FLUCONAZOLE RESISTANCE IN OROPHARYNGEAL CANDIDIASIS

氟康唑治疗口腔鹅口疮非常有效，但 复发性口咽部念珠菌病患者数量增加 在经过反复的疗程后开发出了耐氟康唑的酵母菌 氟康唑治疗。对氟康唑的耐药性可以在单个 酵母菌的持久性菌株，但更常见的是对氟康唑的耐药性 由不同的白色念珠菌菌株或其他菌株出现的结果 假丝酵母菌。高剂量的氟康唑更有效地对抗 小鼠念珠菌病的耐药菌株，但识别 耐药菌株和高剂量处理耐药酵母 氟康唑尚未成立。因此，这项提案的目标是 前瞻性地确定氟康唑耐药的流行病学 口咽念珠菌病与治疗反应的相关性 对氟康唑的耐药性，并评估更高剂量的作用 氟康唑在治疗耐药酵母中的应用。这些目标将是 通过对艾滋病毒感染/艾滋病患者进行纵向评估实现 氟康唑治疗复发性口咽念珠菌病。这个 这些研究的目的是改善口咽癌的治疗 艾滋病毒感染/艾滋病患者中的念珠菌病。的具体目标 这项建议是：1)纵向评估一组患有 复发性口咽念珠菌病与氟康唑的关系 并将这种耐药性与临床反应相关联。 治疗；2)通过分子鉴定建立菌株鉴定 为了建立氟康唑的流行病学- 耐药口咽部念珠菌病；3)相关抗真菌 药敏试验与临床结果的关系及确定其效用 检测氟康唑耐药性的药敏筛选技术 4)评价大剂量氟康唑对耐药酵母菌的抗药性 在念珠菌病的小鼠模型中；5)确定该药的临床实用性 大剂量氟康唑治疗氟康唑耐药患者 酵母菌。

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.