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Impact of donor bacterial infections on solid organ transplant recipient outcomes

Award Number: K01AI137317
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/17/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Impact of donor bacterial infections on solid organ transplant recipient outcomes - PROJECT SUMMARY/ABSTRACT 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$79,500 )
2024	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	5	3/21/2024	NON-COMPETING CONTINUATION	-$79,500
2024	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	5	11/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = -$79,500

Issue Date FY: 2023 ( Subtotal = $133,677 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	5	11/10/2022	NON-COMPETING CONTINUATION	$133,677
														Subtotal = $133,677

Issue Date FY: 2022 ( Subtotal = $169,677 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	4	11/22/2021	NON-COMPETING CONTINUATION	$169,677
														Subtotal = $169,677

Issue Date FY: 2021 ( Subtotal = $151,677 )
2021	2021	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	3	8/24/2021	SUPPLEMENT FOR EXPANSION	$18,000
2021	2021	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	3	11/16/2020	NON-COMPETING CONTINUATION	$133,677
														Subtotal = $151,677

Issue Date FY: 2020 ( Subtotal = $133,677 )
2020	2020	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	2	11/22/2019	NON-COMPETING CONTINUATION	$133,677
														Subtotal = $133,677

Issue Date FY: 2019 ( Subtotal = $133,677 )
2019	2019	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	1	12/14/2018	NEW	$133,677
														Subtotal = $133,677

Grand Total All Awards = $642,885

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Impact of donor bacterial infections on solid organ transplant recipient outcomes

Award Number: K01AI137317

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/17/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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