Baddley John W, Pappas Peter G
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, and Birmingham Veteran's Administration Medical Center, Birmingham, Alabama 35294-0006, USA.
Drugs. 2005;65(11):1461-80. doi: 10.2165/00003495-200565110-00002.
Combination antifungal therapy has been an area of research and clinical interest since systemic antifungals became available decades ago. In vitro and clinical data were generated for some of the more common invasive fungal infections, especially candidiasis, but until very recently few clinical studies were performed. The first invasive fungal infection to be examined in clinical trials with adequate statistical power was cryptococcal meningitis and several of these trials stand out as classical studies in the clinical evaluation of combination antifungal therapy. More recently, since the availability of the newer antifungal agents, including the echinocandins and extended-spectrum triazoles, there has been a growing interest in examining combination antifungal therapy for invasive fungal disease, especially invasive aspergillosis. This is by no means a comprehensive review of all existing experimental data. Instead, the focus is on the clinical data that have been generated to date and on providing insights into potential future clinical directions. For instance, recent clinical data for cryptococcosis confirm that amphotericin B plus flucytosine is the most active combination for patients with cryptococcal meningitis. A recently completed clinical trial in candidaemia suggests a trend towards improved outcomes among patients receiving amphotericin B plus fluconazole versus fluconazole alone. In aspergillosis, several experimental models suggest benefit of a variety of antifungal combinations, but have not been confirmed in prospective clinical trials. Ultimately, the goal is to provide the reader with a comprehensive but useful review to this complicated and often confusing therapeutic dilemma.
自从几十年前全身性抗真菌药物问世以来，联合抗真菌治疗一直是研究和临床关注的领域。针对一些较常见的侵袭性真菌感染，尤其是念珠菌病，已产生了体外和临床数据，但直到最近才开展了很少的临床研究。在具有足够统计学效力的临床试验中研究的首个侵袭性真菌感染是隐球菌性脑膜炎，其中一些试验堪称联合抗真菌治疗临床评估的经典研究。最近，自从包括棘白菌素和广谱三唑类在内的新型抗真菌药物问世以来，对于侵袭性真菌病，尤其是侵袭性曲霉病的联合抗真菌治疗的研究兴趣日益浓厚。这绝不是对所有现有实验数据的全面综述。相反，重点是迄今已产生的临床数据以及对未来潜在临床方向的见解。例如，隐球菌病的近期临床数据证实，两性霉素B加氟胞嘧啶是隐球菌性脑膜炎患者最有效的联合用药。最近一项关于念珠菌血症的临床试验表明，接受两性霉素B加氟康唑的患者与仅接受氟康唑的患者相比，有改善预后的趋势。在曲霉病方面，一些实验模型提示多种抗真菌联合用药有益，但尚未在前瞻性临床试验中得到证实。最终目标是为读者提供对这一复杂且常常令人困惑的治疗难题的全面而有用的综述。
