Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: Towards genotype-guided antimicrobial therapy

Marcus J. Pond; Catherine L. Hall; Victoria F. Miari; Michelle Cole; Ken G. Laing; Heena Jagatia; Emma Harding-Esch; Irene M. Monahan; Timothy Planche; Jason Hinds; Catherine Ison; Stephanie Chisholm; Philip D. Butcher; Syed Tariq Sadiq

doi:10.1093/jac/dkv432

Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: Towards genotype-guided antimicrobial therapy

Marcus J. Pond, Catherine L. Hall, Victoria F. Miari, Michelle Cole, Ken G. Laing, Heena Jagatia, Emma Harding-Esch, Irene M. Monahan, Timothy Planche, Jason Hinds, Catherine Ison, Stephanie Chisholm, Philip D. Butcher, Syed Tariq Sadiq^*

^*Corresponding author for this work

AMR & HCAI Divisional Office

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

Introduction: 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.

Original language	English
Pages (from-to)	897-902
Number of pages	6
Journal	Journal of Antimicrobial Chemotherapy
Volume	71
Issue number	4
DOIs	https://doi.org/10.1093/jac/dkv432
Publication status	Published - 1 Apr 2016

Bibliographical note

Funding Information:
This work was supported by the UK Clinical Research Collaboration (Medical Research Council) Translation Infection Research Initiative Consortium (grant number G0901608). We thank the staff of the Medical Microbiology Department, St George?s University Hospitals NHS Foundation Trust.

Funding Information:
This work was supported by the UK Clinical Research Collaboration (Medical Research Council) Translation Infection Research Initiative Consortium (grant number G0901608). We thank the staff of the Medical Microbiology Department, St George’s University Hospitals NHS Foundation Trust.

Publisher Copyright:
© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

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10.1093/jac/dkv432

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Pond, M. J., Hall, C. L., Miari, V. F., Cole, M., Laing, K. G., Jagatia, H., Harding-Esch, E., Monahan, I. M., Planche, T., Hinds, J., Ison, C., Chisholm, S., Butcher, P. D., & Sadiq, S. T. (2016). Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: Towards genotype-guided antimicrobial therapy. Journal of Antimicrobial Chemotherapy, 71(4), 897-902. https://doi.org/10.1093/jac/dkv432

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title = "Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: Towards genotype-guided antimicrobial therapy",

abstract = "Introduction: 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.",

author = "Pond, \{Marcus J.\} and Hall, \{Catherine L.\} and Miari, \{Victoria F.\} and Michelle Cole and Laing, \{Ken G.\} and Heena Jagatia and Emma Harding-Esch and Monahan, \{Irene M.\} and Timothy Planche and Jason Hinds and Catherine Ison and Stephanie Chisholm and Butcher, \{Philip D.\} and Sadiq, \{Syed Tariq\}",

note = "Funding Information: This work was supported by the UK Clinical Research Collaboration (Medical Research Council) Translation Infection Research Initiative Consortium (grant number G0901608). We thank the staff of the Medical Microbiology Department, St George?s University Hospitals NHS Foundation Trust. Funding Information: This work was supported by the UK Clinical Research Collaboration (Medical Research Council) Translation Infection Research Initiative Consortium (grant number G0901608). We thank the staff of the Medical Microbiology Department, St George{\textquoteright}s University Hospitals NHS Foundation Trust. Publisher Copyright: {\textcopyright} The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.",

year = "2016",

month = apr,

day = "1",

doi = "10.1093/jac/dkv432",

language = "English",

volume = "71",

pages = "897--902",

journal = "Journal of Antimicrobial Chemotherapy",

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publisher = "Oxford University Press",

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Pond, MJ, Hall, CL, Miari, VF, Cole, M, Laing, KG, Jagatia, H, Harding-Esch, E, Monahan, IM, Planche, T, Hinds, J, Ison, C, Chisholm, S, Butcher, PD & Sadiq, ST 2016, 'Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: Towards genotype-guided antimicrobial therapy', Journal of Antimicrobial Chemotherapy, vol. 71, no. 4, pp. 897-902. https://doi.org/10.1093/jac/dkv432

Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: Towards genotype-guided antimicrobial therapy. / Pond, Marcus J.; Hall, Catherine L.; Miari, Victoria F. et al.
In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 4, 01.04.2016, p. 897-902.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples

T2 - Towards genotype-guided antimicrobial therapy

AU - Pond, Marcus J.

AU - Hall, Catherine L.

AU - Miari, Victoria F.

AU - Cole, Michelle

AU - Laing, Ken G.

AU - Jagatia, Heena

AU - Harding-Esch, Emma

AU - Monahan, Irene M.

AU - Planche, Timothy

AU - Hinds, Jason

AU - Ison, Catherine

AU - Chisholm, Stephanie

AU - Butcher, Philip D.

AU - Sadiq, Syed Tariq

N1 - Funding Information: This work was supported by the UK Clinical Research Collaboration (Medical Research Council) Translation Infection Research Initiative Consortium (grant number G0901608). We thank the staff of the Medical Microbiology Department, St George?s University Hospitals NHS Foundation Trust. Funding Information: This work was supported by the UK Clinical Research Collaboration (Medical Research Council) Translation Infection Research Initiative Consortium (grant number G0901608). We thank the staff of the Medical Microbiology Department, St George’s University Hospitals NHS Foundation Trust. Publisher Copyright: © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Introduction: 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.

AB - Introduction: 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.

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U2 - 10.1093/jac/dkv432

DO - 10.1093/jac/dkv432

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AN - SCOPUS:84964334638

SN - 0305-7453

VL - 71

SP - 897

EP - 902

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 4

ER -

Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: Towards genotype-guided antimicrobial therapy

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