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Epidemiologic cutoff values for triazole drugs in Cryptococcus gattii: correlation of molecular type and in vitro
Shawn R Lockhart1, Naureen Iqbal, Carol B Bolden
1Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. gyi2@cdc.gov
Abstract:
Cryptococcus gattii causes infection in tropical and subtropical regions worldwide but has garnered increased attention since its 1999 emergence in North America. C. gattii can be divided into 4 molecular types that may represent cryptic species. Recent evidence has shown that azole antifungal MIC values differ among these molecular types. We tested a large collection of C. gattii isolates for susceptibility to 4 azole drugs. We found that isolates of molecular type VGII have the highest geometric mean (GM) fluconazole MIC values (8.6 microg/mL), while isolates of molecular type VGI have the lowest (1.7 microg/mL). For fluconazole, itraconazole, and voriconazole GM MIC values, VGI < VGIII < VGIV < VGII. The GM MIC values for posaconazole were similarly represented across molecular types, with the exception that VGII < VGIII and VGIV. We used the MIC values to establish preliminary epidemiologic cutoff values for each azole and molecular type of C. gattii.
Insights
Cryptococcus gattii molecular types show varying susceptibility to azole antifungals. Type VGII strains exhibited the highest fluconazole resistance, while VGI strains were most susceptible.
Area of Science:
- Mycology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Cryptococcus gattii is an emerging fungal pathogen causing infections globally.
- This fungus is classified into four molecular types (VGI, VGII, VGIII, VGIV), potentially representing distinct species.
- Previous studies indicated differences in azole antifungal Minimum Inhibitory Concentrations (MICs) among these molecular types.
Purpose of the Study:
- To evaluate the susceptibility of a large collection of Cryptococcus gattii isolates to four azole antifungal drugs.
- To determine if azole antifungal MIC values differ significantly across the four molecular types of C. gattii.
Main Methods:
- Testing Cryptococcus gattii isolates for susceptibility to four azole antifungal agents.
- Calculating geometric mean (GM) MIC values for each azole drug and molecular type.
- Establishing preliminary epidemiologic cutoff values based on MIC data.
Main Results:
- Isolates of molecular type VGII displayed the highest GM fluconazole MIC (8.6 microg/mL), whereas VGI isolates had the lowest (1.7 microg/mL).
- The order of increasing GM MIC values for fluconazole, itraconazole, and voriconazole was VGI < VGIII < VGIV < VGII.
- Posaconazole MIC values showed a similar trend, except VGII isolates had lower MICs than VGIII and VGIV.
Conclusions:
- Significant variations in azole antifungal susceptibility exist among Cryptococcus gattii molecular types.
- Molecular type VGII demonstrates higher resistance to fluconazole, itraconazole, and voriconazole compared to other types.
- The findings support the establishment of molecular type-specific epidemiologic cutoff values for azoles in C. gattii.
