By Marcio Barra
A new antibiotic has been approved for use in the European Union to treat patients with serious Gram-negative bacterial infections requiring hospitalisation.
The drug, Astrazeneca’s Zavicefta, is a fixed combination of avibactam, a new beta-lactamase inhibitor, and ceftazidime, a third generation cephalosporin antibiotic already approved for use in the European Union.
Multidrug-resistant Gram-negative bacteria are increasingly encountered globally, posing serious health risks to the population. The inhibition of the action of beta-lactamases, which play a key role in the development of bacterial resistance, is a standard method of fighting bacterial infections.
Avibactam is a first-in-class non-β-lactam β-lactamase inhibitor. The drug restores the in vitro activity of ceftazidime by protecting it against Ambler class A, class C, and some class D β-lactamases produced by bacteria. The drug has a similar mechanism of action to other β-lactam inhibitors available, acting through covalent modification of a catalytically important nucleophilic serine residue. However, unlike the β-lactam inhibitors, avibactam reacts reversibly with its β-lactamase targets.
Zavicefta was approved by the European Medicines Agency back in April for the treatment of adult patients suffering from complicated intra-abdominal infections (cIAI); Complicated urinary tract infections (cUTI), including pyelonephritis; hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP); and, the treatment of aerobic Gram-negative infections in adult patients who have limited treatment options. This approval by the European Commission allows Astrazeneca to market the drug in all 28 European Union countries as well as Iceland, Norway and Liechtenstein.
Zavicefta is being jointly developed by AstraZeneca and Allergan; AstraZeneca holds the global commercialisation rights, with the exception of North America, where the rights are held Allergan. The drug is already approved in the US by the Food and Drug Administration for the treatment of cUTI including acute pyelonephritis, and complicated intra-abdominal infections. Approval for the drug was based on two Phase II studies, with Phase III results only recently becoming available.