Sepsis

Dr. Peter Smith MBChB, DOH, DTM&H, M.Med (Micro)

PATHCHAT NO 6: DIAGNOSIS OF SEPSIS - IS PRACALCITONIN (PCT) THE IDEAL MARKER?

The clinician's dilemma:

Clinicians are often faced with the decision whether signs of inflammation are due to infectious or non-infectious causes, and they find themselves with the difficult decision of starting antimicrobials that could save the patient's life, or on the other hand treating non-infectious causes of inflammation with antimicrobials that are not necessary and increase cost. Antimicrobials are also potentially toxic, with the added risk of developing anti-microbial resistance.

Sepsis - how to diagnose?

Sepsis is defined as the host response to a suspected or proven infection and is also characterized by the same signs as the systemic inflammatory response syndrome (SIRS, which is an inflammatory state without proven infectious source), including fever, tachycardia, tachypnoea and leukocytosis. These signs are sensitive but non-specific markers of infection prediction as they also occur in non-infectious conditions. In the hospital setting, particularly in the intensive care unit (ICU) setting, co-morbidities, invasive devices, surgery and drugs pave the way for infections caused by organisms that do not usually cause infection. These organisms are difficult to distinguish from contaminating or colonizing flora, including the relative immune-suppressed state of patients in ICU, obscure clinical signs of infection. Therefore there is a need to use a reliable biomarker to diagnose infection.

The ideal biomarker?

The ideal biomarker for sepsis would be readily available, technically easy to perform, inexpensive, highly specific, very sensitive, and highly correlated in quantitative terms with disease severity. No such biomarker exists at present. Despite their shortcomings, a number of existing and candidate biomarker assays are available and can provide useful information. White cell count (WCC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and pro-calcitonin (PCT) are the most widely used and studied of these markers.

Pro-calcitonin (PCT)

PCT is a precursor of the thyroid hormone, calcitonin. It is normally produced in response to hypercalcaemia, the serum levels being negligible. PCT levels are elevated in severe bacterial and fungal infections, but not as significantly in viral infections or auto-immune processes.

The mechanism for PCT production after inflammation and its function is presently unknown. It is thought that PCT is produced by the liver and monocytes, in response to bacterial endo-toxins and pro-inflammatory cytokines. PCT is released into the circulation, which is detectable as early as 4 hours, rising rapidly at 6 hours and remains elevated at 8-24 hours, and clears after the insult is resolved. This is in contrast to CRP where peaking occurs 36 hours after stimulation. In healthy people, plasma PCT concentrations are below 0.5 ng/ml, while PCT concentrations can increase up to 1,000 ng/ml in patients with sepsis, severe sepsis or septic shock (Table 1). Viral infections, bacterial colonisation, localised infections, allergic disorders, autoimmune diseases and transplant rejection do not usually induce a significant PCT response (< 0.5 ng/ml). In critically ill children the admission PCT concentration appears to be a better diagnostic marker of infection than CRP or WCC.

Read the full article here.

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Sepsis