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Small Molecule Suppression of Carbapenem Resistance in NDM-1 Producing Klebsiella pneumoniae

  作者 WORTHINGTON ROBERTA J; BUNDERS CYNTHIA A; REED CATHERINE S; MELANDER CHRISTIAN  
  选自 期刊  ACS Medicinal Chemistry Letters;  卷期  2012年3-5;  页码  357-361  
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[摘要]The already considerable global public health threat of multidrug-resistant Gram-negative bacteria has become even more of a concern following the emergence of New Delhi metallo-beta-lactamase (NDM-1) producing strains of Klebsiella pneumoniae and other Gram-negative bacteria. As an alternative approach to the traditional development of new bactericidal entities, we have identified a 2-aminoimidazole-derived small molecule that acts as an antibiotic adjuvant and is able to suppress resistance of a NDM-1 producing strain of K. pneumoniae to imipenem and meropenem, in addition to suppressing resistance of other beta-lactam nonsusceptible K. pneumoniae strains. The small molecule is able to lower carbapenem minimum inhibitory concentrations by up to 16-fold, while exhibiting little bactericidal activity itself.

 
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