In vitro susceptibility and synergy studies of Aspergillus species to conventional and new agents.
In vitro susceptibility data using a macrodilution broth method on greater than 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 micrograms/ml, and 90% had MICs less than or equal to 4 micrograms/ml; for 5-fluorocytosine [flucytosine (5FC) (n = 60), 35% had MICs less than or equal to 12.5 micrograms/ml; for miconazole (MCL) (n = 18), 39% had MICs less than or equal to 5 micrograms/ml; for ketoconazole (KTZ) four (13%) of 32 isolates had an MIC less than or equal to 3.1 micrograms/ml; for itraconazole (ITZ) (n = 88), 97% had MICs less than or equal to 6.3 micrograms/ml; and for saperconazole (SAP) (n = 20), 90% had MICs less than or equal to 3.1 micrograms/ml. Of Amp B minimum fungicidal concentrations (MFCs) (n = 25), 76% were less than or equal to 4 micrograms/ml; 5% of ketoconazole (n = 20) and no flucytosine (n = 38) MFCs were less than or equal to 25 micrograms/ml; for itraconazole (n = 60), 70% had MFCs less than or equal to 6.3 micrograms/ml, and for saperconazole (n = 20), 75% had MFCs less than or equal to 3.1 micrograms/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.
Denning
D W
DW
Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128.
Hanson
L H
LH
Perlman
A M
AM
Stevens
D A
DA
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects*; D001393:Azoles / Q000494:pharmacology; D004336:Drug Antagonism; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D005437:Flucytosine / Q000494:pharmacology; D017964:Itraconazole; D007654:Ketoconazole / Q000031:analogs & derivatives / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D001393:Azoles; D017964:Itraconazole; D008825:Miconazole; D000666:Amphotericin B; D005437:Flucytosine; C060571:saperconazole; D007654:Ketoconazole