We investigated the in vitro susceptibility of Aspergillus fumigatus to a 2-drug combination of amphotericin B lipid complex (ABLC) with caspofungin (CFG), and the results were compared with those obtained for a pair-wise combination of conventional amphotericin B (c-AMB) with CFG. Conidial suspensions were prepared from 20 clinical isolates of A fumigatus (Microbiology Laboratory, Detroit Medical Center, Detroit, Michigan) susceptible to ABLC (MIC, 1.26 + 1.14 μg/mL), c-AMB (MIC, 1 + 0.0 μg/mL), and CFG (MIC, 64 + 0.0 μg/mL). The in vitro susceptibility of A fumigatus to a 2-drug combination of ABLC or c-AMB with CFG was evaluated by the fractional inhibitory concentration index (FICI) method. The FICI was determined by a 2-dimensional checker- board using the M38-P broth microdilution technique proposed by the National Committee for Clinical Laboratory Standards for MIC testing of conidium-forming filamentous fungi except that the MIC was defined as the concentration of the drug that provided no visible growth. The FICI was calculated by the formula: FICI = (Ac í· Aa) + (Bc í· Ba) where Ac and Bc are the MICs of drugs A and B in combination and Aa and Ba are the MICs of drugs A and B alone. The drug interactions were classified as synergistic (FICI 0.5 but 1 but 2). Combinations of c-AMB + CFG (FICI = 0.42 + 0.12) and ABLC + CFG (FICI = 0.33 + 0.15) provided synergistic interactions. These in vitro data suggest that ABLC and c-AMB in 2-drug combination with an echinocandin is synergistically active against A fumigatus.
Full conference title:
12th Annual Focus on Fungal Infections
- FFI 12th (2002)