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.

Keywords:

• avibactam
• β-lactamases
• ceftazidime
• intra-abdominal infections
• urinary tract infections

Acknowledgments

Editorial assistance was provided by Micron Research Ltd, Ely, UK. As part of the review process, the article was sent to AstraZeneca to review the data accuracy.

Declaration of interests

The author has acted as investigator and speaker for AstraZeneca and Forest Laboratories, LLC. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Editorial assistance was utilized in the production of this manuscript and funding was provided by Forest Laboratories, LLC.