Inhibition of aminoglycoside 6'-N-acetyltransferase type Ib-mediated amikacin resistance in Klebsiella pneumoniae by zinc and copper pyrithione

Antimicrob Agents Chemother. 2015 Sep;59(9):5851-3. doi: 10.1128/AAC.01106-15. Epub 2015 Jul 13.

Abstract

The in vitro activity of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] was inhibited by CuCl2 with a 50% inhibitory concentration (IC50) of 2.8 μM. The growth of an amikacin-resistant Klebsiella pneumoniae strain isolated from a neonate with meningitis was inhibited when amikacin was supplemented by the addition of Zn(2+) or Cu(2+) in complex with the ionophore pyrithione. Coordination complexes between cations and ionophores could be developed for their use, in combination with aminoglycosides, to treat resistant infections.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetyltransferases
  • Amikacin / pharmacology*
  • Aminoglycosides / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology*
  • Klebsiella pneumoniae / metabolism
  • Microbial Sensitivity Tests
  • Organometallic Compounds / pharmacology*
  • Pyridines / pharmacology*
  • Zinc / pharmacology*

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Organometallic Compounds
  • Pyridines
  • copper pyrithione
  • Amikacin
  • Acetyltransferases
  • aminoglycoside N(6')-acetyltransferase
  • Zinc