Editorial: H. pylori Antimicrobial Susceptibility Testing—An Expanding Toolbox

IF 6.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Suvithan Rajadurai, Steven F. Moss
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引用次数: 0

Abstract

Helicobacter pylori (H. pylori) is one of the most common bacterial infections globally and, due to its association with gastric cancer, the leading cause of infection-related malignancy worldwide [1, 2]. Effective eradication of H. pylori has long been challenged by empiric and complicated treatment regimens linked to increasing antimicrobial resistance [3]. Within the UnitedStates, resistance rates to metronidazole, clarithromycin and levofloxacin are 42.1%, 31.5% and 37.6%, respectively [4] leading to a recommendation in the recently published US guidelines against using clarithromycin or levofloxacin unless the strain is known to be sensitive [5].

H. pylori antimicrobial resistance testing is still rarely utilised in routine clinical practice as culture-based testing is slow (often taking one to 2 weeks), often unsuccessful and incontrovertible evidence is still lacking that a ‘tailored’ approach provides superior clinical outcomes over the continuing use of empiric regimens [1]. This is likely to change with the encouragement of more susceptibility testing by national and international authorities [5, 6], and the availability of rapid, sensitive and accurate molecular methods as increasingly used in clinical microbiology practice.

Vasapolli et al. have added to the emerging molecular choices by describing genotypic H. pylori clarithromycin and levofloxacin susceptibility testing by real-time PCR from gastric aspirates harvested at routine upper endoscopy [7]. The results, based on the common gyrase A and 23sRNA mutations that lead to levofloxacin and clarithromycin resistance respectively, [8] were highly concordant with those of conventional phenotypic testing. The rapidity, efficiency and accuracy of this approach could enable endoscopists to both diagnose H. pylori and choose an appropriate regimen based on antimicrobial susceptibility within hours of the procedure.

Gastric aspirate susceptibility testing adds a potential new tool to the growing toolbox of molecular methods, some of which are commercially available. These include biopsy-based PCR, fluorescent in situ hybridisation and next generation sequencing. Stool-based testing (obviating the need for endoscopy) has also been investigated for clarithromycin resistance by PCR as well as for a wider panel of antibiotics by next generation sequencing [9].

Research to this point has demonstrated the feasibility and robustness of these biopsy-dependent or stool-based molecular methods to evaluate H. pylori's susceptibility to clarithromycin and levofloxacin. Resistance to these antibiotics, which is due to a small group of well-defined mutations, is clearly correlated with clinical outcome. Whether molecular testing will be useful for the more complex question of metronidazole resistance remains to be determined [8]. Ultimately, whether H. pylori resistance testing will gain the traction in clinical practice that the experts have deemed to be necessary will depend upon its accuracy, ease of use, cost and demonstration of added value. The gastric aspirate method [7] appears to satisfy the first two of these criteria, thus representing a step towards achieving improved H. pylori eradication rates in routine clinical practice.

Suvithan Rajadurai: writing – original draft. Steven F. Moss: writing – review and editing.

S.F.M.: Consultant Redhill Biopharma, Phathom Pharmaceuticals, Meridian Bioscience and American Molecular Laboratories. S.R.: None.

This article is linked to Vasapolli et al papers. To view these articles, visit https://doi.org/10.1111/apt.18378 and https://doi.org/10.1111/apt.18429.

社论:幽门螺杆菌抗菌药物敏感性检测——一个不断扩大的工具箱
幽门螺杆菌(Helicobacter pylori, H. pylori)是全球最常见的细菌感染之一,由于与胃癌相关,它是全球感染相关恶性肿瘤的主要原因[1,2]。长期以来,有效根除幽门螺杆菌一直受到经验性和复杂的治疗方案的挑战,这些方案与日益增加的抗菌素耐药性有关。在美国,甲硝唑、克拉霉素和左氧氟沙星的耐药率分别为42.1%、31.5%和37.6%,导致美国最近发布的指南中建议,除非已知菌株对克拉霉素或左氧氟沙星敏感,否则不要使用克拉霉素或左氧氟沙星。幽门螺杆菌抗菌素耐药性检测在常规临床实践中仍然很少使用,因为基于培养的检测速度较慢(通常需要1至2周),而且往往不成功,而且仍然缺乏“量身定制”的方法比继续使用经验方案提供更好的临床结果的无可争议的证据[10]。随着国家和国际权威机构鼓励进行更多的药敏试验[5,6],以及快速、敏感和准确的分子方法越来越多地用于临床微生物学实践,这种情况可能会发生变化。Vasapolli等人通过对常规上胃镜采集的胃抽吸物进行实时PCR检测,描述了基因型幽门螺杆菌clarithromycin和左氧氟沙星的敏感性,从而增加了新兴的分子选择。根据常见的gyrase A和23sRNA突变分别导致左氧氟沙星和克拉霉素耐药的结果,[8]与常规表型检测结果高度一致。这种方法的快速、高效和准确使内窥镜医师能够在几个小时内诊断幽门螺旋杆菌并根据抗菌药物敏感性选择合适的治疗方案。胃抽吸药敏试验为不断增长的分子方法工具箱增加了一个潜在的新工具,其中一些已经商业化。其中包括基于活检的PCR,荧光原位杂交和下一代测序。基于粪便的检测(避免内窥镜检查的需要)也已通过聚合酶链反应研究克拉霉素耐药性,并通过下一代测序[9]研究更广泛的抗生素组。到目前为止的研究已经证明了这些依赖于活检或基于粪便的分子方法来评估幽门螺杆菌对克拉霉素和左氧氟沙星的敏感性的可行性和稳健性。对这些抗生素的耐药性是由一小群明确定义的突变引起的,与临床结果明显相关。分子检测是否对甲硝唑耐药性这一更为复杂的问题有用还有待确定。最终,幽门螺杆菌耐药检测是否会在临床实践中获得专家认为必要的牵引力,将取决于其准确性、易用性、成本和附加价值的证明。胃抽吸法[7]似乎满足前两个标准,因此代表着在常规临床实践中实现提高幽门螺杆菌根除率的一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
15.60
自引率
7.90%
发文量
527
审稿时长
3-6 weeks
期刊介绍: Alimentary Pharmacology & Therapeutics is a global pharmacology journal focused on the impact of drugs on the human gastrointestinal and hepato-biliary systems. It covers a diverse range of topics, often with immediate clinical relevance to its readership.
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