Utility of Procalcitonin in the ED

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.

Clinical Scenario:

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

Background:

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).

Summary:

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.

Bottom Line:

The evidence of utility for procalcitonin in infectious processes is weak.

Procalcitonin continues to be a test looking for an indication.

Read More

EMRAP: Procalcitonin Rant

First10EM: Procalcitonin in the ED: The Evidence

REBEL EM: HiTEMP - Procalcitonin Guided Antibiotic Therapy in the ED

REBEL EM: (Dis)utility of Procalcitonin in Lower Respiratory Tract Infections (ProACT)

REBEL EM: The ADAPT-Sepsis Trial: Biomarker-Guided Antibiotic Duration for

Hospitalized Patients with Suspected Sepsis

References

1. 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 HeartFailure) trial. Eur J Heart Fail 2012; 14(3): 278-86. PMID: 22302662

2. 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

3. 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

4. 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

5. Huang DT et al. Procalcitonin-Guided use of Antibiotics for Lower Respiratory Tract

Infection. NEJM 2018; 379(3): 236-249. PMID: 29781385

6. 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

7. 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

8. 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

9. 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