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Synergy between Fluconazole and Ibuprofen by dvjorge ..... Candida & Dysbiosis Forum

Date:   8/17/2014 5:55:57 PM ( 7 years ago ago)
Hits:   4,118

There are several studies pointing to the synergism between Ibuprofen and Fluconazole, specially against resistant candida strains. Here is another one:

Reassessment of the in vitro synergistic effect of fluconazole with the non-steroidal anti-inflammatory agent ibuprofen against Candida albicans.

Arai R, Sugita T, Nishikawa A

Mycoses 2005 Jan; 48(1) :38-41.

We reassessed the in vitro synergistic effect of fluconazole with the non-steroidal anti-inflammatory agent ibuprofen against the pathogenic yeast Candida albicans. No synergistic effect of fluconazole combined with ibuprofen was seen against fluconazole-susceptible strains, but a remarkable effect was seen against fluconazole-resistant strains (FIX index: 0.02-0.03). Furthermore, vigorous growth of the microorganism, the so-called 'Eagle effect', was observed at concentrations higher than the minimal inhibitory concentrations of ibuprofen and fluconazole. Our results suggest that the combination of ibuprofen and fluconazole should prove useful for treating infection caused by fluconazole-resistant C. albicans.

This other is "in vivo" animal model :

Effective reversion of fluconazole resistance by ibuprofen in an animal model

S. Costa-de-Oliveira*, I. M Miranda, E. Ricardo, A. Silva-Dias, A. G Rodrigues, C. Pina-Vaz (Porto, PT)
Objectives: Ibuprofen was found to be an efficient reverter of in vitro fluconazole resistance due to overexpression of efflux pumps1,2; however its in vivo effect is still unproven.The aim of our study was to evaluate in an animal model the effect of ibuprofen associated to fluconazole in the treatment of an invasive infection by a resistant C. albicans isolate.
Methods: A C. albicans resistant (R) strain to fluconazole was obtained by subculturing with serial concentrations of fluconazole a susceptible strain (S) during 30 days. Minimal inhibitory concentrations (MIC) to fluconazole was determined in the presence of 100g/ml of ibuprofen (IBU), an efflux pump blocker1,2.
Comparative transcriptome analysis between the S and the induced resistant strain (R) incubated with and without ibuprofen (RI) was performed using C. albicans DNA microarrays from Agilent Technologies.
The in vivo study was carried out according to the murine candidiasis model. Female BALB/c mice were infected with 5x105 cells in 0.1 ml of sterile saline via the lateral tail vein with the S strain (three groups) or the R strain (three groups). Antifungal therapy was administered intraperitoneally with FLC or IBU or FLC+IBU on both groups 3 hours after microbial challenge and repeated once a day for a total of four days. The kidney fungal burden was determined.
Results: Ibuprofen decreased azole MIC values, the R phenotype changing to S. Microarray analysis identified 836 and 1517 with differential expression in R and RI strains, respectively. The R strain showed overexpression of CDR11, ERG251, CDR4 and the transcription factor UPC2. In the RI and in the S strains those genes were down regulated.
FLC showed to be effective only in the treatment of the infection by the S strain, reducing dramatically the fungal burden. Interestingly, in mice infected with the R strain but treated with FLC + IBU, a significant decrease in the fungal burden was observed. In the absence of FLC, IBU did not display antifungal activity per se.
Conclusions: The in vivo synergic effect between fluconazole and ibuprofen demonstrated herein may represent a hopeful future approach for a better management of antifungal resistance conferred by efflux pump overexpression.
1. Pina-Vaz, C., et al. J Antimicrob Chemother 2005, 4: 678-85
2. Ricardo, E., et al. FEMS Yeast Res 2009, 4: 618-25

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