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

Abstract

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.

Lipase-Responsive Amphotericin B Loaded PCL Nanoparticles for Antifungal Therapies

“…The MIC is defined as the lowest concentration inhibiting the microorganism’s growth [ 7 ]. The results show that AMB exhibited an MIC of 0.25 µg/mL ( Figure S2B ), which is consistent with published studies [ 42 , 43 ]. In comparison, the PCL-AMB NPs exhibited a MIC of 0.06 µg/mL ( Figure S2A ), which is significantly lower than that of the free drug.…”

Synthesis, characterisation, and solution behaviour of Ag(I) bis(phenanthroline-oxazine) complexes and the evaluation of their biological activity against the pathogenic yeast Candida albicans

“…The efficacy of antifungal agents is known to be influenced by media composition (Klepser et al 1997 ; Muller et al 2001 ). In one recent in vitro study, drug activity against central nervous system fungal pathogens, activity in sabouraud-dextrose broth differed markedly compared to cerebeospinal fluid media (al Jalali et al 2019 ). In another investigation, it was noted that growth, adhesion and biofilm formation of Candida species was profoundly affected by choice of media culture (Weerasekera et al 2016 ).…”

Preparation and In Vitro Evaluation of Alginate Microparticles Containing Amphotericin B for the Treatment of Candida Infections

“…Cells were exposed to two concentrations of AmB (0.5 μ g/mL or 4 μ g/mL) for 48 hours at 35°C and the viability ratio and CFU/mL were determined using the cell counting method and plate count method, respectively. These concentrations were chosen in accordance to clinical concentrations reported in the literature [ 50 , 51 ]. The cytotoxicity of blank MCPs at the corresponding concentration used for 0.5 μ g/mL and 4 μ g/mL was also evaluated.…”

“…The concentration of the cell suspension was determined using a hemocytometer and 5 × 10 3 cells were added to tubes containing different concentrations of AmB (0.5 μ g/mL or 4 μ g/mL). The concentrations of AmB used for this study were chosen in accordance with clinical concentrations reported in the literature [ 50 , 51 ]. The sterile test tubes were incubated for 48 hours at 35°C and 250 rpm.…”