A study aimed at better understanding why some critically ill patients develop multidrug-resistant infections is underway by researchers at The University of Texas Health Science Center at Houston (UTHealth). The multi-institution study will enroll patients at Memorial Hermann Hospital-Texas Medical Center and The University of Texas MD Anderson Cancer Center.
The Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised and Critically Ill Patients program received an $11 million grant from the National Institute of Allergy and Infectious Diseases to conduct this five-year study.
The research team will seek to explain the microbial, clinical, and antimicrobial resistance factors of three major multidrug-resistant pathogens: Vancomycin-resistant enterococci, Enterobacterales producing extended spectrum β-lactamases/carbapenemases, and Clostridioides difficile. All three pathogens are resistant to antimicrobial treatment such as antibiotics.
"We want to learn more about how these three classes of organisms colonize the gastrointestinal tract of critically ill patients and, eventually, cause infections in these patient populations," said Cesar A. Arias, MD, MSc, PhD, the study's principal investigator and professor of infectious disease at McGovern Medical School at UTHealth. He is also the Herbert L. and Margaret W. Dupont Chair in Infectious Diseases at UTHealth School of Public Health.
The project will utilize state-of-the-art analysis of the genomes of the pathogens and their potential products - paired with robust microbiome (gut flora) analyses using stool samples, oral swabs, and blood samples.
"An innovative technology, developed in the Texas Children's Hospital Microbiome Center, that uses microbiome datasets with large clinical data, will help us to accurately predict the disease susceptibility of each patient to facilitate personalized infectious disease management," said Tor Savidge, PhD, an associate professor of pathology and immunology at Baylor College of Medicine and a co-principal investigator on this study.
The research team plans to follow the study participants during hospitalization in intensive care units at Memorial Hermann Hospital-Texas Medical Center, as well as those in the bone marrow transplant unit at MD Anderson, to understand why some patients who have these pathogens colonized within their gut do not develop infections, while others do. Colonization means the pathogen is present within the body, and infection means the pathogen is present and making the patient ill. Individuals who are at greater risk for developing a multidrug-resistant bacterial infection are those with weakened immune systems and those taking antibiotics for other infections.
"The goal is to take the data from this study to develop an algorithm that can determine if a patient is low, medium, or high risk, and then based on that knowledge, develop future interventions," said Arias.
The human microbiota is the collective whole of all the trillions of pathogens (bacteria, fungi, protozoa, and viruses) that live inside the body. The largest collection is within the gut. One of the microbiota's main functions is helping regulate the immune system, and any change to the microbiota can affect likelihood of infection from a pathogen.
The program includes researchers from the Center for Antimicrobial Resistance and Microbial Genomics at McGovern Medical School, the Center for Infectious Diseases at UTHealth School of Public Health, MD Anderson, Texas Children's Hospital, Baylor College of Medicine, the University of Houston, Rice University, and the Gulf Coast Consortia.
"This study is critical to improving the clinical outcomes of our cancer patients as they are very vulnerable to deadly infections with antimicrobial-resistant bacteria," said Samuel A. Shelburne, MD, PhD, the deputy chair of the Department of Infectious Diseases, Infection Control and Employee Health at MD Anderson and a co-principal investigator on the study. "Through a cooperative strategy that harnesses unique strengths from investigators across the Texas Medical Center, we seek to leverage microbiome-based science to advance toward our long-term goal of making cancer history," he said.
Other UTHealth investigators include Blake Hanson, PhD, and Brandy McKelvy, MD. Additional investigators include Robert Jenq, MD, and Nadim Ajami, PhD, from MD Anderson; Anthony Haag, PhD, Qinglong Wu, PhD, and Alton Swennes, DVM, of Baylor College of Medicine; Todd Treangen, PhD, and Suzanne Tomlinson, PhD, MBA, of Rice University; and Kevin Garey, PharmD, MS, with the University of Houston.
Funding for this research is provided by the National Institute of Allergy and Infectious Diseases (Grant Number 1P01AI152999-01).