Skip to main content
Top
Published in: Annals of Intensive Care 1/2018

Open Access 01-12-2018 | Research

Adherence to a procalcitonin-guided antibiotic treatment protocol in patients with severe sepsis and septic shock

Authors: Andreas Hohn, Nina Balfer, Bernhard Heising, Sabine Hertel, Jan C. Wiemer, Marcel Hochreiter, Stefan Schröder

Published in: Annals of Intensive Care | Issue 1/2018

Login to get access

Abstract

Background

In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed.

Methods

From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT < 0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes.

Results

Of 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients. Forty-two patients (62.7%) had appropriate PCT measurement series. In patients with appropriate PCT series, median initial PCT (p = 0.001) and peak PCT levels (p < 0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6–9] vs. 12d [IQR 9–16]; p = 0.002). No differences were seen in terms of other clinical outcomes.

Conclusion

In patients with severe sepsis and septic shock, procalcitonin testing was irregular and adherence to a local PCT protocol was low in real clinical life. However, adherently treated patients had a shorter duration of antibiotic treatment without negative clinical outcomes. Procalcitonin peak values and kinetics had a clear impact on the regularity of PCT testing.
Appendix
Available only for authorised users
Literature
1.
go back to reference de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE 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(7):819–27.CrossRefPubMed de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE 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(7):819–27.CrossRefPubMed
2.
go back to reference Matthaiou DK, Ntani G, Kontogiorgi M, Poulakou G, Armaganidis A, Dimopoulos G. An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients. Intensive Care Med. 2012;38(6):940–9.CrossRefPubMed Matthaiou DK, Ntani G, Kontogiorgi M, Poulakou G, Armaganidis A, Dimopoulos G. An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients. Intensive Care Med. 2012;38(6):940–9.CrossRefPubMed
3.
go back to reference Prkno A, Wacker C, Brunkhorst FM, Schlattmann P. Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock—a systematic review and meta-analysis. Crit Care. 2013;17(6):R291.CrossRefPubMedPubMedCentral Prkno A, Wacker C, Brunkhorst FM, Schlattmann P. Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock—a systematic review and meta-analysis. Crit Care. 2013;17(6):R291.CrossRefPubMedPubMedCentral
4.
go back to reference Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med. 2010;38(11):2229–41.CrossRefPubMed Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med. 2010;38(11):2229–41.CrossRefPubMed
5.
go back to reference Tang H, Huang T, Jing J, Shen H, Cui W. Effect of procalcitonin-guided treatment in patients with infections: a systematic review and meta-analysis. Infection. 2009;37(6):497–507.CrossRefPubMed Tang H, Huang T, Jing J, Shen H, Cui W. Effect of procalcitonin-guided treatment in patients with infections: a systematic review and meta-analysis. Infection. 2009;37(6):497–507.CrossRefPubMed
6.
go back to reference Iankova I, Thompson-Leduc P, Kirson NY, Rice B, Hey J, Krause A et al. Efficacy and safety of procalcitonin guidance in patients with suspected or confirmed sepsis: a systematic review and meta-analysis. Crit Care Med. 2018;46(5):691–8.CrossRefPubMed Iankova I, Thompson-Leduc P, Kirson NY, Rice B, Hey J, Krause A et al. Efficacy and safety of procalcitonin guidance in patients with suspected or confirmed sepsis: a systematic review and meta-analysis. Crit Care Med. 2018;46(5):691–8.CrossRefPubMed
7.
go back to reference Huang HB, Peng JM, Weng L, Wang CY, Jiang W, Du B. Procalcitonin-guided antibiotic therapy in intensive care unit patients: a systematic review and meta-analysis. Ann Intensive Care. 2017;7(1):114.CrossRefPubMedPubMedCentral Huang HB, Peng JM, Weng L, Wang CY, Jiang W, Du B. Procalcitonin-guided antibiotic therapy in intensive care unit patients: a systematic review and meta-analysis. Ann Intensive Care. 2017;7(1):114.CrossRefPubMedPubMedCentral
8.
go back to reference Brechot N, Hekimian G, Chastre J, Luyt CE. Procalcitonin to guide antibiotic therapy in the ICU. Int J Antimicrob Agents. 2015;46(Suppl 1):S19–24.CrossRefPubMed Brechot N, Hekimian G, Chastre J, Luyt CE. Procalcitonin to guide antibiotic therapy in the ICU. Int J Antimicrob Agents. 2015;46(Suppl 1):S19–24.CrossRefPubMed
9.
go back to reference Andriolo BN, Andriolo RB, Salomao R, Atallah AN. Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev. 2017;1:Cd010959.PubMed Andriolo BN, Andriolo RB, Salomao R, Atallah AN. Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev. 2017;1:Cd010959.PubMed
10.
go back to reference Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304–77.CrossRefPubMed Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304–77.CrossRefPubMed
11.
go back to reference de With K, Allerberger F, Amann S, Apfalter P, Brodt HR, Eckmanns T, et al. Strategies to enhance rational use of antibiotics in hospital: a guideline by the German society for infectious diseases. Infection. 2016;44(3):395–439.CrossRefPubMedPubMedCentral de With K, Allerberger F, Amann S, Apfalter P, Brodt HR, Eckmanns T, et al. Strategies to enhance rational use of antibiotics in hospital: a guideline by the German society for infectious diseases. Infection. 2016;44(3):395–439.CrossRefPubMedPubMedCentral
12.
13.
go back to reference Hohn A, Schroeder S, Gehrt A, Bernhardt K, Bein B, Wegscheider K, et al. Procalcitonin-guided algorithm to reduce length of antibiotic therapy in patients with severe sepsis and septic shock. BMC Infect Dis. 2013;13:158.CrossRefPubMedPubMedCentral Hohn A, Schroeder S, Gehrt A, Bernhardt K, Bein B, Wegscheider K, et al. Procalcitonin-guided algorithm to reduce length of antibiotic therapy in patients with severe sepsis and septic shock. BMC Infect Dis. 2013;13:158.CrossRefPubMedPubMedCentral
14.
go back to reference Hohn A, Heising B, Hertel S, Baumgarten G, Hochreiter M, Schroeder S. Antibiotic consumption after implementation of a procalcitonin-guided antimicrobial stewardship programme in surgical patients admitted to an intensive care unit: a retrospective before-and-after analysis. Infection. 2015;43(4):405–12.CrossRefPubMed Hohn A, Heising B, Hertel S, Baumgarten G, Hochreiter M, Schroeder S. Antibiotic consumption after implementation of a procalcitonin-guided antimicrobial stewardship programme in surgical patients admitted to an intensive care unit: a retrospective before-and-after analysis. Infection. 2015;43(4):405–12.CrossRefPubMed
16.
go back to reference Ammar AA, Lam SW, Duggal A, Neuner EA, Bass SN, Guzman JA, et al. Compliance with procalcitonin algorithm antibiotic recommendations for patients in medical intensive care unit. Pharmacotherapy. 2017;37(2):177–86.CrossRefPubMed Ammar AA, Lam SW, Duggal A, Neuner EA, Bass SN, Guzman JA, et al. Compliance with procalcitonin algorithm antibiotic recommendations for patients in medical intensive care unit. Pharmacotherapy. 2017;37(2):177–86.CrossRefPubMed
17.
go back to reference Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, 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(9713):463–74.CrossRefPubMed Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, 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(9713):463–74.CrossRefPubMed
18.
go back to reference 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(5):498–505.CrossRefPubMed 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(5):498–505.CrossRefPubMed
19.
go back to reference Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J. 2009;34(6):1364–75.CrossRefPubMed Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J. 2009;34(6):1364–75.CrossRefPubMed
20.
go back to reference Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, 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(9):2048–58.CrossRefPubMed Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, 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(9):2048–58.CrossRefPubMed
21.
go back to reference Svoboda P, Kantorova I, Scheer P, Radvanova J, Radvan M. Can procalcitonin help us in timing of re-intervention in septic patients after multiple trauma or major surgery? Hepatogastroenterology. 2007;54(74):359–63.PubMed Svoboda P, Kantorova I, Scheer P, Radvanova J, Radvan M. Can procalcitonin help us in timing of re-intervention in septic patients after multiple trauma or major surgery? Hepatogastroenterology. 2007;54(74):359–63.PubMed
22.
go back to reference Zahar JR, Timsit JF, Garrouste-Orgeas M, Francais A, Vesin A, Descorps-Declere A, et al. Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality. Crit Care Med. 2011;39(8):1886–95.CrossRefPubMed Zahar JR, Timsit JF, Garrouste-Orgeas M, Francais A, Vesin A, Descorps-Declere A, et al. Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality. Crit Care Med. 2011;39(8):1886–95.CrossRefPubMed
23.
go back to reference Leligdowicz A, Dodek PM, Norena M, Wong H, Kumar A, Kumar A. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med. 2014;189(10):1204–13.CrossRefPubMed Leligdowicz A, Dodek PM, Norena M, Wong H, Kumar A, Kumar A. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med. 2014;189(10):1204–13.CrossRefPubMed
24.
go back to reference Brunkhorst FM, Al-Nawas B, Krummenauer F, Forycki ZF, Shah PM. Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in patients with severe pneumonia. Clin Microbiol Infect. 2002;8(2):93–100.CrossRefPubMed Brunkhorst FM, Al-Nawas B, Krummenauer F, Forycki ZF, Shah PM. Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in patients with severe pneumonia. Clin Microbiol Infect. 2002;8(2):93–100.CrossRefPubMed
25.
go back to reference Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis. Infection. 2000;28(2):68–73.CrossRefPubMed Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis. Infection. 2000;28(2):68–73.CrossRefPubMed
26.
go back to reference 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(1):48–53.CrossRefPubMed 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(1):48–53.CrossRefPubMed
27.
go back to reference Klingele M, Bomberg H, Schuster S, Schafers HJ, Groesdonk HV. Prognostic value of procalcitonin in patients after elective cardiac surgery: a prospective cohort study. Ann Intensive Care. 2016;6(1):116.CrossRefPubMedPubMedCentral Klingele M, Bomberg H, Schuster S, Schafers HJ, Groesdonk HV. Prognostic value of procalcitonin in patients after elective cardiac surgery: a prospective cohort study. Ann Intensive Care. 2016;6(1):116.CrossRefPubMedPubMedCentral
28.
go back to reference Peschanski N, Chenevier-Gobeaux C, Mzabi L, Lucas R, Ouahabi S, Aquilina V, et al. Prognostic value of PCT in septic emergency patients. Ann Intensive Care. 2016;6(1):47.CrossRefPubMedPubMedCentral Peschanski N, Chenevier-Gobeaux C, Mzabi L, Lucas R, Ouahabi S, Aquilina V, et al. Prognostic value of PCT in septic emergency patients. Ann Intensive Care. 2016;6(1):47.CrossRefPubMedPubMedCentral
29.
go back to reference Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164(3):396–402.CrossRefPubMed Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164(3):396–402.CrossRefPubMed
30.
go back to reference Schuetz P, Birkhahn R, Sherwin R, Jones AE, Singer A, Kline JA, et al. Serial procalcitonin predicts mortality in severe sepsis patients: results from the multicenter procalcitonin monitoring sepsis (MOSES) study. Crit Care Med. 2017;45(5):781–9.CrossRefPubMedPubMedCentral Schuetz P, Birkhahn R, Sherwin R, Jones AE, Singer A, Kline JA, et al. Serial procalcitonin predicts mortality in severe sepsis patients: results from the multicenter procalcitonin monitoring sepsis (MOSES) study. Crit Care Med. 2017;45(5):781–9.CrossRefPubMedPubMedCentral
31.
go back to reference Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801–10.CrossRefPubMedPubMedCentral Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801–10.CrossRefPubMedPubMedCentral
Metadata
Title
Adherence to a procalcitonin-guided antibiotic treatment protocol in patients with severe sepsis and septic shock
Authors
Andreas Hohn
Nina Balfer
Bernhard Heising
Sabine Hertel
Jan C. Wiemer
Marcel Hochreiter
Stefan Schröder
Publication date
01-12-2018
Publisher
Springer International Publishing
Published in
Annals of Intensive Care / Issue 1/2018
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-018-0415-5

Other articles of this Issue 1/2018

Annals of Intensive Care 1/2018 Go to the issue