In vitro susceptibility of Cryptococcus gattii clinical isolates

Gómez-López, Alicia; Zaragoza, Óscar; Martins, Marilena dos Anjos; Melhem, Márcia de Souza Carvalho; Rodríguez-Tudela, Juan Luis; Cuenca‐Estrella, Manuel

doi:10.1111/j.1469-0691.2008.02021.x

Cited by 60 publications

(48 citation statements)

References 19 publications

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“…grubii, which agrees with several previous reports (Fernandes et al, 2003;Trilles et al, 2004;Khan et al, 2007Khan et al, , 2009Gomez-Lopez et al, 2008). However, there is divergence of results concerning the antifungal susceptibility patterns of the two species in some other studies, which reported no such difference (Chen et al, 2000;Calvo et al, 2001;Morgan et al, 2006;Tay et al, 2006;Thompson et al, 2009).…”

Section: Discussionsupporting

confidence: 73%

In vitro antifungal susceptibility profiles and genotypes of 308 clinical and environmental isolates of Cryptococcus neoformans var. grubii and Cryptococcus gattii serotype B from north-western India

Chowdhary

Randhawa

Sundar

et al. 2011

Journal of Medical Microbiology

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Section: Discussionsupporting

confidence: 73%

In vitro antifungal susceptibility profiles and genotypes of 308 clinical and environmental isolates of Cryptococcus neoformans var. grubii and Cryptococcus gattii serotype B from north-western India

Chowdhary

Randhawa

Sundar

et al. 2011

Journal of Medical Microbiology

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“…To our knowledge, this is the first study that explores the efficacy of these drugs in a murine C. gattii infection. In contrast to the high in vitro activities of PSC and VRC, which agree with the findings of other authors (13,29), these drugs showed lower efficacy than AMB in vivo against C. gattii. In this study, the high mortality of mice treated with VRC or PSC seems to be associated with the inability of these drugs to reduce the fungal load in the brain despite increased drug levels in the organ.…”

Section: Discussioncontrasting

confidence: 53%

Antifungal Therapy in a Murine Model of Disseminated Infection by Cryptococcus gattii

Pastor

Rodríguez

Pujol

et al. 2010

Antimicrob Agents Chemother

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We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis.Cryptococcosis is an emerging infection commonly involving the lungs, from which it can disseminate to different tissues, usually the central nervous system (CNS) (20,23). Cryptococcus neoformans and Cryptococcus gattii are the main agents responsible for this disease, which can affect both immunosuppressed and healthy individuals. Despite antifungal therapies, this infection still has mortality rates near 20% (20).The first choice in the primary therapy of CNS infections remains fungicidal drugs, with amphotericin B (AMB) alone or in combination with flucytosine being the most widely used (20,23). Fungistatic drugs like itraconazole and fluconazole, with less toxicity, are also used in the maintenance of the therapy and in pulmonary cryptococcosis, but their use in CNS infections has been less than satisfactory. In addition, the extended duration of the therapy with these azoles increases the risk of developing drug resistance (11,23,26). It has been suggested that that C. gattii has a higher pathogenicity than C. neoformans (27), which emphasizes the importance of the correct species identification and makes it necessary to improve and search for alternatives to the current therapy.On the basis of the promising results obtained with posaconazole (PSC) and voriconazole (VRC) against C. neoformans in animal models (1,19,24) and also in a clinical setting (9, 15, 21, 22), we have evaluated in this study the efficacy of PSC, VRC, and AMB in a murine model of disseminated infection by C. gattii. MATERIALS AND METHODSThree clinical isolates of C. gattii, FMR 8394, FMR 8396, and FMR 8410, were used in this study. We tested their in vitro antifungal susceptibilities to AMB, PSC, and VRC by using a broth microdilution method following the CLSI guidelines for yeasts (8).In the in vivo study, male OF1 mice (Charles River, Criffa S.A., Barcelona, Spain) with a mean weight of 30 g were used. The animals were housed in standard boxes with corncob bedding and free access to food and water. All animal care procedures were supervised and approved by the Universitat Rovira i Virgili Animal Welfare Committee. Mice...

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“…This is corroborated by various in vitro studies that have found that C. gattii may be less susceptible than C. neoformans to antifungal agents, in particular, fluconazole (13,17,44); however, other studies report no significant differences in susceptibility (9,43). A possible reason for these contradictory findings is that most studies have not considered genetic or geographic differences within the two Cryptococcus species.…”

mentioning

confidence: 56%

“…While a number of studies have found C. gattii to be less susceptible than C. neoformans to azole drugs, particularly FLC (13,17,44), others have reported no difference between the two species (9,43). Data on susceptibility to AMB and 5FC are even more varied, with comparisons indicating that C. gattii is more resistant than (9), more susceptible than (17), or not different from (43, 44) C. neoformans.…”

Section: Discussionmentioning

confidence: 84%

In Vitro Susceptibility of the Yeast Pathogen Cryptococcus to Fluconazole and Other Azoles Varies with Molecular Genotype

et al. 2010

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Cryptococcosis is primarily caused by Cryptococcus neoformans and Cryptococcus gattii. These two pathogenic species each divide into four distinct molecular genotypes. In this study, we examined whether genotype influenced susceptibility to antifungal drugs used to treat cryptococcosis using the broth microdilution method described by the Clinical and Laboratory Standards Institute. C. gattii isolates belonging to molecular genotype VGII had significantly higher MIC values for flucytosine and all azole antifungal agents tested, particularly fluconazole, than isolates of other C. gattii genotypes. In an extended analysis of fluconazole susceptibility, VGII isolates from the north and west of Australia required higher drug levels for inhibition than those from Vancouver Island, Canada. Within C. neoformans, genotype VNII had significantly lower geometric mean MICs for fluconazole than genotype VNI. These results indicate that cryptococcal species, molecular genotype, and region of origin may be important when deciding treatment options for cryptococcosis.

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In vitro susceptibility of Cryptococcus gattii clinical isolates

Cited by 60 publications

References 19 publications

In vitro antifungal susceptibility profiles and genotypes of 308 clinical and environmental isolates of Cryptococcus neoformans var. grubii and Cryptococcus gattii serotype B from north-western India

In vitro antifungal susceptibility profiles and genotypes of 308 clinical and environmental isolates of Cryptococcus neoformans var. grubii and Cryptococcus gattii serotype B from north-western India

Antifungal Therapy in a Murine Model of Disseminated Infection by Cryptococcus gattii

In Vitro Susceptibility of the Yeast Pathogen Cryptococcus to Fluconazole and Other Azoles Varies with Molecular Genotype

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