title: Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: towards genotype-guided antimicrobial therapy.
abstract: BACKGROUND
  Increasing use of nucleic acid amplification tests (NAATs) as the primary means of diagnosing gonococcal infection has resulted in diminished availability of Neisseria gonorrhoeae antimicrobial susceptibility data. We conducted a prospective diagnostic assessment of a real-time PCR assay (NGSNP) enabling direct detection of gonococcal ciprofloxacin susceptibility from a range of clinical sample types.
  
  
  METHODS
  NGSNP, designed to discriminate an SNP associated with ciprofloxacin resistance within the N. gonorrhoeae genome, was validated using a characterized panel of geographically diverse isolates (n = 90) and evaluated to predict ciprofloxacin susceptibility directly on N. gonorrhoeae-positive NAAT lysates derived from genital (n = 174) and non-genital (n = 116) samples (n = 290), from 222 culture-confirmed clinical episodes of gonococcal infection.
  
  
  RESULTS
  NGSNP correctly genotyped all phenotypically susceptible (n = 49) and resistant (n = 41) panel isolates. Ciprofloxacin-resistant N. gonorrhoeae was responsible for infection in 29.7% (n = 66) of clinical episodes evaluated. Compared with phenotypic susceptibility testing, NGSNP demonstrated sensitivity and specificity of 95.8% (95% CI 91.5%-98.3%) and 100% (95% CI 94.7%-100%), respectively, for detecting ciprofloxacin-susceptible N. gonorrhoeae, with a positive predictive value of 100% (95% CI 97.7%-100%). Applied to urogenital (n = 164), rectal (n = 40) and pharyngeal samples alone (n = 30), positive predictive values were 100% (95% CI 96.8%-100%), 100% (95% CI 87.2%-100%) and 100% (95% CI 82.4%-100%), respectively.
  
  
  CONCLUSIONS
  Genotypic prediction of N. gonorrhoeae ciprofloxacin susceptibility directly from clinical samples was highly accurate and, in the absence of culture, will facilitate use of tailored therapy for gonococcal infection, sparing use of current empirical treatment regimens and enhancing acquisition of susceptibility data for surveillance.
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Pond
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Hall
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Victoria F
authors.initials: VF
authors.lastname: Miari
authors.affiliation: Sexually Transmitted Bacteria Reference Unit, Public Health England, Colindale, London, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Cole
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Ken G
authors.initials: KG
authors.lastname: Laing
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Heena
authors.initials: H
authors.lastname: Jagatia
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK Department of STI/HIV, Public Health England, Colindale, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Harding-Esch
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Monahan
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK Medical Microbiology, South West London Pathology, St George's University Hospitals NHS Foundation Trust, London, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Planche
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Hinds
authors.affiliation: Sexually Transmitted Bacteria Reference Unit, Public Health England, Colindale, London, UK.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Ison
authors.affiliation: Sexually Transmitted Bacteria Reference Unit, Public Health England, Colindale, London, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chisholm
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Butcher
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK Department of Genitourinary & HIV Medicine, St George's University Hospitals NHS Foundation Trust, London, UK Department of STI/HIV, Public Health England, Colindale, London, UK ssadiq@sgul.ac.uk.
authors.forename: Syed Tariq
authors.initials: ST
authors.lastname: Sadiq
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D005835:Genitalia / Q000382:microbiology*; D006069:Gonorrhea / Q000188:drug therapy* / Q000382:microbiology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009344:Neisseria gonorrhoeae / Q000187:drug effects*; D057285:Precision Medicine; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin
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