Université Paris Diderot, Sorbonne Paris Cité, Paris, France Université Pierre et Marie Curie-Paris 6, Paris, France.
Mycoses. 2013 May;56(3):241-9. doi: 10.1111/myc.12011. Epub 2012 Sep 24.
The efficacy of antifungal prophylaxis for prevention of invasive aspergillosis (IA) may depend on whether IA results from recent inhalation of spores or reactivation of latent colonisation. Compare the efficacy of liposomal amphotericin B (LAmB) for prophylaxis in acute and reactivation models of IA. In the acute model, mice immunosuppressed from day 0 were challenged at day 3 with an aerosol of Aspergillus fumigatus. LAmB (15 mg kg(-1) ) was administered at day 0 or at challenge. In the reactivation model, naïve mice exposed to A. fumigatus remained untreated until clearance of spores from the lungs, then immunosuppressed to induce reactivation. A single LAmB dose was administered at start of immunosuppression. In the acute model, a single administration of LAmB at start of immunosuppression was not effective, but an additional administration resulted in a significant decrease in lung fungal burden (P < 0.05 vs. controls). A significant prophylactic efficacy was observed when LAmB was administered once at challenge (P < 0.01). In the reactivation model, a single LAmB administration at start of immunosuppression significantly reduced both reactivation rate and fungal burden vs. controls (P < 0.01). Our results show that the conditions under which IA develop and timing of administration of LAmB were determinant variables for prophylactic efficacy.
抗真菌预防治疗预防侵袭性曲霉菌病(IA)的疗效可能取决于 IA 是否源于近期吸入孢子或潜伏定植的再激活。比较两性霉素 B 脂质体(LAmB)在 IA 急性和再激活模型中的预防效果。在急性模型中,从第 0 天开始免疫抑制的小鼠在第 3 天用烟曲霉的气雾剂进行挑战。在第 0 天或在挑战时给予 LAmB(15 mg/kg)。在再激活模型中,暴露于烟曲霉的未处理小鼠在清除肺部孢子之前未进行任何治疗,然后进行免疫抑制以诱导再激活。在免疫抑制开始时给予单次 LAmB 剂量。在急性模型中,免疫抑制开始时单次给予 LAmB 无效,但额外给予一次可显著降低肺部真菌负荷(P<0.05 与对照组相比)。在挑战时给予 LAmB 一次可显著预防,观察到明显的预防效果(P<0.01)。在再激活模型中,免疫抑制开始时单次给予 LAmB 可显著降低再激活率和真菌负荷与对照组相比(P<0.01)。我们的结果表明,IA 发展的条件和 LAmB 的给药时间是预防疗效的决定因素。