Segment Description: Marin Kollef, MD, a professor in the Department of Internal Medicine, Pulmonary, and Critical Care at Washington University in St. Louis, Missouri, discusses what makes the3-gram dose regimen of ceftolozane/tazobactam unique.
Interview transcript: (modified slightly for readability)
I think the unique part of the 3-gram dosing is there's a history within clinical trials looking at nosocomial pneumonia over the last 20 years where the trials really haven't been designed in an optimal manner. Part of the problem with some of the prior studies has been the dosing of the drug. So, I think there's been this perception in the past that you know we need to have 1 dose for all indications and that just doesn't make sense clinically.
We know that antibiotics have different penetration capabilities within the lung and we've seen some clinical failures in the past that have resulted in unfortunate events. A couple of examples would be the ceftobiprole trial in patients with nosocomial pneumonia; the experience with tigecycline; the doripenem study in patients who had ventilated pneumonia as well; all of which demonstrated that the new drug being evaluated did not do as well. And a lot of that had to do with the way the drug was dosed within the study design.
The ASPECT nosocomial pneumonia study, the 3-gram dose was one of the unique aspects of it because it was tailored for treating gram-negative infections within the lung based on the epithelial lining fluid concentration studies that were done prior to the study.
So, we actually did those studies got the measurements within the lung and then that helped us to design the proper dosing for treating these patients. Having done that, in this non-inferiority study we were able to demonstrate that when we look at 28-day mortality there were no differences between 2 groups—that's what the non-inferiority aspect of the study is meant to do.
But when you actually look at the study there are signals, that even within that trial, there may be some advantages for ceftolozane/tazobactam. As an example, patients who had ventilated HAP did better their mortality was less than the group that got treated with meropenem. And there were other subgroups which will be in the manuscript that will be published highlighting that effect as well.
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