The results from two methodologically identical double-blind studies indicate that telavancin is noninferior to vancomycin based on clinical response in the treatment of hospital-acquired pneumonia due to Gram-positive pathogens.

Protocol 012 Investigators (2020). Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. The Lancet Respiratory Medicine.

Telavancin given once daily is at least as effective as vancomycin for the treatment of patients with complicated skin and skin-structure infections, including those infected with methicillin-resistant S. aureus.

The pharmacokinetics, tolerability, and serum inhibitory and bactericidal titers of telavancin, a new rapidly bactericidal lipoglycopeptide with multiple mechanisms of action against gram-positive pathogens, were assessed in a two-part, randomized, double-blind, placebo-controlled, ascending-dose study with 54 healthy men. In part 1, single ascending intravenous doses of 0.25 to 15 mg/kg of body weight were studied. In part 2, multiple ascending doses (30-min infusions of 7.5 to 15 mg/kg/day) were studied over 7 days. Following the administration of multiple doses, steady state was achieved by days 3 to 4. At day 7 after the administration of telavancin at 7.5, 12.5, and 15 mg/kg/day, peak concentrations in plasma were 96.7, 151.3, and 202.5 g/ml, respectively, and steady-state area-under-the-curve values were 700, 1,033, and 1,165 g ⅐ h/ml, respectively. The elimination half-life ranged from 6.9 to 9.1 h following the administration of doses >5 mg/kg. Most adverse events were mild in severity. At 24 h postinfusion, serum from subjects given telavancin demonstrated potent bactericidal activity against methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae strains. The results suggest that telavancin may be an effective once-daily therapy for serious bacterial infections caused by these pathogens. , abstr. F-2108, 2003). Data from in vitro and animal studies indicate that telavancin has superior activity to ␤-lactams, older glycopeptides (e.g., vancomycin), and the oxazolidinone linezolid (6). This antimicrobial agent is rapidly bactericidal against staphylococci, with Ͼ99.9% killing achieved within 4 h of exposure at concentrations achievable in vivo (8).Unlike most glycopeptides, telavancin has multiple mechanisms of action. In addition to inhibiting peptidoglycan synthesis by blocking the transglycosylation step, telavancin also interacts with the bacterial membrane, dissipating the membrane potential and effecting changes in cell permeability. The multiple mechanisms of action may lead to a lower frequency of resistance (Debavov et al., 43rd ICAAC; K. Krause, D. Debabov, J. Pace, and K. Kaniga, Abstr. 43rd Intersci. Conf. Antimicrob. Agents Chemother., abstr. C1-1810, 2003). The rapid bactericidal activity of this agent may result in a reduction in the duration of therapy and improved clinical outcomes. This paper reports the results of a two-part, randomized, double-blind, placebo-controlled study of sequentially ascending doses of telavancin with healthy adult male subjects. The study objectives were to assess the safety, pharmacokinetics, and pharmacodynamics (serum inhibitory and bactericidal titers) of intravenous (i.v.) telavancin. Study subjects. Eligible male subjects (age, 18 to 50 years; weight, 50 to 100 kg) with no clinically relevant abnormal physical or laboratory findings and normal electrocardiograms (ECGs), blood pressure, and heart rate were included in the study. Subjects had to be able to comply with the study requirements and to provide written inf...

Telavancin is a bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted a randomized, double blind, active-control phase II trial. Patients >18 years of age with complicated skin and skin structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin at 10 mg/kg intravenously every 24 h (q24h) or standard therapy (antistaphylococcal penicillin at 2 g q6h or vancomycin at 1 g q12h). A total of 195 patients were randomized and received at least one dose of study medication. Clinical success rates were similar in all analysis populations at test of cure. In microbiologically evaluable patients with Staphylococcus aureus at baseline (n ‫؍‬ 91), 96% of the telavancin group and 90% of the standard-therapy group were cured. Among patients with methicillin-resistant S. aureus (MRSA) at baseline (n ‫؍‬ 45), clinical cure rates were also 96% for telavancin and 90% for standard therapy. Microbiologic eradication in patients with S. aureus infection was better with telavancin compared to standard therapy (92% versus 78%, P ‫؍‬ 0.07) and significantly better in patients with MRSA (92% versus 68%; P ‫؍‬ 0.04). Therapy was discontinued for an adverse event (AE) in 6% and 3% of the patients receiving telavancin and standard therapy, respectively. Except for two cases of rash in the telavancin group, these AEs were similar in type and severity in the two groups. The overall incidences and severities of AEs and laboratory abnormalities were similar between the two groups. These data support the ongoing studies assessing the efficacy and safety of telavancin in the treatment of serious gram-positive infections, particularly involving MRSA.