Cefiderocol vs High-Dose Meropenem for the Treatment of Patients With Nosocomial Pneumonia

Segment Description: Ryan K. Shields, PharmD, MS, associate professor of medicine at the University of Pittsburgh and content editor for the Multidrug-Resistant Infections section of Contagion®, reacts to a phase 3 study presented at IDWeek 2019 evaluating cefiderocol versus high-dose meropenem for the treatment of patients with nosocomial pneumonia.

Interview transcript: (modified slightly for readability)

Dr. Shields: One of the exciting abstracts that was presented at a late-breaker presentation at IDWeek 2019 was cefiderocol compared to meropenem for patients with hospital or ventilator-associated pneumonia. Now, these are really important data because, up to this point, the only data that we've seen for cefiderocol is a urinary tract infection study where they compared cefiderocol to imipenem for patients with complicated urinary tract infections. Now, we know as clinicians this is a drug that ultimately we may be using for hospital or ventilator-associated pneumonia (HAP/VAP) in our hospitals, so these are the kinds of data we need to know to ultimately know how to position this agent.

In the study, [investigators] randomized about 150 patients to either receive cefiderocol, 2 grams every 8 hours over a 3-hour infusion, or meropenem, 2 grams every 8 hours also over a 3-hour infusion. Now, the dosing of meropenem in this study is particularly important because now we know we're giving dose-optimized meropenem, at a very nice dose, that's going to achieve very nice target attainment even for more resistant pathogens for patients with HAP or VAP. So the dosing of meropenem is unlike other prior studies where they've given only 1 gram every eight hours, so an important differentiator in this particular study.

What the investigators found is that the study patients themselves were moderately ill, about 60% of patients in the study were ventilated and the median APACHE II scores were right around 15, so these patients weren't critically ill and on the doorsteps of death, but they were moderately ill and certainly an important study population that we see in our hospitals. The primary outcome of the study was all-cause mortality at day 14, so you looked at a shorter end point here; many of the other HAP/VAP trials we see look at a 28-day mortality, [and] that was a secondary end point in this study. Ultimately, what the investigators found is that cefiderocol met its non-inferiority margins compared to meropenem, and so the groups were very comparable. In fact, the groups were comparable when broken down by pathogen and also among patients broken down by severity of illness and all other subgroup analyses that they did. The one thing that we'd like to know a little bit more about this trial is 22% of patients after randomization, had a meropenem-resistant isolate isolated from their respiratory tract. We don't have any data on those patients that had meropenem-resistant infections quite yet, but this will certainly be something that we keep an eye out for as the data is published. But so far, this is all good news for cefiderocol. It looks to be at least non-inferior to meropenem for patients with HAP/VAP and these are certainly important data that clinicians needs to know once this drug gets approved and where to use it in your hospitals.

The study, Efficacy and Safety of Cefiderocol versus High-Dose Meropenem in Patients with Nosocomial Pneumonia — Results of a Phase 3 Randomized, Multicenter, Double-Blind, Non-Inferiority Study, was presented Thursday, October 3, 2019, at IDWeek 2019 in Washington, DC.