From the Guidelines
Procalcitonin (PCT) is a valuable biomarker for guiding antibiotic therapy decisions in patients with suspected bacterial infections and sepsis, and its 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. PCT levels typically rise in response to bacterial infections but remain low in viral infections, making it useful for differentiating between these causes. When implementing PCT-guided therapy, clinicians should consider initiating antibiotics when PCT levels exceed 0.25-0.5 ng/mL in suspected infections, with higher thresholds (>0.5 ng/mL) strongly suggesting bacterial infection requiring antibiotic treatment. For antibiotic discontinuation, a PCT decrease of 80% from peak value or levels below 0.25-0.5 ng/mL indicates that antibiotics can safely be stopped, as suggested by the Surviving Sepsis Campaign guidelines 1.
Some key points to consider when using PCT to guide antibiotic therapy include:
- PCT levels should be measured at diagnosis and monitored every 24-48 hours to track infection progression and treatment response 1.
- The physiological basis for PCT's utility lies in its rapid production by various tissues in response to bacterial endotoxins and inflammatory cytokines, while its production is suppressed during viral infections by interferon-gamma 1.
- PCT should always be interpreted alongside clinical assessment and other laboratory findings, as certain conditions like trauma, surgery, and some fungal infections can also elevate PCT levels 1.
- A recent 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.
- The largest systematic review and meta-analysis to date of 16 studies and greater than 5000 patients showed that PCT-guided antibiotic discontinuation appeared to decrease antibiotic utilization by 1 day and improve mortality, although the evidence was of low certainty 1.
Overall, PCT is a useful tool for guiding antibiotic therapy decisions in patients with suspected bacterial infections and sepsis, and its use can help reduce antibiotic duration and improve patient outcomes. However, it should be used in conjunction with clinical assessment and other laboratory findings, and its limitations and potential biases should be considered, as noted in the guidelines and studies 1.
From the Research
Role of Procalcitonin in Guiding Antibiotic Therapy
- Procalcitonin (PCT) is a host-response biomarker that has shown clinical value for assessing the likelihood of bacterial infections and guiding antibiotic treatment 2.
- PCT can help differentiate bacterial from non-bacterial infections and inflammation states, particularly in respiratory illness 2, 3.
- Several trials have found that PCT-guided antibiotic stewardship reduces antibiotic exposure and associated side-effects among patients with respiratory infection and sepsis 2, 4, 5.
Clinical Application of Procalcitonin
- Low PCT levels can help rule out bacterial infection in patients with both low pretest probability for bacterial infection and low-risk general condition 2.
- In high-risk individuals and/or high pretest probability for infection, empiric antibiotic treatment is mandatory, and subsequent monitoring of PCT can help track the resolution of infection and guide decisions regarding early termination of antibiotic treatment 2, 3.
- PCT-guided antibiotic treatment has been shown to reduce the duration of antibiotic treatment and daily defined doses in critically ill patients with a presumed bacterial infection, resulting in a significant decrease in mortality 5.
Limitations and Future Directions
- 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 3.
- Several diseases can produce an elevation of PCT levels, resulting in false positive results 3.
- Future research should examine optimal strategies for implementation of PCT-guided antibiotic therapy in hospitals, its real-world impact on clinical outcomes and costs, and its applicability to immunocompromised patients 4.