In vitro synergy and time-kill assessment of interaction between kanamycin and metronidazole against resistant bacteria

Abstract

This study assessed the influence of combining kanamycin and metronidazole against Gram positive and Gram negative bacteria by agar diffusion, checkerboard and time-kill assays. The test isolates were highly resistant with minimum inhibitory concentrations (MICs) ranging between 15.63 and >250 micro g/ml for kanamycin and between 15.63 and 125 micro g/ml for metronidazole. The antibacterial combinations resulted in drastic decreases in the MICs with an increased antibacterial activity that indicated synergistic interaction against all the bacteria except Acinetobacter calcaoceuticus UP, Enterobacter cloacae ATCC 13047 and Shigella flexneri KZN. The fractional inhibitory concentration indices (FICIs) showed synergy ranging from 0.31 to 0.50, additive interaction with FICI ranging from 0.53 to 1.25 and no antagonistic interaction. Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Bacillus cereus ATCC 10702, E. cloacae ATCC 13047, Klebsiella pneumoniae ATCC 10031, A. calcaoceuticus UP and Micrococcus luteus were totally eliminated by the antibacterial combinations within 24 h of incubation. The lack of antagonism between these antibacterial agents in checkerboard and time-kill assays suggests that kanamycin may prove to be effective in monotherapy and combination therapy. The study indicates the potential beneficial value of combining kanamycin and metronidazole in the treatment of microbial infections in clinical settings.