tcsc3579 Dalbavancin

Dalbavancin(BI-397; MDL-63397) is a semisynthetic lipoglycopeptide, has potent activity against Gram-positive bacteria(MIC50=0.06 mg/L; B. anthracis).

IC50 value: 0.06 mg/L(MIC50; B. anthracis) [1]

Target: Antibiotic

Dalbavancin demonstrated potent in vitro activity against B. anthracis (MIC range, < or =0.03 to 0.5 mg/liter; MIC(50) and MIC(90), 0.06 and 0.25 mg/liter, respectively), which led us to test its efficacy in a murine inhalation anthrax model. At 20 mg/kg, the dalbavancin activity was detectable for 6 days after administration (terminal half-life, 53 h), indicating that long intervals between doses were feasible. The mice were challenged with 50 to 100 times the median lethal dose of the Ames strain of B. anthracis, an inoculum that kills untreated animals within 4 days. The efficacy of dalbavancin was 80 to 100%, as determined by the rate of survival at 42 days, when treatment was initiated 24 h postchallenge with regimens of 15 to 120 mg/kg every 36 h (q36h) or 30 to 240 mg/kg every 72 h (q72h). A regimen of ciprofloxacin known to protect 100% of animals was tested in parallel. Delayed dalbavancin treatment (beginning 36 or 48 h postchallenge) with 60 mg/kg q36h or 120 mg/kg q72h still provided 70 to 100% survival [1]. Dalbavancin features a multifaceted mechanism of action that inhibits bacterial cell wall formation by two different mechanisms that enhances its activity against a wide range of gram-positive bacteria including staphylococci, streptococci, enterococci, and some anaerobes. Additionally, dalbavancin possesses unique pharmacokinetic properties, the most significant of which is a long terminal half-life that allows for once weekly dosing [2].