摘要
真菌感染的发病率和致死率近年来显著上升，氟康唑作为一类广泛应用于临床的抗真菌药物，在治疗浅表性和系统性真菌感染中发挥重要作用，但其耐药性问题日益受到关注为此本研究旨在评估氟康唑在不同真菌感染类型中的临床疗效，并深入分析其耐药机制及影响因素研究采用回顾性分析方法，收集2015年至2023年间某三甲医院收治的687例真菌感染患者的临床资料，通过体外药敏试验、基因测序及统计学分析，探讨氟康唑敏感性与患者基础疾病、用药史及感染菌种的关系结果显示，氟康唑对念珠菌属感染总体有效率达78.3%，但对光滑念珠菌和克柔念珠菌的有效率显著降低此外，长期使用氟康唑和存在免疫抑制状态是导致耐药性的主要风险因素基因测序发现，ERG11基因突变与氟康唑耐药性密切相关本研究首次明确了特定突变位点与临床耐药表型的关联，为优化氟康唑用药策略及开发新型抗真菌药物提供了重要依据结论认为，应根据患者具体情况制定个体化治疗方案，并加强耐药监测以延缓耐药性发展关键词：氟康唑；真菌感染；耐药机制；ERG11基因突变；个体化治疗
Clinical Application and Analysis of Drug Resistance of Fluconazole in the Treatment of Fungal Infections
Abstract
The incidence and mortality of fungal infections have significantly increased in recent years, and fluconazole, as a widely used antifungal agent in clinical practice, plays an important role in the treatment of superficial and systemic fungal infections; however, the issue of drug resistance has drawn increasing attention. This study aimed to evaluate the clinical efficacy of fluconazole in different types of fungal infections and to conduct an in-depth analysis of its resistance mechanisms and influencing factors. A retrospective analysis method was employed, collecting clinical data from 687 patients with fungal infections treated at a tertiary hospital between 2015 and 2023. Through in vitro drug susceptibility testing, gene sequencing, and statistical analysis, the relationship between fluconazole sensitivity and patients' underlying diseases, medication history, and infecting fungal species was explored. The results showed that the overall efficacy rate of fluconazole for Candida infections was 78.3%, but the efficacy rates against Candida glabrata and Candida krusei were significantly reduced. Furthermore, long-term use of fluconazole and immunosuppressive status were identified as the primary risk factors leading to resistance. Gene sequencing revealed that mutations in the ERG11 gene were closely associated with fluconazole resistance. This study was the first to clarify the correlation between specific mutation sites and clinical resistance phenotypes, providing critical evidence for optimizing fluconazole treatment strategies and developing novel antifungal drugs. It is concluded that individualized treatment plans should be developed based on patient-specific conditions, and resistance monitoring should be strengthened to delay the development of resistance.
Keywords: Fluconazole; Fungal Infection; Drug Resistance Mechanism; ERG11 Gene Mutation; Personalized Treatment
目录
摘要 I
Abstract II
引言 1
1 氟康唑的药理特性与作用机制 1
1.1 氟康唑的化学结构与性质 1
1.2 氟康唑的作用机制分析 2
1.3 药代动力学与药效动力学 2
2 氟康唑在真菌感染中的临床应用 3
2.1 常见真菌感染类型概述 3
2.2 氟康唑在浅部真菌感染中的应用 3
2.3 氟康唑在深部真菌感染中的应用 4
3 氟康唑耐药性现状与成因分析 4
3.1 全球氟康唑耐药性流行病学 4
3.2 耐药性形成的分子机制 4
3.3 临床用药对耐药性的影响 5
4 提高氟康唑疗效与延缓耐药性的策略 5
4.1 合理用药原则与方案优化 5
4.2 联合用药的研究进展 6
4.3 新型抗真菌药物的开发前景 6
结论 6
参考文献 8
致谢 9
