Improved method for estimation of azole antifungal inhibitory concentrations againstCandidaspecies, based on azole/antibiotic interactions

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Abstract
Low, reproducible minimal inhibitory concentrations against Candida species, with sharp, precise end points in complex media were achieved for imidazoles (clotrimazole econazole, miconazole, tioconazole and ketoconazole) and triazoles (fluconazole, itraconazole, vibunazole, ICI 153066) by including in the test medium antibacterial antibiotics that bind to the 80S eukaryotic ribosome and inhibit protein synthesis, i.e., blasticidin, cycloheximide, doxycycline, neomycin and gentamicin. The presence of these antibiotics reduced MICs, on average, by 50- to 250-fold. Other protein synthesis inhibitors (rifampicin, erythromycin, lincomycin, clindamycin, chloramphenicol and fusidic acid) were not effective, and the antibiotics did not affect MICs for Aspergillus species. The low azole MICs were in close agreement with MICs obtained in a defined tissue culture-based medium lacking added antibiotics.