Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Olufunmiso O Olajuyigbe^1,2 , Anthony J Afolayan²

¹Biosciences and Biotechnology Department, Babcock University, Ilishan Remo, Ogun State, Nigeria; ²Phytomedicine Research Centre, Department of Botany, University of Fort Hare, Alice, 5700, South Africa.

For correspondence:- Olufunmiso Olajuyigbe Email: funmijuyigbe12@yahoo.com Tel:+27730562219

Received: 17 February 2014 Accepted: 29 March 2015 Published: 26 May 2015

Citation: Olajuyigbe OO, Afolayan AJ. In vitro synergy and time-kill assessment of interaction between kanamycin and metronidazole against resistant bacteria. Trop J Pharm Res 2015; 14(5):837-843 doi: 10.4314/tjpr.v14i5.14

© 2015 The authors.
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Abstract

Purpose: To evaluate the in vitro effects of combining kanamycin and metronidazole against resistant bacteria.

Methods: The influence of combining kanamycin and metronidazole against Gram-positive and Gram-negative bacteria was assessed by agar diffusion, checkerboard and time-kill assays.

Results: The test isolates were highly resistant, with minimum inhibitory concentration (MIC) ranging between 15.63 and >250 µg/ml for kanamycin, and 15.63 and 125 µg/ml for metronidazole. The antibacterial combinations resulted in drastic decrease in MIC with increased antibacterial activity that indicated synergistic interaction against all the bacteria except Acinetobacter calcaoceuticus UP, Enterobacter cloacae ATCC 13047 and Shigella flexneri KZN. Fractional inhibitory concentration index (FICI) showed synergy ranging from 0.31 to 0.50, additive interaction with FICI ranging from 0.53 to 1.25 and absence of antagonistic interaction. Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Bacillus cereus ATCC 10702, Enterobacter cloacae ATCC 13047, Klebsiella pneumoniae ATCC 10031, Acinetobacter calcoaceuticus 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 suggest that kanamycin may be effective in both monotherapy and combination therapy.

Conclusion: The study indicates the potential beneficial value of combining kanamycin and metronidazole in the treatment of microbial infections in clinical settings.

Keywords: Drug-drug interactions, Synergy, Time-kill, Fractional inhibitory concentration index, Kanamycin, Metronidazole, Microbial resistance