Focus on ceftazidime-avibactam for optimizing outcomes in complicated intra-abdominal and urinary tract infections

Abstract

Introduction: Complicated intra-abdominal infections and urinary tract infections are frequently associated with Gram-negative bacteria and treatment can be hampered by the involvement of resistant organisms. A common resistance mechanism is β-lactamase production which confers resistance to β-lactam antibiotics.Areas covered: This article summarizes β-lactamases found among Gram-negative bacteria as well as providing an overview of complicated intra-abdominal infections and urinary tract infections and the impact inappropriate antibiotic therapy and antibiotic resistance has in their treatment. The author reviews the activity of ceftazidime-avibactam, including animal model data and microbiological data from Phase II clinical trials. This article also highlights Phase III clinical trials of ceftazidime-avibactam that are ongoing or completed and briefly discusses other β-lactamase inhibitor combinations currently in development.Expert opinion: The increasing problem and complexity of β-lactamase resistance has been met by resurgence in the development of β-lactamase inhibitor combinations. These show promise in the treatment of resistant infections. One β-lactamase inhibitor in advanced development with a broad spectrum of activity is avibactam, covering class A, class C and some class D enzymes. Importantly, the activity of avibactam also includes carbapenemases such as the KPC and OXA-48. The combination of avibactam with the cephalosporin ceftazidime is attractive, given the spectrum of antimicrobial activity and the low toxicity of the cephalosporin class.