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Updated: Dec 28, 2025
A Soluble Tetrazolium-Based Reduction Assay to Evaluate the Effect of Antibodies on Candida tropicalis Biofilms
Published on: September 16, 2022
In vitro activity of voriconazole and amphotericin B against Candida albicans, Candida krusei, and Cryptococcus
Valentin Al Jalali1, Robert Sauermann1, Sabine Eberl1
1Department of Clinical Pharmacology, Vienna University Hospital, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Purpose:
Fungal central nervous system (CNS) infections show a high mortality rate and only a few antifungal agents are available to treat these infections. We hypothesize that the different biochemical properties of human cerebrospinal fluid (CSF) compared to the standard growth medium lead to the altered activity of antifungal agents in CSF. We investigated the in vitro activity of two of these agents, i.e., amphotericin B (AmB) and voriconazole (VOR), against three different fungi in CSF in comparison to sabouraud-dextrose broth (SDB).
Methods:
CSF samples from patients who did not receive any antibiotics were collected. Time-kill curves were performed in CSF and SDB using static antibiotic concentrations of AmB and VOR against ATCC strains of Candida albicans, Candida krusei, and Cryptococcus neoformans.
Results:
In our experiments, both AmB and VOR showed superior activity in SDB compared to CSF. Nevertheless, AmB achieved fungicidal activity in CSF after 24 h against all test strains. Voriconazole only achieved fungistatic activity against C. albicans and C. neoformans in CSF.
Conclusions:
In summary, our data demonstrate that growth of fungal pathogens but even more importantly activity of antifungal agents against Candida and Cryptococcus species can differ significantly in CSF compared to the standard growth medium. Both findings should be taken into consideration when applying PK/PD simulations to fungal infections of the CNS.
Insights
Antifungal drug activity differs in cerebrospinal fluid (CSF) versus standard media. Amphotericin B (AmB) was fungicidal in CSF, while voriconazole (VOR) was only fungistatic against certain fungi, impacting CNS infection treatment.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Fungal central nervous system (CNS) infections are life-threatening with limited treatment options.
- Cerebrospinal fluid (CSF) biochemical properties may alter antifungal drug efficacy compared to standard growth media.
Purpose of the Study:
- To investigate the in vitro activity of amphotericin B (AmB) and voriconazole (VOR) against fungal pathogens in human CSF.
- To compare antifungal activity in CSF versus sabouraud-dextrose broth (SDB).
Main Methods:
- Time-kill curves were performed using static concentrations of AmB and VOR.
- Tested fungal strains included Candida albicans, Candida krusei, and Cryptococcus neoformans.
- Experiments were conducted in both human CSF and SDB.
Main Results:
- Both AmB and VOR demonstrated reduced activity in CSF compared to SDB.
- AmB achieved fungicidal activity against all tested fungi in CSF within 24 hours.
- VOR exhibited only fungistatic activity against Candida albicans and Cryptococcus neoformans in CSF.
Conclusions:
- Fungal pathogen growth and antifungal agent activity vary significantly between CSF and standard media.
- These differences are critical for pharmacokinetic/pharmacodynamic (PK/PD) simulations in CNS fungal infections.
