Community-associated Clostridium difficile infection and antibiotics: a meta-analysis

J Antimicrob Chemother. 2013 Sep;68(9):1951-61. doi: 10.1093/jac/dkt129. Epub 2013 Apr 25.


Objectives: Antibiotic exposure is the most important risk factor for Clostridium difficile infection (CDI). Most evaluations of antimicrobial risk factors have been conducted in healthcare settings. The objective of this meta-analysis was to evaluate the association between antibiotic exposure and community-associated CDI (CA-CDI) (i.e. symptom onset in the community with no healthcare facility admission within 12 weeks) and to determine the classes of antibiotics posing the greatest risk.

Methods: We searched four electronic databases for subject headings and text words related to CA-CDI and antibiotics. Studies that investigated the risk of CA-CDI associated with antibiotic usage were considered eligible. Data from the identified studies were combined using a random-effects model and ORs were calculated.

Results: Of 910 citations identified, eight studies (n = 30 184 patients) met our inclusion criteria. Antibiotic exposure was associated with an increased risk of CA-CDI (OR 6.91, 95% CI 4.17-11.44, I(2) = 95%). The risk was greatest with clindamycin (OR 20.43, 95% CI 8.50-49.09) followed by fluoroquinolones (OR 5.65, 95% CI 4.38-7.28), cephalosporins (OR 4.47, 95% CI 1.60-12.50), penicillins (OR 3.25, 95% CI 1.89-5.57), macrolides (OR 2.55, 95% CI 1.91-3.39) and sulphonamides/trimethoprim (OR 1.84, 95% CI 1.48-2.29). Tetracyclines were not associated with an increased CDI risk (OR 0.91, 95% CI 0.57-1.45).

Conclusions: Antibiotic exposure was an important risk factor for CA-CDI, but the risk was different amongst different antibiotic classes. The risk was greatest with clindamycin followed by fluoroquinolones and cephalosporins, whereas tetracyclines were not associated with an increased risk.

Keywords: C. difficile; CA-CDI; community-associated CDI.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Clostridioides difficile / growth & development*
  • Clostridium Infections / epidemiology*
  • Clostridium Infections / microbiology
  • Community-Acquired Infections / epidemiology*
  • Community-Acquired Infections / microbiology
  • Drug Utilization
  • Humans
  • Risk Factors


  • Anti-Bacterial Agents