Voriconazole-induced inhibition of the fungicidal activity of amphotericin B in Candida strains with reduced susceptibility to voriconazole: an Effect Not Predicted by the MIC Value Alone
2011 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 55, no 4, 1629-1637 p.Article in journal (Refereed) Published
An antagonistic effect of voriconazole on the fungicidal activity of sequential doses of amphotericin B has previously been demonstrated in Candida albicans strains susceptible to voriconazole. Because treatment failure and the need to switch to other antifungals are expected to occur more often in infections that are caused by resistant strains, it was of interest to study whether the antagonistic effect was still seen in Candida strains with reduced susceptibility to voriconazole. With the hypothesis that antagonism will not occur in voriconazole resistant strains, C. albicans strains with characterized mechanisms of resistance against voriconazole, as well as C. glabrata and C. krusei strains with differences in degree of susceptibility to voriconazole were exposed to voriconazole and amphotericin B alone, simultaneously or sequentially in an in vitro kinetic model. Amphotericin B administered alone or simultaneously with voriconazole resulted in fungicidal activity. When amphotericin B was administered after voriconazole, its activity was reduced in median 61% (range 9-94%). Voriconazole-dependent inhibition of amphotericin B activity differed significantly among the strains but was not correlated with the MIC values (correlation coefficient -0.19; P=0.65). Inhibition was found in C. albicans strains with increases in CDR1 and CDR2 expression but not in the strain with an increase in MDR1 expression. In summary, decreased susceptibility to voriconazole does not abolish voriconazole-dependent inhibition of the fungicidal activity of amphotericin B in voriconazole resistant Candida strains. The degree of interaction could not be predicted by the MIC value alone.
Place, publisher, year, edition, pages
2011. Vol. 55, no 4, 1629-1637 p.
amphotericin B, Candida, interaction, pharmacodynamics, voriconazole
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-134876DOI: 10.1128/AAC.00791-10ISI: 000288594600039PubMedID: 21282443OAI: oai:DiVA.org:uu-134876DiVA: diva2:374002