Background: Mortality of invasive aspergillosis is about 50%, even when using the newer antifungal agents. Thus, there is an interest in combination therapy and how to best administer multiple drugs. In this study we compared the efficacy of LAmB and Mc given together or sequentially. Methods: Swiss Webster mice were immunosuppressed with 100 mg/kg cyclophosphamide q3d, beginning d-3. Day 0, mice were given 5.2-5.7 x 10ex4 A. fumigatus conidia IV and 24h later (n = 14/group) treated with: 6 days of 10mg/kg LAmB, 15 mg/kg LAmB or 5 mg/kg Mc (monotherapy); 6 days of 10 or 15 mg/kg LAmB with 5 mg/kg Mc (concomitant); 3 days with LAmB, then 3 days of Mc (LAmB/Mc) or 3 days with Mc, then 3 days of LAmB (Mc/LAmB) (sequential). Day 8, kidneys (n = 7) were collected for Log CFU/g. Survival (n = 7) was monitored for 28 days. Results: Survival was not statistically different among the treatment groups. LAmB significantly reduced fungal burden (p = 0.0006) and cured most mice when used as monotherapy or combined with Mc. Mc as monotherapy or when given first in sequential therapy was significantly less effective than LAmB. All D5W treated mice died by d14 (CFU/g = 3.86 for moribund animals). Conclusions: LAmB as monotherapy was more effective than Mc in reducing the fungal burden in the kidneys of infected mice. LAmB and Mc were not antagonistic when used concomitantly but the addition of Mc did not increase the efficacy. Delaying LAmB treatment by giving Mc for the first 3 days, significantly reduced LAmB efficacy.
Full conference title:
46th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 46th