Inhibition of Aminoglycoside 6′-N-Acetyltransferase Type Ib-Mediated Amikacin Resistance in Klebsiella pneumoniae by Zinc and Copper Pyrithione

Abstract

ABSTRACTThein vitroactivity of the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib] was inhibited by CuCl2with a 50% inhibitory concentration (IC50) of 2.8 μM. The growth of an amikacin-resistantKlebsiella pneumoniaestrain isolated from a neonate with meningitis was inhibited when amikacin was supplemented by the addition of Zn2+or Cu2+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.