Abstract
BACKGROUND: Community-acquired pneumonia (CAP) substantially contributes to mortality and morbidity globally, with beta-lactams being a primary therapeutic agent. The efficacy of adding macrolides to beta-lactams in CAP treatment remains controversial. Here, we evaluated whether beta-lactam plus macrolide treatment (BLM) is more effective than beta-lactam monotherapy (BL) for preventing CAP mortality. METHODS: We performed a secondary data analysis of a multicenter prospective cohort study involving patients diagnosed with CAP at four institutions. We selected patients treated with either BLM or BL. The primary endpoint was the outcome at the end of the observation period (death or recovery). The secondary endpoints were the length of hospital stay and duration of antibiotic use. Multiple imputations with bootstrapping were used to address missing data. Background characteristics were adjusted via propensity score matching. RESULTS: Of the 3,470 patients initially included in the study, 2,784 were analyzed; 306 received BLM and 2,478 received BL. The average observation period for the groups was 17.0 (± 18.4) and 24.0 days (± 24.6), respectively. After propensity score matching, mortality was similar between the groups (5.06% for BLM vs. 4.98% for BL; difference 0.00, 95% confidence interval [CI] − 3.73 to 3.71), as were recovery rates (91.79% for BLM vs. 91.69% for BL; difference 0.00, 95% CI − 4.48 to 4.82). In the subgroup analysis of patients with severe CAP, mortality was 12.00% for BLM vs. 13.33% for BL (difference 0.00, 95% CI − 20.00 to 16.13), and recovery rates were 82.86% vs. 83.33% (difference 0.00, 95% CI − 20.00 to 20.00). CONCLUSION: Similar outcomes were observed in the mortality and recovery rates between the BLM and BL groups among patients with CAP. Clinicians should thoughtfully weigh the benefits of BLM against the potential risks, including adverse effects and antimicrobial resistance, when managing patients with CAP. TRIAL REGISTRATION: This study protocol was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), identifier UMIN000006909, on December 19, 2011. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12408-x.