Intensive Care Medicine

, Volume 38, Issue 6, pp 940–949 | Cite as

An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients

  • Dimitrios K. Matthaiou
  • Georgia Ntani
  • Marina Kontogiorgi
  • Garyfallia Poulakou
  • Apostolos Armaganidis
  • George Dimopoulos
Systematic Review



We sought to perform a systematic review and meta-analysis of procalcitonin(PCT)-guided antibiotic therapy algorithms for critically ill adult patients.


We performed a search in PubMed and in the Cochrane Central Register of Controlled Trials. Seven evaluable randomised clinical trials (RCTs) were identified and analysed. Primary outcomes included the duration of antibiotic therapy for the first episode of infection and 28-day mortality. Secondary outcomes included length of ICU stay, length of hospitalisation, antibiotic-free days within the first 28 days of hospitalisation, recurrences, and superinfections.


Data on the duration of antibiotic therapy for the first episode of infection were provided in five out of seven included RCTs, while data on 28-day mortality were provided in all of the included RCTs. Duration of antibiotic therapy for the first episode of infection was reduced in favour of PCT-guided treatment [pooled weighted mean difference (WMD) = −3.15 days, random effects model, 95 % confidence interval (CI) −4.36 to −1.95, P < 0.001]. There was no difference in 28-day mortality between the compared arms [fixed effect model (FEM), odds ratio = 0.96, 95 % CI 0.79–1.15, P = 0.63). Antibiotic-free days were increased within the first 28 days of hospitalisation in favour of the PCT-guided treatment arm (pooled WMD = 3.08 days, FEM, 95 % CI 2.06–4.10, P < 0.001). No difference was found regarding the remaining outcomes. Sensitivity analyses including studies of higher quality and studies using the TRACE method to measure PCT yielded similar results.


Procalcitonin-guided antibiotic therapy algorithms could help in reducing the duration of antimicrobial administration without having a negative impact on survival.


Intensive care Gram-negative Procalcitonin Duration Cost 



We would like to thank Prof. Hazel Inskip (MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK) for her kind suggestions during the preparation of the manuscript and Dr. Tannaze Tinati (MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK) for editing the manuscript in its final form.

Conflicts of interest



  1. 1.
    Oczenski W, Fitzgerald RD, Schwarz S (1998) Procalcitonin: a new parameter for the diagnosis of bacterial infection in the peri-operative period. Eur J Anaesthesiol 15:202–209PubMedGoogle Scholar
  2. 2.
    Tang BM, Eslick GD, Craig JC, McLean AS (2007) Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 7:210–217PubMedCrossRefGoogle Scholar
  3. 3.
    Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ, ACCP/SCCM Consensus Conference Committee (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 136 (5 Suppl):e28Google Scholar
  4. 4.
    Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, Vadas L, Pugin J, Geneva Sepsis Network (2001) Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 164:396–402PubMedGoogle Scholar
  5. 5.
    Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589–1596PubMedCrossRefGoogle Scholar
  6. 6.
    Briel M, Schuetz P, Mueller B, Young J, Schild U, Nusbaumer C, Périat P, Bucher HC, Christ-Crain M (2008) Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care. Arch Intern Med 168:2000–2007; discussion 7–8Google Scholar
  7. 7.
    Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Müller B (2004) Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 363:600–607PubMedCrossRefGoogle Scholar
  8. 8.
    Christ-Crain M, Stolz D, Bingisser R, Müller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Müller B (2006) Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 174:84–93PubMedCrossRefGoogle Scholar
  9. 9.
    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 (2009) Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 302:1059–1066CrossRefGoogle Scholar
  10. 10.
    Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Müller C, Huber P, Müller B, Tamm M (2007) Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 131:9–19PubMedCrossRefGoogle Scholar
  11. 11.
    Khan KS, Daya S, Jadad A (1996) The importance of quality of primary studies in producing unbiased systematic reviews. Arch Intern Med 156:661–666PubMedCrossRefGoogle Scholar
  12. 12.
    Moher D, Jadad AR, Tugwell P (1996) Assessing the quality of randomized controlled trials. Current issues and future directions. Int J Technol Assess Health Care 12:195–208PubMedCrossRefGoogle Scholar
  13. 13.
    Higgins JP, Thompson SG (2004) Controlling the risk of spurious findings from meta-regression. Stat Med 23:1663–1682PubMedCrossRefGoogle Scholar
  14. 14.
    Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13PubMedCrossRefGoogle Scholar
  15. 15.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  16. 16.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  17. 17.
    Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, Thornberg KJ, Løken J, Steensen M, Fox Z, Tousi H, Søe-Jensen P, Lauritsen AØ, Strange D, Petersen PL, Reiter N, Hestad S, Thormar K, Fjeldborg P, Larsen KM, Drenck NE, Ostergaard C, Kjær J, Grarup J, Lundgren JD, Procalcitonin And Survival Study (PASS) Group (2011) Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 39:2048–2058PubMedCrossRefGoogle Scholar
  18. 18.
    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 (2010) Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 375:463–474PubMedCrossRefGoogle Scholar
  19. 19.
    Hochreiter M, Köhler T, Schweiger AM, Keck FS, Bein B, von Spiegel T, Schroeder S (2009) Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care 13:R83PubMedCrossRefGoogle Scholar
  20. 20.
    Schroeder S, Hochreiter M, Koehler T, Schweiger AM, Bein B, Keck FS, von Spiegel T (2009) 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 394:221–226PubMedCrossRefGoogle Scholar
  21. 21.
    Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, Marsch S, Azzola A, Rakic J, Mueller B, Tamm M (2009) Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J 34:1364–1375PubMedCrossRefGoogle Scholar
  22. 22.
    Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J (2008) Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 177:498–505PubMedCrossRefGoogle Scholar
  23. 23.
    Svoboda P, Kantorova I, Scheer P, Radvanova J, Radvan M (2007) Can procalcitonin help us in timing of re-intervention in septic patients after multiple trauma or major surgery? Hepatogastroenterology 54:359–363PubMedGoogle Scholar
  24. 24.
    Arnold HM, Micek ST, Skrupky LP, Kollef MH (2011) Antibiotic stewardship in the intensive care unit. Semin Respir Crit Care Med 32:215–227PubMedCrossRefGoogle Scholar
  25. 25.
    Hochreiter M, Schroeder S (2011) Procalcitonin-based algorithm : management of antibiotic therapy in critically ill patients. Anaesthesist 60:661–673PubMedCrossRefGoogle Scholar
  26. 26.
    Heyland DK, Johnson AP, Reynolds SC, Muscedere J (2011) Procalcitonin for reduced antibiotic exposure in the critical care setting: A systematic review and an economic evaluation. Crit Care Med 39:1792–1799PubMedCrossRefGoogle Scholar
  27. 27.
    Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A (2010) Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med 38:2229–2241PubMedCrossRefGoogle Scholar
  28. 28.
    Tang H, Huang T, Jing J, Shen H, Cui W (2009) Effect of procalcitonin-guided treatment in patients with infections: a systematic review and meta-analysis. Infection 37:497–507PubMedCrossRefGoogle Scholar
  29. 29.
    Schuetz P, Chiappa V, Briel M, Greenwald JL (2011) Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med 171:1322–1331PubMedCrossRefGoogle Scholar
  30. 30.
    Hayashi Y, Paterson DL (2011) Strategies for reduction in duration of antibiotic use in hospitalized patients. Clin Infect Dis 52:1232–1240PubMedCrossRefGoogle Scholar
  31. 31.
    Placebo Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT). Available at:
  32. 32.
    Safety and efficacy of procalcitonin guided antibiotic therapy in adult intensive care units (ICU’s) (SAPS). Available at
  33. 33.
    Use of inflammatory biomarkers to guide antibiotic therapy in patients with severe infections. Available at:
  34. 34.
    Procalcitonin guided versus conventional antibiotic therapy in patients with sepsis in the ICU. Available at:

Copyright information

© Copyright jointly held by Springer and ESICM 2012

Authors and Affiliations

  • Dimitrios K. Matthaiou
    • 1
  • Georgia Ntani
    • 2
  • Marina Kontogiorgi
    • 3
  • Garyfallia Poulakou
    • 4
  • Apostolos Armaganidis
    • 3
  • George Dimopoulos
    • 3
  1. 1.Department of Internal Medicine“G. Gennimatas” General HospitalThessalonikiGreece
  2. 2.MRC Lifecourse Epidemiology UnitUniversity of Southampton, Southampton General HospitalSouthamptonUK
  3. 3.Department of Critical CareMedical School, University of Athens, “Attikon” University HospitalAthensGreece
  4. 4.Department of Internal MedicineMedical School, University of Athens, “Attikon” University HospitalAthensGreece

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