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
Highlights
Antibiotic resistance is a serious problem in clinical medicine
The resistance patterns of 37 non-duplicate ESBLproducing Klebsiella pneumoniae clinical isolates were determined against 20 antimicrobial agents by VITEK 2 compact automated system
The resistance pattern of the six tigecycline-resistant isolates is depicted in Table 1 and these isolates were used further to evaluate the efficacy of amikacin-tigecycline combination by checkerboard technique and time-kill assay
Summary
Antibiotic resistance is a serious problem in clinical medicine. The efficacy of treatment with the widely use βlactam antibiotics is constantly challenged by the emergence of new resistant bacterial strains. In Gramnegative bacteria, β-lactamase production is considered the main antibiotic resistant mechanism (Livermore, 2009). Extended spectrum beta-lactamase (ESBL) production is one of the main mechanisms of resistance to β-lactam antibiotics among the family Enterobacteriaceae (Szabó et al, 2001). ESBL-producing Enterobacteriaceae are among the most important and frequent nosocomial pathogens and are resistant to many classes of antibiotics (O'Neill, 2008; Vidaillac et al, 2009). Since the 1980s, there have been numerous reports from different healthcare settings worldwide on outbreaks caused by ESBL-producing Klebsiella pneumoniae “ESBL-KP” (Arpin et al, 2003; Keynan and Rubinstein, 2007)
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