Clinical factors associated with extrapulmonary complications in children with macrolide-resistant

Background: Extrapulmonary complications contribute substantially to the clinical burden of macrolide-resistant Methods: This single-center retrospective matched case-control study included children aged 3-14 years hospitalized between January 2021 and June 2024. Among 684 potentially eligible children identified from electronic medical record and microbiology databases, 448 met the criteria for genotypically confirmed R-MPP. All 52 children who developed extrapulmonary complications during the index hospitalization were included as cases. From 396 children without complications, 156 controls were individually matched at a 1:3 ratio by sex, age within 6 months, and admission date within 30 days. Candidate variables included peak inflammatory biomarkers, nadir platelet count, respiratory and computed tomography (CT) severity, and intervals from symptom onset to medical consultation and macrolide initiation. Complete-case conditional logistic regression stratified by matched set was the primary analysis; least absolute shrinkage and selection operator (LASSO) was used for variable selection, and multiple imputation was performed as a sensitivity analysis. Results: Cases and controls were comparable in age, sex, admission period, nutritional status, residence, vaccination status, household tobacco exposure, and wheezing history. C-reactive protein (CRP) >100 mg/L [matched odds ratio (OR) =3.28; 95% confidence interval (CI): 1.70-6.34], lactate dehydrogenase (LDH) >400 U/L (OR =2.97; 95% CI: 1.56-5.65), macrolide initiation delay >7 days (OR =4.18; 95% CI: 2.16-8.08), and severe CT changes (OR =2.15; 95% CI: 1.08-4.29) were independently associated with complications. A three-variable model incorporating CRP, LDH, and macrolide delay achieved an optimism-corrected area under the receiver operating characteristic (ROC) curve (AUC) of 0.917, with 86.5% sensitivity and 88.5% specificity. A preliminary internal temporal assessment in 44 patients yielded an AUC of 0.892. Conclusions: Elevated CRP, elevated LDH, delayed macrolide initiation, and severe CT changes were associated with extrapulmonary complications in hospitalized children with R-MPP. The simplified model may support clinical classification, but the retrospective design, concurrent biomarker measurement, and limited temporal sample preclude causal interpretation or immediate implementation. Larger multicenter studies are required for formal validation.