Propofol lipidic infusion promotes resistance to antifungals by reducing drug input into the fungal cell

Abstract

Background: The administration of non-antifungal drugs during patient hospitalization might be responsible for discrepancies between in vitro and in vivo susceptibility to antifungals. Propofol is often administered to intensive care units as a sedative.

In Vivo and In Vitro Acquisition of Resistance to Voriconazole by Candida krusei

“…Thus, we were confronted with a case of resistance to VRC acquired in vivo. It should be stressed that the bioavailability and concentrations of the bioactive drug in vivo are highly variable due to several factors, such as different infection sites, concomitant therapies, and the status of the host immune system (24). The C. krusei clinical isolates might have been in contact with subinhibitory concentrations of the antifungal agent for a long period, which were not sufficient to eliminate the organism but were enough to stimulate stress adaptation mechanisms leading to resistance.…”

Candida albicans Antifungal Resistance and Tolerance in Bloodstream Infections: The Triad Yeast-Host-Antifungal

“…Notably, correlation between in vitro susceptibility and treatment success is not always straightforward [18]. The in vivo conditions are significantly different of in vitro, in particular the microorganisms are often under the effect of both antifungal and non-antifungal drugs, as is the typical case of critical care patients [19][20][21]. Besides, C. albicans has particular traits and tricks that makes this yeast a true challenge for clinicians and researchers.…”

A flow cytometry method for testing the susceptibility of Cryptococcus spp. to amphotericin B

“…In one study, the authors used PI to obtain MICs in 3.5 h, which showed good agreement between CLSI and FC methods. 9 In another study, the authors observed that the agreement between CLSI and FC methods ranged from 96 to 99% for Candida albicans. 5 Another study determined the feasibility of direct susceptibility testing of Candida species to fluconazole by a rapid flow cytometric method; a total of 50 Candida strains were identified as positive by the blood culture.…”

“…1,7,8,19,23 FC methods have been advocated because they are more reliable for studies of susceptibility to AMB. 9,[22][23][24][25] The scattered light detected by FC gives intrinsic cellular information, such as size and complexity, but the use of fluorochromes allows for the evaluation of a wide range of physiological or morphological parameters, such as the membrane integrity, pH, membrane potential and viability. 19 The results of the current study suggest that C. neoformans susceptibility to AMB can be tested by FC after treating the yeast with that drug for 4 h. AMB induces primary lesions in the cell membrane, and PI can enter cells after a short incubation period.…”

“…This may be explained by the significant damage that occurs at the cell membrane, which allows PI to access the target. According to previous studies in Candida, the activity of echinocandin could be studied in cells exposed to fungicidal drugs that cause direct membrane damage with PI after treatment for 3 h. 9 AMB has a relatively large structure and acts on the cell membrane of yeast in a way that likely interferes with the uptake of most molecules. Thus, the uptake of PI by AMB-treated cells is significantly reduced compared to untreated cells because the cells become progressively more impermeable in the presence of AMB.…”