Susceptibility profile and epidemiological cut-off values of Cryptococcus neoformans species complex from Argentina.

Epidemiological cut-off values (ECVs) based on minimal inhibitory concentration (MIC) distribution have been recently proposed for some antifungal drug/Cryptococcus neoformans combinations. However, these ECVs vary according to the species studied, being serotypes and the geographical origin of strains, variables to be considered. The aims were to define the wild-type (WT) population of the C. neoformans species complex (C. neoformans) isolated from patients living in Argentina, and to propose ECVs for six antifungal drugs. A total of 707 unique C. neoformans isolates obtained from HIV patients suffering cryptococcal meningitis were studied. The MIC of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole was determined according to the EDef 7.2 (EUCAST) reference document. The MIC distribution, MIC50 , MIC90 and ECV for each of these drugs were calculated. The highest ECV, which included ≥95% of the WT population modelled, was observed for flucytosine and fluconazole (32 μg ml(-1) each). For amphotericin B, itraconazole, voriconazole and posaconazole, the ECVs were: 0.5, 0.5, 0.5 and 0.06 μg ml(-1) respectively. The ECVs determined in this study may aid in identifying the C. neoformans strains circulating in Argentina with decreased susceptibility to the antifungal drugs tested.

Córdoba S ，Isla MG ，Szusz W ，Vivot W ，Altamirano R ，Davel G ... -  《-》

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(®) method. The isolates were highly susceptible to amphotericin B (100% susceptibility at MIC<0.5 μg/mL) and 5-fluorocytosine (87.1% susceptibility at MIC ≤ 4 μg/mL). Geometric mean MIC of amphotericin B and 5-fluorocytosine were 0.102 μg/mL and 0.396 μg/mL, respectively. Fluconazole exhibited the lowest activity in vitro (48.4% susceptibility at MIC ≤ 8 μg/mL) with a significant resistance rate. The activity of itraconazole was also decreased (48.4% susceptibility at MIC ≤ 0.25 μg/mL). The geometric mean MIC of fluconazole stood at 15.14 μg/mL and of itraconazole was 0.144 μg/mL. Cross-resistance among azoles was not common (3.2%), but the parallel increase in fluconazole and itraconazole MIC has been observed (P<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.

Trpković A ，Pekmezović M ，Barać A ，Crnčević Radović L ，Arsić Arsenijević V ... -  《-》

Cryptococcus neoformans-Cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole.

Espinel-Ingroff A ，Aller AI ，Canton E ，Castañón-Olivares LR ，Chowdhary A ，Cordoba S ，Cuenca-Estrella M ，Fothergill A ，Fuller J ，Govender N ，Hagen F ，Illnait-Zaragozi MT ，Johnson E ，Kidd S ，Lass-Flörl C ，Lockhart SR ，Martins MA ，Meis JF ，Melhem MS ，Ostrosky-Zeichner L ，Pelaez T ，Pfaller MA ，Schell WA ，St-Germain G ，Trilles L ，Turnidge J ... -  《-》

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

Nascimento E ，Vitali LH ，Kress MRVZ ，Martinez R ... -  《-》

Development of azole resistance during fluconazole maintenance therapy for AIDS-associated cryptococcal disease.

Friese G ，Discher T ，Füssle R ，Schmalreck A ，Lohmeyer J ... -  《AIDS》