In vitro antifungal activities of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole against Cryptococcus neoformans isolated from cerebrospinal fluid and blood from patients in Serbia

Recently, geographic variations in resistance to agents commonly used in the treatment of cryptococcosis have been reported. Therefore, the antifungal susceptibilities of 31 clinical isolates of Cryptococcus neoformans, collected in Serbia during 10-year period, were investigated. Strains were isolated from cerebrospinal fluid (n = 28) and blood (n = 3), from patients with AIDS (n = 26), lymphoma (n = 4) and kidney transplant recipient (n = 1). The minimal inhibitory concentrations (MICs) of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole were determined by the E-test (R) method. The isolates were highly susceptible to amphotericin B (100% susceptibility at MIC LT 0.5 mu g/mL) and 5-fluorocytosine (87.1% susceptibility at MIC LT = 4 mu g/mL). Geometric mean MIC of amphotericin B and 5-fluorocytosine were 0.102 mu g/mL and 0.396 mu g/mL, respectively. Fluconazole exhibited the lowest activity in vitro (48.4% susceptibility at MIC LT = 8 mu g/mL) with a significant resistance rate. The activity of itraconazole was also decreased (48.4% susceptibility at MIC LT = 0.25 mu g/mL). The geometric mean MIC of fiuconazole stood at 15.14 mu g/mL and of itraconazole was 0.144 mu g/mL. Cross-resistance among azoles was not common (3.2%), but the parallel increase in fluconazole and itraconazole MIC has been observed (P LT 0.01). The low rate of susceptibility to fluconazole stresses the need for active antifungal surveillance of C. neoformans and of the corresponding data from different geographic regions. (C) 2012 Elsevier Masson SAS. All rights reserved