TY - JOUR
T1 - Determining antimicrobial susceptibility in Salmonella enterica serovar Typhimurium through whole genome sequencing
T2 - A comparison against multiple phenotypic susceptibility testing methods
AU - Mensah, Nana
AU - Tang, Yue
AU - Cawthraw, Shaun
AU - Abuoun, Manal
AU - Fenner, Jackie
AU - Thomson, Nicholas R.
AU - Mather, Alison E.
AU - Petrovska-Holmes, Liljana
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/7/2
Y1 - 2019/7/2
N2 - 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.
AB - 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.
KW - Agar dilution
KW - Antimicrobial susceptibility tests
KW - Broth microdilution
KW - Disk diffusion
KW - Salmonella enterica serovar typhimurium
KW - Whole genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85068500216&partnerID=8YFLogxK
U2 - 10.1186/s12866-019-1520-9
DO - 10.1186/s12866-019-1520-9
M3 - Article
C2 - 31266463
AN - SCOPUS:85068500216
SN - 1471-2180
VL - 19
JO - BMC Microbiology
JF - BMC Microbiology
IS - 1
M1 - 148
ER -