achn-490 and Escherichia-coli-Infections

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (bla

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Genotype; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Sisomicin; Young Adult

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Load; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sisomicin

The in vitro activity of plazomicin was evaluated against 300 multidrug resistant (MDR) (carbapenemase and/or ESBL-producing) isolates from four hospitals in Athens, an area where carbapenemase-producing organisms are endemic. Most of the isolates were also resistant to the legacy aminoglycosides with the MIC₅₀/MIC₉₀ to tobramycin, amikacin and gentamicin being 32/>32, 32/>32 and 4/>8 μg/ml, respectively. ACHN-490 retained activity (MICs ≤ 4 μg/ml) against all isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. tested with MIC₅₀ and MIC₉₀ of 1 and 2 μg/ml, respectively, irrespective of their MDR phenotype and it represents a promising alternative for the treatment of the most problematic Gram-negative pathogens.

Topics: Amikacin; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Gentamicins; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sisomicin; Tertiary Care Centers; Tobramycin

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.. 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.. 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.. 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.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; New York City; Polymerase Chain Reaction; Sequence Analysis, DNA; Sisomicin; tRNA Methyltransferases