Systematic review and meta-analysis of the safety of erythromycin compared to clarithromycin in adults and adolescents with pneumonia

J Chemother. 2020 Feb;32(1):1-6. doi: 10.1080/1120009X.2019.1680116. Epub 2019 Oct 25.


Macrolides are recommended for the treatment of community-acquired pneumonia (CAP). It is debatable whether erythromycin is associated with more adverse drug reactions (ADRs) compared to clarithromycin, and both are recommended in clinical practice guidelines. This meta-analysis aim is to compare ADRs in CAP patients treated with erythromycin versus clarithromycin. Two investigators independently searched PubMed, EMBASE and Cochrane Library databases through Feb 07, 2019. Randomized-controlled trials (RCTs) comparing ADRs of monotherapy with erythromycin versus with clarithromycin in adults or adolescents with CAP were included. We estimated risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models and evaluated heterogeneity (I2). Bias risk was assessed using the Cochrane risk of bias tool for RCTs. Five RCTs (total of 693 patients) were included. A significantly higher discontinuation rate due to ADRs was found with erythromycin compared with clarithromycin (RR, 4.347; 95% CI, 2.506-7.539; p < 0.001; I2=0%). Overall, ADRs occurred more significantly with erythromycin compared with clarithromycin (RR, 1.773; 95% CI, 1.423-2.209; p < 0.001; I2=0%). Gastrointestinal (GI) ADRs were higher with erythromycin (RR, 2.678; 95% CI, 1.791-4.006; p < 0.001; I2=5.835%). Restriction of analyses to double-blind RCTs did not change our findings. Based on meta-analysis of RCTs in adults and adolescents with CAP, erythromycin results in more overall ADRs and GI ADRs, as well as a higher rate of discontinuation due to ADRs. Therefore, given that erythromycin is not more effective than clarithromycin, erythromycin should not be selected unless other macrolides cannot be used.

Keywords: Clarithromycin; Erythromycin; Gastrointestinal; Nausea; Pneumonia.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use*
  • Clarithromycin / therapeutic use*
  • Community-Acquired Infections / drug therapy
  • Erythromycin / therapeutic use*
  • Female
  • Humans
  • Male
  • Pneumonia, Bacterial / drug therapy*


  • Anti-Bacterial Agents
  • Erythromycin
  • Clarithromycin