Kartsonis Nicholas, DiNubile Mark J, Bartizal Ken, Hicks Patricia Scott, Ryan Desmond, Sable Carole A
Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
J Acquir Immune Defic Syndr. 2002 Oct 1;31(2):183-7. doi: 10.1097/00126334-200210010-00009.
Caspofungin is a new echinocandin drug with comparable in vitro activity against azole-susceptible and -resistant isolates of that could provide a less toxic alternative to amphotericin B for the management of esophageal candidiasis with clinical or laboratory evidence of decreased susceptibility to fluconazole. The authors retrospectively analyzed its efficacy in adults with endoscopically documented esophagitis from four Phase II and III studies using two definitions of resistance to fluconazole: 1) clinically refractory infection based on failure of esophageal symptoms to improve despite at least 1 week of >or=200 mg/d of fluconazole; or 2) microbiologically resistant infection with either "susceptible dose-dependent" or "resistant" isolates based on MICs of 16 to 32 and >or=64 microg fluconazole/mL, respectively. A favorable response required resolution of all symptoms and substantial improvement in endoscopic findings. Seven of 11 patients (64%) who had been clinically refractory to fluconazole had favorable responses to caspofungin. Eleven of 14 patients (79%) whose isolates had decreased susceptibility to fluconazole had favorable responses to caspofungin, including 5 (83%) of 6 patients infected by isolates with MICs of >or=64 microg fluconazole/mL. Caspofungin appeared to be efficacious therapy for some patients with esophageal candidiasis who were clinically refractory to fluconazole or infected by with reduced susceptibility to fluconazole in vitro.
卡泊芬净是一种新型棘白菌素类药物,对唑类敏感和耐药菌株具有相当的体外活性,对于管理对氟康唑敏感性降低且有临床或实验室证据的食管念珠菌病患者,它可提供一种毒性较低的两性霉素B替代药物。作者回顾性分析了四项II期和III期研究中内镜证实患有食管炎的成人患者使用卡泊芬净的疗效,采用了两种氟康唑耐药定义:1)尽管至少1周每日使用≥200mg氟康唑,但食管症状仍未改善的临床难治性感染;或2)基于氟康唑最低抑菌浓度(MIC)分别为16至32μg/mL和≥64μg/mL的“敏感剂量依赖性”或“耐药”菌株的微生物学耐药感染。良好反应要求所有症状消失且内镜检查结果有显著改善。11例对氟康唑临床难治的患者中有7例(64%)对卡泊芬净有良好反应。14例分离株对氟康唑敏感性降低的患者中有11例(79%)对卡泊芬净有良好反应,包括6例感染MIC≥64μg/mL分离株的患者中的5例(83%)。对于一些对氟康唑临床难治或体外对氟康唑敏感性降低的食管念珠菌病患者,卡泊芬净似乎是一种有效的治疗方法。