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

Eur J Clin Pharmacol. 2025 Jan;81(1):83-91. doi: 10.1007/s00228-024-03775-6. Epub 2024 Nov 18.

Abstract

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; I2 = 0%), 90-day mortality (RR 1.03; 95% CI 0.82 to 1.29; p = 0.83; I2 = 13%), or 30-day mortality (RR 0.90; 75% CI 0.63 to 1.29; p = 0.58; I2 = 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; I2 = 63%) or respiratory insufficiency (RR 0.63; 95% CI 0.29 to 1.35; p = 0.24; I2 = 74%). However, combination therapy significantly improved the treatment success rate (RR 1.17; 95% CI 1.04 to 1.32; p = 0.009; I2 = 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.

Keywords: Antibiotics; Beta-lactam; Community-acquired; Macrolides; Pneumonia.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / therapeutic use
  • Community-Acquired Infections* / drug therapy
  • Community-Acquired Infections* / mortality
  • Drug Therapy, Combination*
  • Hospital Mortality
  • Humans
  • Length of Stay / statistics & numerical data
  • Macrolides* / therapeutic use
  • Pneumonia / drug therapy
  • Pneumonia / mortality
  • Pneumonia, Bacterial / drug therapy
  • Pneumonia, Bacterial / mortality
  • Randomized Controlled Trials as Topic*
  • beta-Lactams* / administration & dosage
  • beta-Lactams* / therapeutic use

Substances

  • beta-Lactams
  • Macrolides
  • Anti-Bacterial Agents