Effectiveness of Early Diagnosis, Prevention, and Treatment of Clostridium difficile Infection [Entered Retrospectively]

Project Summary Title and Description

Effectiveness of Early Diagnosis, Prevention, and Treatment of Clostridium difficile Infection [Entered Retrospectively]
Objectives: To conduct a systematic review and synthesize evidence for differences in the accuracy of diagnostic tests, and the effects of interventions to prevent and treat Clostridium difficile infection (CDI) in adult patients. Data Sources: Searching for relevant literature was conducted in MEDLINE, the Cochrane Library, and Allied and Complementary Medicine (AMED). ClinicalTrials.gov and expert consultants provided leads to additional studies. We also manually searched reference lists from relevant literature. Review Methods: Standard Evidence-based Practice Center methods were employed. Screening of abstracts and full text articles to identify studies meeting inclusion/exclusion criteria was performed by two independent reviewers. High-quality direct comparison studies were used to examine differences in diagnostic tests. Randomized controlled trials (RCTs) were used to examine comparative effectiveness of antibiotic treatment for CDI. Quality of data extraction was checked by separate reviewers. Quality ratings and strength of evidence grading was performed on included studies. Evidence on diagnostic tests was quantitatively synthesized focusing on differences between test sensitivities and specificities. Evidence on antibiotic treatment was quantitatively examined using pooled analysis. Qualitative narrative analysis was used to synthesize evidence from all available study types for environmental prevention and nonstandard prevention and treatment, with the exception of probiotics as primary prevention, for which a forest plot is provided. Results: Overall, literature was sparse and strength of evidence was generally low due to small sample sizes or lack of adequate controls. For diagnostic testing, direct comparisons of commercially available enzyme immunoassays for C. difficile toxins A and B did not find major differences in sensitivity or specificity. Limited evidence suggests that tests for genes related to the production of C. difficile toxins may be more sensitive than immunoassays for toxins A and B while the comparisons of these test specificities were inconsistent. Moderate evidence in favor of antibiotic restriction policies for prevention was found. Environmental preventive interventions such as glove use and disposable thermometers have limited evidence. However, this literature is largely based on controlling outbreaks. Use of multiple component interventions further limits the ability to synthesize evidence in a meaningful way. Numerous potential new forms of treatment are being examined in placebo controlled RCTs, case series, and case reports. For standard treatment, no antimicrobial is clearly superior for the initial cure of CDI. Recurrence is less frequent with fidaxomicin than with vancomycin. Monoclonal antibodies for prevention and fecal flora reconstitution for multiple recurrences appear promising. Conclusions: Given the frequency and severity of CDI and the fact that future reimbursement policy may withhold payment for hospital-acquired infections, this is an under-researched topic. More precise estimates of the magnitude of differences in test sensitivities and specificities are needed. More importantly, studies have not established that any of the possible differences in test accuracy would lead to substantially different patient outcomes in clinical practice. More research on effective treatment and unintended consequences of treatment, such as resistance, is needed. Gut flora may be important, but improved understanding of healthy gut ecology and the complex interactions is necessary before continuing to pursue probiotics.
Authors of Report
Methodology description
This systematic review of the literature will address the following key questions: KQ 1. How do different methods for detection of toxigenic C. difficile to assist with diagnosis of CDI compare in their sensitivity and specificity? o Do the differences in performance measures vary with sample characteristics?  KQ 2. What are effective prevention strategies? o What is the effectiveness of current prevention strategies? o What are the harms associated with prevention strategies? o How sustainable are prevention practices in health care (outpatient, hospital inpatient, extended care) and community settings?  KQ 3. What are the comparative effectiveness and harms of different antibiotic treatments? o Does effectiveness vary by disease severity or strain? o Does effectiveness vary by patient characteristics: age, gender, comorbidity, hospital- versus community-acquired setting? o How do prevention and treatment of CDI affect resistance of other pathogens?  KQ 4. What are the effectiveness and harms of nonstandard adjunctive interventions? o In patients with relapse/recurrent CDI? *** The systematic review data of this published project was retrospectively imported into SRDR by the Brown EPC on behalf of the Minnesota Evidence-based Practice Center and the Agency for Healthcare Research and Quality (AHRQ). For access to the full report available on the AHRQ website, follow this link: http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=772 ***
Funding Source
The Agency for Healthcare Research and Quality (AHRQ)

Key Questions

1. Key Question 1 - Summary of matched comparisons of select assays for C. difficile toxins
2. Key Question 2 - Description of studies evaluating risk factors for CDI
3. Key Question 3 - Prevention interventions
4. Key Question 4 - Studies of Multiple Interventions used together to reduce CDI incidence
5. Key Question 5 - Summary of risk factors for CDI
6. Key Question 6 - Standard Antibiotic treatments
7. Key Question 7 - Nonstandard intervention for treatment of initial and recurrent CDI
8. Key Question 8 - Case studies/series and potential harms of nonstandard interventions for CDI
9. Key Question 9 - Probiotic or prebiotic interventions for prevention of initial and recurrent CDI
10. Key Question 10 - Reviews and Meta-analyses

Associated Extraction Forms

Associated Studies (each link opens a new tab)

Evaluation of diagnostic tests for Clostridium difficile infection.2010
Comparison of BD GeneOhm Cdiff real-time PCR assay with a two-step algorithm and a toxin A/B enzyme-linked immunosorbent assay for diagnosis of toxigenic Clostridium difficile infection.2010
Comparison of ImmunoCard Toxins A&B and the new semiautomated Vidas Clostridium difficile Toxin A&B tests for diagnosis of C. difficile infection.
Comparison of nine commercially available Clostridium difficile toxin detection assays, a real-time PCR assay for C. difficile tcdB, and a glutamate dehydrogenase detection assay to cytotoxin testing and cytotoxigenic culture methods.2009
Clostridium difficile testing in the clinical laboratory by use of multiple testing algorithms.2010
Comparison of three commercial methods for rapid detection of Clostridium difficile toxins A and B from fecal specimens.2008
Diagnostic value of five commercial tests for the rapid diagnosis of Clostridium difficile-associated disease.2008
Evaluation of two rapid immunochromatography tests for the detection of Clostridium difficile toxins.2008
Comparison of real-time PCR for detection of the tcdC gene with four toxin immunoassays and culture in diagnosis of Clostridium difficile infection.2008
Detection of Clostridium difficile toxin: comparison of enzyme immunoassay results with results obtained by cytotoxicity assay.2007
Evaluation of real-time PCR and conventional diagnostic methods for the detection of Clostridium difficile-associated diarrhoea in a prospective multicentre study.2007
Six rapid tests for direct detection of Clostridium difficile and its toxins in fecal samples compared with the fibroblast cytotoxicity assay.2003
Evaluation of methods for detection of toxins in specimens of feces submitted for diagnosis of Clostridium difficile-associated diarrhea.2001
Predicting Clostridium difficile toxin in hospitalized patients with antibiotic-associated diarrhea.2007
Genotypic and phenotypic analysis of Clostridium difficile correlated with previous antibiotic exposure.2006
Proton pump inhibitor therapy is a risk factor for Clostridium difficile-associated diarrhoea.2006
Specific risk factors for Clostridium difficile-associated diarrhea: a prospective, multicenter, case control evaluation.2005
Underlying disease severity as a major risk factor for nosocomial Clostridium difficile diarrhea.2002
Clostridium difficile-associated diarrhea in a VA medical center: clustering of cases, association with antibiotic usage, and impact on HIV-infected patients.2001
Factors associated with nosocomial diarrhea and Clostridium difficile-associated disease on the adult wards of an urban tertiary care hospital.2000
Predicting Clostridium difficile stool cytotoxin results in hospitalized patients with diarrhea.1997
Successful use of feedback to improve antibiotic prescribing and reduce Clostridium difficile infection: a controlled interrupted time series.2007
Interventions to improve antibiotic prescribing practices for hospital inpatients.
Antibiotic prescribing policy and Clostridium difficile diarrhoea.2004
Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile diarrhoea.
An antibiotic policy associated with reduced risk of Clostridium difficile-associated diarrhoea.1999
Nosocomial Clostridium difficile colonisation and disease.1990
Reduction in the incidence of Clostridium difficile-associated diarrhea in an acute care hospital and a skilled nursing facility following replacement of electronic thermometers with single-use disposables.1992
Reduction in vancomycin-resistant Enterococcus and Clostridium difficile infections following change to tympanic thermometers.1998
A randomized crossover study of disposable thermometers for prevention of Clostridium difficile and other nosocomial infections.1998
Two time-series analyses of the impact of antibiotic consumption and alcohol-based hand disinfection on the incidences of nosocomial methicillin-resistant Staphylococcus aureus infection and Clostridium difficile infection.2009
Temporal effects of antibiotic use and hand rub consumption on the incidence of MRSA and Clostridium difficile.2008
Prospective, controlled, cross-over trial of alcohol-based hand gel in critical care units .2008
Reduction in nosocomial transmission of drug-resistant bacteria after introduction of an alcohol-based handrub.2005
Significant impact of terminal room cleaning with bleach on reducing nosocomial Clostridium difficile.
Environmental control to reduce transmission of Clostridium difficile.
Acquisition of Clostridium difficile from the hospital environment.1988
Control of nosocomial transmission of Clostridium difficile based on sporadic case surveillance.1991
Proposed checklist of hospital interventions to decrease the incidence of healthcare-associated Clostridium difficile infection.2009
Impact of hydrogen peroxide vapor room decontamination on Clostridium difficile environmental contamination and transmission in a healthcare setting.2008
Emergence and control of fluoroquinolone-resistant, toxin A-negative, toxin B-positive Clostridium difficile.2007
Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain.2007
Designing a protocol that eliminates Clostridium difficile: a collaborative venture.
Effectiveness of infection control program in controlling nosocomial Clostridium difficile.1998
Successful control of Clostridium difficile infection in an elderly care unit through use of a restrictive antibiotic policy.1997
Management and control of a large outbreak of diarrhoea due to Clostridium difficile.1994
Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use.1994
Risk factors for Clostridium difficile toxin-associated diarrhea.1990
Use of hypochlorite solution to decrease rates of Clostridium difficile-associated diarrhea.2007
Risk factors for Clostridium difficile infection.1998
Fidaxomicin versus vancomycin for Clostridium difficile infection.
Nitazoxanide versus vancomycin in Clostridium difficile infection: a randomized, double-blind study.2009
A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity.
Prospective, randomized inpatient study of oral metronidazole versus oral metronidazole and rifampin for treatment of primary episode of Clostridium difficile-associated diarrhea.2006
Nitazoxanide for the treatment of Clostridium difficile colitis.2006
A double-blind randomized controlled trial of fusidic acid and metronidazole for treatment of an initial episode of Clostridium difficile-associated diarrhoea.2004
Frequent emergence of resistance in Clostridium difficile during treatment of C. difficile-associated diarrhea with fusidic acid.2006
Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea.
Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea.1992
Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens.1989
Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial.1986
Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin.1985
Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis.1983
Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea.1978
A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile-associated diarrhoea: efficacy and safety data of a prematurely interrupted trial.2008
The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii.
Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial.2003
A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease.-- Not Found --
Randomized controlled trial of colestipol in antibiotic-associated colitis.1982
Systemic absorption of oral cholestyramine.1984
Recurrent Clostridium difficile-associated colitis responding to cholestyramine.1986
Effects of combination therapy with direct hemoperfusion using polymyxin B-immobilized fiber and oral vancomycin on fulminant pseudomembranous colitis with septic shock.2007
Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients.1989
Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope.2000
Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series.
Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology.
Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients.
Success of self-administered home fecal transplantation for chronic Clostridium difficile infection.2010
Yoghurt biotherapy: contraindicated in immunosuppressed patients?2002
A case of recurrent Clostridium difficile diarrhea.2007
Saccharomyces cerevisiae fungemia: an emerging infectious disease.2005
Treatment of relapsing Clostridium difficile diarrhoea by administration of a non-toxigenic strain.1987
Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.2008
Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection.
Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea.2005
Safety and immunogenicity of increasing doses of a Clostridium difficile toxoid vaccine administered to healthy adults.2001
Intravenous immunoglobulin for the treatment of severe, refractory, and recurrent Clostridium difficile diarrhea.2006
Intravenous immunoglobulin for resistant Clostridium difficile infection.2006
Use of intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis.2007
Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: an observational study and review of the literature.2010
Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study.
Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo.
The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients.
Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial.
Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea.
Failure of dietary oligofructose to prevent antibiotic-associated diarrhoea.
Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study.
Effect of the prebiotic oligofructose on relapse of Clostridium difficile-associated diarrhea: a randomized, controlled study.2005
Treatment with monoclonal antibodies against Clostridium difficile toxins.2010
Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial.
Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review.2008
Meta-analysis to assess risk factors for recurrent Clostridium difficile infection.
Systematic review of the risk of enteric infection in patients taking acid suppression.2007
How long do nosocomial pathogens persist on inanimate surfaces? A systematic review.2006
Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis.2009
Probiotics for treatment of Clostridium difficile-associated colitis in adults.
Are probiotic or synbiotic preparations effective for the management of clostridium difficile-associated or radiation-induced diarrhea?-- Not Found --
Probiotics for Clostridium difficile-associated diarrhea: focus on Lactobacillus rhamnosus GG and Saccharomyces boulardii.2007
Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease.2006
Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review.2005
Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.
Review article: treatment of Clostridium difficile infection.1997

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