DEVELOPMENT OF RESISTANCE TO A DERIVATIVE OF THE ARYLALIPHATIC AMINOALCOHOLS

Derivatives of 4- (1,1,3,3-tetramethyl butyl) phenoxy-3-(N-alkyl amino)-2-propanol are the novel class of antimicrobial agents, possessing pronounce inhibitory activity against bacteria and fungi. KVM-194 was found to be one of the most promising compounds of this class, preliminary experiments demonstrated its broad spectrum of activity against planktonic microorganisms and biofilms. The aim of the present study was to investigate the development of resistance to KVM-194 in bacteria and fungi. Staphylococcus aureus and Candida albicans were used in all experiments. Microorganisms were grown on the nutrient agar in the presence of subinhibitory concentration of compound. Susceptibility of bacteria and fungi to KVM-194 and officinal antimicrobials was tested every 5 passages. The antimicrobial activity of the 4- (1,1,3,3-tetrametylbutyl) phenoxy-3-(N-alkyl)-2-propanol derivative was investigated by serial broth dilution method. Susceptibility of bacteria and fungi to the officinal antimicrobials was tested by disk diffusion assay. The data obtained suggest no significant changes of C. albicans and S. aureus susceptibility to KVM-194 for 20 passages in the presence of compound. Further studies showed that clotrimazole action on C. albicans was not affected in the experimental conditions, while polyene antimycotics (nystatin and amphotericin B) demonstrate even slightly higher activity. Bacteria S. aureus, grown in the presence of KVM-194, showed no changes in susceptibility to levofloxacin, oxacillin, clindamycin and erythromycin. Thus, obtained results suggest a slow development of KVM-194 resistance in bacteria and fungi and a lack of crossresistance between the compound and officinal antimicrobial agents.