Prevalence of Macrolide-Resistant Mycoplasma pneumoniae Infections After the COVID-19 Pandemic in Southern Italy, 2023–2025

Introduction: The COVID-19 pandemic and associated non-pharmaceutical interventions (NPIs) markedly reduced the circulation of respiratory pathogens. In late 2023, a resurgence of Mycoplasma pneumoniae (MP) infections, including macrolide-resistant strains (MRMP), was documented worldwide. This study aimed to determine MRMP prevalence and epidemiological characteristics in Southern Italy during the post-pandemic period. Methods: Between January 2023 and May 2025, 5362 respiratory specimens were tested for M. pneumoniae and other respiratory pathogens using multiplex real-time polymerase chain reaction (PCR). Macrolide resistance-associated mutations in the 23S rRNA gene were identified through PCR amplification and Sanger sequencing. Data were stratified by age group and clinical setting. Results: MP prevalence peaked at 15.8% in May 2025. Of 305 positive cases, the median age was 10 years, 52.1% were male, and 86.9% were hospitalized. Coinfections occurred in 23.3% of cases, particularly among children < 5 years. Macrolide resistance was detected in 7.5% of MP-positive samples, predominantly the A2063G mutation (96%), with the highest prevalence in patients aged 10–14 years (12.6%). No resistance was identified in ICU patients. Conclusion: The post-pandemic resurgence of M. pneumoniae in Southern Italy, coupled with sustained macrolide resistance, underscores the need for continuous molecular surveillance and targeted antimicrobial stewardship to optimize therapy and prevent further resistance spread.