Antibiotic - telavancin
The growing problem of antibiotic resistance means that new drugs that work by new pathways are urgently needed.
The growing problem of antibiotic resistance means that new drugs that work by new pathways are urgently needed.
Vancomycin is one of the few drugs that remains active against most Gram positive pathogens, and this provided the starting point for researchers at US company Theravance. By adding hydrophobic substituents to the vancomycin core, its activity against vancomycin-resistant enterococci can be restored, while it remains effective against MRSA (methicillin-resistant Staphylococcus aureus).
This has resulted in the developmental lipoglycopeptide antibiotic telavancin, formerly referred to as TD 6424, which has multiple mechanisms of action.1 Several clinical trials have been carried out, including an investigation into its effects on cardiac repolarisation, after preclinical and early clinical data suggested it might have this effect.2 A total of 160 healthy subjects were given placebo, 7.5 or 15mg/kg telavancin or moxifloxacin as a positive control, once a day for three days as IV infusions. ECGs were taken, which showed it had a five millisecond mean effect on cardiac repolarisation.
A Phase II trial was subsequently carried out in 167 patients with complicated Gram positive skin and soft tissue infections.3 In the randomised double blind placebo-controlled trial they were given either intravenous telavancin once a day, one of the standard therapies of antistaphylococcal penicillin four times a day, or vancomycin twice a day. Of those with S. aureus infection, 80% who received telavancin and 77% of those given standard therapy were cured. If the infection was with MRSA, 82% given telavancin were cured compared with 69% of the standard therapy group. The level of discontinuation as a result of adverse events was similar for all patients, at about 5%, and fewer adverse events were reported in those given the experimental drug. Phase III trials are under way.