International travel and sexual transmission mark the expansion of multidrug resistant Shiga toxin-producing Escherichia coli clonal complex 504

Abstract Shiga toxin-producing Escherichia coli (STEC) clonal complex (CC) 504 is a multidrug resistant (MDR) CC associated with international travel and transmission among gay, bisexual and other men-who-have-sex-with-men (GBMSM). We analysed genome sequencing data from 436 CC504 isolates, integrating genomic and epidemiological data to characterise transmission networks and antimicrobial resistance gene content. Phylogenetic analysis identified three intercontinental lineages associated with presumptive GBMSM (pGBMSM) transmission, characterised by azithromycin resistance and sustained domestic circulation following possible importation through travel. Overall, 85% of isolates exhibited MDR, including a novel emerging lineage characterised by carriage of the AmpC bla DHA-1 gene. Serial isolations from the same patient provided evidence of prolonged and chronic infection among pGBMSM. Our findings demonstrate that CC504 STEC has established multiple persistent transmission networks linked to international travel and GBMSM-associated lineages. This study highlights the need to integrate monitoring of sexually transmissible enteric infections within broader sexual health and antimicrobial stewardship frameworks.