Avaliação da suscetibilidade de Candida glabrata resistentes ao fluconazol frente a combinações de antifúngicos

Abstract

In the last decades the invasive mycoses caused by opportunistic fungi has showed a significant growth. The extensive use of azoles showed that the development of resistance of Candida species to these drugs is an emergent phenomenon. C. glabrata typically presents high degree of primary resistance to fluconazole what determine additional difficulties in the therapies. Here two groups of C. glabrata isolates were evaluated: the first formed by strains primarily fluconazole-susceptible and the second generated by the first, was composed by the same isolates after induction of the fluconazole-resistance. The susceptibility tests detected even in the first group, strains azole-resistant as against itraconazole and voriconazole. The induction of resistance to fluconazole was carried out in order to compare the susceptibilities between the two groups against combined drugs. The fluconazole-resistant strains (Group 2) showed MIC ≥ 64 μg/ml and cross-resistance was either detected with fluconazole, voriconazole and itraconazole as well as to other antifungal agents as amphotericin B and caspofungine. The more frequent interaction observed was indifference, however important synergisms were showed against fluconazole-resistant isolates. The best synergism was registered with amphotericin B+ flucytosine (G1 = 61,77% and G2=76,47%). Other synergistic interactions were amphotericin B+ketoconazole (G2=73,53%), amphotericin B+voriconazole (G2=55,88%), amphotericin B+voricoonazole (G2=55,88%), all of them without antagonisms. The highest percentage of the antagonism were observed with ketoconazole+flucytosine (G1=61,77% and G2= 55,88%).