Association Between Neighbourhood-level Antibiotic Utilization and the Rate of Community-Associated C. difficile (CA-CDI) Infection: An Ecological Study

Abstract Background Despite reductions in hospital-associated Clostridioides difficile infection (CDI) incidence in Canada and the United States, the incidence of community-associated CDI (CA-CDI) has remained high. We sought to investigate whether neighbourhood-level variation in antibiotic utilization is associated with CA-CDI. Method We conducted a neighbourhood-level ecological study across 1,520 neighbourhoods in Ontario, Canada. Residents aged ≥66 without hospitalization in the prior 30 days were eligible for inclusion from 2017 to 2023. Antibiotic utilization, CDI cases, and population were identified for each neighbourhood using comprehensive province-wide databases. CA-CDI rate was the outcome (incident cases of CA-CDI/10,000 person-years). Rate of antibiotic utilization (DOT per 1000 person-days) was the primary exposure. The rate-ratio (RR) of CA-CDI associated with increased antibiotic utilization was estimated using negative-binomial regression, adjusting for 8 demographic and health care covariates. We also evaluated risk based on low-, moderate-, and high-risk antibiotic strata based on published literature. Result We identified 19,757 CA-CDI cases. We observed substantial variation in antibiotic utilization across neighbourhoods (Median=21.1 DOT/1000 person-days; interquartile range [IQR], 16.7–25.6). After adjustments, we observed an association between overall antibiotic utilization (RR=1.13 per 10-point increase in DOT; 95% confidence interval [95%CI], 1.09–1.18). A gradient wherein higher risk antibiotic agents were more strongly associated with CA-CDI was apparent (Low-risk: RR=1.08; 95%CI, 1.01–1.15; Moderate-risk: RR=1.27; 95%CI, 1.15–1.39; High-risk: RR=1.73; 95%CI, 1.13–2.66). Discussion Neighbourhoods with higher antibiotic utilization, especially for moderate and high-risk antibiotics, have higher CA-CDI incidence. Reducing variability in neighbourhood antibiotic utilization could help reduce the burden of CDI.