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Trichophyton rubrum, an anthropophilic dermatophyte fungus, is the predominant causative agent of superficial skin infections in human population. There are only scanty reports on drug susceptibility profiling of T. rubrum. Neither mechanisms for drug resistance development nor correlation between in vitro drug susceptibility and in vivo response to treatment is known for that species. In this study, changes in the in vitro susceptibilities to fluconazole (FLZ) and itraconazole (ITZ) among thirty T. rubrum clinical strains subjected to sequential passages in the presence or absence of the azoles were investigated. Each strain was passaged 12 times at 4-week intervals as three parallel cultures, maintained on a drug-free medium (1), and a medium containing FLZ (2) or ITZ (3) at subinhibitory concentrations. Susceptibility to FLZ and ITZ of the original strain and its 3 subcultures was determined by microdilution method. The MIC values of the two azoles remained unaltered for all T. rubrum strains tested, after 12 passages on a drug-free medium. Among the strains grown with FLZ, an increase in the MICs of FLZ and ITZ was noted in 17 (56.7 %) and 19 (63.3 %) strains, respectively. Increased MICs of ITZ and FLZ were demonstrated for 24 (80 %) and 20 (66.7 %) strains that were propagated with ITZ. The results indicate the capacity of T. rubrum to develop resistance toward the azoles after prolonged exposure to these drugs. Resistance of T. rubrum to azoles plays an important role in therapy failures and consequently contributes to persistence and chronicity of the infections. [ABSTRACT FROM AUTHOR]

The drug concentration which inhibited 50% of growth (IC), the lowest drug concentration at which growth was less than 30% of that in a positive control well (IC), the visual minimal inhibitory concentration (MIC), and the minimum fungicidal concentration (MFC), were applied to study the effects of fluconazole, itraconazole, ketoconazole, miconazole, flucytosine, and amphotericin B against 36 isolates of Candida spp. and Cryptococcus neoformans by a broth microdilution technique. When the recommendations established by the NCCLS Subcommittee on Antifungal Susceptibility Tests were applied for the visual reading of the microplates, the results were comparable with those obtained by the turbidimetric methods. Differences between MICs and ICs were observed with miconazole against strains of C. glabrata ( p=0.014) and with flucytosine against strains of C. neoformans ( p=0.041). Differences between MICs and ICs were observed with fluconazole against strains of C. albicans ( p=0.027), C. tropicalis ( p=0.046), and C. neoformans ( p=0.041); with miconazole against strains of C. glabrata ( p=0.014); and with amphotericin B against strains of C. parapsilosis ( p=0.025). Ten additional isolates of C. albicans from AIDS patients suffering from recurrent episodes of oral candidiasis and clinically resistant to fluconazole also were included in this study. The MICs of fluconazole of these strains were significantly higher than those of the control group ( p=0.003). When the turbidimetric parameters were applied for testing the in vitro activity of fluconazole against the above isolates, both IC and IC were capable of discriminating the strains of the two groups ( p=0.002, p=0.001, respectively). Only amphotericin B demonstrated fungicidal activity against all the tested yeasts. [ABSTRACT FROM AUTHOR]