title: Activity of a novel aminoglycoside, ACHN-490, against clinical isolates of Escherichia coli and Klebsiella pneumoniae from New York City.
abstract: OBJECTIVE
  Reports of Enterobacteriaceae resistant to all commonly used antimicrobial agents, including β-lactams, fluoroquinolones and aminoglycosides, are increasing in hospitals worldwide. The activity of ACHN-490, a next-generation aminoglycoside, was examined against clinical isolates of Escherichia coli and Klebsiella pneumoniae from hospitals in New York City, an area where multidrug-resistant organisms are endemic.
  
  
  METHODS
  Unique patient isolates of E. coli and K. pneumoniae were gathered from 16 hospitals located in New York City in 2009 and underwent susceptibility testing to aminoglycosides and ACHN-490. Subsets of isolates were characterized by PCR for the presence of genes encoding aminoglycoside-modifying enzymes, ribosomal methylases and KPC-type carbapenemases.
  
  
  RESULTS
  Although most isolates of E. coli were susceptible to the aminoglycosides, the MIC(90) values of gentamicin, tobramycin and amikacin were 32, 8 and 4 mg/L, respectively. The MIC(90) of ACHN-490 was 1 mg/L. Multidrug resistance, including resistance to aminoglycosides and the presence of bla(KPC), was much more common in isolates of K. pneumoniae. However, the MIC(90) of ACHN-490 for K. pneumoniae was also 1 mg/L. The MICs of ACHN-490 did not correlate with the presence of commonly recovered aminoglycoside-modifying enzymes. Bactericidal activity was evident in most isolates at concentrations 4× the MIC.
  
  
  CONCLUSIONS
  The novel aminoglycoside ACHN-490 retains activity against most isolates of E. coli and K. pneumoniae, including multidrug-resistant strains. Additional studies examining the roles of efflux systems and outer membrane permeability alterations are recommended in isolates with reduced susceptibility to this agent.
authors.affiliation: State University of New York-Downstate Medical Center, Brooklyn, New York, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Landman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Babu
authors.forename: Neha
authors.initials: N
authors.lastname: Shah
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
authors.forename: Martin
authors.initials: M
authors.lastname: Bäcker
authors.forename: Simona
authors.initials: S
authors.lastname: Bratu
authors.forename: John
authors.initials: J
authors.lastname: Quale
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology*; D006761:Hospitals; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009519:New York City; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012853:Sisomicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001618:beta-Lactamases / Q000235:genetics; D012359:tRNA Methyltransferases / Q000235:genetics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012359:tRNA Methyltransferases; D001618:beta-Lactamases; C063912:carbapenemase; C550938:plazomicin; D012853:Sisomicin