Journal
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
Volume 20, Issue 10, Pages 1035-1042Publisher
WILEY
DOI: 10.1002/pds.2198
Keywords
time-varying exposures; antibiotics; acid-suppressive agents; Clostridium difficile infection; effect modification
Ask authors/readers for more resources
Purpose Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea worldwide. We examined the risk of CDI associated with the use of acid-suppressive agents (proton pump inhibitors [PPI] and histamine-2 receptor blockers) and determined whether this risk varied by number or type of antibiotic (high or low CDI risk) received during hospitalization. Methods We conducted a retrospective cohort study of hospitalizations among adult patients at an academic teaching hospital in Rochester, New York, during which two or more days of antibiotics were prescribed. Multivariable marginal Cox proportional hazards models with time-varying exposures were used to examine time to the development of CDI. Results A total of 10154 hospitalizations and 241 cases of CDI, defined as detection of C. difficile toxin in a diarrheal stool sample within 60days of discharge, were identified. PPI use was independently associated with an increased risk of CDI (adjusted hazard ratio = 4.5; 95% confidence interval [CI]= 2.3-9.0). Among hospitalizations during which one, two, three or four, and five or more antibiotics were prescribed, the adjusted hazard ratios for PPI use were 15.7 (CI=6.4-38.8), 4.9 (CI=2.2-11.2), 4.3 (CI=1.9-9.9), and 2.7 (CI=1.2-5.9), respectively (p for interaction=.002). Conclusions The use of PPI is common among patients receiving antibiotics during hospitalization. The greater risk of CDI in relation to PPI among hospitalizations during which fewer or low-risk antibiotics were prescribed suggests a potentially clinically relevant interaction between antibiotics and PPI. Further study is needed to elucidate possible mechanisms for the observed effect. Copyright (C) 2011 John Wiley & Sons, Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available