By Reuters Staff
NEW YORK (Reuters Health) - 2/10/2019
The combined antibacterial ceftolozane-tazobactam, sold as Zerbaxa by Merck, is a safe and effective option for nosocomial pneumonia, according to results of the noninferiority trial that led to approval of the drug for this indication in the U.S. in June.
Nosocomial pneumonia is a common and serious hospital-acquired infection and new treatment options are "urgently needed," the study team notes in The Lancet Infectious Diseases, online September 25.
Ceftolozane is a cephalosporin and tazobactam is a beta-lactamase inhibitor. The study, a double-blind, phase-3 noninferiority trial, enrolled 726 mechanically ventilated adults with Gram-negative nosocomial pneumonia; 362 were randomly assigned to treatment with ceftolozane-tazobactam (2 g ceftolozane plus 1 g tazobactam infused over one hour every eight hours) and 364 were treated with meropenem (1 g infused over one hour every eight hours).
In the intent-to-treat population, 28-day all-cause mortality rates (the primary endpoint) was similar in the ceftolozane/tazobactam arm and the meropenem arm (24.0% and 25.3%, respectively).
There were also no between-group differences in the key secondary endpoint of clinical cure at the "test-of-cure" visit seven to 14 days after the end of therapy (54% and 53%, respectively).
"Ceftolozane-tazobactam was thus non-inferior to meropenem in terms of both 28-day all-cause mortality and clinical cure at test of cure," write Dr. Elizabeth Rhee of Merck & Co and colleagues.
Ceftolozane-tazobactam was well tolerated, and no new safety issues were identified, even at the 3 g dose used in the study, which is higher than the 1.5 g dose approved for other indications, the investigators note.
"High-dose ceftolozane-tazobactam can be used to treat nosocomial pneumonia caused by P aeruginosa (including multidrug-resistant strains), Enterobacteriaceae (including producers of extended-spectrum beta-lactamases), and other Gram-negative pathogens," they conclude.
The authors a linked comment say this trial has several strengths, including a large sample size, procedures to ensure proper blinding, stratification of randomization by diagnosis (ventilator-associated pneumonia vs. ventilated hospital-acquired pneumonia), and even randomization across groups within a geographic region.
"Ceftolozane-tazobactam is a welcome addition to the antibiotic armamentarium for nosocomial pneumonia," write Dr. Andre Kalil of the University of Nebraska, Omaha, and Dr. Alexandre Zavascki of Federal University of Rio Grande do Sul, in Brazil.
"Still, in view of the high dose used in this trial and the limited safety data available, close monitoring and surveillance of clinical practice and phase 4 safety registries will be necessary to better define the risk-benefit profile of this new antimicrobial," they conclude.
The study was funded by Merck & Co. Several authors are employees of the company and/or have financial relationships with the company.
Lancet Infect Dis 2019.
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