Whole-Genome Sequencing to Predict Antimicrobial Susceptibility Profiles in Neisseria gonorrhoeae.


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
12 04 2023
Historique:
received: 20 06 2022
accepted: 01 02 2023
pmc-release: 03 02 2024
medline: 14 4 2023
pubmed: 4 2 2023
entrez: 3 2 2023
Statut: ppublish

Résumé

Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 μg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 μg/mL. Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials.

Sections du résumé

BACKGROUND
Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates.
METHODS
Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility.
RESULTS
A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 μg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 μg/mL.
CONCLUSIONS
Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials.

Identifiants

pubmed: 36735316
pii: 7025705
doi: 10.1093/infdis/jiad027
pmc: PMC10319951
doi:

Substances chimiques

Anti-Bacterial Agents 0
Ciprofloxacin 5E8K9I0O4U
Anti-Infective Agents 0
Azithromycin 83905-01-5

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

917-925

Subventions

Organisme : NIAID NIH HHS
ID : HHSN272201300014I
Pays : United States
Organisme : NIAID NIH HHS
ID : K01 AI136725
Pays : United States
Organisme : FIC NIH HHS
ID : K01 TW012170
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132606
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH080634
Pays : United States
Organisme : World Health Organization
ID : 001
Pays : International
Organisme : NIAID NIH HHS
ID : F32 AI145157
Pays : United States

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Déclaration de conflit d'intérêts

Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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Auteurs

Claire C Bristow (CC)

Department of Medicine, University of California San Diego, La Jolla, California, USA.

Tatum D Mortimer (TD)

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Sheldon Morris (S)

Department of Medicine, University of California San Diego, La Jolla, California, USA.

Yonatan H Grad (YH)

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Olusegun O Soge (OO)

Departments of Global Health, Allergy and Infectious Disease, Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.

Erika Wakatake (E)

Departments of Global Health, Allergy and Infectious Disease, Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.

Rushlenne Pascual (R)

Departments of Global Health, Allergy and Infectious Disease, Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.

Sara McCurdy Murphy (SM)

Social & Scientific Systems, a DLH Holdings Company, Silver Spring, Maryland, USA.

Kyra E Fryling (KE)

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Paul C Adamson (PC)

Division of Infectious Diseases at the David Geffen School of Medicine, University of California, Los Angeles, California, USA.

Jo-Anne Dillon (JA)

Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, Sikkim, Canada.

Nidhi R Parmar (NR)

Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, Sikkim, Canada.

Hai Ha Long Le (HHL)

Department of Microbiology, Mycology and Parasitology, National Hospital of Venereology and Dermatology, Hanoi, Vietnam.
Department of Clinical Microbiology and Parasitology, Hanoi Medical University, Hanoi, Vietnam.

Hung Van Le (H)

Department of Microbiology, Mycology and Parasitology, National Hospital of Venereology and Dermatology, Hanoi, Vietnam.
Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam.

Reyna Margarita Ovalles Ureña (RM)

Laboratorio Nacional Dr. Defillo, Santo Domingo, Dominican Republic.

Nireshni Mitchev (N)

University of KwaZulu-Natal: Durban, KwaZulu-Natal, Glenwood, Durban, South Africa.

Koleka Mlisana (K)

University of KwaZulu-Natal: Durban, KwaZulu-Natal, Glenwood, Durban, South Africa.
National Health Laboratory Service, Johannesburg, South Africa.
Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.

Teodora Wi (T)

World Health Organization, Geneva, Switzerland.

Samuel P Dickson (SP)

Pentara Corporation, Salt Lake City, Utah, USA.

Jeffrey D Klausner (JD)

Department of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

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Classifications MeSH