What is the research about?
A common problem faced by patients with chronic medical conditions is the development of bloodstreams infection caused by Gram-negative bacteria. The most common Gram-negative bacteria to cause bloodstream infections is E. coli. About one in five patients with chronic medical conditions will have a Gram-negative bloodstream infection. The best way to manage these infections is unknown. One common approach is treating patients with intravenous antibiotics for the full duration of therapy. This often means placement of a vascular catheter for patients to receive antibiotics after leaving the hospital. This can be uncomfortable, interfere with activities of daily living, and cause secondary infections or blood clots. The other approach is transitioning the patient from initial intravenous antibiotics to oral antibiotic therapy after he/she is beginning to show clinical improvement. The oral antibiotics commonly used, however, can have important side effects. Both of these approaches have risks and benefits associated with them, but it is unknown which one is the safest and most effective approach for patients.
Who can this research help?
This research will help patients, caregivers, and healthcare workers engage in shared decision making when deciding on the right approach to manage patients with Gram-negative bloodstream infections. Patients at high risk for these infections include pregnant women and those with diabetes, cancer, chronic kidney disease, autoimmune conditions, prostate issues, and spina bifida.
What is the research team doing?
The research team will conduct a randomized controlled trial of patients 18 years of age or older with Gram-negative bloodstream infections across eight hospitals in the United States that will continue for 36 months. The primary question being studied is "What is the safest and most effective treatment approach for adults with Gram-negative bloodstream infections?"
The eight hospitals will include hospitals in cities and rural areas, hospitals with diverse races and ethnicities, and hospitals in different regions of the United States. Each patient meeting the eligibility criteria who provides written consent for participation will be randomly assigned to intravenous therapy or initial intravenous antibiotic therapy followed by early transition to oral therapy.
The research team is using a novel approach to make sure patient perspectives are included in this work. They will have 10 patients or caretakers (i.e., Patient Stakeholder Group) previously treated for bloodstream infections work with the research team to develop a list of all possible outcomes that include measures of clinical success and failure, antibiotic and vascular catheter-related side effects, and quality-of-life issues. They will then rank and group all possible outcomes a patient could experience into five distinct levels. For every patient in the study, the investigators will place their outcome into one of the five ranked outcome levels. The final decision as to whether intravenous or oral step-down therapy is the best approach to treat patients with Gram-negative bloodstream infections will include a sophisticated analysis of which group of patients had a more favorable distribution of ranked outcomes. This is a unique way to evaluate data. It ensures that the outcomes being used to determine which treatment approach is better are based on outcomes that are actually important to patients. Towards the end of the study, the Patient Stakeholder Group will help us develop educational materials for patients with similar problems in the future so they know what questions they should be asking their healthcare providers.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.