January 27, 2015

Diagnosis and Treatment of Clostridium difficile in AdultsA Systematic Review

Author Affiliations
  • 1Division of Infectious Disease, Department of Infection Control, St John Hospital and Medical Center, Detroit, Michigan
  • 2Department of Internal Medicine, Wayne State University, Detroit, Michigan
  • 3Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, University of Michigan Health System, Ann Arbor
  • 4Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan

Copyright 2015 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA. 2015;313(4):398-408. doi:10.1001/jama.2014.17103

Importance  Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased.

Objective  To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥18 years).

Evidence Review  Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process.

Findings  Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases ofCDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI).

Conclusions and Relevance  Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient’s risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.