Microbiology and Risk Factors for Hospital-Associated Bloodstream Infections Among Pediatric Hematopoietic Stem Cell Transplant Recipients.

My research focus is on developing methods to prevent infections and improve treatment outcomes in children.

I am a Pediatric Transplant Infectious Diseases physician-scientist. Clinically, I diagnose and treat infections in immunocompromised children who have either undergone transplantation or who are receiving chemotherapy. My research interests are in utilizing the microbiome to improve clinical outcomes following transplantation. Specifically, I am evaluating the gut microbiomes of children undergoing hematopoietic cell transplantation (HCT) to identify actionable interventions to reduce mucosal barrier injury bloodstream infections and graft-versus-host disease, two significant contributors to post-HCT morbidity.

I am the division chief of Pediatric Infectious Diseases at Duke.  My clinical and research efforts frocus on the prevention and treatmtent of infections in children.  I am the medical director of the pediatric antimicrobial stewardship program at Duke University Hospital and also serve as Co-Director of the Duke Vaccine and Trials Unit.

For most of my career in Pediatric Hematology/Oncology I have focused on the use of stem cell transplant for the treatment of pediatric leukemias (ALL, AML, CML and JMML) and other non-malignant blood disorders, such as sickle cell disease, hemaphagocytic disorders, Wiskott-Aldrich, aplastic anemia, Diamond-Blackfan Anemia, as well as inherited metabolic diseases. In addition to focusing on determining the best use of stem cell transplants for these disorders, I have also been involved in clinical research investigating the prevention and treatment of transplant related morbidity, particularly veno-occlusive disease of the liver, infections and diffuse alveolar hemorrhage. As study chair for the Children's Oncology Group protocol 9904, I was involved in the development, implementation and analysis of a large, international frontline study of childhood acute lymphoblastic leukemia. Results from this study show that a significant number of children with certain favorable cytogenetic abnormalities in their leukemic cells and who have a rapid response to their initial chemotherapy can expect to have a >95% chance of cure when treated with relatively low intensity chemotherapy.  

I have concentrated on providing high quality care for high risk leukemia patients who require high intensity therapies, such as stem cell transplant and immunotherapy.  As a member of the Pediatric Transplant and Cellular Therapy Division I provide clinical care for these patients.  As a member of various cooperative groups and local PI for several drug trials, I have worked to provide better care and more specific therapies for the toxicities associated with stem cell transplant.  

I have also collaborated with the Pediatric Immunology Division to provide a life-saving therapy for a small group of patients with thymic dysfunction, which causes severe immunodeficiency.  Our clinical team now provides support during these patients hospital admissions for donor thymus tissue implantation.  We once again achieved a new record for the number of implanted patients during the 2022-2023 academic year.

My research is broadly focused on elucidating the complex interactions that exist between the host microbiome and exogenous pathogens that cause infections in children. We have several ongoing projects evaluating: 1) the impact of the upper respiratory microbiome on the risk of colonization and invasion by bacterial respiratory pathogens among infants in Botswana; 2) associations between the gut microbiome of pediatric stem cell transplant recipients and the risk of infections (bloodstream infection, C. difficile infection) and graft-versus-host disease; and 3) the role of the gut and respiratory microbiomes in mediating COVID-19 infection susceptibility and disease severity in children. Ultimately, I aim to develop strategies that use targeted modification of the microbiome for the prevention of infections in children.