Addition of Macrolide Antibiotics for Hospital Treatment of Community-Acquired Pneumonia

Abstract Background Guidelines recommend combining macrolides with β-lactam antibiotics for moderate-to-high severity community-acquired pneumonia (CAP); however, macrolides pose risks of adverse events and anti-microbial resistance. Methods We analyzed electronic health data from 8872 adults hospitalized with CAP in Oxfordshire, UK (2016-2024), initially treated with amoxicillin or co-amoxiclav. Using inverse probability treatment weighting, we examined the effects of adjunctive macrolides on 30-day all-cause mortality, time to hospital discharge, and changes in Sequential Organ Failure Assessment (SOFA) score. Results There was no evidence of an association between adjunctive macrolides and 30-day mortality (marginal odds ratio 1.05 [95% CI 0.75-1.47] for amoxicillin with vs. without macrolide; 1.12 [0.93-1.34] for co-amoxiclav with vs. without macrolide); and no evidence of a difference in time to discharge (restricted mean days lost +1.76 days [−1.66, +5.19] for amoxicillin, +0.44 days [−1.63, +2.51] for co-amoxiclav). Macrolide use was not associated with SOFA score decreases. Results were consistent across severity sub-groups and sensitivity analyses with missing covariates imputed. Conclusions At a population level, the addition of macrolides was not associated with improved clinical outcomes for patients with CAP. The potential benefits of additional macrolides should be weighed against the risks of adverse effects and anti-microbial resistance.