直接从生殖器和生殖器外临床样本中准确检测淋病奈瑟菌对环丙沙星的敏感性：迈向基因型指导的抗菌治疗。
Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: towards genotype-guided antimicrobial therapy.
作者信息
Pond Marcus J, Hall Catherine L, Miari Victoria F, Cole Michelle, Laing Ken G, Jagatia Heena, Harding-Esch Emma, Monahan Irene M, Planche Timothy, Hinds Jason, Ison Catherine A, Chisholm Stephanie, Butcher Philip D, Sadiq Syed Tariq
机构信息
Institute for Infection and Immunity, St George's, University of London, London, UK.
Sexually Transmitted Bacteria Reference Unit, Public Health England, Colindale, London, UK.
出版信息
J Antimicrob Chemother. 2016 Apr;71(4):897-902. doi: 10.1093/jac/dkv432. Epub 2016 Jan 26.
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.
引言
核酸扩增检测（NAATs）越来越多地被用作诊断淋病奈瑟菌感染的主要手段，这导致淋病奈瑟菌抗菌药物敏感性数据的可获得性降低。我们对一种实时PCR检测方法（NGSNP）进行了前瞻性诊断评估，该方法能够直接从一系列临床样本类型中检测淋病奈瑟菌对环丙沙星的敏感性。
方法
NGSNP旨在区分淋病奈瑟菌基因组中与环丙沙星耐药相关的单核苷酸多态性（SNP），使用一组具有特征的来自不同地理区域的分离株（n = 90）进行验证，并评估其直接预测来自222例经培养确诊的淋病奈瑟菌感染临床病例的生殖器（n = 174）和非生殖器（n = 116）样本（n = 290）的淋病奈瑟菌阳性NAAT裂解物中环丙沙星敏感性的能力。
结果
NGSNP对所有表型敏感（n = 49）和耐药（n = 41）的参比分离株进行了正确的基因分型。在评估的临床病例中，29.7%（n = 66）的感染由耐环丙沙星的淋病奈瑟菌引起。与表型敏感性检测相比，NGSNP检测环丙沙星敏感淋病奈瑟菌的敏感性和特异性分别为95.8%（95%置信区间91.5% - 98.3%）和100%（95%置信区间94.7% - 100%），阳性预测值为100%（95%置信区间97.7% - 100%）。单独应用于泌尿生殖道（n = 164）、直肠（n = 40）和咽部样本（n = 30）时，阳性预测值分别为100%（95%置信区间96.8% - 100%）、100%（95%置信区间87.2% - 100%）和100%（95%置信区间82.4% - 100%）。
结论
直接从临床样本中对淋病奈瑟菌环丙沙星敏感性进行基因分型预测具有高度准确性，在没有培养的情况下，将有助于为淋病奈瑟菌感染采用针对性治疗，避免使用当前的经验性治疗方案，并加强获取用于监测的敏感性数据。
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