Clinical Pearl: Procalcitonin and Lower Respiratory Tract Infections

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Author: Jordan Kaylor, MD PGY4
Northwestern/McGaw Medical Center

Procalcitonin (PCT) is a serum biomarker that, when paired with clinical judgment, may help guide management of lower respiratory tract infections (LRTIs) in the emergency department (ED). Procalcitonin levels can help clinicians distinguish between bacterial and viral infections and might subsequently guide decisions to initiate or discontinue antibiotics. Procalcitonin is a prohormone of calcitonin. It is an acute-phase reactant synthesized in many tissues and released in response to cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α.1 Normal serum concentrations are <0.05ng/mL, but in bacterial infections, PCT increases to detectable levels within three to four hours (earlier than ESR or CRP).[1] Elevations are not seen in noninfectious inflammatory conditions or viral infections, but are possible in Addisonian crises, malaria, severe fungal infections and medullary thyroid carcinoma.[1] In viral infections, interferon (INF)-ɣ probably decreases PCT release, leading to lower or undetectable serum levels.[2]

Although PCT interpretation depends on the specific assay used, in general, along with clinical judgment, a PCT ≤0.1mcg/L (also expressed as 0.1ng/mL) may be able to exclude bacterial infection as a cause of LRTIs. Values of 0.1-0.25mcg/L make bacterial infection unlikely. Values of 0.25-0.5mcg/L suggest possible bacterial infection, and levels ≥0.5mcg/L indicate probable bacterial infection.[3] When PCT drops to < 0.25mcg/L, antibiotics may be discontinued. In Switzerland, among patients presenting to multiple EDs with symptoms of LRTIs (including those with community-acquired pneumonia, chronic obstructive pulmonary disease [COPD] and acute bronchitis), using a PCT algorithm in addition to clinical judgment safely decreased both antibiotic usage and duration of antibiotic therapy without increasing mortality.[4] These results were supported by a 2012 Cochrane review of 14 trials in various clinical settings, although most were done in Europe or China.[5] Additionally, PCT use has been evaluated in the ED workup of heart failure and may identify concomitant bacterial pneumonia or distinguish between bacterial pneumonia and heart failure.[6] It may also identify patients with COPD exacerbations who will benefit from antibiotic therapy.[7] Of note, trials have generally excluded patients with more severe medical comorbidities, such as HIV with a CD4 count <200, active tuberculosis, neutropenia, history of stem cell transplant, cystic fibrosis, hospital-acquired/healthcare-associated pneumonia or those requiring ICU admission.

Based on the available data, it is hard to say if PCT is ready for routine use when evaluating LRTIs in the ED. Although existing literature suggests PCT values are helpful when combined with clinical judgment, patients from North America and those with multiple medical comorbidities are noticeably absent from current publications. Therefore, it is difficult to infer sensitivities and specificities for PCT’s use in ruling out bacterial LRTIs among medically complex patients in EDs across the United States. More research is necessary before we can routinely initiate or withhold antibiotics based on PCT values.

References:

1. Markanday A. Acute phase reactants in infections: Evidence-based review and a guide for clinicians. Open Forum Infect Dis. 2015;2(3):1-7.
2. Gilbert DN. Procalcitonin as a biomarker in respiratory tract infection. Clin Infect Dis. 2011;52 Suppl 4:S346-50.
3. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: Cluster-randomised, single-blinded intervention trial. Lancet. 2004;363(9409):600-7.
4. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: The ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059-66.
5. Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;9:CD007498.
6. Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C, et al. Antibiotic treatment of exacerbations of COPD: A randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007;131(1):9-19.
7. Alba GA, Truong QA, Gaggin HK, Gandhi PU, De Berardinis B, Magrini L, et al. Diagnostic and prognostic utility of Procalcitonin in patients presenting to the emergency department with Dyspnea. Am J Med. 2016;129(1):96-104 e7.