The role of Procalcitonin in the management of patients with sepsis and respiratory tract infections: from bench to bedside
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Pneumonology Medicine Department, Amalia Fleming General Hospital, Athens, Greece
Pneumonology Physician, Editorial Board Pneumon
Pneumon 2010;23(4):369–375
Sepsis constitutes a clinical syndrome with complex pathophysiological mechanisms, and it is leading cause of mortality in intensive care units (ICUs) worldwide. Guidelines and recommendations published during the last decade have emphasized the need for early recognition and management of patients with sepsis, including timely antibiotic administration. The use of biomarkers such as procalcitonin (PCT), to help in the timely recognition and effective management of sepsis, employed either alone or as a part of a multi-dimensional model, represents one of the contemporary challenges of pulmonary and critical care medicine. Respiratory tract infections represent a significant burden in critical care settings, being a major reason for antibiotic consumption and a major cause of morbidity and mortality. Recent evidence derived from published studies, systematic reviews and meta-analyses supports the use of PCT as a marker for the selection of those patients with lower respiratory tract infections who need antibiotics, both in the ICU setting and in the ward, but with significant inconsistencies. This review aims to cover briefly the rationale for the use of PCT as a biomarker in patients with sepsis, especially those presenting with lower respiratory tract infections, and to provide insights into the possible use of this biomarker in everyday clinical practice.
Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29:1303-1310.
Rivers EP, McIntyre L, Morro DC, et al. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ 2005; 173:1054-1065.
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-1377.
Bozza FA, Salluh JI, Japiassu AM, et al. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 2007; 11:R49.
Levy MM. The electrocardiogram for sepsis: how close are we? Crit Care 2007; 11:144.
Corona A, Bertolini G, Ricotta AM, et al. Variability of treatment duration for bacteraemia in the critically ill: a multinational survey. J Antimicrob Chemother 2003; 52:849-852.
Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 2008; 36:941-952.
Rello J. Bench-to-bedside review: Therapeutic options and issues in the management of ventilator-associated bacterial pneumonia. Crit Care 2005; 9:259-265.
Muller B, Becker KL. Procalcitonin: how a hormone became a marker and mediator of sepsis. Swiss Med Wkly 2001; 131:595- 602.
McDermott M. Endocrine Secrets. 3rd ed. Philadelphia: Hanley&Belfus, 2002;.
Assicot M, Gendrel D, Carsin H, et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993; 341:515-518.
Karzai W, Oberhoffer M, Meier-Hellmann A, et al. Procalcitonin-a new indicator of the systemic response to severe infections. Infection 1997; 25:329-334.
Eberhard OK, Haubitz M, Brunkhorst FM, et al. Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection. Arthritis Rheum 1997; 40:1250- 1256.
Greenspan F, Garden D. Basic and Clinical Endocrinology. 7th ed. USA: Lange Medical Books/McGraw-Hill, 2004;.
Christ-Crain M, Muller B. Procalcitonin in bacterial infections hype, hope, more or less? Swiss Med Wkly 2005; 135:451- 460.
Nijsten MW, Olinga P, The TH, et al. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med 2000; 28:458-461.
Christ-Crain M, Muller B. Calcitonin peptides--the mediators in sepsis or just another fairy tale? Crit Care Med 2008; 36:1684- 1687.
Brahms. Immunofluorescent assay for the determination of PCT (procalcitonin) in human serum and plasma. USA, 2004.
Brahms. Immunoluminometric assay (ILMA) for the determination of PCT (procalcitonin) in human serum and plasma (Coated Tube System). USA, 2004.
Simon L, Gauvin F, Amre DK, et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2004; 39:206-217.
Uzzan B, Cohen R, Nicolas P, et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med 2006; 34:1996-2003.
Tang BM, Eslick GD, Craig JC, et al. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007; 7:210-217.
Jones AE, Fiechtl JF, Brown MD, et al. Procalcitonin test in the diagnosis of bacteremia: a meta-analysis. Ann Emerg Med 2007; 50:34-41.
Castelli GP, Pognani C, Cita M, et al. Procalcitonin as a prognostic and diagnostic tool for septic complications after major trauma. Crit Care Med 2009; 37:1845-1849.
Nobre V, Harbarth S, Graf JD, et al. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008; 177:498-505.
Hochreiter M, Kohler T, Schweiger AM, et al. Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care 2009; 13: R83.
Schroeder S, Hochreiter M, Koehler T, et al. Procalcitonin (PCT)- guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbecks Arch Surg 2009; 394:221-226.
Charles PE, Tinel C, Barbar S, et al. Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome. Crit Care 2009; 13:R38.
Faix JD. Using procalcitonin to diagnose sepsis and the potential for improved antibiotic stewardship. MLO Med Lab Obs 2008; 40:25-26.
Amour J, Birenbaum A, Langeron O, et al. Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery. Crit Care Med 2008; 36:1147-1154.
Shehabi Y, Seppelt I. Pro/Con debate: is procalcitonin useful for guiding antibiotic decision making in critically ill patients? Crit Care 2008; 12:211.
Chirouze C, Schuhmacher H, Rabaud C, et al. Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis 2002; 35:156- 161.
O’Grady NP, Barie PS, Bartlett JG, et al. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med 2008; 36:1330-1349.
Muller B, Schuetz P, Trampuz A. Circulating biomarkers as surrogates for bloodstream infections. Int J Antimicrob Agents 2007; 30 Suppl 1:S16-23.
Goossens H, Ferech M, Vander Stichele R, et al. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 2005; 365:579-587.
Gonzales R, Malone DC, Maselli JH, et al. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis 2001; 33:757-762.
Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 2004; 363:600-607.
Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2006; 174:84-93.
Briel M, Schuetz P, Mueller B, et al. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med 2008; 168:2000- 2007; discussion 2007-2008.
Muller F, Christ-Crain M, Bregenzer T, et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest 2010; 138:121- 129.
Huang DT, Weissfeld LA, Kellum JA, et al. Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia. Ann Emerg Med 2008; 52:48-58 e42.
Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997; 336:243-250.
Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003; 58:377-382.
Jung B, Embriaco N, Roux F, et al. Microbiogical data, but not procalcitonin improve the accuracy of the clinical pulmonary infection score. Intensive Care Med 2010; 36:790-798.
Luyt CE, Combes A, Reynaud C, et al. Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia. Intensive Care Med 2008; 34:1434-1440.
Ramirez P, Garcia MA, Ferrer M, et al. Sequential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia. Eur Respir J 2008; 31:356-362.
Seligman R, Meisner M, Lisboa TC, et al. Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia. Crit Care 2006; 10:R125.
Stolz D, Smyrnios N, Eggimann P, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J 2009; 34:1364-1375.
Hillas G, Vassilakopoulos T, Plantza P, et al. C-reactive protein and procalcitonin as predictors of survival and septic shock in ventilator-associated pneumonia. Eur Respir J 2010; 35:805- 811.
Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet 2007; 370:765-773.
Lacoma A, Prat C, Andreo F, et al. Biomarkers in the management of COPD. European Respiratory Review 2009; 18:96-104.
Lindenauer PK, Pekow P, Gao S, et al. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 2006; 144:894-903.
Puhan MA, Vollenweider D, Latshang T, et al. Exacerbations of chronic obstructive pulmonary disease: when are antibiotics indicated? A systematic review. Respir Res 2007; 8:30.
Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 2007; 131:9-19.
de Kruif MD, Lemaire LC, Giebelen IA, et al. The influence of corticosteroids on the release of novel biomarkers in human endotoxemia. Intensive Care Med 2008; 34:518-522.
Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007; 176:532-555.
Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302:1059-1066.
Yealy DM, Fine MJ. Measurement of serum procalcitonin: a step closer to tailored care for respiratory infections? JAMA 2009; 302:1115-1116.
Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008; 34:17-60.
Becker KL, Snider R, Nylen ES. Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target. Br J Pharmacol 2010; 159:253-264.
Bouadma L, Luyt CE, 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.
Tang H, Huang T, Jing J, et al. Effect of procalcitonin-guided treatment in patients with infections: a systematic review and meta-analysis. Infection 2009; 37:497-507.
Schuetz P, Christ-Crain M, Muller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections--hope for hype? Swiss Med Wkly 2009; 139:318- 326.
Rubulotta F, Marshall JC, Ramsay G, et al. Predisposition, insult/infection, response, and organ dysfunction: A new model for staging severe sepsis. Crit Care Med 2009; 37:1329-1335.