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5-硝基咪唑类药物对阴道毛滴虫临床分离株的作用。

Effect of 5-Nitroimidazole Drugs against Trichomonas vaginalis Clinical Isolates.

机构信息

School of Laboratory Medicine and Medical Science, Department of Medical Microbiology, University of KwaZulu-Natalgrid.16463.36, KwaZulu-Natal, South Africa.

Centre for the AIDS Programme of Research in South Africagrid.428428.0, Durban, South Africa.

出版信息

Microbiol Spectr. 2022 Aug 31;10(4):e0091222. doi: 10.1128/spectrum.00912-22. Epub 2022 Jul 13.

DOI:10.1128/spectrum.00912-22
PMID:35863010
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9430554/
Abstract

Infections with the sexually transmitted parasite Trichomonas vaginalis are normally treated with metronidazole, but cure rates are suboptimal and recurrence rates following treatment are high. Therefore, our objective was to assess the antitrichomonas activities of three other 5-nitroimidazole drugs and compare them with metronidazole. T. vaginalis isolates ( = 94) isolated from South African women presenting with vaginal discharge syndrome at two sexually transmitted disease clinics in KwaZulu-Natal were grown from frozen stock. Twofold serial dilutions (16 to 0.25 mg/L) of metronidazole, tinidazole, ornidazole, and secnidazole were prepared in Diamond's broth. The MICs were read after 48 h of anaerobic incubation at 37°C. An MIC of <2 mg/L was defined as susceptible, an MIC of 2 mg/L was defined as intermediate, and an MIC of >2 mg/L was defined as resistant. Sixty-one percent (57/94) of the T. vaginalis isolates were susceptible to metronidazole, 80% (75/94) were susceptible to tinidazole, 75% (71/94) were susceptible to secnidazole, and 89% (84/94) were susceptible to ornidazole. Resistance levels were 11%, 2%, and 1% for metronidazole, tinidazole, and secnidazole, respectively, while no resistance was observed for ornidazole. Intermediate scores were 28% for metronidazole, 18% for tinidazole, 24% for secnidazole, and 11% for ornidazole. Isolates from a proportion of women with bacterial vaginosis (BV) had higher MICs, and no isolates from women coinfected with another sexually transmitted infectious organism were resistant to any of the antimicrobials tested. This study showed that among T. vaginalis isolates in KwaZulu-Natal, there is no resistance to ornidazole. Of the 5-nitroimidazoles, metronidazole showed the highest level of resistance. The very low levels of resistance for the other three antimicrobials indicate that all three are viable options as a replacement for metronidazole if these findings are found to correlate with clinical outcomes. Trichomonas vaginalis is the most common nonviral sexually transmitted infection associated with reproductive sequelae and HIV acquisition risk worldwide. Despite its role in reproductive health, a high prevalence in South Africa, and the reported metronidazole resistance worldwide, no alternative regimens have been tested against T. vaginalis in our setting. This study compared the susceptibility patterns of three other 5-nitroiminazoles (secnidazole, tinidazole, and ornidazole), which are active against T. vaginalis with metronidazole . Metronidazole, the drug of choice for the treatment of trichomoniasis, showed the highest level of resistance, while the three regimens showed very low levels of resistance. These data indicate that all three are viable options as a replacement for metronidazole if these findings are found to correlate with clinical outcomes.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f3/9430554/6ad552311ddd/spectrum.00912-22-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f3/9430554/ffe93ce5f559/spectrum.00912-22-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f3/9430554/4213742928ed/spectrum.00912-22-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f3/9430554/6ad552311ddd/spectrum.00912-22-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f3/9430554/ffe93ce5f559/spectrum.00912-22-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f3/9430554/4213742928ed/spectrum.00912-22-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f3/9430554/6ad552311ddd/spectrum.00912-22-f003.jpg
摘要

阴道毛滴虫感染通常用甲硝唑治疗,但治愈率不理想,治疗后复发率很高。因此,我们的目的是评估另外三种 5-硝基咪唑类药物的抗滴虫活性,并将其与甲硝唑进行比较。从南非妇女阴道分泌物综合征患者中分离出的阴道毛滴虫( = 94)在夸祖鲁-纳塔尔省两个性传播疾病诊所从冷冻库存中生长。在 Diamond's 肉汤中制备了甲硝唑、替硝唑、奥硝唑和司帕沙星的两倍系列稀释液(16 至 0.25 mg/L)。在 37°C 厌氧孵育 48 小时后读取 MIC。MIC<2 mg/L 定义为敏感,MIC 为 2 mg/L 定义为中介,MIC>2 mg/L 定义为耐药。61%(57/94)的阴道毛滴虫分离株对甲硝唑敏感,80%(75/94)对替硝唑敏感,75%(71/94)对司帕沙星敏感,89%(84/94)对奥硝唑敏感。甲硝唑、替硝唑和司帕沙星的耐药水平分别为 11%、2%和 1%,而奥硝唑无耐药性。甲硝唑、替硝唑和司帕沙星的中介评分分别为 28%、18%、24%和 11%。一些细菌性阴道病(BV)患者的分离株 MIC 较高,没有从同时感染另一种性传播感染病原体的患者中分离出对任何测试抗菌药物耐药的分离株。这项研究表明,在夸祖鲁-纳塔尔省的阴道毛滴虫分离株中,没有对奥硝唑的耐药性。在 5-硝基咪唑类药物中,甲硝唑的耐药性最高。其他三种抗菌药物的耐药水平非常低,这表明如果这些发现与临床结果相关,这三种药物都是甲硝唑的可行替代品。阴道毛滴虫是全球最常见的非病毒性性传播感染,与生殖后遗症和 HIV 感染风险有关。尽管它在生殖健康方面发挥了作用,在南非的流行率很高,并且全球报告了甲硝唑耐药性,但在我们的环境中尚未针对阴道毛滴虫测试替代方案。这项研究比较了三种其他 5-硝基咪唑类药物(司帕沙星、替硝唑和奥硝唑)的敏感性模式,这些药物对阴道毛滴虫有效,而甲硝唑是治疗滴虫病的首选药物。甲硝唑显示出最高水平的耐药性,而这三种方案显示出非常低水平的耐药性。这些数据表明,如果这些发现与临床结果相关,那么这三种药物都是甲硝唑的可行替代品。

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