Academy of Diagnostics & Laboratory Medicine - Scientific Short
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Procalcitonin (PCT) is a marker of bacterial infection, which is currently used to guide antibiotic treatment in septic patients (1). Procalcitonin is a precursor of the hormone calcitonin, which is detectable in the serum of healthy, non-infected individuals when measured with commercial sensitive PCT assays (2). In case of bacterial infections, PCT is raised, primarily in response to bacterial-initiated Toll Like Receptor stimulation and inflammatory cytokines. In contrast, cytokines produced upon viral infections such as Interferon-γ suppress PCT expression, allowing distinction between bacterial and viral infection (3). Procalcitonin has in vivo a half-life of about 24 hours (4) and its levels readily drop upon resolution of infection.
Multiple randomized clinical trials have demonstrated that PCT is a powerful tool to diagnose and follow up sepsis and, most importantly, guide withdrawal from antibiotic treatment in septic patients since reduction of PCT reflects elimination of the pathogen. Additional trials have also suggested that it can be used to guide antibiotic treatment in community-acquired pneumonia infection (5) as well as in symptom exacerbations in Chronic Obstructive Pulmonary Disease patients (6), since it allows distinction of viral and bacterial infections. Nevertheless, recent meta-analyses have questioned the value of PCT in some conditions (7), potentially due to lack of standardization and harmonization of the assays used between different studies.
Given the utility of PCT in diagnosis and treatment, it is of prime importance that PCT assays provide accurate results that are equivalent across the different available platforms. Although most assays are calibrated using the Kryptor method, several External Quality Assessment (EQA) schemes evidenced a lack of comparability between results from different PCT assays, suggesting that result standardization / harmonization has not yet been achieved. This situation could either be due to the non-commutability of EQA materials or to an actual lack of agreement between the different PCT assays. Still, FDA clearance of several assays and some published studies (8, 9) suggest that between methods, agreement is much better than what was observed in EQA schemes, at least between B·R·A·H·M·S-licensed assays. Although high correlation was observed between most assays, highly variable bias remains among immunoassays. Due to the lack of reference standards for PCT, a candidate reference method by isotope dilution mass spectrometry and Certified Reference Materials are being developed. It was agreed that the mass spectrometry method will not be used to recalibrate commercially available immunoassays until such recalibration is demonstrated to be both necessary and feasible.
In cooperation with EMPIR project SeptiMET (10), the IFCC Working Group on PCT (11) is thus conducting an independent study relying on commutable control materials with the objective to properly document and, if revealed, understand the variability of results provided by the different commercially available PCT assays.
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Fellows of the Academy use the designation of FADLM. This designation is equivalent to FACB and FAACC, the previous designations used by fellows of the National Academy of Clinical Biochemistry and AACC Academy. Those groups were rebranded as Academy of Diagnostics & Laboratory Medicine in 2023.
