Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: a cohort study

Question: Is broad-spectrum antibiotic use associated with poor outcomes in community-onset pneumonia after adjusting for confounders? Methods: We performed a retrospective, observational cohort study of 1995 adults with pneumonia admitted from four US hospital emergency departments. We used multivariable regressions to investigate the effect of broad-spectrum antibiotics on 30-day mortality, length of stay, cost and Clostridioides difficile infection (CDI). To address indication bias, we developed a propensity score using multilevel (individual provider) generalised linear mixed models to perform inverse-probability of treatment weighting (IPTW) to estimate the average treatment effect in the treated. We also manually reviewed a sample of mortality cases for antibiotic-associated adverse events. Results: 39.7% of patients received broad-spectrum antibiotics, but drug-resistant pathogens were recovered in only 3%. Broad-spectrum antibiotics were associated with increased mortality in both the unweighted multivariable model (OR 3.8, 95% CI 2.5-5.9; p<0.001) and IPTW analysis (OR 4.6, 95% CI 2.9-7.5; p<0.001). Broad-spectrum antibiotic use by either analysis was also associated with longer hospital stay, greater cost and increased CDI. Healthcare-associated pneumonia was not associated with mortality independent of broad-spectrum antibiotic use. In manual review we identified antibiotic-associated events in 17.5% of mortality cases. Conclusion: Broad-spectrum antibiotics appear to be associated with increased mortality and other poor outcomes in community-onset pneumonia.