Risk of community-associated C. difficile infection by individual antibiotic

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While certain classes of antibiotics are classically associated with Clostridioides difficile infection, data supporting our notions of the strength and magnitude of this association with specific agents are limited. A recent study published in Open Forum Infectious Diseases provides insight.

The authors reviewed an insurance claims database to identify 159,504 cases of community-associated CDI receiving treatment that were matched to 797,020 controls according to age, sex, insurance type and enrollment period prior to diagnosis. Antibiotics received within the 30 days prior to diagnosis were recorded, as were comorbidity indicators and receipt of proton-pump inhibitors and health care visits within 90 days.

CDI cases were more likely to have received a PPI (20% vs. 8.9%) within 90 days or any antibiotic within 30 days (49.4% vs. 9.9%), and had more comorbidities (2.38 vs. 0.91) and health care visits in the 90 days prior (9.8 vs. 3.5). The highest association of any antibiotic with CDI was clindamycin: adjusted odds ratio, 25.4. Among beta-lactams, notable associations included amoxicillin-clavulanate (aOR, 8.5), cefdinir (aOR, 11.0) and cefuroxime (aOR, 9.6); cephalexin (aOR, 2.9) and amoxicillin (aOR, 2.0) were lower. Also somewhat lower were fluoroquinolones: ciprofloxacin (aOR, 6.8), levofloxacin (aOR, 2.5) and moxifloxacin (aOR, 4.7). Trimethoprim-sulfamethoxazole (aOR, 2.2) and linezolid (aOR, 3.6) were associated with modest risk; very little to no risk was observed with azithromycin (aOR, 1.3) and doxycycline (aOR, 0.96). 

While limitations include reliance on claims data rather than clinical or laboratory data and reliance on outpatient data alone, this work nonetheless provides nuance to the discussion of risk of CDI according to antibiotic received and will have important consequences in planning antimicrobial stewardship interventions on multiple levels.

(Miller et al. Open Forum Infect Dis. 2023;ofad413.)