Laboratory Best Practice

PROCALCITONIN FOR ANTIMICROBIAL STEWARDSHIP AND THE MANAGEMENT OF SEPSIS

Background: Procalcitonin (PCT) is a peptide precursor to calcitonin that is associated with the inflammatory response to bacterial infection. Studies have shown PCT levels increasing following bacterial infection (6 hours) and aids in the risk assessment of critically ill patients on their first day of intensive care unit admission for progression to severe sepsis and septic shock.^1-3 Other PCT applications include recognition of infection in febrile infants⁴ and antimicrobial stewardship³.  On average, the half-life of PCT is about 24 hours and is unaffected by neutropenia, corticosteroid therapy, or other immunosuppressive states. In contrast, legacy biomarkers such as C-reactive protein (CRP) have been shown to rise more slowly (12-24 hours) and achieving maximum levels at 48 hours after infection.

Figure 1.

Sepsis Management: PCT levels at ICU admission >2.0 ng/mL are associated with increased risk for severe sepsis or septic shock compared to patients with levels <0.5 ng/mL.⁴ Decreasing PCT of ≤80% from the day that severe sepsis or septic shock was clinically diagnosed to four days after clinical diagnosis is associated with higher 28-day risk of all-cause mortality compared to patients with a decline >80%. The combination of the initial PCT level (≤ 2.0 ng/mL or > 2.0 ng/mL) at diagnosis of severe sepsis or septic shock with the patient’s clinical course and PCT change (“delta”) over time until Day 4 provides critical additional information about the mortality risk. The PCT level on Day 1 can be used to calculate the percent change in PCT level at Day 4 if the Day 0 measurement is unavailable.  Figure 1 illustrates the time course of PCT levels over time following infection and relation to other sepsis biomarkers.⁵ PCT results should always be used with other indicators of sepsis, severe sepsis, and septic shock (e.g., vital signs, white blood cell count, lactate, etc).

Antimicrobial Stewardship: PCT has also been used to support antimicrobial stewardship applications.⁶ Studies have shown 50% of antimicrobial use in the inpatient setting as inappropriate or unnecessary. Evidence now supports the use of PCT for antimicrobial stewardship in lower respiratory tract infections including pneumonia, exacerbations of chronic bronchitis, and asthma exacerbation.

Special Populations: Certain populations such as patients with cardiogenic shock and/or severe tissue injury (e.g., trauma and burns) may exhibit false elevations of PCT.^1,5 The clinical performance of PCT in pediatrics is currently not defined, however, recent studies support further evaluation of this unique population including febrile infants using an algorithm-based approach.⁴

References

1. Christ-Crain and Muller. Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers an mediators. Eur Respir J. 2007;30:556-73.
2. Kibe S, et al. Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother. 2011;66(S2):33-40.
3. Schuetz P, et al. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Medicine. 2011;9:107.
4. Gomez B, et al. Validation of the “Step-by-Step” approach in the management of young febrile infants. Pediatrics 2016;138:1-9.
5. BioMerieux BRAHMS Procalcitonin Assay Product Insert, Accessed on September 22, 2016.
6. Tran NK, et al. Clinical utility of procalcitonin testing in burn patients with severe sepsis. J Burn Care Res [submitted].
7. Li H, et al. Meta-analysis and systematic review of procalcitonin-guided therapy in respiratory tract infections. Antimicrob Agents Chemother. 2011;55:5900-6.