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: 7932552
• 负责人: THOMAS F. PATTERSON
• 金额: $ 6.6万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932552
• 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.

抗真菌耐药性仍然是艾滋病毒感染者管理中的一个重要临床问题 复发性口咽念珠菌病患者。白色念珠菌是最常见的病原体 与症状性疾病相关，但其他念珠菌属物种，例如光滑念珠菌，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耐药性。 在经常接受抗真菌药物治疗的 HIV 感染患者中，抗真菌耐药性尤其明显。 疗程或延长治疗。唑类耐药的分子机制包括 靶酶和增加多药外排泵的表达。快速检测耐药菌 酵母菌可以迅速启动有效的治疗。此外，由于殖民 耐药酵母菌是易感宿主发生全身感染的重要危险因素， 快速检测耐药微生物可能会影响这些患者的经验性抗真菌治疗。因此， 该提案的目标是开发新型诊断平台以快速检测耐药性 体内酵母菌并将该检测与症状感染和复发相关联 口咽念珠菌病。这些目标将通过前瞻性评估艾滋病毒- 出现口咽感染的感染患者，包括使用抗真菌药物的患者 反抗。该提案的具体目标是： i) 连续评估一组 HIV 感染者 患者以确定流行病学和实时分子检测的意义 耐药口腔酵母菌； ii) 开发分子诊断方法来鉴定其他酵母种类 比白色念珠菌，包括光滑念珠菌，并将该检测与显色相关联 培养技术； iii) 开发用于检测体内分子的分子测定法 耐药机制，包括药物流出泵的表达。这些研究将会增加 了解耐药机制的流行病学，确定体内的影响 检测复发时的耐药酵母菌，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群。 与公共卫生的相关性：口腔酵母菌感染（鹅口疮）是患者的重要并发症 患有艾滋病毒/艾滋病。这项研究旨在开发快速分子测试来检测酵母 对抗真菌药物具有抗药性，以便尽早使用更有效的治疗方法。