Erythromycin was less effective compared with clarithromycin for the treatment of community-acquired pneumonia (CAP), according to findings from a systematic review and meta-analysis published in the Journal of Infection and Chemotherapy.

For this systematic review and meta-analysis, researchers searched PubMed, EMBASE, Cochrane Library, and 3 clinical trial registries for studies that compared the efficacy of erythromycin with either azithromycin or clarithromycin among adults and adolescents with CAP. The final analysis included 4 randomized controlled trials (RCTs) that compared erythromycin monotherapy against clarithromycin; no studies on the efficacy of erythromycin monotherapy vs azithromycin were found. The primary outcome was the rate of clinical success.

The 4 RCTs comprised a total of 472 patients with CAP. Of these patients, the mean age ranged from 22 to 54 years, and the mean duration of treatment ranged between 1 and 2 weeks. The most commonly isolated pathogens included Haemophilus influenzae, Streptococcus pneumoniae, H parainfluezae, Moraxella (subgen Branhamella) catarrhalis, Mycoplasma pneumoniae, and Chlamydia pneumoniae. Of H influezae pathogens, partial or full susceptibility to erythromycin and clarithromycin was observed in 63% and 83%, respectively.


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The rate of clinical success was decreased among patients who received erythromycin vs those who received clarithromycin (risk ratio [RR], 0.79; 95% CI, 0.64-0.98; P =.033; I2 =20.27%). The rate of clinical cure (RR, 0.67; 95% CI, 0.48-0.92; P =.014; I2=8.75%) and radiologic success (RR, 0.84; 95% CI, 0.71-0.996; P =.045; I2 =20.12%) associated with erythromycin treatment also was decreased compared with clarithromycin. Clarithromycin treatment was associated with a 33% decreased risk for clinical failure.

The researchers highlighted results from a prior meta-analysis that assessed outcomes of erythromycin treatment against other macrolides among patients with CAP. Results showed that patients who received erythromycin had an increased rate of adverse reactions (RR, 4.35; 95% CI, 2.51-7.54; P <.001). Erythromycin treatment also was associated with an increased rate of gastrointestinal-related adverse reactions (RR, 1.77; 95% CI, 1.42-2.21; P <.001), as well as adverse reactions prompting subsequent treatment discontinuation (RR, 2.68; 95% CI, 1.79-4.01; P <.001).

The researchers acknowledged that erythromycin should be considered during shortages of clarithromycin and azithromycin or in cases where erythromycin might be more affordable to the patient. They hypothesized that the increased efficacy of clarithromycin may result from a longer half-life, increased plasma concentration, and increased activity against a wider spectrum of pathogens related to CAP such as H influenzae.

Limitations of this analysis were the small number of included studies, the small sample sizes, and the lack of studies that compared the efficacy of erythromycin monotherapy against azithromycin for the treatment of CAP.

“Given the fact that erythromycin has lower efficacy and is associated with high rate of discontinuation of the treatment course because of gastrointestinal adverse reactions, it should not be chosen to treat CAP unless other macrolides cannot be used, and the clinical practice guidelines should state this clearly,” the researchers concluded.

Reference

Ashy N, Alharbi L, Alkhamisi R, Alradadi R, Eljaaly K. Efficacy of erythromycin compared to clarithromycin and azithromycin in adults or adolescents with community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials. J Infect Chemother. Published online May 3, 2022. doi:10.1016/j.jiac.2022.04.020