In vitro Synergy and Time-kill Assessment of Interaction between Kanamycin and Metronidazole against Resistant Bacteria

• Published in: Tropical journal of pharmaceutical research Vol. 14; no. 5; p. 837
• Main Authors: Olajuyigbe, Olufunmiso O, Afolayan, Anthony J
• Format: Journal Article
• Language: English
• Published: Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria 01-05-2015
• Subjects: Drug-drug interactions; Fractional inhibitory concentration index; Kanamycin; Metronidazole; Microbial resistance; Synergy; Time-kill
• ISSN: 1596-5996; 1596-9827
• DOI: 10.4314/tjpr.v14i5.14

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
Gramnegative 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.