Genotypic determinants of fluoroquinolone and macrolide resistance in Neisseria gonorrhoeae
Catherine L. Hall A , Mark A. Harrison A , Marcus J. Pond A , Christine Chow A , Emma M. Harding-Esch A B and S. Tariq Sadiq A B C D
+ Author Affiliations
- Author Affiliations
A Applied Diagnostic Research and Evaluation Unit, St George’s University of London, Institute for Infection & Immunity, Cranmer Terrace, Tooting, London SW17 0RE, UK.
B National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
C St George’s University Hospitals NHS Foundation Trust, Blackshaw Road, Tooting, London SW17 0QT, UK.
D Corresponding author. Email: ssadiq@sgul.ac.uk
Sexual Health 16(5) 479-487 https://doi.org/10.1071/SH18225
Submitted: 29 November 2018 Accepted: 1 April 2019 Published: 1 August 2019
Journal Compilation © CSIRO 2019 Open Access CC BY-NC-ND
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.
Additional keywords: 23S rRNA, azithromycin, ciprofloxacin, gyrA, sexually transmissible infections.
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