Antibiotic - ceftaroline fosamil
Bacterial resistance is a growing global problem, particularly for Gram positive bacteria such as Staphylococcus aureus. As a result, new antibiotics that are active against resistant bacteria, whether Gram positive or Gram negative, are very much needed.
Bacterial resistance is a growing global problem, particularly for Gram positive bacteria such as Staphylococcus aureus. As a result, new antibiotics that are active against resistant bacteria, whether Gram positive or Gram negative, are very much needed.
One such agent, ceftaroline fosamil, was developed by Japanese company Takeda, and has been licensed to Forest Labs subsidiary Cerexa, which is carrying out clinical trials.1 The drug is a phosphonate prodrug of the cephalosporin antibiotic ceftaroline, and it is rapidly converted into the active form in the body. It is being developed in prodrug form because ceftaroline itself is too chemically unstable.2 It has a broad spectrum of antibiotic activity and is being investigated for treating community acquired pneumonia, and also complicated skin and skin structure infections caused by methicillin resistant Staphylococcus aureus, against which it shows good activity.
Numerous clinical trials have been carried out. In one, 48 healthy male subjects were given the prodrug as a single intravenous infusion in doses of 50, 100, 250, 500, 750 and 1000mg over one hour, or placebo.3 It was safe and well tolerated at all doses, with most adverse events being mild. The most common of these was headache.
Its safety compared with vancomycin has also been investigated.4 A total of 1,000 hospitalised adult patients with complicated skin and skin structure infections were randomised to receive 600mg of intravenous ceftaroline fosamil over an hour every 12 hours or 1g of intravenous vancomycin every 12 hours, either with or without 1g of intravenous aztreonam every eight hours, for seven to 14 days. Most of the adverse events from ceftaroline were mild, including urinary crystals, insomnia, nausea and rash. A total of 88 of these subjects were evaluable, and the clinical cure rate for the drug was 96.7%, compared with 88.9% for the vancomycin group. In addition, the microbiological response rate for ceftaroline fosamil was 95.2%, whereas the response rate for vancomycin was 85.7%.