Related Experiment Video
Updated: Jul 6, 2026
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Posaconazole against Candida glabrata isolates with various susceptibilities to fluconazole
Elisabetta Spreghini1, Carmelo Massimo Maida, Serena Tomassetti
1Istituto di Malattie Infettive e Medicina Pubblica, Università Politecnica delle Marche, Ancona, Italy.
Abstract:
We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of Candida glabrata with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 microg/ml). POS MICs ranged from < or =0.03 to 0.5 microg/ml; AMB MICs ranged from 0.25 to 2.0 microg/ml, while CAS MICs ranged from 0.03 to 0.25 microg/ml. When FLC MICs increased, so did POS MICs, although we did not observe any isolate with a POS MIC greater than 0.5 mug/ml. Time-kill experiments showed that POS, FLC, and CAS were fungistatic against all isolates, while AMB at eight times the MIC was fungicidal against three out of four isolates of C. glabrata tested. Then, we investigated the activity of POS in an experimental model of disseminated candidiasis using three different isolates of C. glabrata: one susceptible to FLC (S; FLC MICs ranging from 1.0 to 4.0 microg/ml; POS MIC of < or =0.03 microg/ml), one susceptible in a dose-dependent manner (SDD; FLC MICs ranging from 32 to 64 microg/ml; POS MICs ranging from 0.125 to 0.25 microg/ml), and another one resistant to FLC (R; FLC MIC of >64 microg/ml; POS MIC of 0.5 microg/ml). FLC significantly reduced the kidney burden of mice infected with the S strain (P = 0.0070) but not of those infected with the S-DD and R strains. POS was significantly effective against all three isolates at reducing the kidney fungal burden with respect to the controls (P ranging from 0.0003 to 0.029). In conclusion, our data suggest that POS may be a useful option in the management of systemic infections caused by C. glabrata. Additionally, the new triazole may be a therapeutic option in those cases where an FLC-resistant isolate is found to retain a relatively low POS MIC.
Insights
Posaconazole (POS) demonstrates significant antifungal activity against Candida glabrata, including fluconazole (FLC)-resistant strains. In vivo studies show POS effectively reduces fungal burden in disseminated candidiasis models, suggesting its utility in treating resistant infections.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Candida glabrata exhibits increasing resistance to fluconazole (FLC), necessitating alternative antifungal therapies.
- Posaconazole (POS) is a broad-spectrum triazole antifungal agent.
- Understanding the efficacy of POS against diverse FLC susceptibility profiles of C. glabrata is crucial.
Purpose of the Study:
- To evaluate the in vitro and in vivo antifungal activities of POS against clinical isolates of Candida glabrata.
- To compare the efficacy of POS with other antifungal agents like FLC, amphotericin B (AMB), and caspofungin (CAS).
- To assess the therapeutic potential of POS in experimental disseminated candidiasis caused by FLC-resistant C. glabrata.
Main Methods:
- In vitro susceptibility testing (MIC determination) of POS, FLC, AMB, and CAS against four C. glabrata isolates.
- Time-kill kinetic experiments to determine fungistatic or fungicidal activity.
- Experimental model of disseminated candidiasis in mice infected with three C. glabrata isolates (susceptible, dose-dependent, and resistant to FLC).
- Quantification of fungal burden in mouse kidneys to assess treatment efficacy.
Main Results:
- POS exhibited potent in vitro activity against all C. glabrata isolates, with MICs ranging from <=0.03 to 0.5 microg/ml.
- While FLC efficacy decreased with increasing FLC MICs, POS maintained activity.
- In vivo, POS significantly reduced kidney fungal burden in mice infected with FLC-susceptible, dose-dependent, and resistant C. glabrata strains.
- FLC was effective only against the FLC-susceptible strain in the mouse model.
Conclusions:
- Posaconazole demonstrates significant in vitro and in vivo efficacy against Candida glabrata, including strains resistant to fluconazole.
- POS represents a promising therapeutic option for managing systemic C. glabrata infections, particularly those caused by FLC-resistant isolates.
- The study supports the use of POS when FLC-resistant C. glabrata strains with low POS MICs are identified.
Related Concept Videos
01:20Candidiasis
01:15Antifungal Agents
01:27Cryptococcal Meningitis