Useful For

Diagnosis of bacteremia and septicemia in adults and children (including neonates)

Diagnosis of renal involvement in urinary tract infection in children

Diagnosis of bacterial infection in neutropenic patients

Diagnosis, risk stratification, and monitoring of septic shock

Diagnosis of systemic secondary infection post-surgery, and in severe trauma, burns, and multiorgan failure

Differential diagnosis of bacterial versus viral meningitis

Differential diagnosis of community-acquired bacterial versus viral pneumonia

Monitoring of therapeutic response to antibacterial therapy

Specimen Type

Clinical Information

Procalcitonin (ProCT) is a 116 amino acid precursor of calcitonin (CT). ProCT is processed to an N-terminal 57 amino acid peptide. CT (32 amino acid) and a 21 amino acid C-terminal peptide, catacalcin (CCP-1). Expression of this group of peptides is normally limited to thyroid C-cells and, to a small extent, other neuroendocrine cells. CT is the only hormonally active of these peptides. CT is secreted by C-cells in response to hypercalcemia and inhibits bone resorption by osteoclasts, minimizing oscillations in serum calcium and calcium loss.

During severe systemic inflammation, in particular related to bacterial infection, the tissue specific control of CT-related peptides expression breaks down and ProCT and CCP-1 (referred collectively to as ProCT) are secreted in large quantities by many tissues. CT levels do not change. ProCT may contribute to sepsis-related death. Decreased mortality after treatment with anti-ProCT antibodies has been demonstrated in animal models of sepsis.

Noninfectious inflammatory stimuli need to be extremely severe to result in ProCT elevations, making it a more specific marker for severe infections than most other inflammatory markers (cytokines, interleukins, and acute-phase reactants). ProCT elevations are also more sustained than those of most other markers and occur in neutropenic patients. This reduces the risk of false-negative results.

ProCT becomes detectable within 2 to 4 hours after a triggering event and peaks by 12 to 24 hours. ProCT secretion parallels closely the severity of the inflammatory insult, with higher levels associated with more severe disease and declining levels with resolution of illness. In the absence of an ongoing stimulus, ProCT is eliminated with a half-life of 24 to 35 hours, making it suitable for serial monitoring. Finally, the dependence of sustained ProCT elevations on ongoing inflammatory stimuli allows identification of secondary septic events in conditions that can result in noninfectious ProCT elevations, such as cardiac surgery, severe trauma, severe burns, and multiorgan failure. ProCT levels should fall at a predictable pace in the absence of secondary infection.

Interpretation

General considerations:

-In children older than 72 hours and in adults, levels <0.15 ng/mL make a diagnosis of significant bacterial infection unlikely.

-Mild elevations between 0.15 a ng/mL and 2.0 ng/mL are consistent with localized mild-to-moderate bacterial infection, but can also be seen in patients with noninfectious systemic inflammatory response.

-Levels >2.0 ng/mL are highly suggestive of systemic bacterial infection/sepsis or severe localized bacterial infection, such as severe pneumonia, meningitis, or peritonitis. They can also occur after severe noninfectious inflammatory stimuli such as major burns, severe trauma, acute multiorgan failure, or major abdominal or cardiothoracic surgery. In cases of noninfectious elevations, procalcitonin (ProCT) levels should begin to fall after 24 to 48 hours.

-Autoimmune diseases, chronic inflammatory processes, viral infections, and mild localized bacterial infections rarely lead to elevations of ProCT of >0.5 ng/mL.

Specific diagnostic applications, based on the current consensus in the literature:

-Diagnosis of bacteremia and septicemia in adults and children (including neonates):

 - In children <72 hours old, whether born term or preterm, higher cutoff levels may be appropriate. There is no consensus in the literature, but the most recent publications suggest diagnostic cutoffs for the diagnosis of serious bacterial infection of >1.0 ng/mL at birth, > or =100 ng/mL at 24 hours, and > or =50 ng/mL at 48 hours of age. Adult levels should apply at > or = 72 hours.

-Diagnosis of renal involvement in pediatric urinary tract infections:

 - In children with urinary tract infections, a ProCT level of >0.5 ng/mL has a 70% to 90% sensitivity and an 80% to 90% specificity for renal involvement.

-ProCT responses in neutropenic patients are similar to patients with normal neutrophil counts and function, and the cutoffs discussed under general considerations above should be used.

In the appropriate clinical setting, a ProCT of >2.0 ng/mL predicts sepsis and a level of >10 ng/mL indicates likely septic shock. Reported sensitivity and specificity for the diagnosis of sepsis range from 60% to 100%, depending on underlying and coexisting diseases and the patient populations studied. The higher the ProCT level the worse the prognosis. ProCT concentrations of >20 ng/mL are associated with a guarded prognosis. However, universally accepted risk-scoring systems for ProCT levels in sepsis have not been developed. When sepsis has been successfully treated, ProCT levels should fall with a half-life of 24 to 35 hours.

ProCT levels that are elevated in noninfectious, severe inflammatory conditions should start falling within 48 hours of the initial toxic stimulus with a half-life of 24 to 35 hours. Persistent high levels or secondary peaks suggest secondary infection.

A ProCT level of <0.5 ng/mL makes bacterial meningitis very unlikely. Most patients with bacterial meningitis will have ProCT levels of >10 times this level.

With successful antibiotic therapy, ProCT levels should fall with a half-life to 24 to 35 hours.