A new CTTI publication investigates the prospective identification of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) risk factors and antibiotic trial eligibility among hospitalized, critically ill patients at seven European hospitals. The study, PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts, published in Open Forum Infectious Diseases, evaluated 888 critically ill patients receiving ventilation or high levels of supportive oxygen and used existing clinical criteria to predict which patients would develop HABP/VABP. The researchers compared these results to those of a prior CTTI study of U.S. patients, finding that a higher proportion of European patients who were treated for possible HABP/VABP met the pneumonia definition compared to their counterparts in U.S. hospitals. The European patients were also more likely to meet common antibiotic trial eligibility criteria. The results could be applied to the development of new strategies to improve registrational trial feasibility and foster the development of much needed new antibacterial treatments for HABP/VABP. 

Although treatment of possible nosocomial pneumonia is common with patients in the intensive care unit (ICU) receiving respiratory support, more than half of those treated do not fit the standard clinical definitions of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). A new CTTI paper available online in CHEST® Journal, accompanied by an insightful editorial, “Heeding the Prophetic Call,” outlines how the use of simple clinical criteria may help to identify high-risk patients earlier and aid future research to improve prevention and treatment.

The paper highlights the Prospective Identification of Pneumonia in Hospitalized Patients in the ICU (PROPHETIC) study, a large, contemporary, prospective cohort clinical trial designed by CTTI that made several key observations.

“HABP/VABP is associated with high mortality and morbidity and may be caused by multidrug-resistant pathogens,” said John Farley, director of the Office of Infectious Diseases at the FDA.   “Conducting clinical trials in HABP/VABP is challenging, and data to understand the patient population is critical to improve trial feasibility.”

The study sought to define the incidence of HABP/VABP in an ICU population and identify characteristics associated with the development of HABP/VABP to inform the design and conduct of future clinical trials.

The study determined that 32 percent of 4,613 prospectively identified high-risk patients received antibiotics for possible HABP/VABP. It was also determined that only 12 percent of the aforementioned high-risk patients fit the FDA Guidance standard clinical definition of HABP/VABP.

“These findings indicate that the burden of HABP and VABP is significant and there is also some concern about antibiotic overprescription in this high-risk population,” said Vance Fowler, professor of medicine at Duke University. “Receiving antibiotics is itself a risk factor for developing pneumonia, carries risks of adverse events, and may preclude eligibility for HABP/VABP clinical trial enrollment.”

Additionally, the manuscript highlights the common characteristics and treatment exposures researchers identified that were associated with increased odds of developing HABP/VABP in high-risk patients.

“Application of the study results to prospectively identify patients at highest risk for HABP/VABP may help to facilitate the conduct of innovative and efficient clinical trials,” said Pamela Tenaerts, executive director of CTTI. “This will help to promote development of optimal preventive, diagnostic, and treatment strategies to improve management of this disease.”

Learn more about CTTI’s work on HABP/VABP Studies.