KPC-producing Klebsiella pneumoniae strains that harbor AAC(6')-Ib exhibit intermediate resistance to amikacin

Antimicrob Agents Chemother. 2014 Dec;58(12):7597-600. doi: 10.1128/AAC.03831-14. Epub 2014 Oct 6.

Abstract

The aminoglycoside-modifying enzyme AAC(6')-Ib is common among carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains. We investigated amikacin (AMK) activity against 20 AAC(6')-Ib-producing CR-Kp strains. MICs clustered at 16 to 32 μg/ml. By the time-kill study, AMK (1× and 4× the MIC) was bactericidal against 30% and 85% of the strains, respectively. At achievable human serum concentrations, however, the majority of strains showed regrowth, suggesting that AAC(6')-Ib confers intermediate AMK resistance. AMK and trimethoprim-sulfamethoxazole (TMP-SMX) were synergistic against 90% of the strains, indicating that the combination may overcome resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics*
  • Acetyltransferases / metabolism
  • Amikacin / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Drug Resistance, Bacterial / drug effects
  • Drug Resistance, Bacterial / genetics
  • Drug Synergism
  • Gene Expression
  • Humans
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / growth & development
  • Microbial Sensitivity Tests
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Amikacin
  • Acetyltransferases