Telavancin: A novel lipoglycopeptide antimicrobial agent
Ryan J. Attwood and Kerry L. LaPlante
RYAN J. ATTWOOD, PHARM.D., is Postgraduate Year 1 Pharmacy Resident, Henry Ford Hospital, Detroit, MI; at the time of writing he was Pharm.D. degree candidate, University of Rhode Island, Providence. KERRY L. LAPLANTE, PHARM.D., is Assistant Professor of Pharmacy, Department of Pharmacy Practice, University of Rhode Island, Veterans Affairs Medical Center, Providence.
Address correspondence to Dr. LaPlante at the Department of Pharmacy Practice, University of Rhode Island, Veterans Affairs Medical Center (151), Research Building, 830 Chalkstone Avenue, Providence, RI 02908 (kerrytedesco@uri.edu
Purpose.
The pharmacology, activity, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and place in therapy of telavancin are reviewed.
Summary.
Telavancin is a lipoglycopeptide antimicrobial agent under development for use in the treatment of multidrug-resistant gram-positive infections. Telavancin, like vancomycin, inhibits cell-wall biosynthesis by binding to late-stage cell-wall precursors. However, unlike vancomycin, telavancin also depolarizes the bacterial cell membrane and disrupts its functional integrity.
Telavancin has concentration-dependent bactericidal activity and is active against gram-positive aerobic and anaerobic organisms. It is highly protein bound (93%) and has a volume of distribution of 115 mL/kg and a half-life of approximately eight hours. Telavancin is eliminated renally, and a dosage reduction is required in renally impaired patients. Animal models suggest that telavancin may be effective in the treatment of soft-tissue infections, bacteremia, endocarditis, meningitis, and pneumonia caused by gram-positive pathogens. Telavancin was not inferior to standard treatment for complicated skin and soft-tissue infections in two Phase II clinical trials and two Phase III clinical trials.
A new drug application has been submitted for this indication, and Phase III trials to evaluate use in hospital-acquired-pneumonia, including infections caused by methicillin-resistant Staphylococcus aureus (MRSA), are planned. Adverse effects include metallic taste, nausea, vomiting, headache, foamy urine, Q-Tc-interval prolongation, hypokalemia, and serum creatinine increases. In trials evaluating telavancin for skin and soft-tissue infections, the dosage was 10 mg/kg i.v. once daily.
Conclusion.
Telavancin is a promising new agent for gram-positive infections and may offer an alternative to vancomycin for MRSA-associated infections.
American Journal of Health-System Pharmacy
