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Procalcitonin ( PCT) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. It arises once preprocalcitonin is cleaved by endopeptidase. It was first identified by Leonard J. Deftos and Bernard A. Roos in the 1970s. It is composed of 116 and is produced by parafollicular cells (C cells) of the thyroid and by the neuroendocrine cells of the lung and the intestine.
The level of procalcitonin in the blood stream of healthy individuals is below the limit of detection (0.01 μg/L) of clinical assays. The level of procalcitonin rises in a response to a pro-inflammatory stimulus, especially of origin. It is therefore often classed as an acute phase reactant. (2025). 9781437727029, Elsevier. ISBN 9781437727029 The induction period for procalcitonin ranges from 4–12 hours with a half-life spanning anywhere from 22–35 hours. It does not rise significantly with viral or non-infectious inflammations. In the case of viral infections this is due to the fact that one of the cellular responses to a viral infection is to produce interferon gamma, which also inhibits the initial formation of procalcitonin. With the inflammatory cascade and systemic response that a severe infection brings, the blood levels of procalcitonin may rise multiple orders of magnitude with higher values correlating with more severe disease. However, the high procalcitonin levels produced during infections are not followed by a parallel increase in calcitonin or a decrease in serum calcium levels.
PCT is located on the CALC-1 gene on chromosome 11. Bacterial infections induce a universal increase in the CALC-1 gene expression and a release of PCT (>1 μg/mL). Expression of this hormone occurs in a site specific manner. In healthy and non-infected individuals, transcription of PCT only occurs in neuroendocrine tissue, except for the C cells in the thyroid. The formed PCT then undergoes post-translational modifications, resulting in the production small peptides and mature CT by removal of the C-terminal glycine from the immature CT by peptidylglycine α-amidating monooxygenase (PAM). In a microbial infected individual, non-neuroendocrine tissue also secretes PCT by expression of CALC-1. A microbial infection induces a substantial increase in the expression of CALC-1, leading to the production of PCT in all differentiated cell types. The function of PCT synthesized in nonneuroendocrine tissue due to a microbial infection is currently unknown, but, its detection aids in the differentiation of inflammatory processes.
Legend:
✓ = Moderate evidence in favor of PCT
✓✓ = Good evidence in favor of PCT
✓✓✓ = Strong evidence in favor of PCT
~ = Evidence in favor or against the use of PCT, or still undefined
| Abdominal Infections | observational | 0.25 | ~ | PCT may help exclude ischemia and necrosis in bowel blockage | |
| Arthritis | observational | 0.1-0.25 | ✓ | PCT differentiates non-infectious (gout) arthritis from true infection | |
| Bacteremic infections | observational | 0.25 | ✓✓ | Low PCT levels help rule out microbial infections | |
| Bacteremia (primary) | observational | 0.1 | ✓✓ | PCT differentiates contamination from true infection | |
| Bronchitis | RCT | 0.1-0. 5 | ✓✓✓ | PCT reduces antibiotic exposure without adverse outcomes in the ED | |
| COPD exacerbation | RCT | 0.1-0. 5 | ✓✓✓ | PCT reduces antibiotic exposure without adverse outcomes in the ED and hospital | |
| Endocarditis | observational | 2.3 | ✓ | PCT is an independent predictor with high diagnostic accuracy for acute endocarditis | |
| Meningitis | before-after | 0.5 | ✓ | PCT reduces antibiotic exposure during outbreak of viral meningitis | |
| Neutropenia | observational | 0.1-0.5 | ✓ | PCT is helpful at identifying neutropenic patients with systemic bacterial infection | |
| Pancreatitis | observational | 0.25-0.5 | ~ | PCT correlates with severity and extent of infected pancreatitis | |
| Pneumonia | RCT | 0.1-0. 5; 80-90% ↓ | ✓✓✓ | PCT reduces antibiotic without adverse outcomes exposure in the hospital | |
| Postoperative fever | observational | 0.1-0.5 | ✓ | PCT differentiates non-infectious fever from post-operative infections | |
| Postoperative infections | RCT | 0.5-1.0; 75-85% ↓ | ✓✓ | PCT reduces antibiotic exposure without adverse outcomes in the surgical ICU | |
| Severe sepsis/Shock | RCT | 0.25-0.5; 80-90% ↓ | ✓✓✓ | PCT reduces antibiotic exposure without adverse outcomes in the ICU | |
| Upper respiratory tract infections | RCT | 0.1-0.25 | ✓✓ | PCT reduces antibiotic exposure without adverse outcomes in primary care | |
| Urinary tract infections | observational | 0.25 | ✓ | PCT correlates with severity of urinary tract infections | |
| Ventilator-associated pneumonia | RCT | 0.1-0.25 | ✓✓ | PCT reduces antibiotic exposure without adverse outcomes |
A meta-analysis reported a sensitivity of 76% and specificity of 70% for bacteremia.
A 2018 systematic review comparing PCT and C-reactive protein (CRP) found PCT to have a sensitivity of 80% and a specificity of 77% in identifying septic patients. In the study, PCT outperformed CRP in diagnostic accuracy of predicting sepsis.
In a 2018 meta-analysis of randomized trials of over 4400 ICU patients with sepsis, researchers concluded that PCT led therapy resulted in lower mortality and lower antibiotic administration.
In adults with acute respiratory infections, a 2017 systematic review found that PCT-guided therapy reduced mortality, reduced antibiotic use (2.4 fewer days of antibiotics) and led to decreased adverse drug effects across a variety of clinical settings (ED, ICU, primary care clinic).
Procalcitonin-guided treatment limits antibiotic exposure with no increased mortality in patients with acute exacerbation of chronic obstructive pulmonary disease.
Using procalcitonin to guide protocol in acute asthma exacerbation led to reduction in prescriptions of antibiotics in primary care clinics, emergency departments and during hospital admission. This was apparent without an increase in ventilator days or risk of intubation. Be that acute asthma exacerbation is one condition that leads to overuse of antibiotics worldwide, researchers concluded that PCT could help curb over-prescribing.
The European Society of Cardiology recently released a PCT-guided algorithm for administering antibiotics in patients with dyspnea and suspected acute heart failure. The guidelines use a cut off point of .2 ng/mL and above as the point at which to give antibiotics. This coincides with a 2017 review of literature which concluded that PCT can help reduce antibiotic overuse in patients presenting with acute heart failure. In regards to mortality, a meta analysis of over 5000 patients with heart failure concluded that elevated PCT was reliable in predicting short term mortality.
In acute meningitis, serum PCT is useful as a biomarker for sepsis. It can also be of use in determining viral meningitis versus bacterial meningitis. These findings are the result of a 2018 literature review. This followed a 2015 meta analysis that showed that PCT had a sensitivity of 90% and a specificity of 98% in judging viral versus bacterial meningitis. PCT also outperformed other biomarkers such as C-reactive protein.
In children presenting with fever without an apparent source, a PCT level of .5 ng/mL had a sensitivity of 82% and specificity of 86%. At a 5 ng/mL value, the sensitivity and specificity were 61% and 94%. PCT can help the clinical decision making while identifying invasive bacterial infection in children with unexplained fever.
PCT levels correlate with the degree of illness in pediatric patients with sepsis or urinary tract infections making it effective as a prognostic lab value in these patients.
In adult emergency department patients with respiratory tract illnesses, PCT-guided treatment groups had reduced antibiotic use. PCT references ranges are also used to determine the likelihood a patient has systemic infection (sepsis), thereby reducing incidence of unnecessary antibiotic use in cases where sepsis is unlikely.
Although some literature differs in antibiotic cessation requirements the general consensus is stopping antibiotics when procalcitonin levels fall 80% below peak or below 0.5 μg/L at day five or later during antibiotic therapy.
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