Procalcitonin-Guided Antimicrobial Therapy: Current Evidence for Clinical Decision-Making and Practical Limitations

Antimicrobial resistance and unnecessary antibiotic exposure remain significant problems in clinical practice. Procalcitonin (PCT) has emerged as a clinically relevant biomarker to assist in antibiotic decision-making in patients with suspected bacterial infections. PCT levels may increase in response to bacterial infection and changes in disease activity; however, its diagnostic performance and clinical value are context-dependent, and interpretation of its results requires careful consideration of its limitations. This structured narrative review aimed to examine the available evidence on PCT-guided antibiotic therapy, focusing on antibiotic decision-making and the clinical limitations affecting its use in practice. A literature search was conducted using PubMed, Scopus, and Web of Science. The review primarily included randomized controlled trials, meta-analyses, and widely recognized clinical guidelines. Evidence supports the use of PCT mainly for guiding antibiotic discontinuation, helping to reduce antibiotic exposure without adversely affecting major clinical outcomes. In contrast, its role in guiding antibiotic initiation remains limited, particularly in sepsis, where early empirical antibiotic treatment is essential. Non-infectious inflammatory conditions can cause false-positive elevations in PCT. Conversely, early or localized infections may result in false-negative or lower PCT levels. The timing of measurement and variation in threshold values can also affect the interpretation of PCT results. Differences in the application of guideline recommendations across clinical settings may also influence its clinical utility. PCT can support antimicrobial stewardship and antibiotic decision-making but should not be used as a standalone diagnostic tool. PCT results should always be interpreted within the clinical context, alongside clinical assessment and other available diagnostic information, while considering the limitations of the biomarker and the strength of the supporting evidence.