FLUCONAZOLE RESISTANCE IN OROPHARYNGEAL CANDIDIASIS

口咽念珠菌病对氟康唑的耐药性

• 批准号: 2132672
• 负责人: THOMAS F. PATTERSON
• 金额: $ 23.31万
• 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 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2132672
• 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.

氟康唑治疗鹅口疮非常有效，但 复发性口咽念珠菌病患者数量不断增加 经过反复治疗后，已经产生了对氟康唑耐药的酵母菌 氟康唑治疗。 氟康唑耐药性可在一次内形成 酵母菌的持久菌株，但更常见的是氟康唑耐药性 不同白色念珠菌菌株或其他菌株出现的结果 念珠菌属。较高剂量的氟康唑更有效 鼠念珠菌病中存在耐药菌株，但鉴定的效用 抗性分离株和用高剂量处理抗性酵母 氟康唑尚未建立。 因此，本提案的目标是 前瞻性地定义氟康唑耐药的流行病学 口咽念珠菌病，将治疗反应与 氟康唑耐药性，并评估较高剂量的作用 氟康唑治疗耐药酵母菌。 这些目标将是 通过纵向评估 HIV 感染/艾滋病患者来实现 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部疾病的治疗 HIV 感染/艾滋病患者的念珠菌病。 具体目标 该建议是： 1）纵向评估一组患者 氟康唑开发用于复发性口咽念珠菌病 耐药性并将该耐药性与临床反应相关联 治疗; 2) 使用分子表征确定菌株身份 酵母菌以建立氟康唑的流行病学- 耐药口咽念珠菌病； 3) 关联抗真菌药物 根据临床结果进行药敏试验并确定其效用 检测氟康唑耐药的药敏技术的应用 酵母； 4) 评估高剂量氟康唑对耐药酵母的作用 在念珠菌病小鼠模型中； 5) 确定临床效用 大剂量氟康唑治疗氟康唑耐药患者 酵母。