Signatures and determinants for diagnosing infections and methods of use thereof
Antibiotics (Abx) are the world's most misused drugs. Antibiotics misuse occurs when the drug is administered in case of a non-bacterial infection (such as a viral infection) for which it is ineffective. Overall, it is estimated that 40-70% of the worldwide Abx courses are mis-prescribed. The financial and health consequences of Abx over-prescription include the direct cost of the drugs, as well as the indirect costs of their side effects, which are estimated at >$15 billion annually. Furthermore, over-prescription directly causes the emergence of Abx-resistant strains of bacteria, which are recognized as one of the major threats to public health today. This generates an immediate need for reliable diagnostics to assist physicians in correct Abx prescription, especially at the point-of-care (POC) where most Abx are prescribed. Accordingly, some aspects of the present invention provide methods using biomarkers for rapidly detecting the source of infection and administrating the appropriate treatment.
1. A kit comprising a detection assay comprising polypeptide detection reagents comprising labeled monoclonal antibodies immobilized on a solid support, wherein said monoclonal antibodies comprise a first monoclonal antibody that specifically binds to TRAIL polypeptide, a second monoclonal antibody that specifically binds to CRP polypeptide and a third monoclonal antibody that specifically binds to IP10 polypeptide when contacted to a whole blood sample or a fraction thereof from a subject, wherein the detection assay further contains antibodies that bind to no more than two additional polypeptides which are differentially expressed in a statistically significant manner in subjects with a bacterial infection compared to subjects with a viral infection.
2. The kit of claim 1 , further comprising: (i) an antibody that specifically binds to said TRAIL polypeptide at an additional site as to the site to which said first monoclonal antibody binds; (ii) an antibody that specifically binds to said CRP polypeptide at an additional site as to the site to which said second monoclonal antibody binds; and (iii) an antibody that specifically binds to said IP10 polypeptide at an additional site as to the site to which said second monoclonal antibody binds.
3. The kit of claim 2 , wherein each of said antibodies of (i), (ii) and (iii) comprise a detectable label selected from the group consisting of a radioactive label, a fluorescent label, a chemiluminescent label and an enzyme.
4. The kit of claim 3 , wherein said enzyme is horseradish peroxidase or alkaline phosphatase.
5. The kit of claim 1 , wherein the kit contains antibodies that detect no more than three polypeptide determinants.