Genotypic determinants of fluoroquinolone and macrolide resistance in Neisseria gonorrhoeae

Catherine L. Hall, Mark A. Harrison, Marcus J. Pond, Christine Chow, Emma Harding-Esch, S. Tariq Sadiq*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: High rates of antimicrobial resistance (AMR) in Neisseria gonorrhoeae hinder effective treatment, but molecular AMR diagnostics may help address the challenge. This study aimed to appraise the literature for resistance-associated genotypic markers linked to fluoroquinolones and macrolides, to identify and review their use in diagnostics. Methods: Medline and EMBASE databases were searched and data pooled to evaluate associations between genotype and phenotypic resistance. The minimum inhibitory concentration (MIC) cut-offs were ≤ 0.06 mg L-1 for non-resistance to ciprofloxacin and ≤ 0.5 mg L-1 for non-resistance to azithromycin. Results: Diagnostic accuracy estimates were limited by data availability and reporting. It was found that: 1) S91 and D95 mutations in the GyrA protein independently predicted ciprofloxacin resistance and, used together, gave 98.6% (95% confidence interval (CI) 98.0-99.0%) sensitivity and 91.4% (95%CI 88.6-93.7%) specificity; 2) the number of 23S rRNA gene alleles with C2611T or A2059G mutations was highly correlated with azithromycin resistance, with mutation in any allele giving a sensitivity and specificity of 66.1% (95%CI 62.1-70.0%) and 98.9% (95%CI 97.5-99.5%) respectively. Estimated negative (NPV) and positive predictive values (PPV) for a 23S rRNA diagnostic were 98.6% (95%CI 96.8-99.4%) and 71.5% (95%CI 68.0-74.8%) respectively; 3) mutation at amino acid position G45 in the MtrR protein independently predicted azithromycin resistance; however, when combined with 23S rRNA, did not improve the PPV or NPV. Conclusions: Viable candidates for markers of resistance detection for incorporation into diagnostics were demonstrated. Such tests may enhance antibiotic stewardship and treatment options.

Original languageEnglish
Pages (from-to)479-487
Number of pages9
JournalSexual Health
Volume16
Issue number5
DOIs
Publication statusPublished - 2019

Bibliographical note

Funding Information:
This work was supported by the UK Clinical Research Collaboration (Medical Research Council) (http://www.ukcrc.org/) Translation Infection Research Initiative Consortium (grant number G0901608) and by the National Institute for Health Research (NIHR) i4iProgram (https://www.nihr.ac.uk/about-us/how-we-aremanaged/boards-and-panels/ program-boards436and-panels/invention-for-innovation/) (grant number II-LB-0214–20005). The views expressed are those of the authors and not necessarily those of the NIHR, the NHS or the Department of Health. Both grants were awarded to S. Tariq Sadiq.

Publisher Copyright:
© CSIRO 2019 Open Access.

Keywords

  • 23S rRNA
  • azithromycin
  • ciprofloxacin
  • gyrA
  • sexually transmissible infections

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