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

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=30184 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, I2=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.