Genomic Surveillance Reveals Emergence and Spread of Macrolide-Resistant Mycoplasma pneumoniae in Australia During the 2023-2024 Epidemic.

BACKGROUND

The resurgence of Mycoplasma pneumoniae, first reported in China in 2023, was attributed to waning postpandemic immunity with increases in macrolide-resistant M. pneumoniae (MRMP) (> 80%). In Australia, infections peaked in early 2024, particularly among children under 15 years. While MRMP remains low in Europe, North America, and Australia (< 5%), limited routine testing restricts understanding of resistance dynamics. As macrolides are first-line therapy in many settings, MRMP surveillance is essential for guiding empirical treatment.

METHODS

We applied a capture-based targeted metagenomic sequencing (targeted next-generation sequencing [tNGS]) to polymerase chain reaction (PCR)-positive M. pneumoniae specimens (n = 356) from across Australia. This approach enabled whole-genome recovery and MRMP detection directly from clinical specimens, without culture. MRMP detections were benchmarked against PCR and data were analyzed to assess associations between resistance and health care utilization.

RESULTS

This is the first genomics-informed national study of M. pneumoniae in Australia. We recovered 124 high-quality genomes, revealing a genetically diverse population with cocirculation of P1 type 1 (69%) and type 2 (31%). MRMP was identified in 13% of genomes, all belonging to clades that prior to 2024 had only been reported in Asia (ST3 and ST14). MRMP cases were geographically widespread, suggesting importation and local transmission. Unlike reports from China, macrolide-susceptible clades (ST3, ST7, ST17, and ST20) predominated (87%) and were associated with significantly lower health care utilization compared to MRMP cases.

CONCLUSIONS

Our findings demonstrate the utility of tNGS for genomic epidemiology and highlight the need for MRMP surveillance. Although macrolides remain effective in Australia, emerging MRMP strains require close monitoring to inform treatment guidelines and antimicrobial stewardship.