BACKGROUND: Shigella sonnei has caused sexually transmitted enteric infections in men who have sex with men (MSM) in Vancouver. We recently observed a high rate of multidrug-resistant (MDR) S. sonnei bacteremia among persons experiencing homelessness (PEH). We aimed to describe the wider epidemiology, clinical outcomes, and genomics of S. sonnei infections over time. METHODS: A retrospective review of 163 patients with S. sonnei infections was undertaken from 2015 to 2022. We collected demographic, clinical, and microbiological data over 2 time periods: historical (2015-2020) and recent (2021-2022). Severe shigellosis definition included hospitalization, bacteremia, or death. Whole-genome sequencing was performed to identify genotype, infer relatedness, and predict antimicrobial resistance. RESULTS: S. sonnei infections increased from 8.3 (historical period) to 56.5 (recent period) cases/year. Over time, the primary population characteristics associated with shigellosis shifted from MSM (45
98%) to PEH (86
77%). The population intersection between MSM and PEH historically and recently was similar and occurred in 3 (6%) and 10 (9%) of patients, respectively. Severe shigellosis was significantly higher in the recent versus historical period (69 [61%] vs 7 [14%]
P <
.001). A dominant clone of MDR S. sonnei, 3.6.1.1.2 (CipR.MSM5), emerged with resistance to all first- and second-line agents, yet with susceptibility to ceftriaxone. CONCLUSIONS: We observed a substantial increase in severe shigellosis and shift from sexually transmitted S. sonnei infections in MSM to likely environmental transmission among PEH. More severe disease associated with the 3.6.1.1.2 clone of MDR S. sonnei in PEH could be a result of underlying vulnerabilities of the affected population.