A multidisciplinary, collaborative effort involving investigators at 6 organizations is proposed to develop novel, in vitro diagnostic tests (IVD) for severe sepsis (SS) and community acquired pneumonia (CAP).
Specific Aim 1 : Early, accurate identification of sepsis patients who will develop organ dysfunction (SS) is critical for effective management and positive outcome. We propose to develop a rapid, point-of-care (POC) ? IVD for early diagnosis of SS. Our preliminary studies have identified candidate biomarkers of SS that we propose to validate in a prospective clinical study of sepsis at 3 tertiary care hospitals and emergency departments employing proteomic technologies (mass spectrometry and multiplexed immunoassays). Bivariable analyses will be performed to identify and validate biomarker differences between groups. Multivariable analyses will be performed on validated biomarkers to derive a biomarker panel for early diagnosis of SS. The biomarker panel will be compared with prognostic indices, such as metabolic endpoints and APACHE II score. The biomarker panel will be developed into an oligoplex IVD immunoassay performed on a single blood sample on the Biosite Triage platform, with a time-to-result of less than 30 minutes.
Specific Aim 2 : Complications of CAP are major determinants of morbidity and mortality. Early, accurate ? identification of patients with CAP who will have a complicated course or poor outcome (severe CAP) is critical for effective management and positive outcome. We propose to identify biomarkers for early diagnosis of severe CAP by separate analysis of CAP patients in the Aim 1 clinical study. Bi- and multivariable analyses will be performed to identify biomarker differences and derive a biomarker panel for early diagnosis of severe CAP. This panel will be compared with prognostic indices, such as PORT score.
Specific Aim 3 : Currently, initial antimicrobial treatment of sepsis and CAP is empiric. We propose to identify host biomarkers for early differentiation of common etiologic agents in sepsis and CAP, in order to allow more targeted initial therapy, thereby decreasing cost associated with ineffective therapy and lessening likelihood of antibiotic resistance. Bi- and multi-variable analyses will be performed on groups of patients from the Aim 1 study with confirmed sepsis and CAP pathogens (such as pneumococcus) in order to identify ? biomarkers and a biomarker panel for early differentiation of specific class agent in sepsis and CAP. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI066569-03
Application #
7286345
Study Section
Special Emphasis Panel (ZAI1-SR-M (M1))
Program Officer
Korpela, Jukka K
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$500,767
Indirect Cost
Name
National Center for Genome Resources
Department
Type
DUNS #
835700444
City
Santa Fe
State
NM
Country
United States
Zip Code
87505
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