BIOMARKERS for Sepsis and Infection should address important clinical aspects such as
1. Rapid diagnosis of invasive infections contributing to organ dysfunction;
2. Provide information regarding antibiotic susceptibility and
3. Distinguish infection mediated organ dysfunction from non-infectious sepsis mimics.
Review of MDW values for ED patients who have positive blood cultures The gold standard for the diagnosis of bloodstream infections is positive blood cultures. Not all patients with sepsis have positive blood cultures, however patients with blood stream infections and end-organ dysfunction are septic and need to be treated with antibiotics. Two definitions of sepsis currently are used.
The sepsis-2 definitions \[1,2\] are based on a confirmed or suspected infectious source, a systemic response with two or more abnormal systemic inflammatory response syndrome criteria such as hyper or hypothermia, tachycardia, tachypnea and leukopenia or leukocytosis or bandemia and signs of at least one new end organ dysfunction. There is a differentiation between different degrees of disease severity between sepsis, severe sepsis and septic shock. Each of these degrees of illness severity are associated with different morbidity and mortality.
The sepsis-3 definition \[3\] state that sepsis is the bodies response to an infectious agent. The response is assessed using a quick SOFA score (qSOFA) assessment based on tachypnea of equal or greater than 22 breath, systolic hypotension of equal or less than 100 mmHg and changes in mentation measured by a Glasgow Coma Score (GCS) of less than 15 along with the requirement of a new onset of organ dysfunction as measured by a SOFA score of equal or greater than 2.\[4\] Sepsis-3 definition distinguish between sepsis and septic shock only. Septic shock is only present if a patient has 2 or more qSOFA criteria, requires the use of a vasoactive agent to maintain a mean arterial blood pressure of 70 mmHg AND if the lactate is greater than 2 mg/dL. Patients which do not have a qSOFA score of greater than 2 or a SOFA score of less than 2 are considered not septic and as having only a local infection.
Both definitions have the requirement for a proven or suspected infection. Source identification is important, however not always successful. The most common site of infection is the lung. This infection is most commonly viral or bacterial. The second most common site of infection is the genitourinary tract followed by blood stream infections. The diagnosis of blood stream infections (BSI) can be affected by a variety of factors including the collection technique to avoid contamination, the amount of blood volume collected, the timing of collection among other factors. Specifically, the early recognition of blood culture positivity and appropriate early source control are essential for successful treatment of patients with signs of a systemic response to the blood stream infection and end-organ dysfunction. Delay in recognition of blood culture positivity can lead to treatment delays along with possible disease progression.
Studies evaluated the usefulness of monocyte distribution width (MDW) for the assessment of emergency department patients with sepsis. It has been observed that monocyte activation in response to bacteremia leads to increased monocyte size. \[5\] MDW reflects a measure of a change in the size distribution of circulating monocytes. MDW has been evaluated for the aid of sepsis based on the definitions above. \[6\] The study by Crouser showed that the detection diagnosis of sepsis within 12 hours of ED presentation was aided when MDW was added. Similar, Polili et al found that the addition of MDW to the routine White Blood Cell (WBC) counts aids sepsis diagnosis and may be more useful than procalcitonin. \[7\]
It has not yet clearly established that MDW are elevated in bloodstream infections (BSI). BSI are diagnosed using blood cultures as gold standard for diagnosis. Blood cultures have a high sensitivity and specificity.\[8\] Up to thirty forty percent of septic shock patients will be blood culture positive and up to 25-30% negative for any type of culture. However, the diagnosis can take time delaying initiation of appropriate treatment. Additionally, in up to 50 % of cases BSI may be present without blood culture positivity due to the presence of uncultivable organisms or antibiotic treatment started prior to sampling.\[9\] MDW may be useful in not only aiding the diagnosis of sepsis but also in the expedited diagnosis of BSI.
This project will evaluate the usefulness of MDW for the diagnosis of blood culture positivity (BSI) in patients in the ED and reevaluate the usefulness of MDW in patients with BSI and sepsis. Consequently, if MDW indicate a high likelihood of bacteremia; antibiotic management in patients with suspected bacterial infections will be changed and aid appropriate antibiotic administration. On the other hand, a negative MDW test in the ED without additional risk factors or signs of infection (ie. Urinary tract, pneumonia, skin) or suspected severe sepsis or septic shock, patients may be treated supportively without use of antibiotics in the appropriate clinical setting.
