Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection

Antimicrob Agents Chemother. 2013 May;57(5):2326-32. doi: 10.1128/AAC.02176-12. Epub 2013 Mar 11.


The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / classification
  • Clostridioides difficile / drug effects*
  • Clostridioides difficile / physiology
  • Community-Acquired Infections / drug therapy
  • Community-Acquired Infections / epidemiology
  • Community-Acquired Infections / etiology*
  • Community-Acquired Infections / microbiology
  • Databases, Bibliographic
  • Enterocolitis, Pseudomembranous / drug therapy
  • Enterocolitis, Pseudomembranous / epidemiology
  • Enterocolitis, Pseudomembranous / etiology*
  • Enterocolitis, Pseudomembranous / microbiology
  • Humans
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Risk Assessment


  • Anti-Bacterial Agents