Intensive Care Medicine

, Volume 45, Issue 2, pp 172–189 | Cite as

Rationalizing antimicrobial therapy in the ICU: a narrative review

  • Jean-François TimsitEmail author
  • Matteo Bassetti
  • Olaf Cremer
  • George Daikos
  • Jan de Waele
  • Andre Kallil
  • Eric Kipnis
  • Marin Kollef
  • Kevin Laupland
  • Jose-Artur Paiva
  • Jesús Rodríguez-Baño
  • Étienne Ruppé
  • Jorge Salluh
  • Fabio Silvio Taccone
  • Emmanuel Weiss
  • François Barbier


The massive consumption of antibiotics in the ICU is responsible for substantial ecological side effects that promote the dissemination of multidrug-resistant bacteria (MDRB) in this environment. Strikingly, up to half of ICU patients receiving empirical antibiotic therapy have no definitively confirmed infection, while de-escalation and shortened treatment duration are insufficiently considered in those with documented sepsis, highlighting the potential benefit of implementing antibiotic stewardship programs (ASP) and other quality improvement initiatives. The objective of this narrative review is to summarize the available evidence, emerging options, and unsolved controversies for the optimization of antibiotic therapy in the ICU. Published data notably support the need for better identification of patients at risk of MDRB infection, more accurate diagnostic tools enabling a rule-in/rule-out approach for bacterial sepsis, an individualized reasoning for the selection of single-drug or combination empirical regimen, the use of adequate dosing and administration schemes to ensure the attainment of pharmacokinetics/pharmacodynamics targets, concomitant source control when appropriate, and a systematic reappraisal of initial therapy in an attempt to minimize collateral damage on commensal ecosystems through de-escalation and treatment-shortening whenever conceivable. This narrative review also aims at compiling arguments for the elaboration of actionable ASP in the ICU, including improved patient outcomes and a reduction in antibiotic-related selection pressure that may help to control the dissemination of MDRB in this healthcare setting.


Antibiotic stewardship Antimicrobial resistance Empirical therapy Critical illness Carbapenem Outcome Sepsis 


Compliance with ethical standards

Conflicts of interests

Dr. Kollef’s effort was supported by the Barnes-Jewish Hospital Foundation. Dr. Barbier received consulting fees, speaker fees, and conference invitation from MSD, and conference invitation from Pfizer. Dr. De Waele has been consultant for Accelerate Diagnostics, Bayer Healthcare, Grifols, MSD, and Pfizer (all honoraria paid to institution). Dr. Timsit received fees for scientific advisory boards from Pfizer, Bayer pharma, Merck, Nabriva and received fees for lectures from Biomerieux, Pfizer, Merck, Gilead. Dr. Rodríguez-Baño received honoraria for accredited educational activities from Merck and for coordination of a non-product-related research project by Astra-Zeneca. Dr. Ruppé received speaker fees from MSD, Sanofi, and Mobidiag, fees for scientific advisory board from Pathoquest and MaaT Pharma, and consulting fees from DaVolterra. Dr. Daikos reports grants from Pfizer, Gilead, and honoraria from Pfizer, Achaogen, MSD, and Rempex, outside of this work. Dr. Kipnis received fees for scientific advisory boards, lectures, and conference invitation from MSD, for lectures and conference invitations from Pfizer and Fresenius, and conference invitations from LFB and Gilead. Dr. Weiss reports speaker fees form Baxter, MSD, and Gilead, congress and travel reimbursements from MSD and Eumedica, and having participated in an advisory board from Biomerieux.

Supplementary material

134_2019_5520_MOESM1_ESM.docx (189 kb)
Supplementary material 1 (DOCX 189 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jean-François Timsit
    • 1
    • 2
    Email author
  • Matteo Bassetti
    • 3
  • Olaf Cremer
    • 4
  • George Daikos
    • 5
  • Jan de Waele
    • 6
  • Andre Kallil
    • 7
  • Eric Kipnis
    • 8
  • Marin Kollef
    • 9
  • Kevin Laupland
    • 10
  • Jose-Artur Paiva
    • 11
  • Jesús Rodríguez-Baño
    • 12
  • Étienne Ruppé
    • 2
    • 13
  • Jorge Salluh
    • 14
  • Fabio Silvio Taccone
    • 15
  • Emmanuel Weiss
    • 16
    • 17
  • François Barbier
    • 18
  1. 1.Medical and Infectious Diseases ICU, APHP, Bichat-Claude Bernard HospitalParis Cedex 18France
  2. 2.INSERM, IAME, UMR 1137, Paris-Diderot Sorbonne-Paris Cité UniversityParisFrance
  3. 3.Infectious Diseases Division, Department of MedicineUniversity of Udine and Azienda Sanitaria Universitaria Integrata di UdineUdineItaly
  4. 4.Department of Intensive Care MedicineUniversity Medical Center UtrechtUtrechtThe Netherlands
  5. 5.Scool of Medicine, National and Kapodistrian University of AthensAthensGreece
  6. 6.Department of Critical Care MedicineGhent University HospitalGhentBelgium
  7. 7.Department of Internal Medicine, Division of Infectious DiseasesUniversity of Nebraska Medical CenterOmahaUSA
  8. 8.Surgical Critical Care Unit, Department of Anesthesiology, Critical Care and Perioperative MedicineCHU LilleLilleFrance
  9. 9.Critical Care Research, Washington University School of Medicine and Respiratory Care ServicesBarnes-Jewish HospitalSt. LouisUSA
  10. 10.Department of MedicineRoyal Inland HospitalKamloopsCanada
  11. 11.Intensive Care Medicine DepartmentCentro Hospitalar São João and Faculty of Medicine, University of PortoPortoPortugal
  12. 12.Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Hospital Universitario Virgen Macarena, Departament of MedicineUniversity of Sevilla, Biomedicine Institute of Seville (IBiS)SevilleSpain
  13. 13.Bacteriology LaboratoryBichat-Claude Bernard Hospital, APHPParisFrance
  14. 14.Department of Critical Care and Graduate Program in Translational MedicineD’Or Institute for Research and Education, IDORRio De JaneiroBrazil
  15. 15.Department of Intensive CareErasme HospitalBrusselsBelgium
  16. 16.Department of Anesthesiology and Critical CareBeaujon Hospital, AP-HPClichyFrance
  17. 17.INSERM, CRI, UMR 1149, Paris-Diderot Sorbonne-Paris Cité UniversityParisFrance
  18. 18.Medical ICU, La Source Hospital, CHR OrléansOrléansFrance

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