Association between point mutations of macrolide-resistant Mycoplasma pneumoniae and clinical antibiotic treatment efficacy: a meta-analysis

TL;DR

This study finds that double mutations in Mycoplasma pneumoniae lead to worse treatment outcomes than single mutations, and children recover faster from fever regardless of mutation type.

Contribution

This study is the first to establish mutation burden as a key predictive indicator for treatment outcomes in macrolide-resistant Mycoplasma pneumoniae.

Findings

Double mutations in 23S rRNA prolong fever duration and increase severity compared to single mutations.

Children experience shorter fever duration than adults across all mutation genotypes.

Mutation detection is advocated for guiding treatment escalation in high-resistance areas.

Abstract

The increasing macrolide resistance in Mycoplasma pneumoniae is mainly driven by mutations in the V domain of 23S rRNA (A2063G/A2064G), which impairs the efficacy of first-line treatment. Previous meta-analyses failed to distinguish between mutation subtypes or quantify age-specific susceptibility, blurring the clinical significance of different mutation burdens.

To quantify the differential impact of single mutation (A2063G) and double mutation (A2063G + A2064G) on core clinical outcomes and to dissect the age-adjusted effects between children and adults.

We searched PubMed, Web of Science, Embase, Scopus, and CNKI databases (up to June 2025). The Newcastle-Ottawa Scale was used to assess study quality. Random-effects models were applied to handle heterogeneity (I2 > 50%), and subgroup analyses were conducted to compare mutation subtypes and age-stratified effects.

A total of 53 studies (n = 8,960 individuals, covering 5 countries) were included. Double mutations significantly prolonged the duration of fever compared to single mutations (HR = 5.32, 95% CI: 4.27–6.61 vs. HR = 3.66, 95% CI: 1.89–7.09; P < 0.001) and were more likely to cause severe illness (HR = 7.80, 95% CI: 2.51–24.18 vs. HR = 5.89, 95% CI: 2.03–17.08). There was no difference in hospital stay between the two mutation subtypes, but both were longer than the wild type (MD = −3.33 days). The duration of fever in children was shorter than that in adults for all genotypes (overall HR = 3.72 vs. 5.52; double mutation HR = 5.37 vs. 5.66; single mutation HR = 3.85 vs. 4.45; all P < 0.01).

Double mutations in 23S rRNA are an independent prognostic factor more severe than single mutations, establishing mutation burden as a key predictive indicator for the first time. This study shows that children have a faster resolution of fever in all genotypes, highlighting the regulatory role of host age immunity on outcomes. This study advocates for the detection of mutation subtypes in high-resistance areas to guide early treatment escalation and risk stratification monitoring.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251071963, identifier CRD420251071963.

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