Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections

Abstract

Ceftazidime-avibactam (Zavicefta®) is an intravenously administered combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam. In the EU, ceftazidime-avibactam is approved for the treatment of adults with complicated urinary tract infections (cUTIs) [including pyelonephritis], complicated intra-abdominal infections (cIAIs), hospital-acquired pneumonia (HAP) [including ventilator-associated pneumonia (VAP)], and other infections caused by aerobic Gram-negative organisms in patients with limited treatment options. This article discusses the in vitro activity and pharmacological properties of ceftazidime-avibactam, and reviews data on the agent's clinical efficacy and tolerability relating to use in these indications, with a focus on the EU label. Ceftazidime-avibactam has excellent in vitro activity against many important Gram-negative pathogens, including many extended-spectrum β-lactamase-, AmpC-, Klebsiella pneumoniae carbapenemase- and OXA-48-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa isolates; it is not active against metallo-β-lactamase-producing strains. The clinical efficacy of ceftazidime-avibactam in the treatment of cUTI, cIAI and HAP (including VAP) in adults was demonstrated in pivotal phase III non-inferiority trials with carbapenem comparators. Ceftazidime-avibactam treatment was associated with high response rates at the test-of-cure visit in patients with infections caused by ceftazidime-susceptible and -nonsusceptible Gram-negative pathogens. Ceftazidime-avibactam was generally well tolerated, with a safety and tolerability profile consistent with that of ceftazidime alone and that was generally typical of the injectable cephalosporins. Thus, ceftazidime-avibactam represents a valuable new treatment option for these serious and difficult-to-treat infections.