Telavancin

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Gram-positive bacteria, such as staphylococci and β-haemolytic streptococci, are often the cause of skin and skin structure infections (SSSIs), such as cellulitis, wound infections, ulcers and abscesses.[1] Such infections are usually considered to be a complicated SSSI (cSSSI) when the deeper layers of soft tissue are involved and/or surgery is required.[1]

The treatment of cSSSIs caused by resistant strains of Gram-positive pathogens (e.g. meticillin/oxacillin-resistant Staphylococcus aureus [MRSA] and macrolide-resistant Streptococcus pyogenes) is difficult.[1-3] Drug-resistant S. aureus infections, which are often associated with high morbidity and mortality,[4] may require treatment with a glycopeptide antibacterial (e.g. vancomycin), linezolid, daptomycin, or quinupristin with dalfopristin.[1] There is a need for the development of alternative antibacterial treatments for cSSSIs, as multidrug-resistant Gram-positive pathogens continue to emerge and become more prevalent.

Telavancin (Vibativ(TM)) is the first available member of a new class of antibacterials known as lipoglycopeptides. It is administered intravenously once daily, and is active against Gram-positive bacteria, including MRSA. This profile reviews the pharmacological profile of telavancin and its clinical efficacy and tolerability in adult patients with cSSSIs. The efficacy of telavancin in other types of infections caused by Gram-positive bacteria is beyond the scope of this review.

Medical literature on the use of telavancin in cSSSIs was identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database). Additional references were identified from the reference list of published articles. Fully published data have been used where possible, but some recent abstract and/or poster reports have been included for completeness.

1. Pharmacodynamic Profile

Mechanism of Action

* Telavancin, a lipoglycopeptide, is a semisynthetic derivative of vancomycin that contains an additional lipophilic side chain (decylaminoethyl) and an additional negatively charged hydrophilic group (phosphomethyl aminomethyl).[5] It demonstrates bactericidal activity against Gram-positive pathogens via a multifunctional mechanism of action (inhibition of bacterial cell wall synthesis and disruption of cell membrane integrity),[6-8] which accounts for its activity against strains of S. aureus with reduced susceptibility to vancomycin.[9,10]

* Telavancin inhibits late stages of peptidoglycan synthesis and interferes with bacterial cell wall synthesis.[7-9,11] It binds to the D-Ala-D-Ala terminus of pentapeptide peptidoglycan precursors, thereby inhibiting cell wall peptidoglycan crosslinking.[8] Although telavancin shares this mechanism of action with other glycopeptides, telavancin is [approximate]10-fold...