Bloodstream infection detection directly on whole blood

Bloodstream infection detection directly on whole blood
Summary
Bloodstream infection caused by yeast is a life-threatening condition that affects approximately
50,000 patients each year in the United States. Yeast bloodstream infection is a highly lethal
infection associated with mortality rates greater than 40%. Early antifungal administration is
crucial to improve the probability of patient survival. However, the current gold standard for the
diagnosis of yeast bloodstream infection is blood culture (BC), which takes one to five days. To
provide physicians with the needed diagnostic information to properly treat these patients, we are
developing an automated platform for rapid, broad and cost-effective identification of yeast in
whole blood without BC. The new platform is based on Single MOLecule Scanning (SMOLT), a
novel sample preparation and molecular detection method developed at Scanogen.
Here, we propose to complete the development of an automated instrument and the SMOLT-
Yeast assay that will detect most yeast responsible for bloodstream infections directly on whole
blood. We successfully completed or surpassed all Phase II milestones. The SMOLT-Yeast assay
was developed, automated, and tested with clinical samples. To diagnose a patient, a vacutainer
with the patient’s blood is inserted into a disposable cartridge and processed by a desktop
instrument. The new assay demonstrated high analytical and clinical performance with limit of
detection of 1 CFU/mL for 11 yeast species, an overall clinical sensitivity of 94.2% and an overall
clinical specificity of 99.8%. In Phase IIB, we will address all the design improvements that are
needed before the FDA pivotal studies. We will optimize the cartridge design to reduce
manufacturing variability and cost, as well as to increase storage stability (Aim 1 and Aim 2). We
will optimize the instrument design to improve its usability, increase its mechanical stability, and
reduce its size (Aim 3). We will also conduct an in-hospital pilot study to test the assay and the
approach that will be used for the pivotal studies (Aim 4). We have assembled the appropriate
team to accomplish these tasks: assay development scientists that developed the SMOLT
technology and experienced engineers, including the former Vice President of Engineering at
Becton Dickinson. In addition, Scanogen has established a collaboration with a team from the
Johns Hopkins University that will conduct the clinical evaluation and will provide feedback to
ensure that the new system responds to the clinical needs. If successful, the new platform will
significantly improve the outcome of patients with yeast bloodstream infection by providing rapid
results and enabling timely initiation of proper antifungal treatment. Furthermore, the new platform
will have a broader impact by enabling assays targeting other microorganisms that cause
bloodstream infections.

Grant Number: 5R44AI124871-06
NIH Institute/Center: NIH
Principal Investigator: Alfredo Celedon