2. Procalcitonin
Procalcitonin (PCT) is a polypeptide containing 116 amino acids, encoded by the
CALC-1 gene located on chromosome 11 in humans.
It is the precursor form of calcitonin. Usually, it is produced from the thyroidal
parafollicular C cells and the intestinal and pulmonary neuroendocrine cells.
During infection & inflammation, rise is associated with inflammatory cytokines
and bacterial endotoxin, causing increased expression of the CALC-1 gene in
several other body tissues such as the liver, WBCs, kidney, spleen, adipose tissue
and pancreas.
4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 2
3. Synthesis
Procalcitonin synthesis pathways vary in different inflammatory states. In
the absence of systemic inflammation, procalcitonin synthesis is
restricted to thyroid neuroendocrine cells, and the protein is not released
into the blood until it is cleaved into its mature form, calcitonin.
Thus, serum procalcitonin is typically undetectable in healthy persons
when standard assays are used..
4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 3
4. Synthesis
When systemic inflammation is caused by bacterial infection, procalcitonin synthesis
is induced in nearly all tissues and released into the blood.
Known triggers for synthesis include bacterial toxins, such as endotoxin and cytokines
including tumor necrosis factor (TNF)-alpha, interleukin-1-beta, and interleukin-6.
In contrast, procalcitonin synthesis is not induced in most viral infections.
The lack of induction is likely due to cytokines released in viral infections that inhibit
TNF-alpha production, such as interferon-gamma.
4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 4
5. 4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 5
6. Kinetics
Serum procalcitonin levels rise within 2 to 4 hours of an inflammatory stimulus,
typically peaking within 24 to 48 hours.
With resolution of inflammation, procalcitonin levels quickly decline at a predictable
rate. After reaching peak, levels decline by about 50 percent every 1 to 1.5 days.
When the inflammatory stimulus is ongoing, procalcitonin production continues and
levels plateau.
Peak levels roughly correlate with the severity of infection.
4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 6
7. Mildly Elevated Serum Procalcitonin
Conditions associated with mildly elevated serum procalcitonin levels (0.15-2
ng/mL) include the following:
Localized mild to moderate bacterial infection.
Noninfectious systemic inflammatory response.
Untreated end-stage renal failure.
4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 7
8. Elevated Serum Procalcitonin Levels (>2 ng/ml)
Conditions associated with elevated serum procalcitonin levels (>2 ng/mL)
include the following:
Bacterial sepsis
Severe localized bacterial infection (eg, severe pneumonia, meningitis, peritonitis)
Severe noninfectious inflammatory stimuli (eg, major burns, severe trauma, acute
multiorgan failure, major abdominal or cardiothoracic surgery)
Medullary thyroid carcinoma (may exceed 10,000 ng/mL)
4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 8
9. Indications/Applications
To aid in the diagnosis and risk stratification of bacterial sepsis.
To aid in the diagnosis of renal involvement in children with urinary tract
infection.
To aid in distinguishing bacterial from viral infections, including meningitis.
To monitor therapeutic response to antibacterial therapy and reduce antibiotic
exposure.
To aid in the diagnosis of systemic secondary infection after surgery and in
severe trauma, burns, and multiorgan failure.
To aid diagnosis of infected necrosis and associated systemic complications in
acute pancreatitis.
4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 9
10. 4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 10
11. 4/27/2023 DR. MD. SHAFIQUL ISLAM DEWAN, RESIDENT (PULMONOLOGY), DMCH 11
These kinetics are altered in patients with renal dysfunction.
* Procalcitonin has not been well studied in immunocompromised patients, trauma or surgery patients, pregnant women, patients with cystic fibrosis, and patients with chronic kidney disease. The algorithm may not be applicable to these populations or other patients with complex comorbidities.
¶ Optimal thresholds have not been precisely determined. Some experts use a lower threshold, typically 0.1 ng/mL when deciding to discontinue antibiotics.
Δ Decisions to stop antibiotics should be made in combination with clinical judgment and presume that the patient is stable and that a bacterial infection that requires a longer course of therapy, such as CAP complicated by bacteremia, was not identified.
◊ Systemic inflammation due to other causes, such as burns, trauma, surgery, pancreatitis, malaria, or invasive candidiasis can also lead to elevated procalcitonin levels.
§ Reaching a procalcitonin level of <0.25 ng/mL is not a requirement for antibiotic discontinuation. For patients with clinically resolved pneumonia and levels >0.25 ng/mL, clinical judgment alone is adequate.