结核病的诊断和新治疗方案:Xpert MTB/XDR检测能否填补氟喹诺酮类药物检测的空白?

IF 5.4 2区 医学 Q1 MICROBIOLOGY
Derek T Armstrong, Emma C E Baird, Logan Pretty, Karen D'Agostino, Matthew Schwartz, Victoria L Campódonico, Nicole Parrish
{"title":"结核病的诊断和新治疗方案:Xpert MTB/XDR检测能否填补氟喹诺酮类药物检测的空白?","authors":"Derek T Armstrong, Emma C E Baird, Logan Pretty, Karen D'Agostino, Matthew Schwartz, Victoria L Campódonico, Nicole Parrish","doi":"10.1128/jcm.00643-25","DOIUrl":null,"url":null,"abstract":"<p><p>Rapid diagnosis of resistance-conferring mutations to antibiotics used for the treatment of tuberculosis (TB) is critical for patient care and public health control efforts. Prior guidelines included the use of fluoroquinolones (FQs) for the treatment of drug-resistant TB, including multidrug-resistant TB, pre-extensively drug-resistant TB, and extensively drug-resistant TB. More recently, a short-course regimen for antibiotic-susceptible TB was introduced, which includes the use of a FQ, a drug class that diagnostic algorithms in the United States (US) typically do not test for if all first-line agents are susceptible. However, FQ mono-resistance has been documented by previous studies, and for this reason, we tested 319 archived <i>Mycobacterium tuberculosis</i> complex (MTBC) strains spanning a 14-year period of time using the Xpert MTB/XDR assay. Resistance to FQs was detected in 4.4% (14/319) of the isolates tested, with mutations predominating in the <i>gyrA</i> region (13/14; 92.9%). A single isolate (1/14; 7.1%) was found to have a <i>gyrB</i> mutation. A broth microdilution assay demonstrated the minimum inhibitory concentrations for resistant strains that ranged from 0.5 µg/mL to 8.0 µg/mL. Importantly, three strains were FQ mono-resistant and would have been completely missed by standard testing algorithms. Although currently unavailable in the US, the GeneXpert XDR assay has the potential to fill the significant diagnostic gap in susceptibility testing of MTBC resistance to FQs and support the use of the currently recommended short-course regimen.IMPORTANCE This study provides insight into the need for additional rapid testing for the detection of drug resistance (specifically to fluoroquinolones) in tuberculosis (TB) cases in the United States (US). The current regimens for TB treatment rely on knowing resistance patterns to optimize treatment, and missed resistance could have a negative impact on the health of the patient, as well as contribute to increased drug-resistance mutations in new TB cases. There are currently limited platforms for expanded rapid drug resistance testing for TB cases in the US, and this study looks at past TB cases that had drug resistance missed by routine testing.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0064325"},"PeriodicalIF":5.4000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Diagnostics and new treatment regimens for TB: can the Xpert MTB/XDR assay fill the gap for fluoroquinolone testing?\",\"authors\":\"Derek T Armstrong, Emma C E Baird, Logan Pretty, Karen D'Agostino, Matthew Schwartz, Victoria L Campódonico, Nicole Parrish\",\"doi\":\"10.1128/jcm.00643-25\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Rapid diagnosis of resistance-conferring mutations to antibiotics used for the treatment of tuberculosis (TB) is critical for patient care and public health control efforts. Prior guidelines included the use of fluoroquinolones (FQs) for the treatment of drug-resistant TB, including multidrug-resistant TB, pre-extensively drug-resistant TB, and extensively drug-resistant TB. More recently, a short-course regimen for antibiotic-susceptible TB was introduced, which includes the use of a FQ, a drug class that diagnostic algorithms in the United States (US) typically do not test for if all first-line agents are susceptible. However, FQ mono-resistance has been documented by previous studies, and for this reason, we tested 319 archived <i>Mycobacterium tuberculosis</i> complex (MTBC) strains spanning a 14-year period of time using the Xpert MTB/XDR assay. Resistance to FQs was detected in 4.4% (14/319) of the isolates tested, with mutations predominating in the <i>gyrA</i> region (13/14; 92.9%). A single isolate (1/14; 7.1%) was found to have a <i>gyrB</i> mutation. A broth microdilution assay demonstrated the minimum inhibitory concentrations for resistant strains that ranged from 0.5 µg/mL to 8.0 µg/mL. Importantly, three strains were FQ mono-resistant and would have been completely missed by standard testing algorithms. Although currently unavailable in the US, the GeneXpert XDR assay has the potential to fill the significant diagnostic gap in susceptibility testing of MTBC resistance to FQs and support the use of the currently recommended short-course regimen.IMPORTANCE This study provides insight into the need for additional rapid testing for the detection of drug resistance (specifically to fluoroquinolones) in tuberculosis (TB) cases in the United States (US). The current regimens for TB treatment rely on knowing resistance patterns to optimize treatment, and missed resistance could have a negative impact on the health of the patient, as well as contribute to increased drug-resistance mutations in new TB cases. There are currently limited platforms for expanded rapid drug resistance testing for TB cases in the US, and this study looks at past TB cases that had drug resistance missed by routine testing.</p>\",\"PeriodicalId\":15511,\"journal\":{\"name\":\"Journal of Clinical Microbiology\",\"volume\":\" \",\"pages\":\"e0064325\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Microbiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1128/jcm.00643-25\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Microbiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1128/jcm.00643-25","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

快速诊断用于治疗结核病的抗生素产生耐药性的突变对患者护理和公共卫生控制工作至关重要。先前的指南包括使用氟喹诺酮类药物治疗耐药结核病,包括耐多药结核病、预广泛耐药结核病和广泛耐药结核病。最近,引入了一种治疗抗生素敏感结核病的短期方案,其中包括使用FQ,这是美国的诊断算法通常无法检测是否所有一线药物都敏感的一类药物。然而,FQ单耐药已被先前的研究记录,因此,我们使用Xpert MTB/XDR试验检测了319株存档的结核分枝杆菌复合体(MTBC)菌株,时间跨度为14年。检测到对FQs耐药的菌株占4.4%(14/319),其中gyrA区突变居多(13/14;92.9%)。单个分离株(1/14,7.1%)发现gyrB突变。肉汤微量稀释试验表明,对耐药菌株的最低抑制浓度范围为0.5µg/mL至8.0µg/mL。重要的是,有三种菌株是FQ单抗的,标准检测算法会完全忽略它们。虽然目前在美国还没有,但GeneXpert XDR检测有可能填补MTBC对FQs耐药敏感性测试的重大诊断空白,并支持目前推荐的短期方案的使用。重要意义:本研究揭示了在美国对结核病(TB)病例进行耐药性(特别是氟喹诺酮类药物)检测的额外快速检测的必要性。目前的结核病治疗方案依赖于了解耐药性模式来优化治疗,而错过耐药性可能对患者的健康产生负面影响,并导致新发结核病病例中耐药性突变的增加。在美国,目前用于扩大结核病病例快速耐药检测的平台有限,本研究着眼于常规检测遗漏的过去耐药结核病病例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Diagnostics and new treatment regimens for TB: can the Xpert MTB/XDR assay fill the gap for fluoroquinolone testing?

Rapid diagnosis of resistance-conferring mutations to antibiotics used for the treatment of tuberculosis (TB) is critical for patient care and public health control efforts. Prior guidelines included the use of fluoroquinolones (FQs) for the treatment of drug-resistant TB, including multidrug-resistant TB, pre-extensively drug-resistant TB, and extensively drug-resistant TB. More recently, a short-course regimen for antibiotic-susceptible TB was introduced, which includes the use of a FQ, a drug class that diagnostic algorithms in the United States (US) typically do not test for if all first-line agents are susceptible. However, FQ mono-resistance has been documented by previous studies, and for this reason, we tested 319 archived Mycobacterium tuberculosis complex (MTBC) strains spanning a 14-year period of time using the Xpert MTB/XDR assay. Resistance to FQs was detected in 4.4% (14/319) of the isolates tested, with mutations predominating in the gyrA region (13/14; 92.9%). A single isolate (1/14; 7.1%) was found to have a gyrB mutation. A broth microdilution assay demonstrated the minimum inhibitory concentrations for resistant strains that ranged from 0.5 µg/mL to 8.0 µg/mL. Importantly, three strains were FQ mono-resistant and would have been completely missed by standard testing algorithms. Although currently unavailable in the US, the GeneXpert XDR assay has the potential to fill the significant diagnostic gap in susceptibility testing of MTBC resistance to FQs and support the use of the currently recommended short-course regimen.IMPORTANCE This study provides insight into the need for additional rapid testing for the detection of drug resistance (specifically to fluoroquinolones) in tuberculosis (TB) cases in the United States (US). The current regimens for TB treatment rely on knowing resistance patterns to optimize treatment, and missed resistance could have a negative impact on the health of the patient, as well as contribute to increased drug-resistance mutations in new TB cases. There are currently limited platforms for expanded rapid drug resistance testing for TB cases in the US, and this study looks at past TB cases that had drug resistance missed by routine testing.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Clinical Microbiology
Journal of Clinical Microbiology 医学-微生物学
CiteScore
17.10
自引率
4.30%
发文量
347
审稿时长
3 months
期刊介绍: The Journal of Clinical Microbiology® disseminates the latest research concerning the laboratory diagnosis of human and animal infections, along with the laboratory's role in epidemiology and the management of infectious diseases.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信