Combination Antifungal Therapy with FK463 plus Amphotericin B in Treatment of Experimental Pulmonary Aspergillosis.

V. PETRAITIS, R. PETRAITIENE, R.J. LEGUIT, M. CANDELARIO, T. SEIN, J. PETER, A. FIELD-RIDLEY, R. IRWIN, A. GROLL, T.J. WALSH

Abstract: 

FK463(FK) is a novel injectable echinocandin with broad-spectrum fungicidal activity against Candida and fungistatic activity against Aspergillus spp. In order to increase efficacy of FK against experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits, we therefore studied the in vitro and vivo antifungal activity of FK in combination with amphotericin B (AmB) or AmBisome (LAMB). We studied the combination of FK and AmB over a range of therapeutic concentrations (FK (0.002 to 128 µg/ml) and AmB (0.015 to 4 µg/ml)), using checkerboard, timed kill, and MTT assays. These studies demonstrated that AmB and FK in combination were neither synergistic nor antagonistic in their interaction. We then proceeded to investigate the in vivo antifungal activity of FK, LAMB, and AmB. Therapy started 24h after endotracheal inoculation of 1.5x108 Aspergillus fumigatus conidia. Groups consisted of untreated controls(UC), FK at 1(FK1), AmB at 0.1(AmB0.1), LAMB at 0.5(LAMB0.5), FK1+AmB0.1(F+A), or FK1+LAMB0.5(F+L). Survival through the entire study was achieved in 5 (55%) of 9 F+A, 4 (44%) of 9 F+L, 3 (33%) of 9 AmB0.1, and 2 (22%) of 9 LAMB0.5-treated rabbits vs. none of 20 UC (p
1999

abstract No: 

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Full conference title: 

39th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 39th