What is the role of procalcitonin (PCT) in the diagnosis and management of sepsis?

From the Guidelines

Procalcitonin (PCT) is a valuable biomarker in diagnosing bacterial sepsis and guiding antibiotic therapy decisions, with levels >0.5 ng/mL suggesting possible sepsis and levels >2.0 ng/mL strongly indicating sepsis, as supported by the most recent study 1. The primary clinical applications of PCT include differentiating bacterial from viral infections, assessing sepsis severity, and guiding antibiotic stewardship.

Key Points

• PCT levels typically rise within 2-4 hours of bacterial infection onset, and serial measurements are more informative than single values, as declining levels generally indicate resolving infection and can support decisions to discontinue antibiotics safely, potentially reducing antibiotic exposure and resistance development 1.
• For antibiotic management, clinicians often use PCT algorithms where therapy can be discontinued when levels fall below 0.5 ng/mL or decrease by 80% from peak values, as demonstrated by a meta-analysis of 11 RCTs involving 4,482 patients 1.
• PCT is particularly useful because it rises specifically in response to bacterial toxins and inflammatory cytokines during bacterial infections, while remaining relatively low in viral infections or non-infectious inflammatory conditions, although recent studies have shown that PCT may be elevated during severe viral illness, including influenza and COVID-19 1.
• Certain conditions like severe trauma, major surgery, and some cancers can elevate PCT independently of infection, potentially leading to false positives, and therefore, PCT should not be used in isolation but rather integrated with clinical assessment, other laboratory findings, and patient context 1.

Clinical Applications

• PCT can be used to guide antibiotic discontinuation in ICU patients with suspected sepsis, with levels of less than 0.5 µg/L or levels that decrease by greater than or equal to 80% from peak levels indicating that antibiotics can be safely discontinued once patients stabilize 1.
• The use of PCT-based algorithms has been shown to safely reduce antibiotic use in stable, low-risk patients with respiratory infections, and can help with de-escalation of therapy in septic patients, as demonstrated by several RCTs 1.
• However, the literature does not strongly favor the use of PCT over other biomarkers, such as C-reactive protein (CRP), and the diagnostic accuracy of PCT for sepsis has been shown to be moderate, with a sensitivity and specificity of 0.80 and 0.77, respectively, in a systematic review and meta-analysis of 9 studies involving 495 patients in the sepsis and 873 in the nonsepsis groups 1.

From the Research

Pathophysiology of Procalcitonin in Sepsis

• Procalcitonin (PCT) is a biomarker that has been shown to be useful in the diagnosis and management of sepsis 2, 3, 4, 5, 6.
• PCT is a peptide precursor of calcitonin, which is produced by the thyroid gland, and its levels increase in response to bacterial infections 3, 4.
• The role of PCT in sepsis is to help differentiate between bacterial and viral infections, as well as to monitor the response to antimicrobial therapy 2, 5.

Diagnostic Utility of Procalcitonin

• PCT has been shown to have good discriminatory properties to differentiate between bacterial and viral inflammations, with rapidly available results 5.
• The diagnostic accuracy of PCT for sepsis has been evaluated in several studies, with a mean sensitivity of 0.77 and specificity of 0.79 4.
• PCT can be used to guide antibiotic use in patients with respiratory infection and sepsis, by limiting initiation and shortening treatment duration 5.

Clinical Applications of Procalcitonin

• PCT can be used for early risk stratification and prognostication in patients with sepsis, which can help optimize therapeutic decisions 5.
• The use of PCT has been shown to improve patient care by reducing unnecessary antimicrobial therapy and improving outcomes 2, 5.
• PCT kinetics over time can also improve the monitoring of critically ill patients with sepsis, and influence decisions regarding de-escalation of antibiotics 5.

Limitations and Challenges

• PCT is not a universal and perfect biomarker, as it can also be increased in noninfectious disease conditions 2.
• The interpretation of PCT results must be done carefully in the context of medical history, physical examination, and microbiological assessment 4.
• Further research is needed to understand the optimal use of PCT, particularly in combination with other emerging diagnostic tests for sepsis 5, 6.