Denning David W
Education and Research Centre, Wythenshawe Hospital, Southmoor Road, M23 9LT, Manchester, UK.
Lancet. 2003 Oct 4;362(9390):1142-51. doi: 10.1016/S0140-6736(03)14472-8.
The echinocandins are large lipopeptide molecules that are inhibitors of beta-(1,3)-glucan synthesis, an action that damages fungal cell walls. In vitro and in vivo, the echinocandins are rapidly fungicidal against most Candida spp and fungistatic against Aspergillus spp. They are not active at clinically relevant concentrations against Zygomycetes, Cryptococcus neoformans, or Fusarium spp. No drug target is present in mammalian cells. The first of the class to be licensed was caspofungin, for refractory invasive aspergillosis (about 40% response rate) and the second was micafungin. Adverse events are generally mild, including (for caspofungin) local phlebitis, fever, abnormal liver function tests, and mild haemolysis. Poor absorption after oral administration limits use to the intravenous route. Dosing is once daily and drug interactions are few. The echinocandins are widely distributed in the body, and are metabolised by the liver. Results of studies of caspofungin in candidaemia and invasive candidiasis suggest equivalent efficacy to amphotericin B, with substantially fewer toxic effects. Absence of antagonism in combination with other antifungal drugs suggests that combination antifungal therapy could become a general feature of the echinocandins, particularly for invasive aspergillosis.
棘白菌素类是大型脂肽分子，是β-（1,3）-葡聚糖合成的抑制剂，这一作用会破坏真菌细胞壁。在体外和体内，棘白菌素类对大多数念珠菌属具有快速杀菌作用，对曲霉属具有抑菌作用。它们在临床相关浓度下对接合菌、新型隐球菌或镰刀菌属无活性。哺乳动物细胞中不存在药物靶点。该类药物中首个获批的是卡泊芬净，用于治疗难治性侵袭性曲霉病（有效率约40%），第二个是米卡芬净。不良事件一般较轻，包括（卡泊芬净的）局部静脉炎、发热、肝功能检查异常和轻度溶血。口服吸收差限制了其仅能静脉给药。给药频率为每日一次，药物相互作用较少。棘白菌素类在体内广泛分布，由肝脏代谢。卡泊芬净治疗念珠菌血症和侵袭性念珠菌病的研究结果表明，其疗效与两性霉素B相当，但毒性明显更低。与其他抗真菌药物联合使用时无拮抗作用，这表明联合抗真菌治疗可能会成为棘白菌素类的一个普遍特点，尤其是对于侵袭性曲霉病。
