Treatment of recurrent Clostridium difficile infection: a systematic review

Infection. 2014 Feb;42(1):43-59. doi: 10.1007/s15010-013-0496-x. Epub 2013 Jul 10.


Background: Clostridium difficile infection (CDI) recurs in nearly one-third of patients who develop an initial infection. Recurrent CDI (RCDI) is associated with considerable morbidity, mortality, and cost. Treatment for RCDI has not been not well examined.

Methods: A systematic review.

Results: Sixty-four articles were identified evaluating eight different treatment approaches: metronidazole, vancomycin, fidaxomicin, nitazoxanide, rifampin, immunoglobulins, probiotics, and fecal bacteriotherapy. The meta-analysis found vancomycin to have a similar efficacy to metronidazole, although studies used varying doses and durations of therapy. Fidaxomicin was slightly more efficacious than vancomycin, though the number of studies was small. Good evidence for probiotics was limited. Fecal bacteriotherapy was found to be highly efficacious in a single randomized trial.

Conclusion: Metronidazole and vancomycin have good evidence for use in RCDI but heterogeneity in treatment duration and dose precludes robust conclusions. Fidaxomicin may have a role in treatment, but evidence is limited to subgroup analyses. Fecal bacteriotherapy was the most efficacious. Saccharomyces boulardii may have a role as adjunctive treatment.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Anti-Infective Agents / therapeutic use
  • Biological Therapy / methods
  • Clostridioides difficile / isolation & purification*
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / microbiology*
  • Diarrhea / drug therapy*
  • Diarrhea / microbiology*
  • Drug Therapy / methods
  • Humans
  • Metronidazole / therapeutic use
  • Secondary Prevention
  • Treatment Outcome
  • Vancomycin / therapeutic use


  • Anti-Infective Agents
  • Metronidazole
  • Vancomycin