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In vitro interactions of micafungin with amphotericin B against clinical isolates of Candida spp.

ABSTRACT: The in vitro activity of amphotericin B in combination with micafungin was evaluated against 115 isolates representing seven species of Candida. Overall, the percentages of synergistic interactions were 50% and 20% when the MIC-2 (lowest drug concentration to cause a prominent reduction in growth) and MIC-0 (lowest drug concentration to cause 100% growth inhibition) end point criteria, respectively, were used. Antagonism was not observed. Some of the interactions were confirmed by time-kill assays.

SUBMITTER: Serena C

PROVIDER: S-EPMC2292525 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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In vitro interactions of micafungin with amphotericin B against clinical isolates of Candida spp.

Serena Carolina C Mariné Marçal M Quindós Guillermo G Carrillo Alfonso J AJ Cano J F JF Pastor F Javier FJ Guarro Josep J

Antimicrobial agents and chemotherapy 20080128 4

The in vitro activity of amphotericin B in combination with micafungin was evaluated against 115 isolates representing seven species of Candida. Overall, the percentages of synergistic interactions were 50% and 20% when the MIC-2 (lowest drug concentration to cause a prominent reduction in growth) and MIC-0 (lowest drug concentration to cause 100% growth inhibition) end point criteria, respectively, were used. Antagonism was not observed. Some of the interactions were confirmed by time-kill assa ...[more]

PMID: 18227181

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Project description:The direct or indirect interactions that antifungals have with the host immune response may play a significant role in defining their activity in vivo. However, the impact that acquired antifungal resistance has on the immunopharmacologic activity of antifungals is not well described. We assessed the immunopharmacologic activity of caspofungin, micafungin, and voriconazole among isolates of Candida glabrata with or without FKS-mediated echinocandin resistance. Clinical bloodstream isolates of C. glabrata from patients who did (n = 5) or did not (n = 3) develop persistent candidemia and who did (n = 2) or did not (n = 11) harbor FKS gene mutations were included. A cell-based assay was used to compare differences in macrophage activation among isolates when grown in the presence or absence of subinhibitory concentrations of caspofungin, micafungin, or voriconazole. In the absence of antifungals, macrophage activation was significantly lower for index C. glabrata isolates obtained from persistent candidemia patients than for those from nonpersistent patients (33% versus 79% increase over negative controls, respectively; P < 0.01). Growth of isolates possessing wild-type FKS genes in subinhibitory concentrations of micafungin or caspofungin, but not voriconazole, significantly increased macrophage inflammatory responses compared to untreated controls (1.25- to 2.75-fold increase, P < 0.01). For isolates harboring the FKS2 hot spot 1 (HS1) S663P mutation, however, a significant increase was observed only with micafungin treatment (1.75-fold increase versus negative control, P < 0.01). Macrophage activation correlated with the level of unmasking of ?-glucan in the cell wall. The diminished macrophage inflammatory response to isolates that caused persistent candidemia and differential immunopharmacologic activity of echinocandins among FKS mutants suggest that certain strains of C. glabrata may have a higher propensity for immunoevasion and development of antifungal resistance during treatment.

Dataset Information

In vitro interactions of micafungin with amphotericin B against clinical isolates of Candida spp.

Publications

In vitro interactions of micafungin with amphotericin B against clinical isolates of Candida spp.

Similar Datasets

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