What are the causes of elevated procalcitonin levels?

Causes of Elevated Procalcitonin

Bacterial infections are the primary cause of elevated procalcitonin levels, with higher levels correlating with infection severity and systemic involvement. 1, 2

Infectious Causes

Bacterial Infections

• Bacterial sepsis and septic shock - Procalcitonin levels increase progressively along the continuum from systemic inflammatory response syndrome (0.6-2.0 ng/mL), to severe sepsis (2-10 ng/mL), to septic shock (>10 ng/mL) 1
• Bacterial meningitis - Serum concentrations >10.2 ng/mL have shown sensitivity and specificity up to 100% for diagnosing bacterial meningitis in adults 1
• Bacterial pneumonia - Common cause of elevated procalcitonin, though sensitivity (55%) and specificity (76%) for distinguishing bacterial from viral pneumonia are suboptimal 3
• Bacterial co-infections with viral illnesses - Patients with bacterial co-infection during viral illness typically have higher procalcitonin levels than those with pure viral infection 4

Viral Infections

• Severe viral respiratory infections - Despite previous assumptions that viral infections suppress procalcitonin, severe viral infections can elevate procalcitonin levels, particularly in proportion to disease severity 4
• COVID-19 - Approximately 21% of COVID-19 patients without bacterial pneumonia can have elevated procalcitonin levels 1
• Viral sepsis - Some patients with viral sepsis may have elevated procalcitonin levels, though typically lower than in bacterial sepsis 5

Non-Infectious Causes

Physiologic Stress

• Major trauma - Post-traumatic elevations can occur, with levels ranging from 0.1-120 ng/mL in severely burned patients 2
• Major surgery - Surgical stress can trigger procalcitonin release 6
• Shock states (cardiogenic, hemorrhagic) - Can elevate procalcitonin independent of infection 1

Drug-Related Causes

• Drug hypersensitivity reactions - Some drug reactions can cause procalcitonin elevation 1
• Malignant hyperthermia - This rare but serious condition can be associated with elevated procalcitonin 1
• Neuroleptic malignant syndrome - Another rare syndrome that may elevate procalcitonin 1

Clinical Significance and Interpretation

• Procalcitonin levels typically rise within 2-3 hours of infection onset, making it a useful early marker 1
• Levels correlate with severity of bacterial invasion and can be used to monitor response to antibiotics 2
• Normal procalcitonin levels have high negative predictive value for bacterial infection, particularly in meningitis 1, 5

Important Caveats

• Severity correlation - Procalcitonin may be a better indicator of disease severity than bacterial coinfection during viral respiratory infections 4
• False negatives - Some bacterial infections may not elevate procalcitonin, particularly localized infections without systemic involvement 5
• COVID-19 considerations - Procalcitonin can be elevated in COVID-19 without bacterial superinfection, leading to unnecessary antibiotic use 1
• Interpretation challenges - When used for antibiotic stewardship, procalcitonin levels <0.25 ng/mL can help reduce antibiotic use without increasing mortality 1
• Specific pathogens - Procalcitonin may not be elevated with certain pathogens like Legionella and Mycoplasma species, even in the presence of infection 1