1. Academic Validation
  2. Eravacycline (TP-434) is efficacious in animal models of infection

Eravacycline (TP-434) is efficacious in animal models of infection

  • Antimicrob Agents Chemother. 2015 May;59(5):2567-71. doi: 10.1128/AAC.04354-14.
Trudy H Grossman 1 Timothy M Murphy 2 Andrew M Slee 2 Denene Lofland 3 Joyce A Sutcliffe 3
Affiliations

Affiliations

  • 1 Tetraphase Pharmaceuticals, Watertown, Massachusetts, USA tgrossman@tphase.com.
  • 2 Vivisource Laboratories, Waltham, Massachusetts, USA.
  • 3 Tetraphase Pharmaceuticals, Watertown, Massachusetts, USA.
Abstract

Eravacycline is a novel broad-spectrum fluorocycline Antibiotic being developed for a wide range of serious infections. Eravacycline was efficacious in mouse septicemia models, demonstrating 50% protective dose (PD50) values of ≤ 1 mg/kg of body weight once a day (q.d.) against Staphylococcus aureus, including tetracycline-resistant isolates of methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes. The PD50 values against Escherichia coli isolates were 1.2 to 4.4 mg/kg q.d. In neutropenic mouse thigh Infection models with methicillin-sensitive S. aureus (MSSA) and S. pyogenes, eravacycline produced 2 log10 reductions in CFU at single intravenous (i.v.) doses ranging from 0.2 to 9.5 mg/kg. In a neutropenic mouse lung Infection model, eravacycline administered i.v. at 10 mg/kg twice a day (b.i.d.) reduced the level of tetracycline-resistant MRSA in the lung equivalent to that of linezolid given orally (p.o.) at 30 mg/kg b.i.d. At i.v. doses of 3 to 12 mg/kg b.i.d., eravacycline was more efficacious against tetracycline-resistant Streptococcus pneumoniae in a neutropenic lung Infection model than linezolid p.o. at 30 mg/kg b.i.d. Eravacycline showed good efficacy at 2 to 10 mg/kg i.v. b.i.d., producing up to a 4.6 log10 CFU reduction in kidney Bacterial burden in a model challenged with a uropathogenic E. coli isolate. Eravacycline was active in multiple murine models of Infection against clinically important Gram-positive and Gram-negative pathogens.

Figures
Products