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P5.098 Clinical Prediction of Fluoroquinolone Susceptibility, Directly from Residual Routine NAAT Gonococcal-Positive Samples Using a gyrA SNP Detection Assay
  1. V F Miari1,
  2. M J Pond1,
  3. K Laing1,
  4. H Jagatia1,
  5. I Monahan1,
  6. T Planche1,2,
  7. P D Butcher1,
  8. S T Sadiq1,3
  1. 1St George’s University of London, London, UK
  2. 2St George’s Healthcare NHS Trust, Department of Medical Microbiology, London, UK
  3. 3Department of Genitourinary Medicine, St George’s Healthcare NHS Trust, London, UK

Abstract

Background Antimicrobial resistance in Neisseria gonorrhoeae (NG) poses significant challenges for empirical therapy, heightened by nucleic acid amplification tests (NAAT) use over culture for diagnosis. Molecular susceptibility testing, directly on NAAT-positive clinical samples may allow fluoroquinolone use, currently precluded because community resistance rates are > 5%. We determined whether a genotypic resistance test performed directly on NG NAAT positive routine clinical samples predicted susceptibility to ciprofloxacin with > 95% confidence.

Methods A real time PCR SNP detection assay targeting the C > T SNP in codon 91 (S91P) of gyrA, commonly linked with other gyrA resistance associated SNPs, was used on 81 previously identified NG isolates, tested for ciprofloxacin MICs by E-test after sample blinding (Phase 1) and also (Phase 2) on 103 blinded clinical samples from 89 patients, positive by NAAT and culture (25 women, 64 men; 21 cervical, 3 vaginal, 1 urethral, 48 urine, 10 throat and 21 rectal).

Results Phase 1 and Phase 2: 61/81(75%) and 68/103(66%) respectively were phenotypically susceptible to ciprofloxacin; 81/81 and 87/103 respectively of S91P assays worked. Phase 2 assay failure was not associated with sample site. Of Phase 2 assays that worked, predictive values for identifying ciprofloxacin susceptible gonorrhoea, using wild-type (S91P absence), and resistant gonorrhoea, using S91P presence, on clinical samples from: genital sites was 100%(95% CI: 91%–100%)/86%(67%–95%) respectively; non-genital sites was 93%(68%–99%)/92%(65%–99%) respectively; overall was 98%(90%–100%)/88%(73%–95%) respectively. Among all 89 patients, assay use would have identified 47(53%) as treatable with ciprofloxacin, one incorrectly (predictive value of assay for susceptibility 97.9%(88.9%–99.6%). However, nearly 80% of men and 60% of women received treatment for gonorrhoea before these results would have been available.

Conclusions Direct genotypic testing of routine gonococcal NAAT-positive genital samples allows for safe use of ciprofloxacin in gonorrhoea but may have limited impact, particularly for men until available at the point of care.

  • Fluoroquinolone
  • gonorrhoea

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