Abstract
OBJECTIVE: Effective empiric therapy options for Staphylococcus aureus infections are limited by rising rates of resistance to non-beta lactam antimicrobial agents. The use of cumulative susceptibility testing results, antibiograms, are promoted as a tool for improving empiric therapy decisions, but it is unclear how much of the variation in antibiograms between facilities and the associated efficacy of antimicrobial agents is driven by underlying differences in patient characteristics such as comorbidities and prior antibiotic exposure. DESIGN: Retrospective cohort study of 46,866 S. aureus specimens from outpatient settings of the Veterans Health Administration (VHA) from 2021 and 2022 linked to electronic health record information on patient comorbidities, prior antibiotic usage, age and gender. SETTING: Outpatient VHA clinics in the conterminous 48 states plus Washington, DC. METHODS: Hierarchical logistic regression of resistance outcomes among S. aureus specimens to determine how much variation in the likelihood of resistance to five commonly used classes of antibiotics existed after accounting for patient-level characteristics. RESULTS: The likelihood of drug resistance significantly varies across the VHA's outpatient facilities, over and above the patient case mixture seen at each facility. In particular, VHA facilities in the US South and West regions have high likelihood of antibiotic resistance after accounting for patient factors. CONCLUSIONS: Suggest that community-level population or environmental characteristics are thus also associated with the likelihood of antimicrobial resistance in S. aureus. Integration of statistical and spatial analysis of antibiotic susceptibility testing results can help identify places with higher risk of drug-resistance, and thus populations facing limited treatment options, to ensure antibiotic stewardship or other policies have the greatest positive impact.