Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future

Whitney CG, Farley MM, Hadler J, Harrison LH, Lexau C, Reingold A, Lefkowitz L, Cieslak PR, Cetron M, Zell ER, Jorgensen JH, Schuchat A, Active Bacterial Core Surveillance Program of the Emerging Infections Program Network: Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med. 2000, 343: 1917-1924. 10.1056/NEJM200012283432603.

Roberts Rebecca R, Hota B, Ahmad I, Scott Ii RD, Foster Susan D, Abbasi F, Schabowski S, Kampe Linda M, Ciavarella Ginevra G, Supino M, Naples J, Cordell R, Levy SB, Weinstein RA: Hospital and Societal Costs of Antimicrobial-Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship. Clin Infect Dis. 2009, 49: 1175-1184. 10.1086/605630.

Ohl CA, Luther VP: Antimicrobial stewardship for inpatient facilities. J Hosp Med. 2011, 6 (Suppl 1): S4-15.

Lee TH, Goldman L: Evaluation of the patient with acute chest pain. N Engl J Med. 2000, 342: 1187-1195. 10.1056/NEJM200004203421607.

Agnelli G, Becattini C: Acute pulmonary embolism. N Engl J Med. 2010, 363: 266-274. 10.1056/NEJMra0907731.

Muller B, Harbarth S, Stolz D, Bingisser R, Mueller C, Leuppi J, Nusbaumer C, Tamm M, Christ-Crain M: Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007, 7: 10-10.1186/1471-2334-7-10.

Gogos CA, Drosou E, Bassaris HP, Skoutelis A: Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000, 181: 176-180. 10.1086/315214.

Christ-Crain M, Muller B: Procalcitonin in bacterial infections--hype, hope, more or less?. Swiss Med Wkly. 2005, 135: 451-460.

Christ-Crain M, Muller B: Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators. Eur Respir J. 2007, 30: 556-573. 10.1183/09031936.00166106.

Linscheid P, Seboek D, Zulewski H, Keller U, Muller B: Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. Endocrinology. 2005, 146: 2699-2708. 10.1210/en.2004-1424.

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.

Becker KL: Procalcitonin and the Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A Journey from Calcitonin Back to Its Precursors. J Clin Endocrinol Metab. 2004, 89: 1512-1525. 10.1210/jc.2002-021444.

Schuetz P, Mueller B, Trampuz A: Serum procalcitonin for discrimination of blood contamination from bloodstream infection due to coagulase-negative staphylococci. Infection. 2007, 35: 352-355. 10.1007/s15010-007-7065-0.

Muller F, Christ-Crain M, Bregenzer T, Krause M, Zimmerli W, Mueller B, Schuetz P: Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest. 2010, 138: 121-129. 10.1378/chest.10954.

van Nieuwkoop C, Bonten TN, van't Wout JW, Kuijper EJ, Groeneveld GH, Becker MJ, Koster T, Wattel-Louis GH, Delfos NM, Ablij HC, Leyten EM, van Dissel JT: Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study. Crit Care. 2010, 14: R206-10.1186/cc9328.

Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B: Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006, 174: 84-93. 10.1164/rccm.200512-1922OC.

Schuetz P, Christ-Crain M, Albrich W, Zimmerli W, Mueller B: Guidance of antibiotic therapy with procalcitonin in lower respiratory tract infections: insights into the ProHOSP study. Virulence. 2010, 1: 88-92. 10.4161/viru.1.2.10488.

Schuetz P, Suter-Widmer I, Chaudri A, Christ-Crain M, Zimmerli W, Mueller B: Prognostic value of procalcitonin in community-acquired pneumonia. Eur Resp J. 2011, 37: 384-392. 10.1183/09031936.00035610.

Kruger S, Ewig S, Marre R, Papassotiriou J, Richter K, von Baum H, Suttorp N, Welte T: Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes. Eur Respir J. 2008, 31: 349-355. 10.1183/09031936.00054507.

Huang D, Weissfeld L, Kellum J, Yealy D, Kong L, Martino M, Angus D: Risk Prediction With Procalcitonin and Clinical Rules in Community-Acquired Pneumonia. Ann Emerg Med. 2008, 52: 48-58.e2. 10.1016/j.annemergmed.2008.01.003.

Haeuptle J, Zaborsky R, Fiumefreddo R, Trampuz A, Steffen I, Frei R, Christ-Crain M, Muller B, Schuetz P: Prognostic value of procalcitonin in Legionella pneumonia. Eur J Clin Microbiol Infect Dis. 2009, 28: 55-60. 10.1007/s10096-008-0592-5.

Jensen JU, Heslet L, Jensen TH, Espersen K, Steffensen P, Tvede M: Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med. 2006, 34: 2596-2602. 10.1097/01.CCM.0000239116.01855.61.

Schuetz P, Albrich W, Christ-Crain M, Chastre J, Mueller B: Procalcitonin for guidance of antibiotic therapy. Expert Rev Anti Infect Ther. 2010, 8: 575-587. 10.1586/eri.10.25.

Nylen ES, Muller B, Becker KL, Snyder RH: The future diagnostic role of procalcitonin levels: the need for improved sensitivity. Clin Infect Dis. 2003, 36: 823-824. 10.1086/368088.

Steinbach G, Rau B, Debard AL, Javourez JF, Bienvenu J, Ponzio A, Bonfa A, Hubl W, Demant T, Kulpmann WR, Buchholz J, Schumann G: Multicenter evaluation of a new immunoassay for procalcitonin measurement on the Kryptor System. Clin Chem Lab Med. 2004, 42: 440-449. 10.1515/CCLM.2004.077.

Pecile P, Miorin E, Romanello C, Falleti E, Valent F, Giacomuzzi F, Tenore A: Procalcitonin: a marker of severity of acute pyelonephritis among children. Pediatrics. 2004, 114: e249-254. 10.1542/peds.114.2.e249.

Knudsen JB, Fuursted K, Petersen E, Wierup P, Molgaard H, Poulsen SH, Egeblad H: Procalcitonin in 759 patients clinically suspected of infective endocarditis. Am J Med. 2010, 123: 1121-1127. 10.1016/j.amjmed.2010.07.018.

Mueller C, Huber R, Laifer G, Mueller B, Buerkle G, Perruchoud AP: Procalcitonin and the early diagnosis of infective endocarditis. Circulation. 2004, 109: 1707-1710. 10.1161/01.CIR.0000126281.52345.52.

Kafetzis DA, Velissariou IM, Nikolaides P, Sklavos M, Maktabi M, Spyridis G, Kafetzis DD, Androulakakis E: Procalcitonin as a predictor of severe appendicitis in children. Eur J Clin Microbiol Infect Dis. 24: 484-487.

Sand M, Trullen XV, Bechara FG, Pala XF, Sand D, Landgrafe G, Mann B: A prospective bicenter study investigating the diagnostic value of procalcitonin in patients with acute appendicitis. Eur Surg Res. 2009, 43: 291-297. 10.1159/000232939.

Anielski R, Kusnierz-Cabala B, Szafraniec K: An evaluation of the utility of additional tests in the preoperative diagnostics of acute appendicitis. Langenbecks Arch Surg. 2010, 395: 1061-1068. 10.1007/s00423-009-0565-x.

Markogiannakis H, Memos N, Messaris E, Dardamanis D, Larentzakis A, Papanikolaou D, Zografos GC: Manouras: Predictive value of procalcitonin for bowel ischemia and necrosis in bowel obstruction. Surgery. 2011, 149: 394-403. 10.1016/j.surg.2010.08.007.

Gurda-Duda A, Kusnierz-Cabala B, Nowak W, Naskalski JW, Kulig J: Assessment of the prognostic value of certain acute-phase proteins and procalcitonin in the prognosis of acute pancreatitis. Pancreas. 2008, 37: 449-453. 10.1097/MPA.0b013e3181706d67.

Brunkhorst FM, Eberhard OK, Brunkhorst R: Early identification of biliary pancreatitis with procalcitonin. Am J Gastroenterol. 1998, 93: 1191-1192.

Bihari D: Monitoring procalcitonin is of value in acute pancreatitis. BMJ. 2004, 329: 232.

Mofidi R, Suttie SA, Patil PV, Ogston S, Parks RW: The value of procalcitonin at predicting the severity of acute pancreatitis and development of infected pancreatic necrosis: systematic review. Surgery. 2009, 146: 72-81. 10.1016/j.surg.2009.02.013.

Hugle T, Schuetz P, Mueller B, Laifer G, Tyndall A, Regenass S, Daikeler T: Serum procalcitonin for discrimination between septic and non-septic arthritis. Clin Exp Rheumatol. 2008, 26: 453-456.

Butbul-Aviel Y, Koren A, Halevy R, Sakran W: Procalcitonin as a diagnostic aid in osteomyelitis and septic arthritis. Pediatr Emerg Care. 2005, 21: 828-832. 10.1097/01.pec.0000190226.12610.24.

Stryjewski GR, Nylen ES, Bell MJ, Snider RH, Becker KL, Wu A, Lawlor C, Dalton H: Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin precursors for the determination of bacterial sepsis in febrile neutropenic children. Pediat Crit Care Med. 2005, 6: 129-135. 10.1097/01.PCC.0000149317.15274.48.

Sakr Y, Sponholz C, Tuche F, Brunkhorst F, Reinhart K: The role of procalcitonin in febrile neutropenic patients: review of the literature. Infection. 2008, 36: 396-407. 10.1007/s15010-008-7374-y.

Koivula I, S HMLI, Jantunen E, Pulkki K, Kuittinen T, Nousiainen T, Juutilainen A: Elevated procalcitonin predicts Gram-negative sepsis in haematological patients with febrile neutropenia. Scand J Infect Dis. 2011, 43: 471-478. 10.3109/00365548.2011.554855.

Muller B, Peri G, Doni A, Perruchoud AP, Landmann R, Pasqualini F, Mantovani A: High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration. J Leukoc Biol. 2002, 72: 643-649.

de Kruif MD, Lemaire LC, Giebelen IA, Struck J, Morgenthaler NG, Papassotiriou J, Elliott PJ, van der Poll T: The influence of corticosteroids on the release of novel biomarkers in human endotoxemia. Intensive Care Med. 2008, 34: 518-522. 10.1007/s00134-007-0955-x.

Timper K, Grisouard J, Radimerski T, Dembinski K, Peterli R, Haring A, Frey DM, Zulewski H, Keller U, Muller B, Christ-Crain M: Glucose-dependent insulinotropic polypeptide (GIP) induces calcitonin gene-related peptide (CGRP)-I and procalcitonin (Pro-CT) production in human adipocytes. J Clin Endocrinol Metab. 2011, 96: E297-303. 10.1210/jc.2010-1324.

Radimerski TM, Grisouard J, Timper K, Zulewski H, Christ-Crain M, Keller U, Muller B: Role of calcium in lipopolysaccharide-induced calcitonin gene expression in human adipocytes. Innate Immun. 2010.

Linscheid P: In Vitro and in Vivo Calcitonin I Gene Expression in Parenchymal Cells: A Novel Product of Human Adipose Tissue. Endocrinology. 2003, 144: 5578-5584. 10.1210/en.2003-0854.

Schuetz P, Christ-Crain M, Huber AR, Muller B: Long-term stability of procalcitonin in frozen samples and comparison of Kryptor and VIDAS automated immunoassays. Clin Biochem. 2010, 43: 341-344. 10.1016/j.clinbiochem.2009.08.029.

Hubl W, Krassler J, Zingler C, Pertschy A, Hentschel J, Gerhards-Reich C, Mack M, Demant T: Evaluation of a fully automated procalcitonin chemiluminescence immunoassay. Clin Lab. 2003, 49: 319-327.

de Wolf HK, Gunnewiek JK, Berk Y, van den Ouweland J, de Metz M: Comparison of a new procalcitonin assay from roche with the established method on the brahms kryptor. Clin Chem. 2009, 55: 1043-1044. 10.1373/clinchem.2008.117655.

Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B: 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. 10.1016/S0140-6736(04)15591-8.

Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C, Huber P, Muller B, Tamm M: Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007, 131: 9-19. 10.1378/chest.06-1500.

Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U, Regez K, Schoenenberger R, Henzen C, Bregenzer T, Hoess C, Krause M, Bucher HC, Zimmerli W, Mueller B, ProHOSP Study Group: 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. 10.1001/jama.2009.1297.

Kristoffersen KB, Sogaard OS, Wejse C, Black FT, Greve T, Tarp B, Storgaard M, Sodemann M: Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission--a randomized trial. Clin Microbiol Infect. 2009, 15: 481-487. 10.1111/j.1469-0691.2009.02709.x.

Long W, Deng XQ, Tang JG, Xie J, Zhang YC, Zhang Y, Gao YY, Lu G: [The value of serum procalcitonin in treatment of community acquired pneumonia in outpatient]. Zhonghua Nei Ke Za Zhi. 2009, 48: 216-219.

Long W, Deng X, Zhang Y, Lu G, Xie J, Tang J: Procalcitonin-guidance for reduction of antibiotic use in low-risk outpatients with community acquired pneumonia. Respirology. 2011, 16: 819-824. 10.1111/j.1440-1843.2011.01978.x.

Schuetz P, Batschwaroff M, Dusemund F, Albrich W, Burgi U, Maurer M, Brutsche M, Huber AR, Muller B: Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey. Eur J Clin Microbiol Infect Dis. 2010, 29: 269-277. 10.1007/s10096-009-0851-0.

Evans AT, Husain S, Durairaj L, Sadowski LS, Charles-Damte M, Wang Y: Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Lancet. 2002, 359: 1648-1654. 10.1016/S0140-6736(02)08597-5.

Burkhardt O, Ewig S, Haagen U, Giersdorf S, Hartmann O, Wegscheider K, Hummers-Pradier E, Welte T: Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J. 2010, 36: 601-607. 10.1183/09031936.00163309.

Briel M, Christ-Crain M, Young J, Schuetz P, Huber P, Periat P, Bucher HC, Muller B: Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]. BMC Fam Pract. 2005, 6: 34-10.1186/1471-2296-6-34.

Briel M, Schuetz P, Mueller B, Young J, Schild U, Nusbaumer C, Periat P, Bucher HC, Christ-Crain M: Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008, 168: 2000-2007. 10.1001/archinte.168.18.2000. discussion 2007-2008

Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J: Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med. 2008, 177: 498-505.

Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Régnier B, Brun-Buisson C, Chastre J, Wolff M, PRORATA trial group: 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. 10.1016/S0140-6736(09)61879-1.

Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, Marsch S, Azzola A, Rakic J, Mueller B, Timm M: Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J. 2009, 34: 1364-1375. 10.1183/09031936.00053209.

Hochreiter M, Köhler T, Schweiger A, Keck F, Bein B, von Spiegel T, Schroeder S: Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Critical Care. 2009, 13: R83-10.1186/cc7903.

Schroeder S, Hochreiter M, Koehler T, Schweiger AM, Bein B, Keck FS, von Spiegel T: 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. 10.1007/s00423-008-0432-1.

Kruger S, Ewig S, Papassotiriou J, Kunde J, Marre R, von Baum H, Suttor N, Welte T: Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP: results from the German competence network CAPNETZ. Respir Res. 2009, 10: 65-10.1186/1465-9921-10-65.

Kruger S, Ewig S, Kunde J, Hartmann O, Marre R, Suttorp N, Welte T: Assessment of inflammatory markers in patients with community-acquired pneumonia--influence of antimicrobial pre-treatment: results from the German competence network CAPNETZ. Clin Chim Acta. 2010, 411: 1929-1934. 10.1016/j.cca.2010.08.004.

Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY: 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. 10.1097/01.CCM.0000226413.54364.36.

Hunziker S, Hugle T, Schuchardt K, Groeschl I, Schuetz P, Mueller B, Dick W, Eriksson U, Trampuz A: The value of serum procalcitonin level for differentiation of infectious from noninfectious causes of fever after orthopaedic surgery. J Bone Joint Surg Am. 92: 138-148.

Sponholz C, Sakr Y, Reinhart K, Brunkhorst F: Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature. Crit Care. 2006, 10 (5): R145-10.1186/cc5067.

Schuetz P, Affolter B, Hunziker S, Winterhalder C, Fischer M, Balestra GM, Hunziker P, Marsch S: Serum procalcitonin, C-reactive protein and white blood cell levels following hypothermia after cardiac arrest: a retrospective cohort study. Eur J Clin Invest. 2010, 40: 376-381. 10.1111/j.1365-2362.2010.02259.x.

Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, Thornberg KJ, Loken J, Steensen M, Fox Z, Tousi H, Søe-Jensen P, Lauritsen AO, Strange D, Petersen PL, Reiter N, Hestad S, Thormar K, Fjeldborg P, Larsen KM, Drenck NE, Ostergaard C, Kjær J, Grarup J, Lundgren JD, for the The Procalcitonin And Survival Study (PASS) Study Group: 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.

Martinot M, Sordet C, Soubrier M, Puechal X, Saraux A, Liote F, Guggenbuhl P, Legre V, Jaulhac B, Maillefert JF, Zeisel M, Coumaros G, Sibilia J: Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients. Clin Exp Rheumatol. 2005, 23: 303-310.

Riedel S, Melendez JH, An AT, Rosenbaum JE, Zenilman JM: Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am J Clin Pathol. 2011, 135: 182-189. 10.1309/AJCP1MFYINQLECV2.

Gendrel D, Raymond J, Assicot M, Moulin F, Iniguez JL, Lebon P, Bohuon C: Measurement of procalcitonin levels in children with bacterial or viral meningitis. Clin Infect Dis. 1997, 24: 1240-1242. 10.1086/513633.

Marc E, Menager C, Moulin F, Stos B, Chalumeau M, Guerin S, Lebon P, Brunet F, Raymond J, Gendrel D: [Procalcitonin and viral meningitis: reduction of unnecessary antibiotics by measurement during an outbreak]. Arch Pediatr. 2002, 9: 358-364. 10.1016/S0929-693X(01)00793-X.

Mary R, Veinberg F, Couderc R: [Acute meningitidis, acute phase proteins and procalcitonin]. Ann Biol Clin. 2003, 61: 127-137.

Hunziker S, Hugle T, Schuchardt K, Groeschl I, Schuetz P, Mueller B, Dick W, Eriksson U, Trampuz A: The value of serum procalcitonin level for differentiation of infectious from noninfectious causes of fever after orthopaedic surgery. J Bone Joint Surg Am. 2010, 92: 138-148. 10.2106/JBJS.H.01600.