INVITRO 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) less-than-or-equal-to 2-mu-g/ml, and 90% had MICs less-than-or-equal-to 4-mu-g/ml; for 5-fluorocytosine [flucytosine (5FC)] (n = 60), 35% had MICs less-than-or-equal-to 12.5-mu-g/ml; for miconazole (MCL) (n = 18), 39% had MICs less-than-or-equal-to 5-mu-g/ml; for ketoconazole (KTZ) four (13%) of 32 isolates had an MIC less-than-or-equal-to 3.1-mu-g/ml; for itraconazole (ITZ) (n = 88), 97% had MICs less-than-or-equal-to 6.3-mu-g/ml; and for saperconazole (SAP) (n = 20), 90% had MICs less-than-or-equal-to 3.1-mu-g/ml. Of Amp B minimum fungicidal concentrations (MFCs) (n = 25), 76% were less-than-or-equal-to 4-mu-g/ml; 5% of ketoconazole (n = 20) and no flucytosine (n = 38) MFCs were less-than-or-equal-to 25-mu-g/ml; for itraconazole (n = 60), 70% had MFCs less-than-or-equal-to 6.3-mu-g/ml, and for saperconazole (n = 20), 75% had MFCs less-than-or-equal-to 3.1-mu-g/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.