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Procalcitonin (PCT): A Vital Biomarker in Infectious Disease Management

Biochemistry and Synthesis

Procalcitonin (PCT) is a 116-residue peptide that is the pro-hormone of calcitonin and has a molecular mass of about 13 kDa. Normally PCT is synthesized in the thyroid gland in the C-cells, but its production is controlled by a rather complex mechanism. However, in the context of systemic infections, particularly bacterial infections, PCT production is significantly upregulated. In addition to the thyroid gland, many other tissues such as liver, kidney, adipocytes and muscle cells synthesize PCT when stimulated with inflammatory mediators. This extrathyroidal synthesis is mainly stimulated by the bacterial products endotoxins and inflammatory cytokines, including TNF-α, IL-1β, and IL-6. What is special about PCT production during infection is the fact that it escapes normal post-translational processing which would otherwise convert it to calcitonin thus being released into the circulation as the intact prohormone.

Diagnostic Value in Bacterial Infections

PCTs are useful biomarker for the diagnosis of bacterial infections and sepsis. This is because PCT is a much more specific marker of bacterial infections as compared to other parameters including CRP or white blood cell count. PCT levels in the serum are usually suppressed in viral infections and other non-infectious inflammatory diseases thus providing an efficient way of differentiating bacterial from viral infections. The dynamics of PCT are especially relevant in the clinical context: PCT levels start to increase within a few hours from the infection onset, reach their maximum at 24-48 hours and then decrease very rapidly in case of effective treatment. PCT values are usually considered to be normal when they are below 0.05 ng/ml while values of 0.5 ng/ml or above are suggestive of bacterial infection and values of 2 ng/ml or above are considered to be suggestive of sepsis. These characteristics make PCT a very useful marker in the emergency and intensive care units as the timing in initiating the antibiotic therapy is of essence.

Clinical Applications and Decision Making

PCT has evolved the practice of clinical decision-making in a n The main applications include managing antibiotic therapy at the time of initiation and discontinuation, assessing the patient’s response to treatment and the patient’s prognosis in the intensive care unit. In the antibiotic stewardship programs PCT-based algorithms have been found to provide significant reduction in antibiotic use with similar or better patient outcomes. This is especially true in the current time when there is a growing problem of antibiotic resistance.

Limitations and Confounding Factors

Although PCT is a useful biomarker, it has some major flaws which should be taken into account by the clinicians. There are certain conditions that can cause elevated PCT levels in the absence of bacterial infection including major trauma, surgery, severe burns and some autoimmune diseases. Also, there are certain bacterial infections, including localized infections or those caused by intracellular bacteria that may not result in high levels of PCT. Renal impairment can therefore alter PCT clearance thus leading to raised levels. In addition, PCT levels should always be assessed in association with the clinical and laboratory data because no single biomarker can offer absolute diagnostic utility. All these aspects are important so as to ensure that the clinical decision and data analysis are right.

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