Effectiveness of macrolides as add-on therapy to beta-lactams in community-acquired pneumonia: A meta-analysis of randomized controlled trials

• Published in: European journal of clinical pharmacology 2025-01, Vol.81 (1), p.83-91
• Main Authors: Prizão, Vitória Martins, Martins, Otavio Cosendey, de Hollanda Morais, Beatriz Austregésilo de Athayde, Mendes, Beatriz Ximenes, Defante, Maria Luiza Rodrigues, de Moura Souza, Mariana
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antibiotics; beta-Lactams - administration & dosage; beta-Lactams - therapeutic use; Biomedical and Life Sciences; Biomedicine; Clinical trials; Combination therapy; Community-Acquired Infections - drug therapy; Community-Acquired Infections - mortality; Drug Therapy, Combination; Hospital Mortality; Humans; Length of Stay - statistics & numerical data; Macrolides - therapeutic use; Mortality; Pharmacology/Toxicology; Pneumonia; Pneumonia - drug therapy; Pneumonia - mortality; Pneumonia, Bacterial - drug therapy; Pneumonia, Bacterial - mortality; Randomized Controlled Trials as Topic; Review; β-Lactam antibiotics
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-024-03775-6

Purpose This study aims to evaluate whether adding macrolides (MAC) to beta-lactam (BL) monotherapy in the treatment of community-acquired pneumonia (CAP) offers clinical benefits that justify the potential disadvantages or side effects. Methods We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) comparing BL monotherapy to combination therapy with BL and MAC for the in-hospital treatment of CAP. We pooled mean differences ( MD ) for continuous outcomes and risk ratio ( RR ) for binary outcomes, with 95% confidence intervals ( CI ). Results Six RCTs with 2661 participants (52% receiving combination therapy), revealed no significant difference in in-hospital mortality ( RR 0.99; 95% CI 0.78 to 1.25; p  = 0.94; I 2 = 0%), 90-day mortality ( RR 1.03; 95% CI 0.82 to 1.29; p  = 0.83; I 2 = 13%), or 30-day mortality ( RR 0.90; 75% CI 0.63 to 1.29; p  = 0.58; I 2 = 54%). Additionally, no significant differences were observed in the length of hospital stay ( MD 0.51; 95% CI  − 0.50 to 1.51; p  = 0.33; I 2 = 63%) or respiratory insufficiency ( RR 0.63; 95% CI 0.29 to 1.35; p  = 0.24; I 2 = 74%). However, combination therapy significantly improved the treatment success rate ( RR 1.17; 95% CI 1.04 to 1.32; p  = 0.009; I 2 = 0%). Conclusion Our findings suggest that BL + MAC therapy should not be used in all cases of hospitalized patients with CAP. PROSPERO ID: CRD42024516383 — Data of registration: 03/03/2024.