Detection and Significance of Antifungal Resistance in Oropharyngeal Candidiasis

抗真菌耐药性仍然是艾滋病毒感染管理中的一个重要临床问题 复发性口咽部念珠菌病患者。白色念珠菌是最常见的病原体 与有症状的疾病有关，但其他念珠菌物种，如光滑念珠菌也会引起 感染。这些酵母菌很重要，因为它们经常表现出抗真菌的耐药性。 抗真菌耐药性在经常接受抗真菌药物治疗的艾滋病毒感染者中尤为明显。 课程或长期治疗。唑类耐药的分子机制包括 靶向酶和多药外排泵的表达增加。抗药性的快速检测 酵母菌可以迅速启动有效的治疗。此外，因为殖民与 耐药酵母菌是易感宿主发生系统性感染的重要危险因素 对耐药微生物的快速检测可能会影响这些患者的经验性抗真菌治疗。因此， 这项提议的目标是开发新的诊断平台来快速检测耐药性 活体内的酵母菌，并将这种检测与有症状的感染和复发相关联 口咽部念珠菌病。这些目标将通过前瞻性评估艾滋病毒- 出现口咽部感染的感染患者，包括接受抗真菌治疗的患者 抵抗。这项建议的具体目标是：i)对一组艾滋病毒感染者进行连续评估 为了确定患者的流行病学和实时分子检测的意义 耐药口服酵母菌；ii)开发分子诊断方法以鉴定其他酵母种类 白念珠菌，包括光滑念珠菌，并将这种检测与显色相关 培养技术；以及iii)开发检测体内分子的分子检测方法 耐药机制包括药物外排泵的表达。这些研究将会增加 了解流行病学耐药机制，确定体内影响 检测耐药酵母菌对复发的影响，最终改善患者的管理 口咽念珠菌病以及有侵袭性念珠菌病风险的人。 与公共健康相关：口腔酵母菌感染(鹅口疮)是患者的重要并发症 感染艾滋病毒/艾滋病。这项研究的目的是开发快速分子测试来检测酵母 对抗真菌药物有抗药性，以便及早使用更有效的治疗方法。

Antifungal resistance remains an important clinical problem in the management of HIV-infected patients with recurrent oropharyngeal candidiasis. Candida albicans is the most frequent pathogen associated with symptomatic disease but other Candida species, such as C. glabrata, also cause infection. These yeasts are important because they frequently exhibit antifungal resistance. Antifungal resistance has been particularly noted in HIV-infected patients who receive frequent courses or prolonged therapy. Molecular mechanisms of azole resistance include alterations in the target enzyme and increased expression of multidrug efflux pumps. Rapid detection of resistant yeasts could allow prompt initiation of effective therapy. In addition, because colonization with resistant yeasts is an important risk factor in developing systemic infection in susceptible hosts, a rapid test for resistant organisms could impact empirical antifungal therapy in those patients. Thus, the objectives of this proposal are to develop novel diagnostic platforms to rapidly detect resistant yeasts in vivo and to correlate that detection with symptomatic infection and recurrence of oropharyngeal candidiasis. These objectives will be achieved through prospectively evaluating HIV- infected patients presenting with oropharyngeal infection including patients with antifungal resistance. The specific aims of this proposal are: i) to serially evaluate a cohort of HIV-infected patients in order to determine the epidemiology and significance of real-time molecular detection of resistant oral yeasts; ii) to develop molecular diagnostic methods to identify species of yeasts other than Candida albicans, including C. glabrata and to correlate that detection with chromogenic culture techniques; and iii) to develop molecular assays for detecting in vivo molecular mechanisms of resistance including expression of drug efflux pumps. These studies will increase understanding of the epidemiology of resistance mechanisms, determine the impact of in vivo detection of resistant yeasts on recurrence, and ultimately improve management of patients with oropharyngeal candidiasis as well as those at risk for invasive candidiasis. Relevance to public health: Oral yeast infection (thrush) is an important complication in patients with HIV/AIDS. This research is aimed at developing rapid molecular tests to detect yeasts which are resistant to antifungal agents in order to allow early use of more effective therapy.