Synergistic Combination of Amphotericin B and Antiseptic Miramistin May Be Effective in the Fight Against Drug-Resistant Isolates of Candida Fungi

Abstract

Creation of synergistic combinations of antifungal and antiseptic agents can be considered as one of the promising strategies for reducing the spread of drug resistance in pathogenic fungi.Aim. The aim of this work was to study the synergistic antifungal activity of amphotericin B (AMB) and antiseptic miramistin (MST) in their combined use to fight against drug-resistant Candida isolates. Material and methods. One AMB-resistant C.albicans strain (MIC 3.1 µg/ml), sensitive to MST, two isolates of C.albicans with different level of resistance to MST and AMB (MIC 1.6–6.3 µg/ml), and one MST-resistant C.lusitaniae isolate susceptible to AMB (MIC 0.4 µg/ml) were studied. Isolates’ susceptibility to AMB and MST alone was determined by broth microdilution method and time–kill assay, respectively. Individual anti-candida activity of test combinations of 0.001% MST with AMB in 10 or 50 µg/ml concentrations was studied using quantitative time–kill assay.Results. A significant decrease in the growth of all the isolates treated with both test combinations of MST and AMB in comparison with individual medication treatment was observed at each time interval studied (15–60 minutes). As part of the combination, MST exhibited significant synergy with AMB in sublethal concentration of 10 µg/ml against all the isolates. Treatment of the fungi with a combination of MST with AMB in 50 µg/ml concentration caused complete inactivation of all the isolates after 30 minutes. Under these conditions, AMB exhibited separate antifungal activity.Conclusion. These findings suggest the possible effective use of miramistin in combination with amphotericin B against multi-drug resistant isolates of the genus Candida.

Keywords

• candida spp.
• drug resistance
• antiseptic miramistin
• synergy
• amphotericin b