Ceftolozane/Tazobactam Deemed Safe, Effective Against Drug-Resistant P aeruginosa

A dangerous drug-resistant hospital-acquired infection that has raised increasing concern among public health officials can be effectively treated with a drug already on the market, according to new research.

A new study published last month in Clinical Infectious Diseases finds the combination of ceftolozane and tazobactam is safe and effective for patients with drug-resistant Pseudomonas aeruginosa when compared with polymyxins or aminoglycosides.

The findings suggest the novel cephalosporin/beta-lactamase inhibitor would be the better option for patients dealing with multidrug resistant (MDR) or extensively drug resistant (XDR) P aeruginosa infections.

As drug resistance has become a bigger and bigger problem when treating P aeruginosa, providers have increasingly relied on polymyxins and aminoglycosides. Those drugs are a less-than-ideal solution, though, according to study author Jason M. Pogue, PharmD, of the University of Michigan College of Pharmacy, and colleagues. At IDWeek 2019, Contagion® spoke to Pogue, a member of the Contagion® Editorial Advisory Board, about the research.

“Regrettably, these agents are characterized by suboptimal pharmacokinetics, a narrow therapeutic index, and high rates of nephrotoxicity,” Pogue and colleagues wrote. “Moreover polymyxins and aminoglycosides have demonstrated inferior efficacy to first-line options.”

Ceftolozane/tazobactam, which is sold under the brand name Zerbaxa, has shown signs of promise against beta-lactam resistant P aeruginosa, but no one had yet done a direct safety and efficacy comparison of the 2 in such a setting. Pogue and colleagues set out to change that.

To study the question, they set up a retrospective, multicenter study comparing patients who received ceftolozane/tazobactam for drug-resistant P aeruginosa to those who received polymyxins or aminoglycosides. In all, 200 patients were included in the study, split evenly between the 2 therapeutic cohorts. Of those, most (69%) were in the intensive care unit and nearly as many (63%) were on a mechanical ventilator. Forty-two percent of patients were either in septic shock or had severe sepsis at the time of infection. Half of the patients (52%) had ventilator-associated pneumonia, the most common infection type among those in the study.

Pogue and colleagues found 81% of patients who took ceftolozane/tazobactam were clinically cured, which translated to an adjusted odds ratio of 2.63. Acute kidney injury rates were 6% in the ceftolozane/tazobactam group, compared to 34% in the polymyxin/aminoglycoside group (aOR 0.08).

There was no difference in hospital mortality between the 2 groups.

“These findings support the preferential use of ceftolozane/tazobactam over polymyxins and/or aminoglycosides for MDR and XDR P aeruginosa infections,” Pogue and colleagues conclude. “In addition, the findings are consistent with recent data in carbapenem-resistant Enterobacteriaceae that demonstrate that novel beta-lactam/beta-lactamase inhibitors… are superior to traditional, suboptimal regimens for the management of XDR gram-negative infections.”

According to the US Centers for Disease Control and Prevention (CDC), about 13% of the 51,000 hospital-associated P aeruginosa infections each year in the United States are from MDR P aeruginosa. More than 400 people die each year from MDR P aeruginosa, the CDC reports. As a result, the agency put MDR P aeruginosa under the category of “serious threats” in its 2013 report “Antibiotic Resistance Threats in the United States. The CDC was working to update that list with a new version scheduled to come out this year.

For its part, the World Health Organization in 2017 listed P aeruginosa as a bacteria for which new antibiotics are “urgently needed.” P aeruginosa was placed in the “Priority 1: Critical” category.