EFFECT OF AMIKACIN AND IMIPENEM COMBINATION AGAINST PSEUDOMONAS AERUGINOSA ATCC 27853

Abstract

Pseudomonas aeruginosa causes a variety of hospital-acquired infections and develops resistance to diverse classes of antibiotics. Recently, combination therapy has become an attractive strategy to reduce the emergence of antibiotic resistance in bacteria, particularly in P. aeruginosa. Combinations of aminoglycoside such as amikacin and β-lactam antibiotics like imipenem have been performed in clinical settings. However, the antimicrobial effect of amikacin-imipenem combination and the risk of antibiotic resistance development in bacteria have not been clarified, particularly in prolonged periods. In this study, the synergistic activity of amikacin and imipenem combination on P. aeruginosa was evaluated based on Fractional Inhibitory Concentration (FIC) values using a checkerboard assay. Then, the serial exposure of P. aeruginosa to sub-MIC values of each antibiotic or of their combination was performed to assess the antibiotic resistance development over a 14- day period. Moreover, the antimicrobial susceptibility profile was analyzed to evaluate the susceptibility of the antibiotic-exposed P. aeruginosa. As a result, the checkerboard assay showed a synergistic effect between amikacin and imipenem (FIC ≤ 0.5). Besides, when being exposed to sub-MIC values of amikacin, P. aeruginosa significantly developed 256 folds after 14 days, from 0.5 µg/mL to 128 µg/mL. On the other hand, when exposing P. aeruginosa to sub-MIC values of imipenem, the MIC values increased by only 16 folds, from 8 µg/mL to 128 µg/mL. The combination result did not provide a prevention effect on resistance development. The antibiotic-exposed bacteria obtained after 14 days of serial exposure only developed resistance to an aminoglycoside (gentamicin), and a cephalosporin (ceftazidime) but not to other antibiotics. To summarize, using imipenem alone expressed a better effect than amikacin alone. The combination of imipenem and amikacin showed synergistic effect but did not have resistance development prevention effect.