B·R·A·H·M·S PCT (Procalcitonin) Education for Sepsis and Antibiotic Stewardship

U.S. Health Economic Analysis Demonstrates the Cost Reduction Impact of Using B⋅R⋅A⋅H⋅M⋅S PCT to Support Antibiotic Stewardship Versus Standard of Care

 

A new health economic analysis published in the journal PLOS One, compared the cost impact of using B·R·A·H·M·S PCT (Procalcitonin) assays to support antibiotic stewardship decisions versus the standard of care for patients with suspected sepsis or lower respiratory tract infections (LRTI) in the United States. The analysis considered the societal and hospital perspective with a time horizon covering the length of hospital stay. The main endpoints were total costs per patient, including treatment costs and productivity losses, the number of patients with antibiotic resistance or C.difficile infections, and costs per antibiotic day avoided.

Based on the results, the authors concluded that using B·R·A·H·M·S PCT assay to aid in decisions about antibiotic use for hospitalized patients with suspected sepsis and LRTI is associated with a reduction in antibiotic days, a shorter length of stay on the regular ward and the intensive care unit, shorter duration of mechanical ventilation, and fewer patients at risk for antibiotic resistance or C.difficile infection.

Read the full analysis and press release.

Featured Educational Webinars

The Role of PCT in Bacterial Infection and Patient Management: Effective Real-World Strategies

Claim Continuing Education Credit for this educational webinar replays offered through The American Association for Clinical Chemistry (AACC).  

Implementing Procalcitonin: A Team Approach

Featured videos

Dr. Gluck discusses the challenges in diagnosing and treating systemic bacterial infections and the role of procalcitonin in this short video. 

B·R·A·H·M·S PCT is a critical component to reduce unneeded antibiotic usage and limit antibiotic exposure in lower respiratory tract infection (LRTI) and sepsis.

B·R·A·H·M·S PCT is an invaluable marker to help assess presence or absence of a bacterial infection in the emergency department. Clinical insight is given by Dr. Neath in this short informative video. 

Dr. Gluck highlights how B·R·A·H·M·S PCT is used to help assess presence or absence of a bacterial infection in the intensive care unit.

B·R·A·H·M·S PCT can be used to help customize antibiotic therapy for patients with bacterial infections. Dr. Broyles provides real–world insight and experience.

This new video explains the unique kinetics of PCT in response to inflammatory processes resulting from bacterial infection.

2019 Events

ON DEMAND WEBINAR: The Importance of Procalcitonin for Antimicrobial Stewardship in Patients with Lower Respiratory Tract Infections in the Emergency Department

Presented by: John Boreyko, Pharm.D., BCIDP

Watch Now


About B·R·A·H·M·S PCT

B·R·A·H·M·S PCT provides clinicians in the intensive care unit, emergency department, and hospital wards with a sensitive, specific, and STAT biomarker to aid in sepsis assessment for patients in or headed to the intensive care unit. In conjunction with other laboratory findings and clinical assessments, B·R·A·H·M·S PCT provides valuable information on the severity of a bacterial infection—both on presentation and during the course of treatment of the septic patient. The test takes just 20 minutes, therefore, results can be rapidly available to support clinicial decisions. Clinicians in health systems worldwide have relied on B·R·A·H·M·S PCT since 1996 to make patient care decisions with confidence. More than 3,500 publications in both the U.S. and Europe have demonstrated the clinical utility of PCT, defined clinical cut-offs, and treatment algorithms based on the B·R·A·H·M·S PCT assay performance.

Expanding insight for antibiotic use

B·R·A·H·M·S PCT provides clinicians in the emergency department, intensive care unit, and hospital wards with a sensitive, specific, and STAT biomarker that provides newly expanded insight to aid clinicians in making decisions regarding antibiotic therapy, as well as differential diagnosis of bacterial infection and sepsis. The Surviving Sepsis Campaign International Guidelines for Management of Severe Sepsis and Septic Shock (2016) suggests that PCT measurements can be used to support shortening the duration of antimicrobial therapy in sepsis patients.

Insight for initiating antibiotics

As many as 75% of patients with acute respiratory–tract infections are treated with antibiotics, despite a mainly viral cause for these infections.
B·R·A·H·M·S PCT aids clinicians in the emergency room or inpatient hospital settings in determining whether antibiotics are appropriate for patients with suspected or confirmed lower respiratory tract infections (LRTI), defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

B·R·A·H·M·S PCT has been shown to reduce antibiotic prescription rate and exposure duration in LRTI. Duration of antibiotic exposure and antibiotic prescription rates were significantly reduced in the PCT group in comparison to the standard of care group for community–acquired pneumonia (CAP) (n=925), acute exacerbations of COPD (n=228), and bronchitis (n=151) in the ProHosp trial.2

PCT LRTI Antibiotic Cutoffs

Insight for safely discontinuing antibiotics

Paired with clinical assessment, B·R·A·H·M·S PCT also aids decisions about whether to discontinue antibiotic therapy for patients with LRTI, or with suspected or confirmed sepsis.

 

1 Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2016
Schuetz P., Christ-Crain M. et al., Jama 2009; 302(10): 1059-1066. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial

Aiding sepsis risk assessment

B·R·A·H·M·S PCT is a sensitive and specific biomarker of the inflammatory response to bacterial infection. Five PCT levels above 2.0 ng/mL indicate a higher risk for progression to severe sepsis or septic shock. Six PCT levels below 0.5 ng/mL indicate a low likelihood of progression to severe sepsis or septic shock. This information can be obtained in emergency departments and hospital wards prior to admission to the intensive care unit to help determine both severity of illness and adequacy of source control. This initial PCT measurement provides a baseline for comparison with day four PCT.

PCT concentrations and sepsis risk12-14

PCT concentrations and sepsis risk

 

 

  • Less than 0.5 ng/mL—Low risk for progression to severe sepsis and/or septic shock

  • Between 0.5 and 2 ng/mL—Sepsis should be considered

  • Greater than 2 ng/mL—High risk for progression to severe sepsis and/or septic shock
  •  

     

    PCT levels must always be interpreted in the context of other laboratory findings and clinical assessments.


    5. Brunkhorst FM et al: Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med 1998;24(8):888-889.
    6. Hausfater P et al: Serum procalcitonin measurement as diagnostic and prognostic marker in febrile adult patients presenting to the emergency department. Crit Care 2007;11(3):R60. doi:10.1186/cc5926.
    12. Harbarth S et al: Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001;164(3):396-402.
    13. Müller B et al: Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 2000;28(4):977-983. 
    14. Meisner M. Procalcitonin: Biochemistry and Clinical Diagnosis; UNI-MED Verlag AG; 2010.[p1]

    Aiding septic patient management

    Following ICU admission, evaluating multiple B·R·A·H·M·S PCT measurements over consecutive days aids in assessing the response to empiric antibiotic therapy. As the infection is controlled, PCT will decline daily.7 The Procalcitonin Monitoring Sepsis Study (MOSES) showed that sustained elevated PCT levels are an independent risk factor for mortality. PCT levels that decline less than 80% from the baseline within four days are associated with increased all–cause mortality—especially when the baseline PCT measurement is greater than 2.0 ng/mL.

    Assessing PCT kinetics over time provides valuable information regarding patient disposition, response to treatment, and likelihood of survival.

    When using B·R·A·H·M·S PCT for ICU patient management, comparing the baseline PCT level taken on Day 0/1 with subsequent measurements through Day 4, the following assessments of PCT kinetics should be considered8:

    • Decrease in PCT values greater than 80%—Lower risk of all-cause 28-day mortality.
    • Decrease in PCT values less than or equal to 80%—two-fold higher risk of all-cause 28-day mortality.
    • Baseline PCT measurement greater than 2.0 ng/mL—Additional information about the mortality risk when evaluating the patient’s clinical course with PCT measurements on subsequent days.

    PCT levels should always be used in conjunction with other clinical assessments and laboratory findings, and not in isolation.


    7Soni NJ et al: Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis. J Hosp Med  2013;8(9):530-540.
    8Moses Clinical Trial Data. On file Thermo Fisher Scientific 

    Understanding PCT kinetics

    Rapid and sustained response to bacterially induced systemic inflammation, and a half-life of 24 hours, are important hallmarks of PCT as a marker of sepsis risk.

    pct-kinetics

    Following stimulus by a bacterial endotoxin or trauma, PCT plasma concentrations:5,23  

    • Rise 3 to 6 hours after bacterial invasion
    • Are significant after 6 hours
    • Exhibit peak values between 12 to 24 hours
    • Have an observed half–life of approximately 24 hours

    This rapid and sustained response to bacterially induced systemic inflammation is an important hallmark of PCT as a marker of sepsis risk.
    For more information:

     Download  Reducing Antibiotic Exposure brochure


    5. Brunkhorst FM et al: Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med 1998;24(8):888-889.
    23. Meisner M: Procalcitonin: experience with a new diagnostic tool for bacterial infection and systemic inflammation. J Lab Med Medicine 1999;23(5):263-272.

    PCT versus lactate

    The sensitivity and specificity of PCT to the host response to severe bacterial infection, together with its rapid rise after an infectious challenge, offer clinical advantages that complement existing biomarkers for the clinical assessment of the septic patient.

    In addition, lactate does not rise until late in the course of sepsis.18

    pct-vs-lactate

    16. Dellinger RP et al: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41(2):580-637.
    17. Thomas-Rueddel DO et al: Hyperlactatemia is an independent predictor of mortality and denotes distinct subtypes of severe sepsis and septic shock. J Crit Care 2015;30(2):439.e1-439.e6.
    18. Freund Y: Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection. Biomarkers 2012;17(7):590-596.

    Important considerations when interpreting PCT results

    The prognostic value of PCT in the setting of sepsis has not been validated in US patients younger than 18. Increased PCT levels may not always be related to systemic bacterial infection.14,25-27 They may also be associated with:

    • Injuries including major trauma, burns, and heat stroke
    • Acute medical conditions such as biliary pancreatitis, chemical pneumonitis, viral hepatitis and/or decompensated severe cirrhosis (Child-Pugh Class 3), prolonged or severe cardiogenic shock, prolonged severe organ perfusion anomalies, and post-cardiac arrest 
    • Unusual infectious diseases including invasive fungal infections and acute plasmodium falciparum malaria
    • Active medullary C-cell carcinoma, small cell lung carcinoma, and bronchial carcinoid
    • Interventions such as surgery with extracorporeal circulation, treatment with drugs stimulating release of pro-inflammatory cytokines or resulting in anaphylaxis, peritoneal or hemodialysis
    • Neonates during first two days of life

    B·R·A·H·M·S PCT results should be evaluated in context of all laboratory findings and the total clinical status of the patient. In cases where the laboratory results do not agree with the clinical picture or history, additional tests should be performed. Refer to Thermo Scientific B·R·A·H·M·S PCT   package insert for additional information.


    14. Meisner M. Procalcitonin: Biochemistry and Clinical Diagnosis; UNI-MED Verlag AG; 2010.
    25. Meisner M et al: Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med 1998;24(7): 680-684.
    26. Chiesa C et al: Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis 1998;26(3): 664-672.
    27. Reith HB et al: Procalcitonin in early detection of postoperative complications. Dig Surg 1998;15(3):260-265.

    Expanding insight for antibiotic use

    B·R·A·H·M·S PCT provides clinicians in the emergency department, intensive care unit, and hospital wards with a sensitive, specific, and STAT biomarker that provides newly expanded insight to aid clinicians in making decisions regarding antibiotic therapy, as well as differential diagnosis of bacterial infection and sepsis. The Surviving Sepsis Campaign International Guidelines for Management of Severe Sepsis and Septic Shock (2016) suggests that PCT measurements can be used to support shortening the duration of antimicrobial therapy in sepsis patients.

    Insight for initiating antibiotics

    As many as 75% of patients with acute respiratory–tract infections are treated with antibiotics, despite a mainly viral cause for these infections.
    B·R·A·H·M·S PCT aids clinicians in the emergency room or inpatient hospital settings in determining whether antibiotics are appropriate for patients with suspected or confirmed lower respiratory tract infections (LRTI), defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

    B·R·A·H·M·S PCT has been shown to reduce antibiotic prescription rate and exposure duration in LRTI. Duration of antibiotic exposure and antibiotic prescription rates were significantly reduced in the PCT group in comparison to the standard of care group for community–acquired pneumonia (CAP) (n=925), acute exacerbations of COPD (n=228), and bronchitis (n=151) in the ProHosp trial.2

    PCT LRTI Antibiotic Cutoffs

    Insight for safely discontinuing antibiotics

    Paired with clinical assessment, B·R·A·H·M·S PCT also aids decisions about whether to discontinue antibiotic therapy for patients with LRTI, or with suspected or confirmed sepsis.

     

    1 Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2016
    Schuetz P., Christ-Crain M. et al., Jama 2009; 302(10): 1059-1066. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial

    Aiding sepsis risk assessment

    B·R·A·H·M·S PCT is a sensitive and specific biomarker of the inflammatory response to bacterial infection. Five PCT levels above 2.0 ng/mL indicate a higher risk for progression to severe sepsis or septic shock. Six PCT levels below 0.5 ng/mL indicate a low likelihood of progression to severe sepsis or septic shock. This information can be obtained in emergency departments and hospital wards prior to admission to the intensive care unit to help determine both severity of illness and adequacy of source control. This initial PCT measurement provides a baseline for comparison with day four PCT.

    PCT concentrations and sepsis risk12-14

    PCT concentrations and sepsis risk

     

     

  • Less than 0.5 ng/mL—Low risk for progression to severe sepsis and/or septic shock

  • Between 0.5 and 2 ng/mL—Sepsis should be considered

  • Greater than 2 ng/mL—High risk for progression to severe sepsis and/or septic shock
  •  

     

    PCT levels must always be interpreted in the context of other laboratory findings and clinical assessments.


    5. Brunkhorst FM et al: Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med 1998;24(8):888-889.
    6. Hausfater P et al: Serum procalcitonin measurement as diagnostic and prognostic marker in febrile adult patients presenting to the emergency department. Crit Care 2007;11(3):R60. doi:10.1186/cc5926.
    12. Harbarth S et al: Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001;164(3):396-402.
    13. Müller B et al: Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 2000;28(4):977-983. 
    14. Meisner M. Procalcitonin: Biochemistry and Clinical Diagnosis; UNI-MED Verlag AG; 2010.[p1]

    Aiding septic patient management

    Following ICU admission, evaluating multiple B·R·A·H·M·S PCT measurements over consecutive days aids in assessing the response to empiric antibiotic therapy. As the infection is controlled, PCT will decline daily.7 The Procalcitonin Monitoring Sepsis Study (MOSES) showed that sustained elevated PCT levels are an independent risk factor for mortality. PCT levels that decline less than 80% from the baseline within four days are associated with increased all–cause mortality—especially when the baseline PCT measurement is greater than 2.0 ng/mL.

    Assessing PCT kinetics over time provides valuable information regarding patient disposition, response to treatment, and likelihood of survival.

    When using B·R·A·H·M·S PCT for ICU patient management, comparing the baseline PCT level taken on Day 0/1 with subsequent measurements through Day 4, the following assessments of PCT kinetics should be considered8:

    • Decrease in PCT values greater than 80%—Lower risk of all-cause 28-day mortality.
    • Decrease in PCT values less than or equal to 80%—two-fold higher risk of all-cause 28-day mortality.
    • Baseline PCT measurement greater than 2.0 ng/mL—Additional information about the mortality risk when evaluating the patient’s clinical course with PCT measurements on subsequent days.

    PCT levels should always be used in conjunction with other clinical assessments and laboratory findings, and not in isolation.


    7Soni NJ et al: Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis. J Hosp Med  2013;8(9):530-540.
    8Moses Clinical Trial Data. On file Thermo Fisher Scientific 

    Understanding PCT kinetics

    Rapid and sustained response to bacterially induced systemic inflammation, and a half-life of 24 hours, are important hallmarks of PCT as a marker of sepsis risk.

    pct-kinetics

    Following stimulus by a bacterial endotoxin or trauma, PCT plasma concentrations:5,23  

    • Rise 3 to 6 hours after bacterial invasion
    • Are significant after 6 hours
    • Exhibit peak values between 12 to 24 hours
    • Have an observed half–life of approximately 24 hours

    This rapid and sustained response to bacterially induced systemic inflammation is an important hallmark of PCT as a marker of sepsis risk.
    For more information:

     Download  Reducing Antibiotic Exposure brochure


    5. Brunkhorst FM et al: Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med 1998;24(8):888-889.
    23. Meisner M: Procalcitonin: experience with a new diagnostic tool for bacterial infection and systemic inflammation. J Lab Med Medicine 1999;23(5):263-272.

    PCT versus lactate

    The sensitivity and specificity of PCT to the host response to severe bacterial infection, together with its rapid rise after an infectious challenge, offer clinical advantages that complement existing biomarkers for the clinical assessment of the septic patient.

    In addition, lactate does not rise until late in the course of sepsis.18

    pct-vs-lactate

    16. Dellinger RP et al: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41(2):580-637.
    17. Thomas-Rueddel DO et al: Hyperlactatemia is an independent predictor of mortality and denotes distinct subtypes of severe sepsis and septic shock. J Crit Care 2015;30(2):439.e1-439.e6.
    18. Freund Y: Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection. Biomarkers 2012;17(7):590-596.

    Important considerations when interpreting PCT results

    The prognostic value of PCT in the setting of sepsis has not been validated in US patients younger than 18. Increased PCT levels may not always be related to systemic bacterial infection.14,25-27 They may also be associated with:

    • Injuries including major trauma, burns, and heat stroke
    • Acute medical conditions such as biliary pancreatitis, chemical pneumonitis, viral hepatitis and/or decompensated severe cirrhosis (Child-Pugh Class 3), prolonged or severe cardiogenic shock, prolonged severe organ perfusion anomalies, and post-cardiac arrest 
    • Unusual infectious diseases including invasive fungal infections and acute plasmodium falciparum malaria
    • Active medullary C-cell carcinoma, small cell lung carcinoma, and bronchial carcinoid
    • Interventions such as surgery with extracorporeal circulation, treatment with drugs stimulating release of pro-inflammatory cytokines or resulting in anaphylaxis, peritoneal or hemodialysis
    • Neonates during first two days of life

    B·R·A·H·M·S PCT results should be evaluated in context of all laboratory findings and the total clinical status of the patient. In cases where the laboratory results do not agree with the clinical picture or history, additional tests should be performed. Refer to Thermo Scientific B·R·A·H·M·S PCT   package insert for additional information.


    14. Meisner M. Procalcitonin: Biochemistry and Clinical Diagnosis; UNI-MED Verlag AG; 2010.
    25. Meisner M et al: Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med 1998;24(7): 680-684.
    26. Chiesa C et al: Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis 1998;26(3): 664-672.
    27. Reith HB et al: Procalcitonin in early detection of postoperative complications. Dig Surg 1998;15(3):260-265.

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