Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Parasitology. 2020 Nov;147(13):1383-1391. doi: 10.1017/S0031182020001237. Epub 2020 Jul 30.
Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-Nitroimidazoles [metronidazole (MTZ) and tinidazole (TDZ)] are FDA-approved treatments. To better understand treatment failure, we conducted a systematic review on mechanisms of 5-nitroimidazole resistance.
PubMed, ScienceDirect and EMBASE databases were searched using keywords Trichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded.
The search yielded 606 articles, of which 550 were excluded, leaving 58 articles. Trichomonas vaginalis resistance varies and is higher with MTZ (2.2-9.6%) than TDZ (0-2%). Resistance can be aerobic or anaerobic and is relative rather than absolute. Differential expression of enzymes involved in trichomonad energy production and antioxidant defenses affects 5-nitroimidazole drug activation; reduced expression of pyruvate:ferredoxin oxidoreductase, ferredoxin, nitroreductase, hydrogenase, thioredoxin reductase and flavin reductase are implicated in drug resistance. Trichomonas vaginalis infection with Mycoplasma hominis or T. vaginalis virus has also been associated with resistance. Trichomonas vaginalis has two genotypes, with greater resistance seen in type 2 (vs type 1) populations.
5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the T. vaginalis genome. Alternative treatments outside of the 5-nitroimidazole class are needed.
阴道毛滴虫是最常见的非病毒性性传播感染。5-硝基咪唑类药物（甲硝唑[MTZ]和替硝唑[TDZ]）是 FDA 批准的治疗药物。为了更好地了解治疗失败的原因，我们对 5-硝基咪唑类药物耐药的机制进行了系统评价。
使用关键词阴道毛滴虫、滴虫病、5-硝基咪唑、甲硝唑、替硝唑和耐药性，在 PubMed、ScienceDirect 和 EMBASE 数据库中进行搜索。排除非英语语言的文章和其他治疗方法的文章。
搜索结果产生了 606 篇文章，其中 550 篇被排除，留下 58 篇文章。阴道毛滴虫的耐药性存在差异，甲硝唑（2.2-9.6%）的耐药性高于替硝唑（0-2%）。耐药性可以是需氧的也可以是厌氧的，是相对的而不是绝对的。参与滴虫能量产生和抗氧化防御的酶的差异表达会影响 5-硝基咪唑类药物的激活；丙酮酸：铁氧还蛋白氧化还原酶、铁氧还蛋白、硝基还原酶、氢化酶、硫氧还蛋白还原酶和黄素还原酶的表达减少与耐药性有关。阴道毛滴虫感染人支原体或阴道毛滴虫病毒也与耐药性有关。阴道毛滴虫有两种基因型，2 型（与 1 型相比）的耐药性更高。
5-硝基咪唑类耐药是由于参与能量产生或抗氧化防御的酶的差异表达，以及阴道毛滴虫基因组中的基因突变所致。需要寻找 5-硝基咪唑类药物以外的替代治疗方法。
