Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia

Andriy Zhydkov; Mirjam Christ-Crain; Robert Thomann; Claus Hoess; Christoph Henzen; Werner Zimmerli; Beat Mueller; Philipp Schuetz; for the ProHOSP Study Group

doi:10.1515/cclm-2014-0456

Artikel

Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia

Andriy Zhydkov , Mirjam Christ-Crain , Robert Thomann , Claus Hoess , Christoph Henzen , Werner Zimmerli , Beat Mueller , Philipp Schuetz und for the ProHOSP Study Group

Veröffentlicht/Copyright: 11. Juli 2014

Veröffentlicht von

Veröffentlichen auch Sie bei De Gruyter Brill

Manuskript einreichen Informationen für Autor*innen

Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 53 Heft 4

Abstract

Background: The added value of biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC), as adjuncts to clinical risk scores for predicting the outcome of patients with community-acquired pneumonia (CAP) is in question. We investigated the prognostic accuracy of initial and follow-up levels of inflammatory biomarkers in predicting death and adverse clinical outcomes in a large and well-defined cohort of CAP patients.

Methods: We measured PCT, CRP and WBC on days 1, 3, 5, and 7 and followed the patients over 30 days. We applied multivariate regression models and area under the curve (AUC) to investigate associations between these biomarkers, the clinical risk score CURB-65, and clinical outcomes [i.e., death and intensive care unit (ICU) admission].

Results: Of 925 patients with CAP, 50 patients died and 118 patients had an adverse clinical outcome. None of the initial biomarker levels significantly improved the CURB-65 score for mortality prediction. Follow-up biomarker levels showed significant independent association with mortality at days 3, 5, and 7 and with improvements in AUC. Initial PCT and CRP levels were independent prognostic predictors of adverse clinical outcome, and levels of all biomarkers during the course of disease provided additional prognostic information.

Conclusions: This study provides robust insights into the added prognostic value of inflammatory markers in CAP. Procalcitonin, CRP, and to a lesser degree WBC provided some prognostic information on CAP outcomes, particularly when considering their kinetics at days 5 and 7 and when looking at adverse clinical outcomes instead of mortality alone.

Keywords: community-acquired pneumonia (CAP); C-reactive protein (CRP); CURB-65 score; mortality; procalcitonin; severity of illness; white blood cells.

Corresponding author: Prof. Philipp Schuetz, Medical University Clinic, Kantonsspital Aarau, Tellstr. 5, 5001 Aarau, Switzerland, Phone: +41 628389524, Fax: +41 628386945, E-mail: philipp.schuetz@ksa.ch

Acknowledgments

We are grateful to all local physicians, nursing staff, and patients who participated in this study. We especially thank the staff of the emergency room, medical clinics, and central laboratories of the University Hospital Basel, the “Kantonsspitaeler” Liestal, Aarau, Luzern, and Muensterlingen, and the “Bürgerspital” Solothurn for their very helpful assistance, patience, and technical support. We thank the members of the Data Safety and Monitoring Board, namely A. P. Perruchoud, S. Harbarth, and A. Azzola and all members of the ProHOSP Study Group, namely Robert Thomann, MD, Claudine Falconnier, MD, Marcel Wolbers, PhD, Isabelle Widmer, MD, Stefanie Neidert, MD, Thomas Fricker, MD, Claudine Blum, MD, Ursula Schild, RN, Katharina Regez, RN, Rita Bossart, RN, Ronald Schoenenberger, MD, Christoph Henzen, MD, Claus Hoess, MD, Heiner C. Bucher, MD, Ayesha Chaudri, Jeannine Haeuptle, Roya Zarbosky, Rico Fiumefreddo, Melanie Wieland, RN, Charly Nusbaumer, MD, Andres Christ, MD, Roland Bingisser, MD, Kristian Schneider, RN, Christine Vincenzi, RN, Michael Kleinknecht, RN, Brigitte Walz, PhD, Verena Briner, MD, Dieter Conen, MD, Andreas Huber, MD, Jody Staehelin, MD, Chantal Bruehlhardt, RN, Ruth Luginbuehl, RN, Agnes Muehlemann, PhD, Ineke lambinon, Max Zueger, MD, D. Conen, MD, M. Wieland, RN, C. Nusbaumer, MD, C. Bruehlhardt, RN, R. Luginbuehl, RN, A. Huber, MD, B. Walz, RN, M. Zueger, MD, and M.L. Stubbs. Editorial support was provided by Prasad Kulkarni, PhD, CMPP, of Asclepius Medical Communications LLC, Ridgewood, NJ, USA and was funded by the authors.

Author contributions:

All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Financial support: The initial trial was supported by grant SNSF 3200BO-116177/1 and 32003B-135222 from the Swiss National Science Foundation. Prof. Schuetz is supported by the Swiss National Science Foundation (SNSF Professorship, PP00P3_150531 / 1). Prof Christ-Crain is supported by the Swiss National Science Foundation (SNSF Professorship PP0P3_123346).

Employment or leadership: None declared.

Honorarium: Philipp Schuetz, MCC and Beat Mueller have received financial support from BRAHMS/Thermofisher and BioMerieux to attend meetings and have fulfilled speaking engagements. BM has served as a consultant to and received research support from BRAHMS/Thermofisher and BioMerieux. All other authors declare that they have no competing interests.

Competing interest: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intens Care Med 2010;36:222–31.10.1007/s00134-009-1738-3Suche in Google Scholar PubMed PubMed Central

2. Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax 2012;67:71–9.10.1136/thx.2009.129502Suche in Google Scholar PubMed

3. Schneider SM, Veyres P, Pivot X, Soummer AM, Jambou P, Filippi J, et al. Malnutrition is an independent factor associated with nosocomial infections. Br J Nutr 2004;92:105–11.10.1079/BJN20041152Suche in Google Scholar PubMed

4. Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, et al. Avian influenza A (H5N1) infection in humans. N Engl J Med 2005;353:1374–85.10.1056/NEJMra052211Suche in Google Scholar PubMed

5. Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis 2005;11:201–9.10.3201/eid1102.041061Suche in Google Scholar PubMed PubMed Central

6. Woodhead M, Blasi F, Ewig S, Garau J, Huchon M, Leven M, et al. Guidelines for the management of adult lower respiratory tract infections. Clin Microbiol Infect 2011;17(Suppl 6):E1–59.10.1111/j.1469-0691.2011.03672.xSuche in Google Scholar PubMed PubMed Central

7. Menendez R, Martinez R, Reyes S, Mensa J, Filella X, Marcos MA, et al. Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia. Thorax 2009;64:587–91.10.1136/thx.2008.105312Suche in Google Scholar PubMed

8. 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;139:318–26.Suche in Google Scholar

9. Schuetz P, Christ-Crain M, Wolbers M, Schild U, Thomann R, Falconnier C, et al. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial. BMC Health Serv Res 2007;7:102.10.1186/1472-6963-7-102Suche in Google Scholar PubMed PubMed Central

10. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. J Am Med Assoc 2009;302:1059–66.10.1001/jama.2009.1297Suche in Google Scholar PubMed

11. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997;336:243–50.10.1056/NEJM199701233360402Suche in Google Scholar PubMed

12. Thorpe TC, Wilson ML, Turner JE, DiGuiseppi JL, Willert M, Mirrett S, et al. BacT/Alert: an automated colorimetric microbial detection system. J Clin Microbiol 1990;28:1608–12.10.1128/jcm.28.7.1608-1612.1990Suche in Google Scholar PubMed PubMed Central

13. Neill AM, Martin IR, Weir R, Anderson R, Chereshsky A, Epton MJ, et al. Community acquired pneumonia: aetiology and usefulness of severity criteria on admission. Thorax 1996;51:1010–6.10.1136/thx.51.10.1010Suche in Google Scholar PubMed PubMed Central

14. Capelastegui A. Validation of a predictive rule for the management of community-acquired pneumonia. Eur Respir J 2006;27:151–7.10.1183/09031936.06.00062505Suche in Google Scholar PubMed

15. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003;58:377–82.10.1136/thorax.58.5.377Suche in Google Scholar PubMed PubMed Central

16. Niederman MS. Recent advances in community-acquired pneumonia: inpatient and outpatient. Chest 2007;131:1205–15.10.1378/chest.06-1994Suche in Google Scholar PubMed PubMed Central

17. Schuetz P, Koller M, Christ-Crain M, Steyerberg E, Stolz D, Muller C, et al. Predicting mortality with pneumonia severity scores: importance of model recalibration to local settings. Epidemiol Infect 2008;136:1628–37.10.1017/S0950268808000435Suche in Google Scholar PubMed PubMed Central

18. Schuetz P, Litke A, Albrich WC, Mueller B. Blood biomarkers for personalized treatment and patient management decisions in community-acquired pneumonia. Curr Opin Infect Dis 2013;26:159–67.10.1097/QCO.0b013e32835d0becSuche in Google Scholar PubMed

19. Schuetz P, Haubitz S, Mueller B. Do sepsis biomarkers in the emergency room allow transition from bundled sepsis care to personalized patient care? Curr Opin Crit Care 2012;18:341–9.10.1097/MCC.0b013e328354b2c8Suche in Google Scholar PubMed

20. Schuetz P, Amin DN, Greenwald JL. Role of procalcitonin in managing adult patients with respiratory tract infections. Chest 2012;141:1063–73.10.1378/chest.11-2430Suche in Google Scholar PubMed

21. Kruger S, Ewig S, Kunde J, Hartmann O, Marre R, Suttorp N, et al. 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;411:1929–34.10.1016/j.cca.2010.08.004Suche in Google Scholar PubMed

22. Haeuptle J, Zaborsky R, Fiumefreddo R, Trampuz A, Steffen I, Frei R, et al. Prognostic value of procalcitonin in Legionella pneumonia. Eur J Clin Microbiol Infect Dis 2009;28:55–60.10.1007/s10096-008-0592-5Suche in Google Scholar PubMed

23. Huang DT, Weissfeld LA, Kellum JA, Yealy DM, Kong L, Martino M, et al. Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia. Ann Emerg Med 2008;52:48–58e2.10.1016/j.annemergmed.2008.01.003Suche in Google Scholar PubMed PubMed Central

24. Luyt CE, Guerin V, Combes A, Trouillet JL, Ayed SB, Bernard M, et al. Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia. Am J Respir Crit Care Med 2005;171:48–53.10.1164/rccm.200406-746OCSuche in Google Scholar PubMed

25. Seligman R, Meisner M, Lisboa TC, Hertz FT, Filippin TB, Fachel JM, et al. Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia. Crit Care 2006;10:R125.10.1186/cc5036Suche in Google Scholar PubMed PubMed Central

26. Schuetz P, Suter-Widmer I, Chaudri A, Christ-Crain M, Zimmerli W, Mueller B, et al. Prognostic value of procalcitonin in community-acquired pneumonia. Eur Respir J 2011;37:384–92.10.1183/09031936.00035610Suche in Google Scholar PubMed

27. Kruger S, Ewig S, Marre R, Papassotiriou J, Richter K, von Baum H, et al. Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes. Eur Respir J 2008;31:349–55.10.1183/09031936.00054507Suche in Google Scholar PubMed

28. Boussekey N, Leroy O, Alfandari S, Devos P, Georges H, Guery B. Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia. Intens Care Med 2006;32:469–72.10.1007/s00134-005-0047-8Suche in Google Scholar PubMed

29. Hausfater P, Juillien G, Madonna-Py B, Haroche J, Bernard M, Riou B. Serum procalcitonin measurement as diagnostic and prognostic marker in febrile adult patients presenting to the emergency department. Crit Care 2007;11:R60.10.1186/cc5926Suche in Google Scholar PubMed PubMed Central

30. Boussekey N, Leroy O, Georges H, Devos P, d’Escrivan T, Guery B. Diagnostic and prognostic values of admission procalcitonin levels in community-acquired pneumonia in an intensive care unit. Infection 2005;33:257–63.10.1007/s15010-005-4096-2Suche in Google Scholar PubMed PubMed Central

31. Albrich WC, Ruegger K, Dusemund F, Schuetz P, Arici B, Litke A, et al. Biomarker-enhanced triage in respiratory infections: a proof-of-concept feasibility trial. Eur Respir J 2013;42:1064–75.10.1183/09031936.00113612Suche in Google Scholar PubMed PubMed Central

32. Albrich WC, Dusemund F, Ruegger K, Christ-Crain M, Zimmerli W, Bregenzer T, et al. Enhancement of CURB65 score with proadrenomedullin (CURB65-A) for outcome prediction in lower respiratory tract infections: derivation of a clinical algorithm. BMC Infect Dis 2011;11:112.10.1186/1471-2334-11-112Suche in Google Scholar PubMed PubMed Central

Received: 2014-4-28

Accepted: 2014-6-13

Published Online: 2014-7-11

Published in Print: 2015-3-1

Sie haben derzeit keinen Zugang zu diesem Inhalt.

Artikel in diesem Heft

https://doi.org/10.1515/cclm-2014-0456

Schlagwörter für diesen Artikel

community-acquired pneumonia (CAP); C-reactive protein (CRP); CURB-65 score; mortality; procalcitonin; severity of illness; white blood cells.