Antibiotic Exposure and Risk of Community-associated Clostridium difficile infection (CA-CDI): A Self-Controlled Case Series Analysis

Abstract

BackgroundCA-CDI accounts for up to 50% of all CDIs. Case–control studies (CCS) have been used to estimate the odds ratio (OR) of CA-CDI associated with antibiotic exposure. These ORs demonstrate significant heterogeneity across studies. Unlike CCS, a self-controlled case series (SCCS) design can be used to control for all time-invariant confounders leading to less biased effect estimates.MethodsAdults (≥18 years) registered (N = 139,670) with the Barrie and Community Family Health Team (BCFHT) were included in the study. Cases were defined as any patient with an incident case of CA-CDI and ≥1 antibiotic exposure occurring between January 1, 2011 and December 31, 2016. The SCCS model was used to estimate the association between antibiotic exposure and CA-CDI. The SCCS model yields estimates of the relative incidence rate of CA-CDI in exposure periods relative to non-exposure periods within a case. Exposure periods were defined as starting two days after any antibiotic prescription and ending 60 days later. Multiple exposure periods and time-varying confounders due to calendar year were included in the final model. The relative incidence rate ratio (IRR) was estimated using conditional poisson regression analysis. Proton pump inhibitor (PPI) use was included as an effect modifier. Antibiotics were divided into high-risk (fluoroquinolone, clindamycin, and cephalosporin) and low-risk exposures. Research ethics approval was obtained from the BFCHT research ethics board.ResultsAmong 544 total CDI cases, N = 189 CA-CDI cases met the inclusion criteria. Any antibiotic exposure increases the risk by ≥2-fold, with no difference observed between high and low-risk groups (IRR=1.11, 95% CI 0.53–2.36) (Table 1).ConclusionAntibiotic exposure increases the risk of CA-CDI, with IRR estimates similar to those observed for healthcare-associated-CDI. This, along with the control of all time-invariant confounders by the SCCS method suggests a less biased effect estimate previously reported from CCS.Table 1 Variable IRR 95% Confidence Interval P-value Antibiotic Exposure GroupPPINoneYes0.80(0.62–1.03)0.09Low riskYes1.95(0.09–4.24)0.09High riskYes1.20(0.42–3.40)0.73OverallLow risk2.03(1.19–3.47)0.009High risk2.26(1.29–3.98)0.005Disclosures All authors: No reported disclosures.