In vitro activity of SCH-56592 and comparison with activities of amphotericin B and itraconazole against Aspergillus spp.

Abstract

In this study, we investigated the in vitro activity of SCH-56592 (SCH), a new triazole antifungal agent. We compared the activity of SCH with those of itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of Aspergillus spp. by using a microtiter format. Incubation was done at 37 degrees C for 48 h, and MIC endpoints (no growth) were read visually. The medium used for all of the drugs was RPMI 1640 buffered with morpholinepropanesulfonic acid (MOPS) and supplemented with 2% glucose. MICs and minimum fungicidal concentrations (MFCs; killing of > or = 99.99%) were measured for all isolates. The geometric mean (GM) MICs and ranges (in micrograms per milliliter) were as follows: SCH, 0.09 and < or = 0.01 to 1; ITZ, 0.25 and 0.06 to 32; AB, 1.46 and 0.25 to 32. Aspergillus terreus (n = 7) was markedly more susceptible to SCH (GM, 0.05 microg/ml) and ITZ (GM, 0.07 microg/ml) than to AB (GM, 8.8 microg/ml). For all isolates, the GM MFCs and ranges (in micrograms per milliliter) were as follows: SCH, 3.64 and 0.125 to 16; ITZ, 15.09 and 0.125 to 32; AB, 10.3 and 1 to 32. In the drug concentration range tested, 71, 32, and 64% of the isolates against which SCH, ITZ, and AB, respectively, were tested were killed. A reproducibility study was performed with 20% of the isolates; for 11 of the 12 isolates retested, the MIC was the same or within 1 well of the original MIC of each drug. Therefore, in vitro mould testing of SCH is feasible and reproducible. SCH was found to be very active against all species of Aspergillus and at lower concentrations than either ITZ or AB.