Ceftolozane/tazobactam and ceftazidime/avibactam: Two novel β-lactam/β-lactamase inhibitor combination agents for the treatment of resistant Gram-negative bacterial infections

Jordan L. Liscio, Monica V. Mahoney, Elizabeth B. Hirsch

Research output: Contribution to journalReview articlepeer-review

86 Scopus citations

Abstract

The rise in resistant Gram-negative bacteria is a major concern and has led to difficulty in treating multidrug-resistant (MDR) infections. Two recently approved combination antibiotics, ceftolozane/tazobactam and ceftazidime/avibactam, may be effective in treating these resistant infections. Ceftolozane is a novel cephalosporin that has been developed in combination with tazobactam, a recognised β-lactamase inhibitor (BLI). Avibactam is a novel BLI combined with ceftazidime, a cephalosporin with an established history. Both of these β-lactam/BLI combination agents have been shown to retain in vitro activity against selected resistant Gram-negative pathogens, including Enterobacteriaceae and Pseudomonas aeruginosa; notably, ceftazidime/avibactam has demonstrated consistent activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms. Both agents have been approved for the indications of complicated intra-abdominal infection (with metronidazole) and complicated urinary tract infection, and have ongoing phase 3 trials for the treatment of ventilator-associated and nosocomial pneumonia. This manuscript will review current data available regarding the spectrum of activity and clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents. Both agents appear to be well tolerated and show promise in the treatment of MDR Gram-negative infections.

Original languageEnglish (US)
Pages (from-to)266-271
Number of pages6
JournalInternational Journal of Antimicrobial Agents
Volume46
Issue number3
DOIs
StatePublished - Sep 27 2015

Bibliographical note

Funding Information:
Competing interests: MVM has received research funding from Forest Pharmaceuticals/Actavis and consulting honoraria from Cubist Pharmaceuticals; EBH has received research funding from Durata Therapeutics/Actavis and consulting honoraria from Theravance Biopharma. JLL declares no competing interests.

Publisher Copyright:
© 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • ESBL
  • KPC
  • Pseudomonas aeruginosa
  • cIAI
  • cUTI

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