In vitro susceptibility and synergy studies of Aspergillus species to conventional and new agents

In vitro susceptibility data using a macrodilution broth method on >100 isolates of Aspergillus spp. are presented. For amphotericin B (Amp B) (n = 105), 67% had minimum inhibitory concentrations (MICs) ≤2 μg/ml, and 90% had MICs ≤4 μg/ml; for 5-fluorocytosine [flucytosine (5FC)] (n = 60), 35% had MICs ≤12.5 μg/ml; for miconazole (MCL) (n = 18), 39% had MICs ≤5 μg/ml; for ketoconazole (KTZ) four (13%) of 32 isolates had an MIC ≤3.1 μg/ml; for itraconazole (ITZ) (n = 88), 97% had MICs ≤6.3 μg/ml; and for saperconazole (SAP) (n = 20), 90% had MICs ≤3.1 μg/ml. Of Amp B minimum fungicidal concentrations (MFCs) (n = 25), 76% were ≤4 μg/ml; 5% of ketoconazole (n = 20) and no flucytosine (n = 38) MFCs were ≤25 μg/ml; for itraconazole (n = 60), 70% had MFCs ≤6.3 μg/ml, and for saperconazole (n = 20), 75% had MFCs ≤3.1 μg/ml. Drug interaction studies were also performed. For Amp B and rifampin 36 (92%) of 39 showed synergy, for Amp B and flucytosine six (23%) of 26 showed synergy and another six (23%) showed antagonism; 13 (50%) were indifferent. In five Amp B-itraconazole combination studies, synergy and indifference were seen in two each and an additive effect was observed in one. The published literature on in vitro testing methodology and results for Aspergillus spp. is also reviewed, and recommendations for the clinical use of in vitro susceptibility testing are made.