High-dose methylprednisolone influences the physiology and virulence of Candida albicans ambiguously and enhances the candidacidal activity of the polyene antibiotic amphotericin B and the superoxide-generating agent menadione.
Although exposure of Candida albicans cells to high-dose (4 mM) methylprednisolone stimulated microbial growth, germination rate in serum and phospholipase release, it also promoted the recognition of C. albicans cells by polymorphonuclear leukocytes. Pretreatment of C. albicans cells with methylprednisolone did not result in any increase in the pathogenicity of the fungus in intraperitoneal and intravenous mouse assays. Therefore, the virulence of C. albicans is unlikely to increase in patients treated with comparably high-dose methylprednisolone on skin and mucosal membranes. Methylprednisolone treatments also increased the production of conjugated dienes and thiobarbituric acid-reactive substances, and the menadione sensitivity of C. albicans cells, which can be explained by a significant decrease in the specific activities of several antioxidant enzymes. The combination of methylprednisolone with oxidants, e.g. in topical applications, may be of clinical importance when the predisposition to candidiasis is high. Methylprednisolone treatments negatively affected membrane fluidity and decreased the antifungal effects of both the polyene antibiotic nystatin and the ergosterol biosynthesis inhibitor lovastatin, and also enhanced the deleterious effects of the polyene antimycotic amphotericin B on C. albicans cells. These corticosteroid-polyene drug interactions should be considered in the treatment of C. albicans infections in patients with prolonged topical application of corticosteroids.
Gyetvai
Agnes
A
Department of Microbiology and Biotechnology, Faculty of Science, University of Debrecen, Debrecen, Hungary.
Emri
Tamás
T
Fekete
Andrea
A
Varga
Zsuzsa
Z
Gazdag
Zoltán
Z
Pesti
Miklós
M
Belágyi
József
J
Emõdy
Levente
L
Pócsi
István
I
Lenkey
Béla
B
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology; D002463:Cell Membrane Permeability; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000494:pharmacology; D015227:Lipid Peroxidation; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress; D014774:Virulence; D024483:Vitamin K 3 / Q000008:administration & dosage / Q000494:pharmacology*; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology*
D000935:Antifungal Agents; D000975:Antioxidants; D005938:Glucocorticoids; D014815:Vitamins; D024483:Vitamin K 3; D000666:Amphotericin B; D008775:Methylprednisolone