Cappelletty Diane, Eiselstein-McKitrick Kasi
College of Pharmacy, University of Toledo, Toledo, Ohio 43606, USA.
Pharmacotherapy. 2007 Mar;27(3):369-88. doi: 10.1592/phco.27.3.369.
The changing pattern in fungal infections has driven the need to expand the targets of antifungal activity. The echinocandins are the newest addition to the arsenal against fungal infections. Three echinocandins have been approved by the United States Food and Drug Administration: caspofungin, micafungin, and anidulafungin. These agents have a broad spectrum of activity and are similar to each other with respect to in vitro activity against Candida sp, with micafungin and anidulafungin having similar minimum inhibitory concentrations (MICs) that are generally lower than the MIC of capsofungin. The MICs of the echinocandins are highest against Candida parapsilosis; however, whether this will affect clinical outcomes is unknown. Several case reports have identified clinical failure due to elevated MICs with caspofungin or micafungin against Candida albicans, Candida krusei, and C. parapsilosis. Resistance to the echinocandin class was present in some but not all of the isolates. Empiric therapy with one of the echinocandins for candidemia or invasive candidiasis in patients with neutropenia and those without neutropenia appears to be appropriate when one factors in mortality rate, the increasing frequency of non-albicans Candida infections, and the broad spectrum, safety, and fungicidal effect of the echinocandins. After speciation of the organism, continued therapy with an echinocandin can and should be reevaluated. The echinocandins demonstrate similar in vitro and in vivo activity against Aspergillus sp, but only caspofungin is approved for treatment in patients who are intolerant of or refractory to other therapies. Voriconazole and amphotericin B have demonstrated synergy with the echinocandins. The clinical response to combination therapy has been variable; however, the mortality rate appears to be lower with combination therapy than monotherapy. Large controlled trials are needed to determine the role of combination therapy for invasive aspergillosis. Micafungin and anidulafungin generally have a lower frequency of adverse reactions compared with caspofungin. Phlebitis (3.5-25% of patients) and elevated liver enzyme levels (1-15%) occur more often with caspofungin compared with micafungin and anidulafungin (< 8%). Overall, the three echinocandins are relatively safe and effective agents for the treatment of Candida infections.
真菌感染模式的变化促使人们需要扩大抗真菌活性的靶点。棘白菌素类药物是抗真菌感染药物库中的最新成员。三种棘白菌素已获美国食品药品监督管理局批准：卡泊芬净、米卡芬净和阿尼芬净。这些药物具有广泛的活性，在体外对念珠菌属的活性方面彼此相似，米卡芬净和阿尼芬净的最低抑菌浓度（MIC）相似，通常低于卡泊芬净的MIC。棘白菌素类药物对近平滑念珠菌的MIC最高；然而，这是否会影响临床结果尚不清楚。几例病例报告指出，由于卡泊芬净或米卡芬净对白色念珠菌、克柔念珠菌和近平滑念珠菌的MIC升高导致临床治疗失败。部分但并非所有分离株对棘白菌素类药物存在耐药性。考虑到死亡率、非白色念珠菌感染频率的增加以及棘白菌素类药物的广谱性、安全性和杀菌作用，对于中性粒细胞减少和非中性粒细胞减少患者的念珠菌血症或侵袭性念珠菌病，使用其中一种棘白菌素进行经验性治疗似乎是合适的。在确定病原体种类后，可且应当重新评估继续使用棘白菌素进行治疗的方案。棘白菌素类药物对曲霉属在体外和体内均表现出相似的活性，但只有卡泊芬净被批准用于对其他治疗不耐受或难治的患者。伏立康唑和两性霉素B已证明与棘白菌素类药物具有协同作用。联合治疗的临床反应各不相同；然而，联合治疗的死亡率似乎低于单药治疗。需要进行大型对照试验来确定联合治疗在侵袭性曲霉病中的作用。与卡泊芬净相比，米卡芬净和阿尼芬净的不良反应发生率通常较低。与米卡芬净和阿尼芬净（<8%）相比，卡泊芬净导致静脉炎（3.5 - 25%的患者）和肝酶水平升高（1 - 15%）的情况更常见。总体而言，这三种棘白菌素是治疗念珠菌感染相对安全有效的药物。
