What is the significance of procalcitonin (PCT) levels?

From the Guidelines

Procalcitonin (PCT) levels are a valuable biomarker in clinical settings to guide antibiotic therapy decisions, particularly in distinguishing between bacterial and viral infections, and can help reduce unnecessary antibiotic use, as evidenced by a recent meta-analysis of 11 RCTs involving 4,482 patients 1.

Significance of Procalcitonin Levels

The significance of PCT levels lies in their ability to increase specifically with bacterial infections, while remaining relatively low during viral infections or non-infectious inflammatory conditions.

• Normal PCT levels are less than 0.1 ng/mL
• Levels above 0.5 ng/mL suggest possible bacterial infection
• Values exceeding 2.0 ng/mL strongly indicate sepsis or severe bacterial infection PCT levels can be used to support the discontinuation of empiric antibiotics in patients who initially appeared to have sepsis, but subsequently have limited clinical evidence of infection, as suggested by the surviving sepsis campaign guidelines 1.

Clinical Application of Procalcitonin

In clinical practice, PCT can help clinicians determine when to initiate antibiotics and when to safely discontinue them, with serial measurements showing declining levels indicating effective treatment.

• PCT levels begin to rise four hours after exposure to bacteria, reaching a maximum level after six to eight hours 1
• Serum levels of PCT are associated with the severity of the infection, and decrease rapidly after antibiotic treatment 1 However, PCT should always be interpreted alongside clinical assessment and other laboratory findings, as certain conditions like trauma, surgery, and some cancers can cause elevations unrelated to bacterial infection.

Recent Evidence

A recent systematic review and meta-analysis evaluated the diagnostic accuracy of PCT and CRP in the diagnosis of sepsis in adults, and found that PCT had a higher diagnostic accuracy and specificity than CRP 1.

• The overall area under the summary receiver operator characteristic (SROC) curve was 0.85 for PCT, with a sensitivity and specificity of 0.80 and 0.77, respectively
• The authors concluded that there is a moderate degree of value of PCT for diagnosis of sepsis in adult patients Additionally, a meta-analysis of 11 RCTs involving 4,482 patients reported that PCT-guided antibiotic treatment in ICU patients with infection and sepsis patients resulted in improved survival and lower antibiotic treatment duration 1. Therefore, PCT levels can be a useful tool in guiding antibiotic therapy decisions, particularly in distinguishing between bacterial and viral infections, and can help reduce unnecessary antibiotic use, as supported by the most recent and highest quality evidence 1.

From the Research

Significance of Procalcitonin (PCT) Levels

• PCT is a useful biomarker of bacterial infection and its use is associated with reduced duration of antibiotic therapy in intensive care medicine 2.
• PCT can help differentiate bacterial from non-bacterial infections and inflammation states, particularly in respiratory illness 3.
• PCT-guided antibiotic stewardship reduces antibiotic exposure and associated side-effects among patients with respiratory infection and sepsis 3, 4.
• Low PCT levels can help rule out bacterial infection in patients with low pretest probability for bacterial infection and low-risk general condition 3.
• PCT possesses high potential to improve decision-making regarding antibiotic treatment when combined with careful patient assessment, evidence-based clinical algorithms, and continuous notification and regular feedback from all antibiotic stewardship stakeholders 3.

Clinical Applications of PCT

• PCT use is appropriate in algorithms for antibiotic de-escalation and discontinuation, but initiation or escalation of antibiotic therapy should not be based solely on PCT serum levels 2.
• PCT can be used to guide antibiotic therapy in various clinical settings, including emergency departments, regular wards, surgical wards, and intensive care units 2, 5.
• PCT is widely used together with other biomarkers, such as white blood cells (WBC) count and C reactive protein (CRP), to guide antibiotic therapy 6.
• A multi-diagnostic tools approach, including PCT, WBC, and CRP, is fundamental to perform a correct and rapid diagnosis of infection and sepsis in emergency departments 6.

Limitations and Uncertainties

• Interpretation of PCT levels must always comprise the clinical setting and knowledge about assay characteristics 4.
• Only highly sensitive PCT assays should be used in clinical practice, and cut-off ranges must be adapted to the disease and setting 4.
• There are uncertainties on the optimal cut-offs to be used for starting or discontinuing antibiotic treatment in patients with suspected bacterial infection or sepsis, and on the role of PCT variations during antibiotic treatment 5.
• Several diseases can produce an elevation of PCT levels, thus producing false positive results 5.