Olson Jon A, Adler-Moore Jill P, Smith P J, Proffitt Richard T
Department of Biological Sciences, California State Polytechnic University, 3801 West Temple Ave., Pomona, CA 91768, USA.
Antimicrob Agents Chemother. 2005 Dec;49(12):4895-902. doi: 10.1128/AAC.49.12.4895-4902.2005.
While Candida albicans remains the most common Candida isolate, Candida glabrata accounts for approximately 15 to 20% of all Candida infections in the United States. In this study we used immunosuppressed mice infected with C. glabrata to investigate the efficacy of liposomal amphotericin B alone or in combination with the echinocandin caspofungin or micafungin. For monotherapy, mice were given six daily doses of liposomal amphotericin B (3 to 20 mg/kg of body weight), caspofungin (1 to 5 mg/kg), or micafungin (2.5 to 10 mg/kg). With concomitant therapy, mice received liposomal amphotericin B (7.5 mg/kg) in addition to caspofungin (2.5 mg/kg) or micafungin (2.5 mg/kg) for 6 days. For sequential therapy, liposomal amphotericin B was administered on days 1 to 3 and caspofungin or micafungin was given on days 4 to 6; conversely, caspofungin or micafungin was administered on days 1 to 3 and liposomal amphotericin B was given on days 4 to 6. Efficacy was based on the number of CFU per gram of kidney 21 days postchallenge. Monotherapy with liposomal amphotericin B (7.5 to 20 mg/kg) was significantly more effective than no drug treatment (control group) (P < 0.05) and demonstrated a dose-dependent response, with 20 mg/kg lowering the CFU/g from 6.3 to 4.2 (significantly different from the value for the control group [P < 0.001]). Monotherapy with all echinocandin doses lowered the CFU/g from 6.0 to 6.4 to 2.7 to 3.3 (significantly different from the value for the control group [P < 0.001]) with no dose-dependent response. Complete clearance of infection could be achieved only when liposomal amphotericin B was given either concomitantly with caspofungin or micafungin or if liposomal amphotericin B was given sequentially with caspofungin. In conclusion, the combination of liposomal amphotericin B with an echinocandin markedly improved the therapeutic outcome in murine C. glabrata systemic infection.
虽然白色念珠菌仍然是最常见的念珠菌分离株，但光滑念珠菌在美国所有念珠菌感染中约占15%至20%。在本研究中，我们使用感染了光滑念珠菌的免疫抑制小鼠来研究脂质体两性霉素B单独使用或与棘白菌素卡泊芬净或米卡芬净联合使用的疗效。对于单一疗法，给小鼠每日六次剂量的脂质体两性霉素B（3至20mg/kg体重）、卡泊芬净（1至5mg/kg）或米卡芬净（2.5至10mg/kg）。对于联合疗法，小鼠除接受卡泊芬净（2.5mg/kg）或米卡芬净（2.5mg/kg）外，还接受脂质体两性霉素B（7.5mg/kg），持续6天。对于序贯疗法，脂质体两性霉素B在第1至3天给药，卡泊芬净或米卡芬净在第4至6天给药；相反，卡泊芬净或米卡芬净在第1至3天给药，脂质体两性霉素B在第4至6天给药。疗效基于攻击后21天每克肾脏中的菌落形成单位（CFU）数量。脂质体两性霉素B（7.5至20mg/kg）单一疗法比无药物治疗（对照组）显著更有效（P<0.05），并表现出剂量依赖性反应，20mg/kg可使CFU/g从6.3降至4.2（与对照组的值显著不同[P<0.001]）。所有棘白菌素剂量的单一疗法可使CFU/g从6.0至（此处原文有误，推测为6.4）降至2.7至3.3（与对照组的值显著不同[P<0.001]），且无剂量依赖性反应。只有当脂质体两性霉素B与卡泊芬净或米卡芬净联合给药，或脂质体两性霉素B与卡泊芬净序贯给药时，才能实现感染的完全清除。总之，脂质体两性霉素B与棘白菌素联合使用显著改善了小鼠光滑念珠菌全身感染的治疗效果。
