🧭 REBEL Rundown
📌 Key Points
- 🧪 Procalcitonin: Still Searching for a Purpose: No clear benefit in diagnosing bacterial infections or guiding antibiotics in the ED.
- 📉 Worse Than Clinical Judgment: Studies show PCT performs worse than clinical assessment for pneumonia and LRTIs.
- 🧬 Can’t Reliably Differentiate Bacterial vs Viral: Sensitivity 55%, specificity 76% for CAP—too weak to guide antibiotic decisions.
- 💊 Minor Drop in Antibiotic Days—At What Cost?: ADAPT-Sepsis trial: <1 day shorter treatment, possible increase in mortality.
- ❌ IDSA Recommends Against It: Not supported for pneumonia diagnosis or treatment duration outside the ICU.
👉 Bottom Line Up Top
Procalcitonin is a lab looking for an indication. Routine use has not been shown to improve diagnosis of bacterial infections or guide antibiotic therapy or duration.
🤕 Case
A 67 year old man with a history of HTN, DM and CAD presents with cough and fever. His vital signs are HR = 112, BP 102/72, O2 Sat 89% on room air, Temp 102.7. Chest X-ray shows a right middle and lower lobe infiltrates and oxygenation improves on HFNC. You start the patient on ceftriaxone and doxycycline. When you call to admit the patient, the admitting physician requests a procalcitonin level. They ask for this test as it can help determine if the infection is bacterial in nature and it can be followed to guide duration of therapy. While you’re happy to send the level, you’re unsure of the veracity of these claims.
🗣️ What Your Gut Says
May as well send the level!
📝 Introduction
Procalcitonin is a protein that is upregulated during inflammatory states. An elevation in procalcitonin should be specific to bacterial infections. Viral infections should result in decreased procalcitonin levels thus allowing us to differentiate bacterial from viral and help guide antibiotic prescription. However, this differentiation isn’t what we see in real life data.
📈 What The Evidence Says
A 2012 study found that procalcitonin performed worse than clinical judgement in determining if the patient’s cause of shortness of breath was due to any type of pneumonia (Maisal 2012). Similarly, a procalcitonin-guided algorithm did not reduce antibiotic prescribing in patients presenting to the ED with fever (Van der Does 2018). A multicenter observational study of > 1700 patients found that no procalcitonin level could adequately distinguish between bacterial and viral causes of community acquired pneumonia (Self 2017). A 2020 meta-analysis found poor performance characteristics for procalcitonin in identifying which patients need antibiotics (sens 55%, spec 76%) and the authors conclude, “a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP” (Kamat 2020). The ProACT study found no difference in antibiotic prescribing for patients with lower respiratory tract infections when a procalcitonin guided approach was used (Huang 2018). Performance characteristics were similarly poor for sepsis (sens 77%, spec 79%) (Wacker 2013). Ultimately, procalcitonin has no clear reliability for differentiating infectious from non-infectious and bacterial from viral causes.
Over the last 15 years, a number of studies have shown that a procalcitonin algorithm results in a modest decrease in length of antibiotic treatment in ICU patients with sepsis. However, these studies are complicated by the absence of blinding amongst other issues (read more here). The ADAPT-sepsis study (REBEL EM Link), is the largest and highest quality study on this use of procalcitonin. It found a significant reduction in antibiotic treatment length in the procalcitonin group of about 1 day (10.7d vs 9.8d mean difference 0.88 days 95% CI 0.19 to 1.58) (Dark 2025). A difference of less than 1 day is clinically insignificant and, there was an increased (though not statistically significant) rate of death in the procalcitonin group (20.9% vs 19.4%). While there may be a small decrease in days on antibiotics, it is unclear if that decrease comes with a change in mortality.
The Infectious Disease Society of America (IDSA) has weighed in as well. They recommend against procalcitonin use in determining both the utility of antibiotics and the duration of antibiotics in pneumonia (Metlay 2019). The IDSA does give a weak recommendation to use procalcitonin to guide duration of antibiotics in ICU patients but this recommendation does not include the most recent evidence (Barlam 2016).
💬 Our Conclusion
Procalcitonin has limited utility in the diagnosis and management of patients with infectious symptoms. Studies clearly show that in adults, the test cannot be used to differentiate viral from bacterial etiologies to guide antibiotic use. While there may be a slight reduction in days on antibiotics in patients admitted to the ICU, the difference is clinically insignificant and may be accompanied by an increase in mortality.
🚨 Clinical Bottom Line
The evidence of utility for procalcitonin in infectious processes is weak. Procalcitonin continues to be a test looking for an indication.
📚 References
- Maisel A et al. Use of procalcitonin for the diagnosis of pneumonia in patients presenting with a chief complaint of dyspnoea: results from the BACH (Biomarkers in Acute Heart Failure) trial. Eur J Heart Fail 2012; 14(3): 278-86. PMID: 22302662
- Van der Does Y et al. Procalcitonin-Guided Antibiotic Therapy in Patients with Fever in a General Emergency Department Population: A Multicentre Non-Inferiority Randomized Clinical Trial (HiTEMP Study). Clin Microbiol Infect 2018. PMID: 29870855
- Self WH et al. Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clin Infect Dis 2017; 65(2):183-190. PMID: 28407054
- Kamat IS et al. Procalcitonin to Distinguish Viral From Bacterial Pneumonia: A Systematic Review and Meta-analysis. Clin Infect Dis 2020; 70(3): 538-542. PMID: 31241140
- Huang DT et al. Procalcitonin-Guided use of Antibiotics for Lower Respiratory Tract Infection. NEJM 2018; 379(3): 236-249. PMID: 29781385
- Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13(5):426-35. PMID: 23375419
- Dark P et al. Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis The ADAPT-Sepsis Randomized Clinical Trial. JAMA 2025; 333(8): 682-93. PMID: 39652885
- Metlay JP 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. PMID: 31573350
- Barlam TF, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016; 62(10): e51-77. PMID: 27080992
Post Peer Reviewed By: Mark Ramzy, DO (X: @MRamzyDO), and Marco Propersi, DO (X: @Marco_Propersi)
👤 Associate Editor
🔎 Your Deep-Dive Starts Here
The ADAPT-Sepsis Trial: Biomarker-Guided Antibiotic Duration for Hospitalized Patients with Suspected Sepsis
Antibiotic stewardship entails delivering the most appropriate antimicrobial therapy for ...
HiTEMP: Procalcitonin-Guided Antibiotic Therapy in the ED
Background: With CMS core measures requiring timely use of antibiotics in ...
(Dis)Utility of Procalcitonin in Lower Respiratory Tract Infections (ProACT Trial)
Background: The mis- and overuse of antibiotics continues to be ...
Procalcitonin: Useful Test or Useless Pest to Improve Antibiotic Stewardship with Acute Respiratory Infections in the ED?
Background: In patients with an acute respiratory illness (ARI), it is ...
