Pharmacological aspects and spectrum of action of ceftazidime–avibactam: a systematic review

Abstract

Purpose: Ceftazidime–avibactam is an antimicrobial association active against several Enterobacteriaceae species, including those resistant to carbapenem. Considering the importance of this drug in the current panorama of multidrug-resistant bacteria, we performed a systematic review about ceftazidime–avibactam with emphasis on clinical and pharmacological published data. Methods: A systematic search of the medical literature was performed. The databases searched included MEDLINE, EMBASE and Web of Science (until September 2017). The search terms used were ‘avibactam’, ‘NXL104’ and ‘AVE1330A’. Bibliographies from those studies were also reviewed. Ceftazidime was not included as a search term, once relevant studies about avibactam in association with other drugs could be excluded. Only articles in English were selected. No statistical analysis or quality validation was included in this review. Results: A total of 151 manuscripts were included. Ceftazidime–avibactam has limited action against anaerobic bacteria. Avibactam is a potent inhibitor of class A, class C, and some class D enzymes, which includes KPC-2. The best pharmacodynamic profile of ceftazidime–avibactam is ƒT > MIC, validated in an animal model of soft tissue infection. Three clinical trials showed the efficacy of ceftazidime–avibactam in patients with intra-abdominal and urinary infections. Ceftazidime–avibactam has been evaluated versus meropenem/doripenem in hospitalized adults with nosocomial pneumonia, neutropenic patients and pediatric patients. Conclusion: Ceftazidime–avibactam has a favorable pharmacokinetic profile for severe infections and highly active against carbapenemases of KPC-2 type.