Comparative Efficacy of Beta-Lactams and Macrolides in the Treatment of Pediatric Pneumonia: A Systematic Review

Abstract

Background: Pneumonia is an acute infection of the lung parenchyma that is differentiated among three main diagnoses: community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and healthcare-associated pneumonia (HCAP). Though CAP is initially presented as a mild infection, it contributes to childhood mortality rates globally. A vast number of pathogens are the cause of CAP, but the two main causative organisms include Streptococcus pneumoniae and Haemophilus influenzae, with the former causing up to 50% of all childhood cases. In the current treatment guidelines from the Infectious Diseases Society of America (IDSA), amoxicillin is the recommended treatment choice for mild-to-moderate CAP while ampicillin is recommended for cases of severe CAP. Previous studies compared treatment between macrolides and beta-lactams to provide more information on the effectiveness in the pediatric population. Objective: The objective of this article is to systematically review the literature on the comparative efficacy of beta-lactams and macrolides in the treatment of community-acquired pneumonia among children and to evaluate the outcomes that are used to determine drug efficacy in order to provide medication recommendations. Methods: A systematic literature search was conducted in PubMed, TRIP, Cochrane and SCOPUS. Cohort studies and randomized controlled trials between the years 2000 and 2020 that compared the efficacy of amoxicillin and macrolides in treating pediatric pneumonia were included in the systematic review. Eligible patients included patients who were 17 years and younger, diagnosed with community-acquired pneumonia, and were given beta-lactams or macrolides, either as monotherapy or combination. Two reviewers were involved in the appraisal process to assess the quality of the methods used in the selected studies. Results: A total of six articles were eligible according to the inclusion criteria and quality assessment. Four articles compared beta-lactam monotherapy with beta-lactam and macrolide combination therapy, while Kogan R et al. compared macrolide therapy monotherapy with beta-lactam and macrolide combination therapy and Leyenaar JK et al. compared ceftriaxone monotherapy to ceftriaxone plus macrolide combination therapy. The studies defined treatment failure as either a change in antibiotic therapy or hospital admission within 14 days of CAP diagnosis. Three studies used the length of hospital stay as their primary outcome for comparison of treatment efficacy. Four studies showed that the use of macrolides provided better treatment outcomes by reducing hospital stay and treatment failure rates. Beta-lactam and macrolide combination therapy did not show a significant effect on treatment failure compared to beta-lactam monotherapy regimens and it did not affect mortality compared to placebo or diet alone. Within the macrolide class, azithromycin was more clinically significant compared to erythromycin. Conclusion: The use of macrolides as monotherapy or add-on therapy to beta-lactams is more effective in the treatment of community-acquired pneumonia in the pediatric population.