Abstract
Outbreaks of carbapenem-resistant Acinetobacter species have emerged, especially in Singapore. Combination therapy may be the only viable option until new antibiotics are available. The objective of this study was to identify potential antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii and Acinetobacter species in Singapore. From an ongoing surveillance program, two isolates of A. baumannii and an isolate of Acinetobacter species that were multidrug resistant were selected on the basis of their unique resistance mechanisms. The two A. baumannii isolates carried the carbapenemase blaOXA-23-like gene and the Acinetobacter species carried a metallo-β-lactamase IMP-4 gene. Time-kill studies were conducted with approximately 105 CFU ml−1 at baseline with 0.5 times minimum inhibitory concentrations (MICs) of polymyxin B and tigecycline, and at a maximally achievable clinical concentration of meropenem(64 μg ml−1) and rifampicin(2 μg ml−1), alone and in combinations. The MICs (μg ml−1) of Acinetobacter species A105, A. baumannii AB112 and A. baumannii AB8879 to polymyxin B/tigecycline/rifampicin/meropenem were found to be 1/0.5/4/64, 1/4/4/32 and 2/2/2/64, respectively. In time-kill studies, enhanced combined killing effects were observed in the tigecycline–rifampicin combination; the tigecycline–rifampicin and rifampicin–polymyxin B combination; and the rifampicin–polymyxin B combination for Acinetobacter species A105, A. baumannii AB112 and A. baumannii AB8879, respectively, with >5 log kill at 24 h suggesting synergism, with no regrowth observed at 72 h. These findings demonstrate that in vitro synergy of antibiotic combinations in carbapenem-resistant Acinetobacter species may be strain dependent. It may guide us in choosing a preemptive therapy for carbapenem-resistant Acinetobacter species infections and warrants further investigations.
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This study was supported in part by National Medical Research Council and SingHealth Foundation.
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Lim, TP., Tan, TY., Lee, W. et al. In vitro activity of various combinations of antimicrobials against carbapenem-resistant Acinetobacter species in Singapore. J Antibiot 62, 675–679 (2009). https://doi.org/10.1038/ja.2009.99
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DOI: https://doi.org/10.1038/ja.2009.99
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