Efficacy of micafungin alone or in combination against experimental pulmonary aspergillosis
Efficacy of micafungin alone or in combination against experimental pulmonary aspergillosis
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DOI：
10.1080/13693780500148350
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发表时间：
2006-02-01
期刊：
影响因子：
2.9
通讯作者：
Stevens, DA
中科院分区：
文献类型：
--
作者：
Clemons, KV;Stevens, DA
侵袭性肺曲霉菌病的死亡率接近80%，几乎没有可用的治疗选择。在这些研究中，我们检查了米卡芬净（云母）单独或与其他抗真菌药联合治疗免疫抑制DBA/2小鼠鼻内感染烟曲霉10AF分生孢子的肺曲霉病模型的疗效。在最初的研究中，给各组小鼠注射生理盐水，或1、3或10 mg/kg的云母，每日两次，S.C.所有生理盐水对照组和90%未处理的小鼠死于感染。云母的疗效难以评估，因为在10 mg/kg时存在明显的毒性。与生理盐水对照组相比，1 mg/kg剂量的云母显著延长了存活时间（P = 0.008）。3或10 mg/kg（-1）的云母与生理盐水对照组相比接近显著性。治疗方案的疗效无差异。对联合治疗的有效性进行了评估，其中小鼠未接受治疗，云母1 mg/kg/剂，0.8 mg/kg（-1）静脉注射阿替霉素B（AMB），100 mg/kg（-1）口服伊曲康唑（ICZ），或100 mg/kg/剂每日两次皮下注射尼可霉素Z（NIK）。单用AMB、云母+ AMB或云母+ NIK组生存期均明显延长（P < 0.05 ~ 0.02）。ICZ单独、ICZ +云母和NIK单独均未显著延长生存期。在延长存活率方面，Img/kg的单独云母接近显著性。云母和ICZ的组合似乎是潜在的拮抗作用。虽然AMB +云母是有效的，但任何方案均未观察到协同活性。总体而言，这些结果表明，云母对肺曲霉病具有中等活性，并可能与传统AMB联合使用。
Mortality from invasive pulmonary aspergillosis approaches 80% with few useful therapeutic options available. In these studies, we examined the efficacy of micafungin (MICA) alone or in combination with other antifungals in a model of pulmonary aspergillosis in immunosuppressed DBA/2 mice infected intranasally with conidia of Aspergillus fumigatus 10AF. In the initial study, groups of mice were given saline, or 1, 3 or 10 mg kg(-1) of MICA b.i.d., s.c. All saline controls, and 90% of untreated mice succumbed to infection. The efficacy of MICA was difficult to assess because of an apparent toxicity at 10 mg kg(-1). MICA given at 1 mg/kg significantly prolonged survival over the saline controls (P = 0.008). MICA at 3 or 10 mg kg(-1) versus the saline controls approached significance. No treatment regimen differed in efficacy. The efficacy of combination therapy was assessed, with mice given either no treatment, MICA at 1 mg/kg/dose, 0.8 mg kg(-1) of intravenous amphotericin B (AMB), 100 mg kg(-1) of oral itraconazole (ICZ), or 100 mg/kg/ dose of twice-daily subcutaneous nikkomycin Z (NIK). AMB alone and MICA + AMB or MICA + NIK significantly prolonged survival (P < 0.05 -0.02) over that of the controls. ICZ alone, ICZ + MICA and NIK alone did not significantly prolong survival. MICA alone at I mg/kg approached significance in prolonging survival. The combination of MICA and ICZ appeared to be potentially antagonistic. Although AMB + MICA was efficacious, no synergistic activity was noted for any of the regimens. Overall, these results indicate that MICA has moderate activity against pulmonary aspergillosis and might be useful in combination with conventional AMB.