Detection and Significance of Antifungal Resistance in Oropharyngeal Candidiasis

口咽部念珠菌病抗真菌耐药性的检测及意义

• 批准号: 7609197
• 负责人: THOMAS F. PATTERSON
• 金额: $ 49.2万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609197
• 关键词: ABCB1 gene; AIDS/HIV problem; Affect; Antifungal Agents; Antifungal Therapy; Azole resistance; Azoles; Biological Assay; CD4 Positive T Lymphocytes; Candida; Candida albicans; Candida glabrata; Candidiasis; Clinical; Complication; Culture Techniques; Dental Epidemiology; Detection; Disease; Drug Efflux; Enzymes; Epidemiology; Exhibits; Fungal Drug Resistance; Gene Expression; HIV; Infection; Methods; Molecular; Molecular Diagnostic Techniques; Oral; Oral candidiasis; Organism; Oropharyngeal; Patients; Point Mutation; Population; Prevalence; Public Health; Recurrence; Research; Research Personnel; Resistance; Risk; Risk Factors; Sampling; Systemic infection; Techniques; Testing; Time; Yeasts; base; cohort; echinocandin resistance; effective therapy; efflux pump; high risk; improved; in vivo; novel diagnostics; oropharyngeal thrush; overexpression; pathogen; programs; rapid detection; resistance mechanism

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.

抗真菌抗性仍然是HIV感染的管理的重要临床问题 复发性口咽念珠菌病的患者。白色念珠菌是最常见的病原体 与有症状的疾病相关，但其他念珠菌（例如Glabrata）也会引起 感染。这些酵母很重要，因为它们经常表现出抗真菌抗性。 在接受频繁的HIV感染患者中特别注意抗真菌抗药性 课程或长期治疗。取唑的分子机制包括改变 靶酶和多药于外排泵的表达增加。抗性快速检测 酵母菌可以迅速开始有效治疗。另外，因为与 耐药性酵母是发展易感宿主的全身感染的重要危险因素， 对耐药生物的快速测试可能会影响这些患者的经验抗真菌治疗。因此， 该提案的目标是开发新颖的诊断平台以迅速检测到抗性 体内酵母菌，并将检测与症状感染和复发相关 口咽念珠菌病。这些目标将通过前瞻性评估艾滋病毒来实现 感染的患者出现口咽感染，包括抗真菌患者 反抗。该提案的具体目的是：i）串行评估艾滋病毒感染的队列 为了确定实时分子检测的流行病学和意义 抗性口服酵母； ii）开发分子诊断方法来鉴定其他 比白色念珠菌，包括glabrata，并将检测与发色素相关 文化技术； iii）开发用于检测体内分子的分子测定 电阻机制，包括药物外泵的表达。这些研究将增加 了解抗性机制的流行病学，确定体内的影响 在复发时检测耐药性酵母，并最终改善患者的管理 口咽念珠菌病以及有侵入性念珠菌病风险的念珠菌病。 与公共卫生有关：口服酵母菌感染（鹅口疮）是患者的重要复杂性 与艾滋病毒/艾滋病。这项研究旨在开发快速分子测试以检测酵母菌 对抗真菌剂具有抗性，以便尽早使用更有效的治疗。