In vitro activity of amphotericin B and fluconazole in combination with atorvastatin and moxifloxacin against Candida albicans

S. Kustimur, S.J. Fadil, S. Kustimur, A. Kalkanci

Author address: 

Gazi University, ANKARA, Turkey

Abstract: 

Objectives: Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Antifungal effect of non-antifungal compounds such as quinolones and statins has been reported previously. The aim of this study was to investigate the in vitro interaction of moxifloxacin and atorvastatin with fluconazole and amphotericin B against ten isolates of Candida albicans strains which were resistant to amphotericin B. Methods: Drug interaction model was used to analyze the in vitro interaction of antifungal drugs against various C.albicans strains using the microdilution checkerboard method. Drug interaction was classified as synergistic, additive, indifferent or antagonistic on the basis of the fractional inhibitory concentration (FIC) index. The FIC index is the sum of the FICs for each drug; the FIC is defined as the MIC of each drug when used in combination divided by the MIC of the drug when used alone. The final concentrations of the antifungal agents ranged from 0.25 to 128 ug/ml for fluconazole, 0.03 to 16 ug/ml for amphotericin B. The final concentrations of the non-antifungal drugs ranged from 1.25 to 6.25 ug/ml for atorvastatin, 3.5 to 1750 ug/ml for moxifloxacin. MIC endpoints were determined as the first concentration of the antifungal agent, either alone or in combination, at which the turbidity in the well was less than 50% of that in the control well. Results: Synergistic interactions were observed between amphotericin B and atorvastatin against 6 of 10 C. albicans strains. Additive interaction was found in resting 4 strains. Synergy also was found between amphotericin B and moxifloxacin against 3 of 10 C.albicans strains. Additive interaction was found in resting 7 strains. Some antagonistic interactions were observed between atorvastatin and fluconazole against 2 of C. albicans strains. Synergistic interaction was observed between these two drugs against 2 of the strains, while additive effect was found against resting 6 strains. Additive effect was observed between fluconazole and moxifloxacin against 6 of C.albicans strains, tested. Synergy also was found between fluconazole and moxifloxacin against 4 of 10 C.albicans strains. In general, atorvastatin enhanced the activity of antifungal agents more than moxifloxacin against C. albicans . Conclusion: In this study we analyzed the in vitro interactions between antifungal drugs with non-antifungal drugs. Four different combinations, were used in this study to investigate the interactions between amphotericin B and fluconazole each of moxifloxacin and atorvastatin. For the majority of strains, the combination tests showed additive activity. Significant in vitro interactions were found between antifungal agents and atorvastatin or moxifloxacin against C.albicans . This particular analysis can provide a useful tool for the assessment of interactions between antifungal agents and non-antifungal compounds, which alone do not elicit any significant antifungal activity, and possibly of interactions against resistant isolates. Synergy would be the most suitable for routine empirical clinical use, based on clinically achievable drug concentrations with commonly used dosage regimens.
2009

abstract No: 

P010

Full conference title: 

4th Trends in Medical Mycology
    • TIMM 4th (2012)