Small Molecule Suppression of Carbapenem Resistance in NDM-1 Producing Klebsiella pneumoniae
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- 作者：Roberta J. Worthington ; Cynthia A. Bunders ; Catherine S. Reed ; Christian Melander
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：May 10, 2012
- 年：2012
- 卷：3
- 期：5
- 页码：357-361
- 全文大小：219K
- 年卷期：v.3,no.5(May 10, 2012)
- ISSN：1948-5875
文摘
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-尾-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 尾-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.