Antibacterial activity of carbapenem-based combinations againts multidrug-resistant Acinetobacter baumannii

Abstract

Background: Multidrug-resistant (MDR) Acinetobacter baumannii are increasingly encountered and frequently susceptible only to colistin with their MIC values close to resistance breakpoint. Antibacterial activity of two carbapenem-based combinations were explored in order to overcome the bacterial resistance. Material and Method: Thirty clinical isolates of MDR A. baumannii were employed to assess in vitro antibacterial activity of two carbapenem-based regimens. Imipenem combined with colistin and meropenem combined with colistin and sulbactam were the first and second regimens, respectively. All isolates were resistant to imipenem (MIC range: 8-128 ?g/ml) and meropenem (MIC range: 64-256 μg/ml) but still susceptible to colistin (MIC range: 0.5-2 μg/ml). The MIC range of sulbactam was 4-64 μg/ml. None of the isolates produced metallo-β-lactamase. Results: Synergistic antibacterial effect of imipenem combined with colistin was observed against 100 percent of A. baumannii isolates by the checkerboard microdilution panel method. In a subsequent time kill study, the most active concentration of this regimen was the combination of imipenem at the fixed concentration of 32 μg/ml and colistin at the 1/4 of the MIC values of each isolate that exerted significantly higher bactericidal activity than imipenem at 32 μg/ml alone and colistin alone at the 1/4 of the MIC values. The scanning electron micrographs demonstrated major cell morphological change and cell wall destruction after 2-hour exposure to this combination. The triple combinations of meropenem, sulbactam and colistin showed synergy against 96.7 percent of MDR A. baumannii while double combinations of either meropenem and sulbactam, meropenem and colistin, and sulbactam and colistin showed synergy effects of 70%, 73.3% and 53.3%, respectively. The time kill study using ten isolates also showed better killing effect by the triple combination than any of the double combinations. Conclusion: Antibacterial activity against MDR A. baumannii of imipenem plus colistin was superior over any single of the two agents. The addition of sulbactam to meropenem and colistin may further improve their antibacterial activity. The double or triple carbapenem-based combinations offer promising alternatives in the treatment of infections due to MDR A. baumannii.