Antimicrobial Resistance Research is DYNAMITE at Houston Methodist

The Texas Medical Center is home to world leaders in antimicrobial resistance research. With unparalleled expertise in cutting-edge genomic and phenotypic techniques and access to clinical practice and patient care, these experts are uniquely positioned to perform the complex, systems-level studies needed to address antimicrobial resistance (AMR). Recognizing this exceptional opportunity led to the formation, and funding, of a multi-institutional collaborative research program P01 grant led by Arias called DYNAMITE: Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised and Critically Ill Patients.

Among the most relevant multidrug-resistant (MDR) bacteria, vancomycin-resistant enterococci (VRE), extended spectrum β-lactamase producing/carbapenem-resistant Enterobacterales (ESBL-E/CRE) and Clostridioides difficile are considered high priority as they commonly infect severely ill and immunocompromised patients, with few therapeutic options. Because the intestines are the site of initial colonization for each of these pathogens, broad-spectrum antimicrobial therapies can result in their overtaking beneficial gastrointestinal flora increasing the risk of clinical disease. It is currently unclear why only a subset of patients, under apparently similar conditions, develop colonization/disease with AMR. Without accurate identification of high-risk patients, microbiome-based therapeutics are limited, and clinically impactful interventions are difficult to implement. The premise behind the DYNAMITE program is that patient susceptibility to gut-derived nosocomial colonization and subsequent infection is critically dependent on functional microbiota-pathogen interactions that can be detected via a combination of pathogen, host and commensal microbiota analyses. According to Arias, “DYNAMITE is a project that involves five institutions in the medical center, including Baylor College of Medicine, MD Anderson Cancer Center, the University of Houston, Rice University (including the Gulf Coast Consortia) and Houston Methodist, that brings together microbiome, clinical microbiology, omics and bioinformatics expertise to really dissect these interactions very carefully and try to understand this process.” The project currently has two patient cohorts: ICU patients and bone marrow transplant patients, both currently being recruited at Houston Methodist. Bone marrow transplant patients are also planned to be enrolled at MDACC. The goal is to understand the dynamics of the nosocomial infection process, when and where they get infected and with what organisms. Samples collected include stool, blood and oral swabs and the microbiomes of the patients are characterized at the genomic, proteomic and metabolomic levels. The project is ongoing in all ICUs at Houston Methodist and bone marrow transplant units at HMH and MDACC. The DYNAMITE project has three objectives: i) to elucidate the main microbial, clinical and antimicrobial resistance determinants impacting colonization and infection by VRE, ESBL-E/CRE and C. difficile, ii) to evaluate the role of commensal microbiota in VRE, ESBL-E/CRE and C. difficile colonization, and iii) to define the functional aspects of keystone microbiota and mechanisms of protection against colonization/infection. Given the group’s strong history of multi-institutional collaboration on AMR and microbiome science and their access to two major cohorts of critically ill and immunocompromised patients as well as centralized state-of-the art facilities in the Texas Medical Center, the results of these high impact, complementary projects are expected to provide critical foundations for development of novel and more effective preventative, diagnostic and therapeutic approaches to combat gut-derived AMR organisms affecting critically ill patients.