Ceftolozane/tazobactam: a novel antipseudomonal cephalosporin and β-lactamase-inhibitor combination

Abstract

The management of infections caused by multidrug-resistant Gram-negative bacteria, particularly Pseudomonas aeruginosa, continues to be a significant challenge to clinicians. Ceftolozane/tazobactam is a novel antibacterial and β-lactamase-inhibitor combination that has shown appreciable activity against wild-type Enterobacteriaceae and potent activity against P. aeruginosa. Moreover, ceftolozane/tazobactam has not demonstrated cross-resistance to other antimicrobial classes, particularly those affected by extended-spectrum β-lactamases, AmpC β-lactamase, a loss in porin channels, or the overexpression of efflux pumps in P. aeruginosa. Ceftolozane/tazobactam has completed two Phase II clinical trials in complicated intra-abdominal and complicated urinary tract infections. A Phase III, multicenter, prospective, randomized, open-label study has been initiated to evaluate the safety and efficacy of ceftolozane/tazobactam versus piperacillin/tazobactam for the treatment of ventilator-associated pneumonia. A Medline search of articles from inception to May 2013 and references for selected citations was conducted. Data from abstracts presented at conferences were also appraised. This article reviews the antimicrobial, pharmacokinetic, and pharmacodynamic profile of ceftolozane/tazobactam, and discusses its potential role in therapy.

Keywords:

• CXA-201
• CXA-101
• FR264205
• Pseudomonas aeruginosa

Acknowledgments

We would like to thank Philip Tam, PhD for building the chemical structures of ceftolozane and tazobactam. Chemical structures were developed using BKChem software (http://bkchem.zirael.org). We would also like to thank John Mohr, PharmD for provision of data.

Disclosure

The authors report no conflicts of interest in this work. Donald Hsu is a speaker for Astellas, Inc, Optimer Pharmaceuticals, and Merck Inc. The views expressed in this article are solely those of the authors and do not necessarily reflect the views of the Western University of Health Sciences, St Joseph Hospital Orange, Veterans Affairs San Diego Healthcare System, nor University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences.