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

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.