Genomic reconstruction and directed interventions in a multidrug-resistant Shigellosis outbreak in Seattle, WA, USA: a genomic surveillance study.

BACKGROUND

Shigella spp have been associated with community-wide outbreaks in urban settings. We analysed a sustained shigellosis outbreak in Seattle, WA, USA, to understand its origins and mechanisms of antimicrobial resistance, define ongoing transmission patterns, and optimise strategies for treatment and infection control.

METHODS

We did a retrospective study of all Shigella isolates identified from stool samples at the clinical laboratories at Harborview Medical Center and University of Washington Medical Center (Seattle, WA, USA) from May 1, 2017, to Feb 28, 2022. We characterised isolates by species identification, phenotypic susceptibility testing, and whole-genome sequencing. Demographic characteristics and clinical outcomes of the patients were retrospectively examined.

FINDINGS

171 cases of shigellosis were included. 78 (46%) patients were men who have sex with men (MSM), and 88 (52%) were people experiencing homelessness (PEH). Although 84 (51%) isolates were multidrug resistant, 100 (70%) of 143 patients with data on antimicrobial therapy received appropriate empirical therapy. Phylogenomic analysis identified sequential outbreaks of multiple distinct lineages of Shigella flexneri and Shigella sonnei. Discrete clonal lineages (ten in S flexneri and nine in S sonnei) and resistance traits were responsible for infection in different at-risk populations (ie, MSM, PEH), enabling development of effective guidelines for empirical treatment. The most prevalent lineage in Seattle was probably introduced to Washington State via international travel, with subsequent domestic transmission between at-risk groups.

INTERPRETATION

An outbreak in Seattle was driven by parallel emergence of multidrug-resistant strains involving international transmission networks and domestic transmission between at-risk populations. Genomic analysis elucidated not only outbreak origin, but directed optimal approaches to testing, treatment, and public health response. Rapid diagnostics combined with detailed knowledge of local epidemiology can enable high rates of appropriate empirical therapy even in multidrug-resistant infection.

FUNDING

None.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests We declare no competing interests. GST received research funding from GenMark Dx, for work not pertaining to this project. DRL received a K23 Mentored Research Training Award (1K23AR080209-01) from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Disease for work not pertaining to this project. SJS received research grants from Vertex, the Cystic Fibrosis Foundation, and the National Institutes of Health, for work not pertaining to this project. They also received consulting fees from Yale University. CB-C received honoraria for conference presentations on infection prevention and antimicrobial stewardship and received support for attending the meetings for which she received honoraria in 2022: IDWeek, What's New in Medicine, SHEA Spring Conference, and the Providence Annual ID Conference, for work not pertaining to this project. FCF has been a paid consultant to bioMérieux, for work not pertaining to this project. They also received honoraria from Medscape for participation in educational website-based presentations on the diagnosis of enteric infections.