Early Diagnosis, Prevention, and Treatment of C. difficile: Update [Entered Retrospectively]

Project Summary Title and Description

Early Diagnosis, Prevention, and Treatment of C. difficile: Update [Entered Retrospectively]
Objective. Update a 2011 review of differences in accuracy of diagnostic tests and the effects of interventions to prevent and treat C. difficile infection (CDI) in adults. Data sources. Medline, the Cochrane Clinical Trials Registry, EMBASE, from 2010 through April 2015 plus reference lists of included studies and recent systematic reviews. Methods. Two investigators screened abstracts and full texts of identified references for eligibility. Eligible studies included studies of sensitivity and specificity for diagnostic tests in patients at risk for CDI. We included randomized controlled trials or high quality cohort studies enrolling adult patients with CDI or suspected CDI for treatment interventions. Prevention studies also included adult patients at risk for CDI and observational study designs. Two investigators extracted data, assessed individual study risk of bias, and evaluated the strength of evidence for each comparison and outcome. Pooled estimates were analyzed to assess the efficacy and comparative effectiveness of a variety of treatments. Results. We identified 37 diagnostic studies and 56 studies evaluating prevention or treatment interventions to update the review. High-strength evidence showed nucleic amplification tests were sensitive and specific for CDI when using culture as the reference standard. Low-strength evidence found some institutional prevention interventions, such as antibiotic prescribing practices and transmission interruption (terminal room cleaning with hydrogen peroxide vapor and handwashing campaigns) reduces CDI incidence. Low-strength evidence also suggests prevention programs can be sustained over several years. For CDI treatment, vancomycin is more effective than metronidazole (high-strength evidence), and the effect does not vary by severity (moderate-strength evidence). Fidaxomicin remains noninferior to vancomycin for the initial cure of CDI (moderate-strength evidence), but is superior to vancomycin for prevention of recurrent CDI (now high-strength evidence). Although both FMT and probiotics were the subject of a significant number of new studies, the overall high risk of bias of many of these studies necessitated low-strength of evidence ratings. Specifically, low-strength evidence suggests that FMT may have a significant effect on reducing recurrent CDI. Similarly, low-strength evidence suggests that lactobaccilus strains and multiorganism probiotics also can reduce recurrent CDI. However, Saccharomyces boulardii was no more effective than placebo in preventing recurrent CDI. Evidence for FMT for refractory CDI was insufficient. Few studies reported adverse events; when reported, few events were noted. Conclusions. Research on diagnostic testing for and interventions to treat CDI expanded considerably in 4 years. Nucleic acid amplification tests have high sensitivity and specificity for CDI. Vancomycin is more effective than metronidazole for initial CDI, while fidaxomicin is more effective than vancomycin for the prevention of recurrent CDI. FMT and lactobacillus probiotics to restore colonic biodiversity and improve patient resistance to CDI or recurrence have low strength but relatively consistent positive evidence for efficacy.
Authors of Report
Methodology description
Web address not yet available. Data entered retrospectively. Word tables contain basic study information, quality assessments, outcomes evaluated, and adverse events.
Funding Source

Key Questions

1. How do different methods for detection of toxigenic C. difficile to assist with diagnosis of CDI compare in their sensitivity, specificity, and predictive values? a. Overall? b. Do performance measures vary with sample characteristics? c. Does testing strategy impact patient health or health system outcomes?
2. What are effective prevention strategies? a. What is the effectiveness of current prevention strategies? b. What are the harms associated with prevention strategies? c. How sustainable are prevention practices in health care (outpatient, hospital inpatient, extended care) and community settings?
3. What is the comparative effectiveness and harms of different antibiotic treatments? a. Does effectiveness vary by disease severity?
4. What are the effectiveness and harms of other interventions? a. Overall b. In patients with relapse/recurrent CDI.

Associated Extraction Forms

Associated Studies (each link opens a new tab)

Comparison of GenomEra C. difficile and Xpert C. difficile as confirmatory tests in a multistep algorithm for diagnosis of Clostridium difficile infection.2015
Superiority of the DNA amplification assay for the diagnosis of C. difficile infection: a clinical comparison of fecal tests.2012
Evaluation of three enzyme immunoassays and a loop-mediated isothermal amplification test for the laboratory diagnosis of Clostridium difficile infection.2012
Multicenter clinical evaluation of the portrait toxigenic C. difficile assay for detection of toxigenic Clostridium difficile strains in clinical stool specimens.2012
Comparative analysis of different methods to detect Clostridium difficile infection.2013
Multicenter evaluation of the Verigene Clostridium difficile nucleic acid assay.2013
Evaluation of the fully automated BD MAX Cdiff and Xpert C. difficile assays for direct detection of Clostridium difficile in stool specimens.2013
Evaluation of a rapid molecular screening approach for the detection of toxigenic Clostridium difficile in general and subsequent identification of the tcdC Δ117 mutation in human stools.2010
Clinical and laboratory evaluation of a real-time PCR for Clostridium difficile toxin A and B genes.2012
Molecular test based on isothermal helicase-dependent amplification for detection of the Clostridium difficile toxin A gene.2014
Evaluation of six PCR assays in combination with patient related data for the diagnosis of Clostridium difficile-associated infections.2014
Concordance between two enzyme immunoassays for the detection of Clostridium difficile toxins.2010
Evaluation of a new automated homogeneous PCR assay, GenomEra C. difficile, for rapid detection of Toxigenic Clostridium difficile in fecal specimens.2013
A multiplex, internally controlled real-time PCR assay for detection of toxigenic Clostridium difficile and identification of hypervirulent strain 027/ST-1.2012
Performance of Clostridium difficile toxin enzyme immunoassay and nucleic acid amplification tests stratified by patient disease severity.2013
Diagnosis of Clostridium difficile: real-time PCR detection of toxin genes in faecal samples is more sensitive compared to toxigenic culture.2015
Detection of Clostridium difficile toxin A/B genes by multiplex real-time PCR for the diagnosis of C. difficile infection.2012
Comparison of real-time PCR techniques to cytotoxigenic culture methods for diagnosing Clostridium difficile infection.2011
Evaluation of a loop-mediated isothermal amplification assay for diagnosis of Clostridium difficile infections.2011
Comparison of Simplexa universal direct PCR with cytotoxicity assay for diagnosis of Clostridium difficile infection: performance, cost, and correlation with disease.2014
Evaluation of a new molecular test, the BD Max Cdiff, for detection of toxigenic Clostridium difficile in fecal samples.2012
Evaluation of the BD MAX Cdiff assay for the detection of the toxin B gene of Clostridium difficile out of faecal specimens.2013
Diagnosing toxigenic Clostridium difficile: new confidence bounds show culturing increases sensitivity of the toxin A/B enzyme immunoassay and refute gold standards.2012
Rapid and sensitive loop-mediated isothermal amplification test for Clostridium difficile detection challenges cytotoxin B cell test and culture as gold standard.2011
Evaluation of the rapid loop-mediated isothermal amplification assay Illumigene for diagnosis of Clostridium difficile in an outbreak situation.2014
Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection.2013
Evaluation of the BD Max Cdiff assay for the detection of toxigenic Clostridium difficile in human stool specimens.2015
Comparison between the two-step and the three-step algorithms for the detection of toxigenic Clostridium difficile.-- Not Found --
Comparison of two rapid assays for Clostridium difficile Common antigen and a C difficile toxin A/B assay with the cell culture neutralization assay.2010
Comparison of eight commercial enzyme immunoassays for the detection of Clostridium difficile from stool samples and effect of strain type.2012
Evaluation of the Xpert Clostridium difficile assay for the diagnosis of Clostridium difficile infection.2012
Comparison of BD GeneOhm Cdiff and Seegene Seeplex ACE PCR assays using toxigenic Clostridium difficile culture for direct detection of tcdB from stool specimens.2012
Comparison of a frozen human foreskin fibroblast cell assay to an enzyme immunoassay and toxigenic culture for the detection of toxigenic Clostridium difficile.2013
Comparison of commercial molecular assays for toxigenic Clostridium difficile detection in stools: BD GeneOhm Cdiff, XPert C. difficile and illumigene C. difficile.2012
Evaluation of an algorithmic approach in comparison with the Illumigene assay for laboratory diagnosis of Clostridium difficile infection.2013
Comparison of two commercial molecular tests for the detection of Clostridium difficile in the routine diagnostic laboratory.2011
Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials.2014
Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial.2012
Prospective observational study comparing three different treatment regimes in patients with Clostridium difficile infection.2012
Fidaxomicin versus vancomycin for Clostridium difficile infection.2011
A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity.2007
Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea.1996
Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis.1983
Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection.2015
Simple faecal preparation and efficacy of frozen inoculum in faecal microbiota transplantation for recurrent Clostridium difficile infection--an observational cohort study.2015
Intestinal microbiota transplantation, a simple and effective treatment for severe and refractory Clostridium difficile infection.2015
The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema.2014
Recovery of the gut microbiome following fecal microbiota transplantation.2014
Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection.2014
Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.2014
Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study.2014
Faecal microbiota transplantation and bacteriotherapy for recurrent Clostridium difficile infection: a retrospective evaluation of 31 patients.2014
Fecal microbiota transplant for recurrent Clostridium difficile infection: Mayo Clinic in Arizona experience.2013
Fecal microbiome transplantation for recurrent Clostridium difficile infection: report on a case series.2013
Duodenal infusion of donor feces for recurrent Clostridium difficile.2013
Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection.2012
Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients.2012
Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results.2012
Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection.2012
Colonoscopic fecal bacteriotherapy in the treatment of recurrent Clostridium difficile infection--results and follow-up.2011
Results of faecal donor instillation therapy for recurrent Clostridium difficile-associated diarrhoea.2010
Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube.2003
Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients.
Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series.2009
Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study.2014
Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial.2013
Probiotic VSL#3 prevents antibiotic-associated diarrhoea in a double-blind, randomized, placebo-controlled clinical trial.2013
Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.2012
Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.2010
Intake of Lactobacillus plantarum reduces certain gastrointestinal symptoms during treatment with antibiotics.2010
Feasibility and tolerability of probiotics for prevention of antibiotic-associated diarrhoea in hospitalized US military veterans.2008
Effect of a fermented milk combining Lactobacillus acidophilus Cl1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial.2007
Efficacy and safety of Saccharomyces boulardii in prevention of antibiotic-associated diarrhoea due to Helicobacterpylori eradication.2005
Impact of adding prophylactic probiotics to a bundle of standard preventative measures for Clostridium difficile infections: enhanced and sustained decrease in the incidence and severity of infection at a community hospital.2013
Staggered and tapered antibiotic withdrawal with administration of kefir for recurrent Clostridium difficile infection.2014
Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea.2004
Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo.1995
The potential use of cholestyramine to reduce the risk of developing Clostridium difficile-associated diarrhoea in patients receiving long-term intravenous ceftriaxone.2015
A randomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection.2011
Lactoferrin for the prevention of post-antibiotic diarrhoea.2011
Fecal Microbiota Transplantation for Clostridium difficile Infection: The Ochsner Experience.2014
Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection.2014
Efficacy and safety of, and patient satisfaction with, colonoscopic-administered fecal microbiota transplantation in relapsing and refractory community- and hospital-acquired Clostridium difficile infection.2014
Treatment of relapsing Clostridium difficile infection using fecal microbiota transplantation.2013
Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology.2010
Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated diarrhea - a placebo controlled double-blind randomized, multi-center study.2010
Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial.2007
Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study.2006
Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial.2001
The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients.1998
Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study.1989
Antimicrobial stewardship programs in inpatient hospital settings: a systematic review.2014

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