Nucleic Acid Diagnostic Device for Quantifying Bacteremi

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DESCRIPTION (provided by applicant): Positive blood culture results are available in only 34% of such severe sepsis cases and antibiotic selection is usually based on the patient's clinical history. In life threatening cases, treatment is initiated with broad spectrum antibiotics before culture results are obtained because initiating treatment in the first 48 hours can significantly lower mortality rates. IQuum has developed a lab-in-a-tube (Liat(tm)) Analyzer which can be used to detect blood stream infections within 1 hour of patient presentation at an emergency department. This technology enables minimally trained healthcare practitioners to perform a nucleic acid test using whole blood as the sample input. We propose to develop a reverse transcriptase polymerase chain reaction (RT-PCR) diagnostic assay for detecting the 16S ribosomal RNA. Because each cell contains 1,000 to 10,000 copies of rRNA the RT-PCR assay, the expected sensitivity of the device will allow for the detection of bacteremia titers of ~3 cells /10 ml of whole blood. We propose to use BUGS'n BEADS(tm) (Genpoint AS) or lectin coated filters for sample preparation; a method based on an initial adsorption of bacteria to a solid phase matrix with high affinity for bacteria. Alternatively, we will explore nucleic acid specific capture of bacterial rRNA. All of these sample preparation alternatives will be tested using the same diagnostic device. We further propose to obtain FDA approval for a multiplex assay as well as seek CLIA waived status for the device. We propose to file our initial 510(k) focusing on the most common causes of sepsis: Escherichia coli and Staphylococcus sp (both coagulate negative species and S. aureus), which account for ~60% of blood stream infections. Once the device has obtained 510(k) approval for this limited indication of use, we propose to file abbreviated 510(k) for the detection of additional bacteria (listed in the body of the Work Plan) as additional data is acquired during the clinical trial.