ceftriaxone and telavancin

Steady-state concentrations of telavancin, a novel, bactericidal lipoglycopeptide, were determined in the plasma, pulmonary epithelial lining fluid (ELF), and alveolar macrophages (AMs) of 20 healthy subjects. Telavancin at 10 mg of drug/kg of body weight/day was administered as a 1-h intravenous infusion on three successive days, with bronchoalveolar lavage performed on five subjects, each at 4, 8, 12, and 24 h after the last dose. Plasma samples were collected before the first and third infusions and at 1, 2, 3, 4, 8, 12, and 24 h after the third infusion. The plasma telavancin concentration-time profile was as reported previously. Telavancin (mean +/- standard deviation) penetrated well into ELF (3.73 +/- 1.28 microg/ml at 8 h and 0.89 +/- 1.03 microg/ml at 24 h) and extensively into AMs (19.0 +/- 16.8 microg/ml at 8 h, 45.0 +/- 22.4 microg/ml at 12 h, and 42.0 +/- 31.4 microg/ml at 24 h). Mean concentrations in AMs and plasma at 12 h were 45.0 microg/ml and 22.9 microg/ml (mean AM/plasma ratio, 1.93), respectively, and at 24 h were 42.0 microg/ml and 7.28 microg/ml (mean AM/plasma ratio, 6.67), respectively. Over the entire dosing interval, telavancin was present in ELF and AMs at concentrations up to 8-fold and 85-fold, respectively, above its MIC 90 for methicillin-resistant Staphylococcus aureus (0.5 microg/ml). Pulmonary surfactant did not affect telavancin's in vitro antibacterial activity. Telavancin was well tolerated. These results support the proposal for further clinical evaluation of telavancin for treating gram-positive respiratory infections.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Bronchoscopy; Female; Humans; Injections, Intravenous; Lipoglycopeptides; Lung; Macrophages, Alveolar; Male; Methicillin Resistance; Microbial Sensitivity Tests; Pulmonary Surfactants; Staphylococcus aureus; Streptococcus pneumoniae; Treatment Outcome

The in vitro activity of telavancin was tested against 743 predominantly antimicrobial-resistant, gram-positive isolates. Telavancin was highly active against methicillin-resistant staphylococci (MIC(90), 0.5 to 1 microg/ml), streptococci (all MICs, < or =0.12 microg/ml), and VanB-type enterococci (all MICs, < or =2 microg/ml). Time-kill studies demonstrated the potent bactericidal activity of telavancin.

Topics: Aminoglycosides; Anti-Bacterial Agents; Drug Resistance, Bacterial; Enterococcus; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Lipoglycopeptides; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcus; Streptococcus

The in vitro activity of telavancin was tested against 620 gram-positive isolates. For staphylococci, MICs at which 50 and 90% of isolates were inhibited (MIC(50) and MIC(90)) were both 0.25 microg/ml, irrespective of methicillin resistance. MIC(50) and MIC(90) were 0.25 and 0.5 microg/ml for vancomycin-susceptible enterococci and 1 and 2 microg/ml for vancomycin-resistant enterococci, respectively. Streptococcus pneumoniae, group A and B beta-hemolytic streptococci, and viridans streptococci were inhibited by < or =0.12 microg/ml.

Topics: Aminoglycosides; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Europe; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcus aureus; Streptococcus agalactiae; Streptococcus pyogenes; Vancomycin Resistance; Viridans Streptococci