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Ceftolozane/Tazobactam: A Review in Complicated Intra-Abdominal and Urinary Tract Infections

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Abstract

Globally, the increasing prevalence of multidrug-resistant pathogens continues to pose major problems in healthcare systems and, at least in part, is driving an initiative to develop new antibacterials, such as ceftolozane (a cephalosporin β-lactam). Adding a β-lactamase inhibitor (e.g. tazobactam) to a β-lactam extends its spectrum of activity against β-lactamase-producing microorganisms (a key mechanism of resistance to β-lactams). Ceftolozane/tazobactam (Zerbaxa™), a β-lactam/β-lactamase inhibitor combination, is indicated for the treatment of adults with complicated intra-abdominal infections (cIAI) or complicated urinary tract infections (cUTI), including pyelonephritis. In multinational, phase 3 noninferiority trials, intravenous ceftolozane/tazobactam was an effective and generally well tolerated treatment in patients with cIAI or cUTI. In the ASPECT-cIAI trial, ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in terms of clinical cure rates at the test-of-cure (TOC) visit, with clinical cure rates in subgroup analyses consistent with those in the primary analysis. In the ASPECT-cUTI trial, ceftolozane/tazobactam was superior to levofloxacin in terms of composite cure rates (clinical cure plus microbiological eradiation) at the TOC visit. Further clinical experience should help to more definitively position ceftolozane/tazobactam in the treatment of cIAI and cUTI, including in patients with renal impairment. In the meantime, given its very good in vitro activity against extended-spectrum β-lactamase-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa isolates, ceftolozane/tazobactam provides a potential alternative to currently approved antibacterials for empirical treatment of cIAI and cUTI in adults.

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During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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The preparation of this review was not supported by any external funding.

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    Lesley J. Scott

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Lesley Scott is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

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The manuscript was reviewed by: T. Cai, Department of Urology, Santa Chiara Regional Hospital, Trento, Italy; L.E. Nicolle, University of Manitoba, Internal Medicine Health Sciences Center, Winnipeg, Manitoba, Canada; G. Poulakou, 4th Department of Internal Medicine, Athens Medical School, Attikon University General Hospital, Athens, Greece; O.R. Sipahi, Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Bornova Izmir, Turkey.

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Scott, L.J. Ceftolozane/Tazobactam: A Review in Complicated Intra-Abdominal and Urinary Tract Infections. Drugs 76, 231–242 (2016). https://doi.org/10.1007/s40265-015-0524-5

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