Potent synergism of the combination of fluconazole and cyclosporine in Candida albicans.

Détails

ID Serval
serval:BIB_0C5FB7E5E8F7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Potent synergism of the combination of fluconazole and cyclosporine in Candida albicans.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur(s)
Marchetti O., Moreillon P., Glauser M.P., Bille J., Sanglard D.
ISSN
0066-4804 (Print)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
2000
Volume
44
Numéro
9
Pages
2373-2381
Langue
anglais
Résumé
Several types of drugs currently used in clinical practice were screened in vitro for their potentiation of the antifungal effect of the fungistatic agent fluconazole (FLC) on Candida albicans. These drugs included inhibitors of multidrug efflux transporters, antimicrobial agents, antifungal agents, and membrane-active compounds with no antimicrobial activity, such as antiarrhythmic agents, proton pump inhibitors, and platelet aggregation inhibitors. Among the drugs tested in an agar disk diffusion assay, cyclosporine (Cy), which had no intrinsic antifungal activity, showed a potent antifungal effect in combination with FLC. In a checkerboard microtiter plate format, however, it was observed that the MIC of FLC, as classically defined by the NCCLS recommendations, was unchanged when FLC and Cy were combined. Nevertheless, if a different reading endpoint corresponding to the minimal fungicidal concentration needed to decrease viable counts by at least 3 logs in comparison to the growth control was chosen, the combination was synergistic (fractional inhibitory concentration index of <1). This endpoint fitted to the definition of MIC-0 (optically clear wells) and reflected the absence of the trailing effect, which is the result of a residual growth at FLC concentrations greater than the MIC. The MIC-0 values of FLC and Cy tested alone in C. albicans were >32 and >10 microg/ml, respectively, and decreased to 0.5 and 0.625 microg/ml when the two drugs were combined. The combination of 0.625 microg of Cy per ml with supra-MICs of FLC resulted in a potent antifungal effect in time-kill curve experiments. This effect was fungicidal or fungistatic, depending on the C. albicans strain used. Since the Cy concentration effective in vitro is achievable in vivo, the combination of this agent with FLC represents an attractive perspective for the development of new management strategies for candidiasis.
Mots-clé
Agar/metabolism, Antifungal Agents/pharmacology, Candida albicans/drug effects, Culture Media, Cyclosporine/pharmacology, Drug Synergism, Fluconazole/pharmacology, Humans, Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:58
Dernière modification de la notice
20/08/2019 13:33
Données d'usage