In vitro antibacterial activity of imipenem in combination with amikacin or with ciprofloxacin against imipenem resistant-Acinetobacter baumannii

Abstract

Acinetobacter baumannii (A. baumannii) is gram-negative, non-fermentative, non-spore forming, strictly aerobic, oxidase-negative coccobacillary. It has recently become important pathogen causing nosocomial infections, especially in intensive care unit (ICU). There are limited therapeutic alternatives against that species particularly after the evolution of resistance for antimicrobial agents like broad-spectrum beta-lactams, aminoglycosides, fluoroquinolones and imipenem over the last decade. Combination therapy is the other choice in treatment A. baumannii with the aim of decreasing emergence of resistance strains and increasing bacterial killing. The purpose of the present study is to determine the antibacterial activity of the combination of imipenem plus amikacin or plus ciprofloxacin against 30 strains of imipenem resistant-A. Baumannii by time kill method. The concentrations of drugs used is the mean serum concentration at therapeutic dose. Another aim is to detect antibiotic resistant genes in imipenem resistant- A. baumannii by Polymerase Chain Reaction (PCR) technique. All strains were resistant to ciprofloxacin and imipenem. MIC of imipenem ranged from 8-32 microgram/ml, which were low level of resistance. Thirteen isolates (43.33%) were susceptible to amikacin. It was showed that integrase gene were positive in 33.33% of isolates, bla[subscript VEB-1] positive in 6.67% and bla[subscript OXA-23] in 36.67% as tested by PCR. The bla[subscript OXA-1], bla[subscript OXA-2], bla[subscript OXA-10], bla[subscript -IMP] and aac(6') genes could not be detected in all isolates. The carbapenemase activity could be detected in 27 strains (90%) of A. baumannii isolates. All of the bla[subscript OXA-23] gene positive had carbapenemase activity. The antibacterial activity of the combination of imipenem plus amikacin showed the synergistic effect in 3 strains (10%) and the antagonist effect in 1 strain (3.33%). When combined imipenem with ciprofloxacin the synergistic effect could be observed in 1 strain (3.33%) and the antagonist effect in 2 strains (6.67%). Imipenem alone showed bactericidal activity against 1 strain (3.33%) at 6 hour of growth and against 16 strains (53.33%) at 24 hour of growth [BA[subscript 24] = 116.39 log CFU/ml.h]. Amikacin alone showed activity against only 2 strains (6.67%) during the time of study. Ciprofloxacin alone showed no antibactericidal activity against all stains tested. The combination of imipenem plus amikacin showed bactericidal activity against 2 strains (6.67%) at 2 hour of growth and against 28 strains (93.33%) at 24 hour of growth [BA[subscript 24] = 138.83 log CFU/ml-h]. The combination of imipenem plus ciprofloxacin showed bactericidal activity against 2 strains (6.67%) at 6 hour of growth and against 22 strains (73.33%) at 24 hour of growth [BA[subscript 24] = 123.50 log CFU/ml.h]. The results obtained suggested that antibacterial activity of the combination of imipenem plus amikacin or plus ciprofloxacin were higher than antibacterial activity of single drug alone. It is concluded that the combination of imipenem plus amikacin or plus ciprofloxacin could be promising alternatives for the treatment of infection due to imipenem resistant-A. baumannii.