Intensive Care Medicine

, Volume 41, Issue 5, pp 776–795 | Cite as

Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria

  • Matteo Bassetti
  • Jan J. De Waele
  • Philippe Eggimann
  • Josè Garnacho-Montero
  • Gunnar Kahlmeter
  • Francesco Menichetti
  • David P. Nicolau
  • Jose Arturo Paiva
  • Mario Tumbarello
  • Tobias Welte
  • Mark Wilcox
  • Jean Ralph Zahar
  • Garyphallia Poulakou


The antibiotic pipeline continues to diminish and the majority of the public remains unaware of this critical situation. The cause of the decline of antibiotic development is multifactorial and currently most ICUs are confronted with the challenge of multidrug-resistant organisms. Antimicrobial multidrug resistance is expanding all over the world, with extreme and pandrug resistance being increasingly encountered, especially in healthcare-associated infections in large highly specialized hospitals. Antibiotic stewardship for critically ill patients translated into the implementation of specific guidelines, largely promoted by the Surviving Sepsis Campaign, targeted at education to optimize choice, dosage, and duration of antibiotics in order to improve outcomes and reduce the development of resistance. Inappropriate antimicrobial therapy, meaning the selection of an antibiotic to which the causative pathogen is resistant, is a consistent predictor of poor outcomes in septic patients. Therefore, pharmacokinetically/pharmacodynamically optimized dosing regimens should be given to all patients empirically and, once the pathogen and susceptibility are known, local stewardship practices may be employed on the basis of clinical response to redefine an appropriate regimen for the patient. This review will focus on the most severely ill patients, for whom substantial progress in organ support along with diagnostic and therapeutic strategies markedly increased the risk of nosocomial infections.


Antibiotic Bacteria Resistance MRSA Stewardship 



Antimicrobial susceptibility testing


β-Lactam/β-lactamase inhibitors


Clostridium difficile infection


Carbapenem-resistant Enterobacteriaceae


European Center for Diseases Control


Extended-spectrum β-lactamases


Extended-spectrum β-lactamase-producing Εnterobacteriaceae


European Committee on Antimicrobial Susceptibility Testing


Food and Drug Administration


Hospital-acquired pneumonia


Healthcare workers


Intensive care unit


Infectious Diseases Society of America


Klebsiella pneumoniae carbapenemase


Multidrug-resistant organisms


Minimum inhibitory concentration


Modified intention to treat


Methicillin-resistant Staphylococcus aureus




Selective digestive decontamination


Ventilator-associated pneumonia


Verona integron-mediated metallo-β-lactamase


Vancomycin-resistant enterococci



Research made in collaboration with the Critically Ill Patients Study Group (ESGCIP) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).

Conflicts of interest

MB serves on scientific advisory boards for AstraZeneca, Bayer, Cubist, Pfizer Inc, MSD, Tetraphase, and Astellas Pharma Inc.; has received funding for travel or speaker honoraria from Algorithm, Angelini, Astellas Pharma Inc., AstraZeneca, Cubist, Pfizer MSD, Gilead Sciences, Novartis, Ranbaxy, and Teva. GP has received funding for travel or speaker honoraria from Astellas, Gilead, MSD, Novartis, and Pfizer. JGM has received speaker honoraria from Astellas, Gilead, MSD, Novartis, and Pfizer and a scientific grant from Astellas. DPN: Consultant, member of the speakers bureau, or has received research grant funding from AstraZeneca, Bayer, Cubist, Actavis, GSK, Medicines Co., Merck, Pfizer, and Tetraphase. JDW has served on advisory boards for Bayer, Cubist, MSD, and Sumitomo Pharma. PE has received funding for advisory board or speaker honoraria from Astellas, MSD, and Pfizer. MHW has received consulting fees from Abbott Laboratories, Actelion, Astellas, Astra-Zeneca, Bayer, Cerexa, Cubist, Durata, The European Tissue Symposium, The Medicines Company, MedImmune, Merck, Motif Biosciences, Nabriva, Optimer, Paratek, Pfizer, Roche, Sanofi-Pasteur, Seres, Summit, and Synthetic Biologics; and lecture fees from Abbott, Alere, Astellas, Astra-Zeneca, and Pfizer; grant support from Abbott, Actelion, Astellas, bioMerieux, Cubist, Da Volterra, The European Tissue Symposium, Merck, and Summit. The other authors declare no conflict of interests.

Supplementary material

134_2015_3719_MOESM1_ESM.docx (26 kb)
Supplementary material 1 (DOCX 25 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • Matteo Bassetti
    • 1
    • 14
  • Jan J. De Waele
    • 2
  • Philippe Eggimann
    • 3
  • Josè Garnacho-Montero
    • 4
  • Gunnar Kahlmeter
    • 5
  • Francesco Menichetti
    • 6
  • David P. Nicolau
    • 7
  • Jose Arturo Paiva
    • 8
  • Mario Tumbarello
    • 9
  • Tobias Welte
    • 10
  • Mark Wilcox
    • 11
  • Jean Ralph Zahar
    • 12
  • Garyphallia Poulakou
    • 13
  1. 1.Infectious Diseases DivisionSanta Maria Misericordia University HospitalUdineItaly
  2. 2.Department of Critical Care MedicineGhent University HospitalGhentBelgium
  3. 3.Adult Critical Care Medicine and Burn UnitCentre Hospitalier Universitaire Vaudois (CHUV)LausanneSwitzerland
  4. 4.Critical Care UnitVirgen del Rocio University HospitalSevilleSpain
  5. 5.Clinical MicrobiologyCentral HopsitalVäxjöSweden
  6. 6.Infectious Diseases UnitNuovo Ospedale S. ChiaraPisaItaly
  7. 7.Center for Anti-Infective Research and DevelopmentHartford HospitalHartfordUSA
  8. 8.Centro Hospitalar Sao Joao, Faculdade de MedicinaUniversity of PortoPortoPortugal
  9. 9.Institute of Infectious DiseasesCatholic University of the Sacred Heart, A. Gemelli HospitalRomeItaly
  10. 10.Department of Pulmonary MedicineHannover Medical SchoolHannoverGermany
  11. 11.MicrobiologyLeeds Teaching Hospitals and University of LeedsLeedsUK
  12. 12.Unité de prévention et de lutte contre les infections nosocomialesUniversité d’Angers, Centre hospitalo-universitaire d’AngersAngersFrance
  13. 13.4th Department of Internal MedicineAthens University School of Medicine, Attikon University General HospitalAthensGreece
  14. 14.Clinica Malattie InfettiveAzienda Ospedaliera Universitaria Santa Maria della MisericordiaUdineItaly

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