Abstract

The number of extended-spectrum β-lactamases-producing Klebsiella pneumoniae (ESBL-KP) strains is constantly increasing. This is of great concern in human healthcare around the world. In this study, we aimed to evaluate the antimicrobial activity of amikacin-tigecycline combination against six tigecycline-resistant ESBL-KP clinical isolates using disc diffusion method, checkerboard titration assay and time-kill curve technique. Presence of subinhibitory concentration of tigecycline (1 mg/L) enhanced the susceptibility of ESBL-KP isolates to amikacin expressed by the percentage of relative inhibition zone diameter (% RIZD) which ranged from 110 to 167%. The fractional inhibitory concentration indices (FICIs) of amikacin-tigecycline combinations were from 0.31 to 0.75. For KP 125 and KP 135 isolates, combination of tigecycline (2 mg/L) and amikacin (8 mg/L) resulted in 99.99% killing after 24 h incubation. Drastic and rapid bactericidal effect was shown after 6 h incubation against KP 135 in the presence 2 mg/L tigecycline plus 16 mg/L amikacin. In conclusion, the combined effect of amikacin-tigecycline is significantly synergistic at concentrations that were within the clinically achievable serum levels and may be eligible for further evaluation in vivo against ESBL-KP infections to define their utility as an alternative to carbapenems.

Key words: ESBL, Klebsiella pneumoniae, amikacin, tigecycline, checkerboard, Time-kill curve