Procalcitonin as a marker of bacterial infection: CME REVIEW ARTICLE

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OBJECTIVES1. To describe the clinical settings in which measurement of procalcitonin may be of value in diagnosis and management.2. To understand that procalcitonin production is different in bacterial and viral infections and in inflammatory diseases.3. To compare the clinical utility of procalcitonin and other markers of inflammation assessed by the laboratory.4. To understand the importance of sensitivity, specificity and predictive values in laboratory measurements used as markers of infection.Chief Editors\' Note: Each year we publish four review articles for which a total of 4 AMA Category 2 hours can be credited as part of a physician\'s unsupervised learning activities. At the end of the article are questions (with the answers provided) for your consideration. All record keeping for these credit hours is the responsibility of the physician. Do not send the answers to the journal office. Support for the CME Review Articles is provided by an educational grant from Roche Laboratories, Nutley, NJ.HISTORIC BACKGROUNDProcalcitonin (PCT) is the prohormone of calcitonin. It was discovered by chance that PCT increases during infection. This increase has led to the use of PCT as a marker of bacterial infection. By the end of the 1980s it had been shown that PCT increased at the same time as calcitonin in thyroid cancers and certain pulmonary carcinomas. 1–3 In 1992 calcitonin and PCT were systematically determined in burn patients, and PCT values were found to be high in several patients with septicemia in whom calcitonin values were normal. 4 We immediately conducted a prospective study in children, which rapidly showed that PCT was high only in bacterial infections, with no increase of calcitonin, and that initially high PCT values decreased in patients treated with antibiotics, whereas PCT remained constantly low in patients infected with viruses or suffering from inflammatory diseases. 4 Several studies in the 1980s showed an increase in the amounts of immunoreactive calcitonin in patients with severe infections, but this increase probably corresponded to procalcitonin rather than to calcitonin, given the lack of specificity of determinations at the time. 5, 6 Hypocalcemia in septic shock is associated with the inflammatory response and is most marked in infected sepsis patients with high procalcitonin, without this necessarily being the cause of the hypocalcemia. 7These initial results were very convincing, but they originated from a human clinical observation rather than from an experimental demonstration. Current studies on procalcitonin still suffer from two problems. First the phenomenon is purely descriptive; procalcitonin levels increase during bacterial infection or after endotoxin injection, 8 but we do not yet understand the way in which this increase integrates into the cytokine cascade and the inflammatory reaction. The second problem is the absence of a suitable animal model. The murine form of procalcitonin has recently been cloned, but it is currently difficult to show an increase in laboratory animals such as mice, rabbits and dogs. An increase has been shown only in primates, in which the circulating form of PCT is very similar to that of humans.Despite these unknowns PCT was rapidly recognized as a major marker of bacterial infection. Circulating values are generally very low. They have been determined in normal populations of blood donors and are mostly below 0.01 ng/ml. In viral infections and inflammatory diseases, PCT increase slightly but rarely exceed 1 ng/ml. In contrast during severe bacterial infections, circulating PCT levels in the blood may reach 20 to 200 ng/ml. This very large change makes PCT a remarkable marker of bacterial infection, extremely useful in diagnosis and probably also for prognosis.

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