Antibiotic - ceftobiprole medocaril

Novel antibiotics are needed if the threat from bacteria is to be challenged. Cephalosporins have a broad spectrum of activity, are commonly associated with low levels of side effects, and a novel cephalosporin antibiotic is being developed by Basilea Pharmaceutica.

Ceftobiprole medocaril is a prodrug for the fourth generation cephalosporin ceftobiprole, which is rapidly formed from the prodrug in plasma. Several clinical trials have already been carried out, including numerous pharmacokinetic studies. In one, 40 healthy male subjects were given single doses equivalent to 125, 250, 500, 750 and 1000mg of ceftobiprole as a 200 ml infusion over half an hour, and in another, 16 healthy male subjects were given multiple doses equivalent to 500 and 700mg ceftobiprole by similar infusion once a day on days 1 and 8, and twice a day on days 2 and 7. It was well tolerated at all doses, and no serious adverse events were seen. The trials suggested that 750mg twice a day would be best for treating MRSA.^1,2

In a Phase II study, it was given to 40 patients with complicated skin and skin structure infections, mostly caused by staphylococcus and streptococcus species, including four who were suffering from MRSA and 15 from MSSA.³ Doses of 750mg were given twice a day by 30 minute infusion, for seven to 14 days. A total of 35 of the patients were evaluable and were cured of their infection.

Basilea has advanced the drug into Phase III studies, and a multicentre randomised controlled trial is under way, to evaluate its efficacy and safety in comparison to vancomycin in around 700 patients, and is planning further studies in patients with severe infections. The drug has fast track designation for the treatment of these severe skin infections caused by MRSA, and also for the treatment of hospital acquired pneumonia, including infections associated with ventilators associated with MRSA.