Macrolides and β-lactam combo fails to improve clinical outcomes of community-acquired pneumonia: Study

A recent study published in The Journal of Infectious Diseases found that macrolides with β-lactam antibiotics in the treatment of moderate-to-high severity community-acquired pneumonia (CAP) was not completely effective. The guidelines commonly recommend a dual antibiotic approach for treating severe CAP. However, macrolides, while effective against certain bacteria, have been linked to adverse effects and the risk of fostering antimicrobial resistance.

The study was conducted in Oxfordshire, UK, which analyzed the clinical outcomes of 8,872 adults hospitalized with CAP between January 2016 and March 2024. This large-scale study sought to evaluate the impact of adding macrolides to β-lactam regimens, specifically amoxicillin or co-amoxiclav, on patient outcomes such as mortality, hospital discharge timing, and organ function.

The study employed robust statistical methods, including inverse probability treatment weighting, to address variations in baseline severity among patients. Despite the detailed analysis, the results showed no significant improvement in outcomes with the addition of macrolides. The addition of macrolides did not reduce 30-day all-cause mortality. Marginal odds ratios for mortality were 1.05 for amoxicillin with or without macrolides, and 1.12 for co-amoxiclav with or without macrolides, indicating no meaningful difference.

Time to discharge also showed no evidence of improvement. The patients receiving macrolides alongside amoxicillin experienced a slight, statistically insignificant delay (+1.76 days on average), while those on co-amoxiclav saw negligible changes (+0.44 days). The changes in the Sequential Organ Failure Assessment (SOFA) score were unaffected by the use of macrolides. The results remained consistent across analyses stratified by pneumonia severity and sensitivity checks for missing data.

The study highlights the need to weigh the potential benefits of macrolide use against its risks, particularly given the lack of evidence for improved clinical outcomes. While the combination of macrolides with β-lactams is a long-standing practice, these findings suggest that its routine application may not always be justified, especially when considering antimicrobial resistance and side effects.

This research highlight the importance of continuous evaluation of treatment protocols in light of these emerging evidence. Thus, clinicians might need to reconsider the widespread use of macrolides in CAP management, tailoring treatments more precisely to patient needs and minimizing unnecessary risks.

Reference:

Wei, J., Walker, A. S., & Eyre, D. W. (2024). Addition of macrolide antibiotics for hospital treatment of community-acquired pneumonia. In The Journal of Infectious Diseases. Oxford University Press (OUP). https://doi.org/10.1093/infdis/jiae639