头孢曲松减少 2009 至 2017 年荷兰淋病奈瑟菌易感性：从 PenA 镶嵌现象到 A501T/V 非镶嵌现象。

Ceftriaxone Reduced Susceptible Neisseria gonorrhoeae in the Netherlands, 2009 to 2017: From PenA Mosaicism to A501T/V Nonmosaicism.

机构信息

From the Department of Infectious Diseases, Public Health Service Amsterdam, Amsterdam, the Netherlands.

Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.

出版信息

Sex Transm Dis. 2019 Sep;46(9):594-601. doi: 10.1097/OLQ.0000000000001031.

DOI:10.1097/OLQ.0000000000001031

PMID:31415041

Abstract

OBJECTIVES

To compare molecular and epidemiological differences between ceftriaxone-reduced susceptible (CRO-RS) and ceftriaxone-susceptible (CRO-S) N. gonorrhoeae (Ng) and to study the genetic relatedness of CRO-RS isolates.

METHODS

Demographic and clinical data and samples for cultures were routinely collected from gonorrhoea patients visiting the Amsterdam STI clinic in 2009 to 2017. Ng multiantigen sequence typing (NG-MAST) and penA types were compared between CRO-RS and CRO-S Ng (frequency matched on year of isolation and sexual risk group). Minimum spanning trees were produced based on multilocus variable number of tandem repeats analysis for Ng (NG-MLVA) genotypes.

RESULTS

We selected 174 CRO-RS isolates (minimum inhibitory concentration, ≥0.064 mg/L) and 174 CRO-S isolates (minimum inhibitory concentration, ≤0.016 mg/L). Demographic and clinical characteristics of patients were overall comparable between those infected with CRO-RS Ng and CRO-S Ng. However, CRO-RS isolates were more often collected from the pharyngeal site (odds ratios [OR], 3.64; P < 0.001), and patients with CRO-RS Ng were less often human immunodeficiency virus (HIV) and syphilis positive (OR, 0.63; P = 0.041 and OR, 0.58; P = 0.028, respectively). We identified 12 clusters based on NG-MLVA genotypes, including 3 large (>25 isolates) clusters predominantly containing CRO-RS isolates. Those from cluster 1 (n = 32) were mostly from 2009 to 2012 (n = 24; 75.0%), with a mosaic penA XXXIV pattern (n = 27; 84.4%) and belonging to NG-MAST genogroup G1407 (n = 24; 75.0%). Isolates from cluster 2 (n = 29) were mostly from 2013 to 2015 (n = 24; 82.7%), had a nonmosaic penA IX + A501T mutation (n = 22; 75.9%) and NG-MAST G2400 (n = 14; 48.3%). Most isolates from cluster 3 (n = 37) were from 2015 to 2017 (n = 26; 70.2%), had a nonmosaic penA IV + A501V mutation (n = 24; 64.9%) and NG-MAST G2318 (n = 22; 59.5%).

CONCLUSIONS

We observed a shift in the predominant penA (from mosaic toward nonmosaic plus A501T/V mutation), NG-MAST and NG-MLVA types among CRO-RS Ng over time. This indicates a successive spread of different CRO-RS Ng clones.

摘要

目的

比较头孢曲松敏感但降低（CRO-RS）和头孢曲松敏感（CRO-S）淋病奈瑟菌（Ng）之间的分子和流行病学差异，并研究 CRO-RS 分离株的遗传相关性。

方法

2009 年至 2017 年，从阿姆斯特丹性传播感染诊所就诊的淋病患者中常规收集人口统计学和临床数据以及培养样本。对 CRO-RS 和 CRO-S Ng（按分离年份和性风险组匹配频率）的 Ng 多抗原序列分型（NG-MAST）和 penA 型进行比较。基于 Ng 的多位点可变数串联重复分析（NG-MLVA）基因型生成最小跨度树。

结果

我们选择了 174 株 CRO-RS 分离株（最低抑菌浓度≥0.064mg/L）和 174 株 CRO-S 分离株（最低抑菌浓度≤0.016mg/L）。感染 CRO-RS Ng 和 CRO-S Ng 的患者的总体人口统计学和临床特征相似。然而，CRO-RS 分离株更常从咽部采集（比值比[OR]，3.64；P<0.001），CRO-RS Ng 患者的 HIV 和梅毒阳性率较低（OR，0.63；P=0.041 和 OR，0.58；P=0.028）。我们根据 NG-MLVA 基因型确定了 12 个聚类，包括 3 个主要（>25 个分离株）聚类，主要包含 CRO-RS 分离株。来自聚类 1（n=32）的分离株主要来自 2009 年至 2012 年（n=24；75.0%），具有镶嵌 penA XXXIV 模式（n=27；84.4%），属于 NG-MAST 基因群 G1407（n=24；75.0%）。来自聚类 2（n=29）的分离株主要来自 2013 年至 2015 年（n=24；82.7%），具有非镶嵌 penA IX+A501T 突变（n=22；75.9%）和 NG-MAST G2400（n=14；48.3%）。来自聚类 3（n=37）的大多数分离株来自 2015 年至 2017 年（n=26；70.2%），具有非镶嵌 penA IV+A501V 突变（n=24；64.9%）和 NG-MAST G2318（n=22；59.5%）。