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Sexual Health Sexual Health Society
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RESEARCH ARTICLE

Emergence of high-level azithromycin-resistant Neisseria gonorrhoeae causing male urethritis in Johannesburg, South Africa, 2021

Etienne E. Müller https://orcid.org/0000-0002-9800-491X A * , Lindy Y. E. Gumede A , Dumisile V. Maseko A , Mahlape P. Mahlangu A , Johanna M. E. Venter A , Bianca Da Costa Dias A , Duduzile Nhlapho A and Ranmini S. Kularatne A B C
+ Author Affiliations
- Author Affiliations

A Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.

B Department of Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

C Present address: Labtests Auckland and Northland Pathology, Mt Wellington, Auckland, New Zealand.

* Correspondence to: etiennem@nicd.ac.za

Handling Editor: Eric Chow

Sexual Health 21, SH23143 https://doi.org/10.1071/SH23143
Submitted: 31 July 2023  Accepted: 8 November 2023  Published: 30 November 2023

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing

Abstract

Background

In South Africa, Neisseria gonorrhoeae, which is the predominant cause of male urethritis, is treated syndromically using dual ceftriaxone and azithromycin therapy. We determined antimicrobial susceptibilities of N. gonorrhoeae isolates from urethral discharge specimens, and genetically characterised those with elevated minimum inhibitory concentrations (MICs) for first-line antimicrobials.

Methods

Routine antimicrobial susceptibility testing (AST) of N. gonorrhoeae isolates included E-test for ceftriaxone, cefixime and gentamicin and agar dilution for azithromycin and spectinomycin. Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) was performed for isolates with elevated MICs to identify antimicrobial resistance (AMR) determinants, and Neisseria gonorrhoeae Multi-Antigen Sequence Typing (NG-MAST) was used to determine strain relatedness.

Results

N. gonorrhoeae was cultured from urethral discharge swab specimens obtained from 196 of 238 (82.4%) men presenting to a primary healthcare facility in Johannesburg in 2021. All viable isolates were susceptible to extended-spectrum cephalosporins. Four isolates had high azithromycin MICs ranging from 32 mg/L to >256 mg/L and grouped into two novel NG-MAST and NG-STAR groups. Two isolates from Group 1 (NG-MAST ST20366, NG-STAR ST4322) contained mutated mtrR (G45D) and 23S rRNA (A2059G) alleles, while the two isolates from Group 2 (NG-MAST ST20367, NG-STAR ST4323) had different mutations in mtrR (A39T) and 23S rRNA (C2611T).

Conclusions

We report the first cases of high-level azithromycin resistance in N. gonorrhoeae from South Africa. Continued AMR surveillance is critical to detect increasing azithromycin resistance prevalence in N. gonorrhoeae, which may justify future modifications to the STI syndromic management guidelines.

Keywords: antimicrobials, azithromycin, ceftriaxone, gonorrhoea, NG-MAST, NG-STAR, resistance, sub-Saharan Africa, urethritis.

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