Activity of Amphotericin B (AMB), Itraconazole (ITR), and Voriconazole (VOR) against Aspergillus (ASP) and Fusarium (FUS).



Background: While AMB and ITR have activity in invasive aspergillosis, neither appears strongly active in fusariosis. As preliminary studies with VOR have shown good activity, we compared the activity of all 3 drugs against 82 isolates of ASP [A. flavus (AFLA, 27), A. fumigatus (AFUM, 26), A. niger (ANIG, 17), A. terreus (ATER, 9), and A. nidulans (ANID, 3)] and 22 isolates of FUS [F. solani (FSOL, 18), F. oxysporum (FOXY, 4)]. Two ITR-resistant AFUM isolates (a kind gift of Dr. David Denning) were also included. Methods: The tests were performed using an adaptation of the NCCLS M27A microdilution method in RPMI 1640 (RPMI) and Antibiotic Medium 3 with 2% glucose (AM3). Final inoculum was 104:} conidia/mL. The AMB MIC was read at 100% growth inhibition and the ITR and VOR MICs were read at 50% inhibition. Results: Except for ANID, all isolates gave readable MICs at 24h. In general, MICs at 48h and 72h were the same or 1-2x higher than at 24h. Geometric mean (GM) MICs (micro g/mL) and (ranges) at 24h are reported unless otherwise noted. AMB MICs for ASP isolates in RPMI, and AM3 were 0.69 (0.125-2), and 0.34 (0.03-1). AFUM and AFLA had the highest MICs, followed by ATER and ANIG. For FUS, the AMB MICs were 1.94 (1-4) in RPMI and 1.94 (0.5->4) in AM3. ITR MICs for ASP isolates in RPMI and AM3 were 0.2 (0.03-1), and 0.15 (0.03-0.5). The ITR-resistant isolates had ITR MICs of 0.25 & 16 at 24h and >16 at 48h in RPMI. In AM3, the MICs were 0.06-0.125 at both time points. ATER showed lowest ITR MICs of all species in both media. All FSOL isolates had ITR MIC >16 micro g/mL in both RPMI and AM3, while FOXY isolates had MICs of 0.11 (0.03-0.25), and 0.15 (0.03-0.25). VOR MICs in RPMI and AM3 were 0.15 (0.03-1), and 0.16 (0.03-0.5) for ASP and 1.51 (0.25-4), and 0.78 (0.25-2) for FUS. ITR-resistant isolates had VOR MICs of 0.125 in RPMI, and 0.06-0.125 in AM3. Conclusions: (1) A narrow range of AMB MICs was observed using both media for both ASP and FUS, FUS AMB MICs were higher than ASP MICs, & ANIG had the lowest AMB MICs (2) For ITR, only FSOL and the known ITR-resistant isolates of AFUM had elevated MICs. All other isolates had similar low MICs. (3) For VOR, only FSOL had elevated MICs. All other isolates, including the ITR-resistant AFUM isolates, had similar low MICs (4) Use of AM3 lowers MIC values, especially for AMB (5) Evaluation of these data requires in vivo studies.

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38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th