Personalized medicine in sepsis: the coming of age

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Date: July 2013
From: Expert Review of Anti-infective Therapy(Vol. 11, Issue 7)
Publisher: Expert Reviews Ltd.
Document Type: Editorial
Length: 2,112 words
Lexile Measure: 1690L

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Author(s): Eirini Christaki [*] 1

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genomics; individualized medicine; metabolomics; personalized medicine; sepsis; septic shock; transcriptomics

During the past decade, great advances in molecular medicine and clinical pharmacology have made it possible not only better understand disease pathogenesis and facilitate a faster and more accurate diagnosis, but also to tailor therapeutic interventions to the genetic profile of an individual's disease. In the medical fields of hematology and oncology 'omic' medicine has entered daily practice, however its clinical applications in other areas, such as infectious diseases, is still not an everyday reality. Perhaps one of the best examples portraying the need for personalized medicine is sepsis.

Sepsis pathophysiology mainly stems from the host immune response to infection, which is a complex and dynamic process that varies according to the culprit pathogen, the site of infection and host factors such as genetic background and comorbid conditions [1] . One of the reasons that clinical trials investigating immunomodulatory therapies in sepsis have failed, is the fact that septic patients were considered for the most part a homogeneous population, not accounting for individual variability between patients [2] . Lack of specific biomarkers and immunoprofiling tools that could define the exact sepsis stage and functional immune status of each patient at the time those clinical trials were designed and carried out, left no other alternative than to apply therapeutic interventions, whether those were proinflammatory or immunosuppressive, to the entire target population. The importance of patient stratification in clinical trials was shown in a Phase III study, which investigated the efficacy of afelimomab, an anti-TNF monoclonal antibody fragment, and stratified patients according to their IL-6 levels. Panacek et al . demonstrated that 28-day mortality and severity of organ dysfunction was reduced in those patients with elevated IL-6 levels [3] . Therefore, there is both the need to discover specific and clinically useful biomarkers in order to diagnose sepsis, define the host's immune status, monitor treatment and define prognosis and to develop medications that would target the disease profile of each patient . This is in line with a shift in drug development that moves away from the 'one drug fits all' concept since this model may be ineffective, risky and costly, towards theranostics, where therapy will be targeted to those patients that have been identified by a diagnostic test to most likely benefit from the new medication [4] .

Early and accurate diagnosis is of paramount importance in sepsis since delay of appropriate antimicrobial therapy is associated with increased mortality [5] . Diagnostic tools that can provide an accurate result faster than traditional blood cultures, which are also very often negative are therefore needed [6] . Nucleic acid amplification-based tests, such as multiplex PCR for bacterial and fungal detection, can provide a result faster than conventional blood cultures and increase pathogen detection yield [7,8] . Also, novel methods of microbial detection are now available with microarray based pathogen detection platforms [9] . A limitation that still exists with these methods is to validate the clinical utility of a culture negative and PCR positive blood sample...

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Gale Document Number: GALE|A337663382