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J Antimicrob Chemother. 2014 Apr;69(4):881-91. doi: 10.1093/jac/dkt477. Epub 2013 Dec 8.

Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis.

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School of Pathology and Laboratory Medicine, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia, Australia.



To update the evidence for associations between antibiotic classes and hospital-acquired Clostridium difficile infection (HA-CDI).


Electronic databases of journal articles, scholarly theses and conference proceedings using subject headings and keywords related to CDI and antibiotic exposure were searched. Observational epidemiological studies measuring associations between antibiotic classes and HA-CDI were eligible for inclusion. Pooled ORs and 95% CIs were calculated using a random effects model. Study factors identified a priori were examined as sources of heterogeneity. The quality of the studies was assessed using the Newcastle-Ottawa Scale.


Of 569 citations identified, 13 case-control and 1 cohort study (15,938 patients) were included. The strongest associations were found for third-generation cephalosporins (OR = 3.20, 95% CI = 1.80-5.71; n = 6 studies; I(2) = 79.2%), clindamycin (2.86, 2.04-4.02; n = 6; I(2) = 28.5%), second-generation cephalosporins (2.23, 1.47-3.37; n = 6; I(2)  = 48.4%), fourth-generation cephalosporins (2.14, 1.30-3.52; n = 2; I(2)  = 0.0%), carbapenems (1.84, 1.26-2.68; n = 6; I(2) = 0.0%), trimethoprim/sulphonamides (1.78, 1.04-3.05; n = 5; I(2) = 70%), fluoroquinolones (1.66, 1.17-2.35; n = 10; I(2) = 64%) and penicillin combinations (1.45, 1.05-2.02; n = 6; I(2) = 54%). The study population and the timing of measurement of antibiotic exposure were the most common sources of heterogeneity. Study quality scored high for seven studies, moderate for six studies and low for one study.


The risk of HA-CDI remains greatest for cephalosporins and clindamycin, and their importance as inciting agents should not be minimized. The importance of fluoroquinolones should not be overemphasized, particularly if fluoroquinolone-resistant epidemic strains of C. difficile are absent.


antimicrobials; diarrhoea; healthcare facilities; risk factors

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