Epidemic cycles and post-epidemic decline of Mycoplasma pneumoniae in Italian children: implications for empirical macrolide prescribing.

Mycoplasma pneumoniae (MP) circulation has recently re-emerged worldwide, raising concerns about empirical macrolide use in pediatric respiratory infections. We analyzed long-term trends of MP circulation in a tertiary-care pediatric center in Italy between 2017 and 2025. Among 20,539 respiratory molecular tests performed, 648 were positive for MP, with the highest burden observed in children aged 5-12 years. Two epidemic peaks were identified, occurring in 2019 and 2024, followed by a marked and sustained decline in positivity from the last quarter of 2025 onward. Hospitalization was frequent, particularly among patients with underlying comorbidities. Compared with the previous epidemic cycle, the 2024 peak was characterized by higher overall positivity but a lower proportion of hospitalized cases. The sharp post-epidemic reduction in MP circulation underscores the importance of continuous epidemiological surveillance to inform clinical decision-making. These findings support reconsideration of empirical macrolide prescribing during periods of low MP circulation and highlight the role of real-time surveillance data in strengthening antimicrobial stewardship strategies in pediatric care.