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Ceftolozane & Tazobactam Proves Noninferior to Meropenem in Patients with HABP or VABP

Ceftolozane and tazobactam proves noninferior to meropenem in a pivotal phase 3 trial of adult patients with HABP or VABP.

A recent phase 3 trial assessing the safety and effectiveness of Merck & Co.’s ceftolozane and tazobactam (ZERBAXA) for the treatment of adults with ventilated hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) has met its primary endpoints.

The antibacterial combination therapy is comprised of ceftolozane sulfate (a cephalosporin antibacterial drug) and tazobactam sodium (a beta-lactamase inhibitor) has proven noninferior to meropenem in day 28 all-cause mortality as well as in clinical cure rate at the test-of-cure visit.

“HABP and VABP are serious and life-threatening hospital-related pulmonary infections, especially in patients with severe underlying medical conditions,” Dr. Roy Barnes, Merck Research Laboratories’ senior vice president, head of global clinical development, and chief medical officer, said in a recent statement. “The results from the ASPECT-NP study demonstrate the potential role of ZERBAXA for the treatment of patients with HABP and VABP.”

For the prospective, randomized, double-blind phase 3 trial, investigators set out to compare the safety and effectiveness of ceftolozane and tazobactam with meropenem in 736 adults with ventilated HABP or VABP who required intravenous antibiotic therapy. To do this, they administered either a 3g dose of the investigational therapy or 1g dose of meropenem. Doses were administered every 8 hours intravenously for 8 to 14 days; dosing continued for 14 days for Pseudomonas aeruginosa infection.

Currently, ceftolozane (1g) and tazobactam (0.5g) has been approved by the FDA for the treatment of adults with complicated urinary tract infections—including pyelonephritis—caused by several Gram-negative microorganisms. Ceftolozane and tazobactam is also approved to be used in combination for adults with complicated intra-abdominal infections caused by certain Gram-negative and Gram-positive microorganisms.

Zerbaxa has a different approach, in which the cephalosporin β-lactam component is actually a new component. It’s a new cephalosporin that is particularly good at the ability to truly get through the outer membrane of Pseudomonas and resist some of the efflux and so forth,” Yoav Golan, MD, an attending physician at Tufts Medical Center, said in a recent Peer Exchange. “It’s given with an older β-lactamase inhibitor, tazobactam, to allow the antibiotic to resist those β-lactamases.”

Due to the trial’s positive findings, Merck will submit supplemental new drug applications to both the US Food and Drug Administration and the European Medicines Agency to obtain approval for ceftolozane and tazobactam for adult patients with HABP or VABP.

Full results from the trial will be presented at future scientific conferences.