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用新型抗真菌药物、策略和制剂满足侵袭性真菌感染预防和治疗的当前医疗需求。

Addressing current medical needs in invasive fungal infection prevention and treatment with new antifungal agents, strategies and formulations.

作者信息

Pitman Stuart K, Drew Richard H, Perfect John R

机构信息

Specialty Resident in Internal Medicine/Infectious Diseases/AcademiaCampbell University College of Pharmacy and Health Sciences, 200 Hawkins Drive, CC 101 GH, Iowa City, IA 52242 , USA +1 319 356 1616 ;

出版信息

Expert Opin Emerg Drugs. 2011 Sep;16(3):559-586. doi: 10.1517/14728214.2011.607811. Epub 2011 Aug 17.

Abstract

Introduction: Morbidity and mortality associated with invasive fungal infections (IFIs) remains unacceptably high. Such diseases represent a substantial burden to the healthcare system. New options are needed to address antifungal resistance in existing and emerging pathogens and improve treatment outcomes while minimizing drug-related toxicities and interactions. Awareness of new and potential future options is of great value for those healthcare professionals who care for patients with IFIs. Areas covered: A search of PubMed, infectious diseases conference abstracts and reference lists from relevant publications was conducted and relevant information abstracted. This review describes the limitations of existing systemic antifungal therapies (e.g., resistance, drug-drug interactions, drug-related toxicities) and summarizes data regarding several emerging antifungal compounds including (but not limited to) new triazoles (e.g. isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin Z. Agents in clinical trials such as (but not limited to) new triazoles (e.g., isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin are included. New formulations of existing drugs including reformulations of miconazole, posaconazole and amphotericin B are also reviewed. Finally, new or novel administration strategies for existing drugs such as combination antifungal therapy, antifungal dose escalation, adjunctive use of iron chelators and preemptive therapy are discussed. Expert opinion: All present antifungal agents have some deficiencies in antifungal spectra, toxicity, pharmacokinetics and/or drug-drug interactions, making them less than ideal for some fungal infections. Therefore, there remains an urgent need to find safe, effective, rapidly fungicidal, broad-spectrum antifungal agents with excellent pharmacodynamics to effectively eliminate the fungus from the body with short antifungal courses.

摘要

引言

侵袭性真菌感染(IFI)相关的发病率和死亡率仍然高得令人难以接受。此类疾病给医疗系统带来了沉重负担。需要新的选择来应对现有和新出现病原体中的抗真菌耐药性,并改善治疗效果,同时将药物相关毒性和相互作用降至最低。对于照顾IFI患者的医疗专业人员而言,了解新的以及未来可能出现的选择具有重要价值。

涵盖领域

检索了PubMed、传染病会议摘要以及相关出版物的参考文献列表,并提取了相关信息。本综述描述了现有全身用抗真菌疗法的局限性(如耐药性、药物相互作用、药物相关毒性),并总结了几种新出现的抗真菌化合物的数据,包括(但不限于)新型三唑类药物(如艾沙康唑、雷夫康唑)、棘白菌素类药物(如氨曲南)和尼可霉素Z。纳入了处于临床试验阶段的药物,如(但不限于)新型三唑类药物(如艾沙康唑、雷夫康唑)、棘白菌素类药物(如氨曲南)和尼可霉素。还综述了现有药物的新剂型,包括咪康唑、泊沙康唑和两性霉素B的重新配方。最后,讨论了现有药物的新的或新颖的给药策略,如联合抗真菌治疗、抗真菌剂量递增、铁螯合剂的辅助使用和抢先治疗。

专家观点

目前所有的抗真菌药物在抗真菌谱、毒性、药代动力学和/或药物相互作用方面都存在一些不足,这使得它们对于某些真菌感染来说并不理想。因此,迫切需要找到安全、有效、快速杀菌、具有优异药效学的广谱抗真菌药物,以便在短疗程内有效清除体内真菌。

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