Ceftolozane-tazobactam (Zerbaxa®) is a combination of a novel cephalosporin (CXA-101) with the beta-lactamase inhibitor tazobactam. A marketing authorisation application for the treatment of complicated urinary tract infections and complicated intra-abdominal infections was accepted by the EMA in August 2014 but it has not yet been approved for use in the EU.
In this study, the primary endpoint was a composite of microbiological eradication and clinical cure rate (composite cure rate) at 5-9 days after the end of therapy (the test of cure visit). Ceftolozane-tazobactam was shown to be non-inferior to levofloxacin with regards to this endpoint in both the microbiological modified intention-to-treat population (those who showed growth of one or two uropathogens of at least 105 colony-forming units per mL in urine culture) and the per-protocol population.
A related Comment article notes that the increasing prevalence of multidrug-resistant Enterobacteriaceae spp and Pseudomonas aeruginosa among urinary isolates has led to major challenges in the selection of effective antibiotic treatments for complicated urinary-tract infections. In this study, ceftolozane-tazobactam was shown to be superior to levofloxacin both in patients with infections caused by ESBL-producing bacteria (62.3% v 35.1%) and in those with infections caused by levofloxacin-resistant bacteria (60.0% v 39.3%).
These results suggest that ceftolozane-tazobactam could be a useful new treatment option for patients with complicated urinary-tract infections, especially those caused by multidrug-resistant Gram-negative bacteria. Certain features of its clinical use however remain to be addressed, including the optimum duration of therapy and the safety and optimal dosing regimen in patients with renal impairment. The authors of the Comment additionally note that clinicians need to be aware of its limited activity against other important uropathogenic bacteria, including enterococci and carbapenemase-producing Enterobacteriaceae spp.