Plazomicin is effective in a non-human primate pneumonic plague model

Bioorg Med Chem. 2016 Dec 15;24(24):6429-6439. doi: 10.1016/j.bmc.2016.08.049. Epub 2016 Aug 27.

Abstract

The efficacy of plazomicin for pneumonic plague was evaluated in a non-human primate model. African Green monkeys challenged with a lethal aerosol of Yersinia pestis [median (range) of 98 (15-331) LD50s] received placebo (n=12) or 'humanized' dose regimens (6.25, 12.5 or 25mg/kg every 24h) of plazomicin (n=52) after the onset of fever for a duration of 5 or 10days. All animals treated with placebo died, while 36 plazomicin-treated animals survived through study end. The majority (33/36) were either in the 10-day (high-/mid-/low-dose) or 5-day high-dose groups. The findings suggest an exposure range of plazomicin for treatment of pneumonic/bacteremic Y. pestis infection in humans.

Keywords: Aminoglycoside; Animal rule; Plague; Plazomicin; Pneumonia; Yersinia pestis.

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Molecular Conformation
  • Plague / drug therapy*
  • Sisomicin / analogs & derivatives*
  • Sisomicin / chemistry
  • Sisomicin / therapeutic use

Substances

  • plazomicin
  • Sisomicin