Following the approval of the new indication, Contagion® spoke with Yoav Golan, MD, of Tufts University School of Medicine, to discuss the implications of the approval.
Editors Note: Updated on June 4, 2019, at 7:08 PM EDT.
Yesterday, the US Food and Drug Administration (FDA) approved a new indication for Merck’s ceftolozane/tazobactam (Zerbaxa). The approval now allows for the drug to be used to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).
Ceftolozane/tazobactam (Zerbaxa) is a combination treatment of an anti-pseudomonal cephalosporin, ceftolozane, and an extended-spectrum β-lactamase inhibitor, tazobactam. In the United States, ceftolozane/tazobactam was previously indicated for the treatment of complicated urinary tract infections including pyelonephritis caused by certain susceptible gram-negative microorganisms and also in combination with metronidazole for the treatment of complicated intra-abdominal infections. It was first approved by the FDA in 2014.
Following the approval, of the new indication Contagion® spoke with Yoav Golan, MD, attending physician and associate professor of medicine at Tufts University School of Medicine, to discuss the implications of the approval.
Interview transcript: (modified slightly for readability)
Yoav Golan, MD
Contagion®: Why are new agents needed for HABP/VABP treatment?
Golan: In general, we’ve seen an increase of resistance in pathogens that affect humans, particularly, those pathogens that affect humans in hospitals and health care institutions. This is particularly true for hospital-acquired pneumonia, which is an infection that develops in a health care institution, typically in a hospital and is typically caused by an antibiotic-resistant hospital-acquired pathogen. Because of this resistance, many of the antibiotics that we relied upon for many years to treat hospital-acquired pneumonia are not effective anymore. We need newer and better agents to be able to cover those pathogens.
Contagion®: What evidence supports the efficacy of ceftolozane/tazobactam for treating HABP/VABP?
Golan: The starting point for ceftolozane/tazobactam when it comes to pneumonia is a good starting point because when you look at its in vitro activity, the spectrum of coverage of microbes, it is uniquely positioned to cover the type of bacteria that causes hospital and ventilator-acquired pneumonia including some of the most resistant bacteria like Pseudomonas, which has been a particular challenge when we care for these patients.
This has been a particularly good starting point. The next step was the proof of efficacy for ceftolozane/tazobactam in complicated intra-abdominal infections and complicated urinary tract infections, which are infections that are often caused by some types of pathogens that you see in pneumonia.
The third and most important facet of evidence has been the clinical trial itself, the ASPECT-NP study in which Zerbaxa was compared to intravenous meropenem in patients with ventilated hospital-acquired pneumonia and ventilator-associated pneumonia. The study was designed as a non-inferiority study versus meropenem which represents the standard-of-care. Zerbaxa, or ceftolozane/tazobactam, was found to be non-inferior to meropenem in terms of mortality at 28 days as well as cure at test-of-cure visit.
Contagion®: The ASPECT-NP trial was conducted in a critically ill patient population. Why is this patient population important to study?
Golan: From a clinician perspective, the most informative clinical trials are those that involve sick patients with a hard-to-manage infection. Patients whose outcome depends upon effective therapy. The ASPECT-NP study was designed to only include ventilated patients. who are at a high risk of mortality. Proving effectiveness in such group of patients provides meaningful information to clinicians.
Contagion®: What does the approval of ceftolozane/tazobactam bring to clinicians treating patients with HABP/VABP?
Golan: The approval of Zerbaxa for hospital and ventilator-associated pneumonia is important news for clinicians who care for these types of patients; this is for 2 main reasons. The first is the activity of Zerbaxa against multidrug-resistant pathogens that cause pneumonia such as multidrug-resistant Pseudomonas. The other reason is the activity of Zerbaxa against both resistant Pseudomonas as well as ESBL producers.
Most of the currently available antibiotics lack reliable activity against both of these types of bacteria. When initiating empiric therapy for patients with hospital-acquired pneumonia, we often need to choose between better coverage of 1 or the other. Zerbaxa offers the possibility to cover both types of bacteria. This is useful when treating very ill patients who cannot tolerate any delays in the initiation of adequate empiric antibiotic therapy.