ASPECT-NP: Randomized, Double-Blind, Phase III Trial Comparing Efficacy & Safety of Ceftolozane/Tazobactam vs Meropenem in Ventilated Nosocomial Pneumonia Interview with:

Dr. Elizabeth Rhee MD Director, Infectious Disease Clinical Research at Merck

Dr. Rhee

Elizabeth Rhee, MD
Executive Director, Infectious Disease Clinical Research
Merck Research Laboratories What is the background for this study? Would you briefly explain the condition of ventilated nosocomial pneumonias?

Dr. Rhee: Nosocomial pneumonia (NP) is a lung infection that occurs during a hospital stay. NP is often serious, and is associated with high mortality. It is one of the most common health-care associated infections in both the U.S. and Europe, accounting for over 20% of such cases. Gram-negative bacteria, mainly Pseudomonas aeruginosa (PSA) and Enterobacteriaceae, are frequent causes of nosocomial pneumonia. Limited options currently exist for the management of NP caused by Gram-negative pathogens. This is concerning because rates of resistance to Gram-negative bacteria are growing, and they are becoming increasingly difficult to treat.

Forms of nosocomial pneumonia include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and ventilated HAP. High rates of death (ranging from 20% to more than 50%) are especially associated with ventilated HAP. Pseudomonas aeruginosa, a Gram-negative bacterium, is the most common cause of HAP/VAP in both the U.S. and Europe. Patients with NP are often critically ill, requiring ventilator support and time in intensive care, and it was important to look at this population as we explore new options for the treatment of NP.

Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin/beta-lactamase inhibitor combination with broad in vitro activity against Gram-negative pathogens, including multi-drug resistant (MDR) P. aeruginosa and many extended-spectrum beta-lactamase (ESBL) producers. It is FDA approved for complicated intra-abdominal and urinary tract infections in adults at 1.5g (1g ceftolozane/0.5g tazobactam) q8h. C/T is currently being studied at an investigational new dose of 3g (2g/1g) q8h, for the treatment of ventilated nosocomial pneumonia, in the ASPECT-NP Phase 3 trial.

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Clinical Score Predicts Antibiotic Sensitivity to P. aeurginosa  in Hospitalized Patients Interview with:

Dr. Tom Lodise PharmD, Professor Albany College of Health Sciences, NY

Dr. Tom Lodise

Dr. Tom Lodise PharmD, Professor
Albany College of Health Sciences, NY What is the background for this study?

Response: P. aeruginosa (PSA) is intrinsically resistant to many commercially available antibiotics and also has a remarkable capacity to develop resistance to commonly used antibiotics like carbapenems, aminoglycosides, and fluoroquinolones. The terms ‘multidrug resistant’ (MDR) and ‘pan-drug resistant’ are often used to characterize the different patterns of multiple drug resistance exhibited by PSA. Patients with MDR-PSA infections are at an increased risk for delayed receipt of appropriate antimicrobial therapy and ample studies indicated that receipt of delayed appropriate therapy results in substantial increases in morbidity, mortality, and healthcare resource utilization.

Although risk factors for these types of infections have previously been identified in the literature, this study takes identification of risk factors further, and develops two clinical risk scores to estimate the probabilities of carbapenem and extensively beta-lactam non-susceptibility among hospitalized, adult patients with PSA infections based on covariates available on clinical presentation. We focused on these two PSA non-susceptible phenotypes as they represent infections at high risk of delayed appropriate therapy due to resistance against the current commonly prescribed empiric anti-pseudomonal antibiotics.

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Resistance to Carbapenem Antibiotics Doubled in Intensive Care Units Interview with:

Eilish McCann, PhD</strong> Director, Outcomes Research (Center for Observational and Real-World Evidence) Merck

Dr. Eilish McCann

Eilish McCann, PhD
Director, Outcomes Research (Center for Observational and Real-World Evidence)
Merck What is the background for this study?

Response: One of the most pressing challenges facing medicine today is the emergence of bacterial resistance to antibiotics. One area of high concern is the increasing prevalence of resistance to powerful antibiotics like carbapenems, as patients with infections due to carbapenem-resistant bacteria have very few alternate effective treatment options.

In this study we used real-world data from a Becton, Dickinson and Company electronic research data set to analyze over 140,000 bacterial isolates from patients at 342 hospitals across the United States, so that we could investigate where the burden of carbapenem resistance is most acute. Importantly analysis of real-world data in this way allows us to gain insights from a large number of hospitals, giving a broad and nationally representative picture of the resistance burden.

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