Association between point mutations of macrolide-resistant Mycoplasma pneumoniae and clinical antibiotic treatment
Rutong Wang1,2, Junfeng He1,2, Yingqi Feng1,2
1Hunan Province Clinical Medical Research Center for Occupational Diseases, Hunan Prevention and Treatment Institute for Occupational Diseases, Affiliated Prevention and Treatment Institute for Occupational Diseases of University of South China, Hengyang Medical College, University of South China, Changsha, Hunan, China.
Background:
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.
Objective:
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.
Methods:
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.
Results:
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).
Conclusion:
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.
Systematic Review Registration:
https://www.crd.york.ac.uk/PROSPERO/view/CRD420251071963, identifier CRD420251071963.
Insights
Double mutations in 23S rRNA significantly worsen Mycoplasma pneumoniae outcomes compared to single mutations. Children experience faster fever resolution across all genotypes, indicating age-related immune influence.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Macrolide resistance in Mycoplasma pneumoniae is increasing due to 23S rRNA V domain mutations (A2063G/A2064G).
- This resistance compromises first-line treatment efficacy.
- Previous analyses lacked detail on mutation subtypes and age-specific effects.
Purpose of the Study:
- To compare the clinical impact of single (A2063G) versus double (A2063G + A2064G) 23S rRNA mutations.
- To analyze age-adjusted outcomes in children and adults.
Main Methods:
- Systematic search of major databases (PubMed, Web of Science, Embase, Scopus, CNKI) up to June 2025.
- Quality assessment using Newcastle-Ottawa Scale.
- Meta-analysis with random-effects models and subgroup analyses for mutation types and age groups.
Main Results:
- 53 studies (8,960 individuals) were analyzed.
- Double mutations led to significantly longer fever duration and higher severe illness rates than single mutations.
- Children showed shorter fever duration than adults for all genotypes.
Conclusions:
- 23S rRNA double mutations are independent, severe prognostic factors, establishing mutation burden as a key predictor.
- Host age influences outcomes, with children exhibiting faster fever resolution.
- Detecting mutation subtypes is crucial for treatment guidance in high-resistance areas.
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