What causes elevated procalcitonin (PCT) levels?

From the Guidelines

Elevated procalcitonin (PCT) levels are typically caused by bacterial infections, particularly severe systemic infections like sepsis, and can be used to guide antibiotic therapy and distinguish between viral and bacterial etiologies. The most common reasons for elevated procalcitonin include:

• Bacterial sepsis
• Severe bacterial pneumonia
• Bacterial meningitis
• Severe urinary tract infections
• Severe skin/soft tissue infections Procalcitonin levels usually remain low in viral infections or non-infectious inflammatory conditions, as seen in a study published in the Journal of Microbiology, Immunology and Infection in 2023 1. The degree of elevation often correlates with infection severity. If procalcitonin is elevated, a thorough workup for bacterial infection is warranted, including blood cultures, chest x-ray, urinalysis, and other tests as clinically indicated, as suggested by the American Thoracic Society and Infectious Diseases Society of America guideline published in 2019 1. Empiric broad-spectrum antibiotics may be considered while awaiting culture results, especially if sepsis is suspected. Procalcitonin can also be used to guide antibiotic therapy duration, with falling levels suggesting infection resolution and potentially indicating when antibiotics can be safely discontinued, as supported by a study published in the Journal of Microbiology, Immunology and Infection in 2023 1. It's essential to note that procalcitonin can occasionally be elevated in non-bacterial conditions like severe trauma, burns, or some cancers, so clinical context is crucial for interpretation. Serial PCT measurement is recommended in all patients during hospitalization, especially in critically ill or ICU patients, as it may be more predictive of secondary or nosocomial bacterial infection than a single point measurement, as demonstrated by a retrospective, single-center, cohort study 1. A pre-specified rise in PCT by 50%, compared to a previous value at any time point, was significantly associated with the occurrence of secondary bacterial infection in critically ill, COVID-19 patients, highlighting the importance of monitoring PCT levels in these patients 1.

From the Research

Causes of Elevated Procalcitonin (PCT) Levels

Elevated procalcitonin (PCT) levels can be caused by various factors, including:

• Bacterial infections, particularly those caused by Gram-positive and Gram-negative bacteria 2, 3, 4
• Sepsis, a life-threatening condition that occurs when the body's response to an infection becomes uncontrolled 2, 3, 4
• Severe trauma, burns, and medullary carcinoma of the thyroid 5
• Malaria 5
• Diabetic ketoacidosis (DKA), even in the absence of infection 6
• Urosepsis, which can cause higher PCT levels compared to other foci of infection 4

Relationship Between PCT Levels and Disease Severity

Research suggests that PCT levels do not always correlate with disease severity or mortality:

• A study found that higher serum PCT levels did not correlate with indicators of sepsis, severity of disease, or mortality, but were associated with positive blood cultures 3
• Another study found that PCT levels did not correlate with SOFA or APACHE II scores, which are used to assess disease severity 3
• However, PCT levels can be useful in identifying bacterial infections and guiding antibiotic treatment 2, 5

Factors That Influence PCT Levels

Several factors can influence PCT levels, including:

• Type of pathogen, with Streptococcus spp. and Escherichia Coli associated with higher PCT levels 4
• Focus of infection, with urosepsis associated with higher PCT levels 4
• Disease severity, with higher PCT levels potentially indicating a higher risk of severe outcome 5