To evaluate hospital-level variation in using first-line antibiotics for Clostridioides difficile infection (CDI) based on the burden of laboratory-identified (LabID) CDI.

Using data on hospital-level LabID CDI events and antimicrobial use (AU) for CDI (oral/rectal vancomycin or fidaxomicin) submitted to the National Healthcare Safety Network in 2019, we assessed the association between hospital-level CDI prevalence (per 100 patient admissions) and rate of CDI AU (days of therapy per 1,000 days present) to generate a predicted value of AU based on CDI prevalence and CDI test type using negative binomial regression. The ratio of the observed to predicted AU was then used to identify hospitals with extreme discordance between CDI prevalence and CDI AU, defined as hospitals with a ratio outside of the intervigintile range.

Among 963 acute-care hospitals, rate of CDI prevalence demonstrated a positive dose–response relationship with rate of CDI AU. Compared with hospitals without extreme discordance (n = 902), hospitals with lower-than-expected CDI AU (n = 31) had, on average, fewer beds (median, 106 vs 208), shorter length of stay (median, 3.8 vs 4.2 days), and higher proportion of undergraduate or nonteaching medical school affiliation (48% vs 39%). Hospitals with higher-than-expected CDI AU (n = 30) were similar overall to hospitals without extreme discordance.

The prevalence rate of LabID CDI had a significant dose–response association with first-line antibiotics for treating CDI. We identified hospitals with extreme discordance between CDI prevalence and CDI AU, highlighting potential opportunities for data validation and improvements in diagnostic and treatment practices for CDI.