What is the significance of elevated Procalcitonin (PCT) levels?

From the Guidelines

Procalcitonin elevation is a valuable biomarker primarily indicating bacterial infection, particularly sepsis or severe bacterial infections, and should be used to guide antibiotic therapy decisions, with levels above 0.5 ng/mL suggesting bacterial infection and levels exceeding 2.0 ng/mL strongly indicating sepsis or severe bacterial infection. Procalcitonin is most useful for guiding antibiotic therapy decisions, as it rises rapidly during bacterial infections (within 2-4 hours) and decreases quickly when infection resolves, making it helpful for determining when to start antibiotics and when to safely discontinue them 1. Importantly, procalcitonin is more specific than other inflammatory markers like C-reactive protein (CRP) or white blood cell count, as it generally remains low in viral infections and non-infectious inflammatory conditions. However, certain non-infectious conditions can cause elevations, including major trauma, surgery, severe burns, cardiogenic shock, and some autoimmune disorders. Procalcitonin should therefore be interpreted alongside clinical assessment and other diagnostic tests rather than in isolation. Serial measurements are often more valuable than single readings for monitoring treatment response and guiding antibiotic duration.

Some key points to consider when using procalcitonin to guide antibiotic therapy decisions include:

• Normal levels are typically below 0.05 ng/mL
• Values above 0.5 ng/mL suggest bacterial infection
• Levels exceeding 2.0 ng/mL strongly indicate sepsis or severe bacterial infection
• Procalcitonin rises rapidly during bacterial infections (within 2-4 hours) and decreases quickly when infection resolves
• Procalcitonin is more specific than other inflammatory markers like CRP or white blood cell count
• Certain non-infectious conditions can cause elevations, including major trauma, surgery, severe burns, cardiogenic shock, and some autoimmune disorders

It's also important to note that procalcitonin-based algorithms have been shown to safely reduce antibiotic use in stable, low-risk patients with respiratory infections, and that 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 1. Additionally, a recent systematic review and meta-analysis found that PCT-guided antibiotic discontinuation appeared to decrease antibiotic utilization by 1 day and improve mortality, although the evidence was of low certainty 1.

In terms of specific guidelines, the Society of Critical Care Medicine and the Infectious Diseases Society of America recommend against routine use of biomarkers in the setting of sepsis and septic shock, but suggest that measuring PCT or CRP in critically ill patients with a new fever and no clear focus of infection with low to intermediate clinical probability of bacterial infection may be useful in addition to bedside clinical evaluation 1. The Intensive Care Medicine journal also recommends using procalcitonin to guide the interruption of antibiotic therapy in intensive care unit patients, especially those with lower respiratory tract infections, when plasma procalcitonin concentration is below 0.5 ng/mL or has decreased by over 80% from the peak value 1.

Overall, procalcitonin elevation is a valuable biomarker that can be used to guide antibiotic therapy decisions, and its use can help reduce antibiotic utilization and improve patient outcomes. The most recent and highest quality study recommends using a procalcitonin cutoff value of 0.25 ng/mL to guide antibiotic therapy decisions 1.

From the Research

Procalcitonin Elevation

• Procalcitonin (PCT) is a biomarker used to guide antibiotic therapy in critically ill patients 2, 3.
• PCT-based algorithms can help initiate or stop antibiotic therapy, but the strategy should be rethought based on the clinical scenario 2.
• Studies have shown that PCT-guided discontinuation of antibiotics can reduce antibiotic duration without increasing morbidity or mortality in adult ICU patients 3.
• In adult patients with respiratory tract infections, PCT guidance can reduce antibiotic duration, prescription rate, and total antibiotic exposure without affecting morbidity or mortality 3.
• However, PCT should not be used as the sole deciding factor for initiating antimicrobials, and its use should be limited to patients with signs of infection 2.

Relationship with Antibiotic Therapy

• The combination of vancomycin with piperacillin and tazobactam has been shown to be synergistic against methicillin-resistant Staphylococcus aureus (MRSA) 4.
• Meropenem has been compared to piperacillin-tazobactam in critically ill patients with sepsis and septic shock, with meropenem showing a lower mortality rate on ventilator-free days, vasopressor-free days, and hospital-free days 5.
• The pharmacokinetics and efficacy of meropenem/piperacillin/tazobactam (MPT) have been studied in immunocompetent rabbits with chronic indwelling vascular catheters, showing a favorable profile against MRSA infection 6.

Clinical Implications

• PCT-guided antibiotic therapy can help reduce antibiotic usage and improve patient outcomes in certain clinical scenarios 3.
• The use of PCT should be tailored to the individual patient and clinical scenario, taking into account the presence of infection and the need for antibiotic therapy 2.
• Further studies are needed to fully understand the role of PCT in guiding antibiotic therapy and to optimize its use in clinical practice 2, 3.