The potential for development of clinically relevant microbial resistance to rifaximin-α: a narrative review.

IF 19 1区 医学 Q1 MICROBIOLOGY
Clinical Microbiology Reviews Pub Date : 2023-12-20 Epub Date: 2023-11-16 DOI:10.1128/cmr.00039-23
Herbert L DuPont
{"title":"The potential for development of clinically relevant microbial resistance to rifaximin-α: a narrative review.","authors":"Herbert L DuPont","doi":"10.1128/cmr.00039-23","DOIUrl":null,"url":null,"abstract":"<p><p>Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. Its important biologic effects are largely at sub-inhibitory concentration. Although <i>in vitro</i> testing of clinical isolates from rifaximin recipients has revealed rifaximin-resistant strains in some studies, the risk of emergent rifaximin-α resistance appears to be lower than for many other antibiotics. Rifaximin-α has been used for many years for traveler's diarrhea with no apparent increase in resistance levels in causative pathogens. Further, rifaximin-α retains its efficacy after long-term and recurrent usage in chronic gastrointestinal disorders. There are numerous reasons why the risk of microbial resistance to rifaximin-α may be lower than that for other agents, including low intestinal bioavailability in the aqueous colon, the mechanisms of action of rifaximin-α not requiring inhibitory concentrations of drug, and the low risk of cross transmission of rifaximin-α resistance between bacterial species. Reported emergence of vancomycin-resistant <i>Enterococcus</i> in liver-disease patients maintained on rifaximin needs to be actively studied. Further studies are required to assess the possible correlation between <i>in vitro</i> resistance and rifaximin-α efficacy.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0003923"},"PeriodicalIF":19.0000,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732030/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Microbiology Reviews","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1128/cmr.00039-23","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. Its important biologic effects are largely at sub-inhibitory concentration. Although in vitro testing of clinical isolates from rifaximin recipients has revealed rifaximin-resistant strains in some studies, the risk of emergent rifaximin-α resistance appears to be lower than for many other antibiotics. Rifaximin-α has been used for many years for traveler's diarrhea with no apparent increase in resistance levels in causative pathogens. Further, rifaximin-α retains its efficacy after long-term and recurrent usage in chronic gastrointestinal disorders. There are numerous reasons why the risk of microbial resistance to rifaximin-α may be lower than that for other agents, including low intestinal bioavailability in the aqueous colon, the mechanisms of action of rifaximin-α not requiring inhibitory concentrations of drug, and the low risk of cross transmission of rifaximin-α resistance between bacterial species. Reported emergence of vancomycin-resistant Enterococcus in liver-disease patients maintained on rifaximin needs to be actively studied. Further studies are required to assess the possible correlation between in vitro resistance and rifaximin-α efficacy.

利福昔明-α临床相关微生物耐药的发展潜力:叙述性回顾。
利福昔明-α是一种肠道靶向抗生素,适用于多种胃肠道和肝脏疾病。其多方面的作用机制超越了直接的抗菌作用,包括改变细菌毒力,对宿主上皮细胞的细胞保护作用,改善受损的肠通透性,以及通过激活妊娠X受体减少促炎细胞因子的表达。利福昔明-α几乎不被吸收,具有较低的全身药物水平,有助于其良好的安全性。虽然在结肠中存在高浓度的药物,但低水溶性导致结肠药物生物利用度低,从而保护肠道微生物群。利福昔明-α似乎在富含胆汁的小肠中更活跃。其重要的生物效应主要是在亚抑制浓度。尽管对利福昔明接受者的临床分离株进行的体外测试在一些研究中发现了利福昔明耐药菌株,但出现利福昔明-α耐药的风险似乎低于许多其他抗生素。利福昔明-α多年来一直用于旅行者腹泻,在致病病原体的耐药水平没有明显增加。此外,利福昔明-α在长期和反复使用慢性胃肠道疾病后仍保持其疗效。微生物对利福昔明-α的耐药风险可能低于其他药物的耐药风险有很多原因,包括在水结肠中的肠道生物利用度低,利福昔明-α的作用机制不需要药物的抑制浓度,以及利福昔明-α耐药性在细菌物种之间交叉传播的风险低。据报道,在利福昔明维持治疗的肝病患者中出现万古霉素耐药肠球菌需要积极研究。需要进一步的研究来评估体外耐药性与利福昔明-α疗效之间可能的相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Clinical Microbiology Reviews
Clinical Microbiology Reviews 医学-微生物学
CiteScore
54.20
自引率
0.50%
发文量
38
期刊介绍: Clinical Microbiology Reviews (CMR) is a journal that primarily focuses on clinical microbiology and immunology.It aims to provide readers with up-to-date information on the latest developments in these fields.CMR also presents the current state of knowledge in clinical microbiology and immunology.Additionally, the journal offers balanced and thought-provoking perspectives on controversial issues in these areas.
×
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:481959085
Book学术官方微信