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

Chong, Hin Siong; Dagg, Rebecca A.; Malík, Richard; Chen, Sharon; Carter, Dee

doi:10.1128/jcm.01271-10

Cited by 79 publications

(75 citation statements)

References 47 publications

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“…Following their analysis of susceptibility profiles of C. gattii genotypes, Chong et al [49] reported higher MIC values for fluconazole (≥ 64 µg/mL) against C. gattii VGII than against C. gattii VGIII and VGI [48]. Iqbal et al [50] reported differences in the susceptibility profiles of the molecular types of C. gattii, having determined higher MIC values for the VGII subtypes than the VGI and VGIII subtypes.…”

Section: Discussionmentioning

confidence: 99%

Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil

Favalessa

Paula

Dutra

et al. 2014

J Infect Dev Ctries

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Introduction: Cryptococcosis is a systemic fungal infection that affects humans and animals, mainly due to Cryptococcus neoformans and Cryptococcus gattii. Following the epidemic of acquired immunodeficiency syndrome (AIDS), fungal infections by C. neoformans have become more common among immunocompromised patients. Cryptococcus gattii has primarily been isolated as a primary pathogen in healthy hosts and occurs endemically in northern and northeastern Brazil. We to perform genotypic characterization and determine the in vitro susceptibility profile to antifungal drugs of the Cryptococcus species complex isolated from HIV-positive and HIV-negative patients attended at university hospitals in Cuiabá, MT, in the Midwestern region of Brazil. Methodology: Micromorphological features, chemotyping with canavanine-glycine-bromothymol blue (CGB) agar and genotyping by URA5-RFLP were used to identify the species. The antifungal drugs tested were amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole. Minimum inhibitory concentrations (MICs) were determined according to the CLSI methodology M27-A3. Results: Analysis of samples yelded C. neoformans AFLP1/VNI (17/27, 63.0%) and C. gattii AFLP6/VGII (10/27, 37.0%). The MICs ranges for the antifungal drugs were: amphotericin B (0.5-1 mg/L), fluconazole (1-16 mg/L), flucytosine (1-16 mg/L), itraconazole (0.25-0.12 mg/L) and voriconazole (0.06-0.5 mg/L). Isolates of C. neoformans AFLP1/VNI were predominant in patients with HIV/AIDS, and C. gattii VGII in HIV-negative patients. The genotypes identified were susceptible to the antifungal drugs tested. Conclusion: It is worth emphasizing that AFLP6/VGII is a predominant genotype affecting HIV-negative individuals in Cuiabá. These findings serve as a guide concerning the molecular epidemiology of C. neoformans and C. gattii in the State of Mato Grosso.

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Section: Discussionmentioning

confidence: 99%

Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil

Favalessa

Paula

Dutra

et al. 2014

J Infect Dev Ctries

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“…Recent epidemiological studies observed that isolates collected from different geographic regions have altered susceptibilities to fluconazole, as emerging resistance was documented among isolates from the Asia-Pa-cific, Africa/Middle East, and Latin America regions but not among isolates from Europe or North America (458). Furthermore, the molecular genotype of cryptococcal species influences fluconazole susceptibility, with genotype VGII of C. gattii and genotype VNI of C. neoformans displaying elevated fluconazole MICs compared to those of other genotypes within their respective species (102). Finally, it was also found that after initial treatment with fluconazole, relapses of cryptococcal meningitis tended to be associated with elevated levels of fluconazole resistance (55).…”

Section: Cryptococcus Neoformans Drug Resistance: the Azolesmentioning

confidence: 99%

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Shapiro

Robbins

Cowen

2011

Microbiol Mol Biol Rev

499

547

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SUMMARY Pathogenic fungi have become a leading cause of human mortality due to the increasing frequency of fungal infections in immunocompromised populations and the limited armamentarium of clinically useful antifungal drugs. Candida albicans , Cryptococcus neoformans , and Aspergillus fumigatus are the leading causes of opportunistic fungal infections. In these diverse pathogenic fungi, complex signal transduction cascades are critical for sensing environmental changes and mediating appropriate cellular responses. For C. albicans , several environmental cues regulate a morphogenetic switch from yeast to filamentous growth, a reversible transition important for virulence. Many of the signaling cascades regulating morphogenesis are also required for cells to adapt and survive the cellular stresses imposed by antifungal drugs. Many of these signaling networks are conserved in C. neoformans and A. fumigatus , which undergo distinct morphogenetic programs during specific phases of their life cycles. Furthermore, the key mechanisms of fungal drug resistance, including alterations of the drug target, overexpression of drug efflux transporters, and alteration of cellular stress responses, are conserved between these species. This review focuses on the circuitry regulating fungal morphogenesis and drug resistance and the impact of these pathways on virulence. Although the three human-pathogenic fungi highlighted in this review are those most frequently encountered in the clinic, they represent a minute fraction of fungal diversity. Exploration of the conservation and divergence of core signal transduction pathways across C. albicans , C. neoformans , and A. fumigatus provides a foundation for the study of a broader diversity of pathogenic fungi and a platform for the development of new therapeutic strategies for fungal disease.

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“…The results of a number of studies have suggested that differences in in vitro drug susceptibility are correlated with different Cryptococcus species and molecular types (19)(20)(21)(22)(23). MICs of all azoles, particularly fluconazole, appear to be higher for molecular type VGII isolates than for other C. gattii molecular types, primarily VGI, and C. neoformans (19,21,23).…”

mentioning

confidence: 97%

“…MICs of all azoles, particularly fluconazole, appear to be higher for molecular type VGII isolates than for other C. gattii molecular types, primarily VGI, and C. neoformans (19,21,23). There is also growing evidence that antifungal drug susceptibility may vary between geographical locations for the same molecular type (19,21,24).…”

mentioning

confidence: 98%

Antifungal Drug Susceptibility and Phylogenetic Diversity among Cryptococcus Isolates from Dogs and Cats in North America

et al. 2014

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f Molecular types of the Cryptococcus neoformans/Cryptococcus gattii species complex that infect dogs and cats differ regionally and with host species. Antifungal drug susceptibility can vary with molecular type, but the susceptibility of Cryptococcus isolates from dogs and cats is largely unknown. Cryptococcus isolates from 15 dogs and 27 cats were typed using URA5 restriction fragment length polymorphism analysis (RFLP), PCR fingerprinting, and multilocus sequence typing (MLST). Susceptibility was determined using a microdilution assay (Sensititre YeastOne; Trek Diagnostic Systems). MICs were compared among groups. The 42 isolates studied comprised molecular types VGI (7%), VGIIa (7%), VGIIb (5%), VGIIc (5%), VGIII (38%), VGIV (2%), VNI (33%), and VNII (2%), as determined by URA5 RFLP. The VGIV isolate was more closely related to VGIII according to MLST. All VGIII isolates were from cats. All sequence types identified from veterinary isolates clustered with isolates from humans. VGIII isolates showed considerable genetic diversity compared with other Cryptococcus molecular types and could be divided into two major subgroups. Compared with C. neoformans MICs, C. gattii MICs were lower for flucytosine, and VGIII MICs were lower for flucytosine and itraconazole. For all drugs except itraconazole, C. gattii isolates exhibited a wider range of MICs than C. neoformans. MICs varied with Cryptococcus species and molecular type in dogs and cats, and MICs of VGIII isolates were most variable and may reflect phylogenetic diversity in this group. Because sequence types of dogs and cats reflect those infecting humans, these observations may also have implications for treatment of human cryptococcosis.

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

Cited by 79 publications

References 47 publications

Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil

Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Antifungal Drug Susceptibility and Phylogenetic Diversity among Cryptococcus Isolates from Dogs and Cats in North America

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