Introduction Macrolide-resistant Mycoplasma pneumoniae (MRMP) has reached extremely high prevalence among children in Asia. However, genotype -phenotype correlations and their impact on clinical outcomes in pediatric community-acquired pneumonia (CAP) remain insufficiently characterized in many regions of China. This study aimed to determine the prevalence, molecular mechanisms, antimicrobial susceptibility, and clinical characteristics of macrolide resistance in children with M. pneumoniae CAP in Anhui, China. Methods A retrospective cohort study was conducted among 71 pediatric patients with confirmed M. pneumoniae CAP between October 2023 and September 2024. Macrolide resistance was assessed using 23S rRNA domain V sequencing and broth microdilution minimum inhibitory concentration (MIC) testing. Clinical features, laboratory markers, treatment response, and outcomes were descriptively compared between macrolide-resistant M. pneumoniae (MRMP) and macrolide-susceptible M. pneumoniae (MSMP) cases. Results Of the 71 isolates, 67 (94.4%) were macrolide-resistant, predominantly harboring the A2063G mutation (81.7%). The MIC₅₀/MIC₉₀ values for erythromycin and azithromycin were 126/512 μg/mL and 16/126 μg/mL, respectively. Compared with the small MSMP group ( n = 4), children with MRMP appeared to have longer median fever duration (6.5 vs. 4.0 days), longer hospitalization (7.0 vs. 5.0 days), higher hs-CRP (11.2 vs. 4.8 mg/L), higher LDH (258.5 vs. 210.3 U/L), more persistent cough, delayed radiographic resolution, and higher treatment-failure or antibiotic-switch rates (20.9% vs. 0%). Discussion Macrolide resistance exceeded 94% and was mainly driven by the A2063G mutation, accompanied by high MIC values. MRMP infections were associated with prolonged clinical course and elevated inflammatory markers; however, these findings should be interpreted cautiously due to the extremely small comparator group and the descriptive nature of the analysis.
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