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

Costa-de-Oliveira S, Araujo R, Silva-Dias A, Pina-Vaz C, Rodrigues AG - BMC Microbiol. (2008)

Bottom Line: A decrease of the intensity of fluorescence of Candida cells was systematically observed, as well as a significant reduced intracellular uptake of [3H] itraconazole in cells treated with propofol infusion, even after the blockade of efflux pumps.The results obtained when testing with the lipid vehicle were similar.This effect seems to be related to the reduced access and/or permeabilization to fungal cells by antifungals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal. sqco@med.up.pt

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. The purpose of this study was to evaluate the effect of propofol lipidic infusion upon the growth and susceptibility profile of pathogenic fungi. Candida and Aspergillus were studied regarding the ability to grow and its susceptibility profile to antifungals in the presence of propofol infusion (Fresenius(R)) (1.25, 2.5 and 5 mg.ml-1) and its lipidic vehicle. The intensity of fluorescence after staining with FUN1, in the presence and absence of propofol infusion, was determined by flow cytometry. Radioactivity assays were also performed in order to quantify the input of [3H]- itraconazole into the fungal cell in the presence of propofol. Assays were repeated after addition of sodium azide, in order to block efflux pumps.

Results: Propofol infusion promoted budding of Candida and the germination of Aspergillus, latter forming a lipid layer around the hypha. An increase of minimal fungicidal concentrations regarding both Candida and Aspergillus strains was found for all antifungals when incubated simultaneously with propofol infusion. A decrease of the intensity of fluorescence of Candida cells was systematically observed, as well as a significant reduced intracellular uptake of [3H] itraconazole in cells treated with propofol infusion, even after the blockade of efflux pumps. The results obtained when testing with the lipid vehicle were similar.

Conclusion: Propofol infusion, due to its lipidic vehicle, increased the fungal germination and promoted resistance to antifungals. This effect seems to be related to the reduced access and/or permeabilization to fungal cells by antifungals.

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Related in: MedlinePlus

Representative example of Aspergillus fumigatus, after 24 hours of incubation: a. non-treated cells; b. cells treated with 5 mg.ml-1 of propofol infusion; c. cells treated with 5 mg.ml-1 of propofol infusion and washed thrice in sterilized water. (h hypha; p1 lipidic layer around hypha; p2 lipidic drops).
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Figure 1: Representative example of Aspergillus fumigatus, after 24 hours of incubation: a. non-treated cells; b. cells treated with 5 mg.ml-1 of propofol infusion; c. cells treated with 5 mg.ml-1 of propofol infusion and washed thrice in sterilized water. (h hypha; p1 lipidic layer around hypha; p2 lipidic drops).

Mentions: In Candida strains, budding and germ tube formation were similar in presence of all tested concentrations of propofol infusion. In non-albicans strains, the incubation with 5 μg.ml-1 of propofol infusion resulted in a significant increased of cells with buds when comparing to control (71.5% ± 7.46 versus 26.6% ± 4.15, C. parapsilosis n = 5 as a representative example) (p < 0.001). Conversely, a significant reduction of germ tube formation was observed in C. albicans strains comparing with non-treated yeasts (17.3% ± 6.29, versus 76.2% ± 8.69, n = 5) (p < 0.001). Aspergillus conidia germinated in RPMI 1640 culture medium after 4 to 6 hours, the hyphal form being obtained following 10 to 12 hours. Propofol infusion supported the germination of all Aspergillus strains, showing similar values to those obtained in plain RPMI 1640 medium. A significantly higher percentage of germination of A. fumigatus conidia was found in PBS plus propofol and plain propofol infusion in comparison with plain PBS (21% ± 3.6 versus 6% ± 1.6, n = 5) (p = 0.047) following 6 hours at 37°C. Longer incubation periods of conidia with propofol infusion showed lipidic drops or a lipidic layer around the hypha, in all assays and with all strains, which remained present following several washings steps (Figure 1).


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

Costa-de-Oliveira S, Araujo R, Silva-Dias A, Pina-Vaz C, Rodrigues AG - BMC Microbiol. (2008)

Representative example of Aspergillus fumigatus, after 24 hours of incubation: a. non-treated cells; b. cells treated with 5 mg.ml-1 of propofol infusion; c. cells treated with 5 mg.ml-1 of propofol infusion and washed thrice in sterilized water. (h hypha; p1 lipidic layer around hypha; p2 lipidic drops).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2258299&req=5

Figure 1: Representative example of Aspergillus fumigatus, after 24 hours of incubation: a. non-treated cells; b. cells treated with 5 mg.ml-1 of propofol infusion; c. cells treated with 5 mg.ml-1 of propofol infusion and washed thrice in sterilized water. (h hypha; p1 lipidic layer around hypha; p2 lipidic drops).
Mentions: In Candida strains, budding and germ tube formation were similar in presence of all tested concentrations of propofol infusion. In non-albicans strains, the incubation with 5 μg.ml-1 of propofol infusion resulted in a significant increased of cells with buds when comparing to control (71.5% ± 7.46 versus 26.6% ± 4.15, C. parapsilosis n = 5 as a representative example) (p < 0.001). Conversely, a significant reduction of germ tube formation was observed in C. albicans strains comparing with non-treated yeasts (17.3% ± 6.29, versus 76.2% ± 8.69, n = 5) (p < 0.001). Aspergillus conidia germinated in RPMI 1640 culture medium after 4 to 6 hours, the hyphal form being obtained following 10 to 12 hours. Propofol infusion supported the germination of all Aspergillus strains, showing similar values to those obtained in plain RPMI 1640 medium. A significantly higher percentage of germination of A. fumigatus conidia was found in PBS plus propofol and plain propofol infusion in comparison with plain PBS (21% ± 3.6 versus 6% ± 1.6, n = 5) (p = 0.047) following 6 hours at 37°C. Longer incubation periods of conidia with propofol infusion showed lipidic drops or a lipidic layer around the hypha, in all assays and with all strains, which remained present following several washings steps (Figure 1).

Bottom Line: A decrease of the intensity of fluorescence of Candida cells was systematically observed, as well as a significant reduced intracellular uptake of [3H] itraconazole in cells treated with propofol infusion, even after the blockade of efflux pumps.The results obtained when testing with the lipid vehicle were similar.This effect seems to be related to the reduced access and/or permeabilization to fungal cells by antifungals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal. sqco@med.up.pt

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. The purpose of this study was to evaluate the effect of propofol lipidic infusion upon the growth and susceptibility profile of pathogenic fungi. Candida and Aspergillus were studied regarding the ability to grow and its susceptibility profile to antifungals in the presence of propofol infusion (Fresenius(R)) (1.25, 2.5 and 5 mg.ml-1) and its lipidic vehicle. The intensity of fluorescence after staining with FUN1, in the presence and absence of propofol infusion, was determined by flow cytometry. Radioactivity assays were also performed in order to quantify the input of [3H]- itraconazole into the fungal cell in the presence of propofol. Assays were repeated after addition of sodium azide, in order to block efflux pumps.

Results: Propofol infusion promoted budding of Candida and the germination of Aspergillus, latter forming a lipid layer around the hypha. An increase of minimal fungicidal concentrations regarding both Candida and Aspergillus strains was found for all antifungals when incubated simultaneously with propofol infusion. A decrease of the intensity of fluorescence of Candida cells was systematically observed, as well as a significant reduced intracellular uptake of [3H] itraconazole in cells treated with propofol infusion, even after the blockade of efflux pumps. The results obtained when testing with the lipid vehicle were similar.

Conclusion: Propofol infusion, due to its lipidic vehicle, increased the fungal germination and promoted resistance to antifungals. This effect seems to be related to the reduced access and/or permeabilization to fungal cells by antifungals.

Show MeSH
Related in: MedlinePlus