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J Antimicrob Chemother. 2017 Jul 1;72(7):1937-1947. doi: 10.1093/jac/dkx067.

WGS to predict antibiotic MICs for Neisseria gonorrhoeae.

Author information

1
Nuffield Department of Medicine, University of Oxford, Oxford, UK.
2
Oxford National Institute for Health Research Health Protection Research Unit, Oxford, UK.
3
Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
4
National Infection Service, Public Health England, UK.
5
Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, London, UK.
6
Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA.
7
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
8
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
9
National Institute for Health Research Biomedical Research Centre, Oxford, UK.

Abstract

Background:

Tracking the spread of antimicrobial-resistant Neisseria gonorrhoeae is a major priority for national surveillance programmes.

Objectives:

We investigate whether WGS and simultaneous analysis of multiple resistance determinants can be used to predict antimicrobial susceptibilities to the level of MICs in N. gonorrhoeae.

Methods:

WGS was used to identify previously reported potential resistance determinants in 681 N. gonorrhoeae isolates, from England, the USA and Canada, with phenotypes for cefixime, penicillin, azithromycin, ciprofloxacin and tetracycline determined as part of national surveillance programmes. Multivariate linear regression models were used to identify genetic predictors of MIC. Model performance was assessed using leave-one-out cross-validation.

Results:

Overall 1785/3380 (53%) MIC values were predicted to the nearest doubling dilution and 3147 (93%) within ±1 doubling dilution and 3314 (98%) within ±2 doubling dilutions. MIC prediction performance was similar across the five antimicrobials tested. Prediction models included the majority of previously reported resistance determinants. Applying EUCAST breakpoints to MIC predictions, the overall very major error (VME; phenotypically resistant, WGS-prediction susceptible) rate was 21/1577 (1.3%, 95% CI 0.8%-2.0%) and the major error (ME; phenotypically susceptible, WGS-prediction resistant) rate was 20/1186 (1.7%, 1.0%-2.6%). VME rates met regulatory thresholds for all antimicrobials except cefixime and ME rates for all antimicrobials except tetracycline. Country of testing was a strongly significant predictor of MIC for all five antimicrobials.

Conclusions:

We demonstrate a WGS-based MIC prediction approach that allows reliable MIC prediction for five gonorrhoea antimicrobials. Our approach should allow reasonably precise prediction of MICs for a range of bacterial species.

PMID:
28333355
PMCID:
PMC5890716
DOI:
10.1093/jac/dkx067
[Indexed for MEDLINE]
Free PMC Article

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