BAY 73-7388, a novel aminomethylcycline, is highly active in vivo in a murine model of pneumococcal pneumonia

Objectives: BAY 73-7388 is the first antibiotic compound selected from the novel class, the aminomethylcyclines. BAY 73-7388 is under development for the treatment of severe bacterial infections including those caused by strains resistant to current classes of antibiotics.The efficacy of BAY 73-7388 was compared with that of vancomycin (VAN) and linezolid (LZD) in a mouse model of pneumococcal pneumonia. Methods: For lung infections, Streptococcus pneumoniae (strain L3 TV, Serotype 3) was administered intranasally to 5 mice per group, followed by IV antibiotic treatment bid over 2 days.The bacterial counts in the lungs on day 4 were used as read-out. Survival was monitored until day 4 postinfection; surviving mice were sacrificed and bacterial counts in the lung determined. Results: a) Colony forming units (CFU): Bacterial CFU in the lung at day 4 were lower with BAY 73-7388 and VAN in comparison with LZD therapy (reduction in CFU >6 log units at 1 mg/kg BAY 73-7388 vs no reduction in CFU at the same doses of LZD). A 4.5 log unit CFU reduction was only obtained at a 10 mg/kg dose of LZD. b) Survival assays: For BAY 73-7388 and VAN all mice survived at the 3 tested doses (1, 3, and 10 mg/kg). In contrast, for LZD 0, 2, and 4 animals survived when tested at the same dose range. Conclusions: Treatment with BAY 73-7388 is highly effective in an animal model of pneumococcal pneumonia. (BAY 73-7388 was discovered by Paratek Pharmaceuticals, Inc., Boston, MA, and designated PTK 0796.) Introduction Streptococcus pneumoniae is the most frequently isolated p a t h o gen in community-acquired pneumonia and is a significant cause of mortality in humans. BAY 73-7388 is the first compound selected from the novel class of aminomethylcyclines and show s excellent in vitro activity against S. pneumoniae, including multidrug-resistant strains. We report here on the in vivo activity of BAY 73-7388 in comparison with VAN and LZD in an in vivo mouse model of acute pneumonia caused by pneumococci.