Cryptococcus neoformans and C. gattii isolates from both HIV-infected and uninfected patients: antifungal susceptibility and outcome of cryptococcal disease

Resumo

One of the factors causing treatment failure in cryptococcosis is the resistance of Cryptococcus spp. to antifungal drugs, which has motivated the susceptibility assessment of isolates from patients with cryptococcosis, different clinical conditions and infections outcomes. Clinical isolates of Cryptococcus spp. from three different groups of patients were studied in the present investigation: 19 HIV-positive patients with relapsing and/or refractory meningitis (Group 1), 30 HIV-positive patients who experienced a single and limited episode of cryptococcosis (Group 2), and 19 HIV-negative patients with cryptococcosis (Group 3). Eighty C. neoformans var. grubii isolates and 7 C. gattii isolates were studied. The minimum inhibitory concentration (MIC) of amphotericin B, azole drugs and flucytosine was determined for Cryptococcus spp. by broth microdilution test and E-test. The MIC50 and MIC90 were 0.25 and 0.50 µg/mL for amphotericin B, 4.0 and 8.0 µg /mL for fluconazole, 0.06 and 0.25 µg/mL for itraconazole, 0.25 and 0.50 µg/mL for voriconazole, and 8.0 and 16.0 µg/mL for flucytosine, respectively. Amphotericin B and itraconazole showed higher MICs for C. neoformans var. grubii and C. gattii, respectively. The MICs of fluconazole and itraconazole obtained with the E-test were higher than those obtained with broth microdilution. Isolates from non-HIV coinfected were less sensitive to the azoles. There was no difference in the susceptibility of C. neoformans var. grubii isolates from patients with a favorable or unfavorable outcome or along the episodes of relapsing and/or refractory meningitis.