Pathogens causing CAP globally and in countries underrepresented in RCTs were found to be similar, suggesting macrolides may offer similar benefit in all countries.
In community-acquired pneumonia (CAP), adding macrolides to treatment with other antibiotics was associated with decreased 30-day mortality and increased CAP resolution, according to study findings published in the International Journal of Antimicrobial Agents.
Researchers conducted a meta-analysis to explore macrolides’ effect on CAP resolution and mortality, as well as the most common CAP pathogens, both globally and in underreported countries (URCs; ie, countries often left out or underrepresented in major clinical studies).
The investigators searched Scopus, Cochrane, PubMed, and Google Scholar from January 1, 1994, to December 31, 2022, for relevant studies of adult human patients (aged ≥18 years) with at least 20 patients. A total of 3 searches were conducted:
the first search identified meta-analyses performed worldwide on the use of macrolides in CAP; the second search identified research (not just meta-analyses) performed on the use of macrolides for CAP in URCs; and the third search specifically sought CAP pathogen information from URCs.
Endpoints were 30-day CAP mortality, CAP resolution, and epidemiology of CAP pathogens in URCs. The researchers conducted 3 different meta-analyses based on the 3 endpoints.
For the primary endpoint 30-day CAP mortality, the meta-analysis included 31 publications with 58,759 patients; of those, 30,422 received regimens with macrolides and 28,337 were not treated with macrolides. The OR for mortality after 30 days with macrolide treatment was 0.65 (95% CI, 0.51-0.82). Notably, 14 of those 31 publications reported on prevalent pathogens of CAP; the most common pathogens were Streptococcus pneumoniae (14.67%; 95% CI, 8.11%-25.11%), Haemophilus influenzae (3.08%; 95% CI, 1.92%-4.90%), and Klebsiella pneumoniae (1.23%; 95% CI, 0.37%-4.01%).
For the endpoint of the effect of macrolides on CAP resolution, the meta-analysis included 16 publications with 6465 patients — 3201 treated with macrolides and 3264 not treated with macrolides. Among patients who received regimens containing macrolides, the OR for CAP resolution was 1.23 (95% CI, 1.00-1.52; P <.05). Of those 16 publications, 13 reported on the prevalence of CAP pathogens; the most common pathogens were S. pneumoniae (12.68%; 95% CI, 9.36%-16.95%), H. influenzae (6.76%; 95% CI, 3.98%-11.26%), and K. pneumoniae (1.49%; 95% CI, 0.99%-2.24%).
The meta-analysis of the epidemiology of pathogens of CAP in the URCs included 12 publications with 4810 patients. This meta-analysis showed that the most frequently occurring pathogens were S. pneumoniae (24.91%; 95% CI, 16.72%-35.40%), K. pneumoniae (12.90%; 95% CI, 8.23%-19.65%), Mycoplasma pneumoniae (2.59%; 95% CI, 0.85%-7.58%), H. influenzae (6.12%; 95% CI, 4.13%-8.98%), Moraxella catarrhalis (2.38%; 95% CI, 0.91%-6.08%), Chlamydophila pneumoniae (1.12%; 95% CI, 0.23%-5.27%), Pseudomonas aeruginosa (11.51%; 95% CI, 4.37%-27.04%), and Legionella pneumophila (2.25%; 95% CI, 0.56%-8.63%).
Limitations include the limited number of available randomized controlled trials and the heterogeneity of publications on the microbial epidemiology of CAP. Another limitation is the consideration of patients treated with macrolides as 1 group.
“The relative risk for death decreases by 35%, and the rate of pneumonia resolution increases by 23%, signaling clinical efficacy against S pneumoniae, H influenzae, and K pneumoniae, which are the most prevalent pathogens,” stated the investigators. “The microbial epidemiology in the studies used to disclose clinical benefit is similar to the epidemiology of pathogens from the URCs, suggesting that similar clinical benefit may be anticipated in URCs.”
Disclosure: Funding for this meta-analysis was provided by Abbott Products Operations AG. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
References:
Kyprianou M, Dakou K, Aktar A, et al. Macrolides for better resolution of community-acquired pneumonia: a global meta-analysis of clinical outcomes with focus on microbial etiology. Int J Antimicrob Agents. Published online August 2, 2023. doi:10.1016/j.ijantimicag.2023.106942