The addition of macrolides for empiric treatment of patients hospitalized with moderate and high-severity community-acquired pneumonia (CAP) was not associated with improved clinical outcomes, according to a population-level study published this week in the Journal of Infectious Diseases.
Using electronic medical record data from 8,872 adults who were hospitalized with CAP in Oxfordshire, England, from January 1, 2016 through March, 19, 2024, and received initial treatment with amoxicillin or co-amoxiclav, researchers from the University of Oxford examined the effect of adjunctive macrolides on 30-day all-cause mortality, time to hospital discharge, and changes in Sequential Organ Failure Assessment (SOFA) score. While guidelines from the British Thoracic Society and the National Institute for Health and Care Excellence recommend combining macrolides with beta-lactam antibiotics for moderate and high-severity pneumonia to provide coverage of atypical pathogens, existing studies have yielded conflicting evidence on efficacy.
Benefits should be weighed against risk of resistance, side effects
Among 3,239 (36.5%) and 5,633 (63.5%) patients who received baseline amoxicillin or co-amoxiclav, 606 (18.7%) and 1,821 (32.3%) received additional macrolide antibiotics, respectively. After adjustments using inverse probability treatment weighting to address confounding by baseline severity, the researchers found no evidence of an association between the use of additional macrolides and 30-day mortality, with marginal odds ratios of 1.05 (95% confidence interval [CI], 0.75 to 1.47) for amoxicillin with versus without a macrolide and 1.12 (95% CI, 0.93 to 1.34) for co-amoxiclav with versus without a macrolide.
There was also no evidence that the addition of macrolides produced differences in time to discharge among those receiving baseline amoxicillin (restricted mean days lost +1.76 [-1.66 to +5.19]) or co-amoxiclav (+0.44 [-1.63 to +2.51]) or that macrolide use was associated with SOFA score decreases (marginal difference with amoxicillin +0.03 [- 0.19 to +0.25]; co-amoxiclav -0.06 [-0.19 to +0.06]). The results were consistent across varying levels of CAP severity.
The researchers also noted that atypical pathogens were rarely identified.
“Our findings suggest that the benefits of empirical macrolide therapy should be weighed against the risk of resistance and side-effects,” they wrote.
