Characterization of azithromycin-resistant Shigella flexneri serotype 2a isolates using whole genome sequencing in Ontario from 2016 to 2018

Abstract

ABSTRACT Azithromycin-resistant shigellosis is increasing globally. This retrospective analysis of Shigella flexneri serotype 2a isolates from 2016 to 2018 in Ontario found nearly half were azithromycin (47.7%, 72/151) and ciprofloxacin (50.7%, 77/152) resistant. Moreover, 34.7% (25/72) of azithromycin-resistant isolates were also ciprofloxacin-resistant. Four isolates were ceftriaxone-resistant, although all azithromycin-resistant isolates were ceftriaxone-susceptible. Overall, 83.6% (127/152) of all S. flexneri 2a isolates were recovered from males and 97.2% (70/72) of the azithromycin-resistant cases were males. Among the azithromycin-resistant cases, some (8/72) reported international travel. Phylogenetic analysis of azithromycin-resistant isolates revealed two large male-dominated clusters, and one cluster may have been due to importation of resistant strain. Comparison of plasmids isolated from the clusters in Ontario revealed the presence of incFII plasmid with high percentage of similarity to plasmids present in global outbreaks affecting mostly males including men who have sex with men (MSM). These two large azithromycin-resistant clusters are suggestive of an outbreak among MSM, though disease exposure or sexual orientation of patients was unknown. The presence of plasmid-borne azithromycin resistance in ciprofloxacin-resistant isolates is a public health concern. Antimicrobial surveillance is important for patient management, understanding the spread of novel resistance types in local communities which sometimes is introduced by travel. We found ongoing multidrug-resistant outbreaks spanning multiple years affecting males. Reduction of future outbreaks in high-risk communities like MSM requires consorted information flow between laboratory, public health, and physicians. We impart genomic and antimicrobial characteristics of multidrug S. flexneri 2a which may serve as reference by clinicians and public health. IMPORTANCE Oral ciprofloxacin and azithromycin are generally considered as the first-line therapy of shigellosis. Here, we report the emergence and transmission of azithromycin and ciprofloxacin-resistant S. flexneri serotype 2a among male adults in Ontario during 2016–2018. The percentage of azithromycin and ciprofloxacin resistance among S. flexneri 2a is higher compared to previous reports from Canada and United States. Here, we show the genetic basis of the antimicrobial resistance among these unique groups of S. flexneri 2a isolates. We describe a domestically acquired azithromycin-resistant and ciprofloxacin-resistant S. flexneri 2a lineage in Ontario. Combining whole-genome sequencing (WGS) data with travel-associated data helped in understanding dissemination and transmission. We employed WGS, which not only helped us in understanding the genetic-relationship between isolates but also mine information regarding plasmids. In the future, linking WGS, travel-related data, and clinical data can provide enhanced contact tracing and improve public-health management.