A 48-year-old male with a history of COPD, HTN, and high cholesterol comes to the ED with cough, congestion, sore throat and nausea. The patient’s symptoms started this morning and now he presents to you with a temp of 38.9°C, HR 120, RR 16, BP 128/70 and SpO2 of 99% on room air. His exam is benign, he feels better after two nebulizer treatments and acetaminophen, and now has vitals of temp 37.3°C, HR 96, BP 124/70. You are ready to send your patient home with a diagnosis of an upper respiratory infection, but wouldn’t it be great if you had a test showing this patient didn’t have a bacterial source?
Emergency physicians face the challenge of identifying bacterial illness on virtually every clinical shift. Physical examination and current laboratory tests including blood cultures, white blood cell count, and CRP lack sensitivity, specificity, and/or rapidity. Serum lactate, while useful as a marker of severity of illness, has no role in determining the presence or type of infection. The lack of adequate markers leads to both delays in appropriate antibiotics and simultaneous over-treatment of non-bacterial illness. One test may fill this void.
On April 8th, BRAHMS announced that they received FDA approval for their procalcitonin (PCT) test system called “PCT sensitive KRYPTOR®”. The FDA has approved the PCT test system to help risk stratify patients upon ICU admission for the progression to severe sepsis or septic shock. It employs immunofluorescence technology, requires 50 uL of blood or serum, and has an incubation period of 19 minutes. As with other ICU interventions and tests, it’s only a matter of time until the device finds its way into the ED.
Procalcitonin is a prohormone of calcitonin found in the serum of healthy persons at a level of < 0.05 ug/L. It is normally produced in thyroidal C-cells, however, can be produced by virtually all parenchymal cells with a significant stimulus like severe bacterial infection. In 1993, Assicot and colleagues noted that serum PCT levels are elevated in patients with severe bacterial infection, yet remain low in patients with viral infections. Subsequently, elevations in serum PCT have been documented in patients with severe trauma, surgery, heat stroke, cardiogenic shock, autoimmune disease, and fungal and parasitic infections. In addition to being a marker of illness, animal data suggest that PCT may play a pathogenic role in the inflammatory process. Since Assicot and colleagues’ seminal article, several investigators have sought to determine the role of PCT in the evaluation, stratification, and prognostication of patients who are suspected of being infected. However, one of the difficulties of evaluating the existing data is that several investigators use different test thresholds as indicative of a normal or abnormal test.
Taking this data to the bedside, the PCT test has potential use in several ED patient populations. In febrile infants and children with suspected severe bacterial infections (SBI), Andreola and colleagues concluded that PCT is valuable in predicting SBI and more accurate than CRP in infants with fever < 8 hours; however, CRP may be a more appropriate marker because of its higher sensitivity, better availability, lower cost, and longer historical practice. For the diagnosis of bacteremia in the ED, Jones and colleagues demonstrated a moderate diagnostic performance of the PCT test in a meta-analysis. Christ-Crain and colleagues used PCT as part of an algorithm for the decision to prescribe antibiotics to both ambulatory and admitted patients with lower respiratory tract infections. They found significant reductions in antibiotic prescribing with similar clinical outcomes compared to control patients treated with standard antibiotic prescribing practices.
Procalcitonin is theoretically attractive because it is induced in bacterial illness, essentially undetectable in health, and possesses a half-life that allows for a sufficient time window for testing. Although insufficient data exists to support the cost effectiveness or use of procalcitonin in isolation, this test adds one more tool to the emergency physician’s armamentarium when piecing together the puzzle of the possibly infected patient.
Munish Goyal, MD, is an adjunct assistant professor at the University of Pennsylvania School of Medicine