Hossain M A, Ghannoum M A
Center for Medical Mycology, Department of Dermatology, Case Western Reserve University and University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio, OH 44106-5028, USA.
Expert Opin Investig Drugs. 2000 Aug;9(8):1797-813. doi: 10.1517/13543784.9.8.1797.
Systemic fungal infections have been recognised as a major cause of morbidity and mortality during the last two decades. There are only a few therapeutic options for these infections. Severe toxicity, such as impairment of renal function, limits the use of amphotericin B. Flucytosine is associated with side effects and drug resistance. Fluconazole and itraconazole are safer, though emergence of resistance and innate resistance in some fungal pathogens is a concern in their use. Therefore, there is a need for developing novel drugs and/or treatment strategies to combat these infections. In recent years, increased efforts by the pharmaceutical industry and academia have led to the discovery of new re-engineered or reconsidered antifungal agents that are more efficacious, safer and have a broad spectrum of activity. Lipid formulations of polyene antifungal agents, amphotericin B and nystatin, have the advantage of improved therapeutic index. Activity against resistant fungi, high bioavailability, safety and longer half-life are the properties that encourage development of the newer triazoles (e.g., voriconazole, ravuconazole and posaconazole). Echinocandin-like lipopeptide antibiotics are among the antifungal agents with a novel mode of action. In addition to these lead investigational compounds, development of newer antifungal agents is underway.
在过去二十年中，系统性真菌感染已被公认为发病和死亡的主要原因。针对这些感染的治疗选择很少。严重的毒性，如肾功能损害，限制了两性霉素B的使用。氟胞嘧啶存在副作用和耐药性问题。氟康唑和伊曲康唑更安全，不过某些真菌病原体中耐药性的出现以及固有耐药性是其使用过程中令人担忧的问题。因此，需要开发新的药物和/或治疗策略来对抗这些感染。近年来，制药行业和学术界加大了努力，发现了一些经过重新设计或重新考虑的新型抗真菌药物，这些药物更有效、更安全且具有广泛的活性谱。多烯类抗真菌药物两性霉素B和制霉菌素的脂质制剂具有提高治疗指数的优势。对耐药真菌的活性、高生物利用度、安全性和更长的半衰期是促使新型三唑类药物（如伏立康唑、雷夫康唑和泊沙康唑）发展的特性。棘白菌素样脂肽抗生素是具有新型作用模式的抗真菌药物之一。除了这些主要的研究化合物外，新型抗真菌药物的研发也在进行中。
