Antibacterial Activity of Carbapenem-Based Combinations Againts Multidrug-Resistant Acinetobacter baumannii
Pintip Pongpech PhD*, Suparak Amornnopparattanakul MSc**, Sakulthip Panapakdee MSc**, Siriporn Fungwithaya MSc**, Penphun Nannha MSc*, Chertsak Dhiraputra MD***, Amorn Leelarasamee MD****
Affiliation : * Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand ** Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand *** Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand **** Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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 μg/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.
Keywords : Acinetobacter baumannii, Imipenem, Meropenem, Colistin, Sulbactam, Antimicrobial combination, Multidrug- resistance, Synergy
