Pediatrics · Medical Literature
Efficacy of azithromycin sequential therapy combined with montelukast in the treatment of pediatric mycoplasma pneumonia: A meta-analysis.
Abstract
Mycoplasma pneumoniae pneumonia (MPP) stands as a predominant cause of community-acquired respiratory infections in children. With the increasing prevalence of macrolide-resistant Mycoplasma pneumoniae strains, the therapeutic efficacy of azithromycin monotherapy has become a growing concern in clinical practice. Montelukast sodium, a selective leukotriene receptor antagonist, has emerged as a promising adjunctive agent, as it can effectively alleviate airway inflammation and reduce airway hyperresponsiveness. This meta-analysis was designed to systematically evaluate the efficacy and safety of azithromycin sequential therapy combined with montelukast in the management of pediatric MPP. A comprehensive literature search was conducted across PubMed, Embase, Web of Science Core Collection, Wanfang Data, Variant Impact Predictor database, and Chinese National Knowledge Infrastructure from the establishment of each database up to November 2025. Eligible studies were randomized controlled trials (RCTs) that compared azithromycin sequential monotherapy with azithromycin sequential therapy plus montelukast in pediatric patients diagnosed with MPP. Primary outcome measures included overall clinical efficacy, resolution time of key clinical symptoms (cough, wheezing, pulmonary rales, and fever), and the incidence of adverse events. Thirty-six RCTs involving 3450 pediatric patients (1726 in the combination group and 1724 in the azithromycin group) met the inclusion criteria. Compared with azithromycin sequential therapy, combination therapy significantly improved overall clinical efficacy (odds ratio = 4.75, 95% confidence interval [CI]: 3.70-6.10). The addition of montelukast also shortened the resolution time of cough (mean difference [MD] = -3.63, 95% CI: -4.27 to -2.99), wheezing (MD = -1.48, 95% CI: -1.82 to -1.14), pulmonary rales (MD = -2.06, 95% CI: -2.54 to -1.57), and fever (MD = -1.43, 95% CI: -1.89 to -0.96). No significant difference in adverse event rates was observed between groups. Azithromycin sequential therapy combined with montelukast may provide additional therapeutic benefits for the treatment of pediatric MPP, characterized by higher overall clinical efficacy and more rapid resolution of clinical symptoms, without a statistically significant increase in short-term adverse events. Despite the encouraging findings, the included studies were predominantly single-center trials with moderate methodological quality. Therefore, well-designed, large-scale, multicenter RCTs are urgently needed to validate these results and provide more reliable evidence for guiding clinical decision-making.
Clinical relevance
Mycoplasma pneumoniae pneumonia (MPP) is a leading cause of community-acquired respiratory infections in the pediatric population, and the rising prevalence of macrolide-resistant strains is eroding the reliability of azithromycin monotherapy as a standard-of-care regimen. This meta-analysis addresses the urgent clinical gap of optimizing treatment efficacy in children with MPP by evaluating the adjunctive role of montelukast sodium, a selective leukotriene receptor antagonist with established anti-inflammatory and bronchoprotective properties. Clinicians managing pediatric respiratory infections should be aware of this evidence given the dual challenge of antimicrobial resistance and the need to accelerate symptom resolution in a vulnerable patient population.
Key findings
1. Combination therapy (azithromycin sequential therapy + montelukast) significantly improved overall clinical efficacy compared to azithromycin sequential monotherapy, with an odds ratio of 4.75 (95% CI: 3.70–6.10), representing a large treatment effect. 2. The addition of montelukast meaningfully shortened cough resolution time by a mean difference (MD) of −3.63 days (95% CI: −4.27 to −2.99 days) compared to azithromycin alone. 3. Wheezing resolved faster in the combination group, with a MD of −1.48 days (95% CI: −1.82 to −1.14 days). 4. Resolution of pulmonary rales was accelerated by a MD of −2.06 days (95% CI: −2.54 to −1.57 days) in the combination arm. 5. Fever duration was shortened by a MD of −1.43 days (95% CI: −1.89 to −0.96 days) with adjunctive montelukast. 6. No statistically significant difference in adverse event incidence was observed between the combination and monotherapy groups, suggesting an acceptable short-term safety profile for the combination regimen. The meta-analysis pooled 36 RCTs comprising 3,450 pediatric patients (combination group n = 1,726; azithromycin group n = 1,724).
Practice implications
For pediatric patients diagnosed with MPP — particularly in clinical contexts where macrolide resistance is a concern or where prominent airway hyperresponsiveness and wheezing are present — adjunctive montelukast sodium combined with azithromycin sequential therapy should be considered to achieve higher clinical response rates and more rapid resolution of cough, wheezing, rales, and fever. Clinicians should note that the included evidence base is predominantly derived from single-center RCTs of moderate methodological quality, limiting the strength of generalizability, and current practice changes should be applied judiciously pending validation by large-scale, multicenter trials. Adverse event monitoring remains standard but no additional safety burden was identified with the combination approach in the short term, supporting its tolerability in pediatric patients.