8/10/2019 Des Es Calacion Sepsis

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Marc Leone

Carole Bechis

Karine Baumstarck

De-escalation in severe sepsis:

still an important part of our

armamentarium against

antimicrobial resistance,

of course!

Accepted: 28 August 2014Published online: 19 September 2014 Springer-Verlag Berlin Heidelberg andESICM 2014

Dear Editor,We thank Kapoor and Saigal [1] fortheir relevant comments about ourstudy on de-escalation versus contin-uation of empirical antimicrobialtreatment in severe sepsis [2]. Weagree that de-escalation cannot bediscarded on the basis of a singlerandomized clinical trial. Our manu-script does not convey this message.However, this first randomized clini-cal trial is probably a red flag thatmust drive us to better define condi-tions with which de-escalation can besafely performed.

In agreement with observationalstudies [3], our trial in patients withsevere sepsis showed that de-escala-tion did not affect mortality. Incontrast, de-escalation was associatedwith an increased use of antimicro-bials. This finding was reported in arecent cohort of septic patients withneutropenia [4]. Our study suggests

that this was related to an increasednumber of superinfections in the de-escalation group. The duration ofintensive care unit stay was alsoincreased in the de-escalation group.In our opinion, these surprisingresults were never properly addressed

in previous observational studies. Inthose studies, de-escalation wasprobably performed in patients withan adequate response to antibiotics.

This is a major flaw in order to assessthe risk associated with this strategy[5].

We strongly agree that there is aneed for a consensual definition of de-escalation. In our pragmaticapproach, we did not take intoaccount the specific minimum inhib-itory concentration of each organism.That is probably a limitation in ourstudy. However, to our knowledge,there is no evidence showing that astrategy of antibiotic stewardship

based on the minimum inhibitoryconcentration would improve thepatient outcomes.

Our trial attempted to reflect real-life practices. In routine, de-escala-tion is used in both surgical andmedical patients. We agree that de-escalation is probably associated witha higher risk of harm in patients withsuspected polymicrobial infection,such as peritonitis, than in those withpositive blood culture due to catheter-related infection. To our knowledge,

there is no recommendation for aspecific strategy of antimicrobialstewardship depending on those fea-tures. We hope that our results pavethe way for future studies on antibi-otic stewardship in the intensive careunit.

Conflicts of interest Dr. Leone reportedserving as a consultant for LFB. No otherdisclosures were reported.

References

1. Kapoor G, Saigal S (2014) De-escalationin severe sepsis: still an important part ofour armamentarium against antimicrobialresistance. Intensive Care Med. doi:10.1007/s00134-014-3476-4

2. Leone M, Bechis C, Baumstarck K,Lefrant JY, Albanese J, Jaber S, LepapeA, Constantin JM, Papazian L, Bruder N,Allaouchiche B, Bezulier K, Antonini F,

Textoris J, Martin C, for the AZUREANetwork Investigators (2014) De-escalation versus continuation ofempirical antimicrobial treatment insevere sepsis: a multicenter non-blindedrandomized noninferiority trial. IntensiveCare Med. doi:10.1007/s00134-014-3411-8

3. Leone M, Bourgoin A, Cambon S,Dubuc M, Albanese J, Martin C (2003)Empirical antimicrobial therapy of septicshock patients: adequacy and impact onthe outcome. Crit Care Med 31:462467

4. Mokart D, Slehofer G, Lambert J,Sannini A, Chow-Chine L, Brun JP,Berger P, Duran S, Faucher M, Blache

JL, Saillard C, Vey N, Leone M (2014)De-escalation of antimicrobial treatmentin neutropenic patients with severesepsis: results from an observationalstudy. Intensive Care Med 40:4149

5. Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A,Corcia-Palomo Y, Fernandez-Delgado E,Herrera-Melero I, Ortiz-Leyba C,Marquez-Vacaro JA (2014) De-escalation of empirical therapy isassociated with lower mortality inpatients with severe sepsis and septicshock. Intensive Care Med 40:3240

M. Leone ()

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C. BechisService dAnesthesie et de Reanimation,Hopital Nord, Aix Marseille Universite,13015 Marseille, Francee-mail: marc.leone@ap-hm.frTel.: ?33491968655

K. BaumstarckUnitedAide Methodologique a laRecherche Clinique et Epidemiologique,Aix Marseille Universite, Marseille, France

Intensive Care Med (2014) 40:1619DOI 10.1007/s00134-014-3479-1 CORRE S P ONDE NCE

http://dx.doi.org/10.1007/s00134-014-3476-4http://dx.doi.org/10.1007/s00134-014-3411-8http://dx.doi.org/10.1007/s00134-014-3411-8http://dx.doi.org/10.1007/s00134-014-3476-4