Patterns, Predictors, and Intercenter Variability in Empiric Gram-Negative Antibiotic Use Across 928 United States Hospitals

Abstract

Abstract Background Empiric antibiotic use among hospitalized adults in the United States (US) is largely undescribed. Identifying factors associated with broad-spectrum empiric therapy may inform antibiotic stewardship interventions and facilitate benchmarking. Methods We performed a retrospective cohort study of adults discharged in 2019 from 928 hospitals in the Premier Healthcare Database. “Empiric” gram-negative antibiotics were defined by administration before day 3 of hospitalization. Multivariable logistic regression models with random effects by hospital were used to evaluate associations between patient and hospital characteristics and empiric receipt of broad-spectrum, compared to narrow-spectrum, gram-negative antibiotics. Results Of 8 017 740 hospitalized adults, 2 928 657 (37%) received empiric gram-negative antibiotics. Among 1 781 306 who received broad-spectrum therapy, 30% did not have a common infectious syndrome present on admission (pneumonia, urinary tract infection, sepsis, or bacteremia), surgery, or an intensive care unit stay in the empiric window. Holding other factors constant, males were 22% more likely (adjusted odds ratio [aOR], 1.22 [95% confidence interval, 1.22–1.23]), and all non-White racial groups 6%–13% less likely (aOR range, 0.87–0.94), to receive broad-spectrum therapy. There were significant prescribing differences by region, with the highest adjusted odds of broad-spectrum therapy in the US West South Central division. Even after model adjustment, there remained substantial interhospital variability: Among patients receiving empiric therapy, the probability of receiving broad-spectrum antibiotics varied as much as 34+ percentage points due solely to the admitting hospital (95% interval of probabilities: 43%–77%). Conclusions Empiric gram-negative antibiotic use is highly variable across US regions, and there is high, unexplained interhospital variability. Sex and racial disparities in the receipt of broad-spectrum therapy warrant further investigation.