FLUCONAZOLE RESISTANCE IN OROPHARYNGEAL CANDIDIASIS

口咽念珠菌病对氟康唑的耐药性

• 批准号: 2132670
• 负责人: THOMAS F. PATTERSON
• 金额: $ 23.61万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2132670
• 关键词: HIV infections; antifungal agents; candidiasis; dosage; drug resistance; epidemiology; fluconazole; genetic strain; human subject; laboratory mouse; oral pharyngeal disorder

Fluconazole is very effective in the treatment of oral thrush, but an increasing number of patients with recurrent oropharyngeal candidiasis have developed fluconazole-resistant yeasts following repeated courses of fluconazole therapy. Fluconazole resistance can develop in a single persistent strain of yeast, but more commonly fluconazole resistance results from emergence of a different Candida albicans strain or another Candida species. Higher doses of fluconazole are more effective against resistant strains in murine candidiasis, but the utility of identifying resistant isolates and treating resistant yeasts with high doses of fluconazole is not established. Thus, the objectives of this proposal are to define prospectively the epidemiology of fluconazole-resistant oropharyngeal candidiasis, to correlate therapeutic response with fluconazole resistance, and to evaluate the role of higher doses of fluconazole in treating resistant yeasts. These objectives will be achieved by longitudinally evaluating patients with HIV infection/AIDS treated with fluconazole for recurrent oropharyngeal candidiasis. The goal of these studies is to improve the treatment of oropharyngeal candidiasis in patients with HIV infection/AIDS. The specific aims of this proposal are: 1) To longitudinally evaluate a cohort of patients with recurrent oropharyngeal candidiasis for the development of fluconazole resistance and to correlate that resistance with clinical response to therapy; 2) To establish strain identity using molecular characterization of the yeasts in order to establish the epidemiology of fluconazole- resistant oropharyngeal candidiasis; 3) To correlate antifungal susceptibility testing with clinical outcome and to determine the utility of screening susceptibility techniques to detect fluconazole resistant yeasts; 4) To evaluate high doses of fluconazole against resistant yeasts in a murine model of candidiasis; 5) To determine the clinical utility of high doses of fluconazole in treating patients with fluconazole-resistant yeasts.

氟康唑在治疗口腔鹅口疮方面非常有效，但 复发性口咽念珠菌病的患者数量增加 经过重复的课程，已经开发了抗氟康唑的酵母 氟康唑疗法。 氟康唑的抗性可以在一个单一的 酵母的持续菌株，但更常见的是氟康唑的耐药性 来自不同念珠菌菌株或另一种念珠菌的出现的结果 念珠菌。更高剂量的氟康唑更有效地抵抗 鼠类念珠菌病中的抗菌株，但识别的实用性 抗性分离株和高剂量的抗性酵母 氟康唑尚未确定。 因此，该提议的目标是 前瞻性定义抗氟康唑的流行病学 口咽念珠菌病，以将治疗反应与 氟康唑耐药性，并评估较高剂量的作用 氟康唑在治疗抗性酵母中。 这些目标将是 通过纵向评估HIV感染/艾滋病患者的实现 用氟康唑治疗复发性口咽念珠菌病。 这 这些研究的目标是改善口咽的治疗 HIV感染/艾滋病患者的念珠菌病。 具体目的 该建议是：1）纵向评估一群患者 复发性口咽念珠菌病以开发氟康唑 阻力并将其与临床反应相关联 治疗; 2）使用分子表征建立应变身份 为了建立氟康唑的流行病学 - 抗性口咽念珠菌病； 3）关联抗真菌 通过临床结果进行敏感性测试并确定效用 筛选易感技术以检测抗氟康唑的耐药性 酵母； 4）评估对抗性酵母的高剂量氟康唑 在念珠菌病的鼠模型中； 5）确定 高剂量的氟康唑在治疗抗氟康唑的患者中 酵母。