Clostridium difficile infection following systemic antibiotic administration in randomised controlled trials: a systematic review and meta-analysis

Int J Antimicrob Agents. 2016 Jul;48(1):1-10. doi: 10.1016/j.ijantimicag.2016.03.008. Epub 2016 Apr 27.


Antibiotics have been the most important risk factor for Clostridium difficile infection (CDI). However, only data from non-randomised studies have been reviewed. We sought to evaluate the risk for development of CDI associated with the major antibiotic classes by analysing data from randomised controlled trials (RCTs). The PubMed, Cochrane and Scopus databases were searched and the references of selected RCTs were also hand-searched. Eligible studies should have compared only one antibiotic versus another administered systemically. Inclusion of studies comparing combinations of antibiotics was allowed only if the second antibiotic was the same or from the same class or if it was administered in a subset of the enrolled patients who were equally distributed in the two arms. Only a minority of the selected RCTs (79/1332; 5.9%) reported CDI episodes. Carbapenems were associated with more CDI episodes than fluoroquinolones [risk ratio (RR) = 2.44, 95% confidence interval (CI) 1.32-4.49] and cephalosporins (RR = 2.24, 95% CI 1.46-3.42), but not penicillins (RR = 2.53, 95% CI 0.87-7.41). Cephalosporins were associated with more CDIs than penicillins (RR = 2.36, 95% CI 1.32-4.23) and fluoroquinolones (RR = 2.84, 95% CI 1.60-5.06). There was no difference in CDI frequency between fluoroquinolones and penicillins (RR = 1.34, 95% CI 0.55-3.25). Finally, clindamycin was associated with more CDI episodes than cephalosporins and penicillins (RR = 3.92, 95% CI 1.15-13.43). In conclusion, data from RCTs showed that clindamycin and carbapenems were associated with more CDIs than other antibiotics.

Keywords: Antibiotics; Clostridium difficile; Colitis; Diarrhoea.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Administration, Intravenous
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects*
  • Clostridioides difficile / isolation & purification*
  • Clostridium Infections / chemically induced*
  • Clostridium Infections / microbiology*
  • Diarrhea / chemically induced*
  • Diarrhea / microbiology*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Humans
  • Randomized Controlled Trials as Topic


  • Anti-Bacterial Agents