In vitro activity of voriconazole and amphotericin B against Candida albicans, Candida krusei, and Cryptococcus neoformans in human cerebrospinal fluid

• Published in: Infection Vol. 47; no. 4; pp. 565 - 570
• Main Authors: al Jalali, Valentin, Sauermann, Robert, Eberl, Sabine, Zeitlinger, Markus
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2019; Springer Nature B.V
• Subjects: Amphotericin B; Antibiotics; Antifungal agents; Candida albicans; Candida krusei; Central nervous system; Cerebrospinal fluid; Cryptococcus neoformans; Dextrose; Family Medicine; Fungal infections; Fungi; Fungicidal activity; Fungicides; General Practice; Infections; Infectious Diseases; Internal Medicine; Medicine; Medicine & Public Health; Original Paper; Pathogens; Sampling methods; Voriconazole; Yeast; Antifungal activity; Meningitis; PK/PD; Fungal infections; Antifungal agents
• ISSN: 0300-8126; 1439-0973
• DOI: 10.1007/s15010-019-01275-9

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.