Comparative antifungal susceptibility analyses of Cryptococcus neoformans VNI and Cryptococcus gattii VGII from the Brazilian Amazon Region by the Etest, Vitek 2, and the Clinical and Laboratory Standards Institute broth microdilution methods.

Early diagnosis, efficient clinical support, and proper antifungal therapy are essential to reduce death and sequels caused by cryptococcosis. The emergence of resistance to the antifungal drugs commonly used for cryptococcosis treatment is an important issue of concern. Thus, the in vitro antifungal susceptibility of clinical strains from northern Brazil, including C. neoformans VNI (n = 62) and C. gattii VGII (n = 37), to amphotericin B (AMB), 5-flucytosine, fluconazole, voriconazole, and itraconazole was evaluated using the Etest and Vitek 2 systems and the standardized broth microdilution (CLSI-BMD) methodology. According to the CLSI-BMD, the most active in vitro azole was voriconazole (C. neoformans VNI modal MIC of 0.06 μg/ml and C. gattii VGII modal MIC of 0.25 μg/ml), and fluconazole was the least active (modal MIC of 4 μg/ml for both fungi). Modal MICs for amphotericin B were 1 μg/ml for both fungi. In general, good essential agreement (EA) values were observed between the methods. However, AMB presented the lowest EA between CLSI-BMD and Etest for C. neoformans VNI and C. gattii VGII (1.6% and 2.56%, respectively, P < .05 for both). Considering the proposed Cryptococcus spp. epidemiological cutoff values, more than 97% of the studied isolates were categorized as wild-type for the azoles. However, the high frequency of C. neoformans VNI isolates in the population described here that displayed non-wild-type susceptibility to AMB is noteworthy. Epidemiological surveillance of the antifungal resistance of cryptococcal strains is relevant due to the potential burden and the high lethality of cryptococcal meningitis in the Amazon region.

Nishikawa MM ，Almeida-Paes R ，Brito-Santos F ，Nascimento CR ，Fialho MM ，Trilles L ，Morales BP ，da Silva SA ，Santos W ，Santos LO ，Fortes ST ，Cardarelli-Leite P ，Lázera MDS ... -  《-》

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 ... -  《-》

Comparison of Etests and Vitek 2 ® to broth microdilution for the susceptibility testing of Cryptococcus neoformans.

We determined the susceptibility of 102 clinical isolates Cryptococcus neoformans from Durban, South Africa, to amphotericin B, fluconazole, flucytosine, and voriconazole using broth microdilution (BMD) according to the Clinical and Laboratory Standards Institute M27-A3 document and compared these results with Etest and Vitek 2(®). Essential agreement (EA) of Etest and Vitek 2(®) compared to BMD was determined. Low MICs that were below the epidemiological cutoff values of the 4 antifungal agents tested were demonstrated by all isolates. The EA of Etests for fluconazole, amphotericin, and voriconazole was 95.1%, 83.3%, and 91.2%, respectively, and for Vitek 2(®) EA for fluconazole, amphotericin, and flucytosine was 97.1%, 95.1%, and 97.1%, respectively. The Vitek 2(®) showed good agreement with BMD and is a suitable alternative. Etests demonstrated good EA for azoles only. Clinical cryptococcal isolates from Durban remain susceptible to current recommended antifungal therapy.

Mahabeer Y ，Chang CC ，Naidu D ，Dorasamy A ，Lewin S ，Ndung'u T ，Moosa MY ，French M ，Mlisana K ，Coovadia Y ... -  《-》

Cryptococcus neoformans-Cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for amphotericin B and flucytosine.

Espinel-Ingroff A ，Chowdhary A ，Cuenca-Estrella M ，Fothergill A ，Fuller J ，Hagen F ，Govender N ，Guarro J ，Johnson E ，Lass-Flörl C ，Lockhart SR ，Martins MA ，Meis JF ，Melhem MS ，Ostrosky-Zeichner L ，Pelaez T ，Pfaller MA ，Schell WA ，Trilles L ，Kidd S ，Turnidge J ... -  《-》

Molecular epidemiology and in vitro antifungal susceptibility testing of 108 clinical Cryptococcus neoformans sensu lato and Cryptococcus gattii sensu lato isolates from Denmark.

Cryptococcosis is mainly caused by members of the Cryptococcus gattii/Cryptococcus neoformans species complexes. Here, we report the molecular characterisation and in vitro antifungal susceptibility of Danish clinical cryptococcal isolates. Species, genotype, serotype and mating type were determined by amplified fragment length polymorphism (AFLP) fingerprinting and qPCR. EUCAST E.Def 7.2 MICs were determined for amphotericin B, flucytosine, fluconazole, voriconazole and isavuconazole. Most isolates were C. neoformans (serotype A; n = 66) and belonged to genotype AFLP1/VNI (n = 61) or AFLP1B/VNII (n = 5) followed by Cryptococcus deneoformans (serotype D; genotype AFLP2, n = 20), C. neoformans × C. deneoformans hybrids (serotype AD; genotype AFLP3, n = 13) and Cryptococcus curvatus (n = 2). Six isolates were C. gattii sensu lato, and one isolate was a C. deneoformans × C. gattii hybrid (genotype AFLP8). All isolates were amphotericin B susceptible. Flucytosine susceptibility was uniform MIC50 of 4-8 mg l(-1) except for C. curvatus (MICs >32 mg l(-1) ). Cryptococcus gattii sensu lato isolates were somewhat less susceptible to the azoles. MICs of fluconazole (>32 mg l(-1) ), voriconazole (≥0.5 mg l(-1) ) and isavuconazole (0.06 and 0.25 mg l(-1) respectively) were elevated compared to the wild-type population for 1/19 C. deneoformans and 1/2 C. curvatus isolates. Flucytosine MIC was elevated for 1/61 C. neoformans (>32 mg l(-1) ). Antifungal susceptibility revealed species-specific differential susceptibility, but suggested acquired resistance was an infrequent phenomenon.

Hagen F ，Hare Jensen R ，Meis JF ，Arendrup MC ... -  《-》