A Review of Ceftolozane/Tazobactam for the Treatment of Infections Caused by Multidrug-Resistant Pathogens

Multidrug-resistant (MDR) gram-negative bacterial infection is a serious and growing public health threat, in part due to limited treatment options. A novel cephalosporin and β-lactamase inhibitor, ceftolozane/tazobactam, has a broad spectrum of activity against MDR pathogens and is approved for the treatment of complicated intra-abdominal infections in combination with metronidazole and complicated urinary tract infections, including pyelonephritis. This article reviews published data on the clinical pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, clinical efficacy and safety, and dosing and administration of ceftolozane/tazobactam. Searches of MEDLINE from January 2000 to April 2017 were conducted using the following keywords: ceftolozane, tazobactam, and ceftolozane tazobactam. Additional references were identified from a review of the retrieved articles' citations. Ceftolozane is active against organisms producing AmpC β-lactamases and MDR Pseudomonas aeruginosa. The addition of tazobactam enhances activity against extended-spectrum β-lactamase–producing organisms. Data from phase III trials using ceftolozane/tazobactam for the treatment of complicated intra-abdominal infection and complicated urinary tract infections have yielded positive results. Ceftolozane/tazobactam has demonstrated noninferior or superior efficacy to comparators in clinical trials. It has a favorable safety profile and few drug-drug interactions. This novel combination agent has a role in treating MDR infections, particularly P. aeruginosa, although its use should be reserved for patients without other treatment options to limit the risk of resistance. Although case reports of successful treatment have been reported, further investigation is needed into the utility of ceftolozane/tazobactam for the treatment of bacteremia and pneumonia caused by MDR pathogens. Correspondence to: Jamielynn Sebaaly, PharmD, BCPS, Wingate University School of Pharmacy, 515 N. Main St, Wingate, NC 28174. E-mail: j.sebaaly@wingate.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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