Procalcitonin (PCT) is a biomarker that is released in response to bacterial infections and can be used differentiate the etiology of infectious processes. It can be employed as a tool to guide appropriate antibiotic therapy and thus has a role in antibiotic stewardship.
Although procalcitonin is usually produced in the thyroid, during bacterial infections it is released by the neuroendocrine cells of the lung and intestine and as an acute-phase reactant. When produced in the extrathyroidal tissues, it is not cleaved into its usual products and thus there is no increase in serum calcitonin levels. The raised procalcitonin level during inflammation is associated with bacterial endotoxins and lipopolysaccharides as well as inflammatory cytokines. [5, 6] Levels of procalcitonin released in response to viral infections and noninfectious inflammatory stimuli such as autoimmune disease and chronic inflammatory processes are much less pronounced, rarely exceeding 0.5 ng/mL. [7, 8] Indeed, procalcitonin synthesis is hindered in the presence of interferon gamma, which is released in viral infections.
Serum procalcitonin increases 2-4 hours post–bacterial infection and can be detectable for up to 7 days. [2] There are no enzymes in the plasma that break down procalcitonin. Therefore, if procalcitonin enters the circulation, it remains unchanged, with a half-life of 22-26 hours. It is degraded primarily by proteolysis, with minimal renal excretion. [2]
The physiologic importance and regulation of procalcitonin production are not well understood. Several hypotheses suggest that procalcitonin may be involved in the metabolism of calcium, the cytokine network, and the modulation of nitric oxide (NO) synthesis, as well as having pain-relieving effects. [9]
Serum procalcitonin levels can be used to guide treatment in primary care, in the emergency department, and in the intensive care unit (ICU). [2] A Cochrane systematic review of 26 randomized, controlled trials found that procalcitonin-guided therapy for acute respiratory tract infections resulted in a significantly lower mortality rate, was linked to a 2.4-day decrease in antibiotic exposure, and resulted in a reduced risk of antibiotic-associated side effects. Results were similar for different clinical settings and different types of respiratory tract infections. [10]
Studies have shown that, in ICU patients with sepsis, higher procalcitonin levels are associated with a greater risk of progression to severe sepsis and septic shock, worsening the survival prognosis. Procalcitonin levels fall with successful treatment of severe bacterial infection and severe non-infectious inflammatory stimuli. Persistent or recurrent procalcitonin elevation in the latter setting should prompt suspicion of secondary infection.
A study by Bassetti et al indicated that procalcitonin can aid in early demonstration of the etiology of bacterial infection, finding that it has moderate value in detecting gram-negative bacteremia, particularly that resulting from Enterobacteriaceae, within 24 hours of infection. The investigators reported that procalcitonin levels were higher in patients infected with gram-negative bacteria (26.1 ng/mL) than in those with gram-positive or fungal infection (6.9 and 3.3 ng/mL, respectively). Mean C-reactive protein values, however, showed no such differences in value. [11]
Due to the evidence showing that serial procalcitonin levels can reduce inappropriate and excessive use of antibiotics, it is now widely recommended that testing for the protein be integrated into clinical guidelines. Reductions in antibiotic use will result in fewer drug side effects and lower healthcare costs and will slow the spread of antibiotic resistance. [1, 2, 10]
Indications/Applications
Indications for serum procalcitonin measurement include the following:
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To aid in the diagnosis and risk stratification of bacterial sepsis [12, 13]
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To aid in the diagnosis of renal involvement in children with urinary tract infection
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To aid in distinguishing bacterial from viral infections, including meningitis [14]
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To monitor therapeutic response to antibacterial therapy and reduce antibiotic exposure [15, 16, 17, 18, 19]
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To aid in the diagnosis of systemic secondary infection after surgery and in severe trauma, burns, and multiorgan failure [20]
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To aid diagnosis of infected necrosis and associated systemic complications in acute pancreatitis [21]
Proposed applications of serum procalcitonin measurement include the following:
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To aid the choice and timing of the initiation of antibiotic treatment (Procalcitonin Algorithm) for improved antibiotic stewardship
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To assist with elucidating prognosis of severe localized infections (eg, pneumonia) [22]
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To aid with elucidating prognosis of critically ill patients with systemic infection
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Predicting the need of antibiotic treatment in sepsis and to shorten the duration of antibiotics required [23]
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Use as independent predictor of graft failure late after renal transplantation [24]
Procalcitonin versus C-reactive protein
CRP is the most common laboratory marker used in the clinical setting to evaluate systemic inflammatory response to an infectious agent. It is routinely used as a diagnostic, predictor, and monitoring marker in patients with acute sepsis. Several comparison studies have aimed to determine the use of procalcitonin in conjunction with CRP or independent of it, in the setting of severe bacterial infections.
A systematic review by Covington et al found that procalcitonin levels, when used “in conjunction with other diagnostic tools and clinical examination,” have greater sensitivity and specificity than biomarkers such as interleukin 6, CRP, and lactate, in the diagnosis of sepsis and lower respiratory tract infections. [1] Procalcitonin additionally correlated well with the severity of infection and prognosis. [25]
A study by Bouadma et al revealed a substantial reduction in antibiotic exposure in ICU patients with suspected infections who received procalcitonin-guided antibiotic treatment, with such therapy being “non-inferior to standard care with respect to outcomes." [23]
In terms of estimating the severity of infection and the duration and origin of fever, procalcitonin is a more useful diagnostic inflammation parameter than CRP in patients with pediatric neutropenic fever. [26]
In addition, procalcitonin is a useful early diagnostic marker for the detection of bacteremia in febrile neutropenia and has better diagnostic value than CRP. [27]
Considerations
Procalcitonin levels may also be elevated in medullary thyroid carcinoma, [28] small-cell lung carcinoma, [28] paralytic/vascular ileusexhibiting paraneoplastic production, [26] and renal failure. [28]
There may need to be higher procalcitonin thresholds for patients with renal failure or congestive heart disease. [1]
Procalcitonin, although useful in bacterial sepsis, has no value in the assessment of fungal or viral infections and shows no response to intracellular microorganisms (ie,Mycoplasma) or in local infections with no systemic response.
Similar to CRP, clinical conditions associated with high baseline procalcitonin levels include burns, major surgery, and systemic inflammatory processes.
There are insufficient data on procalcitonin ranges in patients who are immunosuppressed. [10] Neutropenia can result in lower procalcitonin levels because (1) procalcitonin is produced in leukocytes, and (2) inflammatory cytokines released by leukocytes mediate procalcitonin production. [1]
