A2063G macrolide-resistant Mycoplasma pneumoniae: epidemic dominance without more frequent pulmonary consolidation or worse short-term in-hospital outcomes in hospitalized children

BACKGROUND: Macrolide resistance is common in pediatric Mycoplasma pneumoniae pneumonia (MPP), but its relationship with clinical phenotype, short-term in-hospital course, and radiographic severity remains uncertain. We aimed to characterize macrolide resistance-associated sites and their clinical correlates in hospitalized children with MPP, focusing on A2063G and pulmonary consolidation. METHODS: This retrospective study included children aged < 14 years hospitalized with MPP at Shantou Central Hospital, China, from January 1 to December 31, 2024. All patients had undergone throat-swab targeted next-generation sequencing within 24 h of admission as part of routine clinical diagnostic work-up. This retrospective study used secondary data extracted from clinical diagnostic reports and electronic medical records. Four macrolide resistance-associated sites were interrogated: A2063G, A2064G, A2067G, and C2617G. Clinical, laboratory, radiographic, and short-term in-hospital outcome variables were compared by A2063G resistance-site status and by pulmonary consolidation. Multivariable logistic regression was performed for A2063G resistance-site status and pulmonary consolidation. Firth penalized logistic regression was used as a sensitivity analysis for the A2063G model. RESULTS: Among 402 hospitalized children with MPP, A2063G was detected in 362 (90.0%), whereas A2064G, A2067G, and C2617G were not detected. Monthly case counts peaked during June-August, while the proportion of A2063G remained consistently high throughout the year. Pulmonary consolidation was present in 103 patients (25.6%) and was less frequent in A2063G-positive than in wild-type cases (23.2% vs. 47.5%, P = 0.002). In multivariable analysis, pulmonary consolidation was independently associated with lower odds of A2063G positivity (OR 0.370, 95% CI 0.187-0.732; P = 0.004). For pulmonary consolidation, A2063G positivity remained independently associated with lower odds after adjustment for age, Tmax_24h, and CRP (OR 0.378, 95% CI 0.190-0.752; P = 0.006). No clear differences were observed by resistance-site status in systemic inflammatory profile, overall clinical course, or in-hospital resource use. Overall, short-term in-hospital outcomes were favorable, with no deaths. CONCLUSIONS: In hospitalized children with MPP from the Chaoshan region of southern China in 2024, A2063G was the dominant macrolide resistance-associated site. In this cohort, A2063G positivity was not accompanied by more frequent pulmonary consolidation, a more severe clinical phenotype based on the available indicators, or worse short-term in-hospital outcomes. These findings suggest that, in pediatric MPP, predominance of a resistance-associated site, radiographic severity, and short-term clinical course may not necessarily vary in parallel.