Michael Menna, DO, is a board-certified, active attending emergency medicine physician at White Plains Hospital in White Plains, New York. A procalcitonin test is a type of blood test used to detect sepsis .
As bacterial drug resistance continues to rise across the globe, it has become of utmost importance to enhance antibiotic stewardship. Procalcitonin (PCT) provides healthcare providers with a more specific marker (specificity of ~79%) for determining the presence of bacterial infections when compared to current measures.
Derrick A. Cleland1; Ambika P. Eranki2. Affiliations 1Nova Southeastern University 2SUNY/Upstate Medical University Last Update: August 11, 2021. Introduction In today’s clinical practice, procalcitonin (PCT) has developed into a promising new biomarker for early detection of (systemic) bacterial infections.
The procalcitonin results can also be used to determine if an infection is likely to be caused by bacteria or a virus. If infection symptoms are severe but the procalcitonin level is low, the cause is more likely viral. This can ensure the appropriate drug therapy and avoid the needless use of antibiotics.
In current clinical practice, several chemical assays have been developed to detect procalcitonin serum levels at varying sensitivities, most displaying functional sensitivity around 0.06 ng/mL. One of the first commercially available assays was a homogenous immunoassay that utilizes time-resolved amplified cryptate emission technology. The assay is composed of sheep polyclonal anti-CT antibody and a monoclonal anti-katacalcin antibody which binds to the CT and katacalcin amino acid sequence of PCT via the sandwich method. The assay takes 19 min to complete, and results are typically obtained within 1 hour following serum draw, using 20 to 50 microliters of plasma or serum. [2][7][9]
Procalcitonin has utility in a number of clinical scenarios, however, current research suggests that PCT levels are most useful in the setting of acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) patients to determine when and if antibiotics should be initiated. The European Respiratory Society/American Thoracic Society guidelines currently state that the use of antibiotics in the setting of COPD exacerbations is controversial because there is inadequate research showing improvement in clinical outcomes following the use of antibiotics. Therefore, they recommend further effectiveness studies and/or the use of biomarkers to determine when antibiotics are clinically appropriate. A biomarker, such as procalcitonin, can thus be utilized to determine if antibiotics are appropriate in the setting of acute COPD exacerbations, which in turn, improves antibiotic stewardship and reduces morbidity associated with unnecessary antibiotic use. [6][13]
Procalcitonin serum levels have been shown to increase 6 to 12 hours following initial bacterial infections and increase steadily 2 to 4 hours following the onset of sepsis. The half-life of PCT is between 20 to 24 hours; therefore, when a proper host immune response and antibiotic therapy are in place, PCT levels decrease accordingly by 50% over 24 hours. [8][5][6]
Riedel S, Melendez JH, An AT, Rosenbaum JE, Zenilman JM. Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am J Clin Pathol. 2011 Feb;135(2):182-9. [PubMed: 21228358]
In today’s clinical practice, procalcitonin (PCT) has developed into a promising new biomarker for early detection of (systemic) bacterial infections. PCT is a 116-amino acid residue that was first explained by Le Moullec et al. in 1984; however, its diagnostic significance was not recognized until 1993. In 1993, Assicot et al. demonstrated a positive correlation between high serum levels of PCT and patients with positive findings for bacterial infection and sepsis (eg, positive blood cultures). Further, they demonstrated that PCT did not elevate in viral infections and that serum levels of PCT would decrease following administration of appropriate antibiotic therapies. Current inflammatory biomarkers, such as C-reactive protein (CRP), lack the specificity required to diagnose bacterial versus non-bacterial infections accurately. Therefore, PCT assays with a specificity of 79%, have since been developed and utilized to more accurately determine if a bacterial species is the cause of a patient’s systemic inflammatory reaction. [1][2][3][4]
As bacterial drug resistance continues to rise across the globe, it has become of utmost importance to enhance antibiotic stewardship. Procalcitonin (PCT) provides healthcare providers with a more specific marker (specificity of ~79%) for determining the presence of bacterial infections when compared to current measures. Therefore, PCT assays can be utilized to determine if antibiotics need to be initiated, discontinued, or changed based on changing serum levels thus decreasing the overall use or misuse of antibiotics. Moreover, the assays have also been shown to be useful as a prognostic indicator for patients in the critical care setting, however, further research needs to be performed in this respect to determine if PCT assays are adequate for this purpose. [4][6]
Under normal homeostasis, pre-procalcitonin undergoes initial synthesis by thyroid C cells. Later this peptide is transformed into procalcitonin via cleavage of a 25-amino acid signal sequence by endopeptidases. The end product calcitonin, the 32-amino acid hormone responsible for serum calcium regulation, is then formed following conversion by the enzyme prohormone convertase. Normally, physiological conditions result in very low serum procalcitonin levels (less than 0.05 ng/mL). However, the synthesis of PCT can be increased (up to 100 to 1000 fold) as a result of endotoxins and/or cytokines (eg, interleukin (IL)- 6, tumor necrosis factor (TNF)-alpha, and IL-1b), which act on various tissues. The extra-thyroid synthesis of PCT has been found to occur in the liver, pancreas, kidney, lung, intestine and within leukocytes; however, it merits noting that the synthesis of PCT has been shown to be suppressed within these tissues in the absence of bacterial infection. In contrast, cytokines, such as interferon (INF)-gamma, which get released following viral infection, lead to down-regulation of PCT, thus highlighting another advantage of PCT assays. [5][6][7]
The test is important because sepsis can be difficult to diagnose and doesn't always cause symptoms in the early stages. It is possible, for example, for procalcitonin levels to be low in the very early stages and increase steeply over the course of hours or days. 4
A procalcitonin level on its own only predicts a likelihood that a type of infection is present. The procalcitonin result is a guide, not a diagnosis. Think of the test result as a sign that further testing should be done, not an actual diagnosis.
In newborns, for example, the procalcitonin level is naturally high. 5 . Serious injuries or surgery can also cause an elevation without the presence of sepsis. 6 Non-septic shock, medications, and cancer can also cause trigger an elevation.
The true value of the procalcitonin level is that it can lead to the early treatment of sepsis. Treating the infection even a few hours earlier can make the difference between an illness that responds to antibiotics and one that lands you in intensive care.
The procalcitonin test is ordered when there is a suspicion of sepsis. It is frequently used in emergency rooms or intensive care units when people show signs of sepsis, including high fever, difficulty breathing, low blood pressure, and confusion.
In a healthy individual, procalcitonin is unlikely to be elevated. If a person is sick, and sepsis is suspected, the procalcitonin test would be ordered to determine if there is a widespread dissemination of the bacterial infection.
People do not receive treatment based on a procalcitonin level alone: the entire scope of their current health is evaluated, and treatment is based on the clinical judgment of the physician. The true value of the procalcitonin level is that it can lead to earlier treatment of sepsis.
Procalcitonin is the precursor protein of the hormone Calcitonin. 3 Both PCT and Calcitonin are distinct proteins.
While this synthesis is limited, it plays an important role in the initiation of PCT synthesis in storage tissues of humans. 4
PCT has shown to be a valuable tool to aid in the diagnosis of neonatal sepsis and safe antibiotic guidance from the first day of life.
Baseline PCT testing, in conjunction with clinical signs and symptoms, may tell you if a bacterial infection is likely or not. Initiation of antibiotic treatment depends on the severity of the illness and the patient’s outcome risk. In high-risk patients with severe illness in the ICU, initiation of empiric antibiotic treatment is based on clinical judgment. In patients with mild illness outside the ICU in which bacterial infection is uncertain, baseline PCT can help clinicians decide whether to initiate antibiotics or consider an alternative diagnosis. 2 (Keep in mind: It only takes approximately 20 minutes to get results.)
PCT is a pro-hormone that is highly sensitive and specific for bacterial infection. PCT provides insights into the risk of a patient having a bacterial infection, as well as the severity of that infection. We’ve shared how PCT can help reduce antibiotic exposure and bolster antibiotic stewardship programs . Let’s dive deeper into the science of what PCT is and how it can aid in differentiation between viral and bacterial infections.
PCT levels should be trended every 24 to 48 hours to determine when the infection has resolved enough that antibiotics can be safely stopped. Discontinuing antibiotic treatment can be considered in clinically stable patients when the PCT level has dropped below the respective cut-offs for sepsis or LRTI, or when it has decreased by ≥ 80% of the peak value
This PCT burst is initiated in all storage tissues (peak 12-24h). Parenchymal tissue is the most common type of tissue in humans. As a result, extreme concentrations of PCT can be generated (100,000-fold increase in contrast to physiological concentrations). 4 The PCT burst continues as long as the stimulus for synthesis exists. 4