Mariné Marçal, Serena Carolina, Pastor F Javier, Guarro Josep
Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201, Reus, Spain.
J Antimicrob Chemother. 2006 Dec;58(6):1295-8. doi: 10.1093/jac/dkl395. Epub 2006 Sep 29.
To develop proper treatments for patients who do not respond to current antifungal treatments, we tested new combinations of antifungal drugs for treating disseminated infections by Candida glabrata in a murine model.
Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous 5-fluorouracil administration. The animals were infected intravenously with 2 x 10(8) cfu of C. glabrata. The efficacies of micafungin combined with amphotericin B, fluconazole or flucytosine, and of amphotericin B combined with fluconazole were evaluated by survival and tissue burden reduction.
Micafungin plus amphotericin B was the most effective combination at reducing tissue burden. Micafungin at 10 mg/kg combined with amphotericin B at 0.75, 1.5 or 3 mg/kg prolonged survival with respect to the monotherapies, but only the second combination showed a synergistic effect in reducing fungal load in spleen and kidney. Amphotericin B at 1.5 mg/kg combined with micafungin at 5, 10 or 20 mg/kg reduced tissue burden with respect to the monotherapies, but the effects of the three combinations were very similar. These results suggest that amphotericin B in combination with micafungin is promising for the treatment of disseminated C. glabrata infections.
为了开发针对目前抗真菌治疗无反应患者的合适治疗方法，我们在小鼠模型中测试了抗真菌药物新组合治疗光滑念珠菌播散性感染的效果。
通过腹腔注射环磷酰胺和静脉注射5-氟尿嘧啶使小鼠中性粒细胞减少。动物静脉注射2×10⁸ cfu的光滑念珠菌。通过生存情况和组织载菌量减少来评估米卡芬净与两性霉素B、氟康唑或氟胞嘧啶联合使用，以及两性霉素B与氟康唑联合使用的疗效。
米卡芬净加两性霉素B在减轻组织载菌量方面是最有效的组合。10 mg/kg的米卡芬净与0.75、1.5或3 mg/kg的两性霉素B联合使用相对于单一疗法延长了生存期，但只有第二种组合在降低脾脏和肾脏真菌载量方面显示出协同作用。1.5 mg/kg的两性霉素B与5、10或20 mg/kg的米卡芬净联合使用相对于单一疗法减轻了组织载菌量，但这三种组合的效果非常相似。这些结果表明，两性霉素B与米卡芬净联合使用有望用于治疗光滑念珠菌播散性感染。
