Procalcitonin & Sepsis
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What is Sepsis?
Sepsis is a life-threatening bodily reaction to infection which occurs when the body’s immune response to an ongoing infection begins to damage its own tissue. As the body’s natural infection-fighting abilities ramp up, releasing a burst of chemicals into the bloodstream, widespread inflammation can lead to a multitude of issues. These can include tissue damage, multi-system organ failure and even death. It most commonly occurs in patients who are already hospitalized, and can progress to septic shock, which is characterized by a dramatic drop in blood pressure. Vulnerable patient populations such as neonates, pediatrics and geriatrics are at even greater risk.
Approximately 1.7 million adult sepsis infections in the United States each year1
Culminates into some 350,000 deaths per year in the U.S.1
Approximately 1.7 million adult sepsis
infections in the United States each year1
Culminates into some 350,000 deaths
per year in the U.S.1
Quick SOFA (qSOFA) scoring
Quick SOFA or qSOFA is a bedside clinical score that serves as a screening tool to identify patients who are likely to have sepsis. When patients have at least two out of the following three clinical criteria, they are deemed at risk of sepsis:
- An altered mental state
- A drop in systolic blood pressure below 100
- An elevated respiratory rate, at or above 22 breaths per minute
Sepsis is often treated with antibiotics, but this comes with a caveat. Since sepsis is a fairly sudden and very serious condition, attempts to prevent the patient’s condition from worsening can contribute to the rampant problem of antibiotic overuse.
Role of Procalcitonin Use in the Management of Sepsis
Septic patients present a challenge for physicians, as there is the need to balance the urgency of prescribing antibiotics with the imperative to avoid injudicious antibiotic use.
Procalcitonin (PCT) is a biomarker used to predict the likelihood of a patient having a bacterial infection and how severe that infection might be, giving clinicians a way to manage antibiotic exposure while also improving patient outcomes. In various studies, PCT-guided antibiotic therapy has been shown to decrease the duration of antibiotic treatment for sepsis,2 decrease antibiotic costs and decrease the annual ICU re-infection rate by 35.1%.3
Monitoring Procalcitonin Levels in Sepsis to Safely Discontinue Antibiotics
PCT can be used for sepsis risk assessment, both during an initial determination and to track trending levels.
Reference range: In apparently healthy people, plasma PCT concentrations are found to be < 0.1 ng/mL
PCT levels below 0.5 ng/mL do not exclude an infection, because localized infections (without systemic signs) may also be associated with such low levels. In addition, if the PCT measurement is done very soon after the systemic infection process has started (usually < 6 hours), values may still be low.
The PCT reference ranges are valuable guidelines for the clinician, but they should always be interpreted in the context of the patient’s clinical condition. Antibiotic treatment should be started or continued on suspicion of infection, particularly in high-risk patients.
PCT values may be elevated in certain medical conditions independent of bacterial infection. Decisions regarding antibiotic therapy should NOT be based solely on procalcitonin concentrations.
Reference range: In apparently healthy people, plasma PCT concentrations are found to be < 0.1 ng/mL
PCT levels below 0.5 ng/mL do not exclude an infection, because localized infections (without systemic signs) may also be associated with such low levels. In addition, if the PCT measurement is done very soon after the systemic infection process has started (usually < 6 hours), values may still be low.
The PCT reference ranges are valuable guidelines for the clinician, but they should always be interpreted in the context of the patient’s clinical condition. Antibiotic treatment should be started or continued on suspicion of infection, particularly in high-risk patients.
PCT values may be elevated in certain medical conditions independent of bacterial infection. Decisions regarding antibiotic therapy should NOT be based solely on procalcitonin concentrations.
In the US, it is recommended that B·R·A·H·M·S PCT levels of > 2.0 µg/L are linked to a high probability of systemic bacterial infection with eventual progression to sepsis/septic shock. Levels below 0.5 indicate a low likelihood. These recommendations differ outside of the United States.
In the US, it is recommended that B·R·A·H·M·S PCT levels of > 2.0 ng/mL are linked to a high probability of systemic bacterial infection with eventual progression to sepsis/septic shock. Levels below 0.5 indicate a low likelihood. These recommendations differ outside of the United States.
In the US, it is recommended that B·R·A·H·M·S PCT levels of > 2.0 ng/mL are linked to a high probability of systemic bacterial infection with eventual progression to sepsis/septic shock. Levels below 0.5 indicate a low likelihood. These recommendations differ outside of the United States.
Aiding assessment of mortality risk
Clinicians can use serial PCT measurements, taken over consecutive days, to help them assess the response to antibiotic therapy and the risk of all-cause mortality among ICU patients. When the infection is controlled, PCT will rapidly decline daily.4 If the PCT level has not significantly declined, the patient and antibiotic therapeutic approach should be reassessed.
A baseline PCT measurement > 2.0 ng/mL on Day 0 is an additional risk factor to consider when evaluating procalcitonin measurements on subsequent days.5
Appropriate interpretation
PCT levels must always be interpreted in the context of laboratory findings and clinical assessments:
- Perform a baseline test on patients with suspected systemic bacterial infections or who are determined to be especially at risk of a bacterial infection or sepsis
- Repeat testing at regular intervals to monitor trending PCT levels
- PCT levels that trend downward may indicate it’s appropriate to cease antibiotic treatment early, reducing the risk of antibiotic overexposure
- Hospitals eager to implement PCT testing for use in sepsis management should have a game plan including an awareness/education campaign, support and performance systems and widespread participation from providers
Health care providers that follow guidelines governing the suggested use of PCT testing in determining whether and when to discontinue antibiotics are better equipped to balance the risks of discontinuing against the risks of overuse.
Changes in PCT
plasma concentration*
Current PCT
plasma concentration*
Decline from peak
PCT ≥ 80%
and clinical improvement
OR
Sepsis < 0.50 ng/mL
Discontinue antibiotics
PCT-supported therapy has been shown to reduce inpatient antibiotic exposure by 23% for critically ill ICU patients7 without negative effects for mortality or length of stay.6-8
*Presented clinical intended uses and cutoffs are approved for CE countries but could differ depending on local regulatory
PCT and sepsis guidelines
The Surviving Sepsis Campaign (SSC) is a global initiative to bring together professional organizations to improve the treatment of sepsis and reduce the high mortality rate associated with the condition. In the 2021 guidelines, the coalition suggested that:9
Measurement of PCT levels can be used to support shortening the duration of antibiotic therapy in sepsis patients.9
The WHO recognizes that in vitro diagnostics (IVDs) are essential for advancing universal health coverage, addressing health emergencies, and promoting healthier populations—the three strategic priorities of the Thirteenth WHO General Programme of Work, 2019-2023.10
Recommendation: PCT to guide antibiotic therapy or discontinuation in sepsis and lower respiratory tract infection (for use only in tertiary care facilities and above)10
B·R·A·H·M·S PCT™ can aid in the decision to discontinue antibiotics for patients recovering from either confirmed or suspected sepsis by identifying the presence or absence of bacterial infection with high sensitivity.
Benefits of Procalcitonin Testing in the Management of Sepsis
Testing procalcitonin levels at the first sign of suspected infection or in high-risk situations can help catch systemic bacterial infections early, allowing for more effective treatment, better outcomes and lower overall cost in the management of sepsis.
Benefits of Procalcitonin Testing in the Management of Sepsis
Testing procalcitonin levels at the first sign of suspected infection or in high-risk situations can help catch systemic bacterial infections early, allowing for more effective treatment, better outcomes and lower overall cost in the management of sepsis.
Assessing risk early and utilizing repeat PCT testing to monitor trending numbers can also help health care professionals determine when it is appropriate to stop antibiotic treatment early. Preventing the incorrect application of antimicrobial therapies can reduce the likelihood of antibiotic resistance by reducing antibiotic exposure rate by up to 50%. That reduction in antibiotic usage is, in turn, associated with better short- and long-term patient outcomes and lower patient care costs.
There are broader benefits to PCT testing as well. Testing and tracking PCT has proven effective in assessing the risk of all-cause mortality among ICU patients.5 Given that cases of sepsis are most common in patients in intensive care, implementation of PCT testing in hospitals for ICU patients can lead to better outcomes across the board.
How to Implement Procalcitonin Testing in Your Hospital
Adapting new testing and treatment protocols can be challenging, but there are ways to streamline procalcitonin implementation to help curb antibiotic overuse and improve patient outcomes.
A proper implementation plan includes the following five elements:
- Education tailored to the facility/individual
- Reminder systems
- Support systems for clinical decision-making
- Performance feedback
- Participation from healthcare providers and lab professionals
- Education tailored to the facility/individual
- Reminder systems
- Support systems for clinical decision-making
- Performance feedback
- Participation from healthcare providers and lab professionals
While some implementation strategies differ depending on region, patient mix, and type of healthcare facility, the need for education remains constant. Creating awareness among patient populations, providers, and even stakeholders is vital for long-term program success. Use the core benefits of PCT as a lodestone, driving home the fact that procalcitonin is safer and better, leading to reduced antibiotic use, better outcomes and lower costs.
The Future of PCT for the Management of Sepsis
Using PCT testing in the diagnosis and management of sepsis is becoming increasingly common. As awareness grows, it’s likely more hospitals will recognize the extensive benefits offered by procalcitonin testing — including better patient outcomes and lower financial impact for both the facility and patients — boosting adoption even further.
Current events like the COVID-19 pandemic shine an even stronger light on the need for solutions to rising antibiotic resistance. Studies that evaluated the use of PCT testing to rationalize antibiotic prescribing in patients with confirmed or suspected cases of COVID-19 found that proper monitoring of procalcitonin levels led to reduced antibiotic use, which suggests a more positive future for antibiotic stewardship.11 Monitoring a procalcitonin level in a septic patient can provide insight on when to safely discontinue antibiotics.
Applying the same logic to sepsis management could make it easier for health care providers to diagnose, track and treat infections without overprescribing antibiotics and putting patients at unnecessary risk.
Helpful Resources
FAQ
Providers looking to implement PCT testing at their hospital or other healthcare facility should follow implementation recommendations for the best chance at gaining support and achieving desired health and economic outcomes.
For more information about optimizing procalcitonin testing or onboarding PCT testing at your hospital, contact the Thermo Fisher team.
PCT is useful in a variety of clinical situations in which there’s potential for a systemic bacterial infection. A partial list of clinical PCT uses include:
- Differentiating between bacterial and viral respiratory tract infections and bacterial versus viral meningitis
- Determining whether antibiotics should be used and for how long
- Monitoring the progress of sepsis and septic shock
- Diagnosing bacteremia and sepsis in adults and children
- Diagnosing renal involvement in pediatric UTI cases
Procalcitonin tests are a relatively simple procedure that mirrors other blood draws for laboratory testing purposes. A designated healthcare professional uses a small needle to collect a blood sample in a test tube or vial. That sample is then transferred to a lab for analysis.
The entire test (minus processing and lab work) typically takes less than five minutes and requires no special preparation.
There is very little risk involved with a procalcitonin test. Risk levels for a PCT test are on par with other tests that involve blood draws, with possible pain, bruising, dizziness or fainting, bleeding, discomfort, swelling and blood clots. There is also a slight risk of infection.12
PCT tests can be used to obtain a baseline in clinical situations that suggest a risk of systemic bacterial infection or sepsis. That typically happens in the ER or ICU when a patient is presumed to have sepsis or septic shock. Testing can be repeated over the next two days to track trending PCT levels.
If antibiotics are introduced, repeat PCT tests should occur every 2-3 days as part of determining whether early antibiotic cessation is recommended or appropriate.
Patients at risk of sepsis who have low PCT levels upon initial testing should be reassessed within six to 24 hours.
PCT levels of > 2.0 ng/mL (US IFU) or ≥ 2.0 ng/mL (IVDR IFU) indicate the patient has a high probability of a systemic bacterial infection and increased risk that the infection could progress to sepsis or septic shock.
Levels of ≥ 0.5 - < 2.0 ng/mL indicate there’s a moderate risk for systemic infection and/or sepsis. As there are other conditions that could cause elevated PCT levels, patients in this bracket should be monitored clinically and reassessed with an additional PCT test within six to 24 hours.
Note that low PCT levels do not definitely mean there is no chance of a bacterial infection. Follow-up evaluations and clinical monitoring are also crucial in these situations.
C-reactive protein (CRP) is an inflammatory biomarker similar to procalcitonin in that it can also be used to diagnose sepsis. PCT is clinically shown to be more sensitive than CRP (77% compared to 75%) and has greater specificity (79% vs just 67%) when used to differentiate between bacterial sepsis and other noninfectious systemic inflammatory responses.13
Elevated PCT also rises to detectable levels earlier in the infection response process, allowing for faster diagnosis.
CRP testing can be more beneficial in cases where a fungal infection is suspected or in patients with renal complications, as CRP levels are not influenced by renal disease or neutropenia.
The test for procalcitonin is a simple blood test. A healthcare professional uses a small needle to extract a blood sample, which is contained in a test tube or vial and sent to a lab for analysis. There’s no preparation required on the patient’s part.
The lab tests for procalcitonin and sends findings back to the ordering physician. Those results are then interpreted alongside other clinical findings and test data to eliminate other possible causes of low or high PCT levels and determine a diagnosis and course of treatment.
- Centers for Disease Control Prevention https://www.cdc.gov/sepsis/what-is-sepsis.html
- Jeon K, Suh JK, Jang EJ, Cho S, Ryu HG, Na S, Hong SB, Lee HJ, Kim JY, Lee SM. Procalcitonin-Guided Treatment on Duration of Antibiotic Therapy and Cost in Septic Patients (PRODA): a Multi-Center Randomized Controlled Trial. J Korean Med Sci. 2019 Apr 15;34(14):e110. doi: 10.3346/jkms.2019.34.e110. PMID: 30977312; PMCID: PMC6460106.
- Hohn A, Schroeder S, Gehrt A, Bernhardt K, Bein B, Wegscheider K, Hochreiter M. Procalcitonin-guided algorithm to reduce length of antibiotic therapy in patients with severe sepsis and septic shock. BMC Infect Dis. 2013 Apr 1;13:158. doi: 10.1186/1471-2334-13-158. PMID: 23547790; PMCID: PMC3616901.
- Soni NJ, Samson DJ, Galaydick JL, Vats V, Huang ES, Aronson N, et al. Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis. J Hosp Med. 2013 Sep;8(9):530-40.
- Schuetz P, Birkhahn R, Sherwin R, et al. Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study. Crit Care Med. 2017;45(5):781–789
- Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): A multicentre randomised controlled trial. Lancet Infect Dis. 2010 Feb 6;375(9713):463-74
- Schuetz P, Christ-Crain M, Thomann R. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: The proHOSP randomized controlled trial. JAMA. 2009 Sep 9;302(10):1059-66
- Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: A randomised study. Eur Respir J. 2009 Dec 1;34(6):1364-75.
- L. Evans et al; Intensive Care Med, 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y
- Second WHO Model List of Essential In Vitro Diagnostics [Internet]. https://www.who.int/publications/i/item/WHO-MVP-EMP-2019.05
- Christina Peters, Kelly Williams, Elena A Un, Louisa Little, Abeer Saad, Katherine Lendrum, Naomi Thompson, Nicholas D Weatherley, Amanda Pegden. Use of procalcitonin for antibiotic stewardship in patients with COVID-19: A quality improvement project in a district general hospital. Clinical Medicine Jan 2021, 21 (1) e71-e76; DOI: 10.7861/ clinmed.2020-0614
- WHO Best Practices for Injections and Related Procedures Toolkit. Geneva: World Health Organization; 2010 Mar. 3, Best practice in phlebotomy and blood collection. Available from: https://www.ncbi.nlm.nig.gov/books/NBK128496
- Dr. C. Kingsburgh. CRP vs PCT: which one to choose and when?. Ampath Chat. June 2018.
