Antibiotic Exposure and Risk of Clostridium difficile Infection: A Retrospective Cohort Study

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Community and Preventive Medicine, 2010.Clostridium difficile Infection (CDI) is a major cause of hospital-acquired diarrhea and is most commonly associated with changes in normal intestinal flora caused by administration of antibiotics. The recent emergence of strains of C. difficile demonstrating new antimicrobial resistance patterns may mean that antibiotics that have seldom been implicated in the past now confer a greater risk of CDI. Few studies have examined increases in the risk of CDI associated with total cumulative dose, duration, or number of antibiotics. Therefore, a retrospective cohort study was conducted to determine the incidence of CDI at Strong Memorial Hospital in 2005 among hospitalizations during which two or more consecutive days of antibiotics were prescribed, and to examine the class, total dose (measured in Defined Daily Doses (DDD)), days, and number of antibiotics in relation to CDI. 10,154 hospitalizations were included in the study. Dose-response relationships were observed, with increasing exposure conferring increasing CDI risk for all dose-related antibiotic measures evaluated. For instance, the risk of CDI for hospitalizations in the second, third, and fourth quartile of DDD was 1.24 (95% CI 0.72, 2.15), 2.77 (1.67, 4.59), and 5.16 (3.02, 8.79) times higher, respectively, as compared to the lowest quartile, even after accounting for the effects of potential confounders. Similar patterns were observed in the estimates for cumulative number of antibiotics and antibiotic days. For comparisons across antibiotic classes, receipt of fluoroquinolones was associated with a four-fold increase in the risk of CDI relative to hospitalizations during which no fluoroquinolones were prescribed (95%CI 2.75, 5.97), independent of other antibiotics received during hospitalization. Cephalosporins, β-lactamase inhibitor combinations, sulfa drugs, and intravenous vancomycin were also associated with a significant increase in risk of CDI. Our results suggest that cumulative antibiotic exposures are associated with the development of CDI. A reduction of patients’ total cumulative exposures to antibiotics and substitution of higher risk antibiotics for lower risk alternatives, when feasible, may reduce the incidence of hospital-acquired CDI