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Evidence for Procalcitonin Testing

Procalcitonin (PCT) is the precursor peptide of calcitonin which under normal circumstances is secreted by thyroid C-cells in response to hypercalcemia. PCT is normally undetectable in serum (<0.05 ng/mL), but is produced in large quantities by many cells in response to bacterial endotoxins and cytokines such as IL-1, IL-6 and TNF. The association between elevated PCT and bacterial infection was first described in 1993. In contrast, viral infections increase secretion of interferon, which attenuates secretion of PCT.

Thus, PCT has been used clinically to distinguish bacterial from viral infections and reduce antimicrobial therapy. PCT rises within 2 to 4 hours of onset of systemic bacterial infection and peaks between 12 and 24 hours. The elimination half-life is 24 to 36 hours.

The strongest evidence supports the use of PCT for managing antibiotic therapy in patients with lower respiratory tract infections and sepsis. A meta-analysis of 8 studies with 3431 patients indicated that PCT monitoring of patients with lower respiratory tract infections resulted in a 31% decrease in antibiotic prescriptions and a decrease in antibiotic therapy duration of 1.3 days (Li H et al. Antimicrob Agents Chemother 2011;53:379-87). A PCT value of <0.25 ng/mL indicated a low risk of bacterial infection while a value > 0.25 ng/mL suggested an increased risk of lower respiratory tract infection requiring antibiotic therapy. In this setting, PCT testing should be repeated within 48 hours to guide antibiotic cessation.

PCT has also been shown to decrease antibiotic exposure by 19 to 38% in patients with sepsis without increasing mortality, length of stay, or persistence of infection. A PCT value of > 0.50 ng/mL is indicative of an increased risk of sepsis, while a value > 2.00 ng/mL is indicative of high-risk sepsis. A PCT level of >10 ng/mL is indicative of septic shock. Mortality is increased when PCT levels are >20 ng/mL. When PCT is elevated, testing should be repeated in 24 hours to guide antibiotic cessation (Bouadma L., et. al. Lancet. 2010; 375: 463-74). Surviving Sepsis Guidelines recommend using PCT to assist clinicians in the discontinuation of empiric antibiotics in patients who initially appear septic, but have no subsequent evidence of infection (Dellinger R., et.al. Critical Care Medicine. 2013; 41(2): 580-637).

PCT is usually low in viral infections, chronic inflammation & autoimmune disease. PCT levels are significantly lower in fungal bloodstream infections than in bacterial bloodstream infections (Cortegiani A., et.al. BMC Anesthesiology. 2014; 14(9):1-9).

PCT may be elevated in clinical situations other than systemic bacterial infections. Severe trauma, major surgery, cardiogenic shock and burns can cause elevations in PCT in the absence of sepsis. PCT can also be falsely elevated in patients with acute kidney injury, end stage renal disease, medullary thyroid cancer, small cell lung cancer and other neuroendocrine tumors such as pheochromocytoma.

In summary, PCT is a valuable test for guiding antibiotic decisions in patients with lower respiratory tract infections and sepsis. The judicious use of PCT in these settings can decrease antibiotic use without adversely affecting patient outcomes. The use of PCT to guide antibiotic stewardship can potentially decrease the incidence of antibiotic resistance.

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