Molecular epidemiology and antifungal susceptibility profiles of clinical Cryptococcus neoformans/Cryptococcus gattii species complex

This study analyzed the in vitro drug sensitivity of Cryptococcus spp. from Guangxi, Southern China. One hundred three strains of Cryptococcus were recovered from 86 patients; 14 were HIV positive and 72 were HIV negative. Ninety-two strains were identified as Cryptococcus neoformans var. grubii, while 11 strains were identified as Cryptococcus gattii (5 C. gattii sensu stricto and 6 Cryptococcus deuterogattii). The recovered strains were tested against commonly used antifungal drugs (fluconazole, amphotericin B, 5-fluorocytosine, itraconazole, and voriconazole) and to novel antifungal drugs (posaconazole and isavuconazole) using CLSI M27-A4 method. The results showed that all isolates were susceptible to most antifungal drugs, of which the minimum inhibitory concentration (MIC) ranges were as follows: 0.05–4 μg/ml for fluconazole, 0.25–1 μg/ml for amphotericin B; 0.0625–2 μg/ml for 5-fluorocytosine, 0.0625–0.25 μg/ml for itraconazole, 0.0078–0.25 μg/ml for voriconazole, 0.0313–0.5 μg/ml for posaconazole, 0.0020–0.125 μg/ml for isavuconazole for C. neoformans var. grubii isolates, and 1–16 μg/ml for fluconazole, 0.125–1 μg/ml for 5-fluorocytosine, 0.25–1 μg/ml for amphotericin B, 0.0625–0.25 μg/ml for itraconazole, 0.0156–0.125 μg/ml for voriconazole, 0.0156–0.25 μg/ml for posaconazole, and 0.0078–0.125 μg/ml for isavuconazole for C. gattii isolates. Furthermore, some C. neoformans var. grubii isolates were found to be susceptible-dose dependent to 5-fluorocytosine and itraconazole. In addition, a reduction in the potency of fluconazole against C. gattii is possible. We observed no statistical differences in susceptibility of C. neoformans var. grubii and C. gattii in the tested strains. Continuous observation of antifungal susceptibility of Cryptococcus isolates is recommended to monitor the emergence of resistant strains.

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Environmental Status of Cryptococcus neoformans and Cryptococcus gattii in Colombia

Journal of Fungi ◽

10.3390/jof7060410 ◽

2021 ◽

Vol 7 (6) ◽

pp. 410

Author(s):

Briggith-Nathalia Serna-Espinosa ◽

Diomedes Guzmán-Sanabria ◽

Maribel Forero-Castro ◽

Patricia Escandón ◽

Zilpa Adriana Sánchez-Quitian

Keyword(s):

Cryptococcus Neoformans ◽

Species Complex ◽

Columba Livia ◽

Systematic Investigation ◽

Cryptococcus Gattii ◽

Eucalyptus Species ◽

Environmental Niche ◽

Worldwide Distribution ◽

Bird Droppings ◽

The Central Nervous System

The genus Cryptococcus comprises more than 80 species, including C. neoformans and C. gattii, which are pathogenic to humans, mainly affecting the central nervous system. The two species differ in geographic distribution and environmental niche. C. neoformans has a worldwide distribution and is often isolated from bird droppings. On the contrary, C. gattii is reported in tropical and subtropical regions and is associated with Eucalyptus species. This review aims to describe the distribution of environmental isolates of the Cryptococcus neoformans species complex and the Cryptococcus gattii species complex in Colombia. A systematic investigation was carried out using different databases, excluding studies of clinical isolates reported in the country. The complex of the species of C. gattii is recovered mainly from trees of the genus Eucalyptus spp., while the complex of the species of C. neoformans is recovered mainly from avian excrement, primarily Columba livia (pigeons) excrement. In addition, greater positivity was found at high levels of relative humidity. Likewise, an association was observed between the presence of the fungus in places with little insolation and cold or temperate temperatures compared to regions with high temperatures.

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Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs

Journal of Medical Microbiology ◽

10.1099/jmm.0.001194 ◽

2020 ◽

Vol 69 (6) ◽

pp. 830-837

Author(s):

Raimunda Sâmia Nogueira Brilhante ◽

José Alexandre Telmos Silva ◽

Géssica dos Santos Araújo ◽

Vandbergue Santos Pereira ◽

Wilker Jose Perez Gotay ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Amphotericin B ◽

Metabolic Activity ◽

Biofilm Formation ◽

Species Complex ◽

Cryptococcus Gattii ◽

Antifungal Drugs ◽

Planktonic Cells ◽

Species Activity ◽

Checkerboard Assay

Introduction. Cryptococcus species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS. Aim. The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of Cryptococcus species. Methodology. Susceptibility testing of darunavir and the common antifungals against 12 members of the Cryptococcus neoformans/Cryptococcus gattii species complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively. Results. Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. All Cryptococcus species strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (P<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (P<0.05). Conclusion. Darunavir presents antifungal activity against planktonic cells of Cryptococcus species and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms of Cryptococcus species. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.

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Molecular typing, in vitro susceptibility and virulence of Cryptococcus neoformans/Cryptococcus gattii species complex clinical isolates from south‐eastern Brazil

Mycoses ◽

10.1111/myc.13174 ◽

2020 ◽

Vol 63 (12) ◽

pp. 1341-1351

Author(s):

Patrícia Helena Grizante Barião ◽

Ludmilla Tonani ◽

Tiago Alexandre Cocio ◽

Roberto Martinez ◽

Érika Nascimento ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Molecular Typing ◽

Species Complex ◽

Cryptococcus Gattii ◽

Clinical Isolates ◽

In Vitro Susceptibility ◽

South Eastern ◽

Eastern Brazil

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Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for the Cryptococcus neoformans-Cryptococcus gattii Species Complex Using the CLSI M27-A3 Broth Microdilution Method

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04055-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 666-668 ◽

Cited By ~ 39

Author(s):

A. Espinel-Ingroff ◽

A. Chowdhary ◽

G. M. Gonzalez ◽

J. Guinea ◽

F. Hagen ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Multicenter Study ◽

Species Complex ◽

Cryptococcus Gattii ◽

Broth Microdilution ◽

Wild Type ◽

Content Type ◽

Microdilution Method ◽

Cutoff Values ◽

Broth Microdilution Method

ABSTRACTEpidemiological cutoff values (ECVs) of isavuconazole are not available forCryptococcusspp. The isavuconazole ECVs based on wild-type (WT) MIC distributions for 438Cryptococcus neoformansnongenotyped isolates, 870 isolates of genotype VNI, and 406Cryptococcus gattiiisolates from six laboratories and different geographical areas were 0.06, 0.12, and 0.25 μg/ml, respectively. These ECVs may aid in detecting non-WT isolates with reduced susceptibilities to isavuconazole.

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