淋病奈瑟菌对氟喹诺酮类和大环内酯类耐药的基因型决定因素。

Genotypic determinants of fluoroquinolone and macrolide resistance in Neisseria gonorrhoeae.

作者信息

Hall Catherine L, Harrison Mark A, Pond Marcus J, Chow Christine, Harding-Esch Emma M, Sadiq S Tariq

机构信息

Applied Diagnostic Research and Evaluation Unit, St George's University of London, Institute for Infection & Immunity, Cranmer Terrace, Tooting, London SW17 0RE, UK.

Applied Diagnostic Research and Evaluation Unit, St George's University of London, Institute for Infection & Immunity, Cranmer Terrace, Tooting, London SW17 0RE, UK; and National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.

出版信息

Sex Health. 2019 Sep;16(5):479-487. doi: 10.1071/SH18225.

DOI:10.1071/SH18225

PMID:31366421

Abstract

UNLABELLED

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.

摘要

未标注

背景淋病奈瑟菌的高抗菌药物耐药率（AMR）阻碍了有效治疗，但分子AMR诊断可能有助于应对这一挑战。本研究旨在评估与氟喹诺酮类和大环内酯类相关的耐药性基因型标记的文献，以识别并综述其在诊断中的应用。

方法

检索Medline和EMBASE数据库并汇总数据，以评估基因型与表型耐药性之间的关联。对环丙沙星不耐药的最低抑菌浓度（MIC）临界值为≤0.06 mg/L，对阿奇霉素不耐药的临界值为≤0.5 mg/L。

结果

诊断准确性评估受数据可用性和报告的限制。发现：1）GyrA蛋白中的S91和D95突变独立预测环丙沙星耐药性，两者结合使用时，敏感性为98.6%（95%置信区间（CI）98.0 - 99.0%），特异性为91.4%（95%CI 88.6 - 93.7%）；2）具有C2611T或A2059G突变的23S rRNA基因等位基因数量与阿奇霉素耐药性高度相关，任何一个等位基因发生突变时，敏感性和特异性分别为66.1%（95%CI 62.1 - 70.0%）和98.9%（95%CI 97.5 - 99.5%）。23S rRNA诊断的估计阴性预测值（NPV）和阳性预测值（PPV）分别为98.6%（95%CI 96.8 - 99.4%）和71.5%（95%CI 68.0 - 74.8%）；3）MtrR蛋白中氨基酸位置G45的突变独立预测阿奇霉素耐药性；然而，与23S rRNA结合时，并未提高PPV或NPV。