Investigating sepsis with biomarkers

#### The bottom line A 65 year old man presents with lethargy, fever, and rigors. On examination his arterial blood pressure is 120/50 mm Hg, he has a mild tachycardia (105 beats/min), and he is febrile (38.7°C), with no other abnormalities. His urine is cloudy and urinary dipstick test shows the presence of leucocytes and nitrate. There is no history of recent travel, urinary symptoms, or drug allergy (including antibiotic sensitivity) and no relevant findings on systems review (such as liver or kidney disease). You promptly establish intravenous access, draw blood for laboratory tests (including blood culture), send a urine sample for microbiology, and administer the first dose of an empirical broad spectrum antibiotic. These clinical signs and symptoms strongly suggest sepsis. However, in a third of patients with sepsis, the causative pathogen cannot be identified.1 The lack of confirmatory evidence of infection often makes the diagnosis of sepsis a challenge. This difficulty is reflected by the inclusion of the words “probable infection” in defining sepsis in the Surviving Sepsis Campaign guidelines (box 1).2 #### Box 1: Definitions and classification of sepsis syndrome2 ##### Systemic inflammatory response syndrome An abnormal increase in two or more of the following parameters:

[1]  B. Phypers,et al.  Lactate physiology in health and disease , 2006 .

[2]  Michael Bauer,et al.  New Approaches to Sepsis: Molecular Diagnostics and Biomarkers , 2012, Clinical Microbiology Reviews.

[3]  C. Sprung,et al.  Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012 , 2013, Intensive Care Medicine.

[4]  T. Clemmer,et al.  Sepsis syndrome: a valid clinical entity , 1989 .

[5]  J. Schrenzel,et al.  Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier? , 2012, Critical Care.

[6]  Peter Schlattmann,et al.  Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. , 2013, The Lancet. Infectious diseases.

[7]  A. Detsky,et al.  Does this adult patient with suspected bacteremia require blood cultures? , 2012, JAMA.

[8]  Alan E. Jones,et al.  Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. , 2010, JAMA.

[9]  France Gauvin,et al.  Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  K. Shah,et al.  Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock , 2010, Journal of Inflammation.

[11]  T. Clemmer,et al.  Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. , 1989, Critical care medicine.

[12]  S. Berliner,et al.  C-reactive protein velocity to distinguish febrile bacterial infections from non-bacterial febrile illnesses in the emergency department , 2009, Critical care.

[13]  J. Yim,et al.  Prognostic Value of Central Venous Oxygen Saturation and Blood Lactate Levels Measured Simultaneously in the Same Patients with Severe Systemic Inflammatory Response Syndrome and Severe Sepsis , 2014, Lung.