal agents, Candida albicans is the dominant one. Various animal models have been developed for investigating gene functions in C. albicans. Zebrafish injection models have increasingly been applied in elucidating C. albicans pathogenesis because of the conserved immunity, prolific fecundity of the zebrafish and the low costs of care systems. In this study, we established a simple, noninvasive zebrafish egg bath infection model, defined its optimal conditions, and evaluated the model with various C. albicans mutant strains. The deletion of SAP6 did not have significant effect on the virulence. By contrast, the deletion of BCR1, CPH1, EFG1, or TEC1 significantly reduced the virulence under current conditions. Furthermore, all embryos survived when co-incubated with bcr1/bcr1, cph1/cph1 efg1/efg1, efg1/efg1, or tec1/tec1 mutant cells. The results indicated that our novel zebrafish model is time-saving and cost effective. PMID:26569623

  5. 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

  6. Procalcitonin Levels in Gram-Positive, Gram-Negative, and Fungal Bloodstream Infections

    PubMed Central

    Ferranti, Marta; Moretti, Amedeo; Al Dhahab, Zainab Salim; Cenci, Elio; Mencacci, Antonella

    2015-01-01

    Procalcitonin (PCT) can discriminate bacterial from viral systemic infections and true bacteremia from contaminated blood cultures. The aim of this study was to evaluate PCT diagnostic accuracy in discriminating Gram-positive, Gram-negative, and fungal bloodstream infections. A total of 1,949 samples from patients with suspected bloodstream infections were included in the study. Median PCT value in Gram-negative (13.8 ng/mL, interquartile range (IQR) 3.4–44.1) bacteremias was significantly higher than in Gram-positive (2.1 ng/mL, IQR 0.6–7.6) or fungal (0.5 ng/mL, IQR 0.4–1) infections (P < 0.0001). Receiver operating characteristic analysis showed an area under the curve (AUC) for PCT of 0.765 (95% CI 0.725–0.805, P < 0.0001) in discriminating Gram-negatives from Gram-positives at the best cut-off value of 10.8 ng/mL and an AUC of 0.944 (95% CI 0.919–0.969, P < 0.0001) in discriminating Gram-negatives from fungi at the best cut-off of 1.6 ng/mL. Additional results showed a significant difference in median PCT values between Enterobacteriaceae and nonfermentative Gram-negative bacteria (17.1 ng/mL, IQR 5.9–48.5 versus 3.5 ng/mL, IQR 0.8–21.5; P < 0.0001). This study suggests that PCT may be of value to distinguish Gram-negative from Gram-positive and fungal bloodstream infections. Nevertheless, its utility to predict different microorganisms needs to be assessed in further studies. PMID:25852221

  7. Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine

    PubMed Central

    Nikiforou, Maria; Jacobs, Esmee M.R.; Kemp, Matthew W.; Hornef, Mathias W.; Payne, Matthew S.; Saito, Masatoshi; Newnham, John P.; Janssen, Leon E.W.; Jobe, Alan H.; Kallapur, Suhas G.; Kramer, Boris W.; Wolfs, Tim G.A.M.

    2016-01-01

    Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (C.albicans). Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic C.albicans infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic C.albicans infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic C.albicans infection. Pregnant sheep received intra-amniotic injections with 107 colony-forming units C.albicans or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of C.albicans. Intra-amniotic C.albicans caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3+ lymphocytes, MPO+ cells and elevated TNF-α and IL-17 mRNA levels. Fluconazole treatment in utero decreased intestinal C.albicans colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic C.albicans caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate C.albicans-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy. PMID:27411776

  8. Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine.

    PubMed

    Nikiforou, Maria; Jacobs, Esmee M R; Kemp, Matthew W; Hornef, Mathias W; Payne, Matthew S; Saito, Masatoshi; Newnham, John P; Janssen, Leon E W; Jobe, Alan H; Kallapur, Suhas G; Kramer, Boris W; Wolfs, Tim G A M

    2016-01-01

    Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (C.albicans). Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic C.albicans infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic C.albicans infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic C.albicans infection. Pregnant sheep received intra-amniotic injections with 10(7) colony-forming units C.albicans or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of C.albicans. Intra-amniotic C.albicans caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3(+) lymphocytes, MPO(+) cells and elevated TNF-α and IL-17 mRNA levels. Fluconazole treatment in utero decreased intestinal C.albicans colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic C.albicans caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate C.albicans-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy. PMID:27411776

  9. Manipulation of Autophagy in Phagocytes Facilitates Staphylococcus aureus Bloodstream Infection

    PubMed Central

    O'Keeffe, Kate M.; Wilk, Mieszko M.; Leech, John M.; Murphy, Alison G.; Laabei, Maisem; Monk, Ian R.; Massey, Ruth C.; Lindsay, Jodi A.; Foster, Timothy J.; Geoghegan, Joan A.

    2015-01-01

    The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of Staphylococcus aureus in the host. To date, the majority of work on S. aureus-phagocyte interactions has focused on neutrophils and, to a lesser extent, macrophages, yet we understand little about the role played by dendritic cells (DCs) in the direct killing of this bacterium. Using bone marrow-derived DCs (BMDCs), we demonstrate for the first time that DCs can effectively kill S. aureus but that certain strains of S. aureus have the capacity to evade DC (and macrophage) killing by manipulation of autophagic pathways. Strains with high levels of Agr activity were capable of causing autophagosome accumulation, were not killed by BMDCs, and subsequently escaped from the phagocyte, exerting significant cytotoxic effects. Conversely, strains that exhibited low levels of Agr activity failed to accumulate autophagosomes and were killed by BMDCs. Inhibition of the autophagic pathway by treatment with 3-methyladenine restored the bactericidal effects of BMDCs. Using an in vivo model of systemic infection, we demonstrated that the ability of S. aureus strains to evade phagocytic cell killing and to survive temporarily within phagocytes correlated with persistence in the periphery and that this effect is critically Agr dependent. Taken together, our data suggest that strains of S. aureus exhibiting high levels of Agr activity are capable of blocking autophagic flux, leading to the accumulation of autophagosomes. Within these autophagosomes, the bacteria are protected from phagocytic killing, thus providing an intracellular survival niche within professional phagocytes, which ultimately facilitates dissemination. PMID:26099586

  10. Bathing With 2% Chlorhexidine Gluconate: Evidence and Costs Associated With Central Line-Associated Bloodstream Infections.

    PubMed

    Shah, Hena N; Schwartz, Jennifer L; Luna, Gaye; Cullen, Deborah L

    2016-01-01

    In a coordinated national effort reported by the Agency for Healthcare Research and Quality, the use of 2% chlorhexidine gluconate (CHG) has reduced the central line-associated bloodstream infection (CLABSI) rate by 40%. Conversely, a recent randomized clinical trial determined that chlorhexidine bathing did not reduce the CLABSI rate. The objectives of this study were to conduct meta-analysis and clarify the effectiveness of 2% CHG bathing by nurses on CLABSIs in adult intensive care unit patients and to determine the contributing costs attributable to CLABSIs and 2% CHG bathing. Eligible studies that included the outcome of bloodstream infection rate for central lines were considered. A rigorous systematic review protocol and software tools available from the Joanna Briggs Institute via OvidSP were used. Agency for Healthcare Research and Quality tools assisted with identifiable CHG bathing costs. Four studies were included in the meta-analysis for the outcome of primary bloodstream infections, and 2 studies narratively supported the meta-analysis. A relative risk of 0.46 with 95% confidence interval (0.34-0.63) was determined. This significant effect is seen in an overall z-score of 4.84 (P < .0001). This meta-analysis supports that 2% CHG reduces CLABSIs. The estimated cost increase of 2% CHG-impregnated cloths is $4.10 versus nonmedicated bathing cloths. The cost associated with a single CLABSI is 10 times more than the cost of using 2% CHG-impregnated cloths. Nursing provides significant influence for the prevention of CLABSIs in critical care via evidence-based best practices. PMID:26633158

  11. Endothelial Cell Stimulation by Candida albicans

    PubMed Central

    Phan, Quynh T.; Filler, Scott G.

    2013-01-01

    The opportunistic fungal pathogen, Candida albicans, enters the bloodstream and causes hematogenously disseminated infection in hospitalized patients. During the initiation of a hematogenously disseminated infection, endothelial cells are one of the first host cells to come in contact with C. albicans. Endothelial cells can significantly influence the local host response to C. albicans by expressing leukocyte adhesion molecules and pro-inflammatory cytokines. Thus, it is of interest to investigate the response of endothelial cells to C. albicans in vitro. We describe the use of real-time PCR and enzyme immunoassays to measure the effects of C. albicans on the endothelial cell production of E-selectin and tumor necrosis factor α in vitro. PMID:19089392

  12. Ca3 fingerprinting of Candida albicans bloodstream isolates from the United States, Canada, South America, and Europe reveals a European clade.

    PubMed

    Pujol, Claude; Pfaller, Michael; Soll, David R

    2002-08-01

    It was previously demonstrated by a cluster analysis that 26 unrelated U.S. isolates of Candida albicans separated into three distinct groups (groups I, II, and III) while South African isolates separated into four distinct groups (groups I, II, III, and SA). To verify the absence or underrepresentation of SA isolates in North America, and to identify which groups are represented in Europe and South America, collections of bloodstream isolates from each geographical locale were analyzed by cluster analyses based on genetic fingerprinting with the Ca3 probe. The results verify that North America is almost devoid of SA isolates (2%). However, the results reveal a new clade, designated group E, relatively specific to Europe. While 26% of a European collection of 46 isolates was composed of group E isolates, only 2% of the 164 North American isolates, 5% of 22 South American isolates, and 1% of 361 South African isolates were composed of group E isolates. The North American collection proved to be the least-diverse collection in regard to group representation. In a comparison of collections from the Northeast, Midwest, and Southwest regions of the United States, Canada, and South America, it was demonstrated that both the U.S. Southwest and the South American collections were devoid of group II isolates. Together these results identify for the first time a European-specific clade and demonstrate clear distinctions in the representations of the five demonstrated clades (groups I, II, III, SA, and E) in different geographical locales. PMID:12149321

  13. Risk and Prognosis of Bloodstream Infections among Patients on Chronic Hemodialysis: A Population-Based Cohort Study

    PubMed Central

    Skov Dalgaard, Lars; Nørgaard, Mette; Jespersen, Bente; Jensen-Fangel, Søren; Østergaard, Lars Jørgen; Schønheyder, Henrik Carl; Søgaard, Ole Schmeltz

    2015-01-01

    Background and Objectives Infections are common complications among patients on chronic hemodialysis. This population-based cohort study aims to estimate risk and case fatality of bloodstream infection among chronic hemodialysis patients. Methods In this population-based cohort study we identified residents with end-stage renal disease in Central and North Jutland, Denmark who had hemodialysis as first renal replacement therapy (hemodialysis patients) during 1995–2010. For each hemodialysis patient, we sampled 19 persons from the general population matched on age, gender, and municipality. Information on positive blood cultures was obtained from regional microbiology databases. All persons were observed from cohort entry until first episode of bloodstream infection, emigration, death, or end of hemodialysis treatment, whichever came first. Incidence-rates and incidence-rate ratios were computed and risk factors for bloodstream infection assessed by Poisson regression. Case fatality was compared by Cox regression. Results Among 1792 hemodialysis patients and 33 618 matched population controls, we identified 461 and 1126 first episodes of bloodstream infection, respectively. Incidence rates of first episode of bloodstream infection were 13.7 (95% confidence interval (CI), 12.5–15.0) per 100 person-years among hemodialysis patients and 0.53 (95% CI, 0.50–0.56) per 100 person-years among population controls. In hemodialysis patients, the most common causative microorganisms were Staphylococcus aureus (43.8%) and Escherichia coli (12.6%). The 30-day case fatality was similar among hemodialysis patients and population controls 16% (95% CI, 13%–20%) vs. 18% (95% CI, 15%–20%). Conclusions Hemodialysis patients have extraordinary high risk of bloodstream infection while short-term case fatality following is similar to that of population controls. PMID:25910221

  14. Whole-Genome Sequencing to Determine Origin of Multinational Outbreak of Sarocladium kiliense Bloodstream Infections

    PubMed Central

    Roe, Chandler C.; Smith, Rachel M.; Vallabhaneni, Snigdha; Duarte, Carolina; Escandón, Patricia; Castañeda, Elizabeth; Gómez, Beatriz L.; de Bedout, Catalina; López, Luisa F.; Salas, Valentina; Hederra, Luz Maria; Fernández, Jorge; Pidal, Paola; Hormazabel, Juan Carlos; Otaíza-O’Ryan, Fernando; Vannberg, Fredrik O.; Gillece, John; Lemmer, Darrin; Driebe, Elizabeth M.; Engelthaler, David M.; Litvintseva, Anastasia P.

    2016-01-01

    We used whole-genome sequence typing (WGST) to investigate an outbreak of Sarocladium kiliense bloodstream infections (BSI) associated with receipt of contaminated antinausea medication among oncology patients in Colombia and Chile during 2013–2014. Twenty-five outbreak isolates (18 from patients and 7 from medication vials) and 11 control isolates unrelated to this outbreak were subjected to WGST to elucidate a source of infection. All outbreak isolates were nearly indistinguishable (<5 single-nucleotide polymorphisms), and >21,000 single-nucleotide polymorphisms were identified from unrelated control isolates, suggesting a point source for this outbreak. S. kiliense has been previously implicated in healthcare-related infections; however, the lack of available typing methods has precluded the ability to substantiate point sources. WGST for outbreak investigation caused by eukaryotic pathogens without reference genomes or existing genotyping methods enables accurate source identification to guide implementation of appropriate control and prevention measures. PMID:26891230

  15. Dynamic Transcript Profiling of Candida albicans Infection in Zebrafish: A Pathogen-Host Interaction Study

    PubMed Central

    Liu, Fu-Chen; Hsu, Po-Chen; Chen, Hsueh-Fen; Peng, Shih-Chi; Chuang, Yung-Jen; Lan, Chung-Yu; Hsieh, Wen-Ping; Wong, David Shan Hill

    2013-01-01

    Candida albicans is responsible for a number of life-threatening infections and causes considerable morbidity and mortality in immunocompromised patients. Previous studies of C. albicans pathogenesis have suggested several steps must occur before virulent infection, including early adhesion, invasion, and late tissue damage. However, the mechanism that triggers C. albicans transformation from yeast to hyphae form during infection has yet to be fully elucidated. This study used a systems biology approach to investigate C. albicans infection in zebrafish. The surviving fish were sampled at different post-infection time points to obtain time-lapsed, genome-wide transcriptomic data from both organisms, which were accompanied with in sync histological analyses. Principal component analysis (PCA) was used to analyze the dynamic gene expression profiles of significant variations in both C. albicans and zebrafish. The results categorized C. albicans infection into three progressing phases: adhesion, invasion, and damage. Such findings were highly supported by the corresponding histological analysis. Furthermore, the dynamic interspecies transcript profiling revealed that C. albicans activated its filamentous formation during invasion and the iron scavenging functions during the damage phases, whereas zebrafish ceased its iron homeostasis function following massive hemorrhage during the later stages of infection. Most of the immune related genes were expressed as the infection progressed from invasion to the damage phase. Such global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection could be crucial in understanding control fungal pathogenesis. PMID:24019870

  16. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction

    PubMed Central

    Coburn, Phillip S.; Wiskur, Brandt J.; Miller, Frederick C.; LaGrow, Austin L.; Astley, Roger A.; Elliott, Michael H.; Callegan, Michelle C.

    2016-01-01

    The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is

  17. Imaging morphogenesis of Candida albicans during infection in a live animal

    NASA Astrophysics Data System (ADS)

    Mitra, Soumya; Dolan, Kristy; Foster, Thomas H.; Wellington, Melanie

    2010-01-01

    Candida albicans is an opportunistic human fungal pathogen that requires an intact host immune response to prevent disease. Thus, studying host-pathogen interactions is critical to understanding and preventing this disease. We report a new model infection system in which ongoing C. albicans infections can be imaged at high spatial resolution in the ears of living mice. Intradermal inoculation into mouse ears with a C. albicans strain expressing green fluorescent protein results in systemic C. albicans infection that can be imaged in vivo using confocal microscopy. We observed filamentous growth of the organism in vivo as well as formation of microabscesses. This model system will allow us to gain significant new information about C. albicans pathogenesis through studies of host-C. albicans interactions in the native environment.

  18. Bacterial bloodstream infections in HIV-infected adults attending a Lagos teaching hospital.

    PubMed

    Adeyemi, Adeleye I; Sulaiman, Akanmu A; Solomon, Bamiro B; Chinedu, Obosi A; Victor, Inem A

    2010-08-01

    An investigation was carried out during October 2005-September 2006 to determine the prevalence of bloodstream infections in patients attending the outpatient department of the HIV/AIDS clinic at the Lagos University Teaching Hospital in Nigeria. Two hundred and one patients--86 males and 115 females--aged 14-65 years were recruited for the study. Serological diagnosis was carried out on them to confirm their HIV status. Their CD4 counts were done using the micromagnetic bead method. Twenty mL of venous blood sample collected from each patient was inoculated into a pair of Oxoid Signal blood culture bottles for 2-14 days. Thereafter, 0.1 mL of the sample was plated in duplicates on MacConkey, blood and chocolate agar media and incubated at 37 degrees C for 18-24 hours. The CD4+ counts were generally low as 67% of 140 patients sampled had < 200 cells/microL of blood. Twenty-six bacterial isolates were obtained from the blood samples and comprised 15 (58%) coagulase-negative staphylococci as follows: Staphylococcus epidermidis (7), S. cohnii cohnii (1), S. cohnii urealyticum (2), S. chromogenes (1), S. warneri (2), S. scuri (1), and S. xylosus (1). Others were 6 (23%) Gram-negative non-typhoid Salmonella spp., S. Typhimurium (4), S. Enteritidis (2); Pseudomonas fluorescens (1), Escherichia coli (1), Ochrobactrum anthropi (1), Moraxella sp. (1), and Chryseobacterium meningosepticum. Results of antimicrobial susceptibility tests showed that coagulase-negative staphylococci had good sensitivities to vancomycin and most other antibiotics screened but were resistant mainly to ampicilin and tetracycline. The Gram-negative organisms isolated also showed resistance to ampicillin, tetracycline, chloramphenicol, and septrin. This study demonstrates that coagulase-negative staphylococci and non-typhoidal Salmonellae are the most common aetiological agents of bacteraemia among HIV-infected adults attending the Lagos University Teaching Hospital, Nigeria. The organisms were

  19. Antimicrobial blue light therapy for Candida albicans burn infection in mice

    NASA Astrophysics Data System (ADS)

    Zhang, Yunsong; Wang, Yucheng; Murray, Clinton K.; Hamblin, Michael R.; Gu, Ying; Dai, Tianhong

    2015-05-01

    In this preclinical study, we investigated the utility of antimicrobial blue light therapy for Candida albicans infection in acutely burned mice. A bioluminescent strain of C. albicans was used. The susceptibilities to blue light inactivation were compared between C. albicans and human keratinocyte. In vitro serial passaging of C. albicans on blue light exposure was performed to evaluate the potential development of resistance to blue light inactivation. A mouse model of acute thermal burn injury infected with the bioluminescent strain of C. albicans was developed. Blue light (415 nm) was delivered to mouse burns for decolonization of C. albicans. Bioluminescence imaging was used to monitor in real time the extent of fungal infection in mouse burns. Experimental results showed that C. albicans was approximately 42-fold more susceptible to blue light inactivation in vitro than human keratinocyte (P=0.0022). Serial passaging of C. albicans on blue light exposure implied a tendency for the fungal susceptibility to blue light inactivation to decrease with the numbers of passages. Blue light reduced fungal burden by over 4-log10 (99.99%) in acute mouse burns infected with C. albicans in comparison to infected mouse burns without blue light therapy (P=0.015).

  20. Late-Onset Bloodstream Infection and Perturbed Maturation of the Gastrointestinal Microbiota in Premature Infants

    PubMed Central

    Randell, Paul; Cox, Michael J.; McClure, Zoë E.; Li, Ming-Shi; Donaldson, Hugo; Langford, Paul R.; Cookson, William O. C. M.; Moffatt, Miriam F.; Kroll, J. Simon

    2015-01-01

    Background Late-onset bloodstream infection (LO-BSI) is a common complication of prematurity, and lack of timely diagnosis and treatment can have life-threatening consequences. We sought to identify clinical characteristics and microbial signatures in the gastrointestinal microbiota preceding diagnosis of LO-BSI in premature infants. Method Daily faecal samples and clinical data were collected over two years from 369 premature neonates (<32 weeks gestation). We analysed samples from 22 neonates who developed LO-BSI and 44 matched control infants. Next-generation sequencing of 16S rRNA gene regions amplified by PCR from total faecal DNA was used to characterise the microbiota of faecal samples preceding diagnosis from infants with LO-BSI and controls. Culture of selected samples was undertaken, and bacterial isolates identified using MALDI-TOF. Antibiograms from bloodstream and faecal isolates were compared to explore strain similarity. Results From the week prior to diagnosis, infants with LO-BSI had higher proportions of faecal aerobes/facultative anaerobes compared to controls. Risk factors for LO-BSI were identified by multivariate analysis. Enterobacteriaceal sepsis was associated with antecedent multiple lines, low birth weight and a faecal microbiota with prominent Enterobacteriaceae. Staphylococcal sepsis was associated with Staphylococcus OTU faecal over-abundance, and the number of days prior to diagnosis of mechanical ventilation and of the presence of centrally-placed lines. In 12 cases, the antibiogram of the bloodstream isolate matched that of a component of the faecal microbiota in the sample collected closest to diagnosis. Conclusions The gastrointestinal tract is an important reservoir for LO-BSI organisms, pathogens translocating across the epithelial barrier. LO-BSI is associated with an aberrant microbiota, with abundant staphylococci and Enterobacteriaceae and a failure to mature towards predominance of obligate anaerobes. PMID:26167683

  1. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    DOE PAGESBeta

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.; Schneewind, Olaf

    2015-01-06

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host Bmore » cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.« less

  2. [Prevention of catheter-related bloodstream infections in the operation room].

    PubMed

    Ema, Yoshiaki; Nishiwaki, Kimitoshi

    2010-05-01

    Catheter-related bloodstream infections (CRBSIs) are recognized as an important and serious problem, especially in an intensive care unit (ICU), since they have far higher infection rates compared to those for other type of intravascular devices. However, in the operation room, there seems to be little concern among anesthesiologists regarding this problem. It is important for anesthesiologists to understand that CRBSIs can be prevented or reduced by evidence-based interventions such as hand hygiene, education in hand washing and alcohol-based hand rubbing, sterile catheter care techniques, proper skin disinfection, maximal barrier precautions during catheter insertion, choice of subclavian vein placement, avoidance of femoral vein placement, and removal of an unnecessary catheter. This evidence is based mainly on findings in ICU patients, but introduction of these interventions into operation rooms may be very useful for reducing perioperative CRBSIs. PMID:20486568

  3. Catheter-related Mycobacterium fortuitum bloodstream infection: rapid identification using MALDI-TOF mass spectrometry.

    PubMed

    Artacho-Reinoso, M J; Olbrich, P; Solano-Paéz, P; Ybot-Gonzalez, P; Lepe, J A; Neth, O; Aznar, J

    2014-04-01

    We present the case of a 6-year-old boy diagnosed with stage III mediastinal Non Hodgkin Lymphoblastic T cell Lymphoma who suffered from catheter-related bloodstream infection (CRBI) due to Mycobacterium fortuitum whilst receiving chemotherapy. Isolation of this rare pathogen was done directly from blood culture and identification was made rapidly within 48 h using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectro-metry as well as specific polymerase chain reaction (PCR)-reverse hybridization method. This allowed prompt directed antibiotic therapy apart from central venous catheter removal and resulted in an excellent clinical response. This case highlights the potential benefit of using MALDI-TOF mass spectrometry, a fast, cost-effective and precise methodology, in the diagnosis and subsequent management of invasive bacterial infection. PMID:24554588

  4. Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

    PubMed

    Gyarmati, P; Kjellander, C; Aust, C; Song, Y; Öhrmalm, L; Giske, C G

    2016-01-01

    Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs. PMID:26996149

  5. Achromobacter Xylosoxidans Bloodstream Infection in Elderly Patient with Hepatocellular Carcinoma: Case Report and Review of Literature

    PubMed Central

    Raghuraman, Kausalya; Ahmed, Nishat H; Baruah, Frincy K; Grover, Rajesh K

    2015-01-01

    Achromobacter xylosoxidansis a nonfermentative Gram-negative organism, known to cause opportunistic infection in humans. We report a case of septicemia in a 76-year-old male patient with underlying hepatocellular carcinoma due to A. xylosoxidans, which showed a different antimicrobial susceptibility pattern from what is usually reported. From aerobic blood culture of the patient, A. xylosoxidans was isolated which was found to be sensitive to amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidime, cefoperazone-sulbactam, meropenem, minocycline, tigecycline, and trimethoprim/sulfamethoxazole. The patient recovered with amoxicillin-clavulanic acid treatment, which was given empirically to the patient. The present case highlights the possible role of amoxicillin-clavulanic acid for treatment of bloodstream infection with A. xylosoxidans. PMID:26417165

  6. Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia

    PubMed Central

    Gyarmati, P.; Kjellander, C.; Aust, C.; Song, Y.; Öhrmalm, L.; Giske, C. G.

    2016-01-01

    Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs. PMID:26996149

  7. Characteristics of catheter-related bloodstream infections in children with intestinal failure: implications for clinical management.

    PubMed

    Drews, Barbara B; Sanghavi, Rinarani; Siegel, Jane D; Metcalf, Pat; Mittal, Naveen K

    2009-01-01

    Catheter-related bloodstream infection is a major cause of mortality and morbidity in the intestinal-failure population. This study reports characteristics of CRBSI with implications for clinical management in parenteral nutrition-dependent children with intestinal failure. The researchers report the rate of central catheter infections, and the causative organisms, as well as identify risk factors in our intestinal-failure patients that would be amenable to preventive measures.The study is a retrospective review of the medical records of 101 patients with intestinal failure (IF), seen in the Intestinal Rehabilitation Clinic at Children's Medical Center of Dallas from May 2005 to March 2007. Catheter-related bloodstream infections (CRBSIs) were categorized as nosocomial or community-acquired. Data collected for each episode include microorganisms isolated from blood and potential risk factors. Z test was done to compare the infection rates.There were 92 episodes of CRBSIs in 45 parenteral nutrition (PN)-dependent patients with central venous catheters (CVC) in place for a total of 13,978 days. Eighty-three percent (n = 76) of CRBSIs developed in the community at a rate of 7.0 per 1,000 days. Seventeen percent (n = 16) nosocomial CRBSIs were observed at a rate of 5.5 per 1,000 catheter days. CRBSI rate was not statistically different between the two groups (7.0 vs. 5.5, p = .378).CRBSI in the intestinal-failure population is due to a wide variety of organisms with numerous risk factors. Education of CVC management with the practice of consistent guidelines may reduce CRBSI incidence, thus reducing the morbidity and mortality in the intestinal-failure patients. PMID:20010229

  8. Bacterial bloodstream infections and antimicrobial susceptibility pattern in pediatric hematology/oncology patients after anticancer chemotherapy

    PubMed Central

    Al-Mulla, Naima A; Taj-Aldeen, Saad J; El Shafie, Sittana; Janahi, Mohammed; Al-Nasser, Abdullah A; Chandra, Prem

    2014-01-01

    Purpose Bloodstream infections in pediatric hematology and oncology represent a major problem worldwide, but this has not been studied in Qatar. In this study, we investigated the burden of infection and the resistance pattern in the bacterial etiology, in the only tertiary pediatric hematology and oncology center in Qatar. Methods All pediatric cancer patients (n=185) were evaluated retrospectively during the period 2004–2011; a total of 70 (38%) patients were diagnosed with bloodstream infections. Bacterial etiology was determined, along with their susceptibility patterns. Neutropenia, duration of neutropenia, fever, duration of fever, and C-reactive protein (CRP) were evaluated throughout the study. Results A total of 70 patients (38%) were diagnosed with acute leukemias, lymphomas, solid tumors, or brain tumors; those patients experienced 111 episodes of bacteremia. The most common Gram-positive (n=64 [55%]) isolates were Staphylococcus epidermidis (n=26), Staphylococcus hominis (n=9), and Staphylococcus haemolyticus (n=7), and the common Gram-negative (n=52 [45%]) isolates were Klebsiella pneumoniae (n=14), Pseudomonas aeruginosa (n=10), and Escherichia coli (n=7). There was a significant association observed between fever with positive blood culture and different types of cancer (P=0.035). The majority of bacteremia (n=68 [61.3%]) occurred in nonneutropenic episodes. Elevated values of CRP (≥5 mg/L) were detected in 82 (95.3%) episodes and were negatively correlated with absolute neutrophil count (ANC) (r=−0.18; P=0.248) among all cases. However, the infection-related fatality rate was 2.2% (n=4), with three caused by Gram-negative pathogens. Multidrug resistant organisms were implicated in 33 (28.4%) cases and caused three of the mortality cases. Conclusion Multidrug resistant organisms cause mortality in pediatric cancer patients. Investigation of antimicrobial susceptibility of these organisms may guide successful antimicrobial therapy and improve

  9. Coordinated Molecular Cross-Talk between Staphylococcus aureus, Endothelial Cells and Platelets in Bloodstream Infection.

    PubMed

    Garciarena, Carolina D; McHale, Tony M; Watkin, Rebecca L; Kerrigan, Steven W

    2015-01-01

    Staphylococcus aureus is an opportunistic pathogen often carried asymptomatically on the human body. Upon entry to the otherwise sterile environment of the cardiovascular system, S. aureus can lead to serious complications resulting in organ failure and death. The success of S. aureus as a pathogen in the bloodstream is due to its ability to express a wide array of cell wall proteins on its surface that recognise host receptors, extracellular matrix proteins and plasma proteins. Endothelial cells and platelets are important cells in the cardiovascular system and are a major target of bloodstream infection. Endothelial cells form the inner lining of a blood vessel and provide an antithrombotic barrier between the vessel wall and blood. Platelets on the other hand travel throughout the cardiovascular system and respond by aggregating around the site of injury and initiating clot formation. Activation of either of these cells leads to functional dysregulation in the cardiovascular system. In this review, we will illustrate how S. aureus establish intimate interactions with both endothelial cells and platelets leading to cardiovascular dysregulation. PMID:26690226

  10. Coordinated Molecular Cross-Talk between Staphylococcus aureus, Endothelial Cells and Platelets in Bloodstream Infection

    PubMed Central

    Garciarena, Carolina D.; McHale, Tony M.; Watkin, Rebecca L.; Kerrigan, Steven W.

    2015-01-01

    Staphylococcus aureus is an opportunistic pathogen often carried asymptomatically on the human body. Upon entry to the otherwise sterile environment of the cardiovascular system, S. aureus can lead to serious complications resulting in organ failure and death. The success of S. aureus as a pathogen in the bloodstream is due to its ability to express a wide array of cell wall proteins on its surface that recognise host receptors, extracellular matrix proteins and plasma proteins. Endothelial cells and platelets are important cells in the cardiovascular system and are a major target of bloodstream infection. Endothelial cells form the inner lining of a blood vessel and provide an antithrombotic barrier between the vessel wall and blood. Platelets on the other hand travel throughout the cardiovascular system and respond by aggregating around the site of injury and initiating clot formation. Activation of either of these cells leads to functional dysregulation in the cardiovascular system. In this review, we will illustrate how S. aureus establish intimate interactions with both endothelial cells and platelets leading to cardiovascular dysregulation. PMID:26690226

  11. Taurolidine Lock Is Superior to Heparin Lock in the Prevention of Catheter Related Bloodstream Infections and Occlusions

    PubMed Central

    Olthof, Evelyn D.; Versleijen, Michelle W.; Huisman–de Waal, Getty; Feuth, Ton; Kievit, Wietske; Wanten, Geert J. A.

    2014-01-01

    Background and Aims Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients. Methods Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation. Results Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9–8.7) for bloodstream infections and 1.9 (95% confidence interval, 1.1–3.1) for occlusions. Conclusions Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin. PMID:25379781

  12. Diagnostic Accuracy of Procalcitonin for Predicting Blood Culture Results in Patients With Suspected Bloodstream Infection

    PubMed Central

    Oussalah, Abderrahim; Ferrand, Janina; Filhine-Tresarrieu, Pierre; Aissa, Nejla; Aimone-Gastin, Isabelle; Namour, Fares; Garcia, Matthieu; Lozniewski, Alain; Guéant, Jean-Louis

    2015-01-01

    Abstract Previous studies have suggested that procalcitonin is a reliable marker for predicting bacteremia. However, these studies have had relatively small sample sizes or focused on a single clinical entity. The primary endpoint of this study was to investigate the diagnostic accuracy of procalcitonin for predicting or excluding clinically relevant pathogen categories in patients with suspected bloodstream infections. The secondary endpoint was to look for organisms significantly associated with internationally validated procalcitonin intervals. We performed a cross-sectional study that included 35,343 consecutive patients who underwent concomitant procalcitonin assays and blood cultures for suspected bloodstream infections. Biochemical and microbiological data were systematically collected in an electronic database and extracted for purposes of this study. Depending on blood culture results, patients were classified into 1 of the 5 following groups: negative blood culture, Gram-positive bacteremia, Gram-negative bacteremia, fungi, and potential contaminants found in blood cultures (PCBCs). The highest procalcitonin concentration was observed in patients with blood cultures growing Gram-negative bacteria (median 2.2 ng/mL [IQR 0.6–12.2]), and the lowest procalcitonin concentration was observed in patients with negative blood cultures (median 0.3 ng/mL [IQR 0.1–1.1]). With optimal thresholds ranging from ≤0.4 to ≤0.75 ng/mL, procalcitonin had a high diagnostic accuracy for excluding all pathogen categories with the following negative predictive values: Gram-negative bacteria (98.9%) (including enterobacteria [99.2%], nonfermenting Gram-negative bacilli [99.7%], and anaerobic bacteria [99.9%]), Gram-positive bacteria (98.4%), and fungi (99.6%). A procalcitonin concentration ≥10 ng/mL was associated with a high risk of Gram-negative (odds ratio 5.98; 95% CI, 5.20–6.88) or Gram-positive (odds ratio 3.64; 95% CI, 3.11–4.26) bacteremia but

  13. Adding innovative practices and technology to central line bundle reduces bloodstream infection rate in challenging pediatric population.

    PubMed

    Pavia, Marianne; Mazza, Marianne

    2016-01-01

    A specialized pediatric hospital serves many patients with short bowel syndrome. The patients' fecal residue plus frequent access of intravenous lines increases bloodstream infection (BSI) risk. To reduce BSIs, the hospital first implemented an alcohol-dispensing disinfection cap and then added 3 more interventions, with both the cap-only phase and the multipronged phase successfully lowering the hospital's BSI rate. PMID:26769282

  14. Outbreak of Tsukamurella spp. Bloodstream Infections among Patients of an Oncology Clinic—West Virginia, 2011–2012

    PubMed Central

    See, Isaac; Nguyen, Duc B.; Chatterjee, Somu; Shwe, Thein; Scott, Melissa; Ibrahim, Sherif; Moulton-Meissner, Heather; McNulty, Steven; Noble-Wang, Judith; Price, Cindy; Schramm, Kim; Bixler, Danae; Guh, Alice Y.

    2015-01-01

    Objective To determine the source and identify control measures of an outbreak of Tsukamurella species bloodstream infections at an outpatient oncology facility. Design Epidemiologic investigation of the outbreak with a case control study. Methods A case was an infection in which Tsukamurella spp. was isolated from a blood or catheter tip culture during January 2011–June 2012 from a patient of the oncology clinic. Laboratory records of area hospitals and patient charts were reviewed. A case-control study was conducted among clinic patients to identify risk factors for Tsukamurella spp. bloodstream infection. Clinic staff were interviewed and infection control practices were assessed. Results Fifteen cases of Tsukamurella (T. pulmonis or T. tyrosinosolvens) bloodstream infection were identified, all in patients with underlying malignancy and indwelling central lines. Median age of case-patients was 68 years; 47% were male. The only significant risk factor for infection was receipt of saline flush from the clinic during September–October 2011 (P=0.03), when the clinic had been preparing saline flush from a common-source bag of saline. Other infection control deficiencies that were identified at the clinic included suboptimal procedures for central line access and preparation of chemotherapy. Conclusion Although multiple infection control lapses were identified, the outbreak was likely caused by improper preparation of saline flush syringes by the clinic. The outbreak demonstrates that bloodstream infections among oncology patients can result from improper infection control practices and highlights the critical need for increased attention to and oversight of infection control in outpatient oncology settings. PMID:24521597

  15. The Impact of Implementation of Bundle to Reduce Catheter-Related Bloodstream Infection Rates

    PubMed Central

    Menegueti, Mayra Goncalves; Ardison, Kym Marcel Martins; Bellissimo-Rodrigues, Fernando; Gaspar, Gilberto Gambero; Martins-Filho, Olindo Assis; Puga, Marcelo Lourencini; Laus, Ana Maria; Basile-Filho, Anibal; Auxiliadora-Martins, Maria

    2015-01-01

    Background The aim of the study was to investigate how control bundles reduce the rate of central venous catheter-associated bloodstream infections (CVC-BSIs) rates in critically ill patients. Methods This is a prospective before-and-after study designed to evaluate whether a set of control measures (bundle) can help prevent CVC-BSI. The bundles included a checklist that aimed to correct practices related to CVC insertion, manipulation, and maintenance based on guidelines of the Center for Disease Control and Prevention (CDC). Results We examined 123 checklists before and 155 checklists after implementation of the training program. Compared with the pre-intervention period, CVC-BSI rates decreased. Hand hygiene techniques were used correctly. CVC-BSI incidence was 9.3 and 5.1 per 1,000 catheter-days before and after the training program, respectively. Conclusions The implementation of a bundle and training program effectively reduces CVC-BSI rates. PMID:26491498

  16. Population-Based Epidemiology and Microbiology of Community-Onset Bloodstream Infections

    PubMed Central

    Church, Deirdre L.

    2014-01-01

    SUMMARY Bloodstream infection (BSI) is a major cause of infectious disease morbidity and mortality worldwide. While a positive blood culture is mandatory for establishment of the presence of a BSI, there are a number of determinants that must be considered for establishment of this entity. Community-onset BSIs are those that occur in outpatients or are first identified <48 h after admission to hospital, and they may be subclassified further as health care associated, when they occur in patients with significant prior health care exposure, or community associated, in other cases. The most common causes of community-onset BSI include Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrobial-resistant organisms, including methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase/metallo-β-lactamase/carbapenemase-producing Enterobacteriaceae, have emerged as important etiologies of community-onset BSI. PMID:25278570

  17. What is new for the prevention of catheter-related bloodstream infections?

    PubMed Central

    2016-01-01

    After the publication in 2011 of latest guidelines of the Centers for Disease Control and Prevention (CDC) for the prevention of catheter-related bloodstream infections (CRBSI) some interesting findings have been published in that field. There has been published that skin disinfection with chlorhexidine alcohol reduced the risk of CRBSI compared to skin disinfection with povidone iodine alcohol, that the implementation of quality improvement interventions reduced the incidence of CRBSI, that the use of chlorhexidine impregnated dressing compared to standard dressings reduced the risk of CRBSI and catheter related cost in an health economic model, and that the use of antimicrobial/antiseptic impregnated catheters reduced the incidence of CRBSI and catheter related cost in clinical studies. PMID:27127772

  18. APSIC guide for prevention of Central Line Associated Bloodstream Infections (CLABSI).

    PubMed

    Ling, Moi Lin; Apisarnthanarak, Anucha; Jaggi, Namita; Harrington, Glenys; Morikane, Keita; Thu, Le Thi Anh; Ching, Patricia; Villanueva, Victoria; Zong, Zhiyong; Jeong, Jae Sim; Lee, Chun-Ming

    2016-01-01

    This document is an executive summary of the APSIC Guide for Prevention of Central Line Associated Bloodstream Infections (CLABSI). It describes key evidence-based care components of the Central Line Insertion and Maintenance Bundles and its implementation using the quality improvement methodology, namely the Plan-Do-Study-Act (PDSA) methodology involving multidisciplinary process and stakeholders. Monitoring of improvement over time with timely feedback to stakeholders is a key component to ensure the success of implementing best practices. A surveillance program is recommended to monitor outcomes and adherence to evidence-based central line insertion and maintenance practices (compliance rate) and identify quality improvement opportunities and strategically targeting interventions for the reduction of CLABSI. PMID:27152193

  19. Brachyspira pilosicoli bloodstream infections: Case report and review of the literature

    PubMed Central

    Bait-Merabet, Lilia; Thille, Arnaud; Legrand, Patrick; Brun-Buisson, Christian; Cattoir, Vincent

    2008-01-01

    Brachyspira pilosicoli is the etiologic agent of human and animal intestinal spirochetosis and is rarely implicated as a cause of bacteremia. Here, we describe the case of a B. pilosicoli spirochetemia in a 53-year-old male patient suffering from cardiogenic shock. This fastidious bacterium was isolated from blood, likely after translocation from the intestinal tract. Blood cultures were positive after 5 days of incubation (one day after the patient's death), highlighting the problem of the recovery of such type of fastidious bacterium. Identification was achieved by molecular methods (16S rRNA sequencing). A review of the English literature found only 8 cases of bacteremia caused by B. pilosicoli, mostly in immunocompromised or critically ill patients. Finally, difficulties in rapid and accurate diagnosis of B. pilosicoli bloodstream infections, in vitro antimicrobial susceptibility of human clinical isolates, and therapeutic options are discussed. PMID:18817558

  20. Rapid Diagnosis of Bloodstream Infections with PCR Followed by Mass Spectrometry

    PubMed Central

    Jordana-Lluch, Elena; Carolan, Heather E.; Giménez, Montserrat; Sampath, Rangarajan; Ecker, David J.; Quesada, M. Dolores; Mòdol, Josep M.; Arméstar, Fernando; Blyn, Lawrence B.; Cummins, Lendell L.; Ausina, Vicente; Martró, Elisa

    2013-01-01

    Achieving a rapid microbiological diagnosis is crucial for decreasing morbidity and mortality of patients with a bloodstream infection, as it leads to the administration of an appropriate empiric antimicrobial therapy. Molecular methods may offer a rapid alternative to conventional microbiological diagnosis involving blood culture. In this study, the performance of a new technology that uses broad-spectrum PCR coupled with mass spectrometry (PCR/ESI-MS) was evaluated for the detection of microorganisms directly from whole blood. A total of 247 whole blood samples and paired blood cultures were prospectively obtained from 175 patients with a suspicion of sepsis. Both sample types were analyzed using the PCR/ESI-MS technology, and the results were compared with those obtained by conventional identification methods. The overall agreement between conventional methods and PCR/ESI-MS performed in blood culture aliquots was 94.2% with 96.8% sensitivity and 98.5% specificity for the molecular method. When comparing conventional methods with PCR/ESI-MS performed in whole blood specimens, the overall agreement was 77.1% with 50% sensitivity and 93.8% specificity for the molecular method. Interestingly, the PCR/ESI-MS technology led to the additional identification of 13 pathogens that were not found by conventional methods. Using the PCR/ESI-MS technology the microbiological diagnosis of bloodstream infections could be anticipated in about half of the patients in our setting, including a small but significant proportion of patients newly diagnosed. Thus, this promising technology could be very useful for the rapid diagnosis of sepsis in combination with traditional methods. PMID:23626775

  1. Should we use closed or open infusion containers for prevention of bloodstream infections?

    PubMed Central

    2010-01-01

    Background Hospitalized patients in critical care settings are at risk for bloodstream infections (BSI). Most BSIs originate from a central line (CL), and they increase length of stay, cost, and mortality. Open infusion containers may increase the risk of contamination and administration-related (CLAB) because they allow the entry of air into the system, thereby also providing an opportunity for microbial entry. Closed infusion containers were designed to overcome this flaw. However, open infusion containers are still widely used throughout the world. The objective of the study was to determine the effect of switching from open (glass, burettes, and semi-rigid) infusion containers to closed, fully collapsible, plastic infusion containers (Viaflex®) on the rate and time to onset of central line-associated bloodstream infections CLABs. Methods An open label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in four ICUs in Mexico. Centers for Disease Control National Nosocomial Infections Surveillance Systems definitions were used to define device-associated infections. Results A total of 1,096 adult patients who had a central line in place for >24 hours were enrolled. The CLAB rate was significantly higher during the open versus the closed container period (16.1 versus 3.2 CLAB/1000 central line days; RR = 0.20, 95% CI = 0.11-0.36, P < 0.0001). The probability of developing CLAB remained relatively constant in the closed container period (1.4% Days 2-4 to 0.5% Days 8-10), but increased in the open container period (4.9% Days 2-4 to 5.4% Days 8-10). The chance of acquiring a CLAB was significantly decreased (81%) in the closed container period (Cox proportional hazard ratio 0.19, P < 0.0001). Mortality was statistically significantly lower during the closed versus the open container period (23.4% versus 16.1%; RR = 0.69, 95% CI = 0.54-0.88, P < 0.01). Conclusions Closed infusion containers significantly reduced

  2. Polymorphisms in Fibronectin Binding Proteins A and B among Staphylococcus aureus Bloodstream Isolates Are Not Associated with Arthroplasty Infection

    PubMed Central

    Sharma-Kuinkel, Batu; Park, Lawrence P.; Rude, Thomas H.; Ruffin, Felicia; Hos, Nina J.; Seifert, Harald; Rieg, Siegbert; Kern, Winfried V.; Lower, Steven K.; Fowler, Vance G.; Kaasch, Achim J.

    2015-01-01

    Background Nonsynonymous single nucleotide polymorphisms (SNPs) in fibronectin binding protein A (fnbA) of Staphylococcus aureus are associated with cardiac device infections. However, the role of fnbA SNPs in S. aureus arthroplasty infection is unknown. Methods Bloodstream S. aureus isolates from a derivation cohort of patients at a single U.S. medical center with S. aureus bacteremia (SAB) and prosthetic hip or knee arthroplasties that were infected (PJI, n = 27) or uninfected (PJU, n = 43) underwent sequencing of fnbA and fnbB. A validation cohort of S. aureus bloodstream PJI (n = 12) and PJU (n = 58) isolates from Germany also underwent fnbA and fnbB sequencing. Results Overall, none of the individual fnbA or fnbB SNPs were significantly associated with the PJI or PJU clinical groups within the derivation cohort. Similarly, none of the individual fnbA or fnbB SNPs were associated with PJI or PJU when the analysis was restricted to patients with either early SAB (i.e., bacteremia occurring <1 year after placement or manipulation of prostheses) or late SAB (i.e., bacteremia >1 year after placement or manipulation of prostheses). Conclusions In contrast to cardiac device infections, there is no association between nonsynonymous SNPs in fnbA or fnbB of bloodstream S. aureus isolates and arthroplasty infection. These results suggest that initial steps leading to S. aureus infection of cardiovascular and orthopedic prostheses may arise by distinct processes. PMID:26606522

  3. Antimicrobial-impregnated catheters for the prevention of catheter-related bloodstream infections

    PubMed Central

    Lorente, Leonardo

    2016-01-01

    Central venous catheters are commonly used in critically ill patients. Such catheterization may entail mechanical and infectious complications. The interest in catheter-related infection lies in the morbidity, mortality and costs that it involved. Numerous contributions have been made in the prevention of catheter-related infection and the current review focuses on the possible current role of antimicrobial impregnated catheters to reduce catheter-related bloodstream infections (CRBSI). There is evidence that the use of chlorhexidine-silver sulfadiazine (CHSS), rifampicin-minocycline, or rifampicin-miconazol impregnated catheters reduce the incidence of CRBSI and costs. In addition, there are some clinical circumstances associated with higher risk of CRBSI, such as the venous catheter access and the presence of tracheostomy. Current guidelines for the prevention of CRBSI recommended the use of a CHSS or rifampicin-minocycline impregnated catheter in patients whose catheter is expected to remain in place > 5 d and if the CRBSI rate has not decreased after implementation of a comprehensive strategy to reduce it. PMID:27152256

  4. Antimicrobial-impregnated catheters for the prevention of catheter-related bloodstream infections.

    PubMed

    Lorente, Leonardo

    2016-05-01

    Central venous catheters are commonly used in critically ill patients. Such catheterization may entail mechanical and infectious complications. The interest in catheter-related infection lies in the morbidity, mortality and costs that it involved. Numerous contributions have been made in the prevention of catheter-related infection and the current review focuses on the possible current role of antimicrobial impregnated catheters to reduce catheter-related bloodstream infections (CRBSI). There is evidence that the use of chlorhexidine-silver sulfadiazine (CHSS), rifampicin-minocycline, or rifampicin-miconazol impregnated catheters reduce the incidence of CRBSI and costs. In addition, there are some clinical circumstances associated with higher risk of CRBSI, such as the venous catheter access and the presence of tracheostomy. Current guidelines for the prevention of CRBSI recommended the use of a CHSS or rifampicin-minocycline impregnated catheter in patients whose catheter is expected to remain in place > 5 d and if the CRBSI rate has not decreased after implementation of a comprehensive strategy to reduce it. PMID:27152256

  5. Bloodstream infections in intensive care unit patients: distribution and antibiotic resistance of bacteria

    PubMed Central

    Russotto, Vincenzo; Cortegiani, Andrea; Graziano, Giorgio; Saporito, Laura; Raineri, Santi Maurizio; Mammina, Caterina; Giarratano, Antonino

    2015-01-01

    Bloodstream infections (BSIs) are among the leading infections in critically ill patients. The case-fatality rate associated with BSIs in patients admitted to intensive care units (ICUs) reaches 35%–50%. The emergence and diffusion of bacteria with resistance to antibiotics is a global health problem. Multidrug-resistant bacteria were detected in 50.7% of patients with BSIs in a recently published international observational study, with methicillin resistance detected in 48% of Staphylococcus aureus strains, carbapenem resistance detected in 69% of Acinetobacter spp., in 38% of Klebsiella pneumoniae, and in 37% of Pseudomonas spp. Prior hospitalization and antibiotic exposure have been identified as risk factors for infections caused by resistant bacteria in different studies. Patients with BSIs caused by resistant strains showed an increased risk of mortality, which may be explained by a higher incidence of inappropriate empirical therapy in different studies. The molecular genetic characterization of resistant bacteria allows the understanding of the most common mechanisms underlying their resistance and the adoption of surveillance measures. Knowledge of epidemiology, risk factors, mechanisms of resistance, and outcomes of BSIs caused by resistant bacteria may have a major influence on global management of ICU patients. The aim of this review is to provide the clinician an update on BSIs caused by resistant bacteria in ICU patients. PMID:26300651

  6. Susceptibility to chlorhexidine amongst multidrug-resistant clinical isolates of Staphylococcus epidermidis from bloodstream infections.

    PubMed

    Hijazi, Karolin; Mukhopadhya, Indrani; Abbott, Felicity; Milne, Kathleen; Al-Jabri, Zaaima J; Oggioni, Marco R; Gould, Ian M

    2016-07-01

    The emergence of Staphylococcus isolates with reduced susceptibility to chlorhexidine is being increasingly reported. We present an update to a previous report showing the continuing efficacy of chlorhexidine-based infection control measures against Staphylococcus aureus over 6 years. In this study, qacA/B genes were screened in Staphylococcus isolates collected over another 6 years in the same intensive care unit in Scotland where chlorhexidine baths form an essential component of long-term control of nosocomial infections. Consistent with our previous study, we report minimal presence of qacA/B in S. aureus strains from screening samples and bacteraemia patients but the new finding of a high proportion of qacA/B carriage in Staphylococcus epidermidis associated with reduced susceptibility to chlorhexidine. S. epidermidis isolates positive for qacA/B were clonally diverse, although 65% of isolates belonged to the multidrug-resistant (MDR) clone ST2. These findings raise concerns in relation to the selection of MDR strains by chlorhexidine and are important in the context of recent evidence emphasising the benefits of targeting bloodstream infections associated with coagulase-negative staphylococci. PMID:27230473

  7. Bloodstream infections in very low birth weight infants with intestinal failure

    PubMed Central

    Cole, Conrad R.; Hansen, Nellie I.; Higgins, Rosemary D.; Bell, Edward F.; Shankaran, Seetha; Laptook, Abbot R.; Walsh, Michele C.; Hale, Ellen C.; Newman, Nancy S.; Das, Abhik; Stoll, Barbara J.

    2011-01-01

    Objective To examine pathogens and other characteristics associated with late-onset bloodstream infections (BSI) in infants with intestinal failure (IF) as a consequence of necrotizing enterocolitis (NEC). Study design Infants 401–1500 grams at birth who survived >72 hours and received care at NICHD Neonatal Research Network centers were studied. Frequency of culture positive BSI and pathogens were compared for infants with medical NEC, NEC managed surgically without IF, and surgical IF. Among infants with IF, duration of parenteral nutrition (PN) and other outcomes were evaluated. Results 932 infants were studied (IF, n=78; surgical NEC without IF, n=452; medical NEC, n=402). The proportion with BSI after NEC diagnosis was higher in infants with IF than with surgical NEC (p=0.007) or medical NEC (p<0.001). Gram positive pathogens were most frequent. Among infants with IF, increased number of infections was associated with longer hospitalization and duration on PN (0, 1, ≥2 infections; median stay (days): 172, 188, 260, p=0.06; median days on PN: 90, 112, 115, p=0.003), and the proportion who achieved full feeds during hospitalization decreased (87%, 67%, 50%, p=0.03). Conclusion Recurrent BSIs are common in VLBW infants with IF. Gram positive bacteria were most commonly identified in these infants. PMID:21840538

  8. The Validation of a Novel Surveillance System for Monitoring Bloodstream Infections in the Calgary Zone

    PubMed Central

    Leal, Jenine R.; Gregson, Daniel B.; Church, Deirdre L.; Henderson, Elizabeth A.; Ross, Terry; Laupland, Kevin B.

    2016-01-01

    Background. Electronic surveillance systems (ESSs) that utilize existing information in databases are more efficient than conventional infection surveillance methods. The objective was to assess an ESS for bloodstream infections (BSIs) in the Calgary Zone for its agreement with traditional medical record review. Methods. The ESS was developed by linking related data from regional laboratory and hospital administrative databases and using set definitions for excluding contaminants and duplicate isolates. Infections were classified as hospital-acquired (HA), healthcare-associated community-onset (HCA), or community-acquired (CA). A random sample of patients from the ESS was then compared with independent medical record review. Results. Among the 308 patients selected for comparative review, the ESS identified 318 episodes of BSI of which 130 (40.9%) were CA, 98 (30.8%) were HCA, and 90 (28.3%) were HA. Medical record review identified 313 episodes of which 136 (43.4%) were CA, 97 (30.9%) were HCA, and 80 (25.6%) were HA. Episodes of BSI were concordant in 304 (97%) cases. Overall, there was 85.5% agreement between ESS and medical record review for the classification of where BSIs were acquired (kappa = 0.78, 95% Confidence Interval: 0.75–0.80). Conclusion. This novel ESS identified and classified BSIs with a high degree of accuracy. This system requires additional linkages with other related databases. PMID:27375749

  9. Epidemiology of bloodstream infections in patients with acute myeloid leukemia undergoing levofloxacin prophylaxis

    PubMed Central

    2013-01-01

    Background Infections are a common cause of morbidity and mortality in patients with acute myeloid leukemia (AML). The evidence for efficacy of antibiotic prophylaxis in reducing the mortality rates and the incidence of bacterial infections was also reported by a systematic review published by Cochrane in 2012. The objective of our study was to report the incidence and the etiology of bloodstream infections in patients with AML undergoing levofloxacin prophylaxis during neutropenic episodes. Methods This was a retrospective study of patients with diagnosis of AML during 2001–2007. Results A total of 81 patients were included in the study. Two hundred and ninetyone neutropenic episodes were studied, of which 181 were febrile. Bacteria isolated from blood cultures were mostly Gram-positives during the induction (80%) and Gram-negatives during the consolidation (72.4%) phases of chemotherapy. Resistance to ciprofloxacin was found in 78.9% of isolated E. coli and it was higher during consolidation and higher than the hospital rate. The production of extended spectrum betalactamases (ESBL) in E. coli strains was reported in 12.1%, below the reported hospital rate during the study period. Conclusions Regular microbiology surveillance is needed to better understand the impact of levofloxacin prophylaxis in neutropenic patients. Our study shows that Gram-positive bacteria are predominant during the induction phase of chemotherapy and Gram-negatives during the consolidation. The rate of fluoroquinolone resistance in the latter setting, even higher than the hospital rate, may suggest to reconsider levofloxacin prophylaxis. PMID:24289496

  10. Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodstream Form Infectivity

    PubMed Central

    Loureiro, Inês; Faria, Joana; Clayton, Christine; Macedo-Ribeiro, Sandra; Santarém, Nuno; Roy, Nilanjan; Cordeiro-da-Siva, Anabela; Tavares, Joana

    2015-01-01

    Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5-phosphate isomerase. This enzyme is absent from humans, which have a structurally unrelated ribose 5-phosphate isomerase type A, and therefore has been proposed as an attractive drug target waiting further characterization. In this study, Trypanosoma brucei ribose 5-phosphate isomerase B showed in vitro isomerase activity. RNAi against this enzyme reduced parasites' in vitro growth, and more importantly, bloodstream forms infectivity. Mice infected with induced RNAi clones exhibited lower parasitaemia and a prolonged survival compared to control mice. Phenotypic reversion was achieved by complementing induced RNAi clones with an ectopic copy of Trypanosoma cruzi gene. Our results present the first functional characterization of Trypanosoma brucei ribose 5-phosphate isomerase B, and show the relevance of an enzyme belonging to the non-oxidative branch of the pentose phosphate pathway in the context of Trypanosoma brucei infection. PMID:25568941

  11. In vitro biofilm production of Candida bloodstream isolates: any association with clinical characteristics?

    PubMed

    Pongrácz, Júlia; Benedek, Kálmán; Juhász, Emese; Iván, Miklós; Kristóf, Katalin

    2016-04-01

    Candida spp. are a leading cause of bloodstream infection (BSI) and are associated with high mortality rates. Biofilm production is a virulence factor of Candida spp., and has been linked with poor clinical outcome. The aim of our study was to assess biofilm production of Candida bloodstream isolates at our institute, and to determine whether in vitro biofilm production is associated with any clinical characteristics of infection. During the four-year study period, 93 cases of Candida BSI were analysed. The most frequently isolated species was C. albicans (66.7 %), followed by C. glabrata (9.7 %), C. parapsilosis (9.7 %), C. tropicalis (9.7 %) and C. krusei (4.3 %). Biofilm production was more prevalent among non-albicans Candida spp. (77.4 %) than C. albicans (30.6 %) (P = 0.02). Abdominal surgery was identified as a risk factor of BSI caused by biofilm producing non-albicans Candida isolates. No risk factors predisposing to bloodstream infection caused by a biofilm producing C. albicans isolate were identified. Biofilm production was not verified as a risk factor of mortality. PMID:26678484

  12. Humoral Immunity Links Candida albicans Infection and Celiac Disease

    PubMed Central

    Fradin, Chantal; Salleron, Julia; Damiens, Sébastien; Moragues, Maria Dolores; Souplet, Vianney; Jouault, Thierry; Robert, Raymond; Dubucquoi, Sylvain; Sendid, Boualem; Colombel, Jean Fréderic; Poulain, Daniel

    2015-01-01

    Objective The protein Hwp1, expressed on the pathogenic phase of Candida albicans, presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase. This had led to the suggestion that C. albicans infection (CI) may be a triggering factor for Celiac disease (CeD) onset. We investigated cross-immune reactivity between CeD and CI. Methods Serum IgG levels against recombinant Hwp1 and serological markers of CeD were measured in 87 CeD patients, 41 CI patients, and 98 healthy controls (HC). IgA and IgG were also measured in 20 individuals from each of these groups using microchips sensitized with 38 peptides designed from the N-terminal of Hwp1. Results CI and CeD patients had higher levels of anti-Hwp1 (p=0.0005 and p=0.004) and anti-gliadin (p=0.002 and p=0.0009) antibodies than HC but there was no significant difference between CeD and CI patients. CeD and CI patients had higher levels of anti-transglutaminase IgA than HC (p=0.0001 and p=0.0039). During CI, the increase in anti-Hwp1 paralleled the increase in anti-gliadin antibodies. Microchip analysis showed that CeD patients were more reactive against some Hwp1 peptides than CI patients, and that some deamidated peptides were more reactive than their native analogs. Binding of IgG from CeD patients to Hwp1 peptides was inhibited by γIII gliadin peptides. Conclusions Humoral cross-reactivity between Hwp1 and gliadin was observed during CeD and CI. Increased reactivity to Hwp1 deamidated peptide suggests that transglutaminase is involved in this interplay. These results support the hypothesis that CI may trigger CeD onset in genetically-susceptible individuals. PMID:25793717

  13. Baicalin prevents Candida albicans infections via increasing its apoptosis rate

    SciTech Connect

    Yang, Shulong; Fu, Yingyuan Wu, Xiuzhen; Zhou, Zhixing; Xu, Jing; Zeng, Xiaoping; Kuang, Nanzhen; Zeng, Yurong

    2014-08-15

    Highlights: • Baicalin increases the ratio of the G0/G1 stages and C. albicans apoptosis. • Baicalin decreases the proliferation index of C. albicans. • Baicalin inhibits the biosynthesis of DNA, RNA and protein in C. albicans. • Baicalin depresses Succinate Dehydrogenase and Ca{sup 2+}–Mg{sup 2+} ATPase in C. albicans. • Baicalin increases the endocytic free Ca{sup 2+} concentration in C. albicans. - Abstract: Background: These experiments were employed to explore the mechanisms underlying baicalin action on Candida albicans. Methodology and principal findings: We detected the baicalin inhibition effects on three isotope-labeled precursors of {sup 3}H-UdR, {sup 3}H-TdR and {sup 3}H-leucine incorporation into C. albicans using the isotope incorporation technology. The activities of Succinate Dehydrogenase (SDH), cytochrome oxidase (CCO) and Ca{sup 2+}–Mg{sup 2+} ATPase, cytosolic Ca{sup 2+} concentration, the cell cycle and apoptosis, as well as the ultrastructure of C.albicans were also tested. We found that baicalin inhibited {sup 3}H-UdR, {sup 3}H-TdR and {sup 3}H-leucine incorporation into C.albicans (P < 0.005). The activities of the SDH and Ca{sup 2+}–Mg{sup 2+} ATPase of C.albicans in baicalin groups were lower than those in control group (P < 0.05). Ca{sup 2+} concentrations of C. albicans in baicalin groups were much higher than those in control group (P < 0.05). The ratio of C.albicans at the G0/G1 stage increased in baicalin groups in dose dependent manner (P < 0.01). There were a significant differences in the apoptosis rate of C.albicans between baicalin and control groups (P < 0.01). After 12–48 h incubation with baicalin (1 mg/ml), C. albicans shown to be markedly damaged under transmission electron micrographs. Innovation and significance: Baicalin can increase the apoptosis rate of C. albicans. These effects of Baicalin may involved in its inhibiting the activities of the SDH and Ca{sup 2+}–Mg{sup 2+} ATPase, increasing

  14. Reduction of Central Line-Associated Bloodstream Infection Rates in Patients in the Adult Intensive Care Unit.

    PubMed

    Wallace, Mary C; Macy, Deborah L

    2016-01-01

    Central line-associated bloodstream infections (CLABSIs) prolong hospital stays and increase cost, morbidity, and mortality. An intensive care unit (ICU) in a suburban Baltimore hospital reduced CLABSI rates to zero in 2012, by revising central venous access device policies and initiatives, which included a bloodstream infection alert system, bundle compliance monitoring and routine evaluation, and use of positive displacement needleless connectors. The hospital's ICU infection rate decreased from 2.9/1000 central-line days in 2010 to 0.8 by 2011, 0 by 2012, and 0.91 in 2013. The utilization ratio was 0.64 in 2011, 0.60 in 2012, and 0.58 in 2013. CLABSI prevention involves all disciplines and requires staff accountability for patient safety. PMID:26714119

  15. Prevalence and Antimicrobial Resistance of Microbes Causing Bloodstream Infections in Unguja, Zanzibar

    PubMed Central

    Onken, Annette; Said, Abdulrahman K.; Jørstad, Melissa; Jenum, Pål A.; Blomberg, Bjørn

    2015-01-01

    Background Bloodstream infections (BSI) are frequent and cause high case-fatality rates. Urgent antibiotic treatment can save patients’ lives, but antibiotic resistance can render antibiotic therapy futile. This study is the first to collect epidemiological data on BSI from Unguja, Zanzibar. Methods Clinical data and blood for culturing and susceptibility testing of isolated microbes were obtained from 469 consecutively enrolled neonates, children and adults presenting with signs of systemic infections at Mnazi Mmoja Hospital (MMH), Zanzibar. Results Pathogenic bacteria were recovered from the blood of 14% of the patients (66/469). The most frequently isolated microbes were Klebsiella pneumoniae, Escherichia coli, Acinetobacter spp. and Staphylococcus aureus. Infections were community-acquired in 56 patients (85%) and hospital-acquired in 8 (12%) (data missing for 2 patients). BSI caused by extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (E. coli, K. pneumoniae) was found in 5 cases, of which 3 were community-acquired and 2 hospital-acquired. Three of these patients died. Six of 7 Salmonella Typhi isolates were multidrug resistant. Streptococcus pneumoniae was found in one patient only. Conclusions This is the first report of ESBL-producing bacteria causing BSI from the Zanzibar archipelago. Our finding of community-acquired BSI caused by ESBL-producing bacteria is alarming, as it implies that these difficult-to-treat bacteria have already spread in the society. In the local setting these infections are virtually impossible to cure. The findings call for increased awareness of rational antibiotic use, infection control and surveillance to counteract the problem of emerging antimicrobial resistance. PMID:26700032

  16. Essential Functional Modules for Pathogenic and Defensive Mechanisms in Candida albicans Infections

    PubMed Central

    Tsai, I-Chun; Lin, Che; Chuang, Yung-Jen

    2014-01-01

    The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for both C. albicans and zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules in C. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms during C. albicans infection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treat C. albicans infection. PMID:24757665

  17. Survey of Physicians’ Perspectives and Knowledge about Diagnostic Tests for Bloodstream Infections

    PubMed Central

    She, Rosemary C.; Alrabaa, Sally; Lee, Seung Heon; Norvell, Meghan; Wilson, Andrew; Petti, Cathy A.

    2015-01-01

    Background Physicians rely on blood culture to diagnose bloodstream infections (BSI) despite its limitations. As new technologies emerge for rapid BSI diagnosis, optimization of their application to patient care requires an understanding of clinicians’ perspectives on BSI diagnosis and how a rapid test would influence medical decisions. Methods We administered a 26-question survey to practitioners in infectious diseases/microbiology, critical care, internal medicine, and hematology/oncology services in USA and Germany about current standards in diagnosing and treating BSI and a hypothetical rapid BSI test. Results Responses from 242 providers had roughly equal representation across specialties. For suspected BSI patients, 78% of practitioners would administer empiric broad spectrum antibiotics although they estimated, on average, that 31% of patients received incorrect antibiotics while awaiting blood culture results. The ability of blood culture to rule in or rule out infection was very/extremely acceptable in 67% and 36%, respectively. Given rapid test results, 60–87% of practitioners would narrow the spectrum of antimicrobial therapy depending on the microorganism detected, with significantly higher percentages when resistance determinants were also tested. Over half of respondents felt a rapid test would be very/extremely influential on clinical practice. Conclusions Limitations of blood culture were perceived as a barrier to patient care. A rapid test to diagnose BSI would impact clinical practice, but the extent of impact may be limited by prevailing attitudes and practices. Opportunities exist for interventions to influence practitioners’ behaviors in BSI management particularly with emergence of newer diagnostic tests. PMID:25811910

  18. Magnet® Hospital Recognition Linked to Lower Central Line-Associated Bloodstream Infection Rates.

    PubMed

    Barnes, Hilary; Rearden, Jessica; McHugh, Matthew D

    2016-04-01

    Central-line-associated bloodstream infections (CLABSI) are among the deadliest heathcare-associated infections, with an estimated 12-25% mortality rate. In 2014, the Centers for Medicare and Medicaid Services (CMS) began to penalize hospitals for poor performance with respect to selected hospital-acquired conditions, including CLABSI. A structural factor associated with high-quality nursing care and better patient outcomes is The Magnet Recognition Program®. The purpose of this study was to explore the relationship between Magnet status and hospital CLABSI rates. We used propensity score matching to match Magnet and non-Magnet hospitals with similar hospital characteristics. In a matched sample of 291 Magnet hospitals and 291 non-Magnet hospitals, logistic regression models were used to examine whether there was a link between Magnet status and CLABSI rates. Both before and after matching, Magnet hospital status was associated with better (lower than the national average) CLABSI rates (OR = 1.60, 95%CI: 1.10, 2.33 after matching). While established programs such as Magnet recognition are consistently correlated with high-quality nursing work environments and positive patient outcomes, additional research is needed to determine whether Magnet designation produces positive patient outcomes or rewards existing excellence. PMID:26809115

  19. New Insight on Epidemiology and Management of Bacterial Bloodstream Infection in Patients with Hematological Malignancies

    PubMed Central

    Menzo, Sara Lo; la Martire, Giulia; Ceccarelli, Giancarlo; Venditti, Mario

    2015-01-01

    Bloodstream infections (BSI) are a significant cause of morbidity and mortality in onco-hematologic patients. The Gram-negative bacteria were the main responsible for the febrile neutropenia in the sixties; their impact declined due to the use of fluoroquinolone prophylaxis. This situation was followed by the gradual emergence of Gram-positive bacteria also following the increased use of intravascular devices and the introduction of new chemotherapeutic strategies. In the last decade, the Gram-negative etiology is raising again because of the emergence of resistant strains that make questionable the usefulness of current strategies for prophylaxis and empirical treatment. Gram-negative BSI attributable mortality is relevant, and the appropriate empirical treatment significantly improves the prognosis; on the other hand the adequate delayed treatment of Gram-positive BSI does not seem to have a high impact on survival. The clinician has to be aware of the epidemiology of his institution and colonizations of his patients to choose the most appropriate empiric therapy. In a setting of high endemicity of multidrug-resistant infections also the choice of targeted therapy can be a challenge, often requiring strategies based on off-label prescriptions and low grade evidence. In this review, we summarize the current evidence for the best targeted therapies for difficult to treat bacteria BSIs and future perspectives in this topic. We also provide a flow chart for a rational approach to the empirical treatment of febrile neutropenia in a multidrug resistant, high prevalence setting. PMID:26185609

  20. Epidemiology and Outcome of Gram-Negative Bloodstream Infection in Children: A Population-Based Study

    PubMed Central

    Al-Hasan, M. N.; Huskins, W. C.; Lahr, B. D.; Eckel-Passow, J. E.; Baddour, L. M.

    2010-01-01

    SUMMARY Population-based studies of gram-negative bloodstream infection (BSI) in children are lacking. Therefore, we performed this population-based investigation in Olmsted County, Minnesota, to determine the incidence rate, site of acquisition, and outcome of gram-negative BSI in children under 18 years old. We used Kaplan-Meier method and Cox proportional hazard regression for mortality analysis. We identified 56 unique children with gram-negative BSI during the past decade. The gender-adjusted incidence rate of gram-negative BSI per 100,000 person-years was 129.7 (95% confidence interval [CI]: 77.8-181.6]) in infants, with a sharp decline to 14.6 (95% CI: 6.0-23.2) and 7.6 (95% CI: 4.3-10.9) in children 1-4 and 5-18 years old, respectively. The urinary tract was the most common identified source of infection (34%) and Escherichia coli was the most common pathogen isolated (38%). Over two-thirds (68%) of children had underlying medical conditions that predisposed to gram-negative BSI. The overall 28-day and 1-year all-cause mortality rates were 11% (95% CI: 3-18%) and 18% (95% CI: 8-28%), respectively. Younger age and number of underlying medical conditions were associated with 28-day and 1-year mortality, respectively. Nosocomial or healthcare-associated acquisition was associated with both 28-day and 1-year mortality. PMID:20598212

  1. Risk factors and outcomes of imipenem-resistant Acinetobacter bloodstream infection in North-eastern Malaysia

    PubMed Central

    Deris, Zakuan Zainy; Shafei, Mohd Nazri; Harun, Azian

    2011-01-01

    Objective To determine the risk factors and outcomes of imipenem-resistant Acinetobacter baumannii (IRAB) bloodstream infection (BSI) cases, since there is very little publication on Acinetobacter baumannii infections from Malaysia. Methods A cross sectional study of 41 cases (73.2%) of imipenem-sensitive Acinetobacter baumanii (ISAB) and 15 cases (26.8%) of IRAB was conducted in a teaching hospital which was located at North-Eastern state of Malaysia. Results There was no independent risk factor for IRAB BSI identified but IRAB BSI was significantly associated with longer bacteraemic days [OR 1.23 (95% CI 1.01, 1.50)]. Although prior use of carbepenems and cephalosporin were higher among IRAB than ISAB group, statistically they were not significant. There was no significant difference in term of outcomes between the two groups. Conclusions Although statistically not significant, this analysis compliments previous publication highlighting the importance of appropriate empiric antibiotic usage in hospital especially carbepenems and need further evaluation with bigger subjects. PMID:23569782

  2. Effect of UV irradiation on lethal infection of mice with Candida albicans.

    PubMed

    Denkins, Y M; Kripke, M L

    1993-02-01

    Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m2 UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicans in the kidneys, in contrast to sensitized, unirradiated mice. PMID:8451288

  3. Microbiological Profile of Organisms Causing Bloodstream Infection in Critically Ill Patients

    PubMed Central

    Orsini, Jose; Mainardi, Carlo; Muzylo, Eliza; Karki, Niraj; Cohen, Nina; Sakoulas, George

    2012-01-01

    Background Bloodstream infection (BSI) is the most frequent infection in critically ill patients. As BSI’s among patients in intensive care units (ICU’s) are usually secondary to intravascular catheters, they can be caused by both Gram-positive and Gram-negative microorganisms as well as fungi. Infection with multidrug-resistant (MDR) organisms is becoming more common, making the choice of empirical antimicrobial therapy challenging. The objective of this study is to evaluate the spectrum of microorganisms causing BSI’s in a Medical-Surgical Intensive Care Unit (MSICU) and their antimicrobial resistance patterns. Methods A prospective observational study among all adult patients with clinical signs of sepsis was conducted in a MSICU of an inner-city hospital in New York City between May 1, 2010 and May 30, 2011. Results A total of 722 adult patients with clinical signs of systemic inflammatory response syndrome (SIRS) and/or sepsis were admitted to the MSICU between May 1, 2010 and May 30, 2011. From those patients, 91 (12.6%) had one or more positive blood culture. A 122 isolates were identified: 72 (59%) were Gram-positive bacteria, 38 (31.1%) were Gram-negative organisms, and 12 (9.8%) were fungi. Thirteen (34.2%) Gram-negative organisms and 14 (19.4%) Gram-positive bacteria were classified as MDR. Conclusions Antimicrobial resistance, particularly among Gram-negative organisms, continues to increase at a rapid rate, especially in the ICU’s. Coordinated infection control interventions and antimicrobial stewardship policies are warranted in order to slow the emergence of resistance. PMID:23226169

  4. Infectious Complications and Morbidities After Neonatal Bloodstream Infections: An Observational Cohort Study.

    PubMed

    Tsai, Ming-Horng; Lee, Chiang-Wen; Chu, Shih-Ming; Lee, I-Ta; Lien, Reyin; Huang, Hsuan-Rong; Chiang, Ming-Chou; Fu, Ren-Huei; Hsu, Jen-Fu; Huang, Yhu-Chering

    2016-03-01

    Few data are available on the clinical characteristics of complications and morbidities after neonatal bloodstream infections (BSIs), understood as any newly infectious focus or organ dysfunction directly related to BSIs but not occur concurrently. However, these bloodstream-associated infectious complications (BSICs) contribute significantly to increased hospital stay, cost, and final mortality.We performed an observational cohort study of unselected neonatal intensive care unit (NICU) patients based on records in a large clinical database. All neonates hospitalized in our NICU with BSI between 2006 and 2013 were reviewed, and those who developed BSICs were analyzed to identify the clinical characteristics and outcomes. Multivariate logistic regression was used to identify independent risk factors for BSICs.Of 975 episodes of neonatal BSI, 101 (10.4%) BSICs occurred in 93 neonates with a median interval of 3 days (range, 0-17 days) after onset of BSI and included newly infectious focuses in 40 episodes (39.6%), major organ dysfunctions after septic shock in 36 episodes (35.6%), and neurological complications after meningitis or septic shock in 34 episodes (33.7%). All patients with BSICs encountered various morbidities, which subsequently resulted in in-hospital death in 30 (32.3%) neonates, critical discharge in 4 (4.3%), and persistent sequelae in 17 (18.3%). After multivariate logistic regression analysis, independent risk factors for BSICs included initial inappropriate antibiotics (odds ratio [OR], 5.54; 95% confidence interval [CI], 3.40-9.01), BSI with septic shock (OR, 5.75; 95% CI, 3.51-9.40), and BSI concurrent with meningitis (OR, 9.20; 95% CI, 4.33-19.56).It is worth noting that a percentage of neonates with BSI encountered subsequent sequelae or died of infections complications, which were significantly associated with initial inappropriate antibiotic therapy, septic shock, and the occurrence of meningitis. Further investigation is warranted to

  5. The impact of HIV infection on blood leukocyte responsiveness to bacterial stimulation in asymptomatic patients and patients with bloodstream infection

    PubMed Central

    Huson, Michaëla A M; Hoogendijk, Arie J; de Vos, Alex F; Grobusch, Martin P; van der Poll, Tom

    2016-01-01

    Introduction HIV-induced changes in cytokine responses to bacteria may influence susceptibility to bacterial infections and the consequent inflammatory response. Methods We examined the impact of HIV on whole blood responsiveness to bacterial stimulation in asymptomatic subjects and patients with bacterial bloodstream infection (BSI). Whole blood was stimulated ex vivo with two bacterial Toll-like receptor agonists (lipopolysaccharide and lipoteichoic acid) and two pathogens (Streptococcus pneumoniae and non-typhoidal Salmonella), which are relevant in HIV-positive patients. Production of interferon-γ, tumour necrosis factor-α, interleukin-1β and interleukin-6 was used as a read-out. Results In asymptomatic subjects, HIV infection was associated with reduced interferon-γ, release after stimulation and priming of the pro-inflammatory cytokine response to non-typhoidal Salmonella. In patients with BSI, we found no such priming effect, nor was there evidence for more profound sepsis-induced immunosuppression in BSI patients with HIV co-infection. Conclusions These results suggest a complex effect of HIV on leukocyte responses to bacteria. However, in patients with sepsis, leukocyte responses were equally blunted in patients with and without HIV infection. PMID:27189532

  6. Increase of mouse resistance to Candida albicans infection by thymosin alpha 1.

    PubMed Central

    Bistoni, F; Marconi, P; Frati, L; Bonmassar, E; Garaci, E

    1982-01-01

    Studies were carried out to assess the ability of thymosin alpha 1 to prolong the survival of mice challenged with Candida albicans. Two- to four-month-old mice were treated with graded doses of thymosin alpha 1 before, after, or before and after intravenous challenge with C. albicans. Significant resistance ot lethal infection was afforded by 100 micrograms of thymosin alpha 1 per kg given before or before and after challenge, whereas no protection was found in mice treated with thymosin alpha 1 administered at any dose level after inoculation. Pretreatment with thymosin alpha 1 also prevented the increased susceptibility to C. albicans infection of mice pretreated with cyclophosphamide on day -6. The results showed that thymosin alpha 1 was capable of protecting untreated or cyclophosphamide-pretreated mice from C. albicans infection at an optimal dose and schedule of administration. PMID:7085074

  7. Influence of tumour condition on the macrophage activity in Candida albicans infection.

    PubMed

    Venturini, J; de Camargo, M R; Félix, M C; Vilani-Moreno, F R; de Arruda, M S P

    2009-07-01

    To better understand the interactions between opportunistic fungi and their hosts, we investigated hydrogen peroxide (H2O2), nitric oxide and TNF-alpha production by peritoneal macrophages from Ehrlich tumour-bearing mice (TBM) during microbial infections. For this purpose, TBM at days 7, 14 and 21 of tumour progression were inoculated intraperitoneally with C. albicans and evaluated after 24 and 72 h. We observed that TBM showed significant increases in H2O2, TNF-alpha levels and fungal clearance at day 7 after C. albicans infection. However, as the tumour advanced, there was a progressive decline in the release of H2O2 and TNF-alpha that was paired with the dissemination of C. albicans. These results demonstrate that protective macrophage activities against Candida albicans are limited to the initial stages of tumour growth; continued solid tumour growth weakened the macrophage response and as a consequence, weakened the host's susceptibility to opportunistic infections. PMID:19522762

  8. Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model.

    PubMed

    Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon; Nile, Christopher

    2015-08-01

    Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections. PMID:26092919

  9. Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

    PubMed Central

    Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F.; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon

    2015-01-01

    Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections. PMID:26092919

  10. Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismutase

    PubMed Central

    Li, Cissy X.; Gleason, Julie E.; Zhang, Sean X.; Bruno, Vincent M.; Cormack, Brendan P.; Culotta, Valeria Cizewski

    2015-01-01

    Copper is both an essential nutrient and potentially toxic metal, and during infection the host can exploit Cu in the control of pathogen growth. Here we describe a clever adaptation to Cu taken by the human fungal pathogen Candida albicans. In laboratory cultures with abundant Cu, C. albicans expresses a Cu-requiring form of superoxide dismutase (Sod1) in the cytosol; but when Cu levels decline, cells switch to an alternative Mn-requiring Sod3. This toggling between Cu- and Mn-SODs is controlled by the Cu-sensing regulator Mac1 and ensures that C. albicans maintains constant SOD activity for cytosolic antioxidant protection despite fluctuating Cu. This response to Cu is initiated during C. albicans invasion of the host where the yeast is exposed to wide variations in Cu. In a murine model of disseminated candidiasis, serum Cu was seen to progressively rise over the course of infection, but this heightened Cu response was not mirrored in host tissue. The kidney that serves as the major site of fungal infection showed an initial rise in Cu, followed by a decline in the metal. C. albicans adjusted its cytosolic SODs accordingly and expressed Cu-Sod1 at early stages of infection, followed by induction of Mn-Sod3 and increases in expression of CTR1 for Cu uptake. Together, these studies demonstrate that fungal infection triggers marked fluctuations in host Cu and C. albicans readily adapts by modulating Cu uptake and by exchanging metal cofactors for antioxidant SODs. PMID:26351691

  11. Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismutase.

    PubMed

    Li, Cissy X; Gleason, Julie E; Zhang, Sean X; Bruno, Vincent M; Cormack, Brendan P; Culotta, Valeria Cizewski

    2015-09-22

    Copper is both an essential nutrient and potentially toxic metal, and during infection the host can exploit Cu in the control of pathogen growth. Here we describe a clever adaptation to Cu taken by the human fungal pathogen Candida albicans. In laboratory cultures with abundant Cu, C. albicans expresses a Cu-requiring form of superoxide dismutase (Sod1) in the cytosol; but when Cu levels decline, cells switch to an alternative Mn-requiring Sod3. This toggling between Cu- and Mn-SODs is controlled by the Cu-sensing regulator Mac1 and ensures that C. albicans maintains constant SOD activity for cytosolic antioxidant protection despite fluctuating Cu. This response to Cu is initiated during C. albicans invasion of the host where the yeast is exposed to wide variations in Cu. In a murine model of disseminated candidiasis, serum Cu was seen to progressively rise over the course of infection, but this heightened Cu response was not mirrored in host tissue. The kidney that serves as the major site of fungal infection showed an initial rise in Cu, followed by a decline in the metal. C. albicans adjusted its cytosolic SODs accordingly and expressed Cu-Sod1 at early stages of infection, followed by induction of Mn-Sod3 and increases in expression of CTR1 for Cu uptake. Together, these studies demonstrate that fungal infection triggers marked fluctuations in host Cu and C. albicans readily adapts by modulating Cu uptake and by exchanging metal cofactors for antioxidant SODs. PMID:26351691

  12. Multiplex PCR assay underreports true bloodstream infections with coagulase-negative staphylococci in hematological patients with febrile neutropenia.

    PubMed

    Reers, Yvonne; Idelevich, Evgeny A; Pätkau, Hanna; Sauerland, Maria Cristina; Tafelski, Sascha; Nachtigall, Irit; Berdel, Wolfgang E; Peters, Georg; Silling, Gerda; Becker, Karsten

    2016-08-01

    SeptiFast multiplex PCR assay was evaluated for detecting true bloodstream infections (BSIs) with coagulase-negative staphylococci (CoNS) in neutropenic hematological patients. Sensitivity for samples representing true CoNS-BSIs was 23.3% with an integrated cutoff and increased to 83.3% if the cutoff was neglected. Hence, the cutoff may prohibit timely targeted antimicrobial therapy. PMID:27220608

  13. Bloodstream infections by Malassezia and Candida species in critical care patients.

    PubMed

    Iatta, Roberta; Cafarchia, Claudia; Cuna, Teresa; Montagna, Osvaldo; Laforgia, Nicola; Gentile, Ottavio; Rizzo, Antonino; Boekhout, Teun; Otranto, Domenico; Montagna, Maria Teresa

    2014-04-01

    Despite being considered an emerging yeast related to immunocompromised individuals, severe infections by Malassezia furfur have not been evaluated. During a one-year survey on yeasts fungemia, 290 neonatal and 17 pediatric patients with intravascular catheters, lipid parenteral nutrition, prolonged ward stay, and surgery were enrolled. In addition, the origin of the infection was investigated by swabbing hand skin of patients, parents, and healthcare workers and medical devices. All biological specimens and swabs were cultured on Sabouraud dextrose agar and Dixon agar. The yeasts identification was based on morphological and biochemical features and by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by sequencing the internal transcribed spacer of nuclear ribosomal DNA. A higher prevalence of M. furfur (2.1%) over Candida spp. (1.4%) caused bloodstream infections (BSIs). Twelve fungemia episodes were recorded: 2 by M. furfur in a pediatric ward and 10 in a neonatal intensive care unit (6 caused by M. furfur and 4 by Candida spp.). M. furfur was also isolated from the skin of all patients with BSIs, from the hand skin of a parent, and from an incubator surface and sheet. Patients with Candida spp. and M. furfur BSIs were successfully treated with intravenous liposomal Amphotericin B. These findings highlight the need for a more accurate etiological diagnosis in high-risk patients by adding lipid-supplemented culture media for Malassezia in the current mycological routine as the clinical features, patient management, and outcomes in both Candida and Malassezia fungemia do not differ. PMID:24576998

  14. Azithromycin and Ciprofloxacin Resistance in Salmonella Bloodstream Infections in Cambodian Adults

    PubMed Central

    Vlieghe, Erika R.; Phe, Thong; De Smet, Birgit; Veng, Chhun H.; Kham, Chun; Bertrand, Sophie; Vanhoof, Raymond; Lynen, Lut; Peetermans, Willy E.; Jacobs, Jan A.

    2012-01-01

    Background Salmonella enterica is a frequent cause of bloodstream infection (BSI) in Asia but few data are available from Cambodia. We describe Salmonella BSI isolates recovered from patients presenting at Sihanouk Hospital Centre of Hope, Phnom Penh, Cambodia (July 2007–December 2010). Methodology Blood was cultured as part of a microbiological prospective surveillance study. Identification of Salmonella isolates was performed by conventional methods and serotyping. Antibiotic susceptibilities were assessed using disk diffusion, MicroScan and E-test macromethod. Clonal relationships were assessed by Pulsed Field Gel Electrophoresis; PCR and sequencing for detection of mutations in Gyrase and Topoisomerase IV and presence of qnr genes. Principal Findings Seventy-two Salmonella isolates grew from 58 patients (mean age 34.2 years, range 8–71). Twenty isolates were identified as Salmonella Typhi, 2 as Salmonella Paratyphi A, 37 as Salmonella Choleraesuis and 13 as other non-typhoid Salmonella spp. Infection with human immunodeficiency virus (HIV) was present in 21 of 24 (87.5%) patients with S. Choleraesuis BSI. Five patients (8.7%) had at least one recurrent infection, all with S. Choleraesuis; five patients died. Overall, multi drug resistance (i.e., co-resistance to ampicillin, sulphamethoxazole-trimethoprim and chloramphenicol) was high (42/59 isolates, 71.2%). S. Typhi displayed high rates of decreased ciprofloxacin susceptibility (18/20 isolates, 90.0%), while azithromycin resistance was very common in S. Choleraesuis (17/24 isolates, 70.8%). Two S. Choleraesuis isolates were extended spectrum beta-lactamase producer. Conclusions and Significance Resistance rates in Salmonella spp. in Cambodia are alarming, in particular for azithromycin and ciprofloxacin. This warrants nationwide surveillance and revision of treatment guidelines. PMID:23272255

  15. Hospital-wide multidisciplinary, multimodal intervention programme to reduce central venous catheter-associated bloodstream infection.

    PubMed

    Zingg, Walter; Cartier, Vanessa; Inan, Cigdem; Touveneau, Sylvie; Theriault, Michel; Gayet-Ageron, Angèle; Clergue, François; Pittet, Didier; Walder, Bernhard

    2014-01-01

    Central line-associated bloodstream infection (CLABSI) is the major complication of central venous catheters (CVC). The aim of the study was to test the effectiveness of a hospital-wide strategy on CLABSI reduction. Between 2008 and 2011, all CVCs were observed individually and hospital-wide at a large university-affiliated, tertiary care hospital. CVC insertion training started from the 3rd quarter and a total of 146 physicians employed or newly entering the hospital were trained in simulator workshops. CVC care started from quarter 7 and a total of 1274 nurses were trained by their supervisors using a web-based, modular, e-learning programme. The study included 3952 patients with 6353 CVCs accumulating 61,366 catheter-days. Hospital-wide, 106 patients had 114 CLABSIs with a cumulative incidence of 1.79 infections per 100 catheters. We observed a significant quarterly reduction of the incidence density (incidence rate ratios [95% confidence interval]: 0.92 [0.88-0.96]; P<0.001) after adjusting for multiple confounders. The incidence densities (n/1000 catheter-days) in the first and last study year were 2.3/1000 and 0.7/1000 hospital-wide, 1.7/1000 and 0.4/1000 in the intensive care units, and 2.7/1000 and 0.9/1000 in non-intensive care settings, respectively. Median time-to-infection was 15 days (Interquartile range, 8-22). Our findings suggest that clinically relevant reduction of hospital-wide CLABSI was reached with a comprehensive, multidisciplinary and multimodal quality improvement programme including aspects of behavioural change and key principles of good implementation practice. This is one of the first multimodal, multidisciplinary, hospital-wide training strategies successfully reducing CLABSI. PMID:24714418

  16. Bacterial Landscape of Bloodstream Infections in Neutropenic Patients via High Throughput Sequencing

    PubMed Central

    Gyarmati, Peter; Kalin, Mats; Öhrmalm, Lars; Giske, Christian G.

    2015-01-01

    Background Bloodstream infection (BSI) is a common and potentially life-threatening complication in patients with hematological malignancies and therapy-induced neutropenia. Administration of broad spectrum antibiotics has substantially decreased the mortality rate in febrile neutropenia, but bacterial infection is documented in only one-third or fewer of the cases. BSI is typically diagnosed by blood culture; however, this method can detect only culturable pathogens. Methods In the present study, a total of 130 blood samples from hematological patients receiving dose-intensive antitumoural treatment were subjected to 16S rRNA PCR and 62 of them were cultured. PCR positive samples were processed to high throughput sequencing by amplifying the V1-V3 regions of the 16S rRNA gene to obtain a full spectrum of bacteria present in BSI. Results Five phyla and 30 genera were identified with sequencing compared to 2 phyla and 4 genera with culture. The largest proportion of bacteria detected by sequencing belonged to Proteobacteria (55.2%), Firmicutes (33.4%) and Actinobacteria (8.6%), while Fusobacteria (0.4%) and Bacteroidetes (0.1%) were also detected. Ninety-eight percent of the bacteria identified by sequencing were opportunistic human pathogens and 65% belonged to the normal human microbiota. Conclusions The present study indicates that BSIs in neutropenic hosts contain a much broader diversity of bacteria, likely with host origin, than previously realized. The elevated ratio of Proteobacteria in BSI corroborates the results found in other systemic inflammatory diseases, such as inflammatory bowel disease or mucosal infections. This knowledge may become of value for tailoring antimicrobial drug administration. PMID:26270467

  17. Incidence, Clinical Characteristics and Attributable Mortality of Persistent Bloodstream Infection in the Neonatal Intensive Care Unit

    PubMed Central

    Hsu, Jen-Fu; Chu, Shih-Ming; Lee, Chiang-Wen; Yang, Pong-Hong; Lien, Reyin; Chiang, Ming-Chou; Fu, Ren-Huei; Huang, Hsuan-Rong; Tsai, Ming-Horng

    2015-01-01

    Background An atypical pattern of neonatal sepsis, characterized by persistent positive blood culture despite effective antimicrobial therapy, has been correlated with adverse outcomes. However, previous studies focused only on coagulate-negative staphylococcus infection. Methods All episodes of persistent bloodstream infection (BSI), defined as 3 or more consecutive positive blood cultures with the same bacterial species, at least two of them 48 hours apart, during a single sepsis episode, were enrolled over an 8-year period in a tertiary level neonatal intensive care unit. These cases were compared with all non-persistent BSI during the same period. Results We identified 81 episodes of persistent BSI (8.5% of all neonatal late-onset sepsis) in 74 infants, caused by gram-positive pathogens (n=38, 46.9%), gram-negative pathogens (n=21, 25.9%), fungus (n=20, 24.7%) and polymicrobial bacteremia (n=2, 2.5%). Persistent BSI does not differ from non-persistent BSI in most clinical characteristics and patient demographics, but tends to have a prolonged septic course, longer duration of feeding intolerance and more frequent requirement of blood transfusions. No difference was observed for death attributable to infection (9.8% vs. 6.5%), but neonates with persistent BSI had significantly higher rates of infectious complications (29.6% vs. 9.2%, P < 0.001), death from all causes (21.6% vs. 11.7%, P = 0.025), and duration of hospitalization among survivors [median (interquartile range): 80.0 (52.5-117.5) vs. 64.0 (40.0-96.0) days, P = 0.005] than those without persistent BSI. Conclusions Although persistent BSI does not contribute directly to increased mortality, the associated morbidities, infectious complications and prolonged septic courses highlight the importance of aggressive treatment to optimize outcomes. PMID:25875677

  18. Lactococcus lactis Catherter-Related Bloodstream Infection in an Infant: Case Report.

    PubMed

    Karaaslan, Ayşe; Soysal, Ahmet; Sarmış, Abdurrahman; Kadayifci, Eda Kepenekli; Cerit, Kıvılcım; Atıcı, Serkan; Söyletir, Güner; Bakır, Mustafa

    2015-01-01

    Lactococcus lactis is a gram-positive coccus that is nonpathogenic in humans. Herein, we present the case of a 1-year-old boy with Down syndrome and Hirschprung's disease (HD) who developed a catheter-related bloodstream infection with L. lactis after gastrointestinal surgery. The patient had been hospitalized in the pediatric surgery unit from birth because of HD, and had undergone the Duhamel-Martin procedure which caused recurrent diarrhea episodes and feeding intolerance. On the infant's 430th day of life, he had an episode of gastroenteritis and feeding intolerance. Because of clinical suspiction of sepsis, blood cultures were taken both from the central venous catheter and peripheral vein, and evidence of a growing microorganism was detected in 2 different central venous catheter blood cultures taken 2 days apart. The colonies were then identified by both the Vitek 2 and Vitek MS systems (bioMérieux, Marseille, France) as L. lactis spp. lactis. The central venous catheter could not be removed because of the absence of a peripheral venous line, and the patient was subsequently successfully treated with vancomycin. Therefore, although Lactococcus species is generally thought to be nonpathogenic, it should still be kept in mind as a potential pathogen in infants. PMID:25672357

  19. Bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal single-center study.

    PubMed

    Kjellander, Christian; Björkholm, Magnus; Källman, Owe; Giske, Christian G; Weibull, Caroline E; Löve, Thorvardur J; Landgren, Ola; Kristinsson, Sigurdur Y

    2016-05-01

    Infectious complications in chronic lymphocytic leukemia (CLL) represent a major cause of morbidity and mortality. The aim of the study was to investigate temporal trends in bloodstream infections (BSIs) among patients with CLL. Individuals with blood cultures were linked to Swedish Cancer Registry and divided into three time periods (1988-1993, 1994-1999, and 2000-2006) according to year of CLL diagnosis. CLL patients (n = 275) with 1092 blood culture episodes were identified and linked to the nationwide Cause of Death Registry and Swedish Patient Registry (to retrieve information on splenectomies). The most common causes of BSI among CLL patients were Escherichia coli (11/43, 15/78, and 9/33), Streptococcus pneumoniae (7/43, 13/78, and 6/33), Pseudomonas aeruginosa (2/43, 8/78, and 3/33), Staphylococcus aureus (1/43, 6/78, and 6/33), and Viridans streptococci (5/43, 6/78, and 2/33). Coagulase-negative staphylococci was the most frequent microorganism found in blood cultures (22/70, 23/106, and 5/41, respectively) but is a frequent contaminant. Based on the largest study to date on BSI in CLL patients, we found a stable proportion of Gram-positive to Gram-negative bacteria and no temporal change of distribution was observed for BSIs 1988-2006. PMID:26976017

  20. Microbiologic characterization of isolates from a dalbavancin clinical trial for catheter-related bloodstream infections.

    PubMed

    Goldstein, Beth P; Jones, Ronald N; Fritsche, Thomas R; Biedenbach, Douglas J

    2006-02-01

    Dalbavancin, a new-generation semisynthetic lipoglycopeptide in phase 3 clinical development, has been documented to be more active than vancomycin or teicoplanin against Gram-positive bacteria, including multidrug-resistant strains, by in vitro testing and in animal models. The human pharmacokinetics of dalbavancin predicts efficacy at weekly dosing intervals. In a phase 2 open-label clinical trial, dalbavancin exhibited superiority when compared with vancomycin against catheter-related bloodstream infection (CR-BSI). The majority of pathogens identified in this study as in clinical practice were coagulase-negative staphylococci (CoNS), necessitating rigorous characterization of duplicate isolates to rule out contaminants and to validate cases for study evaluations. At follow-up for the intent-to-treat population, overall pathogen eradication was 92.3% for dalbavancin and 75.9% for vancomycin. We describe the details of organisms isolated, their epidemiologic/genetic characterization, susceptibility patterns against glycopeptides, and the eradication rates by organism group. In conclusion, dalbavancin was active against all isolated pathogens associated with CR-BSI (CoNS, Staphylococcus aureus and Enterococcus faecalis; all MIC results, < or = 0.25 microg/mL) and achieved significant (P < 0.05) clinical success when compared with vancomycin. PMID:16458124

  1. Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue

    PubMed Central

    Schlecht, Lisa Marie; Peters, Brian M.; Krom, Bastiaan P.; Freiberg, Jeffrey A.; Hänsch, Gertrud M.; Filler, Scott G.

    2015-01-01

    Candida albicans and Staphylococcus aureus are often co-isolated in cases of biofilm-associated infections. C. albicans can cause systemic disease through morphological switch from the rounded yeast to the invasive hyphal form. Alternatively, systemic S. aureus infections arise from seeding through breaks in host epithelial layers although many patients have no documented portal of entry. We describe a novel strategy by which S. aureus is able to invade host tissue and disseminate via adherence to the invasive hyphal elements of Candida albicans. In vitro and ex vivo findings demonstrate a specific binding of the staphylococci to the candida hyphal elements. The C. albicans cell wall adhesin Als3p binds to multiple staphylococcal adhesins. Furthermore, Als3p is required for C. albicans to transport S. aureus into the tissue and cause a disseminated infection in an oral co-colonization model. These findings suggest that C. albicans can facilitate the invasion of S. aureus across mucosal barriers, leading to systemic infection in co-colonized patients. PMID:25332378

  2. Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections*

    PubMed Central

    Brealey, David; Libert, Nicolas; Abidi, Nour Elhouda; O’Dwyer, Michael; Zacharowski, Kai; Mikaszewska-Sokolewicz, Malgorzata; Schrenzel, Jacques; Simon, François; Wilks, Mark; Picard-Maureau, Marcus; Chalfin, Donald B.; Ecker, David J.; Sampath, Rangarajan; Singer, Mervyn

    2015-01-01

    Objective: Early identification of causative microorganism(s) in patients with severe infection is crucial to optimize antimicrobial use and patient survival. However, current culture-based pathogen identification is slow and unreliable such that broad-spectrum antibiotics are often used to insure coverage of all potential organisms, carrying risks of overtreatment, toxicity, and selection of multidrug-resistant bacteria. We compared the results obtained using a novel, culture-independent polymerase chain reaction/electrospray ionization-mass spectrometry technology with those obtained by standard microbiological testing and evaluated the potential clinical implications of this technique. Design: Observational study. Setting: Nine ICUs in six European countries. Patients: Patients admitted between October 2013 and June 2014 with suspected or proven bloodstream infection, pneumonia, or sterile fluid and tissue infection were considered for inclusion. Interventions: None. Measurements and Main Results: We tested 616 bloodstream infection, 185 pneumonia, and 110 sterile fluid and tissue specimens from 529 patients. From the 616 bloodstream infection samples, polymerase chain reaction/electrospray ionization-mass spectrometry identified a pathogen in 228 cases (37%) and culture in just 68 (11%). Culture was positive and polymerase chain reaction/electrospray ionization-mass spectrometry negative in 13 cases, and both were negative in 384 cases, giving polymerase chain reaction/electrospray ionization-mass spectrometry a sensitivity of 81%, specificity of 69%, and negative predictive value of 97% at 6 hours from sample acquisition. The distribution of organisms was similar with both techniques. Similar observations were made for pneumonia and sterile fluid and tissue specimens. Independent clinical analysis of results suggested that polymerase chain reaction/electrospray ionization-mass spectrometry technology could potentially have resulted in altered treatment in up

  3. Limitations of Murine Models for Assessment of Antibody-Mediated Therapies or Vaccine Candidates against Staphylococcus epidermidis Bloodstream Infection.

    PubMed

    Cole, Leah E; Zhang, Jinrong; Kesselly, Augustus; Anosova, Natalie G; Lam, Hubert; Kleanthous, Harry; Yethon, Jeremy A

    2016-04-01

    Staphylococcus epidermidis is normally a commensal colonizer of human skin and mucus membranes, but, due to its ability to form biofilms on indwelling medical devices, it has emerged as a leading cause of nosocomial infections. Bacteremia or bloodstream infection is a frequent and costly complication resulting from biofilm fouling of medical devices. Our goal was to develop a murine model of S. epidermidis infection to identify potential vaccine targets for the prevention of S. epidermidis bacteremia. However, assessing the contribution of adaptive immunity to protection against S. epidermidis challenge was complicated by a highly efficacious innate immune response in mice. Naive mice rapidly cleared S. epidermidis infections from blood and solid organs, even when the animals were immunocompromised. Cyclophosphamide-mediated leukopenia reduced the size of the bacterial challenge dose required to cause lethality but did not impair clearance after a nonlethal challenge. Nonspecific innate immune stimulation, such as treatment with a Toll-like receptor 4 (TLR4) agonist, enhanced bacterial clearance. TLR2 signaling was confirmed to accelerate the clearance of S. epidermidis bacteremia, but TLR2(-/-)mice could still resolve a bloodstream infection. Furthermore, TLR2 signaling played no role in the clearance of bacteria from the spleen. In conclusion, these data suggest that S. epidermidis bloodstream infection is cleared in a highly efficient manner that is mediated by both TLR2-dependent and -independent innate immune mechanisms. The inability to establish a persistent infection in mice, even in immunocompromised animals, rendered these murine models unsuitable for meaningful assessment of antibody-mediated therapies or vaccine candidates. PMID:26857577

  4. Limitations of Murine Models for Assessment of Antibody-Mediated Therapies or Vaccine Candidates against Staphylococcus epidermidis Bloodstream Infection

    PubMed Central

    Zhang, Jinrong; Kesselly, Augustus; Lam, Hubert; Kleanthous, Harry; Yethon, Jeremy A.

    2016-01-01

    Staphylococcus epidermidis is normally a commensal colonizer of human skin and mucus membranes, but, due to its ability to form biofilms on indwelling medical devices, it has emerged as a leading cause of nosocomial infections. Bacteremia or bloodstream infection is a frequent and costly complication resulting from biofilm fouling of medical devices. Our goal was to develop a murine model of S. epidermidis infection to identify potential vaccine targets for the prevention of S. epidermidis bacteremia. However, assessing the contribution of adaptive immunity to protection against S. epidermidis challenge was complicated by a highly efficacious innate immune response in mice. Naive mice rapidly cleared S. epidermidis infections from blood and solid organs, even when the animals were immunocompromised. Cyclophosphamide-mediated leukopenia reduced the size of the bacterial challenge dose required to cause lethality but did not impair clearance after a nonlethal challenge. Nonspecific innate immune stimulation, such as treatment with a Toll-like receptor 4 (TLR4) agonist, enhanced bacterial clearance. TLR2 signaling was confirmed to accelerate the clearance of S. epidermidis bacteremia, but TLR2−/− mice could still resolve a bloodstream infection. Furthermore, TLR2 signaling played no role in the clearance of bacteria from the spleen. In conclusion, these data suggest that S. epidermidis bloodstream infection is cleared in a highly efficient manner that is mediated by both TLR2-dependent and -independent innate immune mechanisms. The inability to establish a persistent infection in mice, even in immunocompromised animals, rendered these murine models unsuitable for meaningful assessment of antibody-mediated therapies or vaccine candidates. PMID:26857577

  5. Clinical significance of coagulase-negative staphylococci isolates from nosocomial bloodstream infections.

    PubMed

    Morad Asaad, Ahmed; Ansar Qureshi, Mohamed; Mujeeb Hasan, Syed

    2016-05-01

    Background Identification of coagulase-negative staphylococci (CoNS) as nosocomial pathogens or contaminants is significant for microbiologists and clinicians. This study aimed to determine the frequency of isolation and antimicrobial resistance patterns of CoNS isolates from nosocomial bloodstream infections (BSIs) and to identify risk factors associated with true bacteremia caused by these emerging pathogens in a Saudi tertiary care hospital. Methods All CoNS-positive cultures from inpatients were identified using the standard methods during a 10-month period. Antimicrobial susceptibility testing was done using the reference broth microdilution method. Results A total of 208 isolates were identified; of these 75 (32.2%) were considered infection associated, and 133 (67.8%) were considered contamination. S. epidermidis accounted for 34.7% of bacteremia cases, followed by S. hominis (21.3%), S. haemolyticus (16%), and S. saprophyticus (12%). Central venous catheters (p ≤ 0.0001), prior antibiotic therapy (p ≤ 0.0001), the occurrence of more than one positive blood culture (p ≤ 0.0001), and intensive care unit (ICU) admission (p = 0.007) were all independently associated with CoNS bacteremia. Overall, all isolates were highly resistant to penicillin (94.7%), oxacillin (90.7%), and erythromycin (85.3%). The rates of susceptibility to vancomycin, daptomycin, and teicoplanin were 98.7%, 98.7%, and 93.3%, respectively. Conclusions Our results further highlight that accurate identification and susceptibility testing of CoNS isolates from nosocomial BSIs are crucial to minimize excessive antibiotic use and unnecessary catheter removal. In addition, daptomycin may be an efficient alternative therapeutic option for CoNS resistant to oxacillin and other commonly used antibiotics. PMID:26666168

  6. ID Learning Unit—Diagnostics Update: Current Laboratory Methods for Rapid Pathogen Identification in Patients With Bloodstream Infections

    PubMed Central

    Rubach, Matthew P.; Hanson, Kimberly E.

    2015-01-01

    Diagnostic assays that rapidly identify bloodstream pathogens have the potential to improve patient outcomes and antibiotic stewardship efforts. Current tests are based on the detection of nucleic acids that are specific to a targeted pathogen or based on organism identification using mass spectrometry. Most rapid assays require a positive blood culture as their sample input and expedite pathogen identification by 24–72 hours. For those assays that also report detection of drug resistance markers, information on antimicrobial resistance is expedited by 48–96 hours. This learning unit reviews the basic principles of rapid microorganism identification assays for bloodstream infections with the aim of assisting clinicians in the interpretation and optimal utilization of test results. PMID:26719845

  7. ID Learning Unit-Diagnostics Update: Current Laboratory Methods for Rapid Pathogen Identification in Patients With Bloodstream Infections.

    PubMed

    Rubach, Matthew P; Hanson, Kimberly E

    2015-12-01

    Diagnostic assays that rapidly identify bloodstream pathogens have the potential to improve patient outcomes and antibiotic stewardship efforts. Current tests are based on the detection of nucleic acids that are specific to a targeted pathogen or based on organism identification using mass spectrometry. Most rapid assays require a positive blood culture as their sample input and expedite pathogen identification by 24-72 hours. For those assays that also report detection of drug resistance markers, information on antimicrobial resistance is expedited by 48-96 hours. This learning unit reviews the basic principles of rapid microorganism identification assays for bloodstream infections with the aim of assisting clinicians in the interpretation and optimal utilization of test results. PMID:26719845

  8. Anti-fungal activity of cathelicidins and their potential role in Candida albicans skin infection.

    PubMed

    López-García, Belén; Lee, Phillip H A; Yamasaki, Kenshi; Gallo, Richard L

    2005-07-01

    Cathelicidins have broad anti-microbial capacity and are important for host defense against skin infections by some bacterial and viral pathogens. This study investigated the activity of cathelicidins against Candida albicans. The human cathelicidin LL-37, and mouse cathelicidin mCRAMP, killed C. albicans, but this fungicidal activity was dependent on culture conditions. Evaluation of the fungal membrane by fluorescent dye penetration after incubation with cathelicidins correlated membrane permeabilization and inhibition of fungal growth. Anti-fungal assays carried out in an ionic environment that mimicked human sweat and with the processed forms of cathelicidin such as are present in sweat found that the cleavage of LL-37 to forms such as RK-31 conferred additional activity against C. albicans. C. albicans also induced an increase in the expression of cathelicidin in mouse skin, but this induction did not confer systemic or subcutaneous resistance as mCRAMP-deficient mice were not more susceptible to C. albicans in blood-killing assays or in an intradermal infection model. Therefore, cathelicidins appear active against C. albicans, but may be most effective as a superficial barrier to infection. PMID:15982310

  9. In Vitro Antifungal Susceptibility Profiles of Candida albicans Complex Isolated from Patients with Respiratory Infections.

    PubMed

    Sharifynia, Somayeh; Badali, Hamid; Sharifi Sorkherizi, Mina; Shidfar, Mohammad Reza; Hadian, Atefe; Shahrokhi, Shadi; Ghandchi, Ghazale; Rezaie, Sassan

    2016-06-01

    Candidiasis, the main opportunistic fungal infection has been increased over the past decades. This study aimed to characterize C.albicans species complex (C.albicans, C.dubliniensis, and C.africana) isolated from patients with respiratory infections by molecular tools and in vitro antifungal susceptibilities by using broth microdilution method according to CLSI M27-A3 guidelines. Totally, 121 respiratory samples were collected from patients with respiratory infections. Of these, 83 strains were germ tube positive and green colonies on chromogenic media, so initially identified as C.albicans species complex and subsequently were classified as C.albicans (89.15%), C.dubliniensis (9.63%), and C.africana (1.2%) based on PCR-RFLP and amplification of hwp1 gene. Minimum inhibitory concentration (MICs) results showed that all tested isolates of C.albicans complex were highly susceptible to triazole drugs. However, caspofungin had highest activity against C.albicans, C.dubliniensis, and C.africana. Our findings indicated the variety of antifungal resistance of Candida strains in different areas. These results may increase the knowledge about the local distribution of the mentioned strains as well as their antifungal susceptibility pattern which play an important role in appropriate therapy. PMID:27306344

  10. Implementing a multifaceted intervention to decrease central line-associated bloodstream infections in SEHA (Abu Dhabi Health Services Company) intensive care units: the Abu Dhabi experience.

    PubMed

    Latif, Asad; Kelly, Bernadette; Edrees, Hanan; Kent, Paula S; Weaver, Sallie J; Jovanovic, Branislava; Attallah, Hadeel; de Grouchy, Kristin K; Al-Obaidli, Ali; Goeschel, Christine A; Berenholtz, Sean M

    2015-07-01

    OBJECTIVE To determine whether implementation of a multifaceted intervention would significantly reduce the incidence of central line-associated bloodstream infections. DESIGN Prospective cohort collaborative. SETTING AND PARTICIPANTS Intensive care units of the Abu Dhabi Health Services Company hospitals in the Emirate of Abu Dhabi. INTERVENTIONS A bundled intervention consisting of 3 components was implemented as part of the program. It consisted of a multifaceted approach that targeted clinician use of evidence-based infection prevention recommendations, tools that supported the identification of local barriers to these practices, and implementation ideas to help ensure patients received the practices. Comprehensive unit-based safety teams were created to improve safety culture and teamwork. Finally, the measurement and feedback of monthly infection rate data to safety teams, senior leaders, and staff in participating intensive care units was encouraged. The main outcome measure was the quarterly rate of central line-associated bloodstream infections. RESULTS Eighteen intensive care units from 7 hospitals in Abu Dhabi implemented the program and achieved an overall 38% reduction in their central line-associated bloodstream infection rate, adjusted at the hospital and unit level. The number of units with a quarterly central line-associated bloodstream infection rate of less than 1 infection per 1,000 catheter-days increased by almost 40% between the baseline and postintervention periods. CONCLUSION A significant reduction in the global morbidity and mortality associated with central line-associated bloodstream infections is possible across intensive care units in disparate settings using a multifaceted intervention. PMID:25871927

  11. Neonatal intensive care unit collaboration to decrease hospital-acquired bloodstream infections: from comparative performance reports to improvement networks.

    PubMed

    Schulman, Joseph; Wirtschafter, David D; Kurtin, Paul

    2009-08-01

    This two-part article provides a general guide to thinking about data-driven clinical performance evaluation and describes two statewide improvement networks anchored in such comparisons. Part 1 examines key ideas for making fair comparisons among providers. Part 2 describes the development of a data-driven collaborative that aims to reduce central line associated bloodstream infections in neonatal ICUs across New York State, and a more mature collaborative in California that has already succeeded in reducing these infections; it provides sufficient detail and tools to be of practical help to others seeking to create such networks. The content illustrates concepts with broad applicability for pediatric quality improvement. PMID:19660632

  12. Impact of infection control training for interns on PICU-acquired bloodstream infections in a middle-income country

    PubMed Central

    Ng, Yun Yun; Abdel-Latif, Mohamed El-Amin; Gan, Chin Seng; Siham, Anis; Zainol, Hasimah; Lum, Lucy Chai See

    2015-01-01

    INTRODUCTION The present study aimed to determine the impact of an extended infection control training programme, which was conducted for all interns posted to the Department of Paediatrics, on the incidence of paediatric intensive care unit (PICU)-acquired bloodstream infections (BSIs) in University Malaya Medical Centre, Malaysia. METHODS The development of nosocomial BSIs during the baseline period (1 January–31 October 2008) and intervention period (1 November–31 December 2009) was monitored. During the intervention period, all paediatric interns underwent training in hand hygiene and aseptic techniques for accessing vascular catheters. RESULTS A total of 25 patients had PICU-acquired BSIs during the baseline period, while 18 patients had PICU-acquired BSIs during the intervention period (i.e. infection rate of 88 per 1,000 and 41 per 1,000 admissions, respectively). The infections were related to central venous catheters (CVCs) in 22 of the 25 patients who had PICU-acquired BSIs during the baseline period and 11 of the 18 patients who had PICU-acquired BSIs during the intervention period. Thus, the incidence rates of catheter-related BSIs were 25.2 per 1,000 CVC-days and 9.3 per 1,000 CVC-days, respectively (p < 0.05). The Paediatric Risk of Standardised Mortality III score was an independent risk factor for PICU-acquired BSIs and the intervention significantly reduced this risk. CONCLUSION The education of medical interns on infection control, a relatively low-cost intervention, resulted in a substantial reduction in the incidence of PICU-acquired BSIs. PMID:26451053

  13. Combination Regimens for Treatment of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections.

    PubMed

    Gomez-Simmonds, A; Nelson, B; Eiras, D P; Loo, A; Jenkins, S G; Whittier, S; Calfee, D P; Satlin, M J; Kubin, C J; Furuya, E Y

    2016-06-01

    Previous studies reported decreased mortality in patients with carbapenemase-producing Klebsiella pneumoniae bloodstream infections (BSIs) treated with combination therapy but included carbapenem-susceptible and -intermediate isolates, as per revised CLSI breakpoints. Here, we assessed outcomes in patients with BSIs caused by phenotypically carbapenem-resistant K. pneumoniae (CRKP) according to the number of in vitro active agents received and whether an extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an extended-spectrum cephalosporin was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates had meropenem or imipenem MICs of ≥4 μg/ml. Univariate and multivariable models were created to identify factors associated with mortality. Of 141 CRKP BSI episodes, 23% were treated with a single active agent (SAA), 26% were treated with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23% were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of ≥16 μg/ml. Thirty-day mortality was 33% overall and did not significantly differ across the four treatment groups in a multivariable model (P = 0.4); mortality was significantly associated with a Pitt bacteremia score of ≥4 (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1; P = 0.1), and immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0; P = 0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAAs versus MAA (26% versus 38%, P = 0.1) or BL versus no BL (26% versus 39%, P = 0.1). In summary, in patients with CRKP BSIs caused by isolates with high carbapenem MICs, the role of combination therapy remains unclear, highlighting the need for prospective studies to identify optimal treatment regimens. PMID:27044555

  14. CHLORHEXIDINE-IMPREGNATED DRESSING FOR PREVENTION OF CATHETER-RELATED BLOODSTREAM INFECTION: A META-ANALYSIS

    PubMed Central

    Safdar, Nasia; O’Horo, John C.; Ghufran, Aiman; Bearden, Allison; Didier, Maria Eugenia; Chateau, Dan; Maki, Dennis G.

    2014-01-01

    Background Catheter related bloodstream infections (CRBSI) are associated with significant morbidity and mortality and effective methods for their prevention are needed. Objective To assess the efficacy of a chlorhexidine-impregnated dressing for prevention of central venous catheter-related colonization and CRBSI using meta-analysis. Data Sources Multiple computerized database searches supplemented by manual searches including relevant conference proceedings. Study Selection Randomized controlled trials (RCT) evaluating the efficacy of a chlorhexidine-impregnated dressing compared with conventional dressings for prevention of catheter colonization and CRBSI. Data Extraction Data were extracted on patient and catheter characteristics and outcomes. Data Synthesis Pooled estimates of the relative risk (RR) and 95% confidence intervals (CI) were obtained using the DerSimonian and Laird random effects model and the Mantel-Haenszel fixed effects model. Heterogeneity was assessed using the Cochran Q statistic and I2. Subgroup analyses were used to explore heterogeneity. Results Nine RCTs met the inclusion criteria. Use of a chlorhexidine-impregnated dressing resulted in a reduced incidence of CRBSI (random effects RR 0.57, 95% CI 0.42–0.79, P=0.002). The incidence of catheter colonization was also markedly reduced in the chlorhexidine-impregnated dressing group (random effects RR 0.51, 95% CI 0.39–0.67, P< 0.001). There was significant benefit for prevention of catheter colonization and CRBSI, including arterial catheters used for hemodynamic monitoring. Other than in low birth weight infants, adverse effects were rare and minor. Conclusions Our analysis shows that a chlorhexidine-impregnated dressing is beneficial in preventing catheter colonization and, more importantly, CRBSI and warrants routine use in patients at high risk of CRBSI and CVC or arterial catheter colonization in ICUs. PMID:24674924

  15. Three Epidemics of Invasive Multidrug-Resistant Salmonella Bloodstream Infection in Blantyre, Malawi, 1998–2014

    PubMed Central

    Feasey, Nicholas A.; Masesa, Clemens; Jassi, Chikondi; Faragher, E. Brian; Mallewa, Jane; Mallewa, Macpherson; MacLennan, Calman A.; Msefula, Chisomo; Heyderman, Robert S.; Gordon, Melita A.

    2015-01-01

    Background. The Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) has routinely collected specimens for blood culture from febrile patients, and cerebrospinal fluid from patients with suspected meningitis, presenting to Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, since 1998. Methods. We present bloodstream infection (BSI) and meningitis surveillance data from 1998 to 2014. Automated blood culture, manual speciation, serotyping, and antimicrobial susceptibility testing were performed at MLW. Population data for minimum-incidence estimates in urban Blantyre were drawn from published estimates. Results. Between 1998 and 2014, 167 028 blood cultures were taken from adult and pediatric medical patients presenting to QECH; Salmonella Typhi was isolated on 2054 occasions (1.2%) and nontyphoidal Salmonella (NTS) serovars were isolated 10 139 times (6.1%), of which 8017 (79.1%) were Salmonella Typhimurium and 1608 (15.8%) were Salmonella Enteritidis. There were 392 cases of NTS meningitis and 9 cases of Salmonella Typhi meningitis. There have been 3 epidemics of Salmonella BSI in Blantyre; Salmonella Enteritidis from 1999 to 2002, Salmonella Typhimurium from 2002 to 2008, and Salmonella Typhi, which began in 2011 and was ongoing in 2014. Multidrug resistance has emerged in all 3 serovars and is seen in the overwhelming majority of isolates, while resistance to third-generation cephalosporins and fluoroquinolones is currently uncommon but has been identified. Conclusions. Invasive Salmonella disease in Malawi is dynamic and not clearly attributable to a single risk factor, although all 3 epidemics were associated with multidrug resistance. To inform nonvaccine and vaccine interventions, reservoirs of disease and modes of transmission require further investigation. PMID:26449953

  16. Bloodstream infections among carriers of carbapenem-resistant Klebsiella pneumoniae: etiology, incidence and predictors.

    PubMed

    Amit, S; Mishali, H; Kotlovsky, T; Schwaber, M J; Carmeli, Y

    2015-01-01

    Carriers of carbapenem-resistant Klebsiella pneumoniae (CRKP) are increasingly recognised through active surveillance in much of the world. We studied incidence, aetiology and predictors of bloodstream infections (BSI) among such carriers. Via a retrospective cohort study conducted in a tertiary care teaching hospital, we examined occurrence of BSI within 45 days of CRKP carrier detection. Three nested case-control studies were conducted to analyse parameters associated with all-cause (ALL), Gram-negative rod (GNR) and CRKP BSI. Cases and controls were compared with respect to demographics, clinical parameters and recent receipt of antibiotics. A total of 431 patients were identified as CRKP carriers (28% by clinical culture, 72% by rectal surveillance), mean age was 75.2 years. Twenty percent of the patients (n = 85) developed BSI, of them 80% (n = 68) with GNR. Of 83 GNR isolates, 58 (70%) were Enterobacteriaceae, of which 19 were CRKP and 20 were extended-spectrum β-lactamase (ESBL) producers (23% and 24% of total GNR, respectively); 29% of the GNR isolates were nonfermenters (14.5% Pseudomonas aeruginosa, 14.5% Acinetobacter baumannii). Mechanical ventilation predicted ALL BSI (p = 0.04), whereas Clostridium difficile-associated diarrhoea predicted GNR BSI (p = 0.04). Receipt of broad-spectrum antibiotics (piperacillin-tazobactam, amikacin, imipenem) was significantly associated with ALL BSI or GNR BSI. No exposure independently predicted CRKP BSI. We conclude that patients detected as CRKP carriers are at high risk for BSI within 45 days of detection, primarily with multidrug-resistant GNR. Lack of predictive factors differentiating between pathogens and associated high mortality raises once more the dilemma regarding the appropriate empiric therapy for CRKP carriers who develop severe sepsis. PMID:25636924

  17. DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?

    PubMed

    Blomfeldt, A; Aamot, H V; Eskesen, A N; Monecke, S; White, R A; Leegaard, T M; Bjørnholt, J V

    2016-08-01

    Providing evidence for microbial genetic determinants' impact on outcome in Staphylococcus aureus bloodstream infections (SABSI) is challenging due to the complex and dynamic microbe-host interaction. Our recent population-based prospective study reported an association between the S. aureus clonal complex (CC) 30 genotype and mortality in SABSI patients. This follow-up investigation aimed to examine the genetic profiles of the SABSI isolates and test the hypothesis that specific genetic characteristics in S. aureus are associated with mortality. SABSI isolates (n = 305) and S. aureus CC30 isolates from asymptomatic nasal carriers (n = 38) were characterised by DNA microarray analysis and spa typing. Fisher's exact test, least absolute shrinkage and selection operator (LASSO) and elastic net regressions were performed to discern within four groups defined by patient outcome and characteristics. No specific S. aureus genetic determinants were found to be associated with mortality in SABSI patients. By applying LASSO and elastic net regressions, we found evidence suggesting that agrIII and cna were positively and setC (=selX) and seh were negatively associated with S. aureus CC30 versus non-CC30 isolates. The genes chp and sak, encoding immune evasion molecules, were found in higher frequencies in CC30 SABSI isolates compared to CC30 carrier isolates, indicating a higher virulence potential. In conclusion, no specific S. aureus genes were found to be associated with mortality by DNA microarray analysis and state-of-the-art statistical analyses. The next natural step is to test the hypothesis in larger samples with higher resolution methods, like whole genome sequencing. PMID:27177754

  18. Prevention of Central Line–Associated Bloodstream Infections Through Quality Improvement Interventions: A Systematic Review and Meta-analysis

    PubMed Central

    Perl, Trish M.; Blot, Koen; Bergs, Jochen; Vogelaers, Dirk; Blot, Stijn; Vandijck, Dominique

    2014-01-01

    This systematic review and meta-analysis examines the impact of quality improvement interventions on central line–associated bloodstream infections in adult intensive care units. Studies were identified through Medline and manual searches (1995–June 2012). Random-effects meta-analysis obtained pooled odds ratios (ORs) and 95% confidence intervals (CIs). Meta-regression assessed the impact of bundle/checklist interventions and high baseline rates on intervention effect. Forty-one before–after studies identified an infection rate decrease (OR, 0.39 [95% CI, .33–.46]; P < .001). This effect was more pronounced for trials implementing a bundle or checklist approach (P = .03). Furthermore, meta-analysis of 6 interrupted time series studies revealed an infection rate reduction 3 months postintervention (OR, 0.30 [95% CI, .10–.88]; P = .03). There was no difference in infection rates between studies with low or high baseline rates (P = .18). These results suggest that quality improvement interventions contribute to the prevention of central line–associated bloodstream infections. Implementation of care bundles and checklists appears to yield stronger risk reductions. PMID:24723276

  19. Nationwide Sentinel Surveillance of Bloodstream Candida Infections in 40 Tertiary Care Hospitals in Spain▿ †

    PubMed Central

    Cisterna, R.; Ezpeleta, G.; Telleria, O.; Guinea, J.; Regueiro, B.; Garcia-Rodríguez, J.; Esperalba, J.

    2010-01-01

    Candidemia studies have documented geographic differences in rates and epidemiology, underscoring the need for surveillance to monitor trends. We conducted prospective candidemia surveillance in Spain to assess the incidence, species distribution, frequency of antifungal resistance, and risk factors for acquiring a Candida infection. Prospective laboratory-based surveillance was conducted from June 2008 to June 2009 in 40 medical centers located around the country. A case of candidemia was defined as the isolation of a Candida species from a blood culture. Incidence rates were calculated per 1,000 admissions. Antifungal susceptibility tests were performed by using broth microdilution assay according to the guidelines of the Clinical and Laboratory Standards Institute. We detected 984 cases, for an overall incidence of 1.09 cases per 1,000 admissions. The crude mortality was 20.20%. Candida albicans was the most common species (49.08%), followed by C. parapsilosis (20.73%), C. glabrata (13.61%), and C. tropicalis (10.77%). Overall, decreased susceptibility to fluconazole occurred in 69 (7.01%) incident isolates. Antifungal resistance was rare, and a moderate linear correlation between fluconazole and voriconazole MICs was observed. This is the largest multicenter candidemia study conducted to date and shows the substantial morbidity and mortality of candidemia in Spain. PMID:20826636

  20. CD4+ T-helper-cell responses in mice with low-level Candida albicans infection.

    PubMed Central

    Mencacci, A; Spaccapelo, R; Del Sero, G; Enssle, K H; Cassone, A; Bistoni, F; Romani, L

    1996-01-01

    Resistance and susceptibility to Candida albicans infection have been shown to be dependent upon the activation of CD4+ T helper (Th) type 1 or Th2 cells, respectively. To study the type, kinetics, and cytokine dependency of CD4+ Th-cell responses in low-level C. albicans infection, susceptible mice were infected with sublethal doses of C. albicans and assessed for parameters of CD4+ Th-dependent immunity. Interleukin (IL)-12 and gamma interferon were always produced early in infection regardless of the pathogen load. In contrast, production of IL-4, and hence Th2-cell reactivity, was strictly dose dependent, being induced at the higher dose of the fungus. Production of IL-12 correlated with a successful control of infection in mice exposed to the lower doses of C. albicans but not with the development of acquired immunity. An antigenic stimulus appeared to be required for IL-12 to induce a protective anticandidal response. Cytokine depletion in vivo revealed that neutralization of IL-4 was protective early but not late in infection, suggesting a different role for IL-4 in the induction versus maintenance of an ongoing anticandidal Th response. Late in infection, an exacerbative effect was also observed upon IL-12 neutralization. These results indicate that the fungal burden and timing of cytokine appearance greatly influence CD4+ Th induction and effector functions in mice with candidiasis. PMID:8945525

  1. Classification of positive blood cultures: computer algorithms versus physicians' assessment - development of tools for surveillance of bloodstream infection prognosis using population-based laboratory databases

    PubMed Central

    2012-01-01

    Background Information from blood cultures is utilized for infection control, public health surveillance, and clinical outcome research. This information can be enriched by physicians’ assessments of positive blood cultures, which are, however, often available from selected patient groups or pathogens only. The aim of this work was to determine whether patients with positive blood cultures can be classified effectively for outcome research in epidemiological studies by the use of administrative data and computer algorithms, taking physicians’ assessments as reference. Methods Physicians’ assessments of positive blood cultures were routinely recorded at two Danish hospitals from 2006 through 2008. The physicians’ assessments classified positive blood cultures as: a) contamination or bloodstream infection; b) bloodstream infection as mono- or polymicrobial; c) bloodstream infection as community- or hospital-onset; d) community-onset bloodstream infection as healthcare-associated or not. We applied the computer algorithms to data from laboratory databases and the Danish National Patient Registry to classify the same groups and compared these with the physicians’ assessments as reference episodes. For each classification, we tabulated episodes derived by the physicians’ assessment and the computer algorithm and compared 30-day mortality between concordant and discrepant groups with adjustment for age, gender, and comorbidity. Results Physicians derived 9,482 reference episodes from 21,705 positive blood cultures. The agreement between computer algorithms and physicians’ assessments was high for contamination vs. bloodstream infection (8,966/9,482 reference episodes [96.6%], Kappa = 0.83) and mono- vs. polymicrobial bloodstream infection (6,932/7,288 reference episodes [95.2%], Kappa = 0.76), but lower for community- vs. hospital-onset bloodstream infection (6,056/7,288 reference episodes [83.1%], Kappa = 0.57) and healthcare-association (3

  2. Predictors of clinical and microbiological treatment failure in neonatal bloodstream infections.

    PubMed

    Hsu, J-F; Chu, S-M; Huang, Y-C; Lien, R; Huang, H-R; Lee, C-W; Chiang, M-C; Fu, R-H; Tsai, M-H

    2015-05-01

    This study aimed to identify independent predictors of clinical and microbiological treatment failure and develop a predictive model for neonates with bloodstream infection (BSI). This study included 1087 episodes of BSIs in 793 neonates in a tertiary-level neonatal intensive care unit of northern Taiwan between 2004 and 2012. Patient demographics, underlying chronic comorbidities, clinical features, antimicrobial treatment and microbiological characteristics were evaluated. The presence of underlying congenital anomalies (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.09 to 4.10) and pulmonary hypertension (OR 3.63, 95% CI 1.70 to 7.74), infections caused by multidrug-resistant gram-negative bacteria (OR 2.89, 95% CI 1.23 to 6.79), group B Streptococcus (OR 3.15, 95% CI 1.33 to 7.46), and fungi (OR 4.13, 95% CI 2.02 to 8.46), a Neonatal Therapeutic Intervention Scoring System score of ≥ 23 (OR 6.96, 95% CI 2.55 to 28.58), inappropriate antibiotics (OR 2.13, 95% CI 1.41 to 3.23), and concomitant meningitis (OR 4.25, 95% CI 2.08 to 8.69) and ventilator-associated pneumonia (OR 2.73, 95% CI 1.22 to 6.13) were identified as independent risk factors for 28-day treatment failure in neonatal BSI. A risk score model was created by adding the points for each independent risk factor, and had a c-statistic of 0.83. Patients with risk scores of 0, 4, 8, 12 and 15 had estimated 28-day treatment failure rates of approximately 3.5%, 17.0%, 53.5%, 86.6% and 95.9%, respectively. This predictive model, calculated after documentation of a BSI, reflects a spectrum of BSI severity and was associated with subsequent treatment failure through illness severity score and case mix variables. This simple score could prove useful in clinical and research settings, and practical in estimating the prognosis. PMID:25749002

  3. Correlation of atherogenesis with an infection of Candida albicans

    PubMed Central

    Nurgeldiyeva, Maya J; Hojakuliyev, Bayram G; Muhammedov, Merdan B

    2014-01-01

    Purpose: To study contents of atherosclerotic plaques for the presence of fungi of the genus Candida; and an analysis of some immunological and biochemical indices in patients with acute coronary syndrome (ACS) that are positive for Candida albicans. Materials and methods: To test for the presence of fungi in an atherosclerotic plaque, we used a method developed by us (patent NO 531, a priority from 6/28/2010). A total of 47 atherosclerotic plaques were obtained during 20 autopsies. In addition, 80 individuals (58 male, 22 female; age range from 29 to 85) with acute coronary syndrome were subjected to a blood biochemical test, including quantification of TNF-α levels and IgG and IgM to Candida albicans was determined. Results: Fungi of the genus Candida were identified in 31.9% (15 out of 47) of atherosclerotic plaques. Particularly, Candida krusii and Candida grabrata were identified in overwhelming majority, although solitary colonies of Candida tropicalis and a single colony of Candida albicans were also detected. 80 (100%) patients were negative for IgM, but 30 (37.5%) were positive for IgG to Candida albicans. TNF-α was detected in a smaller quantity of IgG-negative patients (36.7%) relative to patients of IgG-positive group (70%), however its levels were considerably above in the first group (511.73±195.80 pg/ml) than in the second one (326.68±259.91 pg/ml, P < 0.05). Differences in the levels of ASAT and ALAT in patients positive to Candida albicans and negative for TNF-α were significantly higher than in the rest of patients. Conclusion: It is conceivable that fungi of the genus Candida are capable of inducing an inflammation of the vascular wall that in turn can lead to the development of atherosclerosis. PMID:25232398

  4. Effect of Delta-9-Tetrahydrocannabinol on Mouse Resistance to Systemic Candida albicans Infection

    PubMed Central

    Blumstein, Gideon W.; Parsa, Arya; Park, Anthony K.; McDowell, Beverly L. P.; Arroyo-Mendoza, Melissa; Girguis, Marie; Adler-Moore, Jill P.; Olson, Jon; Buckley, Nancy E.

    2014-01-01

    Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg) in vehicle on days 1–4, 8–11 and 15–18. On day 19, mice were infected with 5×105 C. albicans. We also determined the effect of chronic Δ9-THC (4–64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×104 C. albicans on day 2, followed by a higher challenge with 5×105 C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge. PMID:25057822

  5. Bloodstream Infections in Patients With Pulmonary Arterial Hypertension Treated With Intravenous Prostanoids: Insights From the REVEAL REGISTRY®

    PubMed Central

    Kitterman, Natalie; Poms, Abby; Miller, Dave P.; Lombardi, Sandra; Farber, Harrison W.; Barst, Robyn J.

    2012-01-01

    Objective To evaluate the rate of and potential risk factors for bloodstream infections (BSIs) using data from the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension [PAH] Disease Management) REGISTRY®, which provides current information about patients with PAH. Patients and Methods Patients were enrolled from March 30, 2006, through December 8, 2009, and data on reported BSIs were collected through the third quarter of 2010. Bloodstream infection rates were calculated per 1000 patient-days of risk. Results Of 3518 patients enrolled, 1146 patients received intravenous (IV) prostanoid therapy for more than 1 day (no BSI, n=1023; ≥1 BSI, n=123; total BSI episodes, n=166). Bloodstream infections rates were significantly increased in patients receiving IV treprostinil vs IV epoprostenol (0.36 vs 0.12 per 1000 treatment days; P<.001), primarily due to gram-negative organisms (0.20 vs 0.03 per 1000 treatment days; P<.001). Multivariate analysis adjusting for age, causes of PAH, and year of BSI found that treatment with IV treprostinil was associated with a 3.08-fold increase (95% confidence interval, 2.05-4.62; P<.001) in BSIs of any type and a 6.86-fold increase (95% confidence interval, 3.60-13.07; P<.001) in gram-negative BSIs compared with treatment with IV epoprostenol. Conclusion Compared with IV epoprostenol therapy, treatment with IV treprostinil is associated with a significantly higher rate of gram-negative BSIs; observed differences in BSI rate did not seem to be due to any other analyzed factors. Trial Registration clinicaltrials.gov Identifier: NCT00370214 PMID:22883740

  6. Roles of IL-33 in Resistance and Tolerance to Systemic Candida albicans Infections

    PubMed Central

    Park, Sang Jun; Cho, Hong Rae

    2016-01-01

    IL-33 is a multifunctional cytokine that is released in response to a variety of intrinsic and extrinsic stimuli. The role of IL-33 in Candida albicans infections is just beginning to be revealed. This cytokine has beneficial effects on host defense against systemic C. albicans infections, and it promotes resistance mechanisms by which the immune system eliminates the invading fungal pathogens; and it also elevates host tolerance by reducing the inflammatory response and thereby, potentially, tissue damage. Thus, IL-33 is classified as a cytokine that has evolved functionally to protect the host from damage by pathogens and immunopathology. PMID:27340384

  7. How to Optimize the Use of Blood Cultures for the Diagnosis of Bloodstream Infections? A State-of-the Art

    PubMed Central

    Lamy, Brigitte; Dargère, Sylvie; Arendrup, Maiken C.; Parienti, Jean-Jacques; Tattevin, Pierre

    2016-01-01

    Bloodstream infection (BSI) is a major cause of death in developed countries and the detection of microorganisms is essential in managing patients. Despite major progress has been made to improve identification of microorganisms, blood culture (BC) remains the gold standard and the first line tool for detecting BSIs. Consensus guidelines are available to ensure optimal BSI procedures, but BC practices often deviate from the recommendations. This review provides an update on clinical and technical issues related to blood collection and to BC performance, with a special focus on the blood sample strategy to optimize the sensitivity and specificity of BCs. PMID:27242721

  8. Bench-to-bedside review: Challenges of diagnosis, care and prevention of central catheter-related bloodstream infections in children

    PubMed Central

    2013-01-01

    Central venous catheters (CVCs) are indispensable in modern pediatric medicine. CVCs provide secure vascular access, but are associated with a risk of severe complications, in particular bloodstream infection. We provide a review of the recent literature about the diagnostic and therapeutic challenges of catheter-related bloodstream infection (CRBSI) in children and its prevention. Variations in blood sampling and limitations in blood culturing interfere with accurate and timely diagnosis of CRBSI. Although novel molecular testing methods appear promising in overcoming some of the present diagnostic limitations of conventional blood sampling in children, they still need to solidly prove their accuracy and reliability in clinical practice. Standardized practices of catheter insertion and care remain the cornerstone of CRBSI prevention although their implementation in daily practice may be difficult. Technology such as CVC impregnation or catheter locking with antimicrobial substances has been shown less effective than anticipated. Despite encouraging results in CRBSI prevention among adults, the goal of zero infection in children is still not in range. More high-quality research is needed in the field of prevention, accurate and reliable diagnostic measures and effective treatment of CRBSI in children. PMID:24041298

  9. Cytomegalovirus infection in patients with sepsis due to bloodstream infections: lower risk and better outcomes in new versus already hospitalised intensive care unit admissions.

    PubMed

    R, Osawa; M, Wagener; Ns, Singh

    2016-09-01

    Few studies have examined cytomegalovirus (CMV) reactivation exclusively in immunocompetent patients with sepsis due to bloodstream infections. In a cohort of CMV-seropositive critically ill otherwise non-immunosuppressed patients with sepsis due to bloodstream infection, weekly testing for CMV viraemia was performed. Outcomes were assessed at 30 days or until death/discharge from the intensive care unit (ICU). CMV viraemia developed in 20% (20/100) of the patients. Age (P=0.044) and blood transfusions (P=0.022) were significantly associated with CMV viraemia. There was no difference in the primary endpoint (mortality and/or multi-organ failure) between patients with and without CMV viraemia (P=0.49). However, CMV viraemia was associated with significantly fewer ICU-free days (P=0.023) and fewer ventilator-free days (P=0.031). Patients hospitalised in the ICU for more than 48 hours prior to the onset of bloodstream infection were more likely to develop CMV viraemia (P=0.006), have high-grade viraemia (P=0.010), and fewer ICU-free days (P=0.018) and ventilator-free days (P=0.029) than those admitted within 48 hours of bloodstream infection. Thus, CMV reactivation was associated with fewer ICU- and ventilator-free days, however overall mortality was not affected. Patients already in the ICU at the onset of sepsis had higher risk of CMV reactivation and worse outcomes than new ICU-bound patients suggesting that a targeted approach for interventions for CMV could conceivably be directed towards those with a more protracted course of illness. PMID:27608339

  10. Healthcare-associated bloodstream infections in critically ill patients: descriptive cross-sectional database study evaluating concordance with clinical site isolates

    PubMed Central

    2014-01-01

    Background Healthcare-associated bloodstream infections are related to both increased antibiotic use and risk of adverse outcomes. An in-depth understanding of their epidemiology is essential to reduce occurrence and to improve outcomes by targeted prevention strategies. The objectives of the study were to determine the epidemiology, source and concordance of healthcare-associated bloodstream infections with clinical site isolates. Methods We conducted a descriptive cross-sectional study in critically ill adults admitted to a tertiary semi-closed intensive care unit in England to determine the epidemiology, source and concordance of healthcare-associated bloodstream infections with clinical site isolates. All nosocomial positive blood cultures over a 4-year study period were identified. Pathogens detected and concordances with clinical site are reported as proportions. Results Contaminant pathogens accounted for half of the isolates. The most common non-contaminant pathogens cultured were Pseudomonas spp. (8.0%), Enterococcus spp. (7.3%) and Escherichia coli (5.6%). Central venous catheter-linked bloodstream infections represent only 6.0% of the positive blood cultures. Excluding contaminants and central venous line infections, in only 39.5% of the bloodstream infections could a concordant clinical site source be identified, the respiratory and urinary tracts being the most common. Conclusions Clinical practice should focus on a) improving blood culture techniques to reduce detection of contaminant pathogens and b) ensuring paired clinical site cultures are performed alongside all blood cultures to better understand the epidemiology and potential implications of primary and secondary discordant health-care associated bloodstream infections. PMID:25593750

  11. Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice

    PubMed Central

    Rahal, Elias A.; Constantin, Wissam N.; Zeidan, Nabil; Abdelnoor, Alexander M.

    2015-01-01

    Several antimicrobial and immunosuppressive effects have been attributed to the statins class of antihyperlipidemia drugs. Several studies have also indicated clinical benefits for the use of statins during the management of infections and sepsis. To assess whether the immunosuppressive effects of statins outweigh their antimicrobial effects during a fungal infection BALB/c mice were administered Candida albicans via intraperitoneal injection. These mice received either a co-injection of atorvastatin along with the infection, were treated with one injection of atorvastatin per day for 5 days prior to infection, or were infected and then treated with one injection of atorvastatin for 5 days afterward. Groups that received C. albicans without being treated with atorvastatin were included as controls along with a group that only received phosphate-buffered saline. Mouse survival was then monitored; additionally, serum IFN-γ and IL-4 levels were determined by enzyme linked immunosorbent assay to assess pro-inflammatory and pro-humoral responses, respectively. Atorvastatin administration was capable of altering mouse survival rate with the lowest rate (11.1%) being observed in the group treated for 5 days prior to infection with atorvastatin compared to mice infected but not treated with atorvastatin (44.4%). IFN-γ and IL-4 levels were depressed in all C. albicans-infected groups treated with atorvastatin. The possibility that statin administration may suppress or modulate particular components of the immune system during an infection in man should be further explored in large randomized controlled trials. PMID:26732740

  12. Evaluation of Real-time PCR and Pyrosequencing for Screening Incubating Blood Culture Bottles from Adults with Suspected Bloodstream Infection

    PubMed Central

    McCann, Chase D.; Moore, Miranda S.; May, Larissa S.; McCarroll, Matthew; Jordan, Jeanne A.

    2015-01-01

    Several molecular platforms can identify bacteria associated with bloodstream infections, but require positive culture bottles as starting material. Here we describe results of screening 1140 blood cultures at 8 hours post-inoculation, from 918 eligible adults being evaluated for bloodstream infection. DNA was extracted and analyzed by 16S and/or 23S rRNA real-time PCR/Pyrosequencing. Compared to culture, PCR/Pyrosequencing displayed 90.9% sensitivity, 99.6% specificity, 95.7% PPV, and 99.1% NPV. Overall concordance rate was 98.9% (1127/1140). In four cases with molecular-positive/culture-negative results, medical chart reviews provided evidence of identical bacteria from subsequent blood or concomitant urine/sputum cultures. Nine culture-positive/molecular-negative cases were associated with either polymicrobial growth, grew only in the anaerobic bottle of the clinical pair, and/or were detected by PCR/Pyrosequencing after 8 hours. In summary, this approach accurately detected and identified bacteria in ~91% of culture-confirmed cases significantly sooner than the phenotypic identification was available, having the potential to improve antibiotic stewardship. PMID:25534615

  13. Increased phenotypic switching in strains of Candida albicans associated with invasive infections.

    PubMed Central

    Jones, S; White, G; Hunter, P R

    1994-01-01

    This study reports the rates of phenotypic switching in strains of Candida albicans isolated from superficial and invasive infections. Of 19 invasive strains, 68% showed switching activity, often at very high rates, compared with only 28% of 40 strains isolated from superficial sites (P = 0.004). PMID:7852592

  14. Population-based epidemiology of Staphylococcus aureus bloodstream infection: clonal complex 30 genotype is associated with mortality.

    PubMed

    Blomfeldt, A; Eskesen, A N; Aamot, H V; Leegaard, T M; Bjørnholt, J V

    2016-05-01

    Staphylococcus aureus bloodstream infections (SABSI) are associated with a high burden of morbidity and mortality. The impact of specific S. aureus genotypes on outcome is unclear. The aim of this study was to evaluate the epidemiology and outcome of SABSI, with a special emphasis on the impact of bacterial clonal lineage on mortality. We conducted a 3-year population-based prospective study between 2011 and 2014, including 303 consecutive adult patients. Clinical data were obtained from interviews and medical records. S. aureus isolates were genotyped using DNA microarrays. The incidence rate of SABSI was 27.6 per 100,000 inhabitants [95 % confidence interval (CI) 24.6-31.0]. The median age of the patients was 71 years (interquartile range 56-81 years) and 61.4 % were male. Most SABSI (70.6 %) occurred in hospitals or associated to healthcare, and 34.1 % of these were associated with intravascular catheters. Only five (1.6 %) SABSI were caused by methicillin-resistant S. aureus (MRSA). The 30-day case fatality rate was 20.8 % (95 % CI 16.6-25.7). S. aureus clonal complex 30 [hazard ratio (HR) 3.9; 95 % CI 1.8-8.5, p = 0.001], unknown focus of infection (HR 4.5; 95 % CI 1.9-10.8, p = 0.001) and respiratory tract infection (HR 12.7; 95 % CI 4.6-34.6, p < 0.001) were independent predictors of mortality in a Cox regression analysis after adjusting for age, sex and underlying conditions. A high proportion of potential preventable SABSI calls for effective infection control measures. S. aureus clonal complex 30 genotype was associated with mortality in patients with bloodstream infections. The genetic basis underlying this association remains to be demonstrated. PMID:26873380

  15. CLABSI Conversations: Lessons From Peer-to-Peer Assessments to Reduce Central Line-Associated Bloodstream Infections.

    PubMed

    Pham, Julius Cuong; Goeschel, Christine A; Berenholtz, Sean M; Demski, Renee; Lubomski, Lisa H; Rosen, Michael A; Sawyer, Melinda D; Thompson, David A; Trexler, Polly; Weaver, Sallie J; Weeks, Kristina R; Pronovost, Peter J

    2016-01-01

    A national collaborative helped many hospitals dramatically reduce central line-associated bloodstream infections (CLABSIs), but some hospitals struggled to reduce infection rates. This article describes the development of a peer-to-peer assessment process (CLABSI Conversations) and the practical, actionable practices we discovered that helped intensive care unit teams achieve a CLABSI rate of less than 1 infection per 1000 catheter-days for at least 1 year. CLABSI Conversations was designed as a learning-oriented process, in which a team of peers visited hospitals to surface barriers to infection prevention and to share best practices and insights from successful intensive care units. Common practices led to 10 recommendations: executive and board leaders communicate the goal of zero CLABSI throughout the hospital; senior and unit-level leaders hold themselves accountable for CLABSI rates; unit physicians and nurse leaders own the problem; clinical leaders and infection preventionists build infection prevention training and simulation programs; infection preventionists participate in unit-based CLABSI reduction efforts; hospital managers make compliance with best practices easy; clinical leaders standardize the hospital's catheter insertion and maintenance practices and empower nurses to stop any potentially harmful acts; unit leaders and infection preventionists investigate CLABSIs to identify root causes; and unit nurses and staff audit catheter maintenance policies and practices. PMID:27031355

  16. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    SciTech Connect

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.; Schneewind, Olaf

    2015-01-06

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.

  17. Differential activation of a Candida albicans virulence gene family during infection

    PubMed Central

    Staib, Peter; Kretschmar, Marianne; Nichterlein, Thomas; Hof, Herbert; Morschhäuser, Joachim

    2000-01-01

    The yeast Candida albicans is a harmless commensal in most healthy people, but it causes superficial as well as life-threatening systemic infections in immunocompromised patients. C. albicans can colonize or infect virtually all body sites because of its high adaptability to different host niches, which involves the activation of appropriate sets of genes in response to complex environmental signals. We have used an in vivo expression technology that is based on genetic recombination as a reporter of gene expression to monitor the differential activation of individual members of a gene family encoding secreted aspartic proteinases (Saps), which have been implicated in C. albicans virulence, at various stages of the infection process. Our results demonstrate that SAP expression depends on the type of infection, with different SAP isogenes being activated during systemic disease as compared with mucosal infection. In addition, the activation of individual SAP genes depends on the progress of the infection, some members of the gene family being induced immediately after contact with the host, whereas others are expressed only after dissemination into deep organs. In the latter case, the number of invading organisms determines whether induction of a virulence gene is necessary for successful infection. The in vivo expression technology allows the elucidation of gene expression patterns at different stages of the fungus–host interaction, thereby revealing regulatory adaptation mechanisms that make C. albicans the most successful fungal pathogen of humans and, at the same time, identifying the stage of an infection at which certain virulence genes may play a role. PMID:10811913

  18. A Short-Term Borrelia burgdorferi Infection Model Identifies Tissue Tropisms and Bloodstream Survival Conferred by Adhesion Proteins

    PubMed Central

    Caine, Jennifer A.

    2015-01-01

    Borrelia burgdorferi, the causative agent of Lyme disease in the United States, is able to persist in the joint, heart, skin, and central nervous system for the lifetime of its mammalian host. Borrelia species achieve dissemination to distal sites in part by entry into and travel within the bloodstream. Much work has been performed in vitro describing the roles of many B. burgdorferi outer surface proteins in adhesion to host cell surface proteins and extracellular matrix components, although the biological relevance of these interactions is only beginning to be explored in vivo. A need exists in the field for an in vivo model to define the biological roles of B. burgdorferi adhesins in tissue-specific vascular interactions. We have developed an in vivo model of vascular interaction of B. burgdorferi in which the bacteria are injected intravenously and allowed to circulate for 1 h. This model has shown that the fibronectin binding protein BB0347 has a tropism for joint tissue. We also have shown an importance of the integrin binding protein, P66, in binding to vasculature of the ear and heart. This model also revealed unexpected roles for Borrelia adhesins BBK32 and OspC in bacterial burdens in the bloodstream. The intravenous inoculation model of short-term infection provides new insights into critical B. burgdorferi interactions with the host required for initial survival and tissue colonization. PMID:26015482

  19. Daily Review of Antimicrobial Use Facilitates the Early Optimization of Antimicrobial Therapy and Improves Clinical Outcomes of Patients with Bloodstream Infections.

    PubMed

    Niwa, Takashi; Watanabe, Tamayo; Goto, Takayuki; Ohta, Hirotoshi; Nakayama, Asami; Suzuki, Keiko; Shinoda, Yasutaka; Tsuchiya, Mayumi; Yasuda, Koji; Murakami, Nobuo; Itoh, Yoshinori

    2016-05-01

    Insufficient information is available to confirm the beneficial effects of implementing an antimicrobial stewardship program in reducing mortality of patients with bloodstream infections. A single institutional cohort study was conducted to evaluate clinical outcomes after implementation of a daily review of antimicrobials used to treat patients with bloodstream infections. Subjects were allocated to groups receiving either intervention or nonintervention. After implementation of an antimicrobial stewardship program, the day from the onset of infection required to administer effective intravenous antimicrobial treatment was significantly shortened (p=0.022), and the rate of de-escalation was significantly elevated (p<0.001) compared with the nonintervention group. Further, the rate of 30-d death associated with bloodstream infection was siginificantly reduced from 11.4 to 5.4% (p=0.030) compared with the nonintervention group. The incidence of adverse events was significantly lower in the intervention group than in the nonintervention group (7.7 vs. 28.0%, p<0.001). Our present findings suggest that daily review of the use of antimicrobials was highly effective for optimizing early antimicrobial therapy and improved clinical outcomes of patients with bloodstream infections. PMID:26923491

  20. Bilateral endogenous Candida albicans subretinal abscess with suspected mixed bacterial infection

    PubMed Central

    Arai, Yusuke; Sato, Yukihiro; Yoshida, Atsushi; Kawashima, Hidetoshi; Kaburaki, Toshikatsu; Gomi, Harumi

    2014-01-01

    Purpose Candida albicans subretinal abscess is extremely rare. To our knowledge, only one unilateral case has been reported. Herein, we report one bilateral case. Mixed bacterial infection was also suspected based on broad-range real-time polymerase chain reaction. Methods A 64-year-old man being treated with oral corticosteroids for interstitial pneumonia visited us for visual loss in the left eye. Best corrected visual acuity (BCVA) was 20/20 in the right eye and 8/200 in the left eye. Funduscopy revealed round yellowish-white subretinal lesions with retinal hemorrhage in both eyes. Results Broad-range polymerase chain reaction of the vitreous fluid from the left eye showed a high copy count of bacterial 16s ribosome RNA. Despite large doses of antibiotics, the abscess expanded and vision decreased to light perception in the left eye. Exenteration of the left eye was performed followed by microscopic examination showing Gram-negative bacilli, and C. albicans was also cultured. Antibiotics and the maximum doses of antifungal drugs were administered. However, the abscess in the right eye expanded, and BCVA decreased to 2/200. Vitrectomy and silicone oil tamponade were performed. Vitreous fluid culture revealed C. albicans. At 16 months follow-up, BCVA was stable at 4/200 with healing of the subretinal abscess under silicone oil. Conclusion Since C. albicans subretinal abscess is extremely rare and there was a concurrent mixed bacterial infection, diagnostic procedures in our bilateral case were more complicated than usual. C. albicans infection should be included in the differential diagnosis of subretinal abscesses. PMID:25378901

  1. Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood

    PubMed Central

    Nölling, Jörk; Rapireddy, Srinivas; Amburg, Joel I.; Crawford, Elizabeth M.; Prakash, Ranjit A.; Rabson, Arthur R.

    2016-01-01

    ABSTRACT Bloodstream infections are a leading cause of morbidity and mortality. Early and targeted antimicrobial intervention is lifesaving, yet current diagnostic approaches fail to provide actionable information within a clinically viable time frame due to their reliance on blood culturing. Here, we present a novel pathogen identification (PID) platform that features the use of duplex DNA-invading γ-modified peptide nucleic acids (γPNAs) for the rapid identification of bacterial and fungal pathogens directly from blood, without culturing. The PID platform provides species-level information in under 2.5 hours while reaching single-CFU-per-milliliter sensitivity across the entire 21-pathogen panel. The clinical utility of the PID platform was demonstrated through assessment of 61 clinical specimens, which showed >95% sensitivity and >90% overall correlation to blood culture findings. This rapid γPNA-based platform promises to improve patient care by enabling the administration of a targeted first-line antimicrobial intervention. PMID:27094328

  2. Bloodstream infections caused by multi-drug resistant Proteus mirabilis: Epidemiology, risk factors and impact of multi-drug resistance.

    PubMed

    Korytny, Alexander; Riesenberg, Klaris; Saidel-Odes, Lisa; Schlaeffer, Fransisc; Borer, Abraham

    2016-06-01

    Background The prevalence of antimicrobial co-resistance among ESBL-producing Enterobactereaceae is extremely high in Israel. Multidrug-resistant Proteus mirabilis strains (MDR-PM), resistant to almost all antibiotic classes have been described. The aim was to determine the risk factors for bloodstream infections caused by MDR-PM and clinical outcomes. Methods A retrospective case-control study. Adult patients with PM bacteremia during 7 years were identified retrospectively and their files reviewed for demographics, underlying diseases, Charlson Comorbidity Index, treatment and outcome. Results One hundred and eighty patients with PM-bloodstream infection (BSI) were included; 90 cases with MDR-PM and 90 controls with sensitive PM (S-PM). Compared to controls, cases more frequently were from nursing homes, had recurrent hospital admissions in the past year and received antibiotic therapy in the previous 3 months, were bedridden and suffered from peripheral vascular disease and peptic ulcer disease (p < 0.001). Two-thirds of the MDR-PM isolates were ESBL-producers vs 4.4% of S-PM isolates (p < 0.001, OR = 47.6, 95% CI = 15.9-142.6). In-hospital crude mortality rate of patients with MDR-PM BSI was 37.7% vs 23.3% in those with S-PM BSI (p = 0.0359, OR = 2, 95% CI = 1.4-3.81). Conclusions PM bacteremia in elderly and functionally-dependent patients is likely to be caused by nearly pan-resistant PM strains in the institution; 51.8% of the patients received inappropriate empiric antibiotic treatment. The crude mortality rate of patients with MDR-PM BSI was significantly higher than that of patients with S-PM BSI. PMID:26763474

  3. Clinical and Microbiological Characteristics of Heteroresistant and Vancomycin-Intermediate Staphylococcus aureus from Bloodstream Infections in a Brazilian Teaching Hospital

    PubMed Central

    da Costa, Thaina Miranda; Morgado, Priscylla Guimarães Migueres; Cavalcante, Fernanda Sampaio; Damasco, Andreia Paredes; Nouér, Simone Aranha; dos Santos, Kátia Regina Netto

    2016-01-01

    This study analyzed clinical and microbiological characteristics of heteroresistant (hVISA) and vancomycin-intermediate Staphylococcus aureus (VISA) from bloodstream infections (BSI) in a Brazilian teaching hospital, between 2011 and 2013. Minimum inhibitory concentrations (MIC) of antimicrobials were determined by broth microdilution method and SCCmec was detected by PCR. Isolates with a vancomycin MIC ≥ 2mg/L were cultured on BHI agar with 3, 4 or 6 mg/L (BHIa3, BHIa4 or BHIa6) of vancomycin and BHIa4 with casein (BHIa4ca). Macromethod Etest® and Etest® Glicopeptides Resistance Detection were also used. VISA and hVISA isolates were confirmed by the population analysis profile then typed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Medical data from the patients were obtained from their medical records. Among 110 consecutive isolates, 31 (28%) were MRSA and carried the SCCmec type II (15 isolates) or IV (16 isolates). Vancomycin MIC50 and MIC90 were 1 and 2 mg/L, respectively. MRSA isolates had increased non-susceptibility to daptomycin (p = 0.0003). Six (5%) isolates were VISA, four of which were MRSA, three SCCmec type II/USA100/ST5 and one type IV/USA800/ST3192. One MRSA SCCmec II isolate grew on agar BHIa3, BHIa4 and BHIa4ca, and it was confirmed as hVISA. Among the six VISA isolates, five (83%) grew on BHIa3 and three (50%) on BHI4ca. Four of the six VISA isolates and the one hVISA isolate were from patients who had undergone dialysis. Thus, a possible dissemination of the SCCmec II/USA100/ST5 lineage may have occurred in the hospital comprising the VISA, hVISA and daptomycin non-susceptible S. aureus Brazilian isolates from health care associated bloodstream infections. PMID:27575698

  4. Value of Superficial Cultures for Prediction of Catheter-Related Bloodstream Infection in Long-Term Catheters: a Prospective Study

    PubMed Central

    Martín-Rabadán, P.; Echenagusia, A.; Camúñez, F.; Rodríguez-Rosales, G.; Simó, G.; Echenagusia, M.; Bouza, E.

    2013-01-01

    Cultures taken from the skin and from the hubs of short-term central venous catheters can help us to predict catheter-related bloodstream infections (C-RBSIs). The value of these cultures for such predictions has not been assessed in long-term catheters. Our objective was to assess the value of superficial cultures for the prediction of C-RBSI among patients with long-term catheters. Over a 2-year period, we prospectively obtained cultures from the skin overlying reservoir ports (group A) and from the skin insertion site and hubs of all tunneled catheters (group B). This routine was performed by vascular and interventional radiologists immediately before catheter removal (irrespective of the reason for withdrawal). Swabs were processed semiquantitatively. Catheter tips from both groups were cultured using Maki's semiquantitative technique and sonication. We also performed cultures of the reservoir ports at different sites. C-RBSI was defined as the isolation of the same species of microorganism(s) both in the colonized catheter and in at least 1 peripheral blood culture. We included 372 catheters (group A, 223; group B, 149) during the study period. The catheter colonization rate was 23.4% (87/372), and 28 patients had C-RBSI. Validity index values for the capacity of surface cultures to predict C-RBSI in groups A and B were, respectively, as follows: sensitivity, 23.5% and 45.5%; specificity, 59.7% and 63.0%; positive predictive value, 4.6% and 8.9%; and negative predictive value, 90.4% and 93.5%. Superficial cultures of patients with long-term catheters could help us to rule out the catheter as the portal of entry of bloodstream infections. Superficial cultures (from skin and hubs) proved to be a useful conservative diagnostic tool for ruling out C-RBSI among patients with long-term tunneled catheters and totally implantable venous access ports. PMID:23850957

  5. Use of the VITEK 2 System for Rapid Identification of Clinical Isolates of Staphylococci from Bloodstream Infections

    PubMed Central

    Spanu, Teresa; Sanguinetti, Maurizio; Ciccaglione, Daniela; D'Inzeo, Tiziana; Romano, Lucio; Leone, Fiammetta; Fadda, Giovanni

    2003-01-01

    Staphylococci are an increasing cause of bloodstream infections. Rapid reliable identification of these organisms is essential for accurate diagnosis and prompt effective treatment. We evaluated the ability of the VITEK 2 system (bioMérieux, Inc, Hazelwood, Mo.) to identify these organisms rapidly and accurately. A total of 405 clinically relevant nonduplicate staphylococcal isolates (Staphylococcus aureus, n = 130; coagulase-negative staphylococci, n = 275) collected from blood cultures were tested. VITEK 2 results were considered correct when they were identical to those furnished by the comparison method based on the ID 32 STAPH system (bioMérieux, Marcy l'Etoile, France) plus supplementary manual testing. When discrepancies occurred, isolate identity was verified by molecular typing. The VITEK 2 correctly identified 387 (95.6%) isolates at the species level: 379 (including all but one [99.2%] of 130 S. aureus isolates and 249 of 275 [90.5%] coagulase-negative isolates) were identified by the automated reading; for the other eight, supplemental tests suggested by the manufacturer had to be used. Only one strain (0.2%) was misidentified (Staphylococcus hominis as Staphylococcus epidermidis), and four (1%), all S. epidermidis, were not identified. For the remaining 13 strains (including 10 S. hominis), the VITEK 2 system was unable to discriminate among two species, and no supplemental tests were suggested for conclusive identification. Over 90% of results were obtained within 4 h. These results suggest that the VITEK 2 system can provide rapid, accurate, and reliable species-level identification of staphylococci responsible for bloodstream infections, although there is room for improvement in the identification of certain coagulase-negative species, especially S. hominis. PMID:12958254

  6. Clinical and Microbiological Characteristics of Heteroresistant and Vancomycin-Intermediate Staphylococcus aureus from Bloodstream Infections in a Brazilian Teaching Hospital.

    PubMed

    da Costa, Thaina Miranda; Morgado, Priscylla Guimarães Migueres; Cavalcante, Fernanda Sampaio; Damasco, Andreia Paredes; Nouér, Simone Aranha; Dos Santos, Kátia Regina Netto

    2016-01-01

    This study analyzed clinical and microbiological characteristics of heteroresistant (hVISA) and vancomycin-intermediate Staphylococcus aureus (VISA) from bloodstream infections (BSI) in a Brazilian teaching hospital, between 2011 and 2013. Minimum inhibitory concentrations (MIC) of antimicrobials were determined by broth microdilution method and SCCmec was detected by PCR. Isolates with a vancomycin MIC ≥ 2mg/L were cultured on BHI agar with 3, 4 or 6 mg/L (BHIa3, BHIa4 or BHIa6) of vancomycin and BHIa4 with casein (BHIa4ca). Macromethod Etest® and Etest® Glicopeptides Resistance Detection were also used. VISA and hVISA isolates were confirmed by the population analysis profile then typed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Medical data from the patients were obtained from their medical records. Among 110 consecutive isolates, 31 (28%) were MRSA and carried the SCCmec type II (15 isolates) or IV (16 isolates). Vancomycin MIC50 and MIC90 were 1 and 2 mg/L, respectively. MRSA isolates had increased non-susceptibility to daptomycin (p = 0.0003). Six (5%) isolates were VISA, four of which were MRSA, three SCCmec type II/USA100/ST5 and one type IV/USA800/ST3192. One MRSA SCCmec II isolate grew on agar BHIa3, BHIa4 and BHIa4ca, and it was confirmed as hVISA. Among the six VISA isolates, five (83%) grew on BHIa3 and three (50%) on BHI4ca. Four of the six VISA isolates and the one hVISA isolate were from patients who had undergone dialysis. Thus, a possible dissemination of the SCCmec II/USA100/ST5 lineage may have occurred in the hospital comprising the VISA, hVISA and daptomycin non-susceptible S. aureus Brazilian isolates from health care associated bloodstream infections. PMID:27575698

  7. A cluster of central line-associated bloodstream infections due to rapidly growing nontuberculous mycobacteria in patients with hematologic disorders at a Japanese tertiary care center: an outbreak investigation and review of the literature.

    PubMed

    Tagashira, Yasuaki; Kozai, Yasuji; Yamasa, Hitomi; Sakurada, Masako; Kashiyama, Tetsuya; Honda, Hitoshi

    2015-01-01

    BACKGROUND Rapidly growing nontuberculous mycobacteria (RGM) are considered rare pathogens, causing central line-associated bloodstream infection. We identified an outbreak of central line-associated bloodstream infection due to RGM at a hematology-oncology ward during a 5-month period. DESIGN Outbreak investigation and literature review. SETTING A Japanese tertiary care center. PATIENTS Adults who were hospitalized at the hematology-oncology ward from October 15, 2011, through February 17, 2012. RESULTS A total of 5 patients with a bloodstream infection due to RGM (4 cases of Mycobacterium mucogenicum and 1 case of Mycobacterium canariasense infection) were identified; of these, 3 patients had acute myeloid leukemia, 1 had acute lymphocytic leukemia, and 1 had aplastic anemia. Four of the 5 patients received cord blood transplantation prior to developing the bloodstream infection. All central venous catheters in patients with a bloodstream infection were removed. These patients promptly defervesced after catheter removal and their care was successfully managed without antimicrobial therapy. Surveillance cultures from the environment and water detected M. mucogenicum and M. canariasense in the water supply of the hematology-oncology ward. The isolates from the bloodstream infection and water sources were identical on the basis of 16S-rRNA gene sequencing. CONCLUSIONS The source of RGM in the outbreak of bloodstream infections likely was the ward tap water supply. Awareness of catheter-related bloodstream infections due to nontuberculous mycobacteria should be emphasized, especially where immunocompromised patients are at risk. Also, using antimicrobials after catheter removal to treat central line-associated bloodstream infection due to RGM may not be necessary. Infect Control Hosp Epidemiol 2015;36(1): 76-80. PMID:25627764

  8. Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

    PubMed Central

    Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R.; Birx, Deborah L.; Ratto-Kim, Silvia; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Hu, Haitao

    2016-01-01

    Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548

  9. Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection.

    PubMed

    Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R; Birx, Deborah L; Ratto-Kim, Silvia; Robb, Merlin L; Kim, Jerome H; Michael, Nelson L; Hu, Haitao

    2016-06-01

    Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548

  10. A Web-Based, Hospital-Wide Health Care-Associated Bloodstream Infection Surveillance and Classification System: Development and Evaluation

    PubMed Central

    Tseng, Yi-Ju; Wu, Jung-Hsuan; Lin, Hui-Chi; Chen, Ming-Yuan; Ping, Xiao-Ou; Sun, Chun-Chuan; Shang, Rung-Ji; Sheng, Wang-Huei; Lai, Feipei; Chang, Shan-Chwen

    2015-01-01

    Background Surveillance of health care-associated infections is an essential component of infection prevention programs, but conventional systems are labor intensive and performance dependent. Objective To develop an automatic surveillance and classification system for health care-associated bloodstream infection (HABSI), and to evaluate its performance by comparing it with a conventional infection control personnel (ICP)-based surveillance system. Methods We developed a Web-based system that was integrated into the medical information system of a 2200-bed teaching hospital in Taiwan. The system automatically detects and classifies HABSIs. Results In this study, the number of computer-detected HABSIs correlated closely with the number of HABSIs detected by ICP by department (n=20; r=.999 P<.001) and by time (n=14; r=.941; P<.001). Compared with reference standards, this system performed excellently with regard to sensitivity (98.16%), specificity (99.96%), positive predictive value (95.81%), and negative predictive value (99.98%). The system enabled decreasing the delay in confirmation of HABSI cases, on average, by 29 days. Conclusions This system provides reliable and objective HABSI data for quality indicators, improving the delay caused by a conventional surveillance system. PMID:26392229

  11. Ibuprofen Potentiates the In Vivo Antifungal Activity of Fluconazole against Candida albicans Murine Infection

    PubMed Central

    Miranda, Isabel M.; Silva-Dias, Ana; Silva, Ana P.; Rodrigues, Acácio G.; Pina-Vaz, Cidália

    2015-01-01

    Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression. PMID:25845879

  12. The first reported catheter-related Brevibacterium casei bloodstream infection in a child with acute leukemia and review of the literature.

    PubMed

    Bal, Zumrut Sahbudak; Sen, Semra; Karapinar, Deniz Yilmaz; Aydemir, Sohret; Vardar, Fadil

    2015-01-01

    Brevibacterium spp. are catalase-positive, non-spore-forming, non motile, aerobic Gram-positive rods that were considered apathogenic until a few reports of infections in immunocompromised patients had been published. To the best of our knowledge, this is the first report of B. casei catheter-related bloodstream infection in a child with acute leukemia. We aim to enhance the awareness of pediatric hematology and infectious disease specialists about this pathogen and review of the literature. PMID:25636191

  13. Antimicrobial Resistance and Molecular Epidemiology of Escherichia coli Causing Bloodstream Infections in Three Hospitals in Shanghai, China.

    PubMed

    Wang, Su; Zhao, Sheng-Yuan; Xiao, Shu-Zhen; Gu, Fei-Fei; Liu, Qing-Zhong; Tang, Jin; Guo, Xiao-Kui; Ni, Yu-Xing; Han, Li-Zhong

    2016-01-01

    Escherichia coli (E. coli) is one of the most frequent and lethal causes of bloodstream infections (BSIs). We carried out a retrospective multicenter study on antimicrobial resistance and phylogenetic background of clinical E. coli isolates recovered from bloodstream in three hospitals in Shanghai. E. coli isolates causing BSIs were consecutively collected between Sept 2013 and Sept 2014. Ninety isolates randomly selected (30 from each hospital) were enrolled in the study. Antimicrobial susceptibility testing was performed by disk diffusion. PCR was used to detect antimicrobial resistance genes coding for β-lactamases (TEM, CTX-M, OXA, etc.), carbapenemases (IMP, VIM, KPC, NDM-1 and OXA-48), and phylogenetic groups. eBURST was applied for analysis of multi-locus sequence typing (MLST). The resistance rates for penicillins, second-generation cephalosporins, fluoroquinolone and tetracyclines were high (>60%). Sixty-one of the 90 (67.8%) strains enrolled produced ESBLs and no carbapenemases were found. Molecular analysis showed that CTX-M-15 (25/61), CTX-M-14 (18/61) and CTX-M-55 (9/61) were the most common ESBLs. Phylogenetic group B2 predominated (43.3%) and exhibited the highest rates of ESBLs production. ST131 (20/90) was the most common sequence type and almost assigned to phylogenetic group B2 (19/20). The following sequence types were ST405 (8/90) and ST69 (5/90). Among 61 ESBL-producers isolates, B2 (26, 42.6%) and ST131 (18, 29.5%) were also the most common phylogenetic group and sequence type. Genetic diversity showed no evidence suggesting a spread of these antimicrobial resistant isolates in the three hospitals. In order to provide more comprehensive and reliable epidemiological information for preventing further dissemination, well-designed and continuous surveillance with more hospitals participating was important. PMID:26824702

  14. Antimicrobial Resistance and Molecular Epidemiology of Escherichia coli Causing Bloodstream Infections in Three Hospitals in Shanghai, China

    PubMed Central

    Xiao, Shu-Zhen; Gu, Fei-Fei; Liu, Qing-Zhong; Tang, Jin; Guo, Xiao-Kui; Ni, Yu-Xing; Han, Li-Zhong

    2016-01-01

    Escherichia coli (E. coli) is one of the most frequent and lethal causes of bloodstream infections (BSIs). We carried out a retrospective multicenter study on antimicrobial resistance and phylogenetic background of clinical E. coli isolates recovered from bloodstream in three hospitals in Shanghai. E. coli isolates causing BSIs were consecutively collected between Sept 2013 and Sept 2014. Ninety isolates randomly selected (30 from each hospital) were enrolled in the study. Antimicrobial susceptibility testing was performed by disk diffusion. PCR was used to detect antimicrobial resistance genes coding for β-lactamases (TEM, CTX-M, OXA, etc.), carbapenemases (IMP, VIM, KPC, NDM-1 and OXA-48), and phylogenetic groups. eBURST was applied for analysis of multi-locus sequence typing (MLST). The resistance rates for penicillins, second-generation cephalosporins, fluoroquinolone and tetracyclines were high (>60%). Sixty-one of the 90 (67.8%) strains enrolled produced ESBLs and no carbapenemases were found. Molecular analysis showed that CTX-M-15 (25/61), CTX-M-14 (18/61) and CTX-M-55 (9/61) were the most common ESBLs. Phylogenetic group B2 predominated (43.3%) and exhibited the highest rates of ESBLs production. ST131 (20/90) was the most common sequence type and almost assigned to phylogenetic group B2 (19/20). The following sequence types were ST405 (8/90) and ST69 (5/90). Among 61 ESBL-producers isolates, B2 (26, 42.6%) and ST131 (18, 29.5%) were also the most common phylogenetic group and sequence type. Genetic diversity showed no evidence suggesting a spread of these antimicrobial resistant isolates in the three hospitals. In order to provide more comprehensive and reliable epidemiological information for preventing further dissemination, well-designed and continuous surveillance with more hospitals participating was important. PMID:26824702

  15. Aseptic non-touch technique and catheter-related bloodstream infection in children receiving parenteral nutrition at home

    PubMed Central

    Evans, Victoria; Hughes, Anna; Hill, Susan

    2015-01-01

    Objectives Parenteral nutrition (PN) at home is an acceptable form of delivering long-term PN for children with intestinal failure. Catheter-related bloodstream infection (CRBSI) is one of the serious complications of long-term PN and can lead to increasing morbidity and mortality. Using aseptic non-touch technique (ANTT) was proven to decrease the incidence of CRBSI in hospital patients. In this study we aimed to review the incidence of CRBSI in children receiving PN at home in our institution using the ANTT and a simplified training programme for parents and carers. Methods We retrospectively collected clinical and microbiological data on all children with intestinal failure (IF) who were on treatment with PN at home under our specialist IF rehabilitation service between November 2012 and November 2013. Results Thirty-five children were included, 16 of whom did not have any infection recorded during the study period. The overall CRBSI rate was 1.3 infections per 1000 line-days, with Staphylococcus being the commonest organism. Twenty-one children did not require catheter change and the overall catheter changes were 1.8 per 1000 line-days. Conclusion In this article, we report a low incidence of CRBSI in a single institution by using the principle of ANTT for accessing central venous catheters combined with a simplified, nurse-led, two-week standardised training programme for parents of children going home on PN. PMID:26279849

  16. In vitro susceptibility to methicillin, vancomycin and linezolid of staphylococci isolated from bloodstream infections in eastern Turkey

    PubMed Central

    Tekin, Alicem; Dal, Tuba; Deveci, Özcan; Tekin, Recep; Özcan, Nida; Atmaca, Selahattin; Dayan, Saim

    2014-01-01

    Staphylococcus species are one of the major causes of bacterial bloodstream infections. Multi-resistant staphylococci infections are major therapeutic problems. This study was aimed to detect methicillin, linezolid and vancomycin susceptibilities of Staphylococcus isolates. A total of 870 Staphylococcus strains isolated from blood cultures of hospitalized patients with BSI. Antimicrobial susceptibilities of methicillin, linezolid and vancomycin were detected according to the Clinical and Laboratory Standards Institute (CLSI). A total of 771 (88.6%) isolates were coagulase-negative staphylococci (CoNS). 700 (80.5%) isolates were methicillin-resistant (MR) and 170 (19.5%) were methicillin-susceptible (MS). All the MS isolates were also susceptible to linezolid. However 15 (1.7%) of MR strains were resistant to linezolid. The minimum inhibitory concentration range for the linezolid-resistant isolates by Etest was 6–32 μg/mL. The difference between linezolid susceptibilities for MS and MR staphylococci was not quite statistically significant (p = 0.052). There was no statistically significant difference between S. aureus and CoNS isolates for linezolid susceptibility. All of the isolates were susceptible to vancomycin. In conclusion, linezolid is currently an efficient option for the treatment of methicillin-resistant staphylococci infections. PMID:25477914

  17. Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2

    PubMed Central

    Desai, Jigar V.; Cheng, Shaoji; Ying, Tammy; Nguyen, M. Hong; Clancy, Cornelius J.; Lanni, Frederick; Mitchell, Aaron P.

    2015-01-01

    The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population. PMID:26213976

  18. Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2.

    PubMed

    Desai, Jigar V; Cheng, Shaoji; Ying, Tammy; Nguyen, M Hong; Clancy, Cornelius J; Lanni, Frederick; Mitchell, Aaron P

    2015-01-01

    The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population. PMID:26213976

  19. BAY 41-2272 activates host defence against local and disseminated Candida albicans infections.

    PubMed

    Soeiro-Pereira, Paulo Vítor; Falcai, Angela; Kubo, Christina Arslanian; Antunes, Edson; Condino-Neto, Antonio

    2015-02-01

    In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. PMID:25742266

  20. BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

    PubMed Central

    Soeiro-Pereira, Paulo Vítor; Falcai, Angela; Kubo, Christina Arslanian; Antunes, Edson; Condino-Neto, Antonio

    2015-01-01

    In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. PMID:25742266

  1. Healthcare Burden, Risk Factors, and Outcomes of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections after Stem Cell Transplantation.

    PubMed

    Dandoy, Christopher E; Haslam, David; Lane, Adam; Jodele, Sonata; Demmel, Kathy; El-Bietar, Javier; Flesch, Laura; Myers, Kasiani C; Pate, Abigail; Rotz, Seth; Daniels, Paulina; Wallace, Gregory; Nelson, Adam; Waters, Heather; Connelly, Beverly; Davies, Stella M

    2016-09-01

    Mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBIs) lead to significant morbidity, mortality, and healthcare resource utilization in hematopoietic stem cell transplant (HSCT) patients. Determination of the healthcare burden of MBI-LCBIs and identification of patients at risk of MBI-LCBIs will allow researchers to identify strategies to reduce MBI-LCBI rates. The objective of our study was to describe the incidence, risk factors, timing, and outcomes of MBI-LCBIs in hematopoietic stem cell transplant patients. We performed a retrospective analysis of 374 patients who underwent HSCT at a large free-standing academic children's hospital to determine the incidence, risk factors, and outcomes of patients that developed a bloodstream infection (BSI) including MBI-LCBI, central line-associated BSI (CLABSI), or secondary BSI in the first year after HSCT. Outcome measures included nonrelapse mortality (NRM), central venous catheter removal within 7 days of positive culture, shock, admission to the pediatric intensive care unit (PICU) within 48 hours of positive culture, and death within 10 days of positive culture. One hundred seventy BSIs were diagnosed in 100 patients (27%): 80 (47%) MBI-LCBIs, 68 (40%) CLABSIs, and 22 (13%) secondary infections. MBI-LCBIs were diagnosed at a significantly higher rate in allogeneic HSCT patients (18% versus 7%, P = .007). Reduced-intensity conditioning (OR, 1.96; P = .015) and transplant-associated thrombotic microangiopathy (OR, 2.94; P = .0004) were associated with MBI-LCBI. Nearly 50% of all patients with a BSI developed septic shock, 10% died within 10 days of positive culture, and nearly 25% were transferred to the PICU. One-year NRM was significantly increased in patients with 1 (34%) and more than 1 (56%) BSIs in the first year post-HSCT compared with those who did not develop BSIs (14%) (P ≤ .0001). There was increased 1-year NRM in patients with at least 1 MBI-LCBI (OR, 1.94; P

  2. Case-Control Study of Telavancin as an Alternative Treatment for Gram-Positive Bloodstream Infections in Patients with Cancer.

    PubMed

    Chaftari, Anne-Marie; Hachem, Ray; Jordan, Mary; Garoge, Kumait; Al Hamal, Zainab; El Zakhem, Aline; Viola, George M; Granwehr, Bruno; Mulanovich, Victor; Gagel, Andrew; Reitzel, Ruth; Yousif, Ammar; Jiang, Ying; Raad, Issam

    2016-01-01

    Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CLCR) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CLCR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.). PMID

  3. Case-Control Study of Telavancin as an Alternative Treatment for Gram-Positive Bloodstream Infections in Patients with Cancer

    PubMed Central

    Hachem, Ray; Jordan, Mary; Garoge, Kumait; Al Hamal, Zainab; El Zakhem, Aline; Viola, George M.; Granwehr, Bruno; Mulanovich, Victor; Gagel, Andrew; Reitzel, Ruth; Yousif, Ammar; Jiang, Ying; Raad, Issam

    2015-01-01

    Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CLCR) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CLCR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.) PMID

  4. Cost-effectiveness of employing a total parenteral nutrition surveillance nurse for the prevention of catheter-related bloodstream infections.

    PubMed

    Fraher, M H; Collins, C J; Bourke, J; Phelan, D; Lynch, M

    2009-10-01

    The cost of catheter-related bloodstream infection (CRBSI) is substantial in terms of morbidity, mortality and financial resources. Total parenteral nutrition (TPN) is a recognised risk factor for CRBSI. In 1997, an intravenous nutrition nurse was promoted to TPN surveillance clinical nurse manager (CNM) and quarterly infection audit meetings were introduced to monitor trends in CRBSI. Data were prospectively collected over a 15-year period using specific TPN records in a 535-bed tertiary acute university hospital. A total of 20 439 CVC-days and 307 CRBSIs were recorded. Mean number of infections before, and after, the introduction of a dedicated TPN surveillance CNM were compared. Mean CRBSI per 1000 catheter-days+/-SD was 20.5+/-6.34 prior to 1997 and 14.64+/-7.81 after 1997, representing a mean reduction of 5.84 CRBSIs per 1000 catheter-days (95% CI: -4.92 to 16.60; P=0.05). Mean number of CRBSIs per year+/-SD was 28.3+/-4.93 prior to 1997 and 18.5+/-7.37 after 1997, representing a mean decrease of 9.8 infections per year (95% CI: 0.01 to 19.66; P<0.05). The savings made by preventing 9.8 infections per year were calculated from data on bed-days obtained from the hospital finance office. The cost in hospital days saved per annum was euro135,000. Introduction of a TPN surveillance CNM saved the hospital at least euro78,300 per annum and led to a significant decrease in CRBSIs in TPN patients. PMID:19709776

  5. EGFR and HER2 receptor kinase signaling mediate epithelial cell invasion by Candida albicans during oropharyngeal infection

    PubMed Central

    Zhu, Weidong; Phan, Quynh T.; Boontheung, Pinmanee; Solis, Norma V.; Loo, Joseph A.; Filler, Scott G.

    2012-01-01

    The fungus Candida albicans is the major cause of oropharyngeal candidiasis (OPC). A key feature of this disease is fungal invasion of oral epithelial cells, a process that can occur by active penetration and fungal-induced endocytosis. Two invasins, Als3 and Ssa1, induce epithelial cell endocytosis of C. albicans, in part by binding to E-cadherin. However, inhibition of E-cadherin function only partially reduces C. albicans endocytosis, suggesting that there are additional epithelial cell receptors for this organism. Here, we show that the EGF receptor (EGFR) and HER2 function cooperatively to induce the endocytosis of C. albicans hyphae. EGFR and HER2 interact with C. albicans in an Als3- and Ssa1-dependent manner, and this interaction induces receptor autophosphorylation. Signaling through both EGFR and HER2 is required for maximal epithelial cell endocytosis of C. albicans in vitro. Importantly, oral infection with C. albicans stimulates the phosphorylation of EGFR and HER2 in the oral mucosa of mice, and treatment with a dual EGFR and HER2 kinase inhibitor significantly decreases this phosphorylation and reduces the severity of OPC. These results show the importance of EGFR and HER2 signaling in the pathogenesis of OPC and indicate the feasibility of treating candidal infections by targeting the host cell receptors with which the fungus interacts. PMID:22891338

  6. A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection

    PubMed Central

    Huppler, Anna R.; Whibley, Natasha; Woolford, Carol A.; Childs, Erin E.; He, Jie; Biswas, Partha S.; McGeachy, Mandy J.; Mitchell, Aaron P.

    2015-01-01

    Candida albicans is normally a commensal fungus of the human mucosae and skin, but it causes life-threatening systemic infections in hospital settings in the face of predisposing conditions, such as indwelling catheters, abdominal surgery, or antibiotic use. Immunity to C. albicans involves various immune parameters, but the cytokine interleukin-17A (IL-17A) (also known as IL-17) has emerged as a centrally important mediator of immune defense against both mucosal and systemic candidiasis. Conversely, IL-17A has been suggested to enhance the virulence of C. albicans, indicating that it may exert detrimental effects on pathogenesis. In this study, we hypothesized that a C. albicans strain expressing IL-17A would exhibit reduced virulence in vivo. To that end, we created a Candida-optimized expression cassette encoding murine IL-17A, which was transformed into the DAY286 strain of C. albicans. Candida-derived IL-17A was indistinguishable from murine IL-17A in terms of biological activity and detection in standard enzyme-linked immunosorbent assays (ELISAs). Expression of IL-17A did not negatively impact the growth of these strains in vitro. Moreover, the IL-17A-expressing C. albicans strains showed significantly reduced pathogenicity in a systemic model of Candida infection, mainly evident during the early stages of disease. Collectively, these findings suggest that IL-17A mitigates the virulence of C. albicans. PMID:26150537

  7. Incidence, risk factors and microbiology of central vascular catheter-related bloodstream infection in an intensive care unit.

    PubMed

    Hajjej, Zied; Nasri, Mourad; Sellami, Walid; Gharsallah, Hedi; Labben, Iheb; Ferjani, Mustapha

    2014-03-01

    Although there are many studies about catheter related infection in industrialized countries, very few have analyzed it in emerging countries. The aim of our study was to determine the incidence, microbiological profile and risk factors for catheter-related bloodstream infection (CRBSI) in a Tunisian medical intensive care unit. Over eight months (1 January 2012-30 August 2012) a prospective, observational study was performed in an 18-bed medical surgical intensive care unit at Tunis military hospital. Patients who required central venous catheter (CVC) placement for a duration greater than 48 h were included in the study. Two hundred sixty patients, with a total of 482 CVCs were enrolled. The mean duration of catheterization was 9.6 ± 6.2 days. The incidence for CRBSI and catheter colonization (CC) was 2.4 and 9.3 per 1000 catheter days, respectively. Risk factors independently associated with CRBSI were diabetes mellitus, long duration of catheterization, sepsis at insertion and administration of one or more antibiotics before insertion. The mortality rate among the CRBSI group was 21.8%. The predominant microorganisms isolated from CRBSI and CC episodes were Gram negative bacilli. All Gram negative organisms isolated among dead patients in CRBSI group were Extensive Drug Resistant (XDR). In our study the mortality rate among patients with CRBSI was high despite a low incidence of CRBSI. This high rate can be explained by the high-virulent status of Gram negative bacteria involved in CRBSI. PMID:24508422

  8. Cefazolin versus Nafcillin for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infection in a California Tertiary Medical Center.

    PubMed

    Pollett, S; Baxi, S M; Rutherford, G W; Doernberg, S B; Bacchetti, P; Chambers, H F

    2016-08-01

    Recent observational studies have suggested possible reductions in mortality in patients receiving cefazolin versus antistaphylococcal penicillins. We examined 90-day mortality in patients receiving cefazolin compared to nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI). We identified persons with MSSA BSI admitted to San Francisco General Hospital from January 2008 to July 2013 through a hospital-wide infection surveillance system and confirmed 90-day mortality using U.S. national vital registries. We included persons receiving cefazolin or nafcillin as the predominant intravenous antimicrobial agent; all participants received inpatient Infectious Diseases service consultation. We estimated the association between receipt of cefazolin and 90-day risk of death by multivariate logistic regression, including a propensity score for receiving cefazolin as the second predictor. Of 230 MSSA BSI cases, 30 received nafcillin and 70 received cefazolin as the predominant antimicrobial; 10 died within 90 days, 5 from each group. Unadjusted analysis showed substantial but not statistically significant reduced odds of death in those receiving cefazolin (odds ratio, 0.38; 95% confidence interval [CI], 0.10 to 1.44). Multivariate analysis with propensity scores found a similar adjusted odds ratio (0.40; 95% CI, 0.09 to 1.74; P = 0.22). We found a large reduction in 90-day mortality in those receiving cefazolin compared to nafcillin for MSSA BSI, but this finding was not statistically significant. The magnitude of effect seen in this and other studies justifies further study. PMID:27216053

  9. Surveillance of bloodstream infections in pediatric cancer centers - what have we learned and how do we move on?

    PubMed

    Simon, Arne; Furtwängler, Rhoikos; Graf, Norbert; Laws, Hans Jürgen; Voigt, Sebastian; Piening, Brar; Geffers, Christine; Agyeman, Philipp; Ammann, Roland A

    2016-01-01

    Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients' safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined. PMID:27274442

  10. Surveillance of bloodstream infections in pediatric cancer centers – what have we learned and how do we move on?

    PubMed Central

    Simon, Arne; Furtwängler, Rhoikos; Graf, Norbert; Laws, Hans Jürgen; Voigt, Sebastian; Piening, Brar; Geffers, Christine; Agyeman, Philipp; Ammann, Roland A.

    2016-01-01

    Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients’ safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined. PMID:27274442

  11. The changing epidemiology of group B streptococcus bloodstream infection: a multi-national population-based assessment.

    PubMed

    Ballard, Mark S; Schønheyder, Henrik C; Knudsen, Jenny Dahl; Lyytikäinen, Outi; Dryden, Matthew; Kennedy, Karina J; Valiquette, Louis; Pinholt, Mette; Jacobsson, Gunnar; Laupland, Kevin B

    2016-05-01

    Background Population-based studies conducted in single regions or countries have identified significant changes in the epidemiology of invasive group B streptococcus (GBS) infection. However, no studies have concurrently compared the epidemiology of GBS infections among multiple different regions and countries over time. The study objectives were to define the contemporary incidence and determinants of GBS bloodstream infection (BSI) and assess temporal changes in a multi-national population. Methods Population-based surveillance for GBS BSI was conducted in nine regions in Australia, Canada, Denmark, Sweden, Finland and the UK during 2000-2010. Incidence rates were age- and gender-standardised to the EU population. Results During 114 million patient-years of observation, 3464 cases of GBS BSI were identified for an overall annual incidence of 3.4 patients per 100 000 persons. There were marked differences in the overall (range = 1.8-4.1 per 100 000 person-year) and neonatal (range = 0.19-0.83 per 1000 live births) incidences of GBS BSI observed among the study regions. The overall incidence significantly (p = 0.05) increased. Rates of neonatal disease were stable, while the incidence in individuals older than 60 years doubled (p = 0.003). In patients with detailed data (n = 1018), the most common co-morbidity was diabetes (25%). During the study period, the proportion of cases associated with diabetes increased. Conclusions While marked variability in the incidence of GBS BSI was observed among these regions, it was consistently found that rates increased among older adults, especially in association with diabetes. The burden of this infection may be expected to continue to increase in ageing populations worldwide. PMID:26759190

  12. Closed Catheter Access System Implementation in Reducing the Bloodstream Infection Rate in Low Birth Weight Preterm Infants

    PubMed Central

    Rundjan, Lily; Rohsiswatmo, Rinawati; Paramita, Tiara Nien; Oeswadi, Chrissela Anindita

    2015-01-01

    Background: Bloodstream infection (BSI) is one of the significant causes of morbidity and mortality encountered in a neonatal intensive care unit, especially in developing countries. Despite the implementation of infection control practices, such as strict hand hygiene, the BSI rate in our hospital is still high. The use of a closed catheter access system to reduce BSI related to intravascular catheter has hitherto never been evaluated in our hospital. Objective: To determine the effects of closed catheter access system implementation in reducing the BSI rate in preterm neonates with low birth weight. Methods: Randomized clinical trial was conducted on 60 low birth weight preterm infants hospitalized in the neonatal unit at Cipto Mangunkusumo Hospital, Jakarta, Indonesia from June to September 2013. Randomized subjects either received a closed or non-closed catheter access system. Subjects were monitored for 2 weeks for the development of BSI based on clinical signs, abnormal infection parameters, and blood culture. Results: Closed catheter access system implementation gave a protective effect toward the occurrence of culture-proven BSI (relative risk 0.095, 95% CI 0.011–0.85, p = 0.026). Risk of culture-proven BSI in the control group was 10.545 (95% CI 1.227–90.662, p = 0.026). BSI occurred in 75% of neonates without risk factors of infection in the control group compared to none in the study group. Conclusion: The use of a closed catheter access system reduced the BSI in low birth weight preterm infants. Choosing the right device design, proper disinfection of device, and appropriate frequency of connector change should be done simultaneously. PMID:25853110

  13. Clinical and Molecular Characteristics of Emerging Hypervirulent Klebsiella pneumoniae Bloodstream Infections in Mainland China

    PubMed Central

    Liu, Ying Mei; Li, Bin Bin; Zhang, Yu Yu; Zhang, Wu; Shen, Hong; Li, Hui

    2014-01-01

    Recently, the newly emerged hypervirulent Klebsiella pneumoniae strain (hvKP) has caused great concern globally, but the clinical features and molecular characteristics of bacteremia caused by hvKP are rarely reported in mainland China. Seventy patients with K. pneumoniae bacteremia were investigated to study the clinical features of hvKP infection from 2008 till 2012 in Beijing Chao-Yang Hospital. The molecular characteristics of the hvKP strains were also studied using PCR, multilocus sequence typing, and pulsed-field gel electrophoresis (PFGE) methods. hvKP was identified in 31.4% of the patients with K. pneumoniae bacteremia, which displayed 4 serotypes (K1, K2, K20, and K57). Patients with hvKP infection tended to have no underlying diseases compared to those with classic K. pneumoniae (cKP). More hvKP-positive patients (95.5%) had community-acquired infection than did cKP-infected patients (35.4%) (P < 0.001). The 30-day mortality rate was lower in hvKP-infected patients than in cKP-infected patients (4.5% compared to 16.7%). Resistance to tested antimicrobials was significantly greater in cKP- than in hvKP-infected patients. Two extended-spectrum-beta-lactamase (ESBL)-producing hvKP strains were found. Seven novel sequence types (STs) and 4 new alleles of K. pneumoniae were revealed. A strong correlation was found between two STs (ST23, ST1265) and the K1 serotype. The hvKP isolates (n = 22) had 14 different PFGE patterns, and among them 10 K1 isolates shared similar PFGE patterns. The emerging hvKP strain was prevalent in patients with severe community-acquired infections in healthy individuals in China. Identification of ESBL-producing hvKP strains in hvKP-infected patients will facilitate clinical management of hvKP infection. PMID:24982067

  14. Inhibiting the immunoproteasome exacerbates the pathogenesis of systemic Candida albicans infection in mice.

    PubMed

    Mundt, Sarah; Basler, Michael; Buerger, Stefanie; Engler, Harald; Groettrup, Marcus

    2016-01-01

    Apart from its role in MHC class I antigen processing, the immunoproteasome has recently been implicated in the modulation of T helper cell differentiation under polarizing conditions in vitro and in the pathogenesis of autoimmune diseases in vivo. In this study, we investigated the influence of LMP7 on T helper cell differentiation in response to the fungus Candida albicans. We observed a strong effect of ONX 0914, an LMP7-selective inhibitor of the immunoproteasome, on IFN-γ and IL-17A production by murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans in vitro. Using a murine model of systemic candidiasis, we could confirm reduced generation of IFN-γ- and IL-17A-producing cells in ONX 0914 treated mice in vivo. Interestingly, ONX 0914 treatment resulted in increased susceptibility to systemic candidiasis, which manifested at very early stages of infection. Mice treated with ONX 0914 showed markedly increased kidney and brain fungal burden which resulted in enhanced neutrophil recruitment and immunopathology. Together, these results strongly suggest a role of the immunoproteasome in promoting proinflammatory T helper cells in response to C. albicans but also in affecting the innate antifungal immunity in a T helper cell-independent manner. PMID:26776888

  15. Role of Toll-like receptors in systemic Candida albicans infections.

    PubMed

    Luisa Gil, Maria; Murciano, Celia; Yáñez, Alberto; Gozalbo, Daniel

    2016-01-01

    Toll-like receptors (TLRs) constitute a family of pattern-recognition receptors (PRRs) that recognize molecular signatures of microbial pathogens and function as sensors for infection. Recognition of Candida albicans by TLRs on mature immune cells, such as phagocytic cells, activates intracellular signalling pathways that trigger production of proinflammatory cytokines which are critical for innate host defence and orchestrate the adaptive response. TLR2, and TLR4 in a minor extent, recognize cell wall-associated ligands; endosomal TLR9 and TLR7 recognize DNA and RNA respectively. Interaction of C. albicans with TLRs is a complex process, as TLRs may collaborate with other PRRs and expression of surface-associated fungal ligands depends on the strain and the morphotype (yeasts or hyphae), thus defining the final induced adaptive response (Th1/Th2/Th17). TLRs are also expressed on hematopoietic stem and progenitor cells (HSPCs) where they may play a role in modulating hematopoiesis; engagement of TLR2 induces, upon recognition of C. albicans, the differentiation of HSPCs towards specific subsets of mature myeloid cells. This has opened a new perspective for anti-Candida immunointervention. PMID:26709773

  16. Inhibiting the immunoproteasome exacerbates the pathogenesis of systemic Candida albicans infection in mice

    PubMed Central

    Mundt, Sarah; Basler, Michael; Buerger, Stefanie; Engler, Harald; Groettrup, Marcus

    2016-01-01

    Apart from its role in MHC class I antigen processing, the immunoproteasome has recently been implicated in the modulation of T helper cell differentiation under polarizing conditions in vitro and in the pathogenesis of autoimmune diseases in vivo. In this study, we investigated the influence of LMP7 on T helper cell differentiation in response to the fungus Candida albicans. We observed a strong effect of ONX 0914, an LMP7-selective inhibitor of the immunoproteasome, on IFN-γ and IL-17A production by murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans in vitro. Using a murine model of systemic candidiasis, we could confirm reduced generation of IFN-γ- and IL-17A-producing cells in ONX 0914 treated mice in vivo. Interestingly, ONX 0914 treatment resulted in increased susceptibility to systemic candidiasis, which manifested at very early stages of infection. Mice treated with ONX 0914 showed markedly increased kidney and brain fungal burden which resulted in enhanced neutrophil recruitment and immunopathology. Together, these results strongly suggest a role of the immunoproteasome in promoting proinflammatory T helper cells in response to C. albicans but also in affecting the innate antifungal immunity in a T helper cell-independent manner. PMID:26776888

  17. Candida albicans strain types from the genitalia of patients with and without Candida infection.

    PubMed

    Odds, F C; Abbott, A B; Reed, T A; Willmott, F E

    1983-04-01

    The strain phenotypes of 266 C. albicans isolates from patients attending a genitourinary clinic were determined on the basis of 9 biochemical tests. Analysis of the strain patterns of isolates from the genitalia showed that there were no statistically significant differences between types associated with clinically overt Candida infection and types isolated in the absence of symptoms of candidosis. This finding accords with the traditional view of C. albicans as an opportunistic pathogen, rather than a species containing some strains of high virulence. In cases where isolations were made from the same patient at different times, or from different anatomical sites in the same patient, it was found that usually, but not always, a patient carried the same phenotype at different sites and different times. Similarly, the same strain type was isolated from the genitalis of both partners in a majority of instances where strains were isolated from consorts; however, this was not the case for a substantial minority of couples, particularly in those where high promiscuity appeared to promote considerable mixture and interchange of the C. albicans genital microflora. PMID:6350074

  18. Use of Ceftolozane/Tazobactam in the Treatment of Multidrug-resistant Pseudomonas aeruginosa Bloodstream Infection in a Pediatric Leukemia Patient.

    PubMed

    Aitken, Samuel L; Kontoyiannis, Dimitrios P; DePombo, April M; Bhatti, Micah M; Tverdek, Frank P; Gettys, Suzanne C; Nicolau, David P; Nunez, Cesar A

    2016-09-01

    Multidrug-resistant Pseudomonas aeruginosa is of increasing concern in pediatric patients. Ceftolozane/tazobactam is a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant Pseudomonas; however, no data exist on its use in children. This report summarizes the treatment of a multidrug-resistant P. aeruginosa bloodstream infection in a pediatric leukemia patient with ceftolozane/tazobactam and provides the first description of its pharmacokinetics in pediatrics. PMID:27254038

  19. Draft genome sequence of blaVeb-1, blaoxa-10producing multi-drug resistant (MDR) Pseudomonas aeruginosastrain VRFPA09 recovered from bloodstream infection

    PubMed Central

    Murugan, Nandagopal; Malathi, Jambulingam; Umashankar, Vetrivel; Madhavan, Hajib NarahariRao

    2015-01-01

    Pseudomonas aeruginosa (P. aeruginosa) bacteremia causes significant mortality rate due to emergence of multidrug resistant (MDR) nosocomial infections. We report the draft genome sequence of P. aeruginosa strain VRFPA09, a human bloodstream isolate, phenotypically proven as MDR strain. Whole genome sequencing on VRFPA09, deciphered betalactamase encoding blaveb-1 and blaOXA-10genes and multiple drug resistance, virulence factor encoding genes. PMID:26413042

  20. Draft genome sequence of blaVeb-1, blaoxa-10 producing multi-drug resistant (MDR) Pseudomonas aeruginosa strain VRFPA09 recovered from bloodstream infection.

    PubMed

    Murugan, Nandagopal; Malathi, Jambulingam; Umashankar, Vetrivel; Madhavan, Hajib NarahariRao

    2015-01-01

    Pseudomonas aeruginosa (P. aeruginosa) bacteremia causes significant mortality rate due to emergence of multidrug resistant (MDR) nosocomial infections. We report the draft genome sequence of P. aeruginosa strain VRFPA09, a human bloodstream isolate, phenotypically proven as MDR strain. Whole genome sequencing on VRFPA09, deciphered betalactamase encoding blav(eb-1) and bla(OXA-10) genes and multiple drug resistance, virulence factor encoding genes. PMID:26413042

  1. Carbapenemase-Producing Klebsiella pneumoniae Bloodstream Infections: Lowering Mortality by Antibiotic Combination Schemes and the Role of Carbapenems

    PubMed Central

    Tsaousi, Sophia; Tzouvelekis, Leonidas S.; Anyfantis, Ioannis; Psichogiou, Mina; Argyropoulou, Athina; Stefanou, Ioanna; Sypsa, Vana; Miriagou, Vivi; Nepka, Martha; Georgiadou, Sarah; Markogiannakis, Antonis; Goukos, Dimitris; Skoutelis, Athanasios

    2014-01-01

    Carbapenemase-producing Klebsiella pneumoniae strains (CP-Kps) are currently among the most important nosocomial pathogens. An observational study was conducted during 2009 to 2010 in two hospitals located in a high-prevalence area (Athens, Greece). The aims were (i) to evaluate the clinical outcome of patients with CP-Kp bloodstream infections (BSIs), (ii) to identify predictors of mortality, and (iii) to evaluate the various antibiotic schemes employed. A total of 205 patients with CP-Kp BSIs were identified: 163 (79.5%) were infected with KPC or KPC and VIM, and 42 were infected with VIM producers. For definitive treatment, 103 patients received combination therapy (two or more active drugs), 72 received monotherapy (one active drug), and 12 received therapy with no active drug. The remaining 18 patients died within 48 h after the onset of bacteremia. The all-cause 28-day mortality was 40%. A significantly higher mortality rate was observed in patients treated with monotherapy than in those treated with combination therapy (44.4% versus 27.2%; P = 0.018). The lowest mortality rate (19.3%) was observed in patients treated with carbapenem-containing combinations. In the Cox proportion hazards model, ultimately fatal disease (hazards ratio [HR], 3.25; 95% confidence interval [CI], 1.51 to 7.03; P = 0.003), the presence of rapidly fatal underlying diseases (HR, 4.20; 95% CI, 2.19 to 8.08; P < 0.001), and septic shock (HR, 2.15; 95% CI, 1.16 to 3.96; P = 0.015) were independent predictors of death. Combination therapy was strongly associated with survival (HR of death for monotherapy versus combination, 2.08; 95% CI, 1.23 to 3.51; P = 0.006), mostly due to the effectiveness of the carbapenem-containing regimens. PMID:24514083

  2. Evaluation of Bloodstream Infections During Chemotherapy-Induced Febrile Neutropenia in Patients with Malignant Hematological Diseases: Single Center Experience.

    PubMed

    Piukovics, Klára; Terhes, Gabriella; Lázár, Andrea; Tímár, Flóra; Borbényi, Zita; Urbán, Edit

    2015-09-01

    From year to year, it is important to get an overview of the occurrence of causative agents in febrile neutropenic patients to determine the empiric treatment. Thus our aims were to evaluate a four-year period regarding the prevalence of bloodstream infections and the most important causative agents. During this period, 1,361 patients were treated in our hematology ward because of various hematological disorders. 812 febrile episodes were recorded in 469 patients. At that time, 3,714 blood culture (BC) bottles were sent for microbiological investigations, 759 of them gave positive signal. From the majority of positive blood culture bottles (67.1%), Gram-positive bacteria, mainly coagulase-negative staphylococci (CNS), were grown. Gram-negative bacteria were isolated from 32.9% of the positive blood culture bottles, in these cases the leading pathogen was Escherichia coli. The high prevalence of CNS was attributed to mainly contamination, while lower positivity rate for Gram-negative bacteria was associated with the use of broad-spectrum empiric antibiotic treatment. PMID:26495130

  3. High MICs for Vancomycin and Daptomycin and Complicated Catheter-Related Bloodstream Infections with Methicillin-Sensitive Staphylococcus aureus.

    PubMed

    San-Juan, Rafael; Viedma, Esther; Chaves, Fernando; Lalueza, Antonio; Fortún, Jesús; Loza, Elena; Pujol, Miquel; Ardanuy, Carmen; Morales, Isabel; de Cueto, Marina; Resino-Foz, Elena; Morales-Cartagena, Alejandra; Rico, Alicia; Romero, María P; Orellana, María Ángeles; López-Medrano, Francisco; Fernández-Ruiz, Mario; Aguado, José María

    2016-06-01

    We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011-June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2-5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1-5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. PMID:27192097

  4. Evaluation of Bloodstream Infections During Chemotherapy-Induced Febrile Neutropenia in Patients with Malignant Hematological Diseases: Single Center Experience

    PubMed Central

    Piukovics, Klára; Terhes, Gabriella; Lázár, Andrea; Tímár, Flóra; Borbényi, Zita; Urbán, Edit

    2015-01-01

    From year to year, it is important to get an overview of the occurrence of causative agents in febrile neutropenic patients to determine the empiric treatment. Thus our aims were to evaluate a four-year period regarding the prevalence of bloodstream infections and the most important causative agents. During this period, 1,361 patients were treated in our hematology ward because of various hematological disorders. 812 febrile episodes were recorded in 469 patients. At that time, 3,714 blood culture (BC) bottles were sent for microbiological investigations, 759 of them gave positive signal. From the majority of positive blood culture bottles (67.1%), Gram-positive bacteria, mainly coagulase-negative staphylococci (CNS), were grown. Gram-negative bacteria were isolated from 32.9% of the positive blood culture bottles, in these cases the leading pathogen was Escherichia coli. The high prevalence of CNS was attributed to mainly contamination, while lower positivity rate for Gram-negative bacteria was associated with the use of broad-spectrum empiric antibiotic treatment. PMID:26495130

  5. Risk factors for mortality in patients with bloodstream infections during the pre-engraftment period after hematopoietic stem cell transplantation

    PubMed Central

    Karpov, Igor; Milanovich, Natalia; Uss, Anatoly; Iskrov, Igor

    2016-01-01

    Background Bloodstream infections (BSI) remain a frequent complication during the pre-engraftment period after hematopoietic stem cell transplantation (HSCT), resulting in high mortality rates. This study evaluated risk factors for mortality in hematopoietic stem cell transplant recipients with BSI in the pre-engraftment period. Methods This prospective case control study was performed at the Center of Hematology and Bone Marrow Transplantation in Minsk, Republic of Belarus. Data relating to patient age and gender, date and type of transplantation, conditioning chemotherapy regimen, microorganisms isolated from blood, and antibacterial therapy were prospectively collected from all hematopoietic stem cell recipients with microbiologically proven cases of BSI in the pre-engraftment period. The primary outcome was all-cause 30-day mortality after onset of febrile neutropenia. Results A total of 135 adult patients with microbiologically proven BSI after HSCT were studied, with 65.2% of cases caused by gram-negative microorganisms and 21.5% by non-fermenting bacteria. Inadequate empiric antibacterial therapy and isolation of carbapenem-resistant non-fermenting gram-negative bacteria (Acinetobacter baumannii and Pseudomonas aeruginosa) were independently associated with increased all-cause 30-day mortality in these patients. Conclusion The risk factors for mortality in adult patients with BSI in the pre-engraftment period after HSCT were inadequacy of empirical antibacterial therapy and isolation of carbapenem-resistant A. baumannii or P. aeruginosa. PMID:27382554

  6. High MICs for Vancomycin and Daptomycin and Complicated Catheter-Related Bloodstream Infections with Methicillin-Sensitive Staphylococcus aureus

    PubMed Central

    Viedma, Esther; Chaves, Fernando; Lalueza, Antonio; Fortún, Jesús; Loza, Elena; Pujol, Miquel; Ardanuy, Carmen; Morales, Isabel; de Cueto, Marina; Resino-Foz, Elena; Morales-Cartagena, Alejandra; Rico, Alicia; Romero, María P.; Orellana, María Ángeles; López-Medrano, Francisco; Fernández-Ruiz, Mario; Aguado, José María

    2016-01-01

    We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011–June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2–5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1–5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. PMID:27192097

  7. The clinical diagnostic accuracy of rapid detection of healthcare-associated bloodstream infection in intensive care using multipathogen real-time PCR technology

    PubMed Central

    Dunn, Graham; Chadwick, Paul; Young, Duncan; Bentley, Andrew; Carlson, Gordon; Warhurst, Geoffrey

    2011-01-01

    Background There is growing interest in the potential utility of real-time PCR in diagnosing bloodstream infection by detecting pathogen DNA in blood samples within a few hours. SeptiFast is a multipathogen probe-based real-time PCR system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection and has European regulatory approval. The SeptiFast pathogen panel is suited to identifying healthcare-associated bloodstream infection acquired during complex healthcare, and the authors report here the protocol for the first detailed health-technology assessment of multiplex real-time PCR in this setting. Methods/design A Phase III multicentre double-blinded diagnostic study will determine the clinical validity of SeptiFast for the rapid detection of healthcare-associated bloodstream infection, against the current service standard of microbiological culture, in an adequately sized population of critically ill adult patients. Results from SeptiFast and standard microbiological culture procedures in each patient will be compared at study conclusion and the metrics of clinical diagnostic accuracy of SeptiFast determined in this population setting. In addition, this study aims to assess further the preliminary evidence that the detection of pathogen DNA in the bloodstream using SeptiFast may have value in identifying the presence of infection elsewhere in the body. Furthermore, differences in circulating immune-inflammatory markers in patient groups differentiated by the presence/absence of culturable pathogens and pathogen DNA will help elucidate further the patho-physiology of infection developing in the critically ill. Ethics and dissemination Ethical approval has been granted by the North West 6 Research Ethics Committee (09/H1003/109). Based on the results of this first non-commercial study, independent recommendations will be made to The Department of Health (open-access health technology

  8. Trends of Staphylococcus aureus bloodstream infections in a neonatal intensive care unit from 2000-2009

    PubMed Central

    2014-01-01

    Background Invasive methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infections are major causes of numerous neonatal intensive care unit (NICU) outbreaks. There have been increasing reports of MRSA outbreaks in various neonatal intensive care units (NICUs) over the last decade. Our objective was to review the experience of Staphylococcus aureus sepsis in our NICU in the last decade and describe the trends in the incidence of Staphylococcus aureus blood stream infections from 2000 to 2009. Methods A retrospective perinatal database review of all neonates admitted to our NICU with blood cultures positive for Staphylococcus aureus from (Jan 1st 2000 to December 31st 2009) was conducted. Infants were identified from the database and data were collected regarding their clinical characteristics and co-morbidities, including shock with sepsis and mortality. Period A represents patients admitted in 2000-2003. Period B represents patients seen in 2004-2009. Results During the study period, 156/11111 infants were identified with Staphylococcus aureus blood stream infection: 41/4486 (0.91%) infants in Period A and 115/6625 (1.73%) in Period B (p < 0.0004). Mean gestation at birth was 26 weeks for infants in both periods. There were more MRSA infections in Period B (24% vs. 55% p < 0.05) and they were associated with more severe outcomes. In comparing the cases of MRSA infections observed in the two periods, infants in period B notably had significantly more pneumonia cases (2.4% vs. 27%, p = 0.0005) and a significantly higher mortality rate (0% vs. 15.7%, p = 0.0038). The incidences of skin and soft tissue infections and of necrotizing enterocolitis were not significantly changed in the two periods. Conclusion There was an increase in the incidence of Staphylococcus aureus infection among neonates after 2004. Although MSSA continues to be a problem in the NICU, MRSA infections were more prevalent in the

  9. Typing Candida albicans oral isolates from human immunodeficiency virus-infected patients by multilocus enzyme electrophoresis and DNA fingerprinting.

    PubMed Central

    Boerlin, P; Boerlin-Petzold, F; Goudet, J; Durussel, C; Pagani, J L; Chave, J P; Bille, J

    1996-01-01

    A total of 189 Candida albicans isolates have been typed by multilocus enzyme electrophoresis. The results obtained confirm the clonal mode of reproduction of C. albicans. The C. albicans populations found in the oropharynx of human immunodeficiency virus (HIV)-infected patients, in the oropharynx of healthy carriers, or in association with invasive candidiasis could not be distinguished. No clone or group of clones could be associated with the appearance of clinical disorders or with a reduced in vitro susceptibility to the antifungal agent fluconazole. Multiple and sequential oral isolates from 24 HIV-infected patients were also typed by restriction enzyme analysis with the enzymes EcoRI and HinfI and by use of the Ca3 repetitive probe. The results obtained by the combination of all three typing methods show that all but one patient each carried a unique major C. albicans clone in their oropharynx. The 21 patients with sequential isolates had the same C. albicans clones in their throats during recurrent oropharyngeal candidiasis episodes, independently of clinical status or of changes of in vitro susceptibility to fluconazole. Finally, several isolates of the same C. albicans clone found simultaneously in the oropharynx of a patient may present different levels of susceptibility to fluconazole. PMID:8727910

  10. Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections

    PubMed Central

    Mackie, Joanna; Ballou, Elizabeth R.; Childers, Delma S.; MacCallum, Donna M.; Feldmann, Joerg; Brown, Alistair J. P.

    2016-01-01

    Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection) and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection) to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits—metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease. PMID:27362522

  11. Production and function of cytokines in natural and acquired immunity to Candida albicans infection.

    PubMed Central

    Ashman, R B; Papadimitriou, J M

    1995-01-01

    Host resistance against infections caused by the yeast Candida albicans is mediated predominantly by polymorphonuclear leukocytes and macrophages. Antigens of Candida stimulate lymphocyte proliferation and cytokine synthesis, and in both humans and mice, these cytokines enhance the candidacidal functions of the phagocytic cells. In systemic candidiasis in mice, cytokine production has been found to be a function of the CD4+ T helper (Th) cells. The Th1 subset of these cells, characterized by the production of gamma interferon and interleukin-2, is associated with macrophage activation and enhanced resistance against reinfection, whereas the Th2 subset, which produces interleukins-4, -6, and -10, is linked to the development of chronic disease. However, other models have generated divergent data. Mucosal infection generally elicits Th1-type cytokine responses and protection from systemic challenge, and identification of cytokine mRNA present in infected tissues of mice that develop mild or severe lesions does not show pure Th1- or Th2-type responses. Furthermore, antigens of C. albicans, mannan in particular, can induce suppressor cells that modulate both specific and nonspecific cellular and humoral immune responses, and there is an emerging body of evidence that molecular mimicry may affect the efficiency of anti-Candida responses within defined genetic contexts. PMID:8531890

  12. Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections.

    PubMed

    Hernández-Santos, N; Huppler, A R; Peterson, A C; Khader, S A; McKenna, K C; Gaffen, S L

    2013-09-01

    Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. Despite its prevalence, little is known about C. albicans-specific immunity in the oral mucosa. Vaccines against Candida generate both T helper type 1 (Th1) and Th17 responses, and considerable evidence implicates interleukin (IL)-17 in immunity to OPC. However, IL-17 is also produced by innate immune cells that are remarkably similar to Th17 cells, expressing the same markers and localizing to similar mucosal sites. To date, the relative contribution(s) of Th1, Th17, and innate IL-17-producing cells in OPC have not been clearly defined. Here, we sought to determine the nature and function of adaptive T-cell responses to OPC, using a new recall infection model. Mice subjected to infection and re-challenge with Candida mounted a robust and stable antigen-specific IL-17 response in CD4+ but not CD8+ T cells. There was little evidence for Th1 or Th1/Th17 responses. The Th17 response promoted accelerated fungal clearance, and Th17 cells could confer protection in Rag1-/- mice upon adoptive transfer. Surprisingly, CD4 deficiency did not cause OPC but was instead associated with compensatory IL-17 production by Tc17 and CD3+CD4-CD8- cells. Therefore, classic CD4+Th17 cells protect from OPC but can be compensated by other IL-17-producing cells in CD4-deficient hosts. PMID:23250275

  13. Gold Nanoparticle-Photosensitizer Conjugate Based Photodynamic Inactivation of Biofilm Producing Cells: Potential for Treatment of C. albicans Infection in BALB/c Mice

    PubMed Central

    Sherwani, Mohd. Asif; Tufail, Saba; Khan, Aijaz Ahmed; Owais, Mohammad

    2015-01-01

    Background Photodynamic therapy (PDT) has been found to be effective in inhibiting biofilm producing organisms. We investigated the photodynamic effect of gold nanoparticle (GNP) conjugated photosensitizers against Candida albicans biofilm. We also examined the photodynamic efficacy of photosensitizer (PS) conjugated GNPs (GNP-PS) to treat skin and oral C. albicans infection in BALB/c mice. Methods The biomimetically synthesized GNPs were conjugated to photosensitizers viz. methylene blue (MB) or toluidine blue O (TB). The conjugation of PSs with GNPs was characterized by spectroscopic and microscopic techniques. The efficacy of gold nanoparticle conjugates against C. albicans biofilm was demonstrated by XTT assay and microscopic studies. The therapeutic efficacy of the combination of the GNP conjugates against cutaneous C. albicans infection was examined in mouse model by enumerating residual fungal burden and histopathological studies. Results The GNP-PS conjugate based PDT was found to effectively kill both C. albicans planktonic cells and biofilm populating hyphal forms. The mixture of GNPs conjugated to two different PSs significantly depleted the hyphal C. albicans burden against superficial skin and oral C. albicans infection in mice. Conclusion The GNP-PS conjugate combination exhibits synergism in photodynamic inactivation of C. albicans. The GNP conjugate based PDT can be employed effectively in treatment of cutaneous C. albicans infections in model animals. The antibiofilm potential of PDT therapy can also be exploited in depletion of C. albicans on medical appliances such as implants and catheters etc. PMID:26148012

  14. Protective effect of picolinic acid on mice intracerebrally infected with lethal doses of Candida albicans.

    PubMed Central

    Blasi, E; Mazzolla, R; Pitzurra, L; Barluzzi, R; Bistoni, F

    1993-01-01

    We have studied the effects of picolinic acid (PLA), a product of tryptophan degradation, on mouse susceptibility to intracerebral infection with Candida albicans. We show that intraperitoneal administration of PLA significantly enhances the median survival time of mice inoculated with the lethal challenge. Furthermore, intracerebral administration of this agent induces a protective state against the local lethal infection, the phenomenon depending upon the administration schedule and doses of PLA employed. According to survival data, yeast growth in the brain as well as yeast colonization of the kidneys are drastically reduced in PLA-treated mice compared with those for untreated controls. Northern (RNA) blot analysis of brain tissues demonstrates that mRNA levels specific for tumor necrosis factor and interleukin 1 are augmented and induced, respectively, after inoculation of PLA. These results indicate that PLA has a protective effect likely involving elicitation of a cytokine response in vivo against fungal infections. Images PMID:7506894

  15. Protective effect of muramyl dipeptide analogs against infections of Pseudomonas aeruginosa or Candida albicans in mice.

    PubMed Central

    Fraser-Smith, E B; Matthews, T R

    1981-01-01

    Two analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) were found to give better protection than muramyl dipeptide against intraperitoneal Pseudomonas aeruginosa infection or intravenous Candida albicans infection in mice. The analogs tested were N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and N-acetylmuramyl-L-alpha-amino-butyryl-D-isoglutamine. The optimum treatment was 80 mg/kg per day given once daily for 4 consecutive days before infection by the intraperitoneal, intravenous, or subcutaneous route. Dose response was limited. The compounds were not orally active. Synergism was seen between N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and gentamicin. No postinfection protection was observed. A nonspecific stimulation of macrophage cells by muramyl dipeptide analogs may contribute to the protection because antiinfective activity against Listeria monocytogenes given intraperitoneally was achieved with CBA mice. PMID:7333666

  16. Solitary Candida albicans Infection Causing Fournier Gangrene and Review of Fungal Etiologies

    PubMed Central

    Perkins, Tiffany A; Bieniek, Jared M; Sumfest, Joel M

    2014-01-01

    Polymicrobial bacterial infections are commonly found in cases of Fournier gangrene (FG), although fungal growth may occur occasionally. Solitary fungal organisms causing FG have rarely been reported. The authors describe a case of an elderly man with a history of diabetes who presented with a necrotizing scrotal and perineal soft tissue infection. He underwent emergent surgical debridement with findings of diffuse urethral stricture disease and urinary extravasation requiring suprapubic tube placement. Candida albicans was found to be the single causative organism on culture, and the patient recovered well following antifungal treatment. Fungal infections should be considered as rare causes of necrotizing fasciitis and antifungal treatment considered in at-risk immunodeficient individuals. PMID:25009452

  17. Solitary Candida albicans Infection Causing Fournier Gangrene and Review of Fungal Etiologies.

    PubMed

    Perkins, Tiffany A; Bieniek, Jared M; Sumfest, Joel M

    2014-01-01

    Polymicrobial bacterial infections are commonly found in cases of Fournier gangrene (FG), although fungal growth may occur occasionally. Solitary fungal organisms causing FG have rarely been reported. The authors describe a case of an elderly man with a history of diabetes who presented with a necrotizing scrotal and perineal soft tissue infection. He underwent emergent surgical debridement with findings of diffuse urethral stricture disease and urinary extravasation requiring suprapubic tube placement. Candida albicans was found to be the single causative organism on culture, and the patient recovered well following antifungal treatment. Fungal infections should be considered as rare causes of necrotizing fasciitis and antifungal treatment considered in at-risk immunodeficient individuals. PMID:25009452

  18. Does antimicrobial use density at the ward level influence monthly central line-associated bloodstream infection rates?

    PubMed Central

    Yoshida, Junichi; Harada, Yukiko; Kikuchi, Tetsuya; Asano, Ikuyo; Ueno, Takako; Matsubara, Nobuo

    2014-01-01

    The aim of this study was to elucidate risk factors, including ward antimicrobial use density (AUD), for central line-associated bloodstream infection (CLABSI) as defined by the Centers for Disease Control and Prevention in a 430-bed community hospital using central venous lines with closed-hub systems. We calculated AUD as (total dose)/(defined daily dose × patient days) ×1,000 for a total of 20 drugs, nine wards, and 24 months. Into each line day data, we inputed AUD and device utilization ratios, number of central line days, and CLABSI. The ratio of susceptible strains in isolates were subjected to correlation analysis with AUD. Of a total of 9,997 line days over 24 months, CLABSI was present in 33 cases (3.3 ‰), 14 (42.4%) of which were on surgical wards out of nine wards. Of a total of 43 strains isolated, eight (18.6%) were methicillin-resistant Staphylococcus aureus (MRSA); none of the MRSA-positive patients had received cefotiam before the onset of infection. Receiver-operating characteristic analysis showed that central line day 7 had the highest accuracy. Logistic regression analysis showed the central line day showed an odds ratio of 5.511 with a 95% confidence interval of 1.936–15.690 as did AUD of cefotiam showing an odds ratio of 0.220 with 95% confidence interval of 0.00527–0.922 (P=0.038). Susceptible strains ratio and AUD showed a negative correlation (R2=0.1897). Thus, CLABSI could be prevented by making the number of central line days as short as possible. The preventative role of AUD remains to be investigated. PMID:25525373

  19. In vitro activity of two amphotericin B formulations against Malassezia furfur strains recovered from patients with bloodstream infections.

    PubMed

    Iatta, Roberta; Immediato, Davide; Montagna, Maria Teresa; Otranto, Domenico; Cafarchia, Claudia

    2015-04-01

    Although guidelines for the treatment of Malassezia furfur fungemia are not yet defined, clinical data suggest that amphotericin B (AmB) is effective for treating systemic infections. In the absence of clinical breakpoints for Malassezia yeasts, epidemiological cut-off values (ECVs) are useful to discriminate between isolates with and without drug resistance. This study aimed to compare the distribution of minimal inhibitory concentration (MIC) and the ECVs for AmB of both deoxycholate (d-AmB) and liposomal (l-AmB) formulations of M. furfur isolates. The 84 M. furfur strains analyzed, which included 56 from blood, sterile sites and catheters, and 28 from skin, were isolated from patients with bloodstream infections. MICs were determined by the modified broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI). The l-AmB MIC and the ECVs were two-fold lower than those of d-AmB and a lower l-AmB mean MIC value was found for blood isolates than from skin. The ECVs for l-AmB and d-AmB were 8 mg/l and 32 mg/l, respectively. Three strains (3.6%) showed l-AmB MIC higher than ECV (MIC > 8 mg/l) of which two were isolated from the catheter tip of patients treated with micafugin, l-Amb and fluconazole, and one from skin. The results showed that the l-AmB might be employed for assessing the in vitro antifungal susceptibility of M. furfur by a modified CLSI protocol and that ECVs might be useful for detecting the emergence of resistance. PMID:25631480

  20. A project to reduce the rate of central line associated bloodstream infection in ICU patients to a target of zero.

    PubMed

    Yaseen, Muhammad; Al-Hameed, Fahad; Osman, Khalid; Al-Janadi, Mansour; Al-Shamrani, Majid; Al-Saedi, Asim; Al-Thaqafi, Abdulhakeem

    2016-01-01

    Central venous catheters (CVCs) are life-saving and the majority of patients in intensive care units (ICUs) have them placed in order to receive medicine and fluids. However, the use of these catheters can result in serious bloodstream infections. The rate of Central Line Associated Blood Stream Infection (CLABSI) in Adult Intensive Care Units (ICUs) at King Abdulaziz Medical City Jeddah (KAMC-J) at the start of the project was 2.0/1000 line days in 2008. The Central Line (CL) Bundle by the Institute of Healthcare Improvement (IHI) was implemented at the same time with monitoring of compliance to the CL Bundle. The compliance to CL Bundle was very low at 37% in the same period. A multidisciplinary team was created to improve the compliance to the CL bundle which was expected to have an impact on the rate of CLABSI to achieve zero CLABSI events. The team continued to monitor and evaluate the progress on the compliance to the bundle as well as monitoring the CLABSI events using National Healthcare Safety Network diagnostic criteria. The real reduction in the rate of CLABSI was achieved in 2010 with 0.7/1,000 device days when the compliance to CL Bundle reached up to 98% in that year and 100% in the next two subsequent years. The project still continued and the rate continued to drop and the ultimate target of zero CLABSI was achieved in the year 2014 and maintained in the year 2015 with a sustained compliance of 100% to the CL Bundle. Successful implementation of CL Bundle can help in reducing the rates of CLABSI and achieving zero CLABSI events for a sustained period. PMID:27559470

  1. A project to reduce the rate of central line associated bloodstream infection in ICU patients to a target of zero

    PubMed Central

    Yaseen, Muhammad; Al-Hameed, Fahad; Osman, Khalid; Al-Janadi, Mansour; Al-Shamrani, Majid; Al-Saedi, Asim; Al-Thaqafi, Abdulhakeem

    2016-01-01

    Central venous catheters (CVCs) are life-saving and the majority of patients in intensive care units (ICUs) have them placed in order to receive medicine and fluids. However, the use of these catheters can result in serious bloodstream infections. The rate of Central Line Associated Blood Stream Infection (CLABSI) in Adult Intensive Care Units (ICUs) at King Abdulaziz Medical City Jeddah (KAMC-J) at the start of the project was 2.0/1000 line days in 2008. The Central Line (CL) Bundle by the Institute of Healthcare Improvement (IHI) was implemented at the same time with monitoring of compliance to the CL Bundle. The compliance to CL Bundle was very low at 37% in the same period. A multidisciplinary team was created to improve the compliance to the CL bundle which was expected to have an impact on the rate of CLABSI to achieve zero CLABSI events. The team continued to monitor and evaluate the progress on the compliance to the bundle as well as monitoring the CLABSI events using National Healthcare Safety Network diagnostic criteria. The real reduction in the rate of CLABSI was achieved in 2010 with 0.7/1,000 device days when the compliance to CL Bundle reached up to 98% in that year and 100% in the next two subsequent years. The project still continued and the rate continued to drop and the ultimate target of zero CLABSI was achieved in the year 2014 and maintained in the year 2015 with a sustained compliance of 100% to the CL Bundle. Successful implementation of CL Bundle can help in reducing the rates of CLABSI and achieving zero CLABSI events for a sustained period. PMID:27559470

  2. Outbreak of Burkholderia cepacia bloodstream infection at an outpatient hematology and oncology practice.

    PubMed

    Abe, Karon; D'Angelo, Melissa Tobin; Sunenshine, Rebecca; Noble-Wang, Judith; Cope, James; Jensen, Bette; Srinivasan, Arjun

    2007-11-01

    We investigated an outbreak of infection in 10 patients with blood cultures positive for B. cepacia. All patients had indwelling intravenous catheters. Though we did not identify the source of the organism, our findings support the hypothesis that cross-contamination of multidose medications through the use of the same needle and syringe was a contributing factor. PMID:17926285

  3. Peripheral Intravenous Catheter Placement Is an Underrecognized Source of Staphylococcus aureus Bloodstream Infection

    PubMed Central

    Austin, Eloise D.; Sullivan, Sean B.; Whittier, Susan; Lowy, Franklin D.; Uhlemann, Anne-Catrin

    2016-01-01

    Few studies have focused on the risks of peripheral intravenous catheters (PIVs) as sources for Staphylococcus aureus bacteremia (SAB), a life-threatening complication. We identified 34 PIV-related infections (7.6%) in a cohort of 445 patients with SAB. Peripheral intravenous catheter-related SAB was associated with significantly longer bacteremia duration and thrombophlebitis at old PIV sites rather than current PIVs. PMID:27191005

  4. Detection of Different Bovine Papillomavirus Types and Co-infection in Bloodstream of Cattle.

    PubMed

    Santos, E U D; Silva, M A R; Pontes, N E; Coutinho, L C A; Paiva, S S L; Castro, R S; Freitas, A C

    2016-02-01

    Bovine papillomavirus (BPV) is a diverse group of double-stranded DNA oncogenic viruses. BPVs are classically described as epitheliotropic, however, they have been detected in body fluids, such as blood and semen. The presence of BPV in these sites can have implications for the dissemination of BPV. The aim of this study was to verify the prevalence of BPV types in cattle blood. A total of 57 blood samples were analyzed by PCR using BPV type-specific primers to BPVs 1-6 and 8-10, and subsequent sequencing. Sequencing quality was determined using Staden package with Phred 20. Similarity analysis was performed with BioEdit and BLAST programs to assess the identity with known BPV types. Statistical analysis was performed by Fisher's exact test. The results showed seven different types of BPVs in the blood, with the exception of BPV 5 and 9. This is the first study that demonstrates BPVs 3, 6, 8 and 10 DNA in cattle blood. BPVs 1 and 2 were the viral types most frequent in blood, while BPVs 4 and 10 were the least frequent types. All the samples showed co-infection by at least two BPV types. These data suggest that several BPV types may infect blood cells at the same time and demonstrate the possibility that the BPV infection in non-epithelial tissue can occur without restriction to one or two viral types. These results can contribute to future studies aimed at the control and prevention of papillomaviruses. PMID:24889887

  5. Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia-Pacific region.

    PubMed

    Tan, Thean Yen; Hsu, Li Yang; Alejandria, Marissa M; Chaiwarith, Romanee; Chinniah, Terrence; Chayakulkeeree, Methee; Choudhury, Saugata; Chen, Yen Hsu; Shin, Jong Hee; Kiratisin, Pattarachai; Mendoza, Myrna; Prabhu, Kavitha; Supparatpinyo, Khuanchai; Tan, Ai Ling; Phan, Xuan Thi; Tran, Thi Thanh Nga; Nguyen, Gia Binh; Doan, Mai Phuong; Huynh, Van An; Nguyen, Su Minh Tuyet; Tran, Thanh Binh; Van Pham, Hung

    2016-07-01

    Bloodstream infections caused by Candida species are of increasing importance and associated with significant mortality. We performed a multi-centre prospective observational study to identify the species and antifungal susceptibilities of invasive bloodstream isolates of Candida species in the Asia-Pacific region. The study was carried out over a two year period, involving 13 centers from Brunei, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam. Identification of Candida species was performed at each study center, and reconfirmed at a central laboratory. Susceptibility testing was performed using a commercial broth dilution panel (Sensititre YeastOne YST-010, Thermofisher, United Kingdom) with susceptibility categorisation (S = susceptible, S-DD = susceptible dose-dependent) applied using breakpoints from the Clinical Laboratory Standards Institute. Eight hundred and sixty-one Candida isolates were included in the study. The most common species were C. albicans (35.9%), C. tropicalis (30.7%), C. parapsilosis (15.7%), and C. glabrata (13.6%). Non-albicans species exceeded C. albicans species in centers from all countries except Taiwan. Fluconazole susceptibility was almost universal for C. albicans (S = 99.7%) but lower for C. tropicalis (S = 75.8%, S-DD = 6.1%), C. glabrata (S-DD = 94.9%), and C. parapsilosis (S = 94.8%). Echinocandins demonstrated high rates of in vitro susceptibility (S>99%) against C. albicans, C. tropicalis, and C. parapsilosis This study demonstrates that non-albicans species are the most common isolates from bloodstream infections in most countries in the Asia-Pacific region, with C. tropicalis as the predominant species. Because of the prevalence of reduced susceptibility to fluconazole in non-albicans species, the study indicates that echinocandins should be the antifungal of choice in clinically unstable or high-risk patients with documented candidemia. PMID:26868904

  6. Impact of bloodstream infections on catheter colonization during extracorporeal membrane oxygenation.

    PubMed

    Kim, Dong Wan; Yeo, Hye Ju; Yoon, Seong Hoon; Lee, Seung Eun; Lee, Su Jin; Cho, Woo Hyun; Jeon, Doo Soo; Kim, Yun Seong; Son, Bong Soo; Kim, Do Hyung

    2016-06-01

    There are concerns about secondary extracorporeal membrane oxygenation (ECMO) catheter infections in bacteremic patients. We investigated the association between blood stream infection (BSI) and ECMO catheter colonization. From January 2012 to August 2014, 47 adults who received ECMO support were enrolled. The ECMO catheter tip was cultured at the end of the ECMO procedure. The enrolled patients were classified into two groups according to the presence of BSI during ECMO support and analyzed with respect to ECMO catheter colonization. Of 47 cases, BSI during ECMO was identified in 13 patients (27.7 %). ECMO catheter colonization was identified in 6 (46.2 %) patients in the BSI group and 3 (8.8 %) in the non-BSI group. BSI during ECMO support was independently associated with ECMO catheter colonization [odds ratio (OR) 5.55; 95 % confidence interval (CI) 1.00-30.73; p = 0.049]. The organisms colonizing ECMO catheters in the setting of primary BSI were predominantly Gram-positive cocci and Candida species. Acinetobacter baumannii was the most common colonizing pathogen in the setting of secondary BSI. All the organisms colonizing ECMO catheters were multi-drug resistant organisms, including methicillin-resistant S. aureus, Candida glabrata, and carbapenem-resistant A. baumannii. ECMO catheters may become contaminated with multi-drug resistant pathogens in the presence of BSI. Therefore, ECMO should be applied cautiously in septic patients with bacteremia caused by multi-drug resistant pathogens. PMID:26721824

  7. Effectiveness of a programme to reduce the burden of catheter-related bloodstream infections in a tertiary hospital.

    PubMed

    Martínez-Morel, H R; Sanchez-Payá, J; García-Shimizu, P; Mendoza-García, J L; Tenza-Iglesias, I; Rodríguez-Díaz, J C; Merino-DE-Lucas, E; Nolasco, A

    2016-07-01

    The objective of this study was to assess the effectiveness of a catheter-related bloodstream infection (CR BSI) reduction programme and healthcare workers' compliance with recommendations. A 3-year surveillance programme of CR BSIs in all hospital settings was implemented. As part of the programme, there was a direct observation of insertion and maintenance of central venous catheters (CVCs) to determine performance. A total of 38 education courses were held over the study period and feedback reports with the results of surveillance and recommendations were delivered to healthcare workers every 6 months. A total of 6722 short-term CVCs were inserted in 4982 patients for 58 763 catheter-days. Improvements of compliance with hand hygiene was verified at the insertion (87·1-100%, P < 0·001) and maintenance (51·1-72·1%, P = 0·029) of CVCs; and the use of chlorhexidine for skin disinfection was implemented at insertion (35·7-65·4%, P < 0·001) and maintenance (33·3-45·9%, P < 0·197) of CVCs. There were 266 CR BSI incidents recorded with an annual incidence density of 5·75/1000 catheter-days in the first year, 4·38 in the second year [rate ratio (RR) 0·76, 95% confidence interval (CI) 0·57-1·01] and 3·46 in the third year (RR 0·60, 95% CI 0·44-0·81). The education programme clearly improved compliance with recommendations for CVC handling, and was effective in reducing the burden of CR BSIs. PMID:26758404

  8. A Case-Control Study to Identify Risk Factors for Totally Implantable Central Venous Port-Related Bloodstream Infection

    PubMed Central

    Lee, Guk Jin; Hong, Sook Hee; Roh, Sang Young; Park, Sa Rah; Lee, Myung Ah; Chun, Hoo Geun; Hong, Young Seon; Kang, Jin Hyoung; Kim, Sang Il; Kim, Youn Jeong; Chun, Ho Jong; Oh, Jung Suk

    2014-01-01

    Purpose To date, the risk factors for central venous port-related bloodstream infection (CVPBSI) in solid cancer patients have not been fully elucidated. We conducted this study in order to determine the risk factors for CVP-BSI in patients with solid cancer. Materials and Methods A total of 1,642 patients with solid cancer received an implantable central venous port for delivery of chemotherapy between October 2008 and December 2011 in a single center. CVP-BSI was diagnosed in 66 patients (4%). We selected a control group of 130 patients, who were individually matched with respect to age, sex, and catheter insertion time. Results CVP-BSI occurred most frequently between September and November (37.9%). The most common pathogen was gram-positive cocci (n=35, 53.0%), followed by fungus (n=14, 21.2%). Multivariate analysis identified monthly catheter-stay as a risk factor for CVP-BSI (p=0.000), however, its risk was lower in primary gastrointestinal cancer than in other cancer (p=0.002). Initial metastatic disease and long catheter-stay were statistically significant factors affecting catheter life span (p=0.005 and p=0.000). Results of multivariate analysis showed that recent transfusion was a risk factor for mortality in patients with CVP-BSI (p=0.047). Conclusion In analysis of the results with respect to risk factors, prolonged catheter-stay should be avoided as much as possible. It is necessary to be cautious of CVP-BSI in metastatic solid cancer, especially non-gastrointestinal cancer. In addition, avoidance of unnecessary transfusion is essential in order to reduce the mortality of CVP-BSI. Finally, considering the fact that confounding factors may have affected the results, conduct of a well-designed prospective controlled study is warranted. PMID:25038760

  9. Impact of Inadequate Empirical Therapy on the Mortality of Patients with Bloodstream Infections: a Propensity Score-Based Analysis

    PubMed Central

    Retamar, Pilar; Portillo, María M.; López-Prieto, María Dolores; Rodríguez-López, Fernando; de Cueto, Marina; García, María V.; Gómez, María J.; del Arco, Alfonso; Muñoz, Angel; Sánchez-Porto, Antonio; Torres-Tortosa, Manuel; Martín-Aspas, Andrés; Arroyo, Ascensión; García-Figueras, Carolina; Acosta, Federico; Corzo, Juan E.; León-Ruiz, Laura; Escobar-Lara, Trinidad

    2012-01-01

    The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented. PMID:22005999

  10. Risk factors for late-onset health care-associated bloodstream infections in patients in neonatal intensive care units

    PubMed Central

    Perlman, Sharon E.; Saiman, Lisa; Larson, Elaine L.

    2007-01-01

    Background There are few data comparing risk factors for catheter-related (CR) versus non-CR bloodstream infection (BSI) or for BSI caused by gram-positive versus gram-negative organisms. The aims of this study were to compare risk factors for CR versus non-CR BSI and to compare risk factors for BSI associated with gram-negative versus gram-positive organisms among infants hospitalized in two neonatal intensive care units (NICUs). Methods Data were collected prospectively over a 2-year period to assess risk factors among 2,935 neonates from two NICUs. Results Among all neonates, in addition to low birth weight and presence of a central venous catheter, hospitalization in NICU 1 (relative risk [RR]: 1.60, 95% confidence intervals [CI]: 1.14, 2.24) was a significant predictor of BSI. In neonates with a central catheter total parenteral nutrition (TPN) was a significant risk factor for BSI (RR: 4.69, 95% CI: 2.22, 9.87). Ventilator use was a significant risk factor for CR versus non-CR BSI (RR: 3.74, 95% CI: 1.87, 7.48), and significantly more CR BSI were caused by gram-positive (77.1%) than by gram-negative organisms (61.4%), P = .03. Conclusions This study confirmed that central venous catheters and low birth weight were risk factors for neonates with late-onset healthcare-associated BSI and further elucidated the potential risks associated with TPN and ventilator use in subgroups of neonates with BSI. Additional studies are needed to examine the incremental risk of TPN among infants with central venous catheters and to understand the link between CR BSI and ventilator use. Preventive strategies for BSI in neonates in NICUs should continue to focus on limiting the use of invasive devices. PMID:17433941

  11. A Central Line Care Maintenance Bundle for the Prevention of Catheter-Associated Bloodstream Infection in Non-ICU Settings

    PubMed Central

    O'Neil, Caroline; Ball, Kelly; Wood, Helen; McMullen, Kathleen; Kremer, Pamala; Jafarzadeh, S. Reza; Fraser, Victoria; Warren, David

    2016-01-01

    Objective To evaluate a central line care maintenance bundle to reduce central line-associated bloodstream infection (CLABSI) in non-ICU settings. Design Before-after trial with 12 month follow-up period. Setting 1250-bed teaching hospital. Participants Patients with central lines on eight general medicine wards. Four wards received the intervention and four served as controls. Intervention A multifaceted catheter care maintenance bundle consisting of educational programs for nurses, update of hospital policies, visual aids, a competency assessment, process monitoring, regular progress reports, and consolidation of supplies necessary for catheter maintenance. Results Data were collected for 25,542 catheter-days including 43 CLABSI (rate = 1.68 per 1,000 CL-days) and 4,012 catheter dressing observations. Following the intervention, a 2.5% monthly decrease in the CLABSI incidence density was observed on intervention floors, but this was not statistically significant (95% confidence interval (CI); −5.3 – 0.4). On control floors, there was a smaller, but marginally significant decrease in CLABSI incidence during the study (change in monthly rate = −1.1%; 95% CI, −2.1 - −0.1). Implementation of the bundle was associated with improvement in catheter dressing compliance on intervention wards (78.8% compliance pre-intervention vs. 87.9% during intervention/follow-up; p<0.001) but improvement was also observed on control wards (84.9% compliance pre-intervention vs. 90.9% during intervention/follow-up; P = .001). Conclusions A multi-faceted program to improve catheter care was associated with improvement in catheter dressing care, but no change in CLABSI rates. Additional study is needed to determine strategies to prevent CLABSI in non-ICU patients. PMID:26999746

  12. Association of genotypes with infection types and antifungal susceptibilities in Candida albicans as revealed by recent molecular typing strategies

    PubMed Central

    Bai, Feng-Yan

    2014-01-01

    Candida albicans is a commensal microorganism in the mucosa of healthy individuals, but is also the most common opportunistic fungal pathogen of humans. It causes from benign infections such as oral and vaginal candidiasis to fatal, systematic diseases in immunocompromised or critically ill patients. In addition to improved therapy, the rapid and accurate identification of the disease-causing strains is crucial for diagnosis, clinical treatment and epidemiological studies of candidiasis. A variety of methods for strain typing of C. albicans have been developed. The most commonly used methods with the focus on recently developed molecular typing or DNA-fingerprinting strategies and the recent findings in the association of specific and genetically similar genotypes with certain infection types and the correlation between azole susceptibilities and certain genotypes of C. albicans from China are reviewed. PMID:24772369

  13. Characterization and Clinical Impact of Bloodstream Infection Caused by Carbapenemase-Producing Enterobacteriaceae in Seven Latin American Countries

    PubMed Central

    Villegas, Maria Virginia; Pallares, Christian J.; Hernández-Gómez, Cristhian; Correa, Adriana; Álvarez, Carlos; Rosso, Fernando; Matta, Lorena; Luna, Carlos; Zurita, Jeannete; Mejía-Villatoro, Carlos; Rodríguez-Noriega, Eduardo; Seas, Carlos; Cortesía, Manuel; Guzmán-Suárez, Alfonso; Guzmán-Blanco, Manuel

    2016-01-01

    Introduction Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy. Methods Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information. Results A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001). The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001); however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7–9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1–13.7; p < 0

  14. An Optimized Lock Solution Containing Micafungin, Ethanol and Doxycycline Inhibits Candida albicans and Mixed C. albicans – Staphyloccoccus aureus Biofilms

    PubMed Central

    Lown, Livia; Peters, Brian M.; Walraven, Carla J.; Noverr, Mairi C.; Lee, Samuel A.

    2016-01-01

    Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C. albicans biofilms. Thus, we sought to investigate optimal combinations of micafungin, ethanol, and/or doxycycline as a lock solution. We performed two- and three-drug checkerboard assays to determine the in vitro activity of pairwise or three agents in combination for prevention or treatment of C. albicans biofilms. Optimal lock solutions were tested for activity against C. albicans clinical isolates, reference strains and polymicrobial C. albicans-S. aureus biofilms. A solution containing 20% (v/v) ethanol, 0.01565 μg/mL micafungin, and 800 μg/mL doxycycline demonstrated a reduction of 98% metabolic activity and no fungal regrowth when used to prevent fungal biofilm formation; however there was no advantage over 20% ethanol alone. This solution was also successful in inhibiting the regrowth of C. albicans from mature polymicrobial biofilms, although it was not fully bactericidal. Solutions containing 5% ethanol with low concentrations of micafungin and doxycycline demonstrated synergistic activity when used to prevent monomicrobial C. albicans biofilm formation. A combined solution of micafungin, ethanol and doxycycline is highly effective for the prevention of C. albicans biofilm formation but did not demonstrate an advantage over 20% ethanol alone in these studies. PMID:27428310

  15. Recipient-born bloodstream infection due to extensively drug-resistant Acinetobacter baumannii after emergency heart transplant: report of a case and review of the literature.

    PubMed

    Andini, Roberto; Agrusta, Federica; Mattucci, Irene; Malgeri, Umberto; Cavezza, Giusi; Utili, Riccardo; Durante-Mangoni, Emanuele

    2015-10-01

    Infections due to drug-resistant Gram-negative rods are an emerging risk factor for increased mortality after solid organ transplant. Extensively drug-resistant (XDR) Acinetobacter baumannii (Acb) is a major threat in several critical care settings. The limited available data on the outcome of XDR Acb infections in organ transplant recipients mostly comes from cases of donor-derived infections. However, recipients of life-saving organs are often critically ill patients, staying long term in intensive care units, and therefore at high risk for nosocomial infections. In this report, we describe our experience with the exceedingly complex management of a recipient-born XDR Acb bloodstream infection clinically ensued shortly after heart transplant. We also review the current literature on this mounting issue relevant for intensive care, transplant medicine and infectious diseases. PMID:25828937

  16. Candida albicans Shaving to Profile Human Serum Proteins on Hyphal Surface

    PubMed Central

    Marín, Elvira; Parra-Giraldo, Claudia M.; Hernández-Haro, Carolina; Hernáez, María L.; Nombela, César; Monteoliva, Lucía; Gil, Concha

    2015-01-01

    Candida albicans is a human opportunistic fungus and it is responsible for a wide variety of infections, either superficial or systemic. C. albicans is a polymorphic fungus and its ability to switch between yeast and hyphae is essential for its virulence. Once C. albicans obtains access to the human body, the host serum constitutes a complex environment of interaction with C. albicans cell surface in bloodstream. To draw a comprehensive picture of this relevant step in host-pathogen interaction during invasive candidiasis, we have optimized a gel-free shaving proteomic strategy to identify both, human serum proteins coating C. albicans cells and fungi surface proteins simultaneously. This approach was carried out with normal serum (NS) and heat inactivated serum (HIS). We identified 214 human and 372 C. albicans unique proteins. Proteins identified in C. albicans included 147 which were described as located at the cell surface and 52 that were described as immunogenic. Interestingly, among these C. albicans proteins, we identified 23 GPI-anchored proteins, Gpd2 and Pra1, which are involved in complement system evasion and 7 other proteins that are able to attach plasminogen to C. albicans surface (Adh1, Eno1, Fba1, Pgk1, Tdh3, Tef1, and Tsa1). Furthermore, 12 proteins identified at the C. albicans hyphae surface induced with 10% human serum were not detected in other hypha-induced conditions. The most abundant human proteins identified are involved in complement and coagulation pathways. Remarkably, with this strategy, all main proteins belonging to complement cascades were identified on the C. albicans surface. Moreover, we identified immunoglobulins, cytoskeletal proteins, metabolic proteins such as apolipoproteins and others. Additionally, we identified more inhibitors of complement and coagulation pathways, some of them serpin proteins (serine protease inhibitors), in HIS vs. NS. On the other hand, we detected a higher amount of C3 at the C. albicans surface in

  17. Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans

    PubMed Central

    Dong, Shuai; Shi, Hongxi; Cao, Donghui; Wang, Yicun; Zhang, Xintong; Li, Yan; Gao, Xiang; Wang, Li

    2016-01-01

    Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans. PMID:27558409

  18. Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans.

    PubMed

    Dong, Shuai; Shi, Hongxi; Cao, Donghui; Wang, Yicun; Zhang, Xintong; Li, Yan; Gao, Xiang; Wang, Li

    2016-01-01

    Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans. PMID:27558409

  19. Resistance Markers and Genetic Diversity in Acinetobacter baumannii Strains Recovered from Nosocomial Bloodstream Infections

    PubMed Central

    Martins, Hanoch S. I.; Bomfim, Maria Rosa Q.; França, Rafaela O.; Farias, Luiz M.; Carvalho, Maria Auxiliadora R.; Serufo, José Carlos; Santos, Simone G.

    2014-01-01

    In this study, phenotypic and genotypic methods were used to detect metallo-β-lactamases, cephalosporinases and oxacillinases and to assess genetic diversity among 64 multiresistant Acinetobacter baumannii strains recovered from blood cultures in five different hospitals in Brazil from December 2008 to June 2009. High rates of resistance to imipenem (93.75%) and polymyxin B (39.06%) were observed using the disk diffusion (DD) method and by determining the minimum inhibitory concentration (MIC). Using the disk approximation method, thirty-nine strains (60.9%) were phenotypically positive for class D enzymes, and 51 strains (79.6%) were positive for cephalosporinase (AmpC). Using the E-test, 60 strains (93.75%) were positive for metallo-β-lactamases (MβLs). All strains were positive for at least one of the 10 studied genes; 59 (92.1%) contained blaVIM-1, 79.6% contained blaAmpC, 93.7% contained blaOXA23 and 84.3% contained blaOXA51. Enterobacteria Repetitive Intergenic Consensus (ERIC)-PCR analysis revealed a predominance of certain clones that differed from each other. However, the same band pattern was observed in samples from the different hospitals studied, demonstrating correlation between the genotypic and phenotypic results. Thus, ERIC-PCR is an appropriate method for rapidly clustering genetically related isolates. These results suggest that defined clonal clusters are circulating within the studied hospitals. These results also show that the prevalence of MDR A. baumannii may vary among clones disseminated in specific hospitals, and they emphasize the importance of adhering to appropriate infection control measures. PMID:24477210

  20. Prevalence of Resistant Gram-Negative Bacilli in Bloodstream Infection in Febrile Neutropenia Patients Undergoing Hematopoietic Stem Cell Transplantation

    PubMed Central

    Wang, Ling; Wang, Ying; Fan, Xing; Tang, Wei; Hu, Jiong

    2015-01-01

    Abstract Bloodstream infection (BSI) is an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the causative bacteria and identify risk factors for BSI associated mortality in febrile neutropenia patients undergoing HSCT, we collected the clinical and microbiological data from patients underwent HSCT between 2008 and 2014 and performed a retrospective analysis. Throughout the study period, among 348 episodes of neutropenic fever in patients underwent HSCT, 89 episodes in 85 patients had microbiological defined BSI with a total of 108 isolates. Gram-negative bacteria (GNB) were the most common isolates (76, 70.3%) followed by gram-positive bacteria (GPB, 29, 26.9%) and fungus (3, 2.8%). As to the drug resistance, 26 multiple drug resistance (MDR) isolates were identified. Resistant isolates (n = 23) were more common documented in GNB, mostly Escherichia coli (9/36, 25%) and Klebsiella pneumonia (6/24, 25%). A total of 12 isolated were resistant to carbapenem including 4 K pneumoniae (4/24, 16.7%), 3 Stenotrophomonas maltophilia, and 1 Pseudomonas aeruginosa and other 4 GNB isolates (Citrobacter freumdii, Pseudomonas stutzeri, Acinetobacter baumanii, and Chryseobacterium indologenes). As to the GPB, only 3 resistant isolates were documented including 2 methicillin-resistant isolates (Staphylococcus hominis and Arcanobacterium hemolysis) and 1 vancomycin-resistant Enterococcus faecium. Among these 85 patients with documented BSI, 11 patients died of BSI as primary or associated cause with a BSI-related mortality of 13.1 ± 3.7% and 90-day overall survival after transplantation at 80.0 ± 4.3%. Patients with high-risk disease undergoing allo-HSCT, prolonged neutropenia (≥15 days) and infection with carbapenem-resistant GNB were associated with BSI associated mortality in univariate and multivariate analyses. Our report revealed a prevalence of GNB in BSI of neutropenic patients

  1. Multiplex PCR Allows Rapid and Accurate Diagnosis of Bloodstream Infections in Newborns and Children with Suspected Sepsis▿†§

    PubMed Central

    Lucignano, Barbara; Ranno, Stefania; Liesenfeld, Oliver; Pizzorno, Beatrice; Putignani, Lorenza; Bernaschi, Paola; Menichella, Donato

    2011-01-01

    Sepsis is a major health problem in newborns and children. Early detection of pathogens allows initiation of appropriate antimicrobial therapy that strongly correlates with positive outcomes. Multiplex PCR has the potential to rapidly identify bloodstream infections, compensating for the loss of blood culture sensitivity. In an Italian pediatric hospital, multiplex PCR (the LightCycler SeptiFast test) was compared to routine blood culture with 1,673 samples obtained from 803 children with suspected sepsis; clinical and laboratory information was used to determine the patient infection status. Excluding results attributable to contaminants, SeptiFast showed a sensitivity of 85.0% (95% confidence interval [CI] = 78.7 to 89.7%) and a specificity of 93.5% (95% CI = 92.1 to 94.7%) compared to blood culture. The rate of positive results was significantly higher with SeptiFast (14.6%) than blood culture (10.3%) (P < 0.0001), and the overall positivity rate was 16.1% when the results of both tests were combined. Staphylococcus aureus (11.6%), coagulase-negative staphylococci (CoNS) (29.6%), Pseudomonas aeruginosa (16.5%), and Klebsiella spp. (10.1%) were the most frequently detected. SeptiFast identified 97 additional isolates that blood culture failed to detect (24.7% P. aeruginosa, 23.7% CoNS, 14.4% Klebsiella spp., 14.4% Candida spp.). Among specimens taken from patients receiving antibiotic therapy, we also observed a significantly higher rate of positivity of SeptiFast than blood culture (14.1% versus 6.5%, respectively; P < 0.0001). On the contrary, contaminants were significantly more frequent among blood cultures than SeptiFast (n = 97 [5.8%] versus n = 26 [1.6%]), respectively; P < 0.0001). SeptiFast served as a highly valuable adjunct to conventional blood culture in children, adding diagnostic value and shortening the time to result (TTR) to 6 h. PMID:21471340

  2. Contribution of the BacT/Alert MB Mycobacterium Bottle to Bloodstream Infection Surveillance in Thailand: Added Yield for Burkholderia pseudomallei

    PubMed Central

    Higdon, Melissa; Kaewpan, Anek; Makprasert, Sirirat; Yuenprakhon, Somkhit; Tawisaid, Kittisak; Dejsirilert, Surang; Whistler, Toni; Baggett, Henry C.

    2015-01-01

    Community-acquired bloodstream infections cause substantial morbidity and mortality worldwide, but microbiology capacity and surveillance limitations have challenged good descriptions of pathogen distribution in many regions, including Southeast Asia. Active surveillance for bloodstream infections has been conducted in two rural Thailand provinces for >7 years. Blood specimens were divided into two culture bottles, one optimized for aerobic growth (F bottle) and a second for enhanced growth of mycobacteria (MB bottle), and processed with the BactT/Alert 3D system. Because the routine use of MB culture bottles is resource intensive (expensive and requires prolonged incubation), we assessed the added yield of MB bottles by comparing the proportion of pathogens detected by MB versus that by F bottles from 2005 to 2012. Of 63,066 blood cultures, 7,296 (12%) were positive for at least one pathogen; the most common pathogens were Escherichia coli (28%), Burkholderia pseudomallei (11%), Klebsiella pneumoniae (9%), and Staphylococcus aureus (6%). Two bottles improved the yield overall, but the added yield attributable to the MB bottles was limited to a few pathogens. In addition to the detection of mycobacteria and some fungi, MB bottles improved the detection of B. pseudomallei (27% [MB] versus 8% [F]; P < 0.0001), with added benefit if therapy was initiated prior to the blood culture. The targeted use of MB bottles is warranted for patients at risk for mycobacterial and fungal infections and for infection with B. pseudomallei, a common cause of septicemia in Thailand. PMID:25588650

  3. Biomarkers and Molecular Analysis to Improve Bloodstream Infection Diagnostics in an Emergency Care Unit

    PubMed Central

    Loonen, Anne J. M.; de Jager, Cornelis P. C.; Tosserams, Janna; Kusters, Ron; Hilbink, Mirrian; Wever, Peter C.; van den Brule, Adriaan J. C.

    2014-01-01

    Molecular pathogen detection from blood is still expensive and the exact clinical value remains to be determined. The use of biomarkers may assist in preselecting patients for immediate molecular testing besides blood culture. In this study, 140 patients with ≥ 2 SIRS criteria and clinical signs of infection presenting at the emergency department of our hospital were included. C-reactive protein (CRP), neutrophil-lymphocyte count ratio (NLCR), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels were determined. One ml EDTA blood was obtained and selective pathogen DNA isolation was performed with MolYsis (Molzym). DNA samples were analysed for the presence of pathogens, using both the MagicPlex Sepsis Test (Seegene) and SepsiTest (Molzym), and results were compared to blood cultures. Fifteen patients had to be excluded from the study, leaving 125 patients for further analysis. Of the 125 patient samples analysed, 27 presented with positive blood cultures of which 7 were considered to be contaminants. suPAR, PCT, and NLCR values were significantly higher in patients with positive blood cultures compared to patients without (p < 0.001). Receiver operating characteristic curves of the 4 biomarkers for differentiating bacteremia from non-bacteremia showed the highest area under the curve (AUC) for PCT (0.806 (95% confidence interval 0.699–0.913)). NLCR, suPAR and CRP resulted in an AUC of 0.770, 0.793, and 0.485, respectively. When compared to blood cultures, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for SepsiTest and MagicPlex Sepsis Test were 11%, 96%, 43%, 80%, and 37%, 77%, 30%, 82%, respectively. In conclusion, both molecular assays perform poorly when one ml whole blood is used from emergency care unit patients. NLCR is a cheap, fast, easy to determine, and rapidly available biomarker, and therefore seems most promising in differentiating BSI from non-BSI patients for

  4. Antifungal Susceptibility in Serum and Virulence Determinants of Candida Bloodstream Isolates from Hong Kong

    PubMed Central

    Seneviratne, Chaminda J.; Rajan, Suhasini; Wong, Sarah S. W.; Tsang, Dominic N. C.; Lai, Christopher K. C.; Samaranayake, Lakshman P.; Jin, Lijian

    2016-01-01

    Candida bloodstream infections (CBI) are one of the most common nosocomial infections globally, and they account for a high mortality rate. The increasing global prevalence of drug-resistant Candida strains has also been posing a challenge to clinicians. In this study, we comprehensively evaluated the biofilm formation and production of hemolysin and proteinase of 63 CBI isolates derived from a hospital setting in Hong Kong as well as their antifungal susceptibility both in the presence and in the absence of human serum, using standard methodology. Candida albicans was the predominant species among the 63 CBI isolates collected, and non-albicans Candida species accounted for approximately one third of the isolates (36.5%). Of them, Candida tropicalis was the most common non-albicans Candida species. A high proportion (31.7%) of the CBI isolates (40% of C. albicans isolates, 10% of C. tropicalis isolates, 11% of C. parapsilosis isolates, and 100% of C. glabrata isolates) were found to be resistant to fluconazole. One of the isolates (C. tropicalis) was resistant to amphotericin B. A rising prevalence of drug-resistance CBI isolates in Hong Kong was observed with reference to a previous study. Notably, all non-albicans Candida species, showed increased hemolytic activity relative to C. albicans, whilst C. albicans, C. tropicalis, and C. parapsilosis exhibited proteinase activities. Majority of the isolates were capable of forming mature biofilms. Interestingly, the presence of serum distorted the yeast sensitivity to fluconazole, but not amphotericin B. Taken together, our findings demonstrate that CBI isolates of Candida have the potential to express to varying extent their virulence attributes (e.g., biofilm formation, hemolysin production, and proteinase activity) and these, together with perturbations in their antifungal sensitivity in the presence of serum, may contribute to treatment complication in candidemia. The effect of serum on antifungal activity

  5. Antifungal Susceptibility in Serum and Virulence Determinants of Candida Bloodstream Isolates from Hong Kong.

    PubMed

    Seneviratne, Chaminda J; Rajan, Suhasini; Wong, Sarah S W; Tsang, Dominic N C; Lai, Christopher K C; Samaranayake, Lakshman P; Jin, Lijian

    2016-01-01

    Candida bloodstream infections (CBI) are one of the most common nosocomial infections globally, and they account for a high mortality rate. The increasing global prevalence of drug-resistant Candida strains has also been posing a challenge to clinicians. In this study, we comprehensively evaluated the biofilm formation and production of hemolysin and proteinase of 63 CBI isolates derived from a hospital setting in Hong Kong as well as their antifungal susceptibility both in the presence and in the absence of human serum, using standard methodology. Candida albicans was the predominant species among the 63 CBI isolates collected, and non-albicans Candida species accounted for approximately one third of the isolates (36.5%). Of them, Candida tropicalis was the most common non-albicans Candida species. A high proportion (31.7%) of the CBI isolates (40% of C. albicans isolates, 10% of C. tropicalis isolates, 11% of C. parapsilosis isolates, and 100% of C. glabrata isolates) were found to be resistant to fluconazole. One of the isolates (C. tropicalis) was resistant to amphotericin B. A rising prevalence of drug-resistance CBI isolates in Hong Kong was observed with reference to a previous study. Notably, all non-albicans Candida species, showed increased hemolytic activity relative to C. albicans, whilst C. albicans, C. tropicalis, and C. parapsilosis exhibited proteinase activities. Majority of the isolates were capable of forming mature biofilms. Interestingly, the presence of serum distorted the yeast sensitivity to fluconazole, but not amphotericin B. Taken together, our findings demonstrate that CBI isolates of Candida have the potential to express to varying extent their virulence attributes (e.g., biofilm formation, hemolysin production, and proteinase activity) and these, together with perturbations in their antifungal sensitivity in the presence of serum, may contribute to treatment complication in candidemia. The effect of serum on antifungal activity

  6. An Immunocompromised Child with Bloodstream Infection Caused by Two Escherichia coli Strains, One Harboring NDM-5 and the Other Harboring OXA-48-Like Carbapenemase.

    PubMed

    Hasassri, M Earth; Boyce, Thomas G; Norgan, Andrew; Cunningham, Scott A; Jeraldo, Patricio R; Weissman, Scott; Patel, Robin; Banerjee, Ritu; Pogue, Jason M; Kaye, Keith S

    2016-06-01

    We describe a 16-year-old neutropenic patient from the Middle East with bloodstream infection caused by two carbapenemase-producing Escherichia coli isolates that we characterized by whole-genome sequencing. While one displayed meropenem resistance and was blaNDM positive, the other demonstrated meropenem susceptibility yet harbored blaOXA181 (which encodes a blaOXA48-like enzyme). This report highlights the challenge of laboratory detection of blaOXA48-like enzymes and the clinical implications of genotypic resistance detection in carbapenemase-producing Enterobacteriaceae. PMID:27217442

  7. Long-term, low-dose tigecycline to treat relapsing bloodstream infection due to KPC-producing Klebsiella pneumoniae after major hepatic surgery.

    PubMed

    Morelli, Luca; Tartaglia, Dario; Furbetta, Niccolò; Palmeri, Matteo; Ferranti, Simone; Tagliaferri, Enrico; Di Candio, Giulio; Mosca, Franco

    2015-07-01

    A 68-year-old male underwent a right hepatectomy, resection of the biliary convergence, and a left hepatic jejunostomy for a Klatskin tumour. The postoperative course was complicated by biliary abscesses with relapsing bloodstream infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp). A 2-week course of combination antibiotic therapy failed to provide source control and the bacteraemia relapsed. Success was obtained with a regimen of tigecycline 100mg daily for 2 months, followed by tigecycline 50mg daily for 6 months, then 50mg every 48h for 3 months. No side effects were reported. PMID:25975648

  8. Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015.

    PubMed

    Hasman, Henrik; Hammerum, Anette M; Hansen, Frank; Hendriksen, Rene S; Olesen, Bente; Agersø, Yvonne; Zankari, Ea; Leekitcharoenphon, Pimlapas; Stegger, Marc; Kaas, Rolf S; Cavaco, Lina M; Hansen, Dennis S; Aarestrup, Frank M; Skov, Robert L

    2015-01-01

    The plasmid-mediated colistin resistance gene, mcr-1, was detected in an Escherichia coli isolate from a Danish patient with bloodstream infection and in five E. coli isolates from imported chicken meat. One isolate from chicken meat belonged to the epidemic spreading sequence type ST131. In addition to IncI2, an incX4 replicon was found to be linked to mcr-1. This report follows a recent detection of mcr-1 in E. coli from animals, food and humans in China. PMID:26676364

  9. Difference in time to positivity is useful for the diagnosis of catheter-related bloodstream infection in hematopoietic stem cell transplant recipients.

    PubMed

    Abdelkefi, A; Achour, W; Ben Othman, T; Torjman, L; Ladeb, S; Lakhal, A; Hsaïri, M; Kammoun, L; Ben Hassen, A; Ben Abdeladhim, A

    2005-02-01

    Catheter-related bloodstream infections are associated with recognized morbidity and mortality. Accurate diagnosis of such infections results in proper management of patients and in reducing unnecessary removal of catheters. We carried out a prospective study in a bone marrow transplant unit to assess the validity of a test based on the earlier positivity of central venous blood cultures in comparison with peripheral blood cultures for predicting catheter-related bacteremia. Between May 2002 and June 2004, 38 bloodstream infections with positive simultaneous central venous catheter and peripheral vein blood cultures were included. A total of 22 patients had catheter-related bacteremias and 16 had noncatheter-related bacteremias, using the catheter-tip culture/clinical criteria as the criterion standard to define catheter-related bacteremia. Differential time to positivity of 120 min or more was associated with 86% sensitivity and 87% specificity. In conclusion, differential time to positivity of 120 min or more is sensitive and specific for catheter-related bacteremia in hematopoietic stem cell transplant recipients who have nontunnelled short-term catheters. PMID:15640824

  10. Use of the Tego needlefree connector is associated with reduced incidence of catheter-related bloodstream infections in hemodialysis patients

    PubMed Central

    Brunelli, Steven M; Njord, Levi; Hunt, Abigail E; Sibbel, Scott P

    2014-01-01

    Background and objectives Catheter-related bloodstream infections (CRBSIs) are common in hemodialysis patients using central venous catheters, and catheter occlusion also occurs frequently. The Tego needlefree connector was developed to reduce the incidence of these complications; however, existing studies of its effectiveness and safety are limited. Materials and methods This retrospective analysis compared outcomes among patients of a large dialysis organization receiving in-center hemodialysis using a central venous catheter with either the Tego connector or standard catheter caps between October 1 and June 30, 2013. Incidence rates for intravenous (IV) antibiotic starts, receipt of an IV antibiotic course, positive blood cultures, mortality, and missed dialysis treatments were calculated, and incidence-rate ratios (IRRs) were estimated using Poisson regression models. Utilization of erythropoiesis-stimulating agents (ESAs) and thrombolytics was described for each patient-month and compared using mixed linear models. Models were run without adjustment, adjusted for covariates that were imbalanced between cohorts, or fully adjusted for all potential confounders. Results The analysis comprised 10,652 Tego patients and 6,493 controls. Tego use was independently associated with decreased risk of CRBSI, defined by initiation of IV antibiotics (adjusted IRR 0.92, 95% confidence interval [CI] 0.87–0.97) or initiation of IV antibiotic course (adjusted IRR 0.89, 95% CI 0.84–0.95). Tego use was independently associated with decreased rate of missed dialysis treatments (adjusted IRR 0.98, 95% CI 0.97–1.00); no significant difference between Tego and control cohorts was observed with respect to mortality. Tego use was associated with decreased likelihood of thrombolytic use (adjusted per-month probability of 5.6% versus 6.2% for controls) and lower utilization of ESAs in study months 7–9. Conclusion Use of the Tego connector may reduce the risk of CRBSI and result

  11. Improved hospital-level risk adjustment for surveillance of healthcare-associated bloodstream infections: a retrospective cohort study

    PubMed Central

    2009-01-01

    Background To allow direct comparison of bloodstream infection (BSI) rates between hospitals for performance measurement, observed rates need to be risk adjusted according to the types of patients cared for by the hospital. However, attribute data on all individual patients are often unavailable and hospital-level risk adjustment needs to be done using indirect indicator variables of patient case mix, such as hospital level. We aimed to identify medical services associated with high or low BSI rates, and to evaluate the services provided by the hospital as indicators that can be used for more objective hospital-level risk adjustment. Methods From February 2001-December 2007, 1719 monthly BSI counts were available from 18 hospitals in Queensland, Australia. BSI outcomes were stratified into four groups: overall BSI (OBSI), Staphylococcus aureus BSI (STAPH), intravascular device-related S. aureus BSI (IVD-STAPH) and methicillin-resistant S. aureus BSI (MRSA). Twelve services were considered as candidate risk-adjustment variables. For OBSI, STAPH and IVD-STAPH, we developed generalized estimating equation Poisson regression models that accounted for autocorrelation in longitudinal counts. Due to a lack of autocorrelation, a standard logistic regression model was specified for MRSA. Results Four risk services were identified for OBSI: AIDS (IRR 2.14, 95% CI 1.20 to 3.82), infectious diseases (IRR 2.72, 95% CI 1.97 to 3.76), oncology (IRR 1.60, 95% CI 1.29 to 1.98) and bone marrow transplants (IRR 1.52, 95% CI 1.14 to 2.03). Four protective services were also found. A similar but smaller group of risk and protective services were found for the other outcomes. Acceptable agreement between observed and fitted values was found for the OBSI and STAPH models but not for the IVD-STAPH and MRSA models. However, the IVD-STAPH and MRSA models successfully discriminated between hospitals with higher and lower BSI rates. Conclusion The high model goodness-of-fit and the higher

  12. Propensity Score Analysis of the Role of Initial Antifungal Therapy in the Outcome of Candida glabrata Bloodstream Infections.

    PubMed

    Puig-Asensio, M; Fernández-Ruiz, M; Aguado, J M; Merino, P; Lora-Pablos, D; Guinea, J; Martín-Dávila, P; Cuenca-Estrella, M; Almirante, B

    2016-06-01

    Candida glabrata isolates have reduced in vitro susceptibility to azoles, which raises concerns about the clinical effectiveness of fluconazole for treating bloodstream infection (BSI) by this Candida species. We aimed to evaluate whether the choice of initial antifungal treatment (fluconazole versus echinocandins or liposomal amphotericin B [L-AmB]-based regimens) has an impact on the outcome of C. glabrata BSI. We analyzed data from a prospective, multicenter, population-based surveillance program on candidemia conducted in 5 metropolitan areas of Spain (May 2010 to April 2011). Adult patients with an episode of C. glabrata BSI were included. The main outcomes were 14-day mortality and treatment failure (14-day mortality and/or persistent C. glabrata BSI for ≥48 h despite antifungal initiation). The impact of using fluconazole as initial antifungal treatment on the patients' prognosis was assessed by logistic regression analysis with the addition of a propensity score approach. A total of 94 patients with C. glabrata BSI were identified. Of these, 34 had received fluconazole and 35 had received an echinocandin/L-AmB-based regimen. Patients in the echinocandin/L-AmB group had poorer baseline clinical status than did those in the fluconazole group. Patients in the fluconazole group were more frequently (55.9% versus 28.6%) and much earlier (median time, 3 versus 7 days) switched to another antifungal regimen. Overall, 14-day mortality was 13% (9/69) and treatment failure 34.8% (24/69), with no significant differences between the groups. On multivariate analysis, after adjusting for baseline characteristics by propensity score, fluconazole use was not associated with an unfavorable evolution (adjusted odds ratio [OR] for 14-day mortality, 1.16, with 95% confidence interval [CI] of 0.22 to 6.17; adjusted OR for treatment failure, 0.83, with 95% CI of 0.27 to 2.61). In conclusion, initial fluconazole treatment was not associated with a poorer outcome than that

  13. Activation and Alliance of Regulatory Pathways in C. albicans during Mammalian Infection

    PubMed Central

    Xu, Wenjie; Solis, Norma V.; Ehrlich, Rachel L.; Woolford, Carol A.; Filler, Scott G.; Mitchell, Aaron P.

    2015-01-01

    Gene expression dynamics have provided foundational insight into almost all biological processes. Here, we analyze expression of environmentally responsive genes and transcription factor genes to infer signals and pathways that drive pathogen gene regulation during invasive Candida albicans infection of a mammalian host. Environmentally responsive gene expression shows that there are early and late phases of infection. The early phase includes induction of zinc and iron limitation genes, genes that respond to transcription factor Rim101, and genes characteristic of invasive hyphal cells. The late phase includes responses related to phagocytosis by macrophages. Transcription factor gene expression also reflects early and late phases. Transcription factor genes that are required for virulence or proliferation in vivo are enriched among highly expressed transcription factor genes. Mutants defective in six transcription factor genes, three previously studied in detail (Rim101, Efg1, Zap1) and three less extensively studied (Rob1, Rpn4, Sut1), are profiled during infection. Most of these mutants have distinct gene expression profiles during infection as compared to in vitro growth. Infection profiles suggest that Sut1 acts in the same pathway as Zap1, and we verify that functional relationship with the finding that overexpression of either ZAP1 or the Zap1-dependent zinc transporter gene ZRT2 restores pathogenicity to a sut1 mutant. Perturbation with the cell wall inhibitor caspofungin also has distinct gene expression impact in vivo and in vitro. Unexpectedly, caspofungin induces many of the same genes that are repressed early during infection, a phenomenon that we suggest may contribute to drug efficacy. The pathogen response circuitry is tailored uniquely during infection, with many relevant regulatory relationships that are not evident during growth in vitro. Our findings support the principle that virulence is a property that is manifested only in the distinct

  14. Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology. Supportive Therapy Group-Infectious Diseases Section.

    PubMed

    Viscoli, C; Castagnola, E; Giacchino, M; Cesáro, S; Properzi, E; Tucci, F; Mura, R M; Alvisi, P; Zanazzo, G; Surico, G; Bonetti, F; De Sio, L; Izzi, G; Di Cataldo, A; Ziino, O; Massolo, F; Nardi, M; Santoro, N; Binda, S

    1999-05-01

    A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%). PMID:10505037

  15. Host defence against C. albicans infections in IgH transgenic mice with V(H) derived from a natural anti-keratin antibody.

    PubMed

    Li, Wei; Fu, Meng; An, Jin-Gang; Xing, Ying; Zhang, Ping; Zhang, Xin; Wang, Yao-Chun; Li, Cheng-Xin; Tian, Rong; Su, Wen-Jing; Guan, Hai-Hong; Wang, Gang; Gao, Tian-Wen; Han, Hua; Liu, Yu-Feng

    2007-02-01

    Fungal infections have been increasing and life-threatening in recent years, but host immune responses, especially the humoral immunity, to fungi have not been fully understood. In the present study, we report that natural antibodies from unimmunized mice bind to Candida albicans. We established a monoclonal natural antibody, 3B4, which recognized a surface antigen located at germ tubes of C. albicans. The 3B4 antibody protected mice from C. albicans-induced death in passive immunization, by mechanisms involving suppressing germ tube formation and modulating phagocytosis. Interestingly, 3B4 also bound to a self-antigen keratin. To further study the generation and anti-C. albicans activities of natural antibodies in vivo, we constructed a mu chain transgenic mouse (TgV(H)3B4) using the V(H) gene from 3B4. TgV(H)3B4 had elevated serum anti-keratin/C. albicans IgM, and were resistant to C. albicans infections. Analyses of B cell development showed that in TgV(H)3B4, B cells secreting the anti-keratin/C. albicans antibodies were enriched in the B1 B cell compartment. Our findings reveal an important role of keratin-reactive natural antibodies in anti-C. albicans immune responses, and suggest that keratin may function in selecting B cells into the B1 B cell compartment, where natural antibodies are made to fight fungal infections. PMID:16925788

  16. Detection of catheter-related bloodstream infections by the Gram stain-acridine orange leukocyte cytospin test in hematopoietic stem cell transplant recipients.

    PubMed

    Abdelkefi, A; Achour, W; Torjman, L; Ben Othman, T; Ladeb, S; Lakhal, A; Allouche, H; Ben Hassen, A; Ben Abdeladhim, A

    2006-03-01

    In patients with central venous catheters (CVCs), catheter-related bloodstream infections (CRBI) are a prominent cause of morbidity, excess hospital costs, and in some cases mortality. The aim of this prospective study was to assess the validity of the Gram stain-acridine orange leukocyte cytospin (AOLC) test for the diagnosis of CRBI in hematopoietic stem cell transplant (HSCT) recipients with nontunnelled CVCs, using the differential-time-to-positivity (DTP)/clinical criteria as the criterion standard to define CRBIs. CVCs were externalized, nontunnelled, polyurethane double lumen catheters (Arrows, Readings, USA). All CVCs were placed in the subclavian vein by the infraclavicular approach, in the operating room. Catheters were inserted percutaneously, using the Seldinger technique. Study catheters were not exchanged over guidewires. Between May 2002 and December 2004, a total of 245 consecutive patients were included. Twenty-six of the 245 patients (10.6%) had CRBI as determined by the DTP method. The Gram stain-AOLC was positive in only two patients (7.6%) with a CRBI. Our results suggest that the Gram stain-AOLC test is not useful for the diagnosis of catheter-related bloodstream infection in HSCT recipients.2006. PMID:16462754

  17. Globally dispersed mobile drug-resistance genes in Gram-negative bacterial isolates from patients with bloodstream infections in a US urban general hospital

    PubMed Central

    Adams-Sapper, S.; Sergeevna-Selezneva, J.; Tartof, S.; Raphael, E.; Diep, B. An; Perdreau-Remington, F.

    2012-01-01

    Mobile drug-resistance genes with identical nucleic acid sequences carried by multidrug-resistant Escherichia coli strains that cause community-acquired infections are becomingly increasingly dispersed worldwide. Over a 2-year period, we analysed Gram-negative bacterial (GNB) pathogens from the blood of inpatients at an urban public hospital to determine what proportion of these isolates carried such globally dispersed drug-resistance genes. Of 376 GNB isolates, 167 (44 %) were Escherichia coli, 50 (13 %) were Klebsiella pneumoniae, 25 (7 %) were Pseudomonas aeruginosa, 25 (7 %) were Proteus mirabilis and 20 (5 %) were Enterobacter cloacae; the remainder (24 %) comprised 26 different GNB species. Among E. coli isolates, class 1 integrons were detected in 64 (38 %). The most common integron gene cassette configuration was dfrA17-aadA5, found in 30 (25 %) of 119 drug-resistant E. coli isolates and in one isolate of Moraxella morganii. Extended-spectrum β-lactamase (ESBL) genes were found in 16 E. coli isolates (10 %). These genes with identical sequences were found in nearly 40 % of bloodstream E. coli isolates in the study hospital, as well as in a variety of bacterial species from clinical and non-clinical sources worldwide. Thus, a substantial proportion of bloodstream infections among hospitalized patients were caused by E. coli strains carrying drug-resistance genes that are dispersed globally in a wide variety of bacterial species. PMID:22493279

  18. Controlled clinical evaluation of BACTEC Plus Aerobic/F and BacT/Alert Aerobic FAN bottles for detection of bloodstream infections.

    PubMed Central

    Pohlman, J K; Kirkley, B A; Easley, K A; Basille, B A; Washington, J A

    1995-01-01

    A total of 7,190 blood culture sets were obtained from adult patients with a suspected bloodstream infection. A 20-ml sample of blood was distributed equally between the aerobic FAN bottle which was monitored in the BacT/Alert system and a Plus Aerobic/F bottle which was monitored in the BACTEC 9240 system. A total of 988 positive cultures were obtained from 483 patients; however, only 453 positive cultures from 173 patients met the criteria for volume ( > or = ml per bottle) and clinical significance on the basis of concurrent case review required for data analysis. There were 25 and 68 false positives from the FAN and Plus Aerobic/F bottles, respectively. There were no statistically significant differences between systems in the number of positive cultures or septic episodes by species; however, the total number of Enterobacteriaceae and Pseudomonas aeruginosa isolates combined was significantly greater in the FAN bottle (P = 0.04). Detection times did not differ significantly between systems for positive cultures; however, episodes of Staphylococcus aureus bacteremia were detected significantly more rapidly from the FAN bottle (P = 0.005). There was no significant difference between systems in the detection of bloodstream infections in patients receiving antibiotics at the time of blood culture. PMID:8576333

  19. Candida albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration

    PubMed Central

    Hargarten, Jessica C.; Moore, Tyler C.; Petro, Thomas M.; Nickerson, Kenneth W.

    2015-01-01

    The polymorphic commensal fungus Candida albicans causes life-threatening disease via bloodstream and intra-abdominal infections in immunocompromised and transplant patients. Although host immune evasion is a common strategy used by successful human fungal pathogens, C. albicans provokes recognition by host immune cells less capable of destroying it. To accomplish this, C. albicans white cells secrete a low-molecular-weight chemoattractive stimulant(s) of macrophages, a phagocyte that they are able to survive within and eventually escape from. C. albicans opaque cells do not secrete this chemoattractive stimulant(s). We report here a physiological mechanism that contributes to the differences in the interaction of C. albicans white and opaque cells with macrophages. E,E-Farnesol, which is secreted by white cells only, is a potent stimulator of macrophage chemokinesis, whose activity is enhanced by yeast cell wall components and aromatic alcohols. E,E-farnesol results in up to an 8.5-fold increase in macrophage migration in vitro and promotes a 3-fold increase in the peritoneal infiltration of macrophages in vivo. Therefore, modulation of farnesol secretion to stimulate host immune recognition by macrophages may help explain why this commensal is such a successful pathogen. PMID:26195556

  20. Candida albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration.

    PubMed

    Hargarten, Jessica C; Moore, Tyler C; Petro, Thomas M; Nickerson, Kenneth W; Atkin, Audrey L

    2015-10-01

    The polymorphic commensal fungus Candida albicans causes life-threatening disease via bloodstream and intra-abdominal infections in immunocompromised and transplant patients. Although host immune evasion is a common strategy used by successful human fungal pathogens, C. albicans provokes recognition by host immune cells less capable of destroying it. To accomplish this, C. albicans white cells secrete a low-molecular-weight chemoattractive stimulant(s) of macrophages, a phagocyte that they are able to survive within and eventually escape from. C. albicans opaque cells do not secrete this chemoattractive stimulant(s). We report here a physiological mechanism that contributes to the differences in the interaction of C. albicans white and opaque cells with macrophages. E,E-Farnesol, which is secreted by white cells only, is a potent stimulator of macrophage chemokinesis, whose activity is enhanced by yeast cell wall components and aromatic alcohols. E,E-farnesol results in up to an 8.5-fold increase in macrophage migration in vitro and promotes a 3-fold increase in the peritoneal infiltration of macrophages in vivo. Therefore, modulation of farnesol secretion to stimulate host immune recognition by macrophages may help explain why this commensal is such a successful pathogen. PMID:26195556

  1. Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models

    PubMed Central

    Amorim-Vaz, Sara; Delarze, Eric; Ischer, Françoise; Sanglard, Dominique; Coste, Alix T

    2015-01-01

    The aim of the present study was to identify Candida albicans transcription factors (TFs) involved in virulence. Although mice are considered the gold-standard model to study fungal virulence, mini-host infection models have been increasingly used. Here, barcoded TF mutants were first screened in mice by pools of strains and fungal burdens (FBs) quantified in kidneys. Mutants of unannotated genes which generated a kidney FB significantly different from that of wild-type were selected and individually examined in Galleria mellonella. In addition, mutants that could not be detected in mice were also tested in G. mellonella. Only 25% of these mutants displayed matching phenotypes in both hosts, highlighting a significant discrepancy between the two models. To address the basis of this difference (pool or host effects), a set of 19 mutants tested in G. mellonella were also injected individually into mice. Matching FB phenotypes were observed in 50% of the cases, highlighting the bias due to host effects. In contrast, 33.4% concordance was observed between pool and single strain infections in mice, thereby highlighting the bias introduced by the “pool effect.” After filtering the results obtained from the two infection models, mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were subsequently tested in both hosts to validate previous results. The MBF1 mutant showed impaired infection in both models, while the ZCF6 mutant was only significant in mice infections. The two mutants showed no obvious in vitro phenotypes compared with the wild-type, indicating that these genes might be specifically involved in in vivo adapt PMID:25999923

  2. Impact of hospital care on incidence of bloodstream infection: the evaluation of processes and indicators in infection control study.

    PubMed Central

    Kritchevsky, S. B.; Braun, B. I.; Wong, E. S.; Solomon, S. L.; Steele, L.; Richards, C.; Simmons, B. P.

    2001-01-01

    The Evaluation of Processes and Indicators in Infection Control (EPIC) study assesses the relationship between hospital care and rates of central venous catheter-associated primary bacteremia in 54 intensive-care units (ICUs) in the United States and 14 other countries. Using ICU rather than the patient as the primary unit of statistical analysis permits evaluation of factors that vary at the ICU level. The design of EPIC can serve as a template for studies investigating the relationship between process and event rates across health-care institutions. PMID:11294704

  3. Thymol has antifungal activity against Candida albicans during infection and maintains the innate immune response required for function of the p38 MAPK signaling pathway in Caenorhabditis elegans.

    PubMed

    Shu, Chengjie; Sun, Lingmei; Zhang, Weiming

    2016-08-01

    The Caenorhabditis elegans model can be used to study Candida albicans virulence and host immunity, as well as to identify plant-derived natural products to use against C. albicans. Thymol is a hydrophobic phenol compound from the aromatic plant thyme. In this study, the in vitro data demonstrated concentration-dependent thymol inhibition of both C. albicans growth and biofilm formation during different developmental phases. With the aid of the C. elegans system, we performed in vivo assays, and our results further showed the ability of thymol to increase C. elegans life span during infection, inhibit C. albicans colony formation in the C. elegans intestine, and increase the expression levels of host antimicrobial genes. Moreover, among the genes that encode the p38 MAPK signaling pathway, mutation of the pmk-1 or sek-1 gene decreased the beneficial effects of thymol's antifungal activity against C. albicans and thymol's maintenance of the innate immune response in nematodes. Western blot data showed the level of phosphorylation of pmk-1 was dramatically decreased against C. albicans. In nematodes, treatment with thymol recovered the dysregulation of pmk-1 and sek-1 gene expressions, the phosphorylation level of PMK-1 caused by C. albicans infection. Therefore, thymol may act, at least in part, through the function of the p38 MAPK signaling pathway to protect against C. albicans infection and maintain the host innate immune response to C. albicans. Our results indicate that the p38 MAPK signaling pathway plays a crucial role in regulating the beneficial effects observed after nematodes infected with C. albicans were treated with thymol. PMID:26783030

  4. Evidence for macrophage-mediated protection against lethal Candida albicans infection.

    PubMed Central

    Bistoni, F; Vecchiarelli, A; Cenci, E; Puccetti, P; Marconi, P; Cassone, A

    1986-01-01

    Systemic infection of mice with a Candida albicans strain (PCA-2) incapable of yeast-mycelial conversion conferred protection against a subsequent intravenous challenge with the pathogenic strain of the parent organism, strain CA-6. Protection was nonspecific since it was also detected upon challenge of mice with Staphylococcus aureus. Moreover, the PCA-2 organisms had to be viable, their effects being most evident when they were given intravenously at a dose of 10(6) cells 7 to 14 days prior to microbial challenge. Thus, all mice pretreated with PCA-2 and challenged 14 days later with viable CA-6 cells lived through a 60-day observation period, whereas all control mice not treated with PCA-2 died within 3 days. In an attempt to correlate the immunostimulatory effects observed in vivo with possible modifications in in vitro functions, it was found that administration of PCA-2 was accompanied by an increase in the number of peripheral blood polymorphonuclear cells and by the activation in the spleen of cells with highly candidacidal activity in vitro. Moreover, the adoptive transfer of plastic-adherent cells from PCA-2-infected mice into histocompatible recipients conferred considerable protection against subsequent CA-6 challenge. PMID:3943907

  5. Editorial on low-dose acetylsalicylic acid treatment and impact on short-term mortality in Staphylococcus aureus bloodstream infection: a propensity score-matched cohort study.

    PubMed

    Schoergenhofer, Christian; Schwameis, Michael; Lagler, Heimo; Jilma, Bernd

    2016-05-01

    The manuscript "Low-Dose Acetylsalicylic Acid Treatment and Impact on Short-Term Mortality in Staphylococcus aureus (S. aureus) Bloodstream Infection: A propensity Score-Matched Cohort Study" published in Critical Care Medicine by Osthoff et al. reported an association of aspirin intake with a reduced short-term mortality. Direct anti-microbial effects of aspirin and its metabolite salicylate were suggested in preclinical studies. Especially intriguing is the inclusion of a control group with Escherichia coli (E. coli) blood stream infections in this study, in which aspirin was not associated with an improved outcome. However, as other observational studies also reported benefits of aspirin in critically ill patients, randomized trials are needed to confirm the effects of low-dose aspirin. PMID:27294095

  6. Editorial on low-dose acetylsalicylic acid treatment and impact on short-term mortality in Staphylococcus aureus bloodstream infection: a propensity score-matched cohort study

    PubMed Central

    Schoergenhofer, Christian; Schwameis, Michael; Lagler, Heimo

    2016-01-01

    The manuscript “Low-Dose Acetylsalicylic Acid Treatment and Impact on Short-Term Mortality in Staphylococcus aureus (S. aureus) Bloodstream Infection: A propensity Score-Matched Cohort Study” published in Critical Care Medicine by Osthoff et al. reported an association of aspirin intake with a reduced short-term mortality. Direct anti-microbial effects of aspirin and its metabolite salicylate were suggested in preclinical studies. Especially intriguing is the inclusion of a control group with Escherichia coli (E. coli) blood stream infections in this study, in which aspirin was not associated with an improved outcome. However, as other observational studies also reported benefits of aspirin in critically ill patients, randomized trials are needed to confirm the effects of low-dose aspirin. PMID:27294095

  7. Characterization of the extra-intestinal pathogenic Escherichia coli ST131 clone among isolates recovered from urinary and bloodstream infections in the United Kingdom.

    PubMed

    Ciesielczuk, H; Doumith, M; Hope, R; Woodford, N; Wareham, D W

    2015-12-01

    The multidrug-resistant ST131-O25b clone of Escherichia coli is well established as a significant cause of extra-intestinal infections worldwide. However, there have been only two small regional studies comparing ST131 isolates from the UK. Therefore, we characterized 143 ST131 E. coli (38 urinary, 105 bloodstream) collected between January 2011 and March 2012 from 38 centres located across the UK and Republic of Ireland. Phenotypic and genotypic characterization of clonal isolates revealed high rates of resistance to amoxicillin-clavulanate (56 %), cefotaxime (32 %), ciprofloxacin (79 %), temocillin (69 %, bloodstream isolates only), gentamicin (67 %) and trimethoprim-sulfamethoxazole (59 %). The most frequently detected extended-spectrum beta-lactamase was CTX-M-15 (87 %), predominantly encoded on IncF plasmids, although it was also associated with IncU plasmids in two isolates. The majority of UK ST131 clonal isolates possessed the O25b antigen (97 %) and the H30 fimH allele (92 %), but three serogroups (O19a, O136 and O153) novel to ST131 were identified among our strains. Contrary to previous reports, UK ST131-O16 isolates were typically susceptible to ciprofloxacin and lacked beta-lactamase genes (n = 12/12). In summary, ST131 strains of E. coli circulating in the UK possess characteristic clonal features, but are becoming more diverse than other international ST131 populations. PMID:26445772

  8. The adaptor CARD9 is required for adaptive but not innate immunity to oral mucosal Candida albicans infections.

    PubMed

    Bishu, Shrinivas; Hernández-Santos, Nydiaris; Simpson-Abelson, Michelle R; Huppler, Anna R; Conti, Heather R; Ghilardi, Nico; Mamo, Anna J; Gaffen, Sarah L

    2014-03-01

    Oropharyngeal candidiasis (OPC [thrush]) is an opportunistic infection caused by the commensal fungus Candida albicans. OPC is common in individuals with HIV/AIDS, infants, patients on chemotherapy, and individuals with congenital immune defects. Immunity to OPC is strongly dependent on the interleukin-23 (IL-23)/IL-17R axis, as mice and humans with defects in IL-17R signaling (IL17F, ACT1, IL-17RA) or in genes that direct Th17 differentiation (STAT3, STAT1, CARD9) are prone to mucocutaneous candidiasis. Conventional Th17 cells are induced in response to C. albicans infection via signals from C-type lectin receptors, which signal through the adaptor CARD9, leading to production of Th17-inducing cytokines such as IL-6, IL-1β, and IL-23. Recent data indicate that IL-17 can also be made by numerous innate cell subsets. These innate "type 17" cells resemble conventional Th17 cells, but they can be activated without need for prior antigen exposure. Because C. albicans is not a commensal organism in rodents and mice are thus naive to this fungus, we had the opportunity to assess the role of CARD9 in innate versus adaptive responses using an OPC infection model. As expected, CARD9(-/-) mice failed to mount an adaptive Th17 response following oral Candida infection. Surprisingly, however, CARD9(-/-) mice had preserved innate IL-17-dependent responses to Candida and were almost fully resistant to OPC. Thus, CARD9 is important primarily for adaptive immunity to C. albicans, whereas alternate recognition systems appear to be needed for effective innate responses. PMID:24379290

  9. Effects of glycyrrhizin, an active component of licorice roots, on Candida albicans infection in thermally injured mice

    PubMed Central

    Utsunomiya, T; Kobayashi, M; Herndon, D N; Pollard, R B; Suzuki, F

    1999-01-01

    Due to the generation of burn-associated CD8+ CD11b+ TCR γ/δ+ type 2 T cells (burn-associated type 2 T cells), the susceptibility of thermally injured mice to infection with C. albicans has been shown to be increased by up to 50-fold when compared with normal mice. Glycyrrhizin (GR), an active component of licorice roots, reduced the susceptibility of thermally injured mice to C. albicans infection to levels observed in normal mice. Thermally injured mice inoculated with CD4+ T cells from GR-treated mice were also resistant to C. albicans infection. The following demonstrated that susceptibility to fungal infection was similar in thermally injured mice and normal mice inoculated with T6S cells (a clone of burn-associated type 2 T cells). This susceptibility of T6S mice (normal mice inoculated with T6S cells) was reversible by (i) administration of GR, (ii) inoculation of CD4+ T cells from GR-treated mice, and (iii) injection of a mixture of MoAbs targeted against type 2 cytokines (IL-4 and IL-10). After stimulation with anti-CD3 MoAb, splenic T cells from thermally injured and T6S mice, treated with GR or inoculated with CD4+ T cells from GR-treated mice, did not have type 2 cytokines in culture supernatants. They were present in splenic T cell cultures from thermally injured and T6S mice that were treated with saline or inoculated with naive T cells. These results suggest that GR, by inducing CD4+ T cells which suppress type 2 cytokines produced by burn-associated type 2 T cells, improves the resistance of thermally injured mice to C. albicans. An anti-type 2 T cell action of the CD4+ T cells derived from GR-treated mice was previously described. PMID:10337021

  10. Pathway analysis of Candida albicans survival and virulence determinants in a murine infection model.

    PubMed

    Becker, Jeffrey M; Kauffman, Sarah J; Hauser, Melinda; Huang, Liyin; Lin, Molly; Sillaots, Susan; Jiang, Bo; Xu, Deming; Roemer, Terry

    2010-12-21

    One potentially rich source of possible targets for antifungal therapy are those Candida albicans genes deemed essential for growth under the standard culture (i.e., in vitro) conditions; however, these genes are largely unexplored as drug targets because essential genes are not experimentally amenable to conventional gene deletion and virulence studies. Using tetracycline-regulatable promoter-based conditional mutants, we investigated a murine model of candidiasis in which repressing essential genes in the host was achieved. By adding doxycycline to the drinking water starting 3 days prior to (dox - 3D) or 2 days post (dox + 2D) infection, the phenotypic consequences of temporal gene inactivation were assessed by monitoring animal survival and fungal burden in prophylaxis and acute infection settings. Of 177 selected conditional shut-off strains tested, the virulence of 102 was blocked under both repressing conditions, suggesting that the corresponding genes are essential for growth and survival in a murine host across early and established infection periods. Among these genes were those previously identified as antifungal drug targets (i.e., FKS1, ERG1, and ERG11), verifying that this methodology can be used to validate potential new targets. We also identify genes either conditionally essential or dispensable for in vitro growth but required for survival and virulence, including those in late stage ergosterol synthesis, or early steps in fatty acid or riboflavin biosynthesis. This study evaluates the role of essential genes with respect to pathogen virulence in a large-scale, systems biology context, and provides a general method for gene target validation and for uncovering unexpected antimicrobial targets. PMID:21135205

  11. Clinical Characteristics of Bloodstream Infections Due to Ampicillin-Sulbactam-Resistant, Non-Extended- Spectrum-β-Lactamase-Producing Escherichia coli and the Role of TEM-1 Hyperproduction▿

    PubMed Central

    Waltner-Toews, Rebecca I.; Paterson, David L.; Qureshi, Zubair A.; Sidjabat, Hanna E.; Adams-Haduch, Jennifer M.; Shutt, Kathleen A.; Jones, Mark; Tian, Guo-Bao; Pasculle, Anthony W.; Doi, Yohei

    2011-01-01

    Ampicillin-sulbactam is commonly used as an empirical therapy for invasive infections where Escherichia coli is a potential pathogen. We evaluated the clinical and microbiologic characteristics of bloodstream infection due to E. coli, with focus on cases that were nonsusceptible to ampicillin-sulbactam and not producing extended-spectrum β-lactamase (ESBL). Of a total of 357 unique bacteremic cases identified between 2005 and 2008, 111 (31.1%) were intermediate or resistant to ampicillin-sulbactam by disk testing. In multivariate analysis, a history of liver disease, organ transplant, peptic ulcer disease, and prior use of ampicillin-sulbactam were independent risk factors for bloodstream infection with ampicillin-sulbactam-nonsusceptible E. coli. Among cases that received ampicillin-sulbactam as an empirical therapy, an early clinical response was observed in 65% (22/34) of susceptible cases but in only 20% (1/5) of nonsusceptible cases. Among 50 ampicillin-sulbactam-resistant isolates examined, there was no clonal relatedness and no evidence of production of inhibitor-resistant TEM (IRT). Instead, the resistance was attributed to hyperproduction of TEM-1 β-lactamase in the majority of isolates. However, promoter sequences of blaTEM-1 did not predict resistance to ampicillin-sulbactam. While the plasmid copy number did not differ between representative resistant and susceptible isolates, the relative expression of blaTEM-1 was significantly higher in two of three resistant isolates than in three susceptible isolates. These results suggest high-level blaTEM-1 expression as the predominant cause of ampicillin-sulbactam resistance and also the presence of yet-unidentified factors promoting overexpression of blaTEM-1 in these isolates. PMID:21135189

  12. Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review.

    PubMed Central

    Warhurst, Geoffrey; Dunn, Graham; Chadwick, Paul; Blackwood, Bronagh; McAuley, Daniel; Perkins, Gavin D; McMullan, Ronan; Gates, Simon; Bentley, Andrew; Young, Duncan; Carlson, Gordon L; Dark, Paul

    2015-01-01

    BACKGROUND There is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen deoxyribonucleic acid (DNA) in blood samples within a few hours. SeptiFast (Roche Diagnostics GmBH, Mannheim, Germany) is a multipathogen probe-based system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection. As background to this study, we report a systematic review of Phase III diagnostic accuracy studies of SeptiFast, which reveals uncertainty about its likely clinical utility based on widespread evidence of deficiencies in study design and reporting with a high risk of bias. OBJECTIVE Determine the accuracy of SeptiFast real-time PCR for the detection of health-care-associated bloodstream infection, against standard microbiological culture. DESIGN Prospective multicentre Phase III clinical diagnostic accuracy study using the standards for the reporting of diagnostic accuracy studies criteria. SETTING Critical care departments within NHS hospitals in the north-west of England. PARTICIPANTS Adult patients requiring blood culture (BC) when developing new signs of systemic inflammation. MAIN OUTCOME MEASURES SeptiFast real-time PCR results at species/genus level compared with microbiological culture in association with independent adjudication of infection. Metrics of diagnostic accuracy were derived including sensitivity, specificity, likelihood ratios and predictive values, with their 95% confidence intervals (CIs). Latent class analysis was used to explore the diagnostic performance of culture as a reference standard. RESULTS Of 1006 new patient episodes of systemic inflammation in 853 patients, 922 (92%) met the inclusion criteria and provided sufficient information for analysis. Index test assay failure occurred on 69 (7%) occasions. Adult patients had been exposed to a median of 8 days (interquartile range 4

  13. Balancing Enthusiasm for Innovative Technologies with Optimizing Value: An Approach to Adopt New Laboratory Tests for Infectious Diseases Using Bloodstream Infections as Exemplar

    PubMed Central

    Culbreath, Karissa; Petti, Cathy A.

    2015-01-01

    A number of exciting new technologies have emerged to detect infectious diseases with greater accuracy and provide faster times to result in hopes of improving the provision of care and patient outcomes. However, the challenge in evaluating new methods lies not in the technical performance of tests but in (1) defining the specific advantages of new methods over the present gold standards in a practicable way and (2) understanding how advanced technologies will prompt changes in medical and public health decisions. With rising costs to deliver care, enthusiasm for innovative technologies should be balanced with a comprehensive understanding of clinical and laboratory ecosystems and how such factors influence the success or failure of test implementation. Selecting bloodstream infections as an exemplar, we provide a 6-step model for test adoption that will help clinicians and laboratorians better define the value of a new technology specific to their clinical practices. PMID:26180826

  14. Innovative Use of Existing Public and Private Data Sources for Postmarketing Surveillance of Central Line-Associated Bloodstream Infections Associated With Intravenous Needleless Connectors.

    PubMed

    Tabak, Ying P; Johannes, Richard S; Sun, Xiaowu; Crosby, Cynthia T; Jarvis, William R

    2016-01-01

    The Centers for Medicare and Medicaid Services (CMS) Hospital Compare central line-associated bloodstream infection (CLABSI) data and private databases containing new-generation intravenous needleless connector (study NC) use at the hospital level were linked. The relative risk (RR) of CLABSI associated with the study NCs was estimated, adjusting for hospital characteristics. Among 3074 eligible hospitals in the 2013 CMS database, 758 (25%) hospitals used the study NCs. The study NC hospitals had a lower unadjusted CLABSI rate (1.03 vs 1.13 CLABSIs per 1000 central line days, P < .0001) compared with comparator hospitals. The adjusted RR for CLABSI was 0.94 (95% confidence interval: 0.86, 1.02; P = .11). PMID:27598072

  15. Innovative Use of Existing Public and Private Data Sources for Postmarketing Surveillance of Central Line-Associated Bloodstream Infections Associated With Intravenous Needleless Connectors

    PubMed Central

    Tabak, Ying P.; Johannes, Richard S.; Sun, Xiaowu; Crosby, Cynthia T.

    2016-01-01

    The Centers for Medicare and Medicaid Services (CMS) Hospital Compare central line-associated bloodstream infection (CLABSI) data and private databases containing new-generation intravenous needleless connector (study NC) use at the hospital level were linked. The relative risk (RR) of CLABSI associated with the study NCs was estimated, adjusting for hospital characteristics. Among 3074 eligible hospitals in the 2013 CMS database, 758 (25%) hospitals used the study NCs. The study NC hospitals had a lower unadjusted CLABSI rate (1.03 vs 1.13 CLABSIs per 1000 central line days, P < .0001) compared with comparator hospitals. The adjusted RR for CLABSI was 0.94 (95% confidence interval: 0.86, 1.02; P = .11). PMID:27598072

  16. Bloodstream infections, antibiotic resistance and the practice of blood culture sampling in Germany: study design of a Thuringia-wide prospective population-based study (AlertsNet)

    PubMed Central

    Schmitz, Roland P; Rißner, Florian; Castell, Stefanie; Töpel, Sandra; Jakob, Matthias; Brunkhorst, Frank M; Mikolajczyk, Rafael T

    2015-01-01

    Introduction Bloodstream infections are a major cause of death worldwide; blood culture (BC) sampling remains the most important tool for their diagnosis. Current data suggest that BC rates in German hospitals are considerably lower than recommended; this points to shortfalls in the application of microbiological analyses. Since early and appropriate BC diagnostics are associated with reduced case fatality rates and a shorter duration of antimicrobial therapy, a multicomponent study for the improvement of BC diagnostics was developed. Methods and analysis An electronic BC registry established for the German Federal state of Thuringia is the structural basis of this study. The registry includes individual patient data (microbiological results and clinical data) and institutional information for all clinically relevant positive BCs at the participating centres. First, classic result quality indicators for bloodstream infections (eg, sepsis rates) will be studied using Poisson regression models (adjusted for institutional characteristics) in order to derive relative ranks for feedback to clinical institutions. Second, a target value will be established for the process indicator BC rate. On the basis of this target value, recommendations will be made for a given combination of institutional characteristics as a reference for future use in quality control. An interventional study aiming at the improvement of BC rates will be conducted thereafter. On the basis of the results of a survey in the participating institutions, a targeted educational intervention will be developed. The success of the educational intervention will be measured by changes in the process indicator and the result indicators over time using a pre–post design. Ethics and dissemination Ethics approval was obtained from the Ethics committee of the University Hospital Jena and from the Ethics committee of the State Chamber of Physicians of Thuringia. Findings of AlertsNet will be disseminated through

  17. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment.

    PubMed

    Zarkotou, O; Pournaras, S; Tselioti, P; Dragoumanos, V; Pitiriga, V; Ranellou, K; Prekates, A; Themeli-Digalaki, K; Tsakris, A

    2011-12-01

    Bloodstream infections (BSIs) caused by Klebsiella pneumoniae carbapenemases (KPC)-producing K. pneumoniae (KPC-KP) are associated with high mortality rates. We investigated outcomes, risk factors for mortality and impact of appropriate antimicrobial treatment in patients with BSIs caused by molecularly confirmed KPC-KP. All consecutive patients with KPC-KP BSIs between May 2008 and May 2010 were included in the study and followed-up until their discharge or death. Potential risk factors for infection mortality were examined by a case-control study. Case-patients were those who died from the BSI and control-patients those who survived. Appropriate antimicrobial therapy was defined as treatment with in vitro active antimicrobials for at least 48 h. A total of 53 patients were identified. Overall mortality was 52.8% and infection mortality was 34%. Appropriate antimicrobial therapy was administered to 35 patients; mortality due to infection occurred in 20%. All 20 patients that received combination schemes had favourable infection outcome; in contrast, seven of 15 patients given appropriate monotherapy died (p 0.001). In univariate analysis, risk factors for mortality were age (p <0.001), APACHE II score at admission and infection onset (p <0.001) and severe sepsis (p <0.001), while appropriate antimicrobial treatment (p 0.003), combinations of active antimicrobials (p 0.001), catheter-related bacteraemia (p 0.04), prior surgery (p 0.014) and other therapeutic interventions (p 0.015) were significantly associated with survival. Independent predictors of mortality were age, APACHE II score at infection onset and inappropriate antimicrobial treatment. Among them, appropriate treatment is the only modifiable independent predictor of infection outcome. PMID:21595793

  18. On the CUSP: Stop BSI: Evaluating the relationship between central line–associated bloodstream infection rate and patient safety climate profile

    PubMed Central

    Weaver, Sallie J.; Weeks, Kristina; Pham, Julius Cuong

    2015-01-01

    Background Central line–associated bloodstream infection (CLABSI) remains one of the most common and deadly hospital acquired infections in the United States. Creating a culture of safety is an important part of healthcare–associated infection improvement efforts; however, few studies have robustly examined the role of safety climate in patient safety outcomes. We applied a pattern-based approach to measuring safety climate to investigate the relationship between intensive care unit (ICU) patient safety climate profiles and CLABSI rates. Methods Secondary analyses of data collected from 237 adult ICUs participating in the On the CUSP: Stop BSI project. Unit-level baseline scores on the Hospital Survey on Patient Safety, a survey designed to assess patient safety climate, and CLABSI rates, were investigated. Three climate profile characteristics were examined: profile elevation, variability, and shape. Results Zero-inflated Poisson analyses suggested an association between the relative incidence of CLABSI and safety climate profile shape. K-means cluster analysis revealed 5 climate profile shapes. ICUs with conflicting climates and nonpunitive climates had a significantly higher CLABSI risk compared with ICUs with generative leadership climates. Conclusions Relative CLABSI risk was related to safety climate profile shape. None of the climate profile shapes was related to the odds of reporting zero CLABSI. Our findings support using pattern-based methods for examining safety climate rather than examining the relationships between each narrow dimension of safety climate and broader safety outcomes like CLABSI. PMID:25239711

  19. The Role of Autophagy-Related Proteins in Candida albicans Infections.

    PubMed

    Tam, Jenny M; Mansour, Michael K; Acharya, Mridu; Sokolovska, Anna; Timmons, Allison K; Lacy-Hulbert, Adam; Vyas, Jatin M

    2016-01-01

    Autophagy plays an important role in maintaining cell homeostasis by providing nutrients during periods of starvation and removing damaged organelles from the cytoplasm. A marker in the autophagic process is the reversible conjugation of LC3, a membrane scaffolding protein, to double membrane autophagosomes. Recently, a role for LC3 in the elimination of pathogenic bacteria and fungi, including Candida albicans (C. albicans), was demonstrated, but these organisms reside in single membrane phagosomes. This process is distinct from autophagy and is termed LC3-associated phagocytosis (LAP). This review will detail the hallmarks of LAP that distinguish it from classical autophagy and review the role of autophagy proteins in host response to C. albicans and other pathogenic fungi. PMID:27043636

  20. The Role of Autophagy-Related Proteins in Candida albicans Infections

    PubMed Central

    Tam, Jenny M.; Mansour, Michael K.; Acharya, Mridu; Sokolovska, Anna; Timmons, Allison K.; Lacy-Hulbert, Adam; Vyas, Jatin M.

    2016-01-01

    Autophagy plays an important role in maintaining cell homeostasis by providing nutrients during periods of starvation and removing damaged organelles from the cytoplasm. A marker in the autophagic process is the reversible conjugation of LC3, a membrane scaffolding protein, to double membrane autophagosomes. Recently, a role for LC3 in the elimination of pathogenic bacteria and fungi, including Candida albicans (C. albicans), was demonstrated, but these organisms reside in single membrane phagosomes. This process is distinct from autophagy and is termed LC3-associated phagocytosis (LAP). This review will detail the hallmarks of LAP that distinguish it from classical autophagy and review the role of autophagy proteins in host response to C. albicans and other pathogenic fungi. PMID:27043636

  1. Study of the prevalence and association of ocular chlamydial conjunctivitis in women with genital infection by Chlamydia trachomatis, Mycoplasma genitalium and Candida albicans attending outpatient clinic

    PubMed Central

    Khattab, Rania Abdelmonem; Abdelfattah, Maha Mohssen

    2016-01-01

    AIM To determine the association between chlamydial conjunctivitis and genital infection by Chlamydia trachomatis, Mycoplasma genitalium and Candida albicans, in addition to the possible relationship between cultured bacterial pathogens and oculogenital chlamydial infection. METHODS This study was performed on 100 (50 symptomatic and 50 asymptomatic) women attending the Gynecological and Obstetric outpatient clinic of Alzahra hospital, Alazhar University. Simultaneously a conjunctival swab was taken from these patients. Polymerase chain reaction (PCR) was done on DNA extracted from both vaginal and conjunctival swab samples. Culture for both vaginal and conjunctival swabs was also done. RESULTS Candida albicans was the predominant organism isolated by culture in 20% and 40% of conjunctival and vaginal swabs respectively. By the PCR method, ocular Chlamydia trachomatis was present in 60% of symptomatic women, while genital Chlamydia trachomatis infection was present in 30% of symptomatic women. The results of this method also indicated that 25/50 (50%) vaginal swabs were positive with PCR for Candida albicans versus 15/50 (30%) were PCR positive in conjunctival swab. Mycoplasma genitalium was present in only 10% of vaginal swabs. Concomitant oculogenital PCR positive results for Chlamydia trachomatis and Candida albicans were 30% and 28% respectively. CONCLUSION Ocular Chlamydia trachomatis was associated with genital Chlamydia trachomatis in a high percentage of women followed by Candida albicans. Cultured bacterial organisms do not play a role in enhancement of Chlamydia trachomatis infection. PMID:27588273

  2. National surveillance of nosocomial blood stream infection due to Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program.

    PubMed

    Pfaller, M A; Jones, R N; Messer, S A; Edmond, M B; Wenzel, R P

    1998-05-01

    Surveillance of nosocomial blood stream infections (BSI) in the USA between April 1995 and June 1996 revealed that Candida was the fourth leading cause of nosocomial BSI, accounting for 8% of all infections. Fifty-two percent of 379 episodes of candidemia were due to Candida albicans. In vitro susceptibility studies using the 1997 National Committee for Clinical Laboratory Standards reference method demonstrated that 92% of C. albicans isolates were susceptible to 5-fluorocytosine and 90% were susceptible to fluconazole and itraconazole. Geographic variation in susceptibility of fluconazole and itraconazole was observed. Isolates from the Northwest and Southeast regions were more frequently resistant to fluconazole (13.3-15.5%) and to itraconazole (17.2-20.0%) than those from the Northeast and Southwest regions (2.9-5.5% resistant to fluconazole and itraconazole). Continued surveillance for infections caused by C. albicans and other species of Candida among hospitalized patients is recommended. PMID:9597393

  3. Epidemiology of Candida infection. II. Application of biochemical methods for typing of Candida albicans strains.

    PubMed

    Budak, A

    1990-01-01

    Biochemical profiles of 350 C. albicans isolates from five towns in Poland and from Freiburg in Germany were determined on the basis of nine biochemical tests of Odds and Abbott method. API 20 C AUX system and additionally a resistogram. The analysis of the strains according to Odds' and Abbotts's system showed that investigated strains can be typed into 9 profile codes of common biochemical patterns. There were some differences among the profiles according to their geographical origin and anatomical sources of the isolation. On the basis of the ability C. albicans strains to assimilate of carbon sources, 350 isolates were categorised into 13 separate auxotrophic profiles with the major one: 2,576,174 accounting for 81% of the total. The majority of the investigated isolates were susceptible to antifungal agents (83%). A disproportionate distribution of auxotrophic profiles limited the use of resistogram method and API 20 C AUX as systems for typing C. albicans strains. On the other hand, the method of Odds and Abbott provides valuable criteria for typing of C. albicans. PMID:2130802

  4. Comparative efficacies of Zataria multiflora essential oil and itraconazole against disseminated Candida albicans infection in BALB/c mice

    PubMed Central

    Khosravi, A.R.; Shokri, H.; Tootian, Z.; Alizadeh, M.; Yahyaraeyat, R.

    2009-01-01

    Disseminated candidiasis is a serious problem in public health that results from the invasion of Candida species, in particular Candida albicans. The aim of this study was to compare the efficacies of Zataria multiflora essential oil and itraconazole in clearing C. albicans from the visceral organs of BALB/c mice suffered from disseminated candidiasis. Zataria multiflora essential oil was extracted using Clevenger-type apparatus and analyzed by gas chromatography mass spectrometry (GC-MS). For clearance experiment, mice (20-25 g, N=8 per group) received essential oil at doses of 30, 48 and 64 mg/kg and itraconazole at dose of 200 mg/kg intraperitoneally (IP) 2 days before and after intravenous inoculation of 0.5 × 106 C. albicans blastospores. The treated animals were sacrificed on day 20, and 0.1 g of the tissue homogenates was plated onto specific media. In GC-Mass, the main components of the essential oil were carvacrol (61.29%) and thymol (25.18%). The results demonstrated that IP administration of 64 mg/kg of the essential oil had the highest efficacy in reducing C. albicans and produced 39.5, 21.8, 141.5, 174 and 501-fold reductions in mean CFUs per 0.1 gram in Candida infections of the liver, spleen, lungs, brain and kidneys, respectively, compared to positive control. Itraconazole showed significantly more responsiveness than the essential oil at dose of 30 mg/kg in clearing C. albicans from the kidneys (P<0.02), brain (P<0.02) and spleen (P<0.04), and less responsiveness than that of 64 mg/kg in clearing the organism from the brain (P<0.01), lungs (P<0.0005) and kidneys (P<0.0005), whereas no significant difference was observed between this drug and Z. multiflora at dose of 48 mg/kg. These data explain the increased rate of yeast clearance and reduced dissemination to the viscera of Z. multiflora treated mice. PMID:24031384

  5. Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates.

    PubMed

    Gomez-Simmonds, Angela; Greenman, Michelle; Sullivan, Sean B; Tanner, Joshua P; Sowash, Madeleine G; Whittier, Susan; Uhlemann, Anne-Catrin

    2015-07-01

    Despite the growing importance of carbapenem-resistant Klebsiella pneumoniae (CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R) K. pneumoniae, and susceptible K. pneumoniae isolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of the wzi and blaKPC genes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. The blaKPC-3 gene (30%) was restricted to ST258/wzi154, whereas blaKPC-2 (70%) was observed for several wzi allele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas the K. pneumoniae susceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and the wzi154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted

  6. Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates

    PubMed Central

    Gomez-Simmonds, Angela; Greenman, Michelle; Sullivan, Sean B.; Tanner, Joshua P.; Sowash, Madeleine G.; Whittier, Susan

    2015-01-01

    Despite the growing importance of carbapenem-resistant Klebsiella pneumoniae (CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R) K. pneumoniae, and susceptible K. pneumoniae isolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of the wzi and blaKPC genes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. The blaKPC-3 gene (30%) was restricted to ST258/wzi154, whereas blaKPC-2 (70%) was observed for several wzi allele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas the K. pneumoniae susceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and the wzi154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted

  7. Effectiveness of Practices To Increase Timeliness of Providing Targeted Therapy for Inpatients with Bloodstream Infections: a Laboratory Medicine Best Practices Systematic Review and Meta-analysis

    PubMed Central

    Buehler, Stephanie S.; Madison, Bereneice; Snyder, Susan R.; Derzon, James H.; Saubolle, Michael A.; Weissfeld, Alice S.; Weinstein, Melvin P.; Liebow, Edward B.; Wolk, Donna M.

    2015-01-01

    SUMMARY Background. Bloodstream infection (BSI) is a major cause of morbidity and mortality throughout the world. Rapid identification of bloodstream pathogens is a laboratory practice that supports strategies for rapid transition to direct targeted therapy by providing for timely and effective patient care. In fact, the more rapidly that appropriate antimicrobials are prescribed, the lower the mortality for patients with sepsis. Rapid identification methods may have multiple positive impacts on patient outcomes, including reductions in mortality, morbidity, hospital lengths of stay, and antibiotic use. In addition, the strategy can reduce the cost of care for patients with BSIs. Objectives. The purpose of this review is to evaluate the evidence for the effectiveness of three rapid diagnostic practices in decreasing the time to targeted therapy for hospitalized patients with BSIs. The review was performed by applying the Centers for Disease Control and Prevention's (CDC's) Laboratory Medicine Best Practices Initiative (LMBP) systematic review methods for quality improvement (QI) practices and translating the results into evidence-based guidance (R. H. Christenson et al., Clin Chem 57:816–825, 2011, http://dx.doi.org/10.1373/clinchem.2010.157131). Search strategy. A comprehensive literature search was conducted to identify studies with measurable outcomes. A search of three electronic bibliographic databases (PubMed, Embase, and CINAHL), databases containing “gray” literature (unpublished academic, government, or industry evidence not governed by commercial publishing) (CIHI, NIHR, SIGN, and other databases), and the Cochrane database for English-language articles published between 1990 and 2011 was conducted in July 2011. Dates of search. The dates of our search were from 1990 to July 2011. Selection criteria. Animal studies and non-English publications were excluded. The search contained the following medical subject headings: bacteremia; bloodstream

  8. Candida albicans infection leads to barrier breakdown and a MAPK/NF-κB mediated stress response in the intestinal epithelial cell line C2BBe1.

    PubMed

    Böhringer, Michael; Pohlers, Susann; Schulze, Sylvie; Albrecht-Eckardt, Daniela; Piegsa, Judith; Weber, Michael; Martin, Ronny; Hünniger, Kerstin; Linde, Jörg; Guthke, Reinhard; Kurzai, Oliver

    2016-07-01

    Intestinal epithelial cells (IEC) form a tight barrier to the gut lumen. Paracellular permeability of the intestinal barrier is regulated by tight junction proteins and can be modulated by microorganisms and other stimuli. The polymorphic fungus Candida albicans, a frequent commensal of the human mucosa, has the capacity of traversing this barrier and establishing systemic disease within the host. Infection of polarized C2BBe1 IEC with wild-type C. albicans led to a transient increase of transepithelial electric resistance (TEER) before subsequent barrier disruption, accompanied by a strong decline of junctional protein levels and substantial, but considerably delayed cytotoxicity. Time-resolved microarray-based transcriptome analysis of C. albicans challenged IEC revealed a prominent role of NF-κB and MAPK signalling pathways in the response to infection. Hence, we inferred a gene regulatory network based on differentially expressed NF-κB and MAPK pathway components and their predicted transcriptional targets. The network model predicted activation of GDF15 by NF-κB was experimentally validated. Furthermore, inhibition of NF-κB activation in C. albicans infected C2BBe1 cells led to enhanced cytotoxicity in the epithelial cells. Taken together our study identifies NF-κB activation as an important protective signalling pathway in the response of epithelial cells to C. albicans. PMID:26752615

  9. Investigation of minor species Candida africana, Candida stellatoidea and Candida dubliniensis in the Candida albicans complex among Yaoundé (Cameroon) HIV-infected patients.

    PubMed

    Ngouana, Thierry K; Krasteva, Donika; Drakulovski, Pascal; Toghueo, Rufin K; Kouanfack, Charles; Ambe, Akaba; Reynes, Jacques; Delaporte, Eric; Boyom, Fabrice F; Mallié, Michèle; Bertout, Sébastien

    2015-01-01

    Minor species of the Candida albicans complex may cause overestimation of the epidemiology of C. albicans, and misidentifications could mask their implication in human pathology. Authors determined the occurrence of minor species of the C. albicans complex (C. africana, C. dubliniensis and C. stellatoidea) among Yaoundé HIV-infected patients, Cameroon. Stool, vaginal discharge, urine and oropharyngeal samples were analysed by mycological diagnosis. Isolates were identified by conventional methods and mass spectrometry (MS; carried out by the matrix-assisted laser desorption-ionisation time-of-flight MS protocol). Candida albicans isolates were thereafter submitted to the PCR amplification of the Hwp1 gene. The susceptibility of isolates to antifungal drugs was tested using the Clinical and Laboratory Standards Institute M27-A3 protocol. From 115 C. albicans obtained isolates, neither C. dubliniensis nor C. stellatoidea was observed; two strains of C. africana (422PV and 448PV) were identified by PCR electrophoretic profiles at 700 bp. These two C. africana strains were vaginal isolates. The isolate 448PV was resistant to ketoconazole at the minimal inhibitory concentration of 2 μg ml(-1), and showed reduced susceptibility to amphotericin B at 1 μg ml(-1). This first report on C. africana occurrence in Cameroon brings clues for the understanding of the global epidemiology of this yeast as well as that of minor species of the C. albicans complex. PMID:25289589

  10. A survey of Preventive Measures Used and their Impact on Central Line-Associated Bloodstream Infections (CLABSI) in Intensive Care Units (SPIN-BACC)

    PubMed Central

    2013-01-01

    Background The Quebec central line-associated bloodstream infections (CLABSI) in intensive care units (ICUs) Surveillance Program saw a decrease in CLABSI rates in most ICUs. Given the surveillance trends observed in recent years, we aimed to determine what preventive measures have been implemented, if compliance to measures was monitored and its impact on CLABSI incidence rates. Methods All hospitals participating in the Quebec healthcare-associated infections surveillance program (SPIN-BACC – n = 48) received a 77-question survey about preventive measures implemented and monitored in their ICU. The questionnaire was validated for construct, content, face validity, and reliability. We used Poisson regression to measure the association between compliance monitoring to preventive measures and CLABSI rates. Results Forty-two (88%) eligible hospitals completed the survey. Two components from the maximum barrier precautions were used less optimally: cap (88%) and full sterile body drape (71%). Preventive measures reported included daily review of catheter need (79%) and evaluation of insertion site for the presence of inflammation (90%). Two hospitals rewired lines even if an infection was suspected or documented. In adult ICUs, there was a statistically significant greater decrease in CLABSI rates in ICUs that monitored compliance to preventive insertion measures, after adjusting for teaching status and the number of hospital beds (p = 0.036). Conclusions Hospitals participating to the SPIN-BACC program follow recommendations for CLABSI prevention, but only a minority locally monitor their application. Compliance monitoring of preventive measures for catheter insertion was associated with a decrease in CLABSI incidence rates. PMID:24289473

  11. Risk factors for bloodstream infections due to colistin-resistant KPC-producing Klebsiella pneumoniae: results from a multicenter case-control-control study.

    PubMed

    Giacobbe, D R; Del Bono, V; Trecarichi, E M; De Rosa, F G; Giannella, M; Bassetti, M; Bartoloni, A; Losito, A R; Corcione, S; Bartoletti, M; Mantengoli, E; Saffioti, C; Pagani, N; Tedeschi, S; Spanu, T; Rossolini, G M; Marchese, A; Ambretti, S; Cauda, R; Viale, P; Viscoli, C; Tumbarello, M

    2015-12-01

    The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case-control-control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, ≥3 previous hospitalizations, Charlson score ≥3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score ≥3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals. PMID:26278669

  12. Determinants of Outcome in Hospitalized Patients With Methicillin-Resistant Staphylococcus aureus Bloodstream Infection: Results From National Surveillance in Canada, 2008-2012.

    PubMed

    Simor, Andrew E; Pelude, Linda; Golding, George; Fernandes, Rachel; Bryce, Elizabeth; Frenette, Charles; Gravel, Denise; Katz, Kevin; McGeer, Allison; Mulvey, Michael R; Smith, Stephanie; Weiss, Karl

    2016-04-01

    BACKGROUND Bloodstream infection (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA) is associated with considerable morbidity and mortality. OBJECTIVE To determine the incidence of MRSA BSI in Canadian hospitals and to identify variables associated with increased mortality. METHODS Prospective surveillance for MRSA BSI conducted in 53 Canadian hospitals from January 1, 2008, through December 31, 2012. Thirty-day all-cause mortality was determined, and logistic regression analysis was used to identify variables associated with mortality. RESULTS A total of 1,753 patients with MRSA BSI were identified (incidence, 0.45 per 1,000 admissions). The most common sites presumed to be the source of infection were skin/soft tissue (26.6%) and an intravascular catheter (22.0%). The most common spa types causing MRSA BSI were t002 (USA100/800; 55%) and t008 (USA300; 29%). Thirty-day all-cause mortality was 23.8%. Mortality was associated with increasing age (odds ratio, 1.03 per year [95% CI, 1.02-1.04]), the presence of pleuropulmonary infection (2.3 [1.4-3.7]), transfer to an intensive care unit (3.2 [2.1-5.0]), and failure to receive appropriate antimicrobial therapy within 24 hours of MRSA identification (3.2 [2.1-5.0]); a skin/soft-tissue source of BSI was associated with decreased mortality (0.5 [0.3-0.9]). MRSA genotype and reduced susceptibility to vancomycin were not associated with risk of death. CONCLUSIONS This study provides additional insight into the relative impact of various host and microbial factors associated with mortality in patients with MRSA BSI. The results emphasize the importance of ensuring timely receipt of appropriate antimicrobial agents to reduce the risk of an adverse outcome. PMID:26782274

  13. Implementation of central venous catheter bundle in an intensive care unit in Kuwait: Effect on central line-associated bloodstream infections.

    PubMed

    Salama, Mona F; Jamal, Wafaa; Al Mousa, Haifa; Rotimi, Vincent

    2016-01-01

    Central line-associated bloodstream infection (CLABSIs) is an important healthcare-associated infection in the critical care units. It causes substantial morbidity, mortality and incurs high costs. The use of central venous line (CVL) insertion bundle has been shown to decrease the incidence of CLABSIs. Our aim was to study the impact of CVL insertion bundle on incidence of CLABSI and study the causative microbial agents in an intensive care unit in Kuwait. Surveillance for CLABSI was conducted by trained infection control team using National Health Safety Network (NHSN) case definitions and device days measurement methods. During the intervention period, nursing staff used central line care bundle consisting of (1) hand hygiene by inserter (2) maximal barrier precautions upon insertion by the physician inserting the catheter and sterile drape from head to toe to the patient (3) use of a 2% chlorohexidine gluconate (CHG) in 70% ethanol scrub for the insertion site (4) optimum catheter site selection. (5) Examination of the daily necessity of the central line. During the pre-intervention period, there were 5367 documented catheter-days and 80 CLABSIs, for an incidence density of 14.9 CLABSIs per 1000 catheter-days. After implementation of the interventions, there were 5052 catheter-days and 56 CLABSIs, for an incidence density of 11.08 per 1000 catheter-days. The reduction in the CLABSI/1000 catheter days was not statistically significant (P=0.0859). This study demonstrates that implementation of a central venous catheter post-insertion care bundle was associated with a reduction in CLABSI in an intensive care area setting. PMID:26138518

  14. Clinical comparison of BACTEC 9240 plus aerobic/F resin bottles and the isolator aerobic culture system for detection of bloodstream infections.

    PubMed Central

    Cockerill, F R; Reed, G S; Hughes, J G; Torgerson, C A; Vetter, E A; Harmsen, W S; Dale, J C; Roberts, G D; Ilstrup, D M; Henry, N K

    1997-01-01

    The Plus Aerobic/F resin bottle of the BACTEC 9240 automated blood culture system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) was compared with aerobic culture of the Isolator system (Wampole Laboratories, Cranbury, N.J.) for the detection of bloodstream microorganisms from 6,145 blood cultures collected from adult patients with suspected septicemia. The BACTEC resin bottles were incubated for 7 days, and the sediment from the Isolator tube was inoculated to sheep blood and chocolate agars which were incubated for 72 h and to inhibitory mold, brain heart infusion, and Sabouraud agars which were incubated for 21 days. A total of 622 microorganisms were recovered from 583 blood cultures. The BACTEC resin bottle recovered statistically significantly more pathogens overall than the Isolator system (P = 0.0006). When individual pathogens isolated from either system for a 7-day study period were assessed, it was determined that the BACTEC resin bottle detected statistically significantly more isolates of Staphylococcus aureus (P = 0.0113) and coagulase-negative Staphylococcus spp. (P = 0.0029) than the Isolator system. The BACTEC resin bottle also detected statistically significantly more bloodstream infections (septic episodes) caused by coagulase-negative Staphylococcus spp. (P = 0.0146). The Isolator system recovered statistically significantly more contaminants overall (P < 0.0001), and among this group of microorganisms, recovered statistically significantly more Bacillus spp. (P < 0.0001), coagulase-negative Staphylococcus spp. (P < 0.0001), and viridans group Streptococcus spp. (P = 0.0156). The Isolator system detected statistically significantly more isolates of Histoplasma capsulatum (P = 0.004), but all of these isolates were detected at > or = 7 days of incubation of fungal plates, i.e., after the system to system comparison study period (7 days). In blood culture sets which produced growth of the same pathogen in both systems, there was a

  15. Clinical comparison of BACTEC 9240 plus aerobic/F resin bottles and the isolator aerobic culture system for detection of bloodstream infections.

    PubMed

    Cockerill, F R; Reed, G S; Hughes, J G; Torgerson, C A; Vetter, E A; Harmsen, W S; Dale, J C; Roberts, G D; Ilstrup, D M; Henry, N K

    1997-06-01

    The Plus Aerobic/F resin bottle of the BACTEC 9240 automated blood culture system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) was compared with aerobic culture of the Isolator system (Wampole Laboratories, Cranbury, N.J.) for the detection of bloodstream microorganisms from 6,145 blood cultures collected from adult patients with suspected septicemia. The BACTEC resin bottles were incubated for 7 days, and the sediment from the Isolator tube was inoculated to sheep blood and chocolate agars which were incubated for 72 h and to inhibitory mold, brain heart infusion, and Sabouraud agars which were incubated for 21 days. A total of 622 microorganisms were recovered from 583 blood cultures. The BACTEC resin bottle recovered statistically significantly more pathogens overall than the Isolator system (P = 0.0006). When individual pathogens isolated from either system for a 7-day study period were assessed, it was determined that the BACTEC resin bottle detected statistically significantly more isolates of Staphylococcus aureus (P = 0.0113) and coagulase-negative Staphylococcus spp. (P = 0.0029) than the Isolator system. The BACTEC resin bottle also detected statistically significantly more bloodstream infections (septic episodes) caused by coagulase-negative Staphylococcus spp. (P = 0.0146). The Isolator system recovered statistically significantly more contaminants overall (P < 0.0001), and among this group of microorganisms, recovered statistically significantly more Bacillus spp. (P < 0.0001), coagulase-negative Staphylococcus spp. (P < 0.0001), and viridans group Streptococcus spp. (P = 0.0156). The Isolator system detected statistically significantly more isolates of Histoplasma capsulatum (P = 0.004), but all of these isolates were detected at > or = 7 days of incubation of fungal plates, i.e., after the system to system comparison study period (7 days). In blood culture sets which produced growth of the same pathogen in both systems, there was a

  16. Genetic dissection of azole resistance mechanisms in Candida albicans and their validation in a mouse model of disseminated infection.

    PubMed

    MacCallum, Donna M; Coste, Alix; Ischer, Françoise; Jacobsen, Mette D; Odds, Frank C; Sanglard, Dominique

    2010-04-01

    Principal mechanisms of resistance to azole antifungals include the upregulation of multidrug transporters and the modification of the target enzyme, a cytochrome P450 (Erg11) involved in the 14alpha-demethylation of ergosterol. These mechanisms are often combined in azole-resistant Candida albicans isolates recovered from patients. However, the precise contributions of individual mechanisms to C. albicans resistance to specific azoles have been difficult to establish because of the technical difficulties in the genetic manipulation of this diploid species. Recent advances have made genetic manipulations easier, and we therefore undertook the genetic dissection of resistance mechanisms in an azole-resistant clinical isolate. This isolate (DSY296) upregulates the multidrug transporter genes CDR1 and CDR2 and has acquired a G464S substitution in both ERG11 alleles. In DSY296, inactivation of TAC1, a transcription factor containing a gain-of-function mutation, followed by sequential replacement of ERG11 mutant alleles with wild-type alleles, restored azole susceptibility to the levels measured for a parent azole-susceptible isolate (DSY294). These sequential genetic manipulations not only demonstrated that these two resistance mechanisms were those responsible for the development of resistance in DSY296 but also indicated that the quantitative level of resistance as measured in vitro by MIC determinations was a function of the number of genetic resistance mechanisms operating in any strain. The engineered strains were also tested for their responses to fluconazole treatment in a novel 3-day model of invasive C. albicans infection of mice. Fifty percent effective doses (ED(50)s) of fluconazole were highest for DSY296 and decreased proportionally with the sequential removal of each resistance mechanism. However, while the fold differences in ED(50) were proportional to the fold differences in MICs, their magnitude was lower than that measured in vitro and depended on

  17. Investigation and control of an outbreak of Enterobacter aerogenes bloodstream infection in a neonatal intensive care unit in Fiji.

    PubMed

    Narayan, Swastika A; Kool, Jacob L; Vakololoma, Miriama; Steer, Andrew C; Mejia, Amelita; Drake, Anne; Jenney, Adam; Turton, Jane F; Kado, Joseph; Tikoduadua, Lisi

    2009-08-01

    Ten neonates developed blood stream infection with extended-spectrum beta-lactamase-producing Enterobacter aerogenes in a neonatal intensive care unit in Fiji. The source of the outbreak was traced to a bag of contaminated normal saline in the ward, which was used for multiple patients. All isolates recovered from patients were indistinguishable from the bacteria recovered from the normal saline by pulsed-field gel electrophoresis. The outbreak was controlled using simple infection control practices such as reinforcement of strict hand hygiene policy, provision of single use vials of normal saline, and strict aseptic technique for injections. PMID:19552517

  18. A Central Line Care Maintenance Bundle for the Prevention of Central Line-Associated Bloodstream Infection in Non-Intensive Care Unit Settings.

    PubMed

    O'Neil, Caroline; Ball, Kelly; Wood, Helen; McMullen, Kathleen; Kremer, Pamala; Jafarzadeh, S Reza; Fraser, Victoria; Warren, David

    2016-06-01

    OBJECTIVE To evaluate a central line care maintenance bundle to reduce central line-associated bloodstream infection (CLABSI) in non-intensive care unit settings. DESIGN Before-after trial with 12-month follow-up period. SETTING A 1,250-bed teaching hospital. PARTICIPANTS Patients with central lines on 8 general medicine wards. Four wards received the intervention and 4 served as controls. INTERVENTION A multifaceted catheter care maintenance bundle consisting of educational programs for nurses, update of hospital policies, visual aids, a competency assessment, process monitoring, regular progress reports, and consolidation of supplies necessary for catheter maintenance. RESULTS Data were collected for 25,542 catheter-days including 43 CLABSI (rate, 1.68 per 1,000 catheter-days) and 4,012 catheter dressing observations. Following the intervention, a 2.5% monthly decrease in the CLABSI incidence density was observed on intervention floors but this was not statistically significant (95% CI, -5.3% to 0.4%). On control floors, there was a smaller but marginally significant decrease in CLABSI incidence during the study (change in monthly rate, -1.1%; 95% CI, -2.1% to -0.1%). Implementation of the bundle was associated with improvement in catheter dressing compliance on intervention wards (78.8% compliance before intervention vs 87.9% during intervention/follow-up; P<.001) but improvement was also observed on control wards (84.9% compliance before intervention vs 90.9% during intervention/follow-up; P=.001). CONCLUSIONS A multifaceted program to improve catheter care was associated with improvement in catheter dressing care but no change in CLABSI rates. Additional study is needed to determine strategies to prevent CLABSI in non-intensive care unit patients. Infect Control Hosp Epidemiol 2016;37:692-698. PMID:26999746

  19. Imbalanced Macrophage and Dendritic Cell Activations in Response to Candida albicans in a Murine Model of Diabetes Mellitus.

    PubMed

    Venturini, James; Fraga-Silva, Thais Fernanda Campos; Marchetti, Camila Martins; Mimura, Luiza Ayumi Nishiyama; Conti, Bruno José; Golim, Márjorie de Assis; Mendes, Rinaldo Poncio; de Arruda, Maria Sueli Parreira

    2016-07-01

    Bloodstream infections caused by Candida species are responsible for high morbidity and mortality, and diabetes mellitus (DM) is an important underlying disease in candidemia episodes. Although DM patients show an enhanced proinflammatory profile, they are highly susceptible to mycobacterial and mycotic infections. Attempting to understand this paradox, we investigated if imbalanced macrophage and dendritic cell (DC) activations could be associated to high incidence and/or severity of Candida albicans infection in the hypoinsulinemia-hyperglycemia (HH) milieu. HH alloxan-induced mice were infected with C. albicans and peritoneal aderent phagocytes were co-cultured with or without lipopolyssaccharide or heat-killed C. albicans, and the production of cytotoxic metabolites, cytokines, and chemokines was evaluated. We also evaluated the surface expression of MHC-II and CD86 in splenic DCs. Our findings showed that both uninfected and C. albicans-infected HH mice showed less production of CCL2 and reduced expression of CD86 by peritoneal phagocytes and splenic DCs, respectively. PMID:27105208

  20. Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene

    PubMed Central

    de Repentigny, Louis; Goupil, Mathieu; Jolicoeur, Paul

    2015-01-01

    IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC). Speculation about defective Th17 responses to oral C. albicans infection in the context of HIV infection prompted an investigation of innate and adaptive immune responses to Candida albicans in transgenic mice expressing the genome of HIV-1 in immune cells and displaying an AIDS-like disease. Defective IL-17 and IL-22-dependent mucosal responses to C. albicans were found to determine susceptibility to OPC in these transgenic mice. Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs. CD8+ T-cells recruited to the oral mucosa of the transgenic mice limited the proliferation of C. albicans in these conditions of CD4+ T-cell deficiency. Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination. PMID:26110288

  1. Genetics of Candida albicans.

    PubMed Central

    Scherer, S; Magee, P T

    1990-01-01

    Candida albicans is among the most common fungal pathogens. Infections caused by C. albicans and other Candida species can be life threatening in individuals with impaired immune function. Genetic analysis of C. albicans pathogenesis is complicated by the diploid nature of the species and the absence of a known sexual cycle. Through a combination of parasexual techniques and molecular approaches, an effective genetic system has been developed. The close relationship of C. albicans to the more extensively studied Saccharomyces cerevisiae has been of great utility in the isolation of Candida genes and development of the C. albicans DNA transformation system. Molecular methods have been used for clarification of taxonomic relationships and more precise epidemiologic investigations. Analysis of the physical and genetic maps of C. albicans and the closely related Candida stellatoidea has provided much information on the highly fluid nature of the Candida genome. The genetic system is seeing increased application to biological questions such as drug resistance, virulence determinants, and the phenomenon of phenotypic variation. Although most molecular analysis to data has been with C. albicans, the same methodologies are proving highly effective with other Candida species. Images PMID:2215421

  2. Successful Treatment of Bloodstream Infection Due to Metallo-β-Lactamase-Producing Stenotrophomonas maltophilia in a Renal Transplant Patient.

    PubMed

    Mojica, Maria F; Ouellette, Christopher P; Leber, Amy; Becknell, M Brian; Ardura, Monica I; Perez, Federico; Shimamura, Masako; Bonomo, Robert A; Aitken, Samuel L; Shelburne, Samuel A

    2016-09-01

    Stenotrophomonas maltophilia is an emerging multidrug-resistant (MDR) opportunistic pathogen for which new antibiotic options are urgently needed. We report our clinical experience treating a 19-year-old renal transplant recipient who developed prolonged bacteremia due to metallo-β-lactamase-producing S. maltophilia refractory to conventional treatment. The infection recurred despite a prolonged course of colistimethate sodium (colistin) but resolved with the use of a novel drug combination with clinical efficacy against the patient's S. maltophilia isolate. PMID:27551008

  3. Driving forces of vancomycin-resistant E. faecium and E. faecalis blood-stream infections in children

    PubMed Central

    2014-01-01

    Background Rates of invasive vancomycin-resistant Enterococcus (VRE) in the USA remains on the rise. Efforts to control vancomycin use and nosocomial transmission have had limited success in halting the spread of this pathogen. The role of antibiotic exposure remains a topic of controversy. We evaluated the association between emergence of VRE-blood-stream infections (BSI), aggregate and individual-patient vancomycin- exposure, and clonal transmission of VRE at an academic pediatric tertiary care hospital. Methods E. faecium and E. faecalis isolates recovered from blood specimens from hospitalized children from 2003–2010 were retrieved from the microbiology database. Aggregate vancomycin use and individual-patient vancomycin exposure 6 months preceding each event of bacteremia were recorded. Pulse-field electrophoresis was performed on selected VRE isolates. Results Of 151 episodes of E. faecium and E. faecalis BSI among hospitalized children <18 years of age, 9% (14) were due to VRE. Of these, 5 (36%) were due to nosocomial transmission. Aggregate (r .19, P = 0.3) and individual-patient vancomycin-exposure (X 2  = .26; P = .87) were not associated with VRE-BSI. On bivariate analysis, OR for developing VRE-BSI among patients infected with clonal isolates was 36 (P < .0001). Infection control interventions, rather than antimicrobial stewardship interventions to decrease vancomycin use, proved to be effective in reducing the rates of VRE-BSI. Conclusions In our experience, VRE-BSI was associated with nosocomial transmission and was independent of aggregate and individual-patient vancomycin-exposure. Molecular epidemiology is a crucial tool to differentiate the role of nosocomial transmission and antibiotic exposure in the emergence of invasive VRE infections among hospitalized children. PMID:25206975

  4. Bloodstream Infections Are an Improbable Cause of Positive Serum (1,3)-β-d-Glucan in Hematology Patients

    PubMed Central

    Mikulska, M.; Del Bono, V.; Guolo, F.; Minetto, P.; Gobbi, M.; Ghiso, A.; Bacigalupo, A.; Viscoli, C.

    2014-01-01

    Ninety-one serum samples from 51 hematology patients with bacteremia infections were tested for (1,3)-β-d-glucan (BG). Eleven samples (15%) from 7 patients (14%) were positive for BG. Of these 7 patients with positive BG results, 4 (8%) had invasive aspergillosis and 3 (6%) had no invasive fungal disease. Bacteremia was an unlikely cause of the false-positive BG results. PMID:24990906

  5. Epidemiology and Burden of Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae in a Pediatric Hospital in Senegal

    PubMed Central

    Ndir, Awa; Diop, Amadou; Faye, Pape Makhtar; Cissé, Moussa Fafa; Ndoye, Babacar; Astagneau, Pascal

    2016-01-01

    Context Severe bacterial infections are not considered as a leading cause of death in young children in sub-Saharan Africa. The worldwide emergence of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) could change the paradigm, especially in neonates who are at high risk of developing healthcare-associated infections. Objective To evaluate the epidemiology and the burden of ESBL-E bloodstream infections (BSI). Methods A case-case-control study was conducted in patients admitted in a pediatric hospital during two consecutive years. Cases were patients with Enterobacteriaceae BSI and included ESBL-positive (cases 1) and ESBL-negative BSI (cases 2). Controls were patients with no BSI. Multivariate analysis using a stepwise logistic regression was performed to identify risk factors for ESBL acquisition and for fatal outcomes. A multistate model was used to estimate the excess length of hospital stay (LOS) attributable to ESBL production while accounting for time of infection. Cox proportional hazards models were performed to assess the independent effect of ESBL-positive and negative BSI on LOS. Results The incidence rate of ESBL-E BSI was of 1.52 cases/1000 patient-days (95% CI: 1.2–5.6 cases per 1000 patient-days). Multivariate analysis showed that independent risk factors for ESBL-BSI acquisition were related to underlying comorbidities (sickle cell disease OR = 3.1 (95%CI: 2.3–4.9), malnutrition OR = 2.0 (95%CI: 1.7–2.6)) and invasive procedures (mechanical ventilation OR = 3.5 (95%CI: 2.7–5.3)). Neonates were also identified to be at risk for ESBL-E BSI. Inadequate initial antibiotic therapy was more frequent in ESBL-positive BSI than ESBL-negative BSI (94.2% versus 5.7%, p<0.0001). ESBL-positive BSI was associated with higher case-fatality rate than ESBL-negative BSI (54.8% versus 15.4%, p<0.001). Multistate modelling indicated an excess LOS attributable to ESBL production of 4.3 days. The adjusted end-of-LOS hazard ratio for ESBL

  6. Evaluation of the Broad-Range PCR/ESI-MS Technology in Blood Specimens for the Molecular Diagnosis of Bloodstream Infections

    PubMed Central

    Jordana-Lluch, Elena; Giménez, Montserrat; Quesada, Mª Dolores; Rivaya, Belén; Marcó, Clara; Domínguez, Mª Jesús; Arméstar, Fernando; Martró, Elisa; Ausina, Vicente

    2015-01-01

    Background Rapid identification of the etiological agent in bloodstream infections is of vital importance for the early administration of the most appropriate antibiotic therapy. Molecular methods may offer an advantage to current culture-based microbiological diagnosis. The goal of this study was to evaluate the performance of IRIDICA, a platform based on universal genetic amplification followed by mass spectrometry (PCR/ESI-MS) for the molecular diagnosis of sepsis-related pathogens directly from the patient’s blood. Methods A total of 410 whole blood specimens from patients admitted to Emergency Room (ER) and Intensive Care Unit (ICU) with clinical suspicion of sepsis were tested with the IRIDICA BAC BSI Assay (broad identification of bacteria and Candida spp.). Microorganisms grown in culture and detected by IRIDICA were compared considering blood culture as gold standard. When discrepancies were found, clinical records and results from other cultures were taken into consideration (clinical infection criterion). Results The overall positive and negative agreement of IRIDICA with blood culture in the analysis by specimen was 74.8% and 78.6%, respectively, rising to 76.9% and 87.2% respectively, when compared with the clinical infection criterion. Interestingly, IRIDICA detected 41 clinically significant microorganisms missed by culture, most of them from patients under antimicrobial treatment. Of special interest were the detections of one Mycoplasma hominis and two Mycobacterium simiae in immunocompromised patients. When ICU patients were analyzed separately, sensitivity, specificity, positive and negative predictive values compared with blood culture were 83.3%, 78.6%, 33.9% and 97.3% respectively, and 90.5%, 87.2%, 64.4% and 97.3% respectively, in comparison with the clinical infection criterion. Conclusions IRIDICA is a promising technology that offers an early and reliable identification of a wide variety of pathogens directly from the patient’s blood

  7. Immunoadjuvant activity of amphotericin B as displayed in mice infected with Candida albicans.

    PubMed Central

    Bistoni, F; Vecchiarelli, A; Mazzolla, R; Puccetti, P; Marconi, P; Garaci, E

    1985-01-01

    Mice receiving a single intraperitoneal injection of amphotericin B showed increased resistance to subsequent challenge with either Candida albicans or Staphylococcus aureus. This enhancement of resistance was obvious in terms of both survival criteria and clearance of the intravenously injected organism from different organs. The protective effect of amphotericin B was conditioned by dose, time of drug administration, and size of yeast or bacterial inoculum and was reversed by cyclophosphamide. Effector cells from mice treated with amphotericin B displayed enhanced fungicidal activity in vitro as measured in a short-term 51Cr release assay. Macrophages from intact animals exposed in vitro to amphotericin B also acquired strong candidacidal reactivity. PMID:3890731

  8. Azole resistance in oropharyngeal Candida albicans strains isolated from patients infected with human immunodeficiency virus.

    PubMed Central

    He, X; Tiballi, R N; Zarins, L T; Bradley, S F; Sangeorzan, J A; Kauffman, C A

    1994-01-01

    For 212 oropharyngeal isolates of Candida albicans, the fluconazole MICs for 50 and 90% of strains tested were 0.5 and 16 micrograms/ml, respectively, and those of itraconazole were 0.05 and 0.2 micrograms/ml, respectively. Of 16 isolates for which fluconazole MICs were > 64 micrograms/ml, itraconazole MICs for 14 were < or = 0.8 micrograms/ml and for 2 were > 6.4 micrograms/ml. Most fluconazole-resistant strains remained susceptible to itraconazole; whether itraconazole will prove effective for refractory thrush remains to be shown. PMID:7840596

  9. Principles of a New Protocol for Prediction of Azole Resistance in Candida albicans Infections on the Basis of ERG11 Polymorphisms.

    PubMed

    Caban, Monika; Strapagiel, Dominik; Dziadek, Jarosław; Korycka-Machała, Małgorzata; Grzelak, Agnieszka

    2016-08-01

    In recent years, Candida albicans infections treatment has become a growing problem because, among others, pathogenic strains are capable to develop resistance to the administered drugs. The elaboration of rapid and accurate method of resistance assessment is an important goal of many studies. They aim to avoid inappropriate dosage or drug choice, which may be life threatening in case of severe candidiasis. Here we propose a new protocol to predict C. albicans infections. The resistance prediction is based on high-resolution melt (HRM) analysis of ERG11 gene, especially, at the particularly unstable regions. Two statistically significant nucleotide polymorphisms were detected among twenty-seven strains isolated from saliva, one of which was silent mutation (Glu266Asp, Leu480Leu). We propose also HRM analysis as a convenient, simple and inexpensive method of preliminary selection of C. albicans DNA samples that vary in ERG11 nucleotide sequence within presumed region. Taken together, our study provides firm basis for the development of fast, simple and reliable methodology for diagnosis of C. albicans infections. PMID:27107760

  10. Genetic characteristics and antimicrobial resistance of Staphylococcus epidermidis isolates from patients with catheter-related bloodstream infections and from colonized healthcare workers in a Belgian hospital

    PubMed Central

    2014-01-01

    Background Staphylococcus epidermidis is a pathogen that is frequently encountered in the hospital environment. Healthcare workers (HCWs) can serve as a reservoir for the transmission of S. epidermidis to patients. Methods The aim of this study was to compare and identify differences between S. epidermidis isolated from 20 patients with catheter-related bloodstream infections (CRBSIs) and from the hands of 42 HCWs in the same hospital in terms of antimicrobial resistance, biofilm production, presence of the intercellular adhesion (ica) operon and genetic diversity (pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome (SCC) mec typing). Results S. epidermidis isolates that caused CRBSI were resistant to significantly more non-betalactam drugs than were isolates collected from HCWs. Among the 43 mecA positive isolates (26 from HCWs), the most frequent SCCmec type was type IV (44%). The ica operon was significantly more prevalent in CRBSI isolates than in HCWs (P < 0.05). Weak in vitro biofilm production seemed to correlate with the absence of the ica operon regardless of the commensal or pathogenic origin of the isolate. The 62 isolates showed high diversity in their PFGE patterns divided into 37 different types: 19 harbored only by the CRBSI isolates and 6 shared by the clinical and HCW isolates. MLST revealed a total of ten different sequence types (ST). ST2 was limited to CRBSI-specific PFGE types while the “mixed” PFGE types were ST5, ST16, ST88 and ST153. Conclusion One third of CRBSI episodes were due to isolates belonging to PFGE types that were also found on the hands of HCWs, suggesting that HCW serve as a reservoir for oxacillin resistance and transmission to patients. However, S. epidermidis ST2, mecA-positive and icaA-positive isolates, which caused the majority of clinically severe CRBSI, were not recovered from the HCW’s hands. PMID:24899534

  11. Clinical Outcomes Associated with Polymyxin B Dose in Patients with Bloodstream Infections Due to Carbapenem-Resistant Gram-Negative Rods

    PubMed Central

    Eiras, Daniel P.; Gomez-Simmonds, Angela; Loo, Angela S.; Satlin, Michael J.; Jenkins, Stephen G.; Whittier, Susan; Calfee, David P.; Furuya, E. Yoko

    2015-01-01

    There is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been defined. The purpose of this retrospective study was to evaluate the relationship between PMB dose and clinical outcomes. We included patients with bloodstream infections (BSIs) due to carbapenem-resistant Gram-negative rods who received ≥48 h of intravenous PMB. The objective was to evaluate the association between PMB dose and 30-day mortality, clinical cure at day 7, and development of acute kidney injury (AKI). A total of 151 BSIs were included. The overall 30-day mortality was 37.8% (54 of 151), and the median PMB dosage was 1.3 mg/kg (of total body weight)/day. Receipt of PMB dosages of <1.3 mg/kg/day was significantly associated with 30-day mortality (46.5% versus 26.3%; P = 0.02), and this association persisted in multivariable analysis (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.05 to 1.81; P = 0.04). Eighty-two percent of patients who received PMB dosages of <1.3 mg/kg/day had baseline renal impairment. Clinical cure at day 7 was not significantly different between dosing groups. AKI was more common in patients receiving PMB dosages of ≥250 mg/day (66.7% versus 32.0%; P = 0.03), and this association persisted in multivariable analysis (OR = 4.32; 95% CI = 1.15 to 16.25; P = 0.03). PMB dosages of <1.3 mg/kg/day were administered primarily to patients with renal impairment, and this dosing was independently associated with 30-day mortality. However, dosages of ≥250 mg/day were independently associated with AKI. These data support the use of PMB without dose reduction in the setting of renal impairment. PMID:26324272

  12. Use of Disinfection Cap to Reduce Central-Line–Associated Bloodstream Infection and Blood Culture Contamination Among Hematology–Oncology Patients

    PubMed Central

    Kamboj, Mini; Blair, Rachel; Bell, Natalie; Son, Crystal; Huang, Yao-Ting; Dowling, Mary; Lipitz-Snyderman, Allison; Eagan, Janet; Sepkowitz, Kent

    2016-01-01

    OBJECTIVE In this study, we examined the impact of routine use of a passive disinfection cap for catheter hub decontamination in hematology–oncology patients. SETTING A tertiary care cancer center in New York City METHODS In this multiphase prospective study, we used 2 preintervention phases (P1 and P2) to establish surveillance and baseline rates followed by sequential introduction of disinfection caps on high-risk units (HRUs: hematologic malignancy wards, hematopoietic stem cell transplant units and intensive care units) (P3) and general oncology units (P4). Unit-specific and hospital-wide hospital-acquired central-line–associated bloodstream infection (HA-CLABSI) rates and blood culture contamination (BCC) with coagulase negative staphylococci (CONS) were measured. RESULTS Implementation of a passive disinfection cap resulted in a 34% decrease in hospital-wide HA-CLABSI rates (combined P1 and P2 baseline rate of 2.66–1.75 per 1,000 catheter days at the end of the study period). This reduction occurred only among high-risk patients and not among general oncology patients. In addition, the use of the passive disinfection cap resulted in decreases of 63% (HRUs) and 51% (general oncology units) in blood culture contamination, with an estimated reduction of 242 BCCs with CONS. The reductions in HA-CLABSI and BCC correspond to an estimated annual savings of $3.2 million in direct medical costs. CONCLUSION Routine use of disinfection caps is associated with decreased HA-CLABSI rates among high-risk hematology oncology patients and a reduction in blood culture contamination among all oncology patients. PMID:26394849

  13. Comparison of colistin monotherapy and non-colistin combinations in the treatment of multi-drug resistant Acinetobacter spp. bloodstream infections: A Multicenter retrospective analysis

    PubMed Central

    Balkan, Ilker Inanc; Batirel, Ayse; Karabay, Oguz; Agalar, Canan; Akalin, Serife; Alici, Ozlem; Alp, Emine; Altay, Fatma Aybala; Altin, Nilgun; Arslan, Ferhat; Aslan, Turan; Bekiroglu, Nural; Cesur, Salih; Celik, Aygul Dogan; Dogan, Mustafa; Durdu, Bulent; Duygu, Fazilet; Engin, Aynur; Engin, Derya Ozturk; Gonen, Ibak; Guclu, Ertugrul; Guven, Tumer; Hatipoglu, Cigdem Ataman; Hosoglu, Salih; Karahocagil, Mustafa Kasim; Kilic, Aysegul Ulu; Ormen, Bahar; Ozdemir, Davut; Ozer, Serdar; Oztoprak, Nefise; Sezak, Nurbanu; Turhan, Vedat; Turker, Nesrin; Yilmaz, Hava

    2015-01-01

    Objectives: To compare the efficacy of colistin (COL) monotherapy versus non-COL based combinations in the treatment of bloodstream infections (BSIs) due to multidrug resistant Acinetobacter spp.(MDR-A). Materials and Methods: Retrospective data of 107 MDR-A BSI cases from 27 tertiary centers in Turkey were included. Primary End-Point: 14-day mortality. Secondary End-Points: Microbial eradication and clinical improvement. Results: Thirty-six patients in the COL monotherapy (CM) group and 71 in the non-COL based combinations (NCC) group were included in the study. Mean age was 59.98 ± 20 years (range: 18–89) and 50.5% were male. Median duration of follow-up was 40 days (range: 9–297). The 14-day survival rates were 52.8% in CM and 47.23% in NCC group (P = 0.36). Microbiological eradication was achieved in 69% of CM and 83% of NCC group (P = 0.13). Treatment failure was detected in 22.9% of cases in both CM and NCC groups. Univariate analysis revealed that mean age (P = 0.001), Charlson comorbidity index (P = 0.03), duration of hospital stay before MDR-A BSI (P = 0.04), Pitt bacteremia score (P = 0.043) and Acute Physiology and Chronic Health Evaluation II score (P = 0.05) were significant in terms of 14-day mortality. Advanced age (P = 0.01) and duration of hospital stay before MDR-A BSI (P = 0.04) were independently associated with 14-day mortality in multivariate analysis. Conclusion: No significant difference was detected between CM and non-COL based combinations in the treatment of MDR-A BSIs in terms of efficacy and 14-day mortality. PMID:25821319

  14. Prognosis of patients with methicillin-resistant Staphylococcus aureus bloodstream infection treated with teicoplanin: a retrospective cohort study investigating effect of teicoplanin minimum inhibitory concentrations

    PubMed Central

    2013-01-01

    Background The present study was designed to investigate whether teicoplanin minimum inhibitory concentrations (MICs) of methicillin-resistant Staphylococcus aureus (MRSA) isolates play a role in the prognosis of patient with teicoplanin-treated MRSA bloodstream infection (BSI). Methods Between 1 January 2006 and 31 December 2009, adult patients with teicoplanin-treated MRSA BSI in two Taiwan medical centers were retrospectively enrolled. Their blood MRSA isolates were submitted for determination of MICs to various antibiotics and multi-locus sequence types. All-cause mortalities on Days 14 and 30, as well as clinical response at the end of teicoplanin therapy were treated as endpoints. Results Two hundred seventy adult patients were enrolled and 210 blood MRSA isolates were available. Independent risk factors for un-favorable outcome at the end of teicoplanin therapy included septic shock (p < 0.0001) and an elevated C-reactive protein level (p = 0.0064). The independent risk factors for all-cause Day 14 mortality (13.0%) included the presence of auto-immune diseases (p = 0.0235), septic shock (p = 0.0253) and thrombocytopenia (p = 0.0018). The independent risk factors for all-cause Day 30 mortality (26.3%) included age (p = 0.0102), septic shock (p < 0.0001) and thrombocytopenia (p = 0.0059). Conclusions The current study didn’t find a significant role for teicoplanin MICs in the prognosis of adult patients with teicoplanin-treated MRSA BSI. PMID:23601053

  15. The Effect of Inadequate Initial Empiric Antimicrobial Treatment on Mortality in Critically Ill Patients with Bloodstream Infections: A Multi-Centre Retrospective Cohort Study

    PubMed Central

    Savage, Rachel D.; Fowler, Robert A.; Rishu, Asgar H.; Bagshaw, Sean M.; Cook, Deborah; Dodek, Peter; Hall, Richard; Kumar, Anand; Lamontagne, François; Lauzier, François; Marshall, John; Martin, Claudio M.; McIntyre, Lauralyn; Muscedere, John; Reynolds, Steven; Stelfox, Henry T.; Daneman, Nick

    2016-01-01

    Hospital mortality rates are elevated in critically ill patients with bloodstream infections. Given that mortality may be even higher if appropriate treatment is delayed, we sought to determine the effect of inadequate initial empiric treatment on mortality in these patients. A retrospective cohort study was conducted across 13 intensive care units in Canada. We defined inadequate initial empiric treatment as not receiving at least one dose of an antimicrobial to which the causative pathogen(s) was susceptible within one day of initial blood culture. We evaluated the association between inadequate initial treatment and hospital mortality using a random effects multivariable logistic regression model. Among 1,190 patients (1,097 had bacteremia and 93 had candidemia), 476 (40%) died and 266 (22%) received inadequate initial treatment. Candidemic patients more often had inadequate initial empiric therapy (64.5% versus 18.8%), as well as longer delays to final culture results (4 vs 3 days) and appropriate therapy (2 vs 0 days). After adjustment, there was no detectable association between inadequate initial treatment and mortality among bacteremic patients (Odds Ratio (OR): 1.02, 95% Confidence Interval (CI) 0.70–1.48); however, candidemic patients receiving inadequate treatment had nearly three times the odds of death (OR: 2.89, 95% CI: 1.05–7.99). Inadequate initial empiric antimicrobial treatment was not associated with increased mortality in bacteremic patients, but was an important risk factor in the subgroup of candidemic patients. Further research is warranted to improve early diagnostic and risk prediction methods in candidemic patients. PMID:27152615

  16. Use of Universal 16S rRNA Gene PCR as a Diagnostic Tool for Venous Access Port-Related Bloodstream Infections

    PubMed Central

    Marín, M.; Martín-Rabadán, P.; Echenagusia, A.; Camúñez, F.; Rodríguez-Rosales, G.; Simó, G.; Echenagusia, M.; Bouza, E.

    2013-01-01

    Amplification of the universal 16S rRNA gene using PCR has improved the diagnostic yield of microbiological samples. However, no data have been reported on the reliability of this technique with venous access ports (VAPs). We assessed the utility of 16S rRNA PCR for the prediction of VAP-related bloodstream infection (VAP-RBSI). During a 2-year period, we prospectively received all VAPs removed by interventional radiologists. PCR and conventional cultures were performed using samples from the different VAP sites. We compared the results of PCR with those of conventional culture for patients with confirmed VAP-RBSI. We collected 219 VAPs from 219 patients. Conventional VAP culture revealed 15 episodes of VAP-RBSI. PCR revealed a further 4 episodes in patients undergoing antibiotic therapy which would have gone undetected using conventional culture. Moreover, it had a negative predictive value of 97.8% for the prediction of VAP-RBSI when it was performed using biofilm from the internal surface of the port. In conclusion, universal 16S rRNA PCR performed with samples from the inside of VAPs proved to be a useful tool for the diagnosis of VAP-RBSI. It increased detection of VAP-RBSI episodes by 21.1% in patients undergoing antibiotic therapy whose episodes would have gone undetected using conventional culture. Therefore, we propose a new application of 16S rRNA PCR as a useful tool for the diagnosis of VAP-RBSI in patients receiving antibiotic therapy. PMID:23254136

  17. Catheter Related Bloodstream Infection (CR-BSI) in ICU Patients: Making the Decision to Remove or Not to Remove the Central Venous Catheter

    PubMed Central

    Deliberato, Rodrigo Octávio; Marra, Alexandre R.; Corrêa, Thiago Domingos; Martino, Marinês Dalla Vale; Correa, Luci; dos Santos, Oscar Fernando Pavão; Edmond, Michael B.

    2012-01-01

    Background Approximately 150 million central venous catheters (CVC) are used each year in the United States. Catheter-related bloodstream infections (CR-BSI) are one of the most important complications of the central venous catheters (CVCs). Our objective was to compare the in-hospital mortality when the catheter is removed or not removed in patients with CR-BSI. Methods We reviewed all episodes of CR-BSI that occurred in our intensive care unit (ICU) from January 2000 to December 2008. The standard method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and a positive semi quantitative (>15 CFU) culture of a catheter segment from where the same organism was isolated. The conservative method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and one of the following: (1) differential time period of CVC culture versus peripheral culture positivity of more than 2 hours, or (2) simultaneous quantitative blood culture with 5∶1 ratio (CVC versus peripheral). Results 53 CR-BSI (37 diagnosed by the standard method and 16 by the conservative method) were diagnosed during the study period. There was a no statistically significant difference in the in-hospital mortality for the standard versus the conservative method (57% vs. 75%, p = 0.208) in ICU patients. Conclusion In our study there was a no statistically significant difference between the standard and conservative methods in-hospital mortality. PMID:22403696

  18. Geographical Variability in the Likelihood of Bloodstream Infections Due to Gram-Negative Bacteria: Correlation with Proximity to the Equator and Health Care Expenditure

    PubMed Central

    Carmeli, Yehuda; Perencevich, Eli; Tuite, Ashleigh R.; Mermel, Leonard A.

    2014-01-01

    Objective Infections due to Gram-negative bacteria exhibit seasonal trends, with peak infection rates during warmer months. We hypothesized that the likelihood of a bloodstream infection due to Gram-negative bacteria increases with proximity to the equator. We tested this hypothesis and identified geographical, climatic and social factors associated with this variability. Design We established a network of 23 international centers in 22 cities. Setting: De-identified results of positive blood cultures from 2007–2011 and data sources for geographic, climatic and socioeconomic factors were assembled for each center. Participants Patients at the 23 centers with positive blood cultures. Main outcome Due to variability in the availability of total culture volumes across sites, our primary outcome measure was the fraction of positive blood cultures that yielded Gram-negative bacteria; sources of variability in this outcome measure were explored using meta-regression techniques. Results The mean fraction of bacteremia associated with Gram-negative bacteria was 48.4% (range 26.4% to 61.8%). Although not all sites displayed significant seasonality, the overall P-value for seasonal oscillation was significant (P<0.001). In univariate meta-regression models, temperature, latitude, latitude squared, longitude, per capita gross domestic product and percent of gross domestic product spent on healthcare were all associated with the fraction of bacteremia due to Gram-negative bacteria. In multivariable models, only percent of gross domestic product spent on healthcare and distance from the equator (ie. latitude squared) were significantly associated with the fraction of bacteremia due to Gram-negative bacteria. Conclusions The likelihood of bacteremia due to Gram-negative bacteria varies markedly between cities, in a manner that appears to have both geographic (latitude) and socioeconomic (proportion gross domestic product devoted to health spending) determinants. Thus, the

  19. Klebsiella variicola is a frequent cause of bloodstream infection in the stockholm area, and associated with higher mortality compared to K. pneumoniae.

    PubMed

    Maatallah, Makaoui; Vading, Malin; Kabir, Muhammad Humaun; Bakhrouf, Amina; Kalin, Mats; Nauclér, Pontus; Brisse, Sylvain; Giske, Christian G

    2014-01-01

    Clinical isolates of Klebsiella pneumoniae are divided into three phylogroups and differ in their virulence factor contents. The aim of this study was to determine an association between phylogroup, virulence factors and mortality following bloodstream infection (BSI) caused by Klebsiella pneumoniae. Isolates from all adult patients with BSI caused by K. pneumoniae admitted to Karolinska University Hospital, Solna between 2007 and 2009 (n = 139) were included in the study. Phylogenetic analysis was performed based on multilocus sequence typing (MLST) data. Testing for mucoid phenotype, multiplex PCR determining serotypes K1, K2, K5, K20, K54 and K57, and testing for virulence factors connected to more severe disease in previous studies, was also performed. Data was retrieved from medical records including age, sex, comorbidity, central and urinary catheters, time to adequate treatment, hospital-acquired infection, and mortality, to identify risk factors. The primary end-point was 30- day mortality. The three K. pneumoniae phylogroups were represented: KpI (n = 96), KpII (corresponding to K. quasipneumoniae, n = 9) and KpIII (corresponding to K. variicola, n = 34). Phylogroups were not significantly different in baseline characteristics. Overall, the 30-day mortality was 24/139 (17.3%). Isolates belonging to KpIII were associated with the highest 30-day mortality (10/34 cases, 29.4%), whereas KpI isolates were associated with mortality in 13/96 cases (13.5%). This difference was significant both in univariate statistical analysis (P = 0.037) and in multivariate analysis adjusting for age and comorbidity (OR 3.03 (95% CI: 1.10-8.36). Only three of the isolates causing mortality within 30 days belonged to any of the virulent serotypes (K54, n = 1), had a mucoid phenotype (n = 1) and/or contained virulence genes (wcaG n = 1 and wcaG/allS n = 1). In conclusion, the results indicate higher mortality among patients infected with

  20. Characterization of carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex isolates from nosocomial bloodstream infections in southern Iran.

    PubMed

    Pourabbas, Bahman; Firouzi, Roya; Pouladfar, Gholamreza

    2016-03-01

    Acinetobacter baumannii is an important opportunistic bacterial pathogen responsible for serious infections in hospitalized patients. From a total of 78 consecutive non-repetitive Acinetobacter spp. isolates from patients with blood infections, 61 were carbapenem resistant, which were positive for blaOXA-51-like (96.7%), blaOXA-23-like (77 %), blaOXA-58-like (8.1%) and blaOXA-40-like genes (32.8%) by multiplex PCR. The isolates were identified as A. baumannii (n = 59) and Acinetobacter nosocomialis (n = 2). Also, we found a case of Acinetobacter junii, causing bacteraemia, that possessed the IMP gene. High levels of resistance were observed to fluoroquinolones, aminoglycosides, tigecycline and to the beta-lactam antibiotics, including piperacillin/tazobactam and ampicillin/sulbactam. ISAba1 was present in 96.7% of all Acinetobacter calcoaceticus-baumannii complex (Acb) isolates. Also, 33 (54.1%) and 23 (37.7%) isolates harboured ISAba1 upstream of blaOXA-23-like and blaOXA-51-like genes, respectively, though this was not observed in A. nosocomialis isolates. No relationship was observed between the presence of ISAba1 upstream of oxacillinase genes and the level of carbapenem resistance in all Acb isolates. Only two genes encoding metallo-beta-lactamase (VIM, SPM) were detected in all Acb isolates. This suggests that carbapenem resistance in blood-isolate Acb is mostly due to the presence of acquired carbapenemases. This is the first report from Iran on the identification of A. nosocomialis isolates that possess multiple oxacillinase genes and lack upstream ISAba1. PMID:26747061

  1. Evaluation of Ag containing hydroxyapatite coatings to the Candida albicans infection.

    PubMed

    Ciuca, S; Badea, M; Pozna, E; Pana, I; Kiss, A; Floroian, L; Semenescu, A; Cotrut, C M; Moga, M; Vladescu, A

    2016-06-01

    In this research work, the synthesis of Ag doped hydroxyapatite coatings for dental or orthopedic implants was performed. The main goal was to determine the influence of Ag content on the roughness and antimicrobial performance of the prepared thin films. The films were deposited on Ti6Al4V alloy by means of RF magnetron sputtering. Those coatings were characterized by X-ray diffraction (XRD) and 3D surface profilometry. The antifungal activity after 1 and 7days of culture was evaluated in the presence of Candida albicans (ATCC - 10231). The increase of Ag content increased roughness and reduced the antifungal activity. The results showed that the Ag doped hydroxyapatite coatings can be a potential solution for the improvement of the antifungal activities of Ti based alloy. PMID:27021660

  2. Correlation between in vivo and in vitro studies of modulation of resistance to experimental Candida albicans infection by cyclophosphamide in mice.

    PubMed Central

    Bistoni, F; Baccarini, M; Blasi, E; Marconi, P; Puccetti, P; Garaci, E

    1983-01-01

    Mice receiving a single injection of cyclophosphamide (150 mg/kg) 1 to 6 days before inoculation with viable Candida albicans showed an increased susceptibility to the challenge accompanied by a reduction in peripheral blood polymorphonuclear leukocytes and lymphocytes as well as in spleen cellularity. Several immunological in vitro functions also appeared to be dramatically depressed. Most of these hematological and functional parameters returned to control values by day 9 after cyclophosphamide administration, at a time when resistance to C. albicans infection appeared to be unchanged. However, when exposure to cyclophosphamide occurred 12 to 21 days before inoculation with the live yeast, enhanced resistance was observed with the majority of the animals surviving challenge. To gain some insight into the mechanisms underlying this late increase in resistance to C. albicans infection after cyclophosphamide administration, we analyzed a series of immunological functions, including the in vitro candidacidal activity of polymorphonuclear neutrophils and plastic-adherent and nonadherent spleen cells as well as the activity of natural killer cells and alloreactive T lymphocytes. The results show that a numerical rebound of blood polymorphonuclear neutrophils and the appearance of a highly candidacidal cell population in the spleen may be among the factors underlying the late increase in resistance to C. albicans after administration of cyclophosphamide. PMID:6339410

  3. Correlation between in vivo and in vitro studies of modulation of resistance to experimental Candida albicans infection by cyclophosphamide in mice.

    PubMed

    Bistoni, F; Baccarini, M; Blasi, E; Marconi, P; Puccetti, P; Garaci, E

    1983-04-01

    Mice receiving a single injection of cyclophosphamide (150 mg/kg) 1 to 6 days before inoculation with viable Candida albicans showed an increased susceptibility to the challenge accompanied by a reduction in peripheral blood polymorphonuclear leukocytes and lymphocytes as well as in spleen cellularity. Several immunological in vitro functions also appeared to be dramatically depressed. Most of these hematological and functional parameters returned to control values by day 9 after cyclophosphamide administration, at a time when resistance to C. albicans infection appeared to be unchanged. However, when exposure to cyclophosphamide occurred 12 to 21 days before inoculation with the live yeast, enhanced resistance was observed with the majority of the animals surviving challenge. To gain some insight into the mechanisms underlying this late increase in resistance to C. albicans infection after cyclophosphamide administration, we analyzed a series of immunological functions, including the in vitro candidacidal activity of polymorphonuclear neutrophils and plastic-adherent and nonadherent spleen cells as well as the activity of natural killer cells and alloreactive T lymphocytes. The results show that a numerical rebound of blood polymorphonuclear neutrophils and the appearance of a highly candidacidal cell population in the spleen may be among the factors underlying the late increase in resistance to C. albicans after administration of cyclophosphamide. PMID:6339410

  4. Prevalence of Resistant Gram-Negative Bacilli in Bloodstream Infection in Febrile Neutropenia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Single Center Retrospective Cohort Study.

    PubMed

    Wang, Ling; Wang, Ying; Fan, Xing; Tang, Wei; Hu, Jiong

    2015-11-01

    Bloodstream infection (BSI) is an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the causative bacteria and identify risk factors for BSI associated mortality in febrile neutropenia patients undergoing HSCT, we collected the clinical and microbiological data from patients underwent HSCT between 2008 and 2014 and performed a retrospective analysis. Throughout the study period, among 348 episodes of neutropenic fever in patients underwent HSCT, 89 episodes in 85 patients had microbiological defined BSI with a total of 108 isolates. Gram-negative bacteria (GNB) were the most common isolates (76, 70.3%) followed by gram-positive bacteria (GPB, 29, 26.9%) and fungus (3, 2.8%). As to the drug resistance, 26 multiple drug resistance (MDR) isolates were identified. Resistant isolates (n = 23) were more common documented in GNB, mostly Escherichia coli (9/36, 25%) and Klebsiella pneumonia (6/24, 25%). A total of 12 isolated were resistant to carbapenem including 4 K pneumoniae (4/24, 16.7%), 3 Stenotrophomonas maltophilia, and 1 Pseudomonas aeruginosa and other 4 GNB isolates (Citrobacter freumdii, Pseudomonas stutzeri, Acinetobacter baumanii, and Chryseobacterium indologenes). As to the GPB, only 3 resistant isolates were documented including 2 methicillin-resistant isolates (Staphylococcus hominis and Arcanobacterium hemolysis) and 1 vancomycin-resistant Enterococcus faecium. Among these 85 patients with documented BSI, 11 patients died of BSI as primary or associated cause with a BSI-related mortality of 13.1 ± 3.7% and 90-day overall survival after transplantation at 80.0 ± 4.3%. Patients with high-risk disease undergoing allo-HSCT, prolonged neutropenia (≥15 days) and infection with carbapenem-resistant GNB were associated with BSI associated mortality in univariate and multivariate analyses. Our report revealed a prevalence of GNB in BSI of neutropenic patients undergoing

  5. Controlled Clinical Laboratory Comparison of Two Supplemented Aerobic and Anaerobic Media Used in Automated Blood Culture Systems To Detect Bloodstream Infections

    PubMed Central

    Ziegler, R.; Johnscher, I.; Martus, P.; Lenhardt, D.; Just, H.-M.

    1998-01-01

    A 20-ml blood sample was collected from adult patients with suspected bloodstream infections and distributed equally into the four volume-controlled bottles of a blood culture set consisting of aerobic and anaerobic BACTEC Plus/F bottles and aerobic and anaerobic BacT/Alert FAN bottles. All bottles were incubated in their respective instruments for a standard 5-day protocol or until the instruments signalled positivity. Samples in all bottles with negative results by these instruments were terminally subcultured. A total of 8,390 blood culture sets were obtained during the study period, of which 4,402 (52.5%) met the study criteria. Of these, 946 (21.5%) were positive either by instrument signal or by additional terminal subculture of all negative bottles and yielded growth of microorganisms. Five hundred eighty-nine (13.4%) blood culture sets were considered to have recovered 663 clinically significant organisms. When both the BACTEC and the BacT/Alert systems were used, 465 positive sets were detected; BACTEC alone detected 52 positive sets and BacT/Alert alone detected 72 (P = 0.09). No differences were found between the two systems in microbial recovery rate from blood cultures obtained from patients on antibiotic therapy. Significantly more members of the family Enterobacteriaceae (P < 0.01) were detected from patients without antimicrobial therapy by BacT/Alert than by BACTEC. The false-negative rates were 0.20% for BACTEC and 0.32% for BacT/Alert. A significantly higher false-positive rate was found for BACTEC (P < 0.0001). Both systems were comparable for the time to detection of microorganisms. However, gram-positive bacteria were detected faster by BACTEC and Enterobacteriaceae were detected faster on average by BacT/Alert. We concluded that both systems are comparable in their abilities to recover aerobic and anaerobic organisms from blood cultures and a terminal subculture might not be necessary for either of the two systems. The increased positivity

  6. Ethanol Lock Therapy (E-Lock) in the Prevention of Catheter-Related Bloodstream Infections (CR-BSI) after Major Heart Surgery (MHS): A Randomized Clinical Trial

    PubMed Central

    Pérez-Granda, María Jesús; Barrio, José María; Muñoz, Patricia; Hortal, Javier; Rincón, Cristina; Rabadán, Pablo Martin; Pernia, Maria Sagrario; Bouza, Emilio

    2014-01-01

    Background Lock-therapy with antimicrobials has been used for the treatment and prevention of catheter-related bloodstream infections (CR-BSI). Experiences with Ethanol-Locks (E-locks) have included therapeutic interventions with variable results. Patients undergoing Major Heart Surgery (MHS) are a high-risk population for CR-BSI.The aim of this study was to assess the efficacy and tolerance to E-Locks in the prevention of CR-BSI of patients undergoing MHS. Methods and Findings This is an academic, prospective, randomized, non-blinded and controlled clinical trial assessing the incidence of CR-BSI of patients with E-locks (E-lock) and the tolerance to the procedure in comparison with patients receiving conventional catheter-care (CCC). Patients undergoing MHS with intravascular catheters for more than 48 hours were randomly assigned into treatment or control group by a computer-generated list of randomly assigned numbers. In the treatment group, all their catheter lumens were locked with an ethanol solution at 70% for two hours, every three days (E-Locks). The control group received conventional catheter-care (CCC). Overall, 200 patients with 323 catheters were included in the study, which was stopped after 10 months due to adverse events. Of them, 179 catheters (113 patients) had E-Locks and 144 catheters (87 patients) were CCC. Euroscore Surgical Risk in both groups was 4.04 vs 4.07 p = 0.94 respectively. The results for the E-Locks and CCC were as follows: Incidence of CR-BSI/1000 days of exposure 2.1 vs 5.2 (p = 0.33), catheter tip colonization 14 (7.8%) vs 6 (4.2%) patients (p = 0.17), median length of hospital stay, 15 vs 16 days (p = 0.77). Seven patients (6.19%), all in the ethanol branch, had to discontinue the trial due to intolerance or adverse events. Conclusions We do not recommend prophylaxis of CR-BSI with ethanol-lock on a routine basis in patients undergoing Major Heart Surgery. Trial Registration Clinical Trials.gov NCT01229592

  7. A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae.

    PubMed

    Gutiérrez-Gutiérrez, Belén; Pérez-Galera, Salvador; Salamanca, Elena; de Cueto, Marina; Calbo, Esther; Almirante, Benito; Viale, Pierluigi; Oliver, Antonio; Pintado, Vicente; Gasch, Oriol; Martínez-Martínez, Luis; Pitout, Johann; Akova, Murat; Peña, Carmen; Molina, José; Hernández, Alicia; Venditti, Mario; Prim, Nuria; Origüen, Julia; Bou, German; Tacconelli, Evelina; Tumbarello, Mario; Hamprecht, Axel; Giamarellou, Helen; Almela, Manel; Pérez, Federico; Schwaber, Mitchell J; Bermejo, Joaquín; Lowman, Warren; Hsueh, Po-Ren; Mora-Rillo, Marta; Natera, Clara; Souli, Maria; Bonomo, Robert A; Carmeli, Yehuda; Paterson, David L; Pascual, Alvaro; Rodríguez-Baño, Jesús

    2016-07-01

    The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.). PMID:27139473

  8. A Competitive Infection Model of Hematogenously Disseminated Candidiasis in Mice Redefines the Role of Candida albicans IRS4 in Pathogenesis

    PubMed Central

    Raman, Suresh B.; Nguyen, M. Hong; Cheng, Shaoji; Badrane, Hassan; Iczkowski, Kenneth A.; Wegener, Marilyn; Gaffen, Sarah L.; Mitchell, Aaron P.

    2013-01-01

    Candida albicans IRS4 encodes a protein that regulates phosphatidylinositol-(4,5)-bisphosphate, which was shown to contribute to hematogenously disseminated candidiasis (DC) after several days in the standard mouse model. Our objective was to more accurately define the temporal contributions of IRS4 to pathogenesis. During competition assays in vitro, an irs4-null (Δirs4) mutant exhibited wild-type fitness. In DC experiments, mice were infected intravenously with the Δirs4 mutant, strain CAI-12 (1 × 105 CFU), or a mixture of the strains (0.5 × 105 CFU each). In single-strain infections, quantitative PCR revealed reduced Δirs4 mutant burdens within kidneys at days 1, 4, and 7 but not 6 h. In competitive infections, the Δirs4 mutant was outcompeted by CAI-12 in each mouse at ≥6 h (competitive indices, P ≤ 0.0001). At 4 and 7 days, the Δirs4 mutant burdens during competitive infections were significantly lower than those during single-strain infections (P = 0.01 and P < 0.001, respectively), suggesting increased susceptibility to inflammatory responses. Phagocytic infiltration of kidneys in response to CAI-12 or competitive infections was significantly greater than that in response to Δirs4 mutant infection at days 1 and 4 (P < 0.001), and the Δirs4 mutant was more susceptible to phagocytosis and killing by human polymorphonuclear cells (P = 0.01 and P = 0.006, respectively) and mouse macrophages in vitro (P = 0.04 and P = 0.01, respectively). Therefore, IRS4 contributes to tissue invasion at early stages of DC and mediates resistance to phagocytosis as DC progresses. Microarray analysis revealed remarkably similar gene expression by the Δirs4 mutant and reference strain CAI-12 within blood, suggesting that IRS4 is not significantly involved in the hematogenous stage of disease. A competitive DC model detects attenuated virulence that is not evident with the standard model. PMID:23429534

  9. Candida albicans killing by RAW 264.7 mouse macrophage cells: effects of Candida genotype, infection ratios, and gamma interferon treatment.

    PubMed

    Marcil, A; Harcus, D; Thomas, D Y; Whiteway, M

    2002-11-01

    Phagocytic cells such as neutrophils and macrophages are potential components of the immune defense that protects mammals against Candida albicans infection. We have tested the interaction between the mouse macrophage cell line RAW 264.7 and a variety of mutant strains of C. albicans. We used an end point dilution assay to monitor the killing of C. albicans at low multiplicities of infection (MOIs). Several mutants that show reduced virulence in mouse systemic-infection models show reduced colony formation in the presence of macrophage cells. To permit analysis of the macrophage-Candida interaction at higher MOIs, we introduced a luciferase reporter gene into wild-type and mutant Candida cells and used loss of the luminescence signal to quantify proliferation. This assay gave results similar to those for the end point dilution assay. Activation of the macrophages with mouse gamma interferon did not enhance anti-Candida activity. Continued coculture of the Candida and macrophage cells eventually led to death of the macrophages, but for the RAW 264.7 cell line this was not due to apoptotic pathways involving caspase-8 or -9 activation. In general Candida cells defective in the formation of hyphae were both less virulent in animal models and more sensitive to macrophage engulfment and growth inhibition. However the nonvirulent, hypha-defective cla4 mutant line was considerably more resistant to macrophage-mediated inhibition than the wild-type strain. Thus although mutants sensitive to engulfment are typically less virulent in systemic-infection models, sensitivity to phagocytic macrophage cells is not the unique determinant of C. albicans virulence. PMID:12379711

  10. Enhanced efficacy of synergistic combinations of antimicrobial peptides with caspofungin versus Candida albicans in insect and murine models of systemic infection.

    PubMed

    MacCallum, D M; Desbois, A P; Coote, P J

    2013-08-01

    The objective of this study was to determine whether combinations of antimicrobial peptides (AMPs) with caspofungin display enhanced antifungal activity versus Candida albicans in vitro and in vivo. Three conventional AMPs that satisfied criteria favouring their potential development as novel antifungals were selected for investigation. Colistin sulphate was also included as a cyclic peptide antibiotic used in the clinic. Minimum inhibitory concentrations (MICs) were determined for each antifungal agent and checkerboard assays were used to determine fractional inhibitory concentration index (FICI) values for dual combinations of AMPs or colistin with caspofungin. Viability assays were performed for the same combinations in order to investigate fungicidal interactions. Synergistic antifungal combinations were then tested for efficacy in vivo and compared to monotherapies in wax moth larva and murine models of systemic C. albicans infection. In combination with caspofungin, each of the AMPs [hMUC7-12, DsS3(1-16), hLF(1-11)] and colistin were synergistic and candidacidal in vitro. The treatment of infected wax moth larvae with combinations of caspofungin with hMUC7-12, DsS3(1-16) or colistin resulted in significant enhancements in survival compared to treatment with monotherapies. Notably, the treatment of C. albicans-infected mice with a combination of caspofungin and DsS3(1-16) resulted in the enhancement of survival compared to groups treated with just the individual agents. This study demonstrates that combination therapies containing caspofungin and AMPs or colistin merit further development as potential novel treatments for C. albicans infections. PMID:23572153

  11. Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis.

    PubMed

    Cleary, Ian A; Reinhard, Sara M; Lazzell, Anna L; Monteagudo, Carlos; Thomas, Derek P; Lopez-Ribot, Jose L; Saville, Stephen P

    2016-03-01

    The opportunistic fungal pathogen Candida albicans is an increasingly common threat to human health. Candida albicans grows in several morphologies and mutant strains locked in yeast or filamentous forms have attenuated virulence in the murine model of disseminated candidiasis. Thus, the ability to change shape is important for virulence. The transcriptional repressors Nrg1p and Tup1p are required for normal regulation of C. albicans morphology. Strains lacking either NRG1 or TUP1 are constitutively pseudohyphal under yeast growth conditions, and display attenuated virulence in the disseminated model. To dissect the relative importance of hyphae and pseudohyphae during an infection, we used strains in which the morphological transition could be externally manipulated through controlled expression of NRG1 or TUP1. Remarkably, hyphal form inocula retain the capacity to cause disease. Whilst induction of a pseudohyphal morphology through depletion of TUP1 did result in attenuated virulence, this was not due to a defect in the ability to escape the bloodstream. Instead, we observed that pseudohyphal cells are cleared from tissues much more efficiently than either hyphal (virulent) or yeast form (avirulent) cells, indicating that different C. albicans morphologies have distinct interactions with host cells during an infection. PMID:26851404

  12. Disruption of the Candida albicans TPS1 gene encoding trehalose-6-phosphate synthase impairs formation of hyphae and decreases infectivity.

    PubMed

    Zaragoza, O; Blazquez, M A; Gancedo, C

    1998-08-01

    The TPS1 gene from Candida albicans, which encodes trehalose-6-phosphate synthase, has been cloned by functional complementation of a tps1 mutant from Saccharomyces cerevisiae. In contrast with the wild-type strain, the double tps1/tps1 disruptant did not accumulate trehalose at stationary phase or after heat shock. Growth of the tps1/tps1 disruptant at 30 degreesC was indistinguishable from that of the wild type. However, at 42 degreesC it did not grow on glucose or fructose but grew normally on galactose or glycerol. At 37 degreesC, the yeast-hypha transition in the mutant in glucose-calf serum medium did not occur. During growth at 42 degreesC, the mutant did not form hyphae in galactose or in glycerol. Some of the growth defects observed may be traced to an unbalanced sugar metabolism that reduces the cellular content of ATP. Mice inoculated with 10(6) CFU of the tps1/tps1 mutant did not show visible symptoms of infection 16 days after inoculation, while those similarly inoculated with wild-type cells were dead 12 days after inoculation. PMID:9683476

  13. Skin Immunity to Candida albicans.

    PubMed

    Kashem, Sakeen W; Kaplan, Daniel H

    2016-07-01

    Candida albicans is a dimorphic commensal fungus that colonizes healthy human skin, mucosa, and the reproductive tract. C. albicans is also a predominantly opportunistic fungal pathogen, leading to disease manifestations such as disseminated candidiasis and chronic mucocutaneous candidiasis (CMC). The differing host susceptibilities for the sites of C. albicans infection have revealed tissue compartmentalization with tailoring of immune responses based on the site of infection. Furthermore, extensive studies of host genetics in rare cases of CMC have identified conserved genetic pathways involved in immune recognition and the response to the extracellular pathogen. We focus here on human and mouse skin as a site of C. albicans infection, and we review established and newly discovered insights into the cellular pathways that promote cutaneous antifungal immunity. PMID:27178391

  14. In vitro activities of voriconazole (UK-109,496) against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients with human immunodeficiency virus infection.

    PubMed Central

    Ruhnke, M; Schmidt-Westhausen, A; Trautmann, M

    1997-01-01

    The susceptibility of Candida albicans to a new antifungal triazole, voriconazole (UK-109,496), was investigated in 105 isolates obtained from the oral cavities of patients with human immunodeficiency virus (HIV) infection to study this drug's activity against fluconazole-susceptible and -resistant isolates. MICs were determined by a broth microdilution technique according to document M27-T from the National Committee for Clinical Laboratory Standards and by using a broth microdilution technique and a synthetic high-resolution medium. These antifungal susceptibility testing methods showed high levels of agreement (93% for fluconazole and 86% for voriconazole). Data from in vitro studies showed that voriconazole has good activity against fluconazole-susceptible and -resistant C. albicans isolates; the MICs at which 90% of all isolates were inhibited were 0.19 to 0.39 microgram/ml. We found that for isolates for which fluconazole MICs were high, voriconazole MICs were proportionally higher than those for fluconazole-susceptible C.albicans (P < 0.001). Pretreatment isolates from six patients with fluconazole-refractory esophageal candidiasis were included in the study. For these isolates the MICs were < or = 0.39 microgram/ml, and all patients responded to voriconazole. These results suggest that voriconazole is effective even in the treatment of fluconazole-refractory esophageal candidiasis and should be studied further to determine its clinical relevance in patients with HIV infection. PMID:9055995

  15. Transcriptional Regulators Cph1p and Efg1p Mediate Activation of the Candida albicans Virulence Gene SAP5 during Infection

    PubMed Central

    Staib, Peter; Kretschmar, Marianne; Nichterlein, Thomas; Hof, Herbert; Morschhäuser, Joachim

    2002-01-01

    The opportunistic fungal pathogen Candida albicans can cause superficial as well as systemic infections. Successful adaptation to the different host niches encountered during infection requires coordinated expression of various virulence traits, including the switch between yeast and hyphal growth forms and secretion of aspartic proteinases. Using an in vivo expression technology that is based on genetic recombination as a reporter of gene activation during experimental candidiasis in mice, we investigated whether two signal transduction pathways controlling hyphal growth, a mitogen-activated protein kinase cascade ending in the transcriptional activator Cph1p and a cyclic AMP-dependent regulatory pathway that involves the transcription factor Efg1p, also control expression of the SAP5 gene, which encodes one of the secreted aspartic proteinases and is induced by host signals soon after infection. Our results show that both transcriptional regulators are important for SAP5 activation in vivo. SAP5 expression was reduced in a cph1 mutant, although filamentous growth in infected tissue was not detectably impaired. SAP5 expression was also reduced, but not eliminated, in an efg1 null mutant, although this strain grew exclusively in the yeast form in infected tissue, demonstrating that in contrast to in vitro conditions, SAP5 activation during infection does not depend on growth of C. albicans in the hyphal form. In a cph1 efg1 double mutant, however, SAP5 expression in infected mice was almost completely eliminated, suggesting that the two signal transduction pathways are important for SAP5 expression in vivo. The avirulence of the cph1 efg1 mutant seemed to be caused not only by the inability to form hyphae but also by a loss of expression of additional virulence genes in the host. PMID:11796627

  16. National surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. SCOPE Participant Group. Surveillance and Control of Pathogens of Epidemiologic.

    PubMed

    Pfaller, M A; Jones, R N; Messer, S A; Edmond, M B; Wenzel, R P

    1998-02-01

    A national surveillance program of nosocomial blood stream infections (BSI) in the USA between April 1995 and June 1996 revealed that Candida was the fourth leading cause of nosocomial BSI, accounting for 8% of all infections. Forty-eight percent of 379 episodes of candidemia were due to species other than Candida albicans. The rank order of non-C. albicans species was C. glabrata (20%) > C. tropicalis (11%) > C. parapsilosis (8%) > C. krusei (5%) > other Candida spp. (4%). The species distribution varied according to geographic region, with non-C. albicans species predominating in the Northeast (54%) and Southeast (53%) regions, and C. albicans predominating in the Northwest (60%) and Southwest (70%) regions. In vitro susceptibility studies demonstrated that 95% of non-C. albicans isolates were susceptible to 5-fluorocytosine, and 84% and 75% were susceptible to fluconazole and itraconazole, respectively. Geographic variation in susceptibility to itraconazole, but not other agents, was observed. Isolates from the Northwest and Southeast regions were more frequently resistant to itraconazole (29-30%) than those from the Northeast and Southwest regions (17-18%). Molecular epidemiologic studies revealed possible nosocomial transmission (five medical centers). Continued surveillance for the presence of non-C. albicans species among hospitalized patients is recommended. PMID:9554180

  17. Evaluation of internal transcribed spacer region of ribosomal DNA sequence analysis for molecular characterization of Candida albicans and Candida dubliniensis isolates from HIV-infected patients.

    PubMed

    Millon, L; Piarroux, R; Drobacheff, C; Monod, M; Grenouillet, F; Bulle, B; Bole, J; Blancard, A; Meillet, D

    2002-12-01

    Molecular typing systems have been needed to study Candida colonization in HIV-infected patients, particularly for investigating virulence and fluconazole resistance. Three methods--electrophoretic karyotyping (EK), detection of restriction fragment length polymorphisms (RFLP) and randomly amplified polymorphic DNA analysis (RAPD)--have been most frequently used. In this study, comparative sequence analysis of the internal transcribed spacer (ITS) region of rDNA was evaluated for delineation of Candida isolates from 14 HIV-infected patients. EK, ITS sequence analysis, RFLP and RAPD resulted in 11, 10, 9 and 8 DNA genotypes, respectively, from 39 Candida albicans isolates. The 10 genotypes observed using ITS sequence analysis were defined by six variation sites in the sequence. Molecular typing of sequential oral isolates showed the persistence of the same genotype of C. albicans in nine patients, and genotype variation in one patient. EK and RAPD showed that another patient was co-infected by two distinct genotypes and ITS analysis identified one of the two genotypes as Candida dubliniensis. Comparative ITS sequence analysis is a quick and reproducible method that provides clear and objective results, and it also identifies C. dubliniensis. The discriminatory power of this new typing approach could be improved by concomitant analysis of other DNA polymorphic sequences. PMID:12521117

  18. Propargyl-Linked Antifolates are Dual Inhibitors of Candida albicans and Candida glabrata

    PubMed Central

    2015-01-01

    Species of Candida, primarily C. albicans and with increasing prevalence, C. glabrata, are responsible for the majority of fungal bloodstream infections that cause morbidity, especially among immune compromised patients. While the development of new antifungal agents that target the essential enzyme, dihydrofolate reductase (DHFR), in both Candida species would be ideal, previous attempts have resulted in antifolates that exhibit inconsistencies between enzyme inhibition and antifungal properties. In this article, we describe the evaluation of pairs of propargyl-linked antifolates that possess similar physicochemical properties but different shapes. All of these compounds are effective at inhibiting the fungal enzymes and the growth of C. glabrata; however, the inhibition of the growth of C. albicans is shape-dependent with extended para-linked compounds proving more effective than compact, meta-linked compounds. Using crystal structures of DHFR from C. albicans and C. glabrata bound to lead compounds, 13 new para-linked compounds designed to inhibit both species were synthesized. Eight of these compounds potently inhibit the growth of both fungal species with three compounds displaying dual MIC values less than 1 μg/mL. Analysis of the active compounds shows that shape and distribution of polar functionality is critical in achieving dual antifungal activity. PMID:24568657

  19. Mucosal biofilms of Candida albicans.

    PubMed

    Ganguly, Shantanu; Mitchell, Aaron P

    2011-08-01

    Biofilms are microbial communities that form on surfaces and are embedded in an extracellular matrix. C. albicans forms pathogenic mucosal biofilms that are evoked by changes in host immunity or mucosal ecology. Mucosal surfaces are inhabited by many microbial species; hence these biofilms are polymicrobial. Several recent studies have applied paradigms of biofilm analysis to study mucosal C. albicans infections. These studies reveal that the Bcr1 transcription factor is a master regulator of C. albicans biofilm formation under diverse conditions, though the most relevant Bcr1 target genes can vary with the biofilm niche. An important determinant of mucosal biofilm formation is the interaction with host defenses. Finally, studies of interactions between bacterial species and C. albicans provide insight into the communication mechanisms that endow polymicrobial biofilms with unique properties. PMID:21741878

  20. Discrepancy in assessment of phagosome-lysosome fusion with two lysosomal markers in murine macrophages infected with Candida albicans.

    PubMed Central

    Mor, N; Goren, M B

    1987-01-01

    Phagosome-lysosome fusion (P-LF) was studied in cultured mouse resident peritoneal macrophages after phagocytosis of Candida albicans. The macrophages were labeled with acridine orange (AO), the electronopaque colloidal Thorotrast, or both markers. After phagocytosis of heat-killed C. albicans, both markers were delivered to more than 95% of phagosomes. After ingestion of viable C. albicans by labeled cells, delivery of AO to phagosomes was highly suppressed (90%), and yet Thorotrast delivery was almost universal. After phagocytosis and 60 min of incubation, about 10 to 20% of the yeasts were killed, and a similar fraction of phagosomes was stained by the fluorescent marker. The evidence from Thorotrast transfer and assessment of yeast viability indicates that C. albicans largely resists intracellular killing by resident macrophages in the face of entirely uninhibited P-LF. We infer that AO must transfer to nearly all of the phagosomes but that it is evidently recognizable only in those in which the yeasts have been killed or possibly severely injured. This conclusion constitutes yet another limitation in the usefulness of AO for studying P-LF. Images PMID:3298062

  1. Meningococcal Infections

    MedlinePlus

    ... are a type of bacteria that cause serious infections. The most common infection is meningitis, which is an inflammation of the ... also cause other problems, including a serious bloodstream infection called sepsis. Meningococcal infections can spread from person ...

  2. Mixed biofilms formed by C. albicans and non-albicans species: a study of microbial interactions.

    PubMed

    Santos, Jéssica Diane dos; Piva, Elisabete; Vilela, Simone Furgeri Godinho; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2016-01-01

    Most Candida infections are related to microbial biofilms often formed by the association of different species. The objective of this study was to evaluate the interactions between Candida albicans and non-albicans species in biofilms formed in vitro. The non-albicans species studied were:Candida tropicalis, Candida glabrata and Candida krusei. Single and mixed biofilms (formed by clinical isolates of C. albicans and non-albicans species) were developed from standardized suspensions of each strain (10(7) cells/mL), on flat-bottom 96-well microtiter plates for 48 hour. These biofilms were analyzed by counting colony-forming units (CFU/mL) in Candida HiChrome agar and by determining cell viability, using the XTT 2,3-bis (2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide colorimetric assay. The results for both the CFU/mL count and the XTT colorimetric assay showed that all the species studied were capable of forming high levels of in vitro biofilm. The number of CFU/mL and the metabolic activity of C. albicans were reduced in mixed biofilms with non-albicans species, as compared with a single C. albicans biofilm. Among the species tested, C. krusei exerted the highest inhibitory action against C. albicans. In conclusion, C. albicans established antagonistic interactions with non-albicans Candida species in mixed biofilms. PMID:26981754

  3. Positions and Numbers of FKS Mutations in Candida albicans Selectively Influence In Vitro and In Vivo Susceptibilities to Echinocandin Treatment

    PubMed Central

    Tscherner, M.; Schaller, M.; Kuchler, K.; Mair, C.; Sartori, B.; Istel, F.; Arendrup, M. C.; Lass-Flörl, C.

    2014-01-01

    Candidemia is the fourth most common kind of microbial bloodstream infection, with Candida albicans being the most common causative species. Echinocandins are employed as the first-line treatment for invasive candidiasis until the fungal species is determined and confirmed by clinical diagnosis. Echinocandins block the FKS glucan synthases responsible for embedding β-(1,3)-d-glucan in the cell wall. The increasing use of these drugs has led to the emergence of antifungal resistance, and elevated MICs have been associated with single-residue substitutions in specific hot spot regions of FKS1 and FKS2. Here, we show for the first time the caspofungin-mediated in vivo selection of a double mutation within one allele of the FKS1 hot spot 1 in a clinical isolate. We created a set of isogenic mutants and used a hematogenous murine model to evaluate the in vivo outcomes of echinocandin treatment. Heterozygous and homozygous double mutations significantly enhance the in vivo resistance of C. albicans compared with the resistance seen with heterozygous single mutations. The various FKS1 hot spot mutations differ in the degree of their MIC increase, substance-dependent in vivo response, and impact on virulence. Our results demonstrate that echinocandin EUCAST breakpoint definitions correlate with the in vivo response when a standard dosing regimen is used but cannot predict the in vivo response after a dose escalation. Moreover, patients colonized by a C. albicans strain with multiple mutations in FKS1 have a higher risk for therapeutic failure. PMID:24733467

  4. Bone Infections

    MedlinePlus

    ... of the body, bones can get infected. The infections are usually bacterial, but can also be fungal. ... bloodstream. People who are at risk for bone infections include those with diabetes, poor circulation, or recent ...

  5. Tigecycline Lock Therapy for Catheter-Related Bloodstream Infection Caused by KPC-Producing Klebsiella pneumoniae in Two Pediatric Hematological Patients.

    PubMed

    Foresti, Sergio; Di Bella, Stefano; Rovelli, Attilio; Sala, Alessandra; Verna, Marta; Bisi, Luca; Nisii, Carla; Gori, Andrea

    2015-12-01

    Catheter-related bacteremias carry high mortality rates in hematological patients. When a multidrug-resistant microorganism is involved, the catheter should ideally be removed; however, this approach is not always possible. Tigecycline lock therapy was used in two pediatric oncohematological patients with intravascular catheter-related infection due to KPC-producing Klebsiella pneumoniae. The catheter was salvaged in both cases, and the patients were later discharged. Our experience suggests the usefulness of this approach in treating this type of infection. PMID:26459892

  6. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study.

    PubMed

    Stewardson, Andrew J; Allignol, Arthur; Beyersmann, Jan; Graves, Nicholas; Schumacher, Martin; Meyer, Rodolphe; Tacconelli, Evelina; De Angelis, Giulia; Farina, Claudio; Pezzoli, Fabio; Bertrand, Xavier; Gbaguidi-Haore, Houssein; Edgeworth, Jonathan; Tosas, Olga; Martinez, Jose A; Ayala-Blanco, M Pilar; Pan, Angelo; Zoncada, Alessia; Marwick, Charis A; Nathwani, Dilip; Seifert, Harald; Hos, Nina; Hagel, Stefan; Pletz, Mathias; Harbarth, Stephan

    2016-08-18

    We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34-2.42, HR = 1.81; 95% CI: 1.49-2.20 and HR = 2.42; 95% CI: 1.66-3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2-9.4, 11.5 days; 95% CI: 11.5-11.6 and 13.3 days; 95% CI: 13.2-13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8-5.9) but not hazard of death (1.16; 95% CI: 0.98-1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13-2.35), excess LOS (4.9 days; 95% CI: 1.1-8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae. PMID:27562950

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

    MedlinePlus

    ... and 2014 13 percent decrease in hospital-onset methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (bloodstream infections) between 2011 ... Clostridium difficile infections ( C. difficile ), and hospital-onset ... Staphylococcus aureus (MRSA) bacteremia (bloodstream infections). To read ...

  8. Antifungal Susceptibility Profiles of Bloodstream Yeast Isolates by Sensititre YeastOne over Nine Years at a Large Italian Teaching Hospital

    PubMed Central

    Posteraro, Brunella; Spanu, Teresa; Fiori, Barbara; De Maio, Flavio; De Carolis, Elena; Giaquinto, Alessia; Prete, Valentina; De Angelis, Giulia; Torelli, Riccardo; D'Inzeo, Tiziana; Vella, Antonietta; De Luca, Alessio; Tumbarello, Mario; Ricciardi, Walter

    2015-01-01

    Sensititre YeastOne (SYO) is an affordable alternative to the Clinical and Laboratory Standards Institute (CLSI) reference method for antifungal susceptibility testing. In this study, the MICs of yeast isolates from 1,214 bloodstream infection episodes, generated by SYO during hospital laboratory activity (January 2005 to December 2013), were reanalyzed using current CLSI clinical breakpoints/epidemiological cutoff values to assign susceptibility (or the wild-type [WT] phenotype) to systemic antifungal agents. Excluding Candida albicans (57.4% of all isolates [n = 1,250]), the most predominant species were Candida parapsilosis complex (20.9%), Candida tropicalis (8.2%), Candida glabrata (6.4%), Candida guilliermondii (1.6%), and Candida krusei (1.3%). Among the non-Candida species (1.9%), 7 were Cryptococcus neoformans and 17 were other species, mainly Rhodotorula species. Over 97% of Candida isolates were susceptible (WT phenotype) to amphotericin B and flucytosine. Rates of susceptibility (WT phenotype) to fluconazole, itraconazole, and voriconazole were 98.7% in C. albicans, 92.3% in the C. parapsilosis complex, 96.1% in C. tropicalis, 92.5% in C. glabrata, 100% in C. guilliermondii, and 100% (excluding fluconazole) in C. krusei. The fluconazole-resistant isolates consisted of 6 C. parapsilosis complex isolates, 3 C. glabrata isolates, 2 C. albicans isolates, 2 C. tropicalis isolates, and 1 Candida lusitaniae isolate. Of the non-Candida isolates, 2 C. neoformans isolates had the non-WT phenotype for susceptibility to fluconazole, whereas Rhodotorula isolates had elevated azole MICs. Overall, 99.7% to 99.8% of Candida isolates were susceptible (WT phenotype) to echinocandins, but 3 isolates were nonsusceptible (either intermediate or resistant) to caspofungin (C. albicans, C. guilliermondii, and C. krusei), anidulafungin (C. albicans and C. guilliermondii), and micafungin (C. albicans). However, when the intrinsically resistant non-Candida isolates were included

  9. Draft Genome Sequence of Colistin-Resistant Acinetobacter baumannii Strain VB22595 Isolated from a Central Line-Associated Bloodstream Infection.

    PubMed

    Veeraraghavan, Balaji; Anandan, Shalini; Ragupathi, Naveen Kumar Devanga; Vijayakumar, Saranya; Sethuvel, Dhiviya Prabaa Muthuirulandi; Biswas, Indranil

    2016-01-01

    Acinetobacter baumannii is an important emerging pathogen that causes health care-associated infections. In this study, we determined the genome of a multidrug-resistant clinical strain, VB22595, isolated from a hospital in Southern India. The draft genome indicates that strain VB22595 encodes a genome of ~3.92 Mb in size and does not contain plasmid derived MCR-1 for colistin resistance. PMID:27516521

  10. Effect of metallo-β-lactamase production and multidrug resistance on clinical outcomes in patients with Pseudomonas aeruginosa bloodstream infection: a retrospective cohort study

    PubMed Central

    2013-01-01

    Background Blood stream infections (BSI) with Pseudomonas aeruginosa lead to poor clinical outcomes. The worldwide emergence and spread of metallo-β-lactamase (MBL) producing, often multidrug-resistant organisms may further aggravate this problem. Our study aimed to investigate the effect of MBL-producing P. aeruginosa (MBL-PA) and various other resistance phenotypes on clinical outcomes. Methods A retrospective cohort study was conducted in three German hospitals. Medical files from 2006 until 2012 were studied, and a number of 113 patients with P. aeruginosa BSI were included. The presence of VIM, IMP and NDM genes was detected using molecular techniques. Genetic relatedness was assessed through multilocus sequence typing (MLST). The effect of resistance patterns or MBL production on clinical outcomes was investigated by using multivariate Cox regression models. Results In-hospital mortality was significantly higher in patients with MBL-PA and multidrug-resistant P. aeruginosa. However, neither BSI with MBL-PA nor BSI with various resistance phenotypes of P. aeruginosa were independently associated with mortality or length of hospital stay. In multivariate models, the SAPS II score (HR 1.046), appropriate definitive treatment (HR range 0.25-0.26), and cardiovascular disease (HR range 0.44-0.46) were independent predictors of mortality. Concomitant infections were associated with an excess length of stay (HR < 1). Conclusions Medication with appropriate antimicrobial agents at any time during the course of infection remains the key for improving clinical outcomes in patients with P. aeruginosa BSI and should be combined with a strict implementation of routine infection control measures. PMID:24176052

  11. Draft Genome Sequence of Colistin-Resistant Acinetobacter baumannii Strain VB22595 Isolated from a Central Line-Associated Bloodstream Infection

    PubMed Central

    Veeraraghavan, Balaji; Anandan, Shalini; Ragupathi, Naveen Kumar Devanga; Vijayakumar, Saranya; Sethuvel, Dhiviya Prabaa Muthuirulandi

    2016-01-01

    Acinetobacter baumannii is an important emerging pathogen that causes health care-associated infections. In this study, we determined the genome of a multidrug-resistant clinical strain, VB22595, isolated from a hospital in Southern India. The draft genome indicates that strain VB22595 encodes a genome of ~3.92 Mb in size and does not contain plasmid derived MCR-1 for colistin resistance. PMID:27516521

  12. Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling

    PubMed Central

    Moyes, David L.; Shen, Chengguo; Murciano, Celia; Runglall, Manohursingh; Richardson, Jonathan P.; Arno, Matthew; Aldecoa-Otalora, Estibaliz; Naglik, Julian R.

    2014-01-01

    Background. The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage. Methods. Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray. Signal pathway activation was monitored by Western blotting and transcription factor enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans–induced damage protection was determined using chemical inhibitors. Results. Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses. Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated. We demonstrate that PI3K/Akt signaling is independent of NF-κB and MAPK signaling and plays a key role in epithelial immune activation and damage protection via mammalian target of rapamycin (mTOR) activation. Conclusions. PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-κB or MAPK signaling. PMID:24357630

  13. Daptomycin antibiotic lock therapy for hemodialysis patients with Gram-positive bloodstream infections following use of tunneled, cuffed hemodialysis catheters: retrospective single center analysis.

    PubMed

    Yen, Hung-Wen; Yang, Wu-Chang; Tarng, Der-Cherng; Yang, Chih-Yu; Chuang, Chiao-Lin; Huang, Ling-Ju; Lin, Pei-Yu; Wang, Chih-Chun; Li, Szu-Yuan

    2016-04-01

    Catheter-related blood stream infection (CRBSI) is a major complication in hemodialysis patients. We assessed the efficacy of systemic daptomycin (DPT) plus DPT antibiotic lock therapy (DPT-ALT) for catheter salvage in patients with Gram-positive CRBSIs. This is a retrospective study of hemodialysis patients with tunneled and cuffed hemodialysis catheters. All patients were from a single institution in Taipei and received systemic DPT plus DPT-ALT for the treatment of Gram-positive CRBSI. Successful resolution of CRBSI was implemented. Resolution of fever within 48 hours, negative result of repeated blood cultures after resolution of fever, no clinical evidence of CRBSI relapse and no need for catheter removal were measured. Fifteen hemodialysis patients received DPT-ALT for CRBSI, nine with coagulase-negative Staphylococcus (CONS), two with methicillin-resistant Staphylococcus aureus (MRSA), three with methicillin-sensitive Staphylococcus aureus (MSSA) and one with polymicrobial infections. Systemic DPT plus DPT-ALT cured 11 patients (73.3%). Treatment failed in all three MRSA cases (two with MRSA and one with MRSA + Enterococcus faecalis). Retrospective design and small sample size were the limitations of this study. Systemic DPT plus DPT-ALT appears to be a promising treatment for CRBSI from CONS and MSSA, but not for MRSA CRBSI. Systemic DPT plus DPT-ALT should be considered for patients with CRBSIs caused by certain species. PMID:26549513

  14. Successful Salvage of Central Venous Catheters in Patients with Catheter-Related or Central Line-Associated Bloodstream Infections by Using a Catheter Lock Solution Consisting of Minocycline, EDTA, and 25% Ethanol.

    PubMed

    Raad, Issam; Chaftari, Anne-Marie; Zakhour, Ramia; Jordan, Mary; Al Hamal, Zanaib; Jiang, Ying; Yousif, Ammar; Garoge, Kumait; Mulanovich, Victor; Viola, George M; Kanj, Soha; Pravinkumar, Egbert; Rosenblatt, Joel; Hachem, Ray

    2016-06-01

    In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites. In vitro and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheter in situ Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively; P < 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.). PMID:27001822

  15. Impact of conversion from an open ward design paediatric intensive care unit environment to all isolated rooms environment on incidence of bloodstream infections and antibiotic resistance in Southern Israel (2000 to 2008).

    PubMed

    Lazar, I; Abukaf, H; Sofer, S; Peled, N; Leibovitz, E

    2015-01-01

    We studied the epidemiology, microbiology, clinical aspects and outcome of bloodstream infections (BSI) in a tertiary paediatric intensive care unit. All BSI episodes were prospectively identified and analysed. The paediatric intensive care unit moved in 2006 from an open-plan unit to a new (all single room) unit. Three hundred and fifty-three BSI episodes occurred in 299 of 4162 patients. Overall, BSI incidence was 85 per 1000 hospitalised children. Fewer BSI episodes occurred during the last two years of the study (2007 to 2008), compared with 2000 to 2006 (70 of 1061 admissions, 6.5% versus 283 of 3101 admissions, 9.1%, respectively, P=0.01). There were 127 of 340 (37.4%) community-acquired and 213 of 340 (62.6%) nosocomial BSI episodes (31 of 1000 and 51 of 1000, respectively). Nosocomial BSI episodes decreased during 2007 to 2008 versus 2000 to 2006 (37.7% versus 55.8%, P=0.03). In 448 instances, pathogens were isolated, 231 (52%) Gram-positive and 188 (42%) Gram-negative. Coagulase-negative Staphylococci, S. pneumoniae and S. aureus (41.1%, 19.9% and 11.7%, respectively) were the most common Gram-positive and Enterobacteriaceae spp. the most frequent Gram-negative organisms (45.2%, of them Klebsiella spp. and E. coli 40% and 29.4%, respectively). A significant decrease was recorded during 2007 to 2008 in Enterobacteriaceae resistance to piperacillin, gentamicin and ciprofloxacin. Thirty of 299 (10%, 9 with S. pneumoniae-BSI) patients died. A significant decrease in BSI and nosocomial incidence and Enterobacteriaceae spp. antibiotic resistance was recorded following the conversion of the paediatric intensive care unit from an open ward to an all isolated rooms environment. PMID:25579287

  16. Disruption in Candida albicans of the TPS2 gene encoding trehalose-6-phosphate phosphatase affects cell integrity and decreases infectivity.

    PubMed

    Zaragoza, Oscar; de Virgilio, Claudio; Pontón, José; Gancedo, Carlos

    2002-05-01

    The gene CaTPS2 encoding trehalose-6-phosphate (T6P) phosphatase from Candida albicans has been cloned and disrupted in this organism. The Catps2/Catps2 mutant did not accumulate trehalose but accumulated high levels of T6P. Disruption of the two copies of the CaTPS2 gene did not abolish growth even at 42 degrees C, but decreased the growth rate. In the stationary phase, the Catps2/Catps2 mutant aggregated, more than 50% of its cells became permeable to propidium iodide and a large amount of protein was found in the culture medium. Aggregation occurred only at pH values higher than 7 and was avoided by osmoprotectants; it was never observed during the exponential phase of growth. The mutant formed colonies with a smooth border on Spider medium. Mice inoculated with 1.5 x 10(6) c.f.u. of wild-type cells died after 8 days, while 80% of those inoculated with the same number of c.f.u. of the Catps2/Catps2 mutant survived for at least 1 month. Reintroduction of the wild-type CaTPS2 gene in the Catps2/Catps2 mutant abolished the phenotypes described. It is hypothesized that the accumulation of T6P interferes with the assembly of a normal cell wall. PMID:11988502

  17. GENETIC CONTROL OF CANDIDA ALBICANS BIOFILM DEVELOPMENT

    PubMed Central

    Finkel, Jonathan S.; Mitchell, Aaron P.

    2014-01-01

    Preface Candida species cause frequent infections due to their ability to form biofilms – surface-associated microbial communities – primarily on implanted medical devices. Increasingly, mechanistic studies have identified the gene products that participate directly in Candida albicans biofilm formation, as well as the regulatory circuitry and networks that control their expression and activity. These studies have revealed new mechanisms and signals that govern C. albicans biofilm formation and associated drug resistance, thus providing biological insight and therapeutic foresight. PMID:21189476

  18. Carbon source-induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen Candida albicans

    PubMed Central

    Ene, Iuliana V; Heilmann, Clemens J; Sorgo, Alice G; Walker, Louise A; de Koster, Chris G; Munro, Carol A; Klis, Frans M; Brown, Alistair J P

    2012-01-01

    The major fungal pathogen Candida albicans can occupy diverse microenvironments in its human host. During colonization of the gastrointestinal or urogenital tracts, mucosal surfaces, bloodstream, and internal organs, C. albicans thrives in niches that differ with respect to available nutrients and local environmental stresses. Although most studies are performed on glucose-grown cells, changes in carbon source dramatically affect cell wall architecture, stress responses, and drug resistance. We show that growth on the physiologically relevant carboxylic acid, lactate, has a significant impact on the C. albicans cell wall proteome and secretome. The regulation of cell wall structural proteins (e.g. Cht1, Phr1, Phr2, Pir1) correlated with extensive cell wall remodeling in lactate-grown cells and with their increased resistance to stresses and antifungal drugs, compared with glucose-grown cells. Moreover, changes in other proteins (e.g. Als2, Gca1, Phr1, Sap9) correlated with the increased adherence and biofilm formation of lactate-grown cells. We identified mating and pheromone-regulated proteins that were exclusive to lactate-grown cells (e.g. Op4, Pga31, Pry1, Scw4, Yps7) as well as mucosa-specific and other niche-specific factors such as Lip4, Pga4, Plb5, and Sap7. The analysis of the corresponding null mutants confirmed that many of these proteins contribute to C. albicans adherence, stress, and antifungal drug resistance. Therefore, the cell wall proteome and secretome display considerable plasticity in response to carbon source. This plasticity influences important fitness and virulence attributes known to modulate the behavior of C. albicans in different host microenvironments during infection. PMID:22997008

  19. Beyond Candida albicans: Mechanisms of immunity to non-albicans Candida species.

    PubMed

    Whibley, Natasha; Gaffen, Sarah L

    2015-11-01

    The fungal genus Candida encompasses numerous species that inhabit a variety of hosts, either as commensal microbes and/or pathogens. Candida species are a major cause of fungal infections, yet to date there are no vaccines against Candida or indeed any other fungal pathogen. Our knowledge of immunity to Candida mainly comes from studies on Candida albicans, the most frequent species associated with disease. However, non-albicans Candida (NAC) species also cause disease and their prevalence is increasing. Although research into immunity to NAC species is still at an early stage, it is becoming apparent that immunity to C. albicans differs in important ways from non-albicans species, with important implications for treatment, therapy and predicted demographic susceptibility. This review will discuss the current understanding of immunity to NAC species in the context of immunity to C. albicans, and highlight as-yet unanswered questions. PMID:26276374

  20. Epidemiology and clinical outcomes of bloodstream infections caused by extended-spectrum β-lactamase-producing Escherichia coli in patients with cancer.

    PubMed

    Ha, Young Eun; Kang, Cheol-In; Cha, Min Kyeong; Park, So Yeon; Wi, Yu Mi; Chung, Doo Ryeon; Peck, Kyong Ran; Lee, Nam Yong; Song, Jae-Hoon

    2013-11-01

    Patients with cancer can be vulnerable to infection with antimicrobial-resistant pathogens such as extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. A cohort study was performed to evaluate the epidemiology and impact of ESBL-producing Escherichia coli (ESBL-EC) bacteraemia on the outcomes of adult patients with cancer. During the 2.5-year study period, a total of 350 cases of E. coli bacteraemia were documented in cancer patients, of which 95 (27.1%) were due to ESBL-EC. Significant factors associated with ESBL-EC bacteraemia were liver disease, immunosuppressant use, recent surgery, and prior use of cephalosporins or fluoroquinolones. The overall 30-day mortality rate was 14.9% (52/350), and the mortality rate was higher in patients with ESBL-EC than in those without ESBL-EC (22.1% vs.12.2%; P=0.02). Multivariate analysis showed that ESBL-EC was an independent risk factor for mortality (odds ratio=3.01, 95% confidence interval 1.45-6.28; P=0.003), along with the presence of septic shock, mechanical ventilation, the severity of underlying diseases, and pneumonia as a source of bacteraemia. Of the 69 isolates in which ESBLs and their molecular relationships were studied, 68 (98.6%) produced CTX-M-type and 51 (73.9%) produced CTX-M-14 and/or CTX-M-15. Twenty-four sequence types (STs) were identified among CTX-M-14- and CTX-M-15-producing E. coli isolates, with ST131 being the most prevalent (12/51; 23.5%). In conclusion, this study confirms that CTX-M-producing E. coli and ST131, which have been shown to be an emerging public health threat, are widely prevalent in cancer patients and can adversely affect the outcome of E. coli bacteraemia in these patients. PMID:24071027

  1. Mucins Suppress Virulence Traits of Candida albicans

    PubMed Central

    Kavanaugh, Nicole L.; Zhang, Angela Q.; Nobile, Clarissa J.; Johnson, Alexander D.

    2014-01-01

    ABSTRACT Candida albicans is the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic invasions. Mucus, the gel that coats all wet epithelial surfaces, accommodates C. albicans as part of the normal microbiota, where C. albicans resides asymptomatically in healthy humans. Through a series of in vitro experiments combined with gene expression analysis, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology in C. albicans in which a range of genes related to adhesion, filamentation, and biofilm formation are downregulated. We also show that corresponding traits are suppressed, rendering C. albicans impaired in forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggest that mucins can manipulate C. albicans physiology, and we hypothesize that they are key environmental signals for retaining C. albicans in the host-compatible, commensal state. PMID:25389175

  2. Epidemiology and Risk Factors for Echinocandin Nonsusceptible Candida glabrata Bloodstream Infections: Data From a Large Multisite Population-Based Candidemia Surveillance Program, 2008–2014

    PubMed Central

    Vallabhaneni, Snigdha; Cleveland, Angela A.; Farley, Monica M.; Harrison, Lee H.; Schaffner, William; Beldavs, Zintar G.; Derado, Gordana; Pham, Cau D.; Lockhart, Shawn R.; Smith, Rachel M.

    2015-01-01

    Background. Echinocandins are first-line treatment for Candida glabrata candidemia. Echinocandin resistance is concerning due to limited remaining treatment options. We used data from a multisite, population-based surveillance program to describe the epidemiology and risk factors for echinocandin nonsusceptible (NS) C glabrata candidemia. Methods. The Centers for Disease Control and Prevention's Emerging Infections Program conducts population-based laboratory surveillance for candidemia in 4 metropolitan areas (7.9 million persons; 80 hospitals). We identified C glabrata cases occurring during 2008–2014; medical records of cases were reviewed, and C glabrata isolates underwent broth microdilution antifungal susceptibility testing. We defined echinocandin-NS C glabrata (intermediate or resistant) based on 2012 Clinical and Laboratory Standards Institute minimum inhibitory concentration breakpoints. Independent risk factors for NS C glabrata were determined by stepwise logistic regression. Results. Of 1385 C glabrata cases, 83 (6.0%) had NS isolates (19 intermediate and 64 resistant); the proportion of NS isolates rose from 4.2% in 2008 to 7.8% in 2014 (P < .001). The proportion of NS isolates at each hospital ranged from 0% to 25.8%; 3 large, academic hospitals accounted for almost half of all NS isolates. In multivariate analysis, prior echinocandin exposure (adjusted odds ratio [aOR], 5.3; 95% CI, 2.6–1.2), previous candidemia episode (aOR, 2.5; 95% CI, 1.2–5.1), hospitalization in the last 90 days (aOR, 1.9; 95% CI, 1.0–3.5, and fluconazole resistance [aOR, 3.6; 95% CI, 2.0–6.4]) were significantly associated with NS C glabrata. Fifty-nine percent of NS C glabrata cases had no known prior echinocandin exposure. Conclusion. The proportion of NS C glabrata isolates rose significantly during 2008–2014, and NS C glabrata frequency differed across hospitals. In addition to acquired resistance resulting from prior drug exposure, occurrence of NS C

  3. [Investigation of plasmid-mediated quinolone resistance genes in quinolone-resistant Escherichia coli and Klebsiella spp. isolates from bloodstream infections].

    PubMed

    Buruk, Celal Kurtuluş; Öztel Ocak, Hikmet; Bayramoğlu, Gülçin; Aydın, Faruk

    2016-04-01

    One of the treatment options of Escherichia coli and Klebsiella spp. infections which are the most common opportunistic pathogens of gram-negative sepsis is quinolones. Resistance to quinolones which act by disrupting DNA synthesis has been increasing. Horizontal transfer of plasmid-mediated quinolone resistance (PMQR) genes play an important role in the spread of resistance. The data about the prevalence of PMQR genes in our country is quite limited. The aim of this study was to investigate the presence of known PMQR genes namely qnrA, qnrB, qnrC, qnrS, qnrD, aac(6')-Ib-cr, qepA and oqxAB amongst quinolone-resistant E. coli and Klebsiella spp. strains isolated from blood cultures. One hundred twenty seven E.coli and 66 Klebsiella isolates detected as nalidixic acid- and/or ciprofloxacin-resistant by phenotypical methods, from 193 blood samples of 187 patients admitted to Karadeniz Technical University, Faculty of Medicine, Department of Medical Microbiology, Bacteriology Unit of Patient Service Laboratory between January 2012 to August 2013 were included in the study. The presence of PMQR genes were investigated by polymerase chain reaction (PCR) and for the detection of aac(6')-Ib-cr variants PCR-restriction fragment length polymorphism (PCR-RFLP) method was used. The positive bands were sequenced using the same primers, and aligned with formerly defined resistance gene sequences, and confirmed. In the study, 56.7% (72/127) of E.coli and 19.7% (13/66) of Klebsiella spp. isolates, with a total of 44% (85/193) of all the isolates were found to be phenotypically resistant to quinolones. Of the 13 resistant Klebsiella isolates, 11 were K.pneumoniae, and two were K.oxytoca. Extended-spectrum beta-lactamase (ESBL)-producing isolates showed higher resistance (50/80, 62.5%) to quinolones than the negative ones (35/113, 30.9%). The prevalence of quinolone resistance genes among resistant E. coli and Klebsiella spp. isolates was determined as qnrA, 1.4% and 15.4%; qnrB, 4

  4. Candida albicans Biofilms and Human Disease

    PubMed Central

    Nobile, Clarissa J.; Johnson, Alexander D.

    2016-01-01

    In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species. PMID:26488273

  5. Emerging technologies for rapid identification of bloodstream pathogens.

    PubMed

    Kothari, Atul; Morgan, Margie; Haake, David A

    2014-07-15

    Technologies for rapid microbial identification are poised to revolutionize clinical microbiology and enable informed decision making for patients with life-threatening bloodstream infections. Species identification of microorganisms in positive blood cultures can be performed in minutes using commercial fluorescence in situ hybridization tests or mass spectroscopy. Microorganisms in positive blood cultures can also be identified within 1-2.5 hours using automated polymerase chain reaction-based systems that can also detect selected antibiotic resistance markers, such as methicillin resistance. When combined with antibiotic stewardship programs, these approaches improve clinical outcomes and reduce healthcare expenditures. Tests for direct detection in whole blood samples are highly desirable because of their potential to identify bloodstream pathogens without waiting 1-2 days for blood cultures to become positive. However, results for pathogen detection in whole blood do not overlap with those of conventional blood culture techniques and we are still learning how best to use these approaches. PMID:24771332

  6. Candida albicans biofilm chip (CaBChip) for high-throughput antifungal drug screening.

    PubMed

    Srinivasan, Anand; Lopez-Ribot, Jose L; Ramasubramanian, Anand K

    2012-01-01

    Candida albicans remains the main etiological agent of candidiasis, which currently represents the fourth most common nosocomial bloodstream infection in US hospitals. These opportunistic infections pose a growing threat for an increasing number of compromised individuals, and carry unacceptably high mortality rates. This is in part due to the limited arsenal of antifungal drugs, but also to the emergence of resistance against the most commonly used antifungal agents. Further complicating treatment is the fact that a majority of manifestations of candidiasis are associated with the formation of biofilms, and cells within these biofilms show increased levels of resistance to most clinically-used antifungal agents. Here we describe the development of a high-density microarray that consists of C. albicans nano-biofilms, which we have named CaBChip. Briefly, a robotic microarrayer is used to print yeast cells of C. albicans onto a solid substrate. During printing, the yeast cells are enclosed in a three dimensional matrix using a volume as low as 50 nL and immobilized on a glass substrate with a suitable coating. After initial printing, the slides are incubated at 37 °C for 24 hours to allow for biofilm development. During this period the spots grow into fully developed "nano-biofilms" that display typical structural and phenotypic characteristics associated with mature C. albicans biofilms (i.e. morphological complexity, three dimensional architecture and drug resistance). Overall, the CaBChip is composed of ~750 equivalent and spatially distinct biofilms; with the additional advantage that multiple chips can be printed and processed simultaneously. Cell viability is estimated by measuring the fluorescent intensity of FUN1 metabolic stain using a microarray scanner. This fungal chip is ideally suited for use in true high-throughput screening for antifungal drug discovery. Compared to current standards (i.e. the 96-well microtiter plate model of biofilm formation

  7. FAQs about Catheter-Associated Bloodstream Infections

    MedlinePlus

    ... Wear a mask, cap, sterile gown, and sterile gloves when putting in the catheter to keep it ... putting in the catheter. • Clean their hands, wear gloves, and clean the catheter opening with an antiseptic ...

  8. Shear stress modulates the thickness and architecture of Candida albicans biofilms in a phase-dependent manner

    PubMed Central

    Mukherjee, Pranab K.; Chand, David V.; Chandra, Jyotsna; Anderson, James M.; Ghannoum, Mahmoud A.

    2010-01-01

    Summary Biofilm formation plays an integral role in catheter-associated bloodstream infections caused by Candida albicans. Biofilms formed on catheters placed intravenously are exposed to shear stress caused by blood flow. In this study, we investigated whether shear stress affects the ability of C. albicans to form biofilms. Candida biofilms were formed on catheter discs and exposed to physiological levels of shear stress using a rotating disc system (RDS). Control biofilms were grown under conditions of no flow. Tetrazolium (XTT) assay and dry weight (DW) measurements were used to quantify metabolic activity and biofilm mass respectively. Confocal scanning laser microscopy (CSLM) was used to evaluate architecture and biofilm thickness. After 90 min, cells attached under no-flow exhibited significantly greater XTT activity and DW than those under shear. However, by 24 h, biofilms formed under both conditions had similar XTT activities and DW. Interestingly, thickness of biofilms formed under no-flow was significantly greater after 24 h than of those formed under shear stress, demonstrating that shear exposure results in thinner, but denser biofilms. These studies suggest that biofilm architecture is modulated by shear in a phase-dependent manner. PMID:19076284

  9. Competitive Interactions between C. albicans, C. glabrata and C. krusei during Biofilm Formation and Development of Experimental Candidiasis

    PubMed Central

    Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; Vilela, Simone Furgeri Godinho; dos Santos, Jéssica Diane; de Barros, Patrícia Pimentel; Prata, Márcia Cristina de Azevedo; Anbinder, Ana Lia; Fuchs, Beth Burgwyn; Jorge, Antonio Olavo Cardoso; Mylonakis, Eleftherios; Junqueira, Juliana Campos

    2015-01-01

    In this study, we evaluated the interactions between Candida albicans, Candida krusei and Candida glabrata in mixed infections. Initially, these interactions were studied in biofilms formed in vitro. CFU/mL values of C. albicans were lower in mixed biofilms when compared to the single biofilms, verifying 77% and 89% of C. albicans reduction when this species was associated with C. glabrata and C. krusei, respectively. After that, we expanded this study for in vivo host models of experimental candidiasis. G. mellonella larvae were inoculated with monotypic and heterotypic Candida suspensions for analysis of survival rate and quantification of fungal cells in the haemolymph. In the groups with single infections, 100% of the larvae died within 18 h after infection with C. albicans. However, interaction groups achieved 100% mortality after 72 h of infection by C. albicans-C. glabrata and 96 h of infection by C. albicans-C. krusei. C. albicans CFU/mL values from larvae hemolymph were lower in the interacting groups compared with the monoespecies group after 12 h of infection. In addition, immunosuppressed mice were also inoculated with monotypic and heterotypic microbial suspensions to induce oral candidiasis. C. albicans CFU/mL values recovered from oral cavity of mice were higher in the group with single infection by C. albicans than the groups with mixed infections by C. albicans-C. glabrata and C. albicans-C. krusei. Moreover, the group with single infection by C. albicans had a higher degree of hyphae and epithelial changes in the tongue dorsum than the groups with mixed infections. We concluded that single infections by C. albicans were more harmful for animal models than mixed infections with non-albicans species, suggesting that C. albicans establish competitive interactions with C. krusei and C. glabrata during biofilm formation and development of experimental candidiasis. PMID:26146832

  10. Comparison of albicans vs. non-albicans candidemia in French intensive care units

    PubMed Central

    2010-01-01

    Introduction Candidemia raises numerous therapeutic issues for intensive care physicians. Epidemiological data that could guide the choice of initial therapy are still required. This analysis sought to compare the characteristics of intensive care unit (ICU) patients with candidemia due to non-albicans Candida species with those of ICU patients with candidemia due to Candida albicans. Methods A prospective, observational, multicenter, French study was conducted from October 2005 to May 2006. Patients exhibiting candidemia developed during ICU stay and exclusively due either to one or more non-albicans Candida species or to C. albicans were selected. The data collected included patient characteristics on ICU admission and at the onset of candidemia. Results Among the 136 patients analyzed, 78 (57.4%) had candidemia caused by C. albicans. These patients had earlier onset of infection (11.1 ± 14.2 days after ICU admission vs. 17.4 ± 17.7, p = 0.02), higher severity scores on ICU admission (SOFA: 10.4 ± 4.7 vs. 8.6 ± 4.6, p = 0.03; SAPS II: 57.4 ± 22.8 vs. 48.7 ± 15.5, P = 0.015), and were less often neutropenic (2.6% vs. 12%, p = 0.04) than patients with candidemia due to non-albicans Candida species. Conclusions Although patients infected with Candida albicans differed from patients infected with non-albicans Candida species for a few characteristics, no clinical factor appeared pertinent enough to guide the choice of empirical antifungal therapy in ICU. PMID:20507569

  11. Candida albicans Airway Exposure Primes the Lung Innate Immune Response against Pseudomonas aeruginosa Infection through Innate Lymphoid Cell Recruitment and Interleukin-22-Associated Mucosal Response

    PubMed Central

    Mear, Jean Baptiste; Gosset, Philippe; Kipnis, Eric; Faure, Emmanuel; Dessein, Rodrigue; Jawhara, Samir; Fradin, Chantal; Faure, Karine; Poulain, Daniel; Sendid, Boualem

    2014-01-01

    Pseudomonas aeruginosa and Candida albicans are two pathogens frequently encountered in the intensive care unit microbial community. We have demonstrated that C. albicans airway exposure protected against P. aeruginosa-induced lung injury. The goal of the present study was to characterize the cellular and molecular mechanisms associated with C. albicans-induced protection. Airway exposure by C. albicans led to the recruitment and activation of natural killer cells, innate lymphoid cells (ILCs), macrophages, and dendritic cells. This recruitment was associated with the secretion of interleukin-22 (IL-22), whose neutralization abolished C. albicans-induced protection. We identified, by flow cytometry, ILCs as the only cellular source of IL-22. Depletion of ILCs by anti-CD90.2 antibodies was associated with a decreased IL-22 secretion and impaired survival after P. aeruginosa challenge. Our results demonstrate that the production of IL-22, mainly by ILCs, is a major and inducible step in protection against P. aeruginosa-induced lung injury. This cytokine may represent a clinical target in Pseudomonas aeruginosa-induced lung injury. PMID:24166952

  12. Candida albicans, plasticity and pathogenesis.

    PubMed

    Poulain, Daniel

    2015-06-01

    The yeast Candida albicans has emerged as a major public health problem during the past two decades. The spectrum of diseases caused by this species ranges from vaginal infections, which affect up to 75% of the women at least once in their lifetime, to deep infections in hospitalized patients which lead to high morbidity and mortality rates. Candida albicans may also play a role in the persistence or worsening of some chronic inflammatory bowel diseases. Active research is now improving our understanding of the molecular mechanisms and genetic factors in the yeast and its host which influence the development of disease. Despite these advances and the availability of a more extensive therapeutic arsenal, current progress in the control of nosocomial infections due to Candida remains limited, mainly due to the difficulties in diagnosing these infections. The biologist has a key role to play in establishing a dialogue with the clinician in order to identify the saprophyte/pathogen transition in patients as early as possible. This review provides a quick synopsis of the modern concepts of Candida pathogenesis with some representative examples illustrating the specifics traits of this yeast in terms of pathogenic adaptation. PMID:23962107

  13. Types of Haemophilus influenzae Infections

    MedlinePlus

    ... many different kinds of infections. These infections can range from mild ear infections to severe diseases, like bloodstream infections. When the bacteria invade parts of the body that are normally free from germs, like spinal fluid or blood, this ...

  14. A novel protein kinase is essential in bloodstream Trypanosoma brucei.

    PubMed

    Jensen, Bryan C; Booster, Nick; Vidadala, Rama Subba Rao; Maly, Dustin J; Parsons, Marilyn

    2016-07-01

    Human African trypanosomiasis a fatal disease for which no vaccines exist and treatment regimens are difficult. Here, we evaluate a Trypanosoma brucei protein kinase, AEK1, as a potential drug target. Conditional knockouts confirmed AEK1 essentiality in bloodstream forms. For chemical validation, we overcame the lack of AEK1 inhibitors by creating parasites expressing a single, functional analog-sensitive AEK1 allele. Analog treatment of mice infected with this strain delayed parasitemia and death, with one-third of animals showing no parasitemia. These studies validate AEK1 as a drug target and highlight the need for further understanding of its function. PMID:27018127

  15. Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis

    PubMed Central

    Tati, Swetha; Davidow, Peter; McCall, Andrew; Hwang-Wong, Elizabeth; Rojas, Isolde G.; Cormack, Brendan; Edgerton, Mira

    2016-01-01

    Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because of its inability to form hyphae, are understudied. Since both Candida albicans and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we examined their co-adhesion in vitro and observed adhesion of C. glabrata only to C. albicans hyphae microscopically. Mice were infected sublingually with C. albicans or C. glabrata individually, or with both species concurrently, to study their ability to cause OPC. Infection with C. glabrata alone resulted in negligible infection of tongues; however, colonization by C. glabrata was increased by co-infection or a pre-established infection with C. albicans. Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata. C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans. Thus, we found a near essential requirement for the presence of C. albicans for both initial colonization and establishment of OPC infection by C. glabrata. PMID:27029023

  16. Gymnemic acids inhibit hyphal growth and virulence in Candida albicans.

    PubMed

    Vediyappan, Govindsamy; Dumontet, Vincent; Pelissier, Franck; d'Enfert, Christophe

    2013-01-01

    Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine. PMID:24040201

  17. Uptake and antifungal activity of oligonucleotides in Candida albicans

    PubMed Central

    Disney, Matthew D.; Haidaris, Constantine G.; Turner, Douglas H.

    2003-01-01

    Candida albicans is a significant cause of disease in immunocompromised humans. Because the number of people infected by fungal pathogens is increasing, strategies are being developed to target RNAs in fungi. This work shows that oligonucleotides can serve as therapeutics against C. albicans. In particular, oligonucleotides are taken up from cell culture medium in an energy-dependent process. After uptake, oligonucleotides, including RNA, remain mostly intact after 12 h in culture. For culture conditions designed for mammalian cells, intracellular concentrations of oligonucleotides in C. albicans exceed those in COS-7 mammalian cells, suggesting that uptake can provide selective targeting of fungi over human cells. A 19-mer 2′OMe (oligonucleotide with a 2′-O-methyl backbone) hairpin is described that inhibits growth of a C. albicans strain at pH < 4.0. This pH is easily tolerated in some parts of the body subject to C. albicans infections. In vivo dimethyl sulfate modification of ribosomal RNA and the decreased rate of protein synthesis suggest that this hairpin's activity may be due to targeting the ribosome in a way that does not depend on base pairing. Addition of anti-C. albicans oligonucleotides to COS-7 mammalian cells has no effect on cell growth. Evidently, oligonucleotides can selectively serve as therapeutics toward C. albicans and, presumably, other pathogens. Information from genome sequencing and functional genomics studies on C. albicans and other pathogens should allow rapid design and testing of other approaches for oligonucleotide therapies. PMID:12552085

  18. Sensitization of Candida albicans to terbinafine by berberine and berberrubine

    PubMed Central

    LAM, PIKLING; KOK, STANTON HON LUNG; LEE, KENNETH KA HO; LAM, KIM HUNG; HAU, DESMOND KWOK PO; WONG, WAI YEUNG; BIAN, ZHAOXIANG; GAMBARI, ROBERTO; CHUI, CHUNG HIN

    2016-01-01

    Candida albicans (C. albicans) is an opportunistic fungal pathogen, particularly observed in immunocompromised patients. C. albicans accounts for 50–70% of cases of invasive candidiasis in the majority of clinical settings. Terbinafine, an allylamine antifungal drug, has been used to treat fungal infections previously. It has fungistatic activity against C. albicans. Traditional Chinese medicines can be used as complementary medicines to conventional drugs to treat a variety of ailments and diseases. Berberine is a quaternary alkaloid isolated from the traditional Chinese herb, Coptidis Rhizoma, while berberrubine is isolated from the medicinal plant Berberis vulgaris, but is also readily derived from berberine by pyrolysis. The present study demonstrates the possible complementary use of berberine and berberrubine with terbinafine against C. albicans. The experimental findings assume that the potential application of these alkaloids together with reduced dosage of the standard drug would enhance the resulting antifungal potency. PMID:27073630

  19. Humoral immune responses to Candida albicans complement receptor 3-related protein in the atopic subjects with vulvovaginal candidiasis. Novel sensitive marker for Candida infection.

    PubMed

    Paulovičová, Ema; Bujdáková, Helena; Chupáčová, Jarmila; Paulovičová, Lucia; Kertys, Pavol; Hrubiško, Martin

    2015-03-01

    In vitro evaluation of specific anti-Candida albicans sera antibodies based on synthetically prepared complement receptor 3-related protein (CR3-RP) mimicking the structure of native complement receptor 3 in a cohort of 72 patients with atopy and recurrent Candida vulvovaginitis (RVC) revealed effective humoral response against Candida CR3-RP. The most significant have been IgM and IgA isotype antibodies (33 and 47% positive cases, respectively). The quantitative evaluation of anti-CR3RP isotype antibodies was confronted with results of commercial ELISA anti-C. albicans antibodies diagnostics based on C. albicans cell wall mannan and β-glucan antigens, the most significant correlation being observed with anti-CR3-RP IgM and anti-β-D-glucan IgM (r(2) = 0.624) followed by isotype IgA (r(2) = 0.381). The immunogenicity and immunoreactivity of CR3RP antigen in RVC patients' sera had been evaluated with regard to the results reached by counterimmunoelectrophoresis and heterogeneous enzyme immunoassay. Obviously, synthetically prepared CR3-RP mimicking the Candida cell-wall-derived structure moiety represents a promising immunological tool not only for Candida serodiagnostics, but also prospectively for follow-up of targeted antifungal therapy and as promising Candida vaccine candidate. PMID:25673750

  20. Effect of Tetrandrine against Candida albicans Biofilms

    PubMed Central

    Zhao, Lan-Xue; Li, De-Dong; Hu, Dan-Dan; Hu, Gan-Hai; Yan, Lan; Wang, Yan; Jiang, Yuan-Ying

    2013-01-01

    Candida albicans is the most common human fungal pathogen and has a high propensity to develop biofilms that are resistant to traditional antifungal agents. In this study, we investigated the effect of tetrandrine (TET) on growth, biofilm formation and yeast-to-hypha transition of C. albicans. We characterized the inhibitory effect of TET on hyphal growth and addressed its possible mechanism of action. Treatment of TET at a low concentration without affecting fungal growth inhibited hyphal growth in both liquid and solid Spider media. Real-time RT-PCR revealed that TET down-regulated the expression of hypha-specific genes ECE1, ALS3 and HWP1, and abrogated the induction of EFG1 and RAS1, regulators of hyphal growth. Addition of cAMP restored the normal phenotype of the SC5314 strain. These results indicate that TET may inhibit hyphal growth through the Ras1p-cAMP-PKA pathway. In vivo, at a range of concentrations from 4 mg/L to 32 mg/L, TET prolonged the survival of C. albicans-infected Caenorhabditis elegans significantly. This study provides useful information for the development of new strategies to reduce the incidence of C. albicans biofilm-associated infections. PMID:24260276

  1. Manipulation of host diet to reduce gastrointestinal colonization by the opportunistic pathogen Candida albicans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal ...

  2. Initiation of phospholipomannan β-1,2 mannosylation involves Bmts with redundant activity, influences its cell wall location and regulates β-glucans homeostasis but is dispensable for Candida albicans systemic infection.

    PubMed

    Courjol, F; Mille, C; Hall, R A; Masset, A; Aijjou, R; Gow, N A R; Poulain, D; Jouault, T; Fradin, C

    2016-01-01

    Pathogenic and non-pathogenic fungi synthesize glycosphingolipids, which have a crucial role in growth and viability. Glycosphingolipids also contribute to fungal-associated pathogenesis. The opportunistic yeast pathogen Candida albicans synthesizes phospholipomannan (PLM), which is a glycosphingolipid of the mannosylinositol phosphorylceramide family. Through its lipid and glycan moieties, PLM contributes to the initial recognition of the yeast, causing immune system disorder and persistent fungal disease through activation of host signaling pathways. The lipid moiety of PLM activates the deregulation signaling pathway involved in yeast phagocytosis whereas its glycan moiety, composed of β-1,2 mannosides (β-Mans), participates to inflammatory processes through a mechanism involving Galectin-3. Biosynthesis of PLM β-Mans involves two β-1,2 mannosyltransferases (Bmts) that initiate (Bmt5) and elongate (Bmt6) the glycan chains. After generation of double bmtsΔ mutants, we show that Bmt5 has redundant activity with Bmt2, which can replace Bmt5 in bmt5Δ mutant. We also report that PLM is located in the inner layer of the yeast cell wall. PLM seems to be not essential for systemic infection of the yeast. However, defect of PLM β-mannosylation increases resistance of C. albicans to inhibitors of β-glucans and chitin synthesis, highlighting a role of PLM in cell wall homeostasis. PMID:26427558

  3. Chlorhexidine Gluconate Cleansing in Preventing Central Line Associated Bloodstream Infection and Acquisition of Multi-drug Resistant Organisms in Younger Patients With Cancer or Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-02-22

    Bacterial Infection; Benign Neoplasm; Malignant Neoplasm; Methicillin-Resistant Staphylococcus Aureus Infection; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  4. Colonization of congenitally athymic, gnotobiotic mice by Candida albicans.

    PubMed Central

    Balish, E; Balish, M J; Salkowski, C A; Lee, K W; Bartizal, K F

    1984-01-01

    Colony counts, scanning electron microscopy, and light microscopy were used to assess the capacity of Candida albicans to colonize (naturally) and infect the alimentary tract of adult and neonatal (athymic [nu/nu] or heterozygous [+/nu] littermates) germfree BALB/c mice. When exposed to yeast-phase C. albicans, the alimentary tract of adult germfree mice (nu/nu or +/nu) is quickly (within 24 to 48 h) colonized with yeast cells. Neither morbidity nor mortality was evident in any mice that were colonized with a pure culture of C. albicans for 6 months. Yeast cells of C. albicans predominated on mucosal surfaces in the oral cavities and vaginas of adult athymic and heterozygous mice. In both genotypes, C. albicans hyphae were observed in keratinized tissue on the dorsal posterior tongue surface and in the cardial-atrium section of the stomach. Conversely, neonatal athymic or heterozygous mice, born to germfree or C. albicans-colonized mothers, do not become heavily colonized or infected with C. albicans until 11 to 15 days after birth. Although yeast cells adhered to some mucosal surfaces in vivo, neither widespread mucocutaneous candidiasis, i.e., invasion of mucosal surfaces with C. albicans hyphae, nor overwhelming systemic candidiasis was evident in neonatal (nu/nu or +/nu) mice. Thus, even in the absence of functional T-cells and a viable bacterial flora, athymic and heterozygous littermate mice (adult or neonatal BALB/c) that are colonized with a pure culture of C. albicans manifest resistance to extensive mucocutaneous and systemic candidiasis. Images PMID:6372689

  5. Oxidative stress of photodynamic antimicrobial chemotherapy inhibits Candida albicans virulence

    NASA Astrophysics Data System (ADS)

    Kato, Ilka Tiemy; Prates, Renato Araujo; Tegos, George P.; Hamblin, Michael R.; Simões Ribeiro, Martha

    2011-03-01

    Photodynamic antimicrobial chemotherapy (PACT) is based on the principal that microorganisms will be inactivated using a light source combined to a photosensitizing agent in the presence of oxygen. Oxidative damage of cell components occurs by the action of reactive oxygen species leading to cell death for microbial species. It has been demonstrated that PACT is highly efficient in vitro against a wide range of pathogens, however, there is limited information for its in vivo potential. In addition, it has been demonstrated that sublethal photodynamic inactivation may alter the virulence determinants of microorganisms. In this study, we explored the effect of sublethal photodynamic inactivation to the virulence factors of Candida albicans. Methylene Blue (MB) was used as photosensitizer for sublethal photodynamic challenge on C. albicans associated with a diode laser irradiation (λ=660nm). The parameters of irradiation were selected in causing no reduction of viable cells. The potential effects of PACT on virulence determinants of C. albicans cells were investigated by analysis of germ tube formation and in vivo pathogenicity assays. Systemic infection was induced in mice by the injection of fungal suspension in the lateral caudal vein. C. albicans exposed to sublethal photodynamic inactivation formed significantly less germ tube than untreated cells. In addition, mice infected with C. albicans submitted to sublethal PACT survived for a longer period of time than mice infected with untreated cells. The oxidative damage promoted by sublethal photodynamic inactivation inhibited virulence determinants and reduced in vivo pathogenicity of C. albicans.

  6. Antimicrobial blue light inactivation of Candida albicans: In vitro and in vivo studies.

    PubMed

    Zhang, Yunsong; Zhu, Yingbo; Chen, Jia; Wang, Yucheng; Sherwood, Margaret E; Murray, Clinton K; Vrahas, Mark S; Hooper, David C; Hamblin, Michael R; Dai, Tianhong

    2016-07-01

    Fungal infections are a common cause of morbidity, mortality and cost in critical care populations. The increasing emergence of antimicrobial resistance necessitates the development of new therapeutic approaches for fungal infections. In the present study, we investigated the effectiveness of an innovative approach, antimicrobial blue light (aBL), for inactivation of Candida albicans in vitro and in infected mouse burns. A bioluminescent strain of C. albicans was used. The susceptibilities to aBL (415 nm) were compared between C. albicans and human keratinocytes. The potential development of aBL resistance by C. albicans was investigated via 10 serial passages of C. albicans on aBL exposure. For the animal study, a mouse model of thermal burn infected with the bioluminescent C. albicans strain was used. aBL was delivered to mouse burns approximately 12 h after fungal inoculation. Bioluminescence imaging was performed to monitor in real time the extent of infection in mice. The results obtained from the studies demonstrated that C. albicans was approximately 42-fold more susceptible to aBL than human keratinocytes. Serial passaging of C. albicans on aBL exposure implied a tendency of reduced aBL susceptibility of C. albicans with increasing numbers of passages; however, no statistically significant difference was observed in the post-aBL survival rate of C. albicans between the first and the last passage (P>0.05). A single exposure of 432 J/cm(2) aBL reduced the fungal burden in infected mouse burns by 1.75-log10 (P=0.015). Taken together, our findings suggest aBL is a potential therapeutic for C. albicans infections. PMID:26909654

  7. Delinking CARD9 and IL-17: CARD9 Protects against Candida tropicalis Infection through a TNF-α-Dependent, IL-17-Independent Mechanism.

    PubMed

    Whibley, Natasha; Jaycox, Jillian R; Reid, Delyth; Garg, Abhishek V; Taylor, Julie A; Clancy, Cornelius J; Nguyen, M Hong; Biswas, Partha S; McGeachy, Mandy J; Brown, Gordon D; Gaffen, Sarah L

    2015-10-15

    Candida is the third most common cause of bloodstream infections in hospitalized patients. Immunity to C. albicans, the most frequent species to be isolated in candidiasis, involves a well-characterized Dectin-1/caspase-associated recruitment domain adaptor 9 (CARD9)/IL-17 signaling axis. Infections caused by non-albicans Candida species are on the rise, but surprisingly little is known about immunity to these pathogens. In this study, we evaluated a systemic infection model of C. tropicalis, a clinically relevant, but poorly understood, non-albicans Candida. Mice lacking CARD9 were profoundly susceptible to C. tropicalis, displaying elevated fungal burdens in visceral organs and increased mortality compared with wild-type (WT) controls. Unlike C. albicans, IL-17 responses were induced normally in CARD9(-/-) mice following C. tropicalis infection. Moreover, there was no difference in susceptibility to C. tropicalis infection between WT and IL-23p19(-/-), IL-17RA(-/-), or Act1(-/-) mice. However, TNF-α expression was markedly impaired in CARD9(-/-) mice. Consistently, WT mice depleted of TNF-α were more susceptible to C. tropicalis, and CARD9-deficient neutrophils and monocytes failed to produce TNF-α following stimulation with C. tropicalis Ags. Both neutrophils and monocytes were necessary for defense against C. tropicalis, because their depletion in WT mice enhanced susceptibility to C. tropicalis. Disease in CARD9(-/-) mice was not due to defective neutrophil or monocyte recruitment to infected kidneys. However, TNF-α treatment of neutrophils in vitro enhanced their ability to kill C. tropicalis. Thus, protection against systemic C. tropicalis infection requires CARD9 and TNF-α, but not IL-17, signaling. Moreover, CARD9-dependent production of TNF-α enhances the candidacidal capacity of neutrophils, limiting fungal disease during disseminated C. tropicalis infection. PMID:26336150

  8. Delinking CARD9 and IL-17: CARD9 Protects against Candida tropicalis Infection through a TNF-α–Dependent, IL-17–Independent Mechanism

    PubMed Central

    Whibley, Natasha; Jaycox, Jillian R.; Reid, Delyth; Garg, Abhishek V.; Taylor, Julie A.; Clancy, Cornelius J.; Nguyen, M. Hong; Biswas, Partha S.; McGeachy, Mandy J.; Brown, Gordon D.

    2015-01-01

    Candida is the third most common cause of bloodstream infections in hospitalized patients. Immunity to C. albicans, the most frequent species to be isolated in candidiasis, involves a well-characterized Dectin-1/caspase-associated recruitment domain adaptor 9 (CARD9)/IL-17 signaling axis. Infections caused by non-albicans Candida species are on the rise, but surprisingly little is known about immunity to these pathogens. In this study, we evaluated a systemic infection model of C. tropicalis, a clinically relevant, but poorly understood, non-albicans Candida. Mice lacking CARD9 were profoundly susceptible to C. tropicalis, displaying elevated fungal burdens in visceral organs and increased mortality compared with wild-type (WT) controls. Unlike C. albicans, IL-17 responses were induced normally in CARD9−/− mice following C. tropicalis infection. Moreover, there was no difference in susceptibility to C. tropicalis infection between WT and IL-23p19−/−, IL-17RA−/−, or Act1−/− mice. However, TNF-α expression was markedly impaired in CARD9−/− mice. Consistently, WT mice depleted of TNF-α were more susceptible to C. tropicalis, and CARD9-deficient neutrophils and monocytes failed to produce TNF-α following stimulation with C. tropicalis Ags. Both neutrophils and monocytes were necessary for defense against C. tropicalis, because their depletion in WT mice enhanced susceptibility to C. tropicalis. Disease in CARD9−/− mice was not due to defective neutrophil or monocyte recruitment to infected kidneys. However, TNF-α treatment of neutrophils in vitro enhanced their ability to kill C. tropicalis. Thus, protection against systemic C. tropicalis infection requires CARD9 and TNF-α, but not IL-17, signaling. Moreover, CARD9-dependent production of TNF-α enhances the candidacidal capacity of neutrophils, limiting fungal disease during disseminated C. tropicalis infection. PMID:26336150

  9. Candida albicans and Enterococcus faecalis in the gut

    PubMed Central

    Garsin, Danielle A; Lorenz, Michael C

    2013-01-01

    The fungus Candida albicans and the gram-positive bacterium Enterococcus faecalis are both normal residents of the human gut microbiome and cause opportunistic disseminated infections in immunocompromised individuals. Using a nematode infection model, we recently showed that co-infection resulted in less pathology and less mortality than infection with either species alone and this was partly explained by an interkingdom signaling event in which a bacterial-derived product inhibits hyphal morphogenesis of C. albicans. In this addendum we discuss these findings in the contest of other described bacterial-fungal interactions and recent data suggesting a potentially synergistic relationship between these two species in the mouse gut as well. We suggest that E. faecalis and C. albicans promote a mutually beneficial association with the host, in effect choosing a commensal lifestyle over a pathogenic one. PMID:23941906

  10. In vitro activity of eugenol against Candida albicans biofilms.

    PubMed

    He, Miao; Du, Minquan; Fan, Mingwen; Bian, Zhuan

    2007-03-01

    Most manifestations of candidiasis are associated with biofilm formation occurring on the surfaces of host tissues and medical devices. Candida albicans is the most frequently isolated causative pathogen of candidiasis, and the biofilms display significantly increased levels of resistance to the conventional antifungal agents. Eugenol, the major phenolic component of clove essential oil, possesses potent antifungal activity. The aim of this study was to investigate the effects of eugenol on preformed biofilms, adherent cells, subsequent biofilm formation and cell morphogenesis of C. albicans. Eugenol displayed in vitro activity against C. albicans cells within biofilms, when MIC(50) for sessile cells was 500 mg/L. C. albicans adherent cell populations (after 0, 1, 2 and 4 h of adherence) were treated with various concentrations of eugenol (0, 20, 200 and 2,000 mg/L). The extent of subsequent biofilm formation were then assessed with the tetrazolium salt reduction assay. Effect of eugenol on morphogenesis of C. albicans cells was observed by scanning electron microscopy (SEM). The results indicated that the effect of eugenol on adherent cells and subsequent biofilm formation was dependent on the initial adherence time and the concentration of this compound, and that eugenol can inhibit filamentous growth of C. albicans cells. In addition, using human erythrocytes, eugenol showed low hemolytic activity. These results indicated that eugenol displayed potent activity against C. albicans biofilms in vitro with low cytotoxicity and therefore has potential therapeutic implication for biofilm-associated candidal infections. PMID:17356790

  11. Induction of apoptosis in oral epithelial cells by Candida albicans.

    PubMed

    Villar, C Cunha; Chukwuedum Aniemeke, J; Zhao, X-R; Huynh-Ba, G

    2012-12-01

    During infection, interactions between Candida albicans and oral epithelial cells result in oral epithelial cell death. This is clinically manifested by the development of oral mucosal ulcerations generally associated with discomfort. In vitro studies have shown that C. albicans induces early apoptotic alterations in oral epithelial cells; however, these studies have also shown that treatment of infected cells with caspase inhibitors does not prevent their death. The reasons for these contradictory results are unknown and it is still not clear if C. albicans stimulates oral epithelial signaling pathways that promote apoptotic cell death. Activation of specific death pathways in response to microbial organisms plays an essential role in modulating the pathogenesis of a variety of infectious diseases. The aim of this study was to (i) characterize C. albicans-induced apoptotic morphological alterations in oral epithelial cells, and (ii) investigate the activation of apoptotic signaling pathways and expression of apoptotic genes during infection. Candida albicans induced early apoptotic changes in over 50% of oral epithelial cells. However, only 15% of those showed mid-late apoptotic alterations. At the molecular level, C. albicans caused a loss of the mitochondrial transmembrane potential and translocation of mitochondrial cytochrome c. Caspase-3/9 activities increased only during the first hours of infection. Moreover, poly[ADP ribose] polymerase 1 was cleaved into apoptotic and necrotic-like fragments. Finally, five anti-apoptotic genes were significantly upregulated and two pro-apoptotic genes were downregulated during infection. Altogether, these findings indicate that epithelial apoptotic pathways are activated in response to C. albicans, but fail to progress and promote apoptotic cell death. PMID:23134609

  12. Molecular genetic techniques for gene manipulation in Candida albicans

    PubMed Central

    Xu, Qiu-Rong; Yan, Lan; Lv, Quan-Zhen; Zhou, Mi; Sui, Xue; Cao, Yong-Bing; Jiang, Yuan-Ying

    2014-01-01

    Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains. PMID:24759671

  13. Molecular Insights into the Fungus-Specific Serine/Threonine Protein Phosphatase Z1 in Candida albicans

    PubMed Central

    Chen, Emily; Choy, Meng S.; Petrényi, Katalin; Kónya, Zoltán; Erdődi, Ferenc; Dombrádi, Viktor; Peti, Wolfgang

    2016-01-01

    ABSTRACT The opportunistic pathogen Candida is one of the most common causes of nosocomial bloodstream infections. Because candidemia is associated with high mortality rates and because the incidences of multidrug-resistant Candida are increasing, efforts to identify novel targets for the development of potent antifungals are warranted. Here, we describe the structure and function of the first member of a family of protein phosphatases that is specific to fungi, protein phosphatase Z1 (PPZ1) from Candida albicans. We show that PPZ1 not only is active but also is as susceptible to inhibition by the cyclic peptide inhibitor microcystin-LR as its most similar human homolog, protein phosphatase 1α (PP1α [GLC7 in the yeast Saccharomyces cerevisiae]). Unexpectedly, we also discovered that, despite its 66% sequence identity to PP1α, the catalytic domain of PPZ1 contains novel structural elements that are not present in PP1α. We then used activity and pulldown assays to show that these structural differences block a large subset of PP1/GLC7 regulatory proteins from effectively binding PPZ1, demonstrating that PPZ1 does not compete with GLC7 for its regulatory proteins. Equally important, these unique structural elements provide new pockets suitable for the development of PPZ1-specific inhibitors. Together, these studies not only reveal why PPZ1 does not negatively impact GLC7 activity in vivo but also demonstrate that the family of fungus-specific phosphatases—especially PPZ1 from C. albicans—are highly suitable targets for the development of novel drugs that specifically target C. albicans without cross-reacting with human phosphatases. PMID:27578752

  14. Candida albicans, the opportunist. A cellular and molecular perspective.

    PubMed

    Dupont, P F

    1995-02-01

    Candida albicans causes the majority of opportunistic fungal infections. The yeast's commensualistic relationship with humans enables it, when environmental conditions are favorable, to multiply and replace much of the normal flora. Virulence factors of C. albicans, enabling the organism to adhere to and penetrate host tissues, involve specific molecular interactions between the cells of the fungus and the host. Localized disease, such as oral candidiasis, onychomycosis, and vaginitis, results. These infections are usually limited to surfaces of the host, and can be quickly and successfully controlled by the use of one of the available antifungal agents. Candida albicans infections typically become systemic and life threatening when the host is immunocompromised. Depending on the immune defect in the host, one of the spectrum of Candida diseases can develop. If successful treatment of these patients is to be achieved, modulation of the immune deficit, as well as the use of an appropriate antifungal drug, must become a routine part of therapeutic interventions. PMID:7877106

  15. Interleukin 17-Mediated Host Defense against Candida albicans

    PubMed Central

    Sparber, Florian; LeibundGut-Landmann, Salomé

    2015-01-01

    Candida albicans is part of the normal microbiota in most healthy individuals. However, it can cause opportunistic infections if host defenses are breached, with symptoms ranging from superficial lesions to severe systemic disease. The study of rare congenital defects in patients with chronic mucocutaneous candidiasis led to the identification of interleukin-17 (IL-17) as a key factor in host defense against mucosal fungal infection. Experimental infections in mice confirmed the critical role of IL-17 in mucocutaneous immunity against C. albicans. Research on mouse models has also contributed importantly to our current understanding of the regulation of IL-17 production by different cellular sources and its effector functions in distinct tissues. In this review, we highlight recent findings on IL-17-mediated immunity against C. albicans in mouse and man. PMID:26274976

  16. Proinflammatory chemokines during Candida albicans keratitis.

    PubMed

    Yuan, Xiaoyong; Hua, Xia; Wilhelmus, Kirk R

    2010-03-01

    Chemotactic cytokines mediate the recruitment of leukocytes into infected tissues. This study investigated the profile of chemokines during experimental Candida albicans keratitis and determined the effects of chemokine inhibition on leukocyte infiltration and fungal growth during murine keratomycosis. Scarified corneas of BALB/c mice were topically inoculated with C. albicans and monitored daily over one week for fungal keratitis. After a gene microarray for murine chemokines compared infected corneas to controls, real-time reverse transcription polymerase chain reaction (RT-PCR) and immunostaining assessed chemokine expression in infected and mock-inoculated corneas. An anti-chemokine antibody was then administered subconjunctivally and evaluated for effects on clinical severity, corneal inflammation, fungal recovery, and cytokine expression. Of 33 chemokine genes examined by microarray, 6 CC chemokines and 6 CXC chemokines were significantly (P<0.05) upregulated more than two-fold. Chemokine (CC-motif) ligand 3 (CCL3) was upregulated 108-fold (P=0.03) by real-time RT-PCR within one day after fungal inoculation and remained increased 28-fold (P=0.02) at one week, and its in situ expression increased in the epithelium and stroma of infected corneas. Compared to the control antibody-treated group, eyes treated with anti-CCL3 antibody showed reduced clinical severity (P<0.05), less corneal neovascularization (P=0.02), and fewer inflammatory cells infiltrating corneal tissue, but the amount of recoverable fungi was not significantly (P=0.4) affected. Anti-CCL3 treatment significantly (P=0.01) reduced the expression of tumor necrosis factor and interleukin-1beta in infected corneas. These results indicate that chemokines, especially the CC chemokine CCL3, play important roles in the acute inflammatory response to C. albicans corneal infection. PMID:20005222

  17. In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.

    PubMed

    Reitzel, Ruth A; Rosenblatt, Joel; Hirsh-Ginsberg, Cheryl; Murray, Kimberly; Chaftari, Anne-Marie; Hachem, Ray; Raad, Issam

    2016-09-01

    The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment. PMID:27297475

  18. Candida albicans keratitis in an immunocompromised patient

    PubMed Central

    Hassan, H Mohammed J; Papanikolaou, Theocharis; Mariatos, Georgios; Hammad, Amany; Hassan, Hala

    2010-01-01

    Purpose When investigating a case of unexplained corneal ulceration, we need to think of fungal infection and any predisposing factors. Methods A case study of a corneal ulceration in a patient who was HIV positive with a devastating visual outcome. Results Therapeutic corneal graft was necessary due to corneal perforation. Immunocompromised state of patient was retrospectively diagnosed. Conclusions Candida albicans keratitis is an opportunistic infection of a compromised cornea, and sometimes unknowingly compromised host, which can be initially misdiagnosed. Despite intensive antifungal therapy, occasionally patients require corneal grafting to improve vision, and before it is possible to establish an accurate diagnosis. PMID:21060674

  19. Candida albicans Fungaemia following Traumatic Urethral Catheterisation in a Paraplegic Patient with Diabetes Mellitus and Candiduria Treated by Caspofungin

    PubMed Central

    Vaidyanathan, Subramanian; Soni, Bakul; Hughes, Peter; Singh, Gurpreet

    2013-01-01

    A 58-year-old paraplegic male, with long-term indwelling urethral catheter, developed catheter block. The catheter was changed, but blood-stained urine was drained intermittently. A long segment of the catheter was seen lying outside his penis, which indicated that the balloon of Foley catheter had been inflated in urethra. The misplaced catheter was removed and a new catheter was inserted correctly. Gentamicin 160 mg was given intravenously; meropenem 1 gram every eight hours was prescribed; antifungals were not given. Twenty hours later, this patient developed distension of abdomen, tachycardia, and hypotension; he was not arousable. Computed tomography of abdomen revealed inflamed uroepithelium of right renal pelvis and ureter, 4 mm lower ureteric calculus with gas in right ureter proximally, and vesical calculus containing gas in its matrix. Urine and blood culture yielded Candida albicans. Identical sensitivity pattern of both isolates suggested that the source of the bloodstream infection was most likely urine. Both isolates formed consistently high levels of biofilm formation in vitro as assessed using a biofilm biomass stain, and high levels of resistance to voriconazole were observed. Both amphotericin B and caspofungin showed good activity against the biofilms. HbA1c was 111 mmol/mol. This patient was prescribed human soluble insulin and caspofungin 70 mg followed by 50 mg daily intravenously. He recovered fully from candidemia. PMID:24223316

  20. Development of DNA probes for Candida albicans

    SciTech Connect

    Cheung, L.L.; Hudson, J.B.

    1988-07-01

    An attempt was made to produce DNA probes that could be used as a rapid and efficient means of detecting candidiasis (invasive Candida infection) in immunocompromised patients. Whole DNA from Candida albicans was digested with restriction endonuclease, and the resulting fragments were randomly cloned into a plasmid vector. Several recombinant plasmids were evaluated for cross-hybridization to various other Candida species, other fungal DNAs, and to nonfungal DNAs. Cross reactions were observed between the probes and different yeasts, but none with unrelated DNAs. Some recombinants were genus-specific, and two of these were applied to the analysis of C. albicans growth curves. It became evident that, although both /sup 32/P- and biotin-labelled probes could be made quite sensitive, a possible limitation in their diagnostic potential was the poor liberation of Candida DNA from cells. Thus, better methods of treatment of clinical specimens will be required before such probes will be useful in routine diagnosis.

  1. Human Epithelial Cells Discriminate between Commensal and Pathogenic Interactions with Candida albicans

    PubMed Central

    Rast, Timothy J.; Kullas, Amy L.; Southern, Peter J.; Davis, Dana A.

    2016-01-01

    The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage. PMID:27088599

  2. Heparin-Binding Motifs and Biofilm Formation by Candida albicans

    PubMed Central

    Green, Julianne V.; Orsborn, Kris I.; Zhang, Minlu; Tan, Queenie K. G.; Greis, Kenneth D.; Porollo, Alexey; Andes, David R.; Long Lu, Jason; Hostetter, Margaret K.

    2013-01-01

    Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequence-based search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms. PMID:23904295

  3. Lactobacillus acidophilus ATCC 4356 inhibits biofilm formation by C. albicans and attenuates the experimental candidiasis in Galleria mellonella

    PubMed Central

    Vilela, Simone FG; Barbosa, Júnia O; Rossoni, Rodnei D; Santos, Jéssica D; Prata, Marcia CA; Anbinder, Ana Lia; Jorge, Antonio OC; Junqueira, Juliana C

    2015-01-01

    Probiotic strains of Lactobacillus have been studied for their inhibitory effects on Candida albicans. However, few studies have investigated the effect of these strains on biofilm formation, filamentation and C. albicans infection. The objective of this study was to evaluate the influence of Lactobacillus acidophilus ATCC 4356 on C. albicans ATCC 18804 using in vitro and in vivo models. In vitro analysis evaluated the effects of L. acidophilus on the biofilm formation and on the capacity of C. albicans filamentation. For in vivo study, Galleria mellonella was used as an infection model to evaluate the effects of L. acidophilus on candidiasis by survival analysis, quantification of C. albicans CFU/mL, and histological analysis. The direct effects of L. acidophilus cells on C. albicans, as well as the indirect effects using only a Lactobacillus culture filtrate, were evaluated in both tests. The in vitro results showed that both L. acidophilus cells and filtrate were able to inhibit C. albicans biofilm formation and filamentation. In the in vivo study, injection of L. acidophilus into G. mellonella larvae infected with C. albicans increased the survival of these animals. Furthermore, the number of C. albicans CFU/mL recovered from the larval hemolymph was lower in the group inoculated with L. acidophilus compared to the control group. In conclusion, L. acidophilus ATCC 4356 inhibited in vitro biofilm formation by C. albicans and protected G. mellonella against experimental candidiasis in vivo. PMID:25654408

  4. Cigarette smoke-exposed Candida albicans increased chitin production and modulated human fibroblast cell responses.

    PubMed

    Alanazi, Humidah; Semlali, Abdelhabib; Perraud, Laura; Chmielewski, Witold; Zakrzewski, Andrew; Rouabhia, Mahmoud

    2014-01-01

    The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC) on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P < 0.01) sensitive to oxidation but significantly (P < 0.01) resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P < 0.01) slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers. PMID:25302312

  5. Cigarette Smoke-Exposed Candida albicans Increased Chitin Production and Modulated Human Fibroblast Cell Responses

    PubMed Central

    Alanazi, Humidah; Semlali, Abdelhabib; Perraud, Laura; Chmielewski, Witold; Zakrzewski, Andrew

    2014-01-01

    The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC) on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P < 0.01) sensitive to oxidation but significantly (P < 0.01) resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P < 0.01) slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers. PMID:25302312

  6. Possible inhibition of N. gonnorrhoeae by C. albicans. A clinical study.

    PubMed

    Wallin, J; Gnarpe, H

    1975-06-01

    A probably sifnificant difference (p smaller that 0.05) in the occurrence of gonorrhoea was found between women with and without concomitant C. albicans infection. Although this difference could support the recently reported inhibitory effect by C. albicans on N. gonorrhoeae in vitro another explanation might be the possibility that too many women with vaginal candidiasis and no risk for a gonococcal infection were included in the material. There was nothing to support the in vivo effect of C. albicans on N. gonorrhoeae as negative gonococcal cultures in women known to have been exposed to N. gonorrhoeae could not be correlated with the presence of C. albicans. Until the clinical importance of the inhibitory factor of C. albicans has been studied further, the clinician has to be aware of the possibility of false negative gonococcal cultures from women with vaginal candidiasis. PMID:806326

  7. Spaceflight enhances cell aggregation and random budding in Candida albicans.

    PubMed

    Crabbé, Aurélie; Nielsen-Preiss, Sheila M; Woolley, Christine M; Barrila, Jennifer; Buchanan, Kent; McCracken, James; Inglis, Diane O; Searles, Stephen C; Nelman-Gonzalez, Mayra A; Ott, C Mark; Wilson, James W; Pierson, Duane L; Stefanyshyn-Piper, Heidemarie M; Hyman, Linda E; Nickerson, Cheryl A

    2013-01-01

    This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans-induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid

  8. Surface electrical charge of bloodstream trypomastigotes of Trypanosoma cruzi strains.

    PubMed

    de Sousa, M A

    1983-01-01

    Bloodstream trypomastigotes of some Trypanosoma cruzi strains were processed through DEAE-cellulose columns under standardized conditions. The results obtained suggest mainly that these strains present different surface charges, that there are subpopulations of bloodstream trypomastigotes as regards electrical charges and that the broad forms are less negative than the slender ones. PMID:6443631

  9. Severe Bloodstream Infection due to KPC-Producer E coli in a Renal Transplant Recipient Treated With the Double-Carbapenem Regimen and Analysis of In Vitro Synergy Testing

    PubMed Central

    Oliva, Alessandra; Cipolla, Alessia; Gizzi, Francesca; D’Abramo, Alessandra; Favaro, Marco; De Angelis, Massimiliano; Ferretti, Giancarlo; Russo, Gianluca; Iannetta, Marco; Mastroianni, Claudio M.; Mascellino, Maria T.; Vullo, Vincenzo

    2016-01-01

    Abstract Transplant recipients are at high risk of infections caused by multidrug resistant microorganisms. Due to the limited therapeutic options, innovative antimicrobial combinations against carbapenem-resistant Enterobacteriaceae causing severe infections are necessary. A 61-year-old woman with a history of congenital solitary kidney underwent renal transplantation. The postoperative course was complicated by nosocomial pneumonia due to Stenotrophomonas maltophilia and pan-sensitive Escherichia coli, successfully treated with antimicrobial therapy. On postoperative day 22, diagnosis of surgical site infection and nosocomial pneumonia with concomitant bacteremia due to a Klebisella pneumoniae carbapenemase-producer E coli was made. The patient was treated with the double-carbapenem regimen (high dose of meropenem plus ertapenem) and a potent synergistic and bactericidal activity of this un-conventional therapeutic strategy was observed in vitro. Despite a microbiological response with prompt negativity of blood cultures, the patient faced a worse outcome because of severe hemorrhagic shock. The double-carbapenem regimen might be considered as a rescue therapy in those subjects, including transplant recipients, in whom previous antimicrobial combinations failed or when colistin use might be discouraged. Performing in vitro synergy testing should be strongly encouraged in cases of infections caused by pan-drug resistant strains, especially in high-risk patients. PMID:26886594

  10. A Monoclonal Antibody Directed against a Candida albicans Cell Wall Mannoprotein Exerts Three Anti-C. albicans Activities

    PubMed Central

    Moragues, María D.; Omaetxebarria, Miren J.; Elguezabal, Natalia; Sevilla, María J.; Conti, Stefania; Polonelli, Luciano; Pontón, José

    2003-01-01

    Antibodies are believed to play a role in the protection against Candida albicans infections by a number of mechanisms, including the inhibition of adhesion or germ tube formation, opsonization, neutralization of virulence-related enzymes, and direct candidacidal activity. Although some of these biological activities have been demonstrated individually in monoclonal antibodies (MAbs), it is not clear if all these anti-C. albicans activities can be displayed by a single antibody. In this report, we characterized a monoclonal antibody raised against the main target of salivary secretory immunoglobulin A in the cell wall of C. albicans, which exerts three anti-C. albicans activities: (i) inhibition of adherence to HEp-2 cells, (ii) inhibition of germination, and (iii) direct candidacidal activity. MAb C7 reacted with a proteinic epitope from a mannoprotein with a molecular mass of >200 kDa predominantly expressed on the C. albicans germ tube cell wall surface as well as with a number of antigens from Candida lusitaniae, Cryptococcus neoformans, Aspergillus fumigatus, and Scedosporium prolificans. MAb C7 caused a 31.1% inhibition in the adhesion of C. albicans to HEp-2 monolayers and a 55.3% inhibition in the adhesion of C. albicans to buccal epithelial cells, produced a 38.5% decrease in the filamentation of C. albicans, and exhibited a potent fungicidal effect against C. albicans, C. lusitaniae, Cryptococcus neoformans, A. fumigatus, and S. prolificans, showing reductions in fungal growth ranging from 34.2 to 88.7%. The fungicidal activity showed by MAb C7 seems to be related to that reported by antibodies mimicking the activity of a killer toxin produced by the yeast Pichia anomala, since one of these MAbs also reacted with the C. albicans mannoprotein with a molecular mass of >200 kDa. Results presented in this study support the concept of a family of microbicidal antibodies that could be useful in the treatment of a wide range of microbial infections when used

  11. Interplay between the Gastric Bacterial Microbiota and Candida albicans during Postantibiotic Recolonization and Gastritis

    PubMed Central

    Mason, Katie L.; Erb Downward, John R.; Falkowski, Nicole R.; Young, Vincent B.; Kao, John Y.

    2012-01-01

    The indigenous bacterial microbiome of the stomach, including lactobacilli, is vital in promoting colonization resistance against Candida albicans. However, there are gaps in our understanding about C. albicans gastric colonization versus disease, especially during the postantibiotic recovery phase. This study compared the gastric responses to C. albicans strains CHN1 and SC5314 in microbiome-disturbed and germfree mice to elucidate the contribution of the indigenous microbiota in C. albicans colonization versus disease and yeast-bacterium antagonism during the post-cefoperazone recolonization period. C. albicans can prevent the regrowth of Lactobacillus spp. in the stomach after cefoperazone and promote increased colonization by Enterococcus spp. Using a culture-independent analysis, the effects of oral cefoperazone on the gastric bacterial microbiota were observed to last at least 3 weeks after the cessation of the antibiotic. Disturbance of the gastric bacterial community by cefoperazone alone was not sufficient to cause gastritis, C. albicans colonization was also needed. Gastritis was not evident until after day 7 in cefoperazone-treated infected mice. In contrast, in germfree mice which lack a gastric microbiota, C. albicans induced gastric inflammation within 1 week of inoculation. Therefore, the gastric bacterial community in cefoperazone-treated mice during the first week of postantibiotic recolonization was sufficient to prevent the development of gastritis, despite being ineffective at conferring colonization resistance against C. albicans. Altogether, these data implicate a dichotomy between C. albicans colonization and gastric disease that is bacterial microbiome dependent. PMID:21986629

  12. Candida albicans clades.

    PubMed

    Soll, David R; Pujol, Claude

    2003-10-24

    DNA fingerprinting with the complex probe Ca3 has revealed the following five Candida albicans clades: group I, group II, group III, group SA and group E. These groups exhibit geographical specificity. Group SA is relatively specific (i.e., highly enriched) to South Africa, group E is relatively specific to Europe, and group II is absent in the Southwest USA and South America. The maintenance of deep-rooted clades side by side in the same geographical locale and the apparent absence of subclade structure suggest little recombination between clades, but higher rates of recombination within clades. Exclusive 5-fluorocytosine resistance in the majority of group I isolates reinforces the above conclusions on recombination, and demonstrates that clades differ phenotypically. The ramifications of these findings with regard to pathogenesis are discussed. In particular, these findings lay to rest the idea that one strain represents all strains of C. albicans, support the need for a worldwide analysis of population structure and clade-specific phenotypic characteristics, and demonstrate that in the future, pathogenic characteristics must be analyzed in representatives from all five clades. PMID:14556989

  13. Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans

    PubMed Central

    Li, Xiuyun; Hou, Yinglong; Yue, Longtao; Liu, Shuyuan; Du, Juan

    2015-01-01

    Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in C. albicans and examines potential targets for the development of new antifungal drugs. PMID:26195510

  14. Plant-derived decapeptide OSIP108 interferes with Candida albicans biofilm formation without affecting cell viability.

    PubMed

    Delattin, Nicolas; De Brucker, Katrijn; Craik, David J; Cheneval, Olivier; Fröhlich, Mirjam; Veber, Matija; Girandon, Lenart; Davis, Talya R; Weeks, Anne E; Kumamoto, Carol A; Cos, Paul; Coenye, Tom; De Coninck, Barbara; Cammue, Bruno P A; Thevissen, Karin

    2014-05-01

    We previously identified a decapeptide from the model plant Arabidopsis thaliana, OSIP108, which is induced upon fungal pathogen infection. In this study, we demonstrated that OSIP108 interferes with biofilm formation of the fungal pathogen Candida albicans without affecting the viability or growth of C. albicans cells. OSIP108 displayed no cytotoxicity against various human cell lines. Furthermore, OSIP108 enhanced the activity of the antifungal agents amphotericin B and caspofungin in vitro and in vivo in a Caenorhabditis elegans-C. albicans biofilm infection model. These data point to the potential use of OSIP108 in combination therapy with conventional antifungal agents. In a first attempt to unravel its mode of action, we screened a library of 137 homozygous C. albicans mutants, affected in genes encoding cell wall proteins or transcription factors important for biofilm formation, for altered OSIP108 sensitivity. We identified 9 OSIP108-tolerant C. albicans mutants that were defective in either components important for cell wall integrity or the yeast-to-hypha transition. In line with these findings, we demonstrated that OSIP108 activates the C. albicans cell wall integrity pathway and that its antibiofilm activity can be blocked by compounds inhibiting the yeast-to-hypha transition. Furthermore, we found that OSIP108 is predominantly localized at the C. albicans cell surface. These data point to interference of OSIP108 with cell wall-related processes of C. albicans, resulting in impaired biofilm formation. PMID:24566179

  15. Candida albicans commensalism in the gastrointestinal tract.

    PubMed

    Neville, B Anne; d'Enfert, Christophe; Bougnoux, Marie-Elisabeth

    2015-11-01

    Candida albicans is a polymorphic yeast species that often forms part of the commensal gastrointestinal mycobiota of healthy humans. It is also an important opportunistic pathogen. A tripartite interaction involving C. albicans, the resident microbiota and host immunity maintains C. albicans in its commensal form. The influence of each of these factors on C. albicans carriage is considered herein, with particular focus on the mycobiota and the approaches used to study it, models of gastrointestinal colonization by C. albicans, the C. albicans genes and phenotypes that are necessary for commensalism and the host factors that influence C. albicans carriage. PMID:26347504

  16. Effect of Candida albicans on Intestinal Ischemia-reperfusion Injury in Rats

    PubMed Central

    Yan, Lei; Wu, Chun-Rong; Wang, Chen; Yang, Chun-Hui; Tong, Guang-Zhi; Tang, Jian-Guo

    2016-01-01

    Background: Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperfusion injury (IIRI), and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa. This study aimed to explore the effect of C. albicans on IIRI. Methods: Fifty female Wistar rats were divided into five groups according to the status of C. albicans infection and IIRI operation: group blank and sham; group blank and IIRI; group cefoperazone plus IIRI; group C. albicans plus cefoperazone and IIRI (CCI); and group C. albicans plus cefoperazone and sham. The levels of inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and diamine oxidase (DAO) measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine. Histological scores were used to assess the mucosal damage, and the C. albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier. Results: The levels of inflammatory factors TNF-α, IL-6, and IL-1β in serum and intestine were higher in rats undergone both C. albicans infection and IIRI operation compared with rats in other groups. The levels of DAO (serum: 44.13 ± 4.30 pg/ml, intestine: 346.21 ± 37.03 pg/g) and Chiu scores (3.41 ± 1.09) which reflected intestinal mucosal disruption were highest in group CCI after the operation. The number of C. albicans translocated into blood was most in group CCI ([33.80 ± 6.60] ×102 colony forming unit (CFU)/ml). Conclusion: Intestinal C. albicans infection worsened the IIRI-induced disruption of intestinal mucosal barrier and facilitated the subsequent C. albicans translocation and dissemination. PMID:27411459

  17. Enigmatic Presence of Mitochondrial Complex I in Trypanosoma brucei Bloodstream Forms

    PubMed Central

    Surve, Sachin; Heestand, Meredith; Panicucci, Brian

    2012-01-01

    The presence of mitochondrial respiratory complex I in the pathogenic bloodstream stages of Trypanosoma brucei has been vigorously debated: increased expression of mitochondrially encoded functional complex I mRNAs is countered by low levels of enzymatic activity that show marginal inhibition by the specific inhibitor rotenone. We now show that epitope-tagged versions of multiple complex I subunits assemble into α and β subcomplexes in the bloodstream stage and that these subcomplexes require the mitochondrial genome for their assembly. Despite the presence of these large (740- and 855-kDa) multisubunit complexes, the electron transport activity of complex I is not essential under experimental conditions since null mutants of two core genes (NUBM and NUKM) showed no growth defect in vitro or in mouse infection. Furthermore, the null mutants showed no decrease in NADH:ubiquinone oxidoreductase activity, suggesting that the observed activity is not contributed by complex I. This work conclusively shows that despite the synthesis and assembly of subunit proteins, the enzymatic function of the largest respiratory complex is neither significant nor important in the bloodstream stage. This situation appears to be in striking contrast to that for the other respiratory complexes in this parasite, where physical presence in a life-cycle stage always indicates functional significance. PMID:22158713

  18. Candida dubliniensis: an appraisal of its clinical significance as a bloodstream pathogen.

    PubMed

    Khan, Ziauddin; Ahmad, Suhail; Joseph, Leena; Chandy, Rachel

    2012-01-01

    A nine-year prospective study (2002-2010) on the prevalence of Candida dubliniensis among Candida bloodstream isolates is presented. The germ tube positive isolates were provisionally identified as C. dubliniensis by presence of fringed and rough colonies on sunflower seed agar. Subsequently, their identity was confirmed by Vitek2 Yeast identification system and/or by amplification and sequencing of the ITS region of rDNA. In all, 368 isolates were identified as C. dubliniensis; 67.1% came from respiratory specimens, 11.7% from oral swabs, 9.2% from urine, 3.8% from blood, 2.7% from vaginal swabs and 5.4% from other sources. All C. dubliniensis isolates tested by Etest were susceptible to voriconazole and amphotericin B. Resistance to fluconazole (≥8 µg/ml) was observed in 2.5% of C. dubliniensis isolates, 7 of which occurred between 2008-2010. Of note was the diagnosis of C. dubliniensis candidemia in 14 patients, 11 of them occurring between 2008-2010. None of the bloodstream isolate was resistant to fluconazole, while a solitary isolate showed increased MIC to 5-flucytosine (>32 µg/ml) and belonged to genotype 4. A review of literature since 1999 revealed 28 additional cases of C. dubliniensis candidemia, and 167 isolates identified from blood cultures since 1982. In conclusion, this study highlights a greater role of C. dubliniensis in bloodstream infections than hitherto recognized. PMID:22396802

  19. Caprylic acid in the effective treatment of intractable medical problems of frequent urination, incontinence, chronic upper respiratory infection, root canalled tooth infection, ALS, etc., caused by asbestos & mixed infections of Candida albicans, Helicobacter pylori & cytomegalovirus with or without other microorganisms & mercury.

    PubMed

    Omura, Yoshiaki; O'Young, Brian; Jones, Marilyn; Pallos, Andrew; Duvvi, Harsha; Shimotsuura, Yasuhiro

    2011-01-01

    There are many causes of frequent urination. Whenever water or fluids are consumed, the patient has to urinate within 10 or 20 min. Often urinary bladder examinations & blood tests show no significant abnormalities, & treatment by anti-bacterial or anti-viral agents does not improve the symptoms significantly. In intractable frequent urination with difficulty holding urine, as well as other intractable medical problems such as frequent coughing, white pus in gingiva, infection of the apex of a root canalled tooth, slow-healing wounds, & ALS, the authors often found coexisting mixed infections of Candida albicans (C.A.), Helicobacter pylori (H.P.), & Cytomegalovirus (CMV) with or without additional bacterial (Chlamydia trachomatis, etc.) or viral infections & increased Asbestos, with or without Hg deposits. We often found various degrees of mixed infections with C.A., H.P., & CMV in the external sphincters of the urethra & in the Trigone of the urinary bladder which consists of (1) a horizontal, band-like area between the 2 ureter openings & (2) the funnel shaped part of the Trigone at the lower half of the urinary bladder. In the coexistence of significant amounts of C.A., H.P. & CMV, the infection cannot be reduced by otherwise effective medicines for H.P. & CMV. However, one optimal dose of Diflucan, or Caprylic acid taken orally or externally applied, rapidly reduced the symptoms significantly. We found the best treatment is to give a combination of an optimal dose of Caprylic acid orally in the form of "CaprilyCare" or "Caprylic Acid," with a capsule of Omega-3 Fish Oil as an anti-viral agent, Amoxicillin, Substance Z & a Cilantro tablet. We found that an optimal dose of Caprylic acid increases normal cell telomere (NCT) to a desirable 750 ng BDORT units while Diflucan increases NCT by only 25 ng BDORT units, & with Omega-3 fish oil, leads to a mutual cancellation of both drugs. Thus, Caprylic acid is superior to & less expensive than Diflucan, & has potential

  20. A morphogenetic regulatory role for ethyl alcohol in Candida albicans.

    PubMed

    Chauhan, Nitin M; Raut, Jayant S; Karuppayil, S Mohan

    2011-11-01

    Regulation of morphogenesis through the production of chemical signalling molecules such as isoamyl alcohol, 2-phenylethyl alcohol, 1-dodecanol, E-nerolidol and farnesol is reported in Candida albicans. The present study focuses on the effect of ethyl alcohol on C. albicans dimorphism and biofilm development. Ethyl alcohol inhibited germ tube formation induced by the four standard inducers in a concentration-dependent manner. The germ tube inhibitory concentration (4%) did not have any effect on the growth and viability of C. albicans cells. Ethyl alcohol also inhibited the elongation of germ tubes. Four percentage of ethyl alcohol significantly inhibited biofilm development on polystyrene and silicone surfaces. We suggest a potential morphogenetic regulatory role for ethyl alcohol, which may influence dissemination, virulence and establishment of infection. PMID:21605190

  1. Vaginal yeast infection

    MedlinePlus

    Yeast infection - vagina; Vaginal candidiasis; Monilial vaginitis ... Most women have a vaginal yeast infection at some time. Candida albicans is a common type of fungus. It is often found in small amounts in the vagina , ...

  2. Vaginal yeast infection

    MedlinePlus

    Yeast infection - vagina; Vaginal candidiasis; Monilial vaginitis ... Most women have a vaginal yeast infection at some time. Candida albicans is a common type of fungus. It is often found in small amounts in the ...

  3. Oxidative stress responses in the human fungal pathogen, Candida albicans.

    PubMed

    Dantas, Alessandra da Silva; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

    2015-01-01

    Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

  4. Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae.

    PubMed

    Brennan, Marc; Thomas, David Y; Whiteway, Malcolm; Kavanagh, Kevin

    2002-10-11

    Candida albicans is a dimorphic human pathogen in which the yeast to hyphal switch may be an important factor in virulence in mammals. This pathogen has recently been shown to also kill insects such as the Greater Wax Moth Galleria mellonella when injected into the haemocoel of the insect larvae. We have investigated the effect of previously characterised C. albicans mutations that influence the yeast to hyphal transition on virulence in G. mellonella larvae. There is a good correlation between the virulence of these mutants in the insect host and the virulence measured through systemic infection of mice. Although the predominant cellular species detected in G. mellonella infections is the yeast form of C. albicans, mutations that influence the hyphal transition also reduce pathogenicity in the insect. The correlation with virulence measured in the mouse infection system suggests that Galleria may provide a convenient and inexpensive model for the in vivo screening of mutants of C. albicans. PMID:12381467

  5. Spaceflight Enhances Cell Aggregation and Random Budding in Candida albicans

    PubMed Central

    Woolley, Christine M.; Barrila, Jennifer; Buchanan, Kent; McCracken, James; Inglis, Diane O.; Searles, Stephen C.; Nelman-Gonzalez, Mayra A.; Ott, C. Mark; Wilson, James W.; Pierson, Duane L.; Stefanyshyn-Piper, Heidemarie M.; Hyman, Linda E.; Nickerson, Cheryl A.

    2013-01-01

    This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans–induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid

  6. Ocimum sanctum essential oil inhibits virulence attributes in Candida albicans.

    PubMed

    Khan, Amber; Ahmad, Aijaz; Xess, Immaculata; Khan, Luqman A; Manzoor, Nikhat

    2014-03-15

    Candida albicans is an opportunistic human fungal pathogen which causes disease mainly in immunocompromised patients. Activity of hydrolytic enzymes is essential for virulence of C. albicans and so is the capacity of these cells to undergo transition from yeast to mycelial form of growth. Ocimum sanctum is cultivated worldwide for its essential oil which exhibits medicinal properties. This work evaluates the anti-virulence activity of O. sanctum essential oil (OSEO) on 22 strains of C. albicans (including a standard strain ATCC 90028) isolated from both HIV positive and HIV negative patients. Candida isolates were exposed to sub-MICs of OSEO. In vitro secretion of proteinases and phospholipases was evaluated by plate assay containing BSA and egg yolk respectively. Morphological transition from yeast to filamentous form was monitored microscopically in LSM. For genetic analysis, respective genes associated with morphological transition (HWP1), proteinase (SAP1) and phospholipase (PLB2) were also investigated by Real Time PCR (qRT-PCR). Results were analyzed using Student's t-test. OSEO inhibits morphological transition in C. albicans and had a significant inhibitory effect on extracellular secretion of proteinases and phospholipases. Expression profile of respective selected genes associated with C. albicans virulence by qRT-PCR showed a reduced expression of HWP1, SAP1 and PLB2 genes in cells treated with sub-inhibitory concentrations of OSEO. This work suggests that OSEO inhibits morphological transition in C. albicans and decreases the secretion of hydrolytic enzymes involved in the early stage of infection as well as down regulates the associated genes. Further studies will assess the clinical application of OSEO and its constituents in the treatment of fungal infections. PMID:24252340

  7. [Candida albicans endocarditis after pulmonary artery banding].

    PubMed

    Talvard, M; Paranon, S; Dulac, Y; Mansir, T; Kreitmann, B; Acar, P

    2009-08-01

    Endocarditis is uncommon in infants and is exceptionally related to Candida albicans on pulmonary banding. We report on a case in a 7-month-old infant who had pulmonary artery banding for a ventricular septal defect and who presented with candidal endocarditis. Banding was chosen because of the patient's poor trophic and unstable status, which could be risky for surgery involving extracorporeal circulation. A few weeks after the banding, the patient developed systemic Candida infection, which was treated successfully. At 7 months, cardiac failure appeared without fever or inflammatory signs. Cardiac echography showed that the banding was not protective as well as a hyperechogenic image on the pulmonary bifurcation. The angioscan showed a hypodense thrombus. Emergency surgery was performed consisting of pulmonary artery exploration, thrombectomy, and ventricular septal defect closure. The exploration showed a pulmonary artery perforation caused by the infected pseudoaneurysm and the migration of the banding into the pulmonary artery. The anatomopathologic analysis of the vegetation identified multisensitive Candida albicans. After surgery and prolonged antifungal treatment, progression was satisfactory. PMID:19525096

  8. Direct Screening of Blood by PCR and Pyrosequencing for a 16S rRNA Gene Target from Emergency Department and Intensive Care Unit Patients Being Evaluated for Bloodstream Infection

    PubMed Central

    Moore, M. S.; McCarroll, M. G.; McCann, C. D.; May, L.; Younes, N.

    2015-01-01

    three-quarters of all culture-confirmed cases of bacteremia directly from blood in significantly less time than standard culture but cannot be used to rule out infection. PMID:26511737

  9. IL-17 Signaling in Host Defense Against Candida albicans

    PubMed Central

    Gaffen, Sarah L.; Hernandez-Santos, Nydiaris; Peterson, Alanna C.

    2012-01-01

    The discovery of the Th17 lineage in 2005 triggered a major change in how immunity to infectious diseases is viewed. Fungal infections, in particular, have long been a relatively understudied area of investigation in terms of the host immune response. Candida albicans is a commensal yeast that colonizes mucosal sites and skin. In healthy individuals it is non-pathogenic, but in conditions of immune deficiency, this organism can cause a variety of infections associated with considerable morbidity. Candida can also cause disseminated infections that have a high mortality rate and are a major clinical problem in hospital settings. Although immunity to Candida albicans was long considered to be mediated by Th1 cells, new data in both rodent models and in humans have revealed an essential role for the Th17 lineage, and in particular its signature cytokine IL-17. PMID:21717069

  10. Inhibition of Candida albicans virulence factors by novel levofloxacin derivatives.

    PubMed

    Shafreen, Raja Mohamed Beema; Raja Mohamed, Beema Shafreen; Muthamil, Subramanian; Subramanian, Muthamil; Pandian, Shunmugiah Karutha; Shunmugiah, Karutha Pandian

    2014-08-01

    Candida albicans is an important opportunistic fungal pathogen, responsible for biofilm associated infections in immunocompromised patients. The aim of the present study was to investigate the antibiofilm properties of novel levofloxacin derivatives on C. albicans biofilms. The levofloxacin derivatives at their Biofilm Inhibitory Concentrations (BIC) were able to inhibit the biofilms of C. albicans, the yeast-to-hyphal transition and were also able to disrupt their mature biofilms. Furthermore, Real-time PCR analysis showed that the expression of ergosterol biosynthesis pathway gene (ERG11) and the efflux pump-encoding genes (CDR1 and MDR1) was decreased upon treatment with the levofloxacin derivatives. The total ergosterol content quantified using UV spectrophotomer showed decrease in ergosterol in the presence of levofloxacin derivatives. Overall, levofloxacin derivatives (6a, 6c and 7d) are capable of inhibiting C. albicans virulence factors. Therefore, these compounds with potential therapeutic implications can be used as new strategy to treat biofilm-related candidal infections. PMID:24723295

  11. Water: the bloodstream of the biosphere.

    PubMed Central

    Ripl, Wilhelm

    2003-01-01

    Water, the bloodstream of the biosphere, determines the sustainability of living systems. The essential role of water is expanded in a conceptual model of energy dissipation, based on the water balance of whole landscapes. In this model, the underlying role of water phase changes--and their energy-dissipative properties--in the function and the self-organized development of natural systems is explicitly recognized. The energy-dissipating processes regulate the ecological dynamics within the Earth's biosphere, in such a way that the development of natural systems is never allowed to proceed in an undirected or random way. A fundamental characteristic of self-organized development in natural systems is the increasing role of cyclic processes while loss processes are correspondingly reduced. This gives a coincidental increase in system efficiency, which is the basis of growing stability and sustainability. Growing sustainability can be seen as an increase of ecological efficiency, which is applicable at all levels up to whole landscapes. Criteria for necessary changes in society and for the design of the measures that are necessary to restore sustainable landscapes and waters are derived. PMID:14728789

  12. When Prostate Cancer Circulates in the Bloodstream

    PubMed Central

    Vlaeminck-Guillem, Virginie

    2015-01-01

    Management of patients with prostate cancer is currently based on imperfect clinical, biological, radiological and pathological evaluation. Prostate cancer aggressiveness, including metastatic potential, remains difficult to accurately estimate. In an attempt to better adapt therapeutics to an individual (personalized medicine), reliable evaluation of the intrinsic molecular biology of the tumor is warranted, an