Efficacy and short-term safety of intravenous omadacycline as second-line therapy for macrolide- unresponsive Mycoplasma pneumoniae pneumonia in children: a retrospective cohort study.

OBJECTIVE: To evaluate the efficacy and short-term safety of omadacycline as second-line therapy for macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) in children aged 8-16 years. METHODS: A total of 64 hospitalized children with MUMPP admitted between September 2023 and December 2024 were enrolled. Children with persistent fever (>38.0 °C) after 72 hours of azithromycin monotherapy were assigned to receive intravenous omadacycline (n=18) or continued azithromycin (n=46). Omadacycline was dosed according to body surface area (BSA)-based scaling from the approved adult regimen (loading dose on day 1; maintenance dose once daily for 7 days). Primary outcome: time to defervescence (TTD). Secondary outcomes: 72-hour defervescence rate, radiological improvement, corticosteroid use, and adverse events. Three-month follow-up included dental examinations. RESULTS: Omadacycline achieved shorter TTD than continued macrolides (50.78 ± 20.71 vs. 72.46 ± 25.61 hours; P = 0.002) and higher 72-hour defervescence rate (55.6% vs. 26.1%; P = 0.026). On multivariate linear regression, continued macrolide therapy (B = 13.43 h, 95% CI: 2.02-24.84, P = 0.022), positive 23S rRNA mutation status (B = 20.85 h, 95% CI: 10.94-30.77, P<0.001), and systemic corticosteroid use (B = 21.21 h, 95% CI: 10.79-31.62, P<0.001) were independently associated with prolonged TTD. No significant difference was observed in radiological improvement (P = 0.668). Corticosteroid requirement was significantly lower in the omadacycline group than in the macrolide group (27.8% vs. 67.4%; P = 0.004). Adverse events were comparable (5.6% vs. 8.7%; P = 0.645). At 3-month follow-up, no clinically significant changes were observed in hematological indices, hepatic or renal function, or cardiac enzyme profiles, and dental examination revealed no discoloration or enamel hypoplasia in any patient. CONCLUSION: In this retrospective cohort, omadacycline as second-line therapy was associated with significantly faster fever resolution than continued macrolide treatment, with acceptable short-term safety profiles over a 3-month follow-up. Prospective randomized trials are needed to confirm these findings.