Relationship between Antibiotic Exposure and Subsequent Clostridium Difficile-Associated Diarrhea

Abstract

Objective

The objective of this study was to assess the relationship between antibiotic exposure and subsequent Clostridium difficile-associated diarrhea (CDAD) in hospitalized patients.

Methods

A retrospective, case-control study with data collected between October 1, 2005 and March 31, 2006 was conducted. Cases consisted of patients with a documented new onset of diarrhea occurring a minimum of 72 hours following admission to the hospital and accompanied by a positive C. difficile toxin A and B enzyme immunoassay. Two controls were matched to each case according to known risk factors for CDAD other than antibiotic use. A complete assessment of antibiotic use was made, including all regimens the patient received during the previous 8 weeks. The difference in antibiotic use in cases and controls was tested using the chi-square test. The association between specific antibiotic classes and subsequent CDAD was evaluated with an odds ratio.

Results

Prior antibiotic exposure was observed more frequently in these cases than in controls (P = 0.035). Specifically, third-generation cephalosporins were found to be significantly associated with CDAD (odds ratio, 4.64; 95% confidence interval, 1.64 to 13.14).

Conclusion

This study showed that prior antibiotic exposure is associated with increased incidence of subsequent CDAD. Specifically, third-generation cephalosporins were statistically associated with CDAD. Although results did not reach statistical significance, this study suggests that potential associations may exist between CDAD and prior exposure to antipseudomonal penicillins, cefepime, carbapenems, fluoroquinolones, and intravenous vancomycin.