FLUCONAZOLE RESISTANCE IN OROPHARYNGEAL CANDIDIASIS

口咽念珠菌病对氟康唑的耐药性

• 批准号: 6080503
• 负责人: THOMAS F. PATTERSON
• 金额: $ 25.18万
• 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 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6080503
• 关键词: Candida albicans; HIV infections; antifungal agents; autoradiography; candidiasis; clinical research; clinical trials; dosage; drug resistance; drug screening /evaluation; epidemiology; fluconazole; genetic strain; human subject; human therapy evaluation; longitudinal human study; medical complication; northern blottings; nucleic acid sequence; oral pharyngeal disorder; outcomes research; patient care management; relapse /recurrence

DESCRIPTION: (Adapted from Applicant's Abstract) Fluconazole resistance has become an important problem in the management of HIV-infected patients with recurrent oropharyngeal candidiasis (OPC). Fluconazole resistance can develop in a persistent strain or from emergence of a new resistant strain. Cross-resistance to other antifungals is common. Molecular mechanisms of fluconazole resistance include alterations in the target enzyme, increased efflux of drug mediated by two types of multidrug pumps, and changes in plasma membrane sterols. The prevalance of these mechanisms and the correlation between mechanisms of resistance and antifungal management strategies has not been determined. The use of highly active retroviral therapy has reduced the incidence of oropharyngeal candidiasis in some patients, but the impact of antiretroviral therapy on recurrence of infection and specific mechanisms of resistance is not known. Thus, the objectives of this proposal are to investigate the molecular epidemiology of antifungal resistance in oropharyngeal candidiasis and to correlate efficacy of antifungal therapy with mechanisms of resistance. These objectives will be achieved through the unique opportunity to analyze mechanisms of resistance in a collection of over 4,500 yeast isolates collected prospectively from over 291 episodes of thrush in 64 patients serially evaluated. The specific aims of this proposal are: 1) to evaluate the impact of highly active antiretroviral therapy on oropharyngeal candidiasis and to determine the efficacy of high dose fluconazole in oropharyngeal candidiasis due to yeasts with decreased susceptibility in order to establish the effect of therapeutic strategies on development of resistance; 2) to determine the epidemiology of molecular mechanisms of resistance in oropharyngeal candidiasis and to assess the correlation between resistance mechanisms and antifungal management strategies and response to treatment; and 3) to characterize molecular resistance mechanisms in selected clinical isolate without known resistance mechanisms, assess the correlation between treatment strategies and resistance mechanisms, and ultimately result in improved management of patients with oropharyngeal candidiasis.

描述：（改编自申请人的摘要）氟康唑耐药性已 成为HIV感染者管理中的一个重要问题 复发性口咽念珠菌病（OPC）。可能会产生氟康唑耐药性 在持续的菌株或新的耐药菌株的出现中。 对其他抗真菌药物的交叉耐药性很常见。分子机制 氟康唑耐药性包括靶酶的改变、增加 由两种类型的多药泵介导的药物流出以及血浆的变化 膜甾醇。这些机制的普遍性和相关性 耐药机制和抗真菌管理策略之间尚未 已确定。高活性逆转录病毒疗法的使用减少了 部分患者口咽部念珠菌病发病率较高，但影响 抗逆转录病毒治疗对感染复发的影响及其具体机制 电阻未知。因此，本提案的目标是 研究抗真菌耐药性的分子流行病学 口咽念珠菌病并将抗真菌治疗的疗效与 抵抗机制。这些目标将通过独特的方式实现 有机会分析 4,500 多个样本中的耐药机制 从 64 年超过 291 次鹅口疮发作中前瞻性收集的酵母分离物 对患者进行连续评估。该提案的具体目标是：1） 评估高效抗逆转录病毒治疗对口咽部的影响 念珠菌病并确定高剂量氟康唑治疗念珠菌病的疗效 口咽念珠菌病是由敏感性降低的酵母菌引起的 确定治疗策略对耐药性发展的影响； 2）确定耐药分子机制的流行病学 口咽部念珠菌病与耐药性之间的相关性评估 机制和抗真菌管理策略以及对治疗的反应；和 3) 表征所选临床分离株的分子耐药机制 在没有已知耐药机制的情况下，评估治疗之间的相关性 策略和抵抗机制，并最终导致改善 口咽念珠菌病患者的管理。