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意大利维罗纳性传播感染门诊男性性工作者的生殖和非生殖样本中的抗生素耐药相关突变。

antibiotic resistance-associated mutations in genital and extragenital samples from men-who-have-sex-with-men attending a STI clinic in Verona, Italy.

机构信息

Microbiology Section, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.

School of Health Statistics and Biometrics, University of Verona, Verona, Italy.

出版信息

Front Cell Infect Microbiol. 2023 Mar 31;13:1155451. doi: 10.3389/fcimb.2023.1155451. eCollection 2023.

DOI:10.3389/fcimb.2023.1155451
PMID:37065200
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10102577/
Abstract

BACKGROUND

(MG) is one of the most warning emerging sexually transmitted pathogens also due to its ability in developing resistance to antibiotics. MG causes different conditions ranging from asymptomatic infections to acute mucous inflammation. Resistance-guided therapy has demonstrated the best cure rates and macrolide resistance testing is recommended in many international guidelines. However, diagnostic and resistance testing can only be based on molecular methods, and the gap between genotypic resistance and microbiological clearance has not been fully evaluated yet. This study aims at finding mutations associated with MG antibiotic resistance and investigating the relationship with microbiological clearance amongst MSM.

METHODS

From 2017 to 2021, genital (urine) and extragenital (pharyngeal and anorectal swabs) biological specimens were provided by men-who-have-sex-with-men (MSM) attending the STI clinic of the Infectious Disease Unit at the Verona University Hospital, Verona, Italy. A total of 1040 MSM were evaluated and 107 samples from 96 subjects resulted positive for MG. Among the MG-positive samples, all those available for further analysis (n=47) were considered for detection of mutations known to be associated with macrolide and quinolone resistance. 23S rRNA, and genes were analyzed by Sanger sequencing and Allplex™ MG and AziR Assay (Seegene).

RESULTS

A total of 96/1040 (9.2%) subjects tested positive for MG in at least one anatomical site. MG was detected in 107 specimens: 33 urine samples, 72 rectal swabs and 2 pharyngeal swabs. Among them, 47 samples from 42 MSM were available for investigating the presence of mutations associated with macrolide and quinolone resistance: 30/47 (63.8%) showed mutations in 23S rRNA while 10/47 (21.3%) in or genes. All patients with positive Test of Cure (ToC) after first-line treatment with azithromycin (n=15) were infected with 23S rRNA-mutated MG strains. All patients undergoing second-line moxifloxacin treatment (n=13) resulted negative at ToC, even those carrying MG strains with mutations in gene (n=6).

CONCLUSION

Our observations confirm that mutations in 23S rRNA gene are associated with azithromycin treatment failure and that mutations in gene alone are not always associated with phenotypic resistance to moxifloxacin. This reinforces the importance of macrolide resistance testing to guide the treatment and reduce antibiotic pressure on MG strains.

摘要

背景

(MG)是一种最具警示性的新兴性传播病原体,也因其能够对抗生素产生耐药性而备受关注。MG 可引起从无症状感染到急性粘液炎症等不同病症。耐药性指导治疗已显示出最佳的治愈率,许多国际指南都推荐进行大环内酯类耐药性检测。然而,诊断和耐药性检测只能基于分子方法,并且基因型耐药性与微生物清除之间的差距尚未得到充分评估。本研究旨在寻找与 MG 抗生素耐药性相关的突变,并调查其与男男性行为者(MSM)中微生物清除之间的关系。

方法

2017 年至 2021 年,意大利维罗纳大学医院传染病科性传播感染诊所的男男性接触者(MSM)提供了生殖器(尿液)和生殖器外(咽和肛门拭子)生物标本。共评估了 1040 名 MSM,其中 107 名来自 96 名受试者的样本 MG 检测呈阳性。在 MG 阳性样本中,所有可用于进一步分析的样本(n=47)均用于检测与大环内酯类和喹诺酮类耐药性相关的已知突变。23S rRNA 和 基因通过 Sanger 测序和 Allplex™MG 和 AziR 检测(Seegene)进行分析。

结果

96/1040(9.2%)名受试者至少在一个解剖部位检测到 MG 阳性。107 个标本中检测到 MG:33 个尿液样本,72 个直肠拭子和 2 个咽拭子。其中,42 名 MSM 的 47 个样本可用于调查与大环内酯类和喹诺酮类耐药性相关的突变情况:30/47(63.8%)在 23S rRNA 中显示突变,10/47(21.3%)在 或 基因中显示突变。所有接受一线阿奇霉素治疗后治疗成功检测(ToC)阳性的患者(n=15)均感染了 23S rRNA 突变的 MG 菌株。所有接受二线莫西沙星治疗的患者(n=13)在 ToC 时均呈阴性,即使那些携带 基因突变的 MG 菌株(n=6)也是如此。

结论

我们的观察结果证实,23S rRNA 基因中的突变与阿奇霉素治疗失败有关,而 基因中的突变单独与莫西沙星表型耐药性无关。这再次强调了进行大环内酯类耐药性检测以指导治疗和减少对 MG 菌株的抗生素压力的重要性。

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