The principal treatment for end-stage organ failure is solid organ transplantation (SOT). One of the most significant challenges facing organ transplantation is the limited supply of donor organs. As a result, there is substantial clinical and public health interest in expanding the donor pool to include those organs that have historically been discarded. Specifically, donors with positive bacterial cultures have been inconsistently utilized, because there have been several reports of donors transmitting bacteria to their organ recipients via the allograft, causing donor-derived bacterial infections (DDBIs). DDBIs have been linked in limited data to poor outcomes including vascular anastomosis dehiscence, overwhelming infection, and death. In some cases, the poor outcomes were attributed to the fact that the positive donor culture was not identified before transplant and there was a delay in recipient diagnosis and treatment. Conversely, there have also been case series describing safe transplantation of organs from donors with positive bacterial cultures. Thus, the true impact of donor bacterial infection or colonization on SOT recipients remains unclear. In this study, we plan to address this knowledge gap by studying a large, multicenter cohort of SOT recipients and their donors. This cohort will be built upon an existing multicenter research infrastructure of transplant centers, as well as our unique research collaboration with the local organ procurement organization, which coordinates transplantations in our region. In addition, we will be able to collect bacterial isolates from donors and recipients at our large transplant center in order to perform molecular testing. Specifically, we plan to:
(AIM 1) Determine the risk factors associated with acquiring a DDBI in SOT recipients; (Secondary AIM 1) Compare whole genome sequencing (WGS) versus phenotypic characterization to define DDBI in a subpopulation of SOT recipients;
(AIM 2) Determine the association between positive donor bacterial cultures and time to (a) first bacterial infection and (b) graft failure or death;
(AIM 3) Determine the predictors of positive donor cultures identified after organ transplantation. The results of this study will be important for the field of transplantation as it wrestles with how to safely expand the donor pool.
The aims are combined with a robust training plan that includes formal education in biostatistics and epidemiology, the development of advanced analytic skills for clinical and genome data, formal benchmarks for progress including presentation at seminars and international conferences, and extensive research experience under the guidance of an expert mentoring and advisory team. This proposal will form a strong foundation for my continued development toward a career as an independent investigator with a program of research focused on improving outcomes among SOT recipients.
The proposed research will determine the risk factors for donor-derived bacterial infections (DDBIs) in solid organ transplant (SOT) recipients, evaluate new molecular methods for diagnosing DDBIs, assess the impact of positive donor bacterial cultures on SOT recipient outcomes, and determine the predictors of positive donor cultures identified after transplantation. These studies will answer fundamental questions about whether the use of donors with positive bacterial cultures is associated with negative clinical outcomes in the recipients. Given the scarcity of donor organs and profound need to expand access to solid organs, this research will have significant public health implications.