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硝唑尼特和替唑尼特对甲硝唑敏感及耐药的临床分离株均表现出高活性。

Nitazoxanide and tizoxanide demonstrate high levels of activity against metronidazole-susceptible and metronidazole-resistant clinical isolates.

作者信息

Graves Keonte J, Williamson John C, Novak Jan, Tiwari Hemant K, Secor W Evan, Muzny Christina A

机构信息

Division of Infectious Diseases, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.

Department of Internal Medicine, Section on Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

出版信息

Microbiol Spectr. 2025 Jul;13(7):e0271724. doi: 10.1128/spectrum.02717-24. Epub 2025 May 22.

DOI:10.1128/spectrum.02717-24
PMID:40401974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12210956/
Abstract

UNLABELLED

is the most common non-viral sexually transmitted infection worldwide. We compared the activity of the thiazolide nitazoxanide (NTZ) and its metabolite, tizoxanide (TIZ), with the activity of the Food and Drug Administration-approved 5-nitroimidazoles (metronidazole [MTZ], tinidazole [TDZ], and secnidazole [SEC]) against MTZ-susceptible and MTZ-resistant clinical isolates. Frozen, stored clinical isolates ( = 36) were cultured in Diamond's trypticase-yeast-maltose media supplemented with heat-inactivated horse serum and an antibiotic cocktail. Drug-susceptibility assays for the thiazolides (NTZ and TIZ) and the 5-nitroimidazoles (MTZ, TDZ, and SEC) were performed to determine the minimum lethal concentrations (MLCs) for each isolate and the median MLC for each drug. Of the 36 isolates cultured, 18 were MTZ resistant and 18 were MTZ susceptible. For the 18 MTZ-resistant strains, the median MLCs for MTZ, TDZ, and SEC were 100, 25, and 50 µg/mL, respectively. By contrast, the median MLCs for NTZ and TIZ were considerably lower at 1.6 and 0.8 µg/mL, respectively. The similarity in thiazolide MLCs in all strains, regardless of sensitivity to MTZ, suggests that NTZ and TIZ act via a different mechanism than the 5-nitroimidazoles. Future investigations will focus on the activity of NTZ and TIZ as well as the efficacy of thiazolides used as monotherapy or as combination therapy, particularly in -infected patients who do not respond to 5-nitroimidazole treatment.

IMPORTANCE

Investigating drug resistance and alternative treatment options for is crucial due to the increasing prevalence of persistent infections and the potential failure of standard therapies (i.e., 5-nitroimidazoles). Trichomoniasis can lead to significant health complications, including increased susceptibility to sexually transmitted infections and adverse pregnancy outcomes. The rise of 5-nitroimidazole drug-resistant strains poses a challenge to effective treatment, necessitating ongoing research to understand the mechanisms behind this resistance. Exploring alternative treatments, such as novel pharmacological agents like nitazoxanide and tizoxanide, could provide more effective options for managing these persistent infections. Additionally, comprehensive investigations can help inform public health strategies and reduce transmission rates. Ultimately, prioritizing research in this area is essential for improving patient outcomes and safeguarding reproductive health.

摘要

未标注

滴虫病是全球最常见的非病毒性性传播感染。我们比较了噻唑类药物硝唑尼特(NTZ)及其代谢产物替唑尼特(TIZ)的活性,以及美国食品药品监督管理局批准的5-硝基咪唑类药物(甲硝唑[MTZ]、替硝唑[TDZ]和塞克硝唑[SEC])对MTZ敏感和MTZ耐药临床分离株的活性。将冷冻保存的临床分离株(n = 36)在补充有热灭活马血清和抗生素混合物的戴蒙德胰蛋白酶酵母麦芽糖培养基中培养。对噻唑类药物(NTZ和TIZ)和5-硝基咪唑类药物(MTZ, TDZ和SEC)进行药敏试验,以确定每种分离株的最低致死浓度(MLC)和每种药物的MLC中位数。在培养的36株分离株中,18株对MTZ耐药,18株对MTZ敏感。对于18株MTZ耐药菌株,MTZ、TDZ和SEC的MLC中位数分别为100、25和50 μg/mL。相比之下,NTZ和TIZ的MLC中位数则低得多,分别为1.6和0.8 μg/mL。无论对MTZ的敏感性如何,所有菌株中噻唑类药物MLC的相似性表明,NTZ和TIZ的作用机制与5-硝基咪唑类药物不同。未来的研究将集中在NTZ和TIZ的活性以及噻唑类药物作为单一疗法或联合疗法的疗效上,特别是在对5-硝基咪唑治疗无反应的滴虫感染患者中。

重要性

由于持续性感染的患病率不断上升以及标准疗法(即5-硝基咪唑类药物)可能失效,研究滴虫病的耐药性和替代治疗方案至关重要。滴虫病可导致严重的健康并发症,包括增加对性传播感染的易感性和不良妊娠结局。5-硝基咪唑耐药菌株的出现对有效治疗构成挑战,需要持续研究以了解这种耐药性背后的机制。探索替代治疗方法,如硝唑尼特和替唑尼特等新型药物制剂,可为管理这些持续性感染提供更有效的选择。此外,全面的研究有助于为公共卫生策略提供信息并降低传播率。最终,优先开展该领域的研究对于改善患者预后和保护生殖健康至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d52/12210956/eb80b3b9528d/spectrum.02717-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d52/12210956/eb80b3b9528d/spectrum.02717-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d52/12210956/eb80b3b9528d/spectrum.02717-24.f001.jpg

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Amixicile: A Concept Therapeutic for Treatment of Chronic Anaerobic Infections.阿米西icile:一种用于治疗慢性厌氧菌感染的概念性疗法。
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