Determining antimicrobial susceptibility in Salmonella enterica serovar Typhimurium through whole genome sequencing: A comparison against multiple phenotypic susceptibility testing methods

Nana Mensah, Yue Tang, Shaun Cawthraw, Manal Abuoun, Jackie Fenner, Nicholas R. Thomson, Alison E. Mather, Liljana Petrovska-Holmes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Background: UK public health organisations perform routine antimicrobial susceptibility tests (ASTs) to characterise the potential for antimicrobial resistance in Salmonella enterica serovars. Genetic determinants of these resistance mechanisms are detectable by whole genome sequencing (WGS), however the viability of WGS-based genotyping as an alternative resistance screening tool remains uncertain. We compared WGS-based genotyping, disk diffusion and agar dilution to the broth microdilution reference AST for 102 Salmonella enterica serovar Typhimurium (S. Typhimurium) isolates across 11 antimicrobial compounds. Results: Genotyping concordance, interpreted using epidemiological cut-offs (ECOFFs), was 89.8% (1007/1122) with 0.83 sensitivity and 0.96 specificity. For seven antimicrobials interpreted using Salmonella clinical breakpoints, genotyping produced 0.84 sensitivity and 0.88 specificity. Although less accurate than disk diffusion (0.94 sensitivity, 0.93 specificity) and agar dilution (0.83 sensitivity, 0.98 specificity), genotyping performance improved to 0.89 sensitivity and 0.97 specificity when two antimicrobials with relatively high very major error rates were excluded (streptomycin and sulfamethoxazole). Conclusions: An 89.8% concordance from WGS-based AST predictions using ECOFF interpretations suggest that WGS would serve as an effective screening tool for the tracking of antimicrobial resistance mechanisms in S. Typhimurium. For use as a standalone clinical diagnostic screen, further work is required to reduce the error rates for specific antimicrobials.

Original languageEnglish
Article number148
JournalBMC Microbiology
Volume19
Issue number1
DOIs
Publication statusPublished - 2 Jul 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 The Author(s).

Keywords

  • Agar dilution
  • Antimicrobial susceptibility tests
  • Broth microdilution
  • Disk diffusion
  • Salmonella enterica serovar typhimurium
  • Whole genome sequencing

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