The use of macrolides in the treatment of community-acquired pneumonia: risks and benefits

This Journal club aims to evaluate the recent evidence about the potential benefits of macrolides as add-on therapy in the treatment of community-acquired pneumonia (CAP), an area where the data remain conflicting. Four studies with diverse methodology (the ACCESS trial, a Greek cohort study, a UK-based cohort study and a recent meta-analysis) have aimed to assess either potential immunomodulatory effects, clinical response or hard end-points like mortality when macrolides are added to the treatment regimen for hospitalised patients with CAP. The ACCESS trial, a randomised controlled trial (RCT), demonstrated improved early clinical response and immunomodulatory effects with clarithromycin, while the Greek cohort study showed reduced 28-day mortality and delayed organ dysfunction with clarithromycin. The cohort study from the UK found no added benefit of macrolides on 30-day mortality or decline in Sequential Organ Failure Assessment score. The recent meta-analysis supported a survival advantage of macrolides, favouring clarithromycin over azithromycin. However, study limitations like heterogeneity, confounding risks and the lack of head-to-head comparisons of individual macrolides remain of concern. Macrolide treatment decisions may benefit from individualised risk assessment; however, future research should focus on identifying subgroups who might benefit from macrolides and comparative analyses of macrolide agents through large-scale RCTs.