title: KPC-producing Klebsiella pneumoniae strains that harbor AAC(6')-Ib exhibit intermediate resistance to amikacin.
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.
authors.affiliation: Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Derek N
authors.initials: DN
authors.lastname: Bremmer
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Ellen G
authors.initials: EG
authors.lastname: Press
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Reem
authors.initials: R
authors.lastname: Almaghrabi
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA shieldsrk@upmc.edu.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000583:Amikacin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D015870:Gene Expression; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000583:Amikacin; D000123:Acetyltransferases