Review Article| Volume 36, ISSUE 4, P897-909, December 2022

Download started.


Uses of Procalcitonin as a Biomarker in Critical Care Medicine

  • Ryan C. Maves
    Corresponding author. Section on Infectious Diseases, Atrium Health Wake Forest Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157.
    Department of Internal Medicine, Section of Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Department of Anesthesiology, Section of Critical Care Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
    Search for articles by this author
  • Chukwunyelu H. Enwezor
    Department of Internal Medicine, Section of Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC, USA
    Search for articles by this author


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Infectious Disease Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Kumar A.
        • Roberts D.
        • Wood K.E.
        • et al.
        Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.
        Crit Care Med. 2006; 34: 1589-1596
        • Taylor S.P.
        • Anderson W.E.
        • Beam K.
        • et al.
        The Association Between Antibiotic Delay Intervals and Hospital Mortality Among Patients Treated in the Emergency Department for Suspected Sepsis.
        Crit Care Med. 2021; 49: 741-747
        • Comstedt P.
        • Storgaard M.
        • Lassen A.T.
        The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study.
        Scand J Trauma Resusc Emerg Med. 2009; 17: 67
        • Shappell C.N.
        • Klompas M.
        • Ochoa A.
        • et al.
        Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department.
        Crit Care Med. 2021; 49: e1144-e1150
        • Zboromyrska Y.
        • Cilloniz C.
        • Cobos-Trigueros N.
        • et al.
        Evaluation of the Magicplex Sepsis Real-Time Test for the Rapid Diagnosis of Bloodstream Infections in Adults.
        Front Cell Infect Microbiol. 2019; 9: 56
        • Grumaz S.
        • Grumaz C.
        • Vainshtein Y.
        • et al.
        Enhanced Performance of Next-Generation Sequencing Diagnostics Compared With Standard of Care Microbiological Diagnostics in Patients Suffering From Septic Shock.
        Crit Care Med. 2019; 47: e394-e402
        • Le Moullec J.M.
        • Jullienne A.
        • Chenais J.
        • et al.
        The complete sequence of human preprocalcitonin.
        FEBS Lett. 1984; 167: 93-97
        • Assicot M.
        • Gendrel D.
        • Carsin H.
        • et al.
        High serum procalcitonin concentrations in patients with sepsis and infection.
        Lancet. 1993; 341: 515-518
        • Linscheid P.
        • Seboek D.
        • Nylen E.S.
        • et al.
        In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue.
        Endocrinology. 2003; 144: 5578-5584
        • Self W.H.
        • Grijalva C.G.
        • Williams D.J.
        • et al.
        Procalcitonin as an Early Marker of the Need for Invasive Respiratory or Vasopressor Support in Adults With Community-Acquired Pneumonia.
        Chest. 2016; 150: 819-828
        • Huang D.T.
        • Weissfeld L.A.
        • Kellum J.A.
        • et al.
        Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia.
        Ann Emerg Med. 2008; 52: 48-58 e2
        • Ramirez P.
        • Ferrer M.
        • Marti V.
        • et al.
        Inflammatory biomarkers and prediction for intensive care unit admission in severe community-acquired pneumonia.
        Crit Care Med. 2011; 39: 2211-2217
        • Bloos F.
        • Marshall J.C.
        • Dellinger R.P.
        • et al.
        Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study.
        Crit Care. 2011; 15: R88
        • Schuetz P.
        • Maurer P.
        • Punjabi V.
        • et al.
        Procalcitonin decrease over 72 hours in US critical care units predicts fatal outcome in sepsis patients.
        Crit Care. 2013; 17: R115
        • 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: 781-789
        • Restrepo M.I.
        • Mortensen E.M.
        • Velez J.A.
        • et al.
        A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU.
        Chest. 2008; 133: 610-617
        • Gadsby N.J.
        • Russell C.D.
        • McHugh M.P.
        • et al.
        Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia.
        Clin Infect Dis. 2016; 62: 817-823
        • Gilbert D.
        • Gelfer G.
        • Wang L.
        • et al.
        The potential of molecular diagnostics and serum procalcitonin levels to change the antibiotic management of community-acquired pneumonia.
        Diagn Microbiol Infect Dis. 2016; 86: 102-107
        • Self W.H.
        • Balk R.A.
        • Grijalva C.G.
        • et al.
        Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia.
        Clin Infect Dis. 2017; 65: 183-190
        • Gautam S.
        • Cohen A.J.
        • Stahl Y.
        • et al.
        Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia.
        Thorax. 2020; 75: 974-981
        • Carbonell R.
        • Moreno G.
        • Martin-Loeches I.
        • et al.
        Prognostic Value of Procalcitonin and C-Reactive Protein in 1608 Critically Ill Patients with Severe Influenza Pneumonia.
        Antibiotics (Basel). 2021; : 10
        • Metlay J.P.
        • Waterer G.W.
        • Long A.C.
        • 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: e45-e67
        • Schuetz P.
        Procalcitonin Is Useful for Evaluating Patients with Ambiguous Presentation and for Early Discontinuation of Antibiotics in Community-acquired Pneumonia.
        Am J Respir Crit Care Med. 2020; 201: 744-745
        • Maves R.C.
        Procalcitonin Is Not an Adequate Tool for Antimicrobial De-Escalation in Sepsis.
        Crit Care Med. 2020; 48: 1848-1850
        • Yahav D.
        • Franceschini E.
        • Koppel F.
        • et al.
        Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial.
        Clin Infect Dis. 2019; 69: 1091-1098
        • Molina J.
        • Cisneros J.M.
        Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by enterobacterales: a randomized, controlled trial: authors' response.
        Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2021;
        • Chastre J.
        • Wolff M.
        • Fagon J.Y.
        • et al.
        Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.
        JAMA. 2003; 290: 2588-2598
        • Capellier G.
        • Mockly H.
        • Charpentier C.
        • et al.
        Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment.
        PloS one. 2012; 7e41290
        • Yi S.H.
        • Hatfield K.M.
        • Baggs J.
        • et al.
        Duration of Antibiotic Use Among Adults With Uncomplicated Community-Acquired Pneumonia Requiring Hospitalization in the United States.
        Clin Infect Dis. 2018; 66: 1333-1341
        • Vaughn V.M.
        • Flanders S.A.
        • Snyder A.
        • et al.
        Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study.
        Ann Intern Med. 2019; 171: 153-163
        • Feazel L.M.
        • Malhotra A.
        • Perencevich E.N.
        • et al.
        Effect of antibiotic stewardship programmes on Clostridium difficile incidence: a systematic review and meta-analysis.
        J Antimicrob Chemother. 2014; 69: 1748-1754
        • Ruttimann S.
        • Keck B.
        • Hartmeier C.
        • et al.
        Long-term antibiotic cost savings from a comprehensive intervention program in a medical department of a university-affiliated teaching hospital.
        Clin Infect Dis. 2004; 38: 348-356
        • Niwa T.
        • Shinoda Y.
        • Suzuki A.
        • et al.
        Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital.
        Int J Clin Pract. 2012; 66: 999-1008
        • Hanretty A.M.
        • Gallagher J.C.
        Shortened Courses of Antibiotics for Bacterial Infections: A Systematic Review of Randomized Controlled Trials.
        Pharmacotherapy. 2018; 38: 674-687
        • Bouadma L.
        • Luyt C.E.
        • Tubach F.
        • et al.
        Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.
        Lancet. 2010; 375: 463-474
        • de Jong E.
        • van Oers J.A.
        • Beishuizen A.
        • et al.
        Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial.
        Lancet Infect Dis. 2016; 16: 819-827
        • Shehabi Y.
        • Sterba M.
        • Garrett P.M.
        • et al.
        Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. A randomized controlled trial.
        Am J Respir Crit Care Med. 2014; 190: 1102-1110
        • Jensen J.U.
        • Hein L.
        • Lundgren B.
        • et al.
        Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial.
        Crit Care Med. 2011; 39: 2048-2058
        • Balk R.A.
        • Kadri S.S.
        • Cao Z.
        • et al.
        Effect of Procalcitonin Testing on Health-care Utilization and Costs in Critically Ill Patients in the United States.
        Chest. 2017; 151: 23-33
        • Meier M.A.
        • Branche A.
        • Neeser O.L.
        • et al.
        Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials.
        Clin Infect Dis. 2019; 69: 388-396
        • Vaughn V.M.
        • Gandhi T.N.
        • Petty L.A.
        • et al.
        Empiric Antibacterial Therapy and Community-onset Bacterial Coinfection in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19): A Multi-hospital Cohort Study.
        Clin Infect Dis. 2021; 72: e533-e541
        • Hughes S.
        • Troise O.
        • Donaldson H.
        • et al.
        Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting.
        Clin Microbiol Infect. 2020; 26: 1395-1399
        • Wang L.
        • Amin A.K.
        • Khanna P.
        • et al.
        An observational cohort study of bacterial co-infection and implications for empirical antibiotic therapy in patients presenting with COVID-19 to hospitals in North West London.
        J Antimicrob Chemother. 2021; 76: 796-803
        • Vacheron C.H.
        • Lepape A.
        • Savey A.
        • et al.
        Increased Incidence of Ventilator-Acquired Pneumonia in Coronavirus Disease 2019 Patients: A Multicentric Cohort Study.
        Crit Care Med. 2022; 50: 449-459
        • Grasselli G.
        • Scaravilli V.
        • Mangioni D.
        • et al.
        Hospital-Acquired Infections in Critically Ill Patients With COVID-19.
        Chest. 2021; 160: 454-465
        • Hedberg P.
        • Ternhag A.
        • Giske C.G.
        • et al.
        Ventilator-Associated Lower Respiratory Tract Bacterial Infections in COVID-19 Compared With Non-COVID-19 Patients.
        Crit Care Med. 2022;
        • Rose A.N.
        • Baggs J.
        • Wolford H.
        • et al.
        Trends in Antibiotic Use in United States Hospitals During the Coronavirus Disease 2019 Pandemic.
        Open Forum Infect Dis. 2021; 8: ofab236
        • Nazerian P.
        • Gagliano M.
        • Suardi L.R.
        • et al.
        Procalcitonin for the differential diagnosis of COVID-19 in the emergency department. Prospective monocentric study.
        Intern Emerg Med. 2021; 16: 1733-1735
        • Tong-Minh K.
        • van der Does Y.
        • Engelen S.
        • et al.
        High procalcitonin levels associated with increased intensive care unit admission and mortality in patients with a COVID-19 infection in the emergency department.
        BMC Infect Dis. 2022; 22: 165
        • Shen Y.
        • Cheng C.
        • Zheng X.
        • et al.
        Elevated Procalcitonin Is Positively Associated with the Severity of COVID-19: A Meta-Analysis Based on 10 Cohort Studies.
        Medicina (Kaunas). 2021; : 57
        • Williams E.J.
        • Mair L.
        • de Silva T.I.
        • et al.
        Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study.
        The J Hosp Infect. 2021; 110: 103-107
        • Cortes M.F.
        • de Almeida B.L.
        • Espinoza E.P.S.
        • et al.
        Procalcitonin as a biomarker for ventilator associated pneumonia in COVID-19 patients: Is it an useful stewardship tool?.
        Diagn Microbiol Infect Dis. 2021; 101: 115344
        • Peters C.
        • Williams K.
        • Un E.A.
        • et al.
        Use of procalcitonin for antibiotic stewardship in patients with COVID-19: A quality improvement project in a district general hospital.
        Clin Med (Lond). 2021; 21: e71-e76
        • Heesom L.
        • Rehnberg L.
        • Nasim-Mohi M.
        • et al.
        Procalcitonin as an antibiotic stewardship tool in COVID-19 patients in the intensive care unit.
        J Glob Antimicrob Resist. 2020; 22: 782-784
        • Hesselink D.A.
        • Burgerhart J.S.
        • Bosmans-Timmerarends H.
        • et al.
        Procalcitonin as a biomarker for severe Plasmodium falciparum disease: a critical appraisal of a semi-quantitative point-of-care test in a cohort of travellers with imported malaria.
        Malar J. 2009; 8: 206
        • Thanachartwet V.
        • Desakorn V.
        • Sahassananda D.
        • et al.
        Serum Procalcitonin and Peripheral Venous Lactate for Predicting Dengue Shock and/or Organ Failure: A Prospective Observational Study.
        Plos Negl Trop Dis. 2016; 10: e0004961
        • Cortegiani A.
        • Misseri G.
        • Ippolito M.
        • et al.
        Procalcitonin levels in candidemia versus bacteremia: a systematic review.
        Crit Care. 2019; 23: 190
        • Grace E.
        • Turner R.M.
        Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy.
        Clin Infect Dis. 2014; 59: 1761-1767
        • Avrillon V.
        • Locatelli-Sanchez M.
        • Folliet L.
        • et al.
        Lung cancer may increase serum procalcitonin level.
        Infect Disord Drug Targets. 2015; 15: 57-63
        • Chaftari A.M.
        • Hachem R.
        • Reitzel R.
        • et al.
        Role of Procalcitonin and Interleukin-6 in Predicting Cancer, and Its Progression Independent of Infection.
        PLoS One. 2015; 10e0130999
        • Schneider R.
        • Cohen M.J.
        • Benenson S.
        • et al.
        Procalcitonin in hemodialysis patients presenting with fever or chills to the emergency department.
        Intern Emerg Med. 2020; 15: 257-262
        • Tao M.
        • Zheng D.
        • Liang X.
        • et al.
        Diagnostic value of procalcitonin for bacterial infections in patients undergoing hemodialysis: a systematic review and meta-analysis.
        Ren Fail. 2022; 44: 81-93
        • Level C.
        • Chauveau P.
        • Guisset O.
        • et al.
        Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure.
        Crit Care. 2003; 7: R160-R166
        • Soulountsi V.
        • Schizodimos T.
        • Kotoulas S.C.
        Deciphering the epidemiology of invasive candidiasis in the intensive care unit: is it possible?.
        Infection. 2021; 49: 1107-1131
        • Clancy C.J.
        • Nguyen M.H.
        Diagnosing Invasive Candidiasis.
        J Clin Microbiol. 2018; 56
        • Evans L.
        • Rhodes A.
        • Alhazzani W.
        • et al.
        Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.
        Crit Care Med. 2021; 49: e1063-e1143
        • Tillett W.S.
        • Cambier M.J.
        • McCormack J.E.
        The Treatment of Lobar Pneumonia and Pneumococcal Empyema with Penicillin.
        Bull N Y Acad Med. 1944; 20: 142-178
        • Huang D.T.
        • Yealy D.M.
        • Filbin M.R.
        • et al.
        Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection.
        New Engl J Med. 2018; 379: 236-249
        • Seymann G.B.
        • Bevins N.
        • Wu C.
        • et al.
        Prevalence of Discordant Procalcitonin Use at an Academic Medical Center.
        Am J Clin Pathol. 2021;
        • El Haddad H.
        • Chaftari A.M.
        • Hachem R.
        • et al.
        Biomarkers of Sepsis and Bloodstream Infections: The Role of Procalcitonin and Proadrenomedullin With Emphasis in Patients With Cancer.
        Clin Infect Dis. 2018; 67: 971-977
        • Park J.E.
        • Lee B.
        • Yoon S.J.
        • et al.
        Complementary Use of Presepsin with the Sepsis-3 Criteria Improved Identification of High-Risk Patients with Suspected Sepsis.
        Biomedicines. 2021; : 9
        • Que Y.A.
        • Guessous I.
        • Dupuis-Lozeron E.
        • et al.
        Prognostication of Mortality in Critically Ill Patients With Severe Infections.
        Chest. 2015; 148: 674-682
        • van Houten C.B.
        • de Groot J.A.H.
        • Klein A.
        • et al.
        A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): a double-blind, multicentre, validation study.
        Lancet Infect Dis. 2017; 17: 431-440