Overview

Procalcitonin (PCT) is a serum biomarker of inflammation that is suggested to help distinguish between bacterial vs other causes of inflammation.

While its use has increased in recent years, the situations in which it has been validated are few and the data is controversial. As with many of our tests and studies, it can be a useful data point to add to the overall clinical scenario, but it should not be relied upon as a marker of truth.

Evidence

Studies involving procalcitonin are generally designed using the PCT treatment algorithm as follows:

• In patients with lower respiratory tract infections (LRIs): recommend to stop antibiotics if PCT <0.25ng/mL, continue if >0.25ng/mL
• In ICU patients with sepsis: when PCT drops below 0.5ng/mL, can discontinue antibiotics or if PCT drops >80% from peak in one day, can discontinue antibiotics

The Data

• For patients with LRIs who are clinically stable:
  • 2017 Cochrane Review
    • Decreased 30-day mortality for those who received treatment following the PCT guided algorithm (adjusted OR 0.83, 95% CI 0.70 to 0.99) vs usual care
    • Reduced antibiotic exposure time by 2.4 days (5.7 versus 8.1 days, 95% CI -2.71 to -2.15) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82)
      • Of note current CAP guidelines only recommend a 5-day treatment course so the clinical relevance of this decrease is debatable
  • 2018 NEJM trial
    • No difference in adverse outcomes or antibiotic exposure time
• For patients with sepsis in the ICU:
  • Decreased median length of antibiotic exposure. 7.5 versus 9.3 defined daily doses (between-group absolute difference 2.69, 95% CI 1.26-4.12) in PCT arm vs standard of care
  • Decreased 28-day mortality. 20% in PCT arm vs 25% in the standard of care (between-group absolute difference 5.4%, 95% CI 1.2-9.5)
• For the accuracy of procalcitonin in the diagnosis of bacterial vs viral CAP:
  • For discriminating bacterial pathogens from viral: area under ROC was 0.73 (95% CI, 0.69-0.77)
  • At PCT cutoff of 0.1ng/ml, sensitivity and specificity for identifying the presence of a bacterial pathogen were 80.9% (95% CI, 75.3%-85.7%) and 51.6% (95% CI, 46.6%-56.5%) respectively

Clinical Use

• There is not enough data to support withholding antibiotics in a patient with a low PCT when a bacterial infection is on the differential. The IDSA guidelines for CAP and VAP/HAP do not recommend using procalcitonin to determine initial antibiotic management
• For patients who have a low PCT (<0.25ng/mL) and a diagnosis of something other than a bacterial pneumonia is most likely, it may be appropriate to discontinue antibiotics
• For critically ill patients in the ICU with sepsis, when the PCT drops below 0.5ng/mL or there is a >80% decrease from peak, this might indicate that antibiotics should be discontinued

Key Points

• PCT has been studied in primarily two scenarios and one should extrapolate to other situations with caution.
• A low PCT should not be used to justify withholding antibiotics in a clinical scenario where bacterial infection is on the differential.
• PCT use in critically ill patients in the ICU might help guide when to discontinue antibiotics.
• PCT can add to clinical decision making but should not be relied on when other clinical signs are suggestive of an underlying bacterial process.

Rhee C. Using Procalcitonin to Guide Antibiotic Therapy. Open Forum Infect Dis. 2016;4(1):ofw249. Published 2016 Dec 7. doi:10.1093/ofid/ofw249

Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017;10(10):CD007498. Published 2017 Oct 12. doi:10.1002/14651858.CD007498.pub3

de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819‐827. doi:10.1016/S1473-3099(16)00053-0

Justin J Choi, Matthew W McCarthy, Matthew S Simon, et al. Clinical Progress Note: Procalcitonin in the Diagnosis and Management of Community-Acquired Pneumonia in Hospitalized Adults. J. Hosp. Med 2019;11;691-693. Published online first August 21, 2019.. doi:10.12788/jhm.3272

Huang DT, Yealy DM, Filbin MR, et al. Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection. N Engl J Med. 2018;379(3):236‐249. doi:10.1056/NEJMoa1802670

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST

Andre C. Kalil, Mark L. Metersky, Michael Klompas, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society, Clinical Infectious Diseases, Volume 63, Issue 5, 1 September 2016, Pages e61–e111, https://doi.org/10.1093/cid/ciw353

Self WH, Balk RA, Grijalva CG, et al. Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clin Infect Dis. 2017;65(2):183-190. doi:10.1093/cid/cix317