Genomic characterization of multidrug-resistant extended-spectrum β-lactamase-producing Vibrio cholerae O1 strains from 2022 cholera outbreak in Kenya.

Abstract

Background: In mid-2021, a global surge in cholera cases was reported. This study characterized Vibrio cholerae O1 isolates obtained from faecal samples of cholera-positive cases during the 2022 cholera outbreak in Kenya.

Methods: A total of 202 V. cholerae were confirmed through serogroup and serotype characterization by slide agglutination. Susceptibility testing was done using the Kirby-Bauer disc diffusion method, and ESBL production confirmed using the double-disc synergy test. WGS was performed on Illumina and ONT platforms, followed by bioinformatics analysis.

Results: All the isolates were identified as V. cholerae O1 of Ogawa serotype, with 99% classified as MDR and 98.5% positive for ESBL production. Notably, the isolates were resistant to azithromycin, one of the recommended antibiotics for cholera treatment. MDR was linked to the acquisition of an IncC plasmid (pVCMLK181) carrying seven resistance genes, including mph(A), mph(E) and msr(E), which confer resistance to azithromycin, and the blaPER-7 ESBL gene. Resistance to nalidixic acid was associated with mutations in QRDRs of gyrA and parC. The isolates also carried SXT/R391-like ICE, ICEVchInd5 featuring a 10 kb deletion and mapped to the 7PET-AFR13 lineage. Phylogenetic analysis revealed a close relationship to other highly drug-resistant AFR13 strains reported in Tanzania, Comoros and Mayotte.

Conclusions: The high prevalence of multidrug resistance in cholera isolates emphasizes the need for continuous surveillance to monitor the evolution of MDR V. cholerae O1 strains and calls for consideration of deployment of alternative management and prevention options including oral cholera vaccines and long-term improvement of water, sanitation and hygiene (WASH) infrastructure and practice.