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Intensive Care Medicine

, Volume 40, Issue 10, pp 1399–1408 | Cite as

De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial

  • Marc Leone
  • Carole Bechis
  • Karine Baumstarck
  • Jean-Yves Lefrant
  • Jacques Albanèse
  • Samir Jaber
  • Alain Lepape
  • Jean-Michel Constantin
  • Laurent Papazian
  • Nicolas Bruder
  • Bernard Allaouchiche
  • Karine Bézulier
  • François Antonini
  • Julien Textoris
  • Claude Martin
  • For the AZUREA Network Investigators
Seven-Day Profile Publication

Abstract

Background

In patients with severe sepsis, no randomized clinical trial has tested the concept of de-escalation of empirical antimicrobial therapy. This study aimed to compare the de-escalation strategy with the continuation of an appropriate empirical treatment in those patients.

Methods

This was a multicenter non-blinded randomized noninferiority trial of patients with severe sepsis who were randomly assigned to de-escalation or continuation of empirical antimicrobial treatment. Recruitment began in February 2012 and ended in April 2013 in nine intensive care units (ICUs) in France. Patients with severe sepsis were assigned to de-escalation (n = 59) or continuation of empirical antimicrobial treatment (n = 57). The primary outcome was to measure the duration of ICU stay. We defined a noninferiority margin of 2 days. If the lower boundary of the 95 % confidence interval (CI) for the difference in patients assigned to the de-escalation group was less than 2 days, as compared with that of patients assigned to the continuation group, de-escalation was considered to be noninferior to the continuation strategy. Secondary outcomes included mortality at 90 days, occurrence of organ failure, number of superinfections, and number of days with antibiotics during the ICU stay.

Results

The median duration of ICU stay was 9 [interquartile range (IQR) 5–22] days in the de-escalation group and 8 [IQR 4–15] days in the continuation group, respectively (P = 0.71). The mean difference was 3.4 (95 % CI −1.7 to 8.5). A superinfection occurred in 16 (27 %) patients in the de-escalation group and six (11 %) patients in the continuation group (P = 0.03). The numbers of antibiotic days were 9 [7–15] and 7.5 [6–13] in the de-escalation group and continuation group, respectively (P = 0.03). Mortality was similar in both groups.

Conclusion

As compared to the continuation of the empirical antimicrobial treatment, a strategy based on de-escalation of antibiotics resulted in prolonged duration of ICU stay. However, it did not affect the mortality rate.

Keywords

Sepsis Antibiotics De-escalation Empirical Stewardship 

Notes

Acknowledgments

We thank Jean-Charles Reynier, Loundoun Anderson, and Pascal Auquier. We also thank Charlotte Kelway for her attentive reading of our manuscript.

Conflicts of interest

The authors have completed and submitted the International Committee of Medical Journal Editors (ICMJE) Form for Disclosure of Potential conflicts of interest. Dr Leone reported serving as consultant for LFB. Dr. Constantin reported receiving payment for lectures from Baxter, Drager, Fresenius-Kabi, LFB, Convatec, MSD, Maquet, and Hospal. No other disclosures were reported.

Supplementary material

134_2014_3411_MOESM1_ESM.docx (107 kb)
Supplementary material 1 (DOCX 107 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2014

Authors and Affiliations

  • Marc Leone
    • 1
    • 2
  • Carole Bechis
    • 1
  • Karine Baumstarck
    • 3
  • Jean-Yves Lefrant
    • 4
  • Jacques Albanèse
    • 5
  • Samir Jaber
    • 6
  • Alain Lepape
    • 7
  • Jean-Michel Constantin
    • 8
  • Laurent Papazian
    • 2
    • 9
  • Nicolas Bruder
    • 10
  • Bernard Allaouchiche
    • 11
  • Karine Bézulier
    • 12
  • François Antonini
    • 1
  • Julien Textoris
    • 2
  • Claude Martin
    • 1
  • For the AZUREA Network Investigators
  1. 1.Service d’anesthésie et de réanimationHôpital NordMarseilleFrance
  2. 2.Unité de Recherche sur les Maladies Infectieuses et Tropicales ÉmergentesCentre National de la Recherche Scientifique–Unité Mixte de Recherche 7278, Aix Marseille UniversitéMarseilleFrance
  3. 3.Unité d’Aide Méthodologique à la Recherche Clinique et EpidémiologiqueAix Marseille UniversitéMarseilleFrance
  4. 4.Service des Réanimations Pôle Anesthésie Réanimation Douleur UrgenceCHU NîmesNîmesFrance
  5. 5.Hôpital La ConceptionMarseilleFrance
  6. 6.Hôpital Saint-EloiMontpellierFrance
  7. 7.Hôpitaux Lyon SudLyonFrance
  8. 8.Réanimation polyvalenteHôpital universitaire EstaingClermont-FerrantFrance
  9. 9.Hôpital NordMarseilleFrance
  10. 10.Hôpital la TimoneMarseilleFrance
  11. 11.Hôpital Edouard HerriotLyonFrance
  12. 12.Centre d’Investigation Clinique 9502Aix Marseille Université, Assistance Publique Hôpitaux de MarseilleMarseilleFrance

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