1) What is Procalcitonin (PCT)?
Answer: Procalcitonin is the inactive form of the hormone Calcitonin. Thus, it is also called the peptide precursor of the hormone Calcitonin. Calcitonin is involved in calcium homeostasis. Procalcitonin is a biomarker produced by the human body that exhibits greater specificity in identifying sepsis and can diagnose bacterial infection. Procalcitonin is composed of 116 amino acids. The parafollicular cells (C cells) of the thyroid and, to an extent by the neuroendocrine cells of the lung and the intestine are responsible for the production of Procalcitonin.
2) What are the different uses of Procalcitonin as a biomarker?
Answer: The different uses of Procalcitonin as a biomarker include:
- Procalcitonin is used to diagnose the severity of renal failure in urinary tract infections in children. The half-life of Plasma PCT in patients with severe renal dysfunction is 35-40 hours, whereas the half-life of Plasma PCT in healthy patients is 24 hours.
- Procalcitonin is a promising biomarker for diagnosing and monitoring medullary thyroid carcinoma.
- Procalcitonin helps to monitor the therapeutic response to antibacterial therapy.
- Procalcitonin is also used to diagnose, stratify risk, and monitor septic shock.
- Procalcitonin has also been shown to be a valuable biomarker for diagnosis of clinically relevant bacterial infections, including:
- Lower Respiratory Tract Infections
- Secondary bacterial infections in COVID-19 pneumonia
- There is a systemic secondary infection in severe trauma, burns, multiorgan failure, and post-surgery.
- Bacteremia and septicemia in neonates, children, and adults.
- Bacterial infection in neutropenic patients
3) Can procalcitonin level elevate if there is no bacterial infection?
Answer: Yes, Procalcitonin levels can get falsely elevated (false positive) in the following cases:
- Severe Trauma
- Surgery
- Cardiac Shock
- Burns
- Malaria
- Systemic vasculitis (Granulomatosis with Polyangiitis, Kawasaki disease, Adult Onset Stills Disease, and Goodpasture’s syndrome)
- End-Stage Renal Disease
- Patients with the following diseases:
- Acute or chronic viral hepatitis
- Decompensated severe liver cirrhosis (Child-Pugh Class C).
- Patients under treatment with OKT3 antibodies, OK-432, interleukins, TNF-alpha, and other drugs stimulating the release of pro-inflammatory cytokines or resulting in anaphylaxis.
Similarly, Procalcitonin levels can be Falsely decreased (False negative) in the following cases:
- Localized infections (osteomyelitis, abscess, subacute endocarditis)
- Procalcitonin checked too early
4) What are the adverse effects of inappropriate use of Antibiotics?
Answer: When overprescribed or used for too long, antibiotics result in a condition called Antibiotic Resistance. The pathogens develop resistance power to the attack of Antibiotics. These antibiotic-resistant pathogens are more challenging to treat, face a higher risk of adverse outcomes, require more extended hospital stays, and incur significantly higher costs to the health care system.
5) What is the PCT cut-off value for different bacterial infections?
Answer: The reference values of Procalcitonin for different age groups include:
- Adults and children ≥72 hours after birth: ≤ 0.15 ng/mL
- Children < 72 hours: <2.0 ng/mL at birth, rises to ≤ 20 ng/mL at 18-30 hours of age, then falls to ≤ 0.15 ng/mL by 72 hours of age
Here are the cut-off points of Procalcitonin for assessment of different bacterial infections: - Less than 0.50 ng/mL: It shows low risk for sepsis and the possibility of local bacterial infection.
- More than 0.50 and less than 2.00 ng/mL: It shows the possibility of sepsis and other conditions.
- More than 2.00 and less than 10.00 ng/mL: It shows that there are likely chances of sepsis.
- More than 10.00 ng/mL: It shows the probability of severe bacterial sepsis or septic shock.
- Less than 0.10 ng/mL: It shows an improbable chance of bacterial infection in the lower respiratory tract.
- More than 0.10 and less than 0.25 ng/mL: It shows that bacterial infection in the lower respiratory tract is unlikely.
- More than 0.25 and less than 0.50 ng/mL: It shows that there are likely chances of bacterial infection in the lower respiratory tract.
- More than 0.50 ng/mL: It shows very likely chances of bacterial infection in the lower respiratory tract.
- <0.50 ng/mL: bacterial meningitis very unlikely
- Cut off 0.50 ng/mL for patients with Stage 5 chronic kidney disease (GFR < 15 ml/min), hemodialysis, and peritoneal dialysis patients.
6) How is procalcitonin used to assist clinicians in determining the duration of antibiotics needed to treat respiratory tract infections and undifferentiated sepsis?
Answer: Below is the conditions that are considered while using procalcitonin to determine the duration of antibiotics for treating respiratory tract infections and undifferentiated sepsis:
Condition 1: If the PCT value is <0.3 µg/L, cessation of antibiotics is strongly encouraged. Antibiotics should only be continued if the condition is clinically unstable. However, for patients with Stage 5 chronic kidney disease, hemodialysis, and peritoneal dialysis, the cut-off value is 0.5 ng/mL.
Condition 2: If the PCT value is between 0.3-0.5 µg/L, or drop by ≥ 80%, then cessation of antibiotics is encouraged. Antibiotics should only be continued if the condition is clinically unstable. However, the cut-off value is 0.25 ng/mL for patients with lower respiratory tract infections.
Condition 3: If the PCT value is ≥ 0.5 µg/L and decreases by < 80%, then cessation of antibiotics is discouraged.
Condition 4: If the PCT value is ≥ 0.5 µg/L and rising or not decreasing, then cessation of antibiotics is strongly discouraged.
7) How does Procalcitonin differ from other markers of infection?
Answer: There are different biomarkers of infection apart from Procalcitonin in humans, including:
- Lactate
- C-reactive protein (CRP)
- Blood Cultures
- White Blood Cell Count
However, the sensitivity and specificity for diagnosing bacterial infection and its severity make PCT unique.
The benefits of using PCT in comparison to other biomarkers include:
- Sensitivity of 89% and specificity of 94 % for bacterial infection.
- PCT levels are not affected by corticosteroids, most autoimmune diseases, or oncology therapy.
- The bacterial burden gets easily reflected..
8) What is the Procalcitonin Test?
Answer: Procalcitonin Test is a blood test used to determine the procalcitonin level in the human body. Procalcitonin level helps the physician diagnose bacterial infection and guide better antibiotic therapy.
The process is simple. The blood sample collected from the patient is centrifuged approximately at 3000 rpm for ten minutes within 30 minutes of collection. The serum is then separated from the blood. The laboratory technician then checks for the presence of serum Procalcitonin. Procalcitonin level above 0.20 ng/mL indicates a systemic bacterial infection.
References
- Procalcitonin FAQS. Accessed at
https://www.thermofisher.com/procalcitonin/wo/en/learning-center/faqs.html - Procalcitonin Frequently Asked Questions – Stanford Medicine. Accessed at
https://med.stanford.edu/content/dam/sm/bugsanddrugs/documents/clinicalpathways/SHC-Procalcitonin-FAQ.pdf - Procalcitonin. Accessed at
https://www.questdiagnostics.com/healthcare-professionals/clinical-education-center/faq/faq46 - What is procalcitonin (PCT)? Accessed at
https://www.medscape.com/answers/2096589-179642/what-is-procalcitonin-pct - PCT, Mayo Clinic Laboratories. Accessed at
https://www.mayocliniclabs.com/test-catalog/Overview/83169#Clinical-and-Interpretive - Specimen collection and processing instructions for PROCALCITONIN test [Internet]. Geisingermedicallabs.com. [cited 2022 Feb 13]. Available from: https://www.geisingermedicallabs.com/catalog/details.cfm?tid=2034