title: Eravacycline (TP-434) is efficacious in animal models of infection.
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.
authors.affiliation: Tetraphase Pharmaceuticals, Watertown, Massachusetts, USA tgrossman@tphase.com.
authors.forename: Trudy H
authors.initials: TH
authors.lastname: Grossman
authors.affiliation: Vivisource Laboratories, Waltham, Massachusetts, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Murphy
authors.affiliation: Vivisource Laboratories, Waltham, Massachusetts, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Slee
authors.affiliation: Tetraphase Pharmaceuticals, Watertown, Massachusetts, USA.
authors.forename: Denene
authors.initials: D
authors.lastname: Lofland
authors.affiliation: Tetraphase Pharmaceuticals, Watertown, Massachusetts, USA.
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Sutcliffe
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D000069349:Linezolid / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000188:drug therapy / Q000382:microbiology; D011704:Pyelonephritis / Q000188:drug therapy / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013754:Tetracyclines / Q000494:pharmacology / Q000627:therapeutic use*; D013848:Thigh / Q000382:microbiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D013754:Tetracyclines; C571179:eravacycline; D000069349:Linezolid