Morris Michele I, Villmann Mark
Division of Infectious Disease, School of Medicine, University of Miami, FL 33136, USA.
Am J Health Syst Pharm. 2006 Oct 1;63(19):1813-20. doi: 10.2146/ajhp050464.p2.
The chemistry, pharmacology, spectrum of activity, resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, drug interactions, dosage and administration, cost, and place in therapy of echinocandins are reviewed.
Three echinocandins are currently available: caspofungin, micafungin, and anidulafungin. The principal mechanism of action of the echinocandins is the noncompetitive inhibition of beta-(1,3)-D-glucan synthase, an essential component of the cell wall of many fungi that is not present in mammalian cells. Echinocandins exhibit fungicidal activity against Candida species, including triazole-resistant isolates, and fungistatic activity against Aspergillus species. While fungistatic against mold, echinocandins may hold promise for the treatment of these pathogens when given in combination with amphotericin B or broad-spectrum triazoles, such as voriconazole. To date, resistance to echinocandins has been reported in only two patients. Echinocandins exhibit concentration-dependent activity against Candida species. In clinical trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as antifungal prophylaxis in hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis. Anidulafungin received approved labeling from the Food and Drug Administration in February 2006. Clinical efficacy data will be forthcoming.
Echinocandins are fungicidal against yeast and fungistatic against mold. Their limited toxicity profile and minimal drug-drug interactions make them an attractive new option for the treatment of invasive fungal infections. Their cost may limit their use as initial therapy for patients with fungemia in medical centers or intensive care units with a high rate of triazoleresistant Candida infections.
综述棘白菌素类药物的化学性质、药理学、活性谱、耐药性、药代动力学、药效学、临床疗效、不良反应、药物相互作用、剂量与用法、成本以及在治疗中的地位。
目前有三种棘白菌素类药物可用：卡泊芬净、米卡芬净和阿尼芬净。棘白菌素类药物的主要作用机制是非竞争性抑制β-(1,3)-D-葡聚糖合酶，这是许多真菌细胞壁的重要组成部分，而哺乳动物细胞中不存在该酶。棘白菌素类药物对念珠菌属具有杀菌活性，包括对三唑耐药的菌株，对曲霉属具有抑菌活性。虽然对霉菌是抑菌作用，但当与两性霉素B或广谱三唑类药物（如伏立康唑）联合使用时，棘白菌素类药物可能对这些病原体的治疗有前景。迄今为止，仅在两名患者中报道了对棘白菌素类药物的耐药性。棘白菌素类药物对念珠菌属表现出浓度依赖性活性。在临床试验中，卡泊芬净已证明对治疗念珠菌血症、食管念珠菌病和发热性中性粒细胞减少有效。米卡芬净已证明对造血干细胞移植受者有抗真菌预防作用，并可用于治疗食管念珠菌病。阿尼芬净于2006年2月获得美国食品药品监督管理局批准的标签。临床疗效数据即将公布。
棘白菌素类药物对酵母菌具有杀菌作用，对霉菌具有抑菌作用。其有限的毒性和最小的药物相互作用使其成为治疗侵袭性真菌感染的有吸引力的新选择。其成本可能会限制其在三唑耐药念珠菌感染发生率高的医疗中心或重症监护病房中作为真菌血症患者初始治疗的应用。
