In Vivo Efficacy of Novel Monobactam LYS228 in Murine Models of Carbapenemase-Producing Klebsiella pneumoniae Infection

Antimicrob Agents Chemother. 2019 Mar 27;63(4):e02214-18. doi: 10.1128/AAC.02214-18. Print 2019 Apr.

Abstract

LYS228 has potent antibacterial activity against carbapenem-resistant strains of Enterobacteriaceae LYS228 was efficacious in neutropenic thigh models established with Klebsiella pneumoniae producing KPC-2 or NDM-1; pretreatment with uranyl nitrate considerably shifted calculated static doses of LYS228. In murine ascending pyelonephritis, LYS228 reduced bacterial burden in kidney, urine, and bladder. The successful treatment of murine infection models established with carbapenem-resistant K. pneumoniae further supports the clinical development of LYS228.

Keywords: LYS228; neutropenic thigh model; pyelonephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism*
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • Carbapenem-Resistant Enterobacteriaceae / metabolism
  • Carbapenems / pharmacology
  • Disease Models, Animal
  • Female
  • Klebsiella Infections / drug therapy*
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / metabolism
  • Mice
  • Monobactams / pharmacology*
  • Pyelonephritis / drug therapy
  • Pyelonephritis / microbiology
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Monobactams
  • beta-Lactamases
  • carbapenemase