title: Focus on ceftazidime-avibactam for optimizing outcomes in complicated intra-abdominal and urinary tract infections.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Anti-Infective Research and Development Hartford Hospital , 80 Seymour Street, Hartford, CT 06102-5037 , USA +1 860 972 3941 ; +1 860 545 3992 ; david.nicolau@hhchealth.org.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D053961:Azabicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002442:Ceftazidime / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy* / Q000382:microbiology; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D065093:beta-Lactamase Inhibitors; D002442:Ceftazidime
keywords: avibactam; ceftazidime; intra-abdominal infections; urinary tract infections; β-lactamases