Procalcitonin Levels: The Ultimate Guide for Use in Sepsis

On By eddyjoemdIn Procalcitonin, Sepsis and Septic Shock

I’ve always had a strong interest in Procalcitonin and how to use it appropriately for our hospitalized patients in the ICU. For that reason, I am creating this work-in-progress page to take a deep dive into all evidence-based clinical questions you and I may have regarding procalcitonin. This post will be continuously updated. Don’t trust what I write and read the cited articles for yourself as this is not peer-reviewed and I’m just a dude pretending to be a doctor (kidding obviously) writing stuff on the internets. First published on 03/07/2021. Date of last update: 02/23/2023.

Table of Contents

  • Where Does Procalcitonin Come From?
  • Procalcitonin vs. CRP
  • Clinical Uses
    • Ruling in or ruling out pneumonia
    • Use in Bacteremia
    • Aspiration Pneumonia
    • COPD
    • Differentiating Bacterial vs. Viral Community Acquired Pneumonia
    • COVID-19
  • Cost

Where does procalcitonin come from?

Vijayan et al. has a neat schematic which illustrates the origin of procalcitonin.

Procalcitonin vs. CRP (Article Shared on 2/23/23)

Póvoa, P., Coelho, L., Dal-Pizzol, F. et al. How to use biomarkers of infection or sepsis at the bedside: guide to clinicians. Intensive Care Med 49, 142–153 (2023). https://doi.org/10.1007/s00134-022-06956-y
Link to Article
Link to FULL FREE PDF

What does the FDA recommend for Procalcitonin?

“with antibiotics strongly discouraged for procalcitonin levels <0.1 μg per liter, discouraged for levels 0.1 to 0.25 μg per liter, recommended for levels >0.25 to 0.5 μg per liter, and strongly recommended for levels >0.5 μg per liter” per Huang et al.

Using procalcitonin to initiate antibiotics

Should we be using procalcitonin to tell us when to initiate antibiotics? Lam et al. published a systematic review and meta-analysis about using procalcitonin versus usual care to determine if using procalcitonin helps to save lives. They used a cutoff of 0.5-1.0mcg/L or greater to initiate antibiotics. After including 3 studies and almost 900 patients in each group, there was no difference in mortality.

Lam SW, Bauer SR, Fowler R, Duggal A. Systematic Review and Meta-Analysis of Procalcitonin-Guidance Versus Usual Care for Antimicrobial Management in Critically Ill Patients: Focus on Subgroups Based on Antibiotic Initiation, Cessation, or Mixed Strategies. Crit Care Med. 2018 May;46(5):684-690. doi: 10.1097/CCM.0000000000002953. PMID: 29293146.
Link to Article

Peng F, Chang W, Xie JF, Sun Q, Qiu HB, Yang Y. Ineffectiveness of procalcitonin-guided antibiotic therapy in severely critically ill patients: A meta-analysis. Int J Infect Dis. 2019 Aug;85:158-166. doi: 10.1016/j.ijid.2019.05.034. Epub 2019 Jun 21. PMID: 31229612.
Link to Article
Link to FULL FREE PDF

Procalcitonin to Rule-In or Rule-Out Pneumonia

People don’t quite understand the limitations of procalcitonin results.
If you are going to order a test, you need to know what to do with it when it comes back.
The company that created the lab test tells us that procalcitonin can help rule in or rule out bacterial infection.
This is not medical advice, read these data for yourself.
On their website, they state “Baseline PCT testing, in conjunction with clinical signs and symptoms, may tell you if a bacterial infection is likely or not.“
Are they lying to us, though?
A place where procalcitonin would be useful is to distinguish bacterial from viral pneumonia.
Turns out that it is not very useful for this indication.
A systematic review and meta-analysis published in 2019 looked at whether procalcitonin is useful or useless for this indication.
Over 2400 patients and 12 studies were reviewed.
The area under the curve is 0.73.
In case you’re rusty at statistics, this means the test is “acceptable”.
When deciding about something as important as antibiotics, acceptable is not acceptable.
If we cannot use it to distinguish bacterial from viral pneumonia, then why in the world are we making clinical decisions off of it?
A positive procalcitonin does not mean infection and a negative procalcitonin does not rule it out.
There are other ways to use procalcitonin but this is not it.

Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, Griffin MR, Metersky ML, Musher DM, Restrepo MI, Whitney CG. 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 Oct 1;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST. PMID: 31573350; PMCID: PMC6812437.
Link to Article
Link to FULL FREE PDF

Procalcitonin use in Bacteremia

Oh my good friend, #procalcitonin, we are doing you so wrong. Sometimes we ignore you to stop antibiotics, sometimes we use you inappropriately to differentiate between bacterial and viral infections and end up under treating bacterial infections. I plan on clearing up a bunch of confusion within the next few months but this shall be article one on the subject. This is where I do feel that checking procalcitonin levels is actually useful and now there’s additional data to support it. Trending it to see if you can discontinue antibiotics early, much to the chagrin of some of my #infectiousdisease colleagues, is a place where it is definitely useful. The caveat is that it has to be elevated in the first place. I’m sure we’ve all seen septic patients with a negative procal at this stage of our careers, as frustrating as that may be. Those are the nuisances of these tests that, if employed correctly, will make you one of the Masters of the Universe. Sorry, my nerd brain is on full swing this morning. 

Meier MA, Branche A, Neeser OL, Wirz Y, Haubitz S, Bouadma L, Wolff M, Luyt CE, Chastre J, Tubach F, Christ-Crain M, Corti C, Jensen JS, Deliberato RO, Kristoffersen KB, Damas P, Nobre V, Oliveira CF, Shehabi Y, Stolz D, Tamm M, Mueller B, Schuetz P. Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials. Clin Infect Dis. 2019 Jul 18;69(3):388-396. doi: 10.1093/cid/ciy917. PMID: 30358811.
Link to Article
Link to FULL FREE PDF

Using Procalcitonin for Antibiotic Stewardship in Aspiration Pneumonia

Labro G, Aptel F, Puyraveau M, Paillot J, Pili Floury S, Merdji H, Helms J, Piton G, Ecarnot F, Kuteifan K, Quenot JP, Capellier G; PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial investigators. Impact on antimicrobial consumption of procalcitonin-guided antibiotic therapy for pneumonia/pneumonitis associated with aspiration in comatose mechanically ventilated patients: a multicenter, randomized controlled study. Ann Intensive Care. 2021 Oct 12;11(1):145. doi: 10.1186/s13613-021-00931-4. PMID: 34636974.
Link to Article
Link to FULL FREE PDF

Procalcitonin and COPD

Can Procalcitonin be used to rule in or rule out bacterial infection in acute exacerbation of COPD? No per the data found by Daubin et al. In this retrospective study including 275 patients, they crunched numbers and found that the AUC was 0.6x which means it is slightly better than flipping a coin.

Daubin C, Fournel F, Thiollière F, Daviaud F, Ramakers M, Polito A, Flocard B, Valette X, Du Cheyron D, Terzi N, Fartoukh M, Allouche S, Parienti JJ; from the PROCALCIVIR and BPCTrea study group. Ability of procalcitonin to distinguish between bacterial and nonbacterial infection in severe acute exacerbation of chronic obstructive pulmonary syndrome in the ICU. Ann Intensive Care. 2021 Mar 6;11(1):39. doi: 10.1186/s13613-021-00816-6. PMID: 33675432.
Link to Article
Link to FULL FREE PDF

Differentiating Viral vs. Bacterial Community Acquired Pneumonia

Le Bel J, Hausfater P, Chenevier-Gobeaux C, Blanc FX, Benjoar M, Ficko C, Ray P, Choquet C, Duval X, Claessens YE; ESCAPED study group. Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan. Crit Care. 2015 Oct 16;19:366. doi: 10.1186/s13054-015-1083-6. PMID: 26472401; PMCID: PMC4608327.
Link to Article
Link to FULL FREE PDF

Differentiating bacteremia from Candidemia

Cortegiani A, Misseri G, Ippolito M, Bassetti M, Giarratano A, Martin-Loeches I, Einav S. Procalcitonin levels in candidemia versus bacteremia: a systematic review. Crit Care. 2019 May 28;23(1):190. doi: 10.1186/s13054-019-2481-y. Erratum in: Crit Care. 2019 Oct 11;23(1):322. PMID: 31138262; PMCID: PMC6537202.
Link to Article
Link to FULL FREE PDF

Procalcitonin in COVID-19

Can we use procalcitonin to rule in or rule out secondary infections in patients with COVID-19? Wolfisberg et al. stated that “it is not yet clear whether PCT can be used as a marker of bacterial coinfection for COVID-19 patients in the same way it has been used in other respiratory diseases”. They also pointed out that, upon arrival to the ED, the incidence of co-infection of COVID with something bacterial was only 7%.

A more recent paper by Patel et al. looking retrospectively at 165 patients.

Wolfisberg S, Gregoriano C, Schuetz P. Procalcitonin for individualizing antibiotic treatment: an update with a focus on COVID-19. Crit Rev Clin Lab Sci. 2021 Sep 13:1-12. doi: 10.1080/10408363.2021.1975637. Epub ahead of print. PMID: 34517744; PMCID: PMC8442987.
Link to Article
Link to FULL FREE PDF

Procalcitonin for Antibiotic Cessation

Lam SW, Bauer SR, Fowler R, Duggal A. Systematic Review and Meta-Analysis of Procalcitonin-Guidance Versus Usual Care for Antimicrobial Management in Critically Ill Patients: Focus on Subgroups Based on Antibiotic Initiation, Cessation, or Mixed Strategies. Crit Care Med. 2018 May;46(5):684-690. doi: 10.1097/CCM.0000000000002953. PMID: 29293146.
Link to Article

Abx cessation in VAP

Beye F, Vigneron C, Dargent A, Prin S, Andreu P, Large A, Quenot JP, Bador J, Bruyere R, Charles PE. Adhering to the procalcitonin algorithm allows antibiotic therapy to be shortened in patients with ventilator-associated pneumonia. J Crit Care. 2019 Oct;53:125-131. doi: 10.1016/j.jcrc.2019.05.022. Epub 2019 May 31. PMID: 31228763.
Link to (NOT FREE) Article

Is Procalcitonin Cost Effective?

Citations on Procalcitonin:

Vijayan AL, Vanimaya, Ravindran S, Saikant R, Lakshmi S, Kartik R, G M. Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy. J Intensive Care. 2017 Aug 3;5:51. doi: 10.1186/s40560-017-0246-8. PMID: 28794881; PMCID: PMC5543591.
Link to Article
Link to FULL FREE PDF

Kamat IS, Ramachandran V, Eswaran H, Guffey D, Musher DM. Procalcitonin to Distinguish Viral From Bacterial Pneumonia: A Systematic Review and Meta-analysis. Clin Infect Dis. 2020 Jan 16;70(3):538-542. doi: 10.1093/cid/ciz545. PMID: 31241140.
Link to Article
Link to FULL FREE PDF

Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 2010 Sep;5(9):1315-6. doi: 10.1097/JTO.0b013e3181ec173d. PMID: 20736804.
Link to Article
Link to FULL FREE PDF

Meier MA, Branche A, Neeser OL, Wirz Y, Haubitz S, Bouadma L, Wolff M, Luyt CE, Chastre J, Tubach F, Christ-Crain M, Corti C, Jensen JS, Deliberato RO, Kristoffersen KB, Damas P, Nobre V, Oliveira CF, Shehabi Y, Stolz D, Tamm M, Mueller B, Schuetz P. Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials. Clin Infect Dis. 2019 Jul 18;69(3):388-396. doi: 10.1093/cid/ciy917. PMID: 30358811.
Link to Article
Link to FULL FREE PDF

Labro G, Aptel F, Puyraveau M, Paillot J, Pili Floury S, Merdji H, Helms J, Piton G, Ecarnot F, Kuteifan K, Quenot JP, Capellier G; PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial investigators. Impact on antimicrobial consumption of procalcitonin-guided antibiotic therapy for pneumonia/pneumonitis associated with aspiration in comatose mechanically ventilated patients: a multicenter, randomized controlled study. Ann Intensive Care. 2021 Oct 12;11(1):145. doi: 10.1186/s13613-021-00931-4. PMID: 34636974.
Link to Article
Link to FULL FREE PDF

Daubin C, Fournel F, Thiollière F, Daviaud F, Ramakers M, Polito A, Flocard B, Valette X, Du Cheyron D, Terzi N, Fartoukh M, Allouche S, Parienti JJ; from the PROCALCIVIR and BPCTrea study group. Ability of procalcitonin to distinguish between bacterial and nonbacterial infection in severe acute exacerbation of chronic obstructive pulmonary syndrome in the ICU. Ann Intensive Care. 2021 Mar 6;11(1):39. doi: 10.1186/s13613-021-00816-6. PMID: 33675432.
Link to Article
Link to FULL FREE PDF

Meier MA, Branche A, Neeser OL, Wirz Y, Haubitz S, Bouadma L, Wolff M, Luyt CE, Chastre J, Tubach F, Christ-Crain M, Corti C, Jensen JS, Deliberato RO, Kristoffersen KB, Damas P, Nobre V, Oliveira CF, Shehabi Y, Stolz D, Tamm M, Mueller B, Schuetz P. Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials. Clin Infect Dis. 2019 Jul 18;69(3):388-396. doi: 10.1093/cid/ciy917. PMID: 30358811.
Link to Article
Link to FULL FREE PDF

Le Bel J, Hausfater P, Chenevier-Gobeaux C, Blanc FX, Benjoar M, Ficko C, Ray P, Choquet C, Duval X, Claessens YE; ESCAPED study group. Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan. Crit Care. 2015 Oct 16;19:366. doi: 10.1186/s13054-015-1083-6. PMID: 26472401; PMCID: PMC4608327.
Link to Article
Link to FULL FREE PDF

Wolfisberg S, Gregoriano C, Schuetz P. Procalcitonin for individualizing antibiotic treatment: an update with a focus on COVID-19. Crit Rev Clin Lab Sci. 2021 Sep 13:1-12. doi: 10.1080/10408363.2021.1975637. Epub ahead of print. PMID: 34517744; PMCID: PMC8442987.
Link to Article
Link to FULL FREE PDF

Patel N, Adams C, Brunetti L, Bargoud C, Teichman AL, Choron RL. Evaluation of Procalcitonin’s Utility to Predict Concomitant Bacterial Pneumonia in Critically Ill COVID-19 Patients. J Intensive Care Med. 2022 Nov;37(11):1486-1492. doi: 10.1177/08850666221108636. Epub 2022 Jun 16. PMID: 35711161; PMCID: PMC9207592.
Link to Article
Link to FULL FREE PDF

Huang DT, Yealy DM, Filbin MR, Brown AM, Chang CH, Doi Y, Donnino MW, Fine J, Fine MJ, Fischer MA, Holst JM, Hou PC, Kellum JA, Khan F, Kurz MC, Lotfipour S, LoVecchio F, Peck-Palmer OM, Pike F, Prunty H, Sherwin RL, Southerland L, Terndrup T, Weissfeld LA, Yabes J, Angus DC; ProACT Investigators. Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection. N Engl J Med. 2018 Jul 19;379(3):236-249. doi: 10.1056/NEJMoa1802670. Epub 2018 May 20. PMID: 29781385; PMCID: PMC6197800.
Link to Article
Link to FULL FREE PDF

Self WH, Balk RA, Grijalva CG, Williams DJ, Zhu Y, Anderson EJ, Waterer GW, Courtney DM, Bramley AM, Trabue C, Fakhran S, Blaschke AJ, Jain S, Edwards KM, Wunderink RG. Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clin Infect Dis. 2017 Jul 15;65(2):183-190. doi: 10.1093/cid/cix317. PMID: 28407054; PMCID: PMC5850442.
Link to Article
Link to FULL FREE PDF

Kip MMA, van Oers JA, Shajiei A, Beishuizen A, Berghuis AMS, Girbes AR, de Jong E, de Lange DW, Nijsten MWN, IJzerman MJ, Koffijberg H, Kusters R. Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients: results from a randomised controlled multicentre trial in the Netherlands. Crit Care. 2018 Nov 13;22(1):293. doi: 10.1186/s13054-018-2234-3. PMID: 30424796; PMCID: PMC6234639.
Link to Article
Link to FULL FREE PDF

Kyriazopoulou E, Liaskou-Antoniou L, Adamis G, Panagaki A, Melachroinopoulos N, Drakou E, Marousis K, Chrysos G, Spyrou A, Alexiou N, Symbardi S, Alexiou Z, Lagou S, Kolonia V, Gkavogianni T, Kyprianou M, Anagnostopoulos I, Poulakou G, Lada M, Makina A, Roulia E, Koupetori M, Apostolopoulos V, Petrou D, Nitsotolis T, Antoniadou A, Giamarellos-Bourboulis EJ. Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial. Am J Respir Crit Care Med. 2021 Jan 15;203(2):202-210. doi: 10.1164/rccm.202004-1201OC. PMID: 32757963; PMCID: PMC7874409.
Link to Article
Link to FULL FREE PDF

Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bucher HC, Annane D, Reinhart K, Falsey AR, Branche A, Damas P, Nijsten M, de Lange DW, Deliberato RO, Oliveira CF, Maravić-Stojković V, Verduri A, Beghé B, Cao B, Shehabi Y, Jensen JS, Corti C, van Oers JAH, Beishuizen A, Girbes ARJ, de Jong E, Briel M, Mueller B. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018 Jan;18(1):95-107. doi: 10.1016/S1473-3099(17)30592-3. Epub 2017 Oct 13. PMID: 29037960.
Link to Article
Link to FULL FREE PDF

Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, Griffin MR, Metersky ML, Musher DM, Restrepo MI, Whitney CG. 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 Oct 1;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST. PMID: 31573350; PMCID: PMC6812437.
Link to Article
Link to FULL FREE PDF

How to support my work

I have written “The Vasopressor & Inotrope Handbook: A Practical Guide for Healthcare Professionals,” a must-read for those in the field! You have several options to get a copy while supporting my endeavors. If you’re in the US, you can order directly from me with a special touch: A SIGNED COPY. Please note that I handle these shipments personally, so I appreciate your patience.

For quicker delivery or international orders, I recommend purchasing through Amazon. It is also available for KINDLE. When you use these affiliate links, I earn an additional commission at no extra cost to you, which is a great way to support my work.

Stay tuned for the audiobook version, which will soon be available on Audible. It’s an exciting addition that I’m eager to share with you!

Disclaimer

Although great care has been taken to ensure that the information in this post is accurate, eddyjoe, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom. Check out additional posts on Sepsis and Septic Shock HERE.