UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL: Thiamine for Delirium Prevention in Hematopoietic

Stem Cell Transplantation

Year of Grant: 2017

Location: United States


Bloodstream infection (BSI) is a severe complication, and a major cause of mortality in leukemia. Hematological patients undergoing chemotherapy are particularly susceptible to BSI due to chemotherapy-induced neutropenia. BSI results in a worsened prognosis, extended hospital stays and increased healthcare costs. Rapid diagnosis of BSI is essential as the prognosis of the patients improves with early detection, while organ dysfunction and septic shock can develop if the infection is not treated in time.


BSI is routinely treated with empirical broad-spectrum antibiotics, which are ineffective against fungi, viruses and resistant or aspecific bacteria. Aspecific antimicrobial treatment increases the chance of generating resistant strains, it lengthens hospital stay and is associated with increased mortality.


Blood culture is used as a gold standard to diagnose BSI. This technique selectively detectsmicroorganisms which are able to grow in blood culture. However, most fungal strains or viruses cannot be cultivated in this medium, even though they are frequently detected with other techniques and play an important role in the pathophysiology of BSI. Blood culture typically only detects monomicrobial infections due to bacterial interference. Recent studies using high-throughput sequencing indicate that most BSI cases appear to be polymicrobial. Blood culture takes several days to perform depending on the growth of the microorganisms, while first-line antimicrobial treatment have to be administered within hours. Additionally, blood culture detection also requires expensive instrumentation.


Molecular methods using hybridization and amplification techniques are also available for pathogen detection in BSI. However, their sensitivity and specificity is hindered by human background DNA, and their detection range is limited to the applied probe and primer design.


The group is collaborating with the Children’s Hospital of Illinois Department of Hematology for sample collection. Approximately 300 blood samples from leukemic patients with suspected BSI will be collected and tested. Validation will include the evaluation of the performance of the assays in regard to their sensitivity, specificity and detection range. The assays will be performed by at least two people in the group to evaluate intra-laboratory variability and repeatability. The results will be compared to results from standard blood culture, commercial pathogen detection kit (SeptiFast) and high-throughput sequencing.