Antibiotic combination indications for the treatment of community-acquired acute pneumonia

Empirical dual combination therapy with beta-lactam and macrolide is often the standard treatment of community-acquired acute pneumonia (CAP) in adults hospitalized in non-intensive care units. However, several recent studies question this standard treatment. The present literature review analyzes available data that compare beta-lactam monotherapy and dual antibiotic therapies in moderate CAP. Macrolides are associated with frequent adverse events (digestive, cardiovascular) as well as with an increase in bacterial resistance, and their clinical benefit in non-severe forms of CAP has yet to be proven. Three randomized trials of good quality did not show any reduction in mortality in patients treated with dual antibiotic therapy, and a large-scale observational real-life study did not show the clinical advantage of dual antibiotic therapy. Only patients with severe CAP could benefit from the addition of a macrolide as it covers atypical bacteria (and potentially because of its immuno-modulatory properties). Considering the current state of knowledge, beta-lactam monotherapy seems to be enough and preferable in moderate CAP, thus allowing to reduce exposure to macrolides and their consequences. The 2025 guidelines confirm the absence of indication for dual antibiotic therapy for mild documented CAP (except for Panton-Valentine leukocidin-producing S. aureus). Empirical dual antibiotic therapy is also recommended for patients hospitalized for severe CAP, with rapid de-escalation to monotherapy depending on the clinical evolution and microbiological results.