Clinical and Genomic Investigation of an International Ceftriaxone- and Azithromycin-Resistant Shigella sonnei Cluster among Men Who Have Sex with Men, Montréal, Canada 2017–2019

ABSTRACT Multidrug-resistant (MDR) Shigella sonnei have become prevalent among men who have sex with men and have become a global public health concern. From June 2017 to April 2019, 32 men were infected with MDR S. sonnei acquired locally, in Montréal, which was suggestive of an outbreak. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), phylogenetic analysis, antimicrobial resistance and virulence characterization, and association to international clusters were performed. The outbreak strain was ceftriaxone- and azithromycin-resistant due to the acquisition of bla CTX-M-27 , and mphA and ermB genes, respectively, with reduced susceptibility to ciprofloxacin due to a single point mutation ( gyrA S83L). One out of 27 patients treated with a fluoroquinolone experienced microbiological failure. Epidemiological evidence first supported by a rare unique MDR Shigella sonnei documented only in men in 2017 followed by similar pulsed-field gel electrophoresis profiles was confirmed by WGS. A core genome high-quality single-nucleotide variant (hqSNV)-based phylogeny found a median of 6 hqSNV differences among isolates. Virulence gene content was investigated, but no Shiga toxins were detected. An international cluster of highly related isolates was identified (PDS000019750.208) and belonged to the 3.7.29.1.4.1 S. sonnei genotype (Global III VN2.KH1.Aus). Genomic analysis revealed that this Montréal cluster was connected to other documented outbreaks in Australia, the United States, and the United Kingdom. This study highlights the urgent need for public health measures to focus on the prevention and the early detection of S. sonnei , since global transmission patterns of MDR strains is concerning and few antimicrobial treatment options are available. IMPORTANCE Shigella sonnei , an important foodborne pathogen, recently became a frequent sexually transmitted agent involved in large and persistent outbreaks globally among men who have sex with men. Most strains also harbor several multidrug-resistant (MDR) determinants of particular concern. This study characterizes an outbreak strain at the source of an important MDR cluster identified in Montréal in 2017. Associations were made to many high-profile international outbreaks, and the causative S. sonnei lineage of these clusters was identified, which was not evident in past reports. The worldwide occurrence of this strain is of concern since treatment with antimicrobials like ceftriaxone and azithromycin may not be effective, and rare microbiological failures have been documented in patients treated with ciprofloxacin. Our investigation highlights the threats of Shigella spp. infection and the necessity for antimicrobial susceptibility monitoring in order to mitigate S. sonnei ’s impact on public health and to avoid transmission to other at-risk communities.