Telavancin (TD-6424), a semisynthetic
lipoglycopeptide vancomycin-derivative, is a novel
antimicrobial agent developed by Theravance for overcoming resistant
Gram-positive bacterial infections, specifically methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration (USFDA) had approved
telavancin in 2009 for the treatment of complicated skin and skin structure
infections (cSSSIs) caused by Gram-positive bacteria, including MRSA (S. aureus, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus anginosus group, or Enterococcus faecalis).
Telavancin has two proposed mechanisms of action. In vitro,
telavancin has a rapid, concentration-dependent bactericidal effect, due to disruption of cell membrane integrity.
Telavancin has demonstrable in vitro activity against aerobic and anaerobic Gram-positive bacteria.
Telavancin and
vancomycin have similar spectra of activity. Gram-negative bacteria are usually non-susceptible to
telavancin.
Telavancin has been successfully tested in various animal models of
bacteremia,
endocarditis,
meningitis, and
pneumonia. Phase II
Telavancin versus Standard
Therapy for Treatment of Complicated Skin and
Soft-Tissue Infections due to Gram-Positive Bacteria (FAST 1 and FAST 2) and phase III [Assessment of
Telavancin in Complicated Skin and Skin Structure
Infections 1 (ATLAS 1 and ATLAS 2)] clinical trials have been conducted for evaluating
telavancin's efficacy and safety in cSSSIs. Phase III clinical trials have been carried out for evaluating
telavancin's safety and efficacy in
nosocomial pneumonia [Assessment of
Telavancin for Treatment of
Hospital acquired Pneumonia 1 and 2 (ATTAIN 1 and ATTAIN 2)]. A phase II randomized, double-blind, clinical trial has been carried out for evaluating
telavancin's safety and efficacy in uncomplicated S. aureus
bacteremia [
Telavancin for Treatment of Uncomplicated S. aureus
Bacteremia (ASSURE)]. Pacemaker lead-related
infective endocarditis due to a
vancomycin intermediate S. aureus (VISA) strain (non-
daptomycin susceptible) was successfully treated with parenteral
telavancin for 8 weeks.
Telavancin extensively binds to
serum albumin (~93%) and has a relatively small volume of distribution.
Telavancin is not biotransformed by any
cytochrome P450 microsomal
enzymes and excreted mainly in the urine. Though well-tolerated, worrisome adverse effects, including renal dysfunction and QTc prolongation are of potential concern. Given its extensive binding to
plasma proteins, long half-life, and a long post-
antibiotic effect, it represents a promising addition to the therapeutic armamentarium in combating
infections caused by resistant Gram-positive pathogens, namely, MRSA.