2388. High-risk antibiotics associated with Clostridioides difficile infection: a national, multicenter analysis

BACKGROUND: Historically, antibiotics with the highest Clostridioides difficile infection (CDI) risk included clindamycin, advanced-spectrum penicillins, and cephalosporins; however, a recent CDI epidemic involving fluoroquinolone (FQ)-resistant ribotype 027-added FQs as a high-risk class. Now that the ribotype 027 strain is part of an endemic population of C. difficile strains, no contemporary analysis of high-risk antibiotics and CDI risk has been conducted. The primary objective of this study was to identify the strongest antibiotic predictors for CDI. METHODS: This was a case–control study in the national United States Veterans Health Administration (VHA). The study included patients 18–89 years old with an ICD-9-CM code for CDI (008.45), a positive stool test, and active CDI therapy between 2002 and 2014. A random sample of VHA patients without a CDI ICD-9-CM code served as the control cohort. Antibiotic use was defined as any use in the 90 days prior to inclusion. Antibiotic risk factors for CDI were evaluated in a multivariable logistic regression model that included 33 covariates. Results were validated in non-VA patients at a quaternary care medical center in Houston, TX. RESULTS: A total of 85,451 VHA patients were included (26,149 CDI patients and 59,302 controls). FQs were most commonly prescribed: 24.9% (CDI group) and 7.3% (controls). Strongest predictors of CDI included carbapenems (OR 54.39, 95% CI 25.42–116.36), advanced-spectrum penicillins (OR 41.54; 95% CI 31.49–54.78), third/fourth-generation cephalosporins (OR 17.35; 95% CI 14.49–20.77), clindamycin (OR 3.63; 95% CI 3.26–4.02), and FQs (OR 1.48; 95% CI 1.40–1.57). Macrolides (OR 0.83; 95% CI 0.77–0.91) and tetracyclines (OR 0.58; 95 CI 0.51–0.66) were negatively associated with CDI risk. In a validation cohort of 68,795 patients, carbapenems (OR 2.19; 95% CI 1.86–2.57), third/fourth-generation cephalosporins (OR 1.70; 95% CI 1.50–1.93), and advanced-spectrum penicillins (OR 1.64; 95% CI 1.42–1.89) were also the strongest predictors for CDI. FQs were not significantly associated with CDI. CONCLUSION: Although FQs were the most prescribed antibiotic class, carbapenems were the strongest predictor of CDI development in a national cohort of veterans and a validation cohort. DISCLOSURES: All authors: No reported disclosures.