Early Diagnosis of Sepsis Using Serum Biomarkers

Terence Chan; Frank Gu

Disclosures

Expert Rev Mol Diagn. 2011;11(5):487-496. 

In This Article

Sepsis

Sepsis is a growing problem worldwide, associated with a mortality rate as high as 60%.[1,2] It is estimated that severe sepsis affects over 750,000 people in the USA alone each year, resulting in an annual cost of almost US$17 billion,[3] underscoring the costly consequences of sepsis. It is a highly detrimental problem for infants[4–8] and the elderly,[9] as well as immunocompromized and critically ill patients.[9] Sepsis remains a common and expensive problem in developing nations, where sepsis is known to affect up to 30 of every 1000 live births.[10,11]

It is important to note that sepsis is not a true disease, but rather an innate physiological response by the immune system to infection.[12] The majority of studies define sepsis as a systemic inflammatory response to bacterial, fungal or viral infections.[12,13] In the clinical setting, several other physiological symptoms must be presented to diagnose sepsis.[9,14–17] The common treatment for patients suspected of sepsis is the administration of broad-spectrum antimicrobials.[1,5,9,10,18–23] The gold standard of sepsis diagnosis has traditionally been the use of microbial cultures to identify the source of illness.[1,11] However, the major limitation of using cultures is the length of time required to develop cultures to identifiable quantities. Cultures are also reported to be insensitive under several conditions,[19,21,23–30] including slow-growing and noncultivatable microorganisms and microorganisms present at very low concentrations. In light of these disadvantages, alternative diagnostic methods using molecular-based tests have been developed to enable rapid and/or automated diagnosis of sepsis. These tests include ELISA kits, flow cytometry, immunoluminometric assays, PCR tests, automated microbiological systems and FISH techniques. In parallel to the development of faster and more sensitive detection methods of infectious microbes is the development of systems monitoring abnormal changes in specific serum protein biomarker concentrations. A biomarker is best defined as 'a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes [or] pathogenic processes,' as previously described by Doherty et al..[31] Hundreds of biomarkers have been studied in an attempt to identify a reliable marker able to fulfill the need for quicker, more specific and more accurate diagnosis of sepsis.[24] The purpose of this article is to give an overview of the most commonly studied biomarkers of sepsis and infectious ailments, with a focus on each biomarker's diagnostic accuracy (DA).

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