Epidemiologic cutoff values for triazole drugs in Cryptococcus gattii: correlation of molecular type and in vitro susceptibility

Lockhart, Shawn R.; Iqbal, Naureen; Bolden, Carol B.; DeBess, Emilio; Marsden-Haug, Nicola; Worhle, Ron; Thakur, Rameshwari; Harris, Julie

doi:10.1016/j.diagmicrobio.2012.02.018

Cited by 57 publications

(55 citation statements)

References 40 publications

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“…In general, for any of the tested antifungal drugs, C. gattii VGIII (48), and VGII isolates had higher MICs than the isolates of all other C. gattii molecular types (19). VGII isolates in this study appeared to have higher MICs for most antifungal drugs than the isolates of all other C. gattii molecular types, although the relatively low number of VGII isolates in this study limited our ability to document significance and to compare our results with those of other investigators.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

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confidence: 96%

“…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).…”

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confidence: 98%

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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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Section: Discussionmentioning

confidence: 99%

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confidence: 96%

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

et al. 2014

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“…Subsequently, MICs of fluconazole were noted to be increased among isolates from C. gattii VGII case clusters (see discussion below). This prompted an ongoing large-scale study of MIC CBPs and of epidemiological MIC cutoff values (ECVs) based on MIC distributions of wildtype strains (357)(358)(359) ). ECVs are useful adjuncts for identifying isolates with acquired or intrinsic resistance or those that need further study.…”

Section: Epidemiological Cutoff Values For C Gattiimentioning

confidence: 99%

Cryptococcus gattii Infections

2014

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SUMMARY Understanding of the taxonomy and phylogeny of Cryptococcus gattii has been advanced by modern molecular techniques. C. gattii probably diverged from Cryptococcus neoformans between 16 million and 160 million years ago, depending on the dating methods applied, and maintains diversity by recombining in nature. South America is the likely source of the virulent C. gattii VGII molecular types that have emerged in North America. C. gattii shares major virulence determinants with C. neoformans , although genomic and transcriptomic studies revealed that despite similar genomes, the VGIIa and VGIIb subtypes employ very different transcriptional circuits and manifest differences in virulence phenotypes. Preliminary evidence suggests that C. gattii VGII causes severe lung disease and death without dissemination, whereas C. neoformans disseminates readily to the central nervous system (CNS) and causes death from meningoencephalitis. Overall, currently available data indicate that the C. gattii VGI, VGII, and VGIII molecular types more commonly affect nonimmunocompromised hosts, in contrast to VGIV. New, rapid, cheap diagnostic tests and imaging modalities are assisting early diagnosis and enabling better outcomes of cerebral cryptococcosis. Complications of CNS infection include increased intracranial pressure, severe neurological sequelae, and development of immune reconstitution syndrome, although the mortality rate is low. C. gattii VGII isolates may exhibit higher fluconazole MICs than other genotypes. Optimal therapeutic regimens are yet to be determined; in most cases, initial therapy with amphotericin B and 5-flucytosine is recommended.

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“…AFLP6) has been implicated in the PNW outbreak, and VGIIa and VGIIb are considered, respectively, the major and minor outbreak types, along with the emergence of a novel genotype, VGIIc (14). C. gattii clinical and environmental isolates demonstrate various susceptibilities to several classes of antifungals (15,16), with a high proportion of isolates from the PNW showing lower susceptibilities to fluconazole (17).…”

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Isavuconazole Activity against Aspergillus lentulus, Neosartorya udagawae, and Cryptococcus gattii, Emerging Fungal Pathogens with Reduced Azole Susceptibility

Datta¹,

Rhee²,

Byrnes³

et al. 2013

J Clin Microbiol

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Epidemiologic cutoff values for triazole drugs in Cryptococcus gattii: correlation of molecular type and in vitro susceptibility

Cited by 57 publications

References 40 publications

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

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

Cryptococcus gattii Infections

Isavuconazole Activity against Aspergillus lentulus, Neosartorya udagawae, and Cryptococcus gattii, Emerging Fungal Pathogens with Reduced Azole Susceptibility

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