Journal of
Microbiology and Antimicrobials

  • Abbreviation: J. Microbiol. Antimicrob.
  • Language: English
  • ISSN: 2141-2308
  • DOI: 10.5897/JMA
  • Start Year: 2009
  • Published Articles: 160

Full Length Research Paper

In vitro synergistic activity of amikacin combined with subinhibitory concentration of tigecycline against extended spectrum β-lactamase-producing Klebsiella pneumoniae

Elsayed Aboulmagd1,2*, Abdulrahman A. Alsultan1, Hamdan I. Al Mohammad1, Soad Al-Badry1 and Eman M. Hussein1
  1Department of Biomedical Sciences, Division of Medical Microbiology, College of Medicine, King Faisal University, Kingdom of Saudi Arabia. 2Department of Microbiology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Email: [email protected]

  •  Accepted: 23 April 2013
  •  Published: 30 May 2013

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