Nonlinear age-season dynamics and macrolide resistance of Mycoplasma pneumoniae: a large pediatric cohort study during the post-pandemic resurgence.

BACKGROUND

Mycoplasma pneumoniae (MP) is a major cause of community-acquired pneumonia in children and demonstrates distinct age- and season-dependent patterns. However, nonlinear risk profiles, the burden of severe complications, and macrolide resistance remain incompletely characterized in large pediatric cohorts.

OBJECTIVE

To describe the epidemiological features of MP infection in a large pediatric pneumonia cohort, delineate nonlinear associations of age and season with MP-related risks, and evaluate macrolide resistance patterns and the burden of plastic bronchitis (PB).

METHODS

We retrospectively analyzed MP qPCR results from pharyngeal swab specimens obtained from 175,350 children with acute respiratory infections. Targeted next-generation sequencing (tNGS) (n = 333) was conducted in a clinically selected subgroup of refractory/severe cases. Restricted cubic splines (RCS) and multivariable logistic regression assessed the nonlinear associations of age and month of onset with MP detection, hospitalization, and severe MPP risks.

RESULTS

MP infection exhibited clear age- and season-dependent patterns. RCS analysis revealed a prominent nonlinear relationship with age, with a clinically meaningful inflection point at 8 years: in children ≤ 8 years, risk of MP detection, hospitalization, and severe MPP increased significantly with each additional year of age (adjusted ORs 1.335, 1.378, and 1.111, respectively; all p < 0.001), whereas risks plateaued or declined after age 8. School-aged children (6-12 years) accounted for the largest proportion of MP-positive cases (53.4%), while MP-infected infants had markedly higher hospitalization rates (84.3% vs. 22.3% in school-aged children, p < 0.001). Seasonally, risk rose progressively from May-June, peaked in September-October, and maintained high levels throughout the winter. In the clinically selected subgroup of refractory or severe cases, macrolide resistance was highly prevalent, with monthly detection ranging from 71.4% to 100%. PB occurred in 0.41% (115/28,178) of MP-positive cases, exclusively among those with severe Mycoplasma pneumoniae pneumonia (SMPP) (4.62% among documented SMPP cases during the study period).

CONCLUSIONS

MP-related risks in children show distinct nonlinear patterns, with a peak around 8 years of age and a predominant high-risk window extending from autumn through winter. Macrolide resistance was highly prevalent (71.4%-100%) in a clinically selected subgroup of refractory/severe cases, underscoring the urgent need for rapid molecular diagnostics and alternative treatment strategies. Although uncommon, PB represents a severe complication of MPP that requires timely bronchoscopic intervention.

CLINICAL TRIAL NUMBER: Not applicable.