Infection-related ventilator-associated complications in ICU patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae

  • François Barbier
  • Sébastien Bailly
  • Carole Schwebel
  • Laurent Papazian
  • Élie Azoulay
  • Hatem Kallel
  • Shidasp Siami
  • Laurent Argaud
  • Guillaume Marcotte
  • Benoît Misset
  • Jean Reignier
  • Michaël Darmon
  • Jean-Ralph Zahar
  • Dany Goldgran-Toledano
  • Étienne de Montmollin
  • Bertrand Souweine
  • Bruno Mourvillier
  • Jean-François Timsit
  • for the OUTCOMEREA Study Group
Original

Abstract

Purpose

To investigate the clinical significance of infection-related ventilator-associated complications (IVAC) and their impact on carbapenem consumption in mechanically ventilated (MV) patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE).

Methods

Inception cohort study from the French prospective multicenter OUTCOMEREA database (17 ICUs, 1997–2015) including all ESBLE carriers (systematic rectal swabbing at admission then weekly and/or urinary or superficial surgical site colonisation) with MV duration > 48 h and ≥ 1 episode of IVAC after carriage documentation. All ICU-acquired infections were microbiologically documented.

Results

The 318 enrolled ESBLE carriers (median age 68 years; males 67%; medical admission 68%; imported carriage 53%) experienced a total of 576 IVAC comprising 361 episodes (63%) without documented infection, 124 (21%) related to infections other than ventilator-associated pneumonia (VAP), 73 (13%) related to non-ESBLE VAP and 18 (3%) related to ESBLE VAP. Overall, ESBLE infections accounted for only 43 episodes (7%). Carbapenem exposure within the preceding 3 days was the sole independent predictor of ESBLE infection as the causative event of IVAC, with a protective effect (adjusted odds ratio 0.2, 95% confidence interval 0.05–0.6; P < 0.01). Carbapenems were initiated in 9% of IVAC without infection, 15% of IVAC related to non-VAP infections, 42% of IVAC related to non-ESBLE VAP, and 56% of IVAC related to ESBLE VAP (ESBLE VAP versus non-ESBLE VAP: P = 0.43).

Conclusions

IVAC in ESBLE carriers mostly reflect noninfectious events but act as a strong driver of empirical carbapenem consumption. ESBLE infections are scarce yet hard to predict, strengthening the need for novel diagnostic approaches and carbapenem-sparing alternatives.

Keywords

Extended-spectrum beta-lactamase Mechanical ventilation Ventilator-associated pneumonia Carbapenem Outcome 

Notes

Acknowledgements

Members of the OUTCOMEREA Study Group—Scientific Committee: Jean-François Timsit (Medical and Infectious Diseases ICU, Bichat-Claude Bernard Hospital, Paris, France; UMR 1137 Inserm-Paris Diderot university IAME, F75018, Paris); Elie Azoulay (Medical ICU, Saint Louis Hospital, Paris, France); Maïté Garrouste-Orgeas (ICU, Saint-Joseph Hospital, Paris, France); Jean-Ralph Zahar (Infection Control Unit, Angers Hospital, Angers, France); Christophe Adrie (Physiology, Cochin Hospital, Paris, France); Michael Darmon (Medical ICU, Saint Etienne University Hospital, St Etienne, France); and Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, and UMR 1137 Inserm, Paris Diderot university IAME, F75018, Paris, France).

Biostatistical and information system expertise: Jean-Francois Timsit (Medical and Infectious Diseases ICU, Bichat-Claude Bernard Hospital, Paris, France; UMR 1137 Inserm –Paris Diderot university IAME, F75018, Paris); Corinne Alberti (Medical Computer Sciences and Biostatistics Department, Robert Debré Hospital, Paris, France); Adrien Français (Integrated Research Center U823, Grenoble, France); Aurélien Vesin (OUTCOMEREA organization and Integrated Research Center U823, Grenoble, France); Stephane Ruckly (OUTCOMEREA organization and Inserm UMR 1137 IAME, F75018, Paris); Sébastien Bailly (Grenoble university hospital Inserm UMR 1137 IAME, F75018, Paris) and Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, and Inserm UMR 1137 IAME, F75018, Paris, France); Frederik Lecorre (Supelec, France); Didier Nakache (Conservatoire National des Arts et Métiers, Paris, France); and Aurélien Vannieuwenhuyze (Tourcoing, France).

Investigators of the OUTCOMEREA database: Dr Romain HERNU, Christophe Adrie (ICU, CH Melun, and Physiology, Cochin Hospital, Paris, France); Carole Agasse (medical ICU, university hospital Nantes, France); Bernard Allaouchiche (ICU, Pierre benite Hospital, Lyon, France); Olivier Andremont (ICU, Bichat Hospital, Paris, France); Pascal Andreu (CHU Dijon, Dijon, France); Laurent Argaud (Medical ICU, Hospices Civils de Lyon, Lyon, France); Claire Ara-Somohano (Medical ICU, University Hospital, Grenoble, France); Elie Azoulay (Medical ICU, Saint Louis Hospital, Paris, France); François Barbier (medical-surgical ICU, Orleans, France), Déborah Boyer (ICU, CHU Rouen, France), Jean-Pierre Bedos (ICU, Versailles Hospital, Versailles, France); Thomas Baudry (Medial ICU, Edouard Heriot hospital, Lyon France), Jérome Bedel (ICU, Versailles Hospital, Versailles, France), Julien Bohé (ICU, Hôpital Pierre Benite, Lyon France), Lila Bouadma (ICU, Bichat Hospital, Paris, France); Jeremy Bourenne (Réanimation des urgencies, Timone-2; APHM, Marseille, France); Noel Brule (medical ICU, university hospital Nantes, France); Cédric Brétonnière (medical ICU, university hospital Nantes, France); Christine Cheval (ICU, Hyeres Hospital, Hyeres, France); Julien Carvelli (Réanimation des urgencies, Timone-2; APHM, Marseille, France);Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, France); Elisabeth Coupez (ICU, G Montpied Hospital, Clermont-Ferrand, France); Martin Cour Medial ICU, Edouard Heriot hospital, Lyon France), Michael Darmon (ICU, Saint Etienne Hospital, Saint Etienne, France); Etienne de Montmollin (ICU, Delafontaine Hospital, Saint Denis), Loa Dopeux (ICU, G Montpied Hospital, Clermont-Ferrand, France); Anne-Sylvie Dumenil (Antoine Béclère Hospital, Clamart, France); Claire Dupuis (Bichat hospital and UMR 1137 Inserm –Paris Diderot university IAME, F75018, Paris, France), Jean-Marc Forel (AP HM, Medical ICU, Hôpital Nord Marseille), Marc Gainnier (Réanimation des urgencies, Timone-2; APHM, Marseille, France), Charlotte Garret (medical ICU, university hospital Nantes, France); Steven Grangé (ICU, CHU Rouen, France), Antoine Gros (ICU, Versailles Hospital, Versailles, France), Akim Haouache (Surgical ICU, H Mondor Hospital, Creteil, France); Romain Hernu (Medical ICU, Hospices Civils de Lyon, Lyon, France); Tarik Hissem (ICU, Eaubonne, France), Vivien Hon Tua Ha (ICU, CH Meaux, France); Sébastien Jochmans (ICU, CH Melun); Jean-Baptiste Joffredo (ICU, G Montpied Hospital, Clermont-Ferrand, France); Hatem Kallel (ICU, Cayenne General Hospital, Cayenne, France); Guillaume Lacave (ICU, Versailles Hospital, Versailles, France), Alexandre Lautrette (ICU, G Montpied Hospital, Clermont-Ferrand, France); Virgine Lemiale (Medical ICU, Saint Louis Hospital, Paris, France); Mathilde Lermuzeaux (ICU, Bichat Hospital, Paris, France), Guillaume Marcotte (Surgical ICU, Hospices Civils de Lyon, Lyon, France); Jordane Lebut (ICU, Bichat Hospital, Paris, France); Maxime Lugosi (Medical ICU, University Hospital Grenoble, Grenoble, France); Eric Magalhaes (ICU, Bichat Hospital, Paris, France), Sibylle Merceron (ICU, Versailles Hospital, Versailles, France), Bruno Mourvillier (ICU, Bichat Hospital, Paris, France); Benoît Misset (ICU, Saint-Joseph Hospital, Paris, France and Medical ICU CHU Rouen, France); Bruno Mourvillier (ICU, Bichat Hospital, Paris, France); Mathild Neuville (ICU, Bichat Hospital, Paris, France), Laurent Nicolet (medical ICU, university hospital Nantes, France); Johanna Oziel (Medico-surgical ICU, hôpital Avicenne APHP, Bobigny, France), Laurent Papazian (Hopital Nord, Marseille, France), Benjamin Planquette (pulmonology ICU, George Pompidou hospital Hospital, Paris, France); Jean-Pierre Quenot (CHU Dijon, Dijon, France); Aguila Radjou (ICU, Bichat Hospital, Paris, France), Marie Simon (Medial ICU, Edouard Heriot hospital, Lyon France), Romain Sonneville (ICU, Bichat Hospital, Paris, France), Jean Reignier (medical ICU, university hospital Nantes, France); Bertrand Souweine (ICU, G Montpied Hospital, Clermont-Ferrand, France); Carole Schwebel (ICU, A Michallon Hospital, Grenoble, France); Shidasp Siami (ICU, Eaubonne, France); Roland Smonig (ICU, Bichat Hospital, Paris, France); Gilles Troché (ICU, Antoine Béclère Hospital, Clamart, France); Marie Thuong (ICU, Delafontaine Hospital, Saint Denis, France); Guillaume Thierry (ICU, Saint-Louis Hospital, Paris, France); Dany Toledano (ICU, Gonesse Hospital, Gonesse, France); Guillaume Van Der Meersch, Medical Surgical ICU, university hospital Avicenne), Marion Venot (Medical ICU, Saint Louis Hospital, Paris, France); Olivier Zambon (medical ICU, university hospital Nantes, France);

Study Monitors: Julien Fournier, Caroline Tournegros, Stéphanie Bagur, Mireille Adda, Vanessa Vindrieux, Sylvie de la Salle, Pauline Enguerrand, Loic Ferrand, Vincent Gobert, Stéphane Guessens, Helene Merle, Nadira Kaddour, Boris Berthe, Samir Bekkhouche, Kaouttar Mellouk, Mélaine Lebrazic, Carole Ouisse, Diane Maugars, Christelle Aparicio, Igor Theodose, Manal Nouacer, Veronique Deiler, Myriam Moussa, Atika Mouaci, Nassima Viguier and Sophie Letrou.

Author contributions

Study design, data analysis and interpretation of the result: FB, SB, JFT. Data acquisition: CS, LP, EA, HK, SS, LA, GM, BM, JR, MD, JRZ, GDT, EdM, BS, BM. Writing of the article: FB, SB, JFT. Critical revision for important intellectual content: CS, LP, EA, HK, SS, LA, GM, BM, JR, MD, JRZ, GDT, EdM, BS, BM. Approval of the submitted article: all authors.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest relative to the present study.

Supplementary material

134_2018_5154_MOESM1_ESM.docx (96 kb)
Supplementary material 1 (DOCX 97 kb)
134_2018_5154_MOESM2_ESM.docx (22 kb)
Supplementary material 2 (DOCX 21 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature and ESICM 2018

Authors and Affiliations

  • François Barbier
    • 1
  • Sébastien Bailly
    • 2
  • Carole Schwebel
    • 3
  • Laurent Papazian
    • 4
  • Élie Azoulay
    • 5
  • Hatem Kallel
    • 6
  • Shidasp Siami
    • 7
  • Laurent Argaud
    • 8
  • Guillaume Marcotte
    • 9
  • Benoît Misset
    • 10
  • Jean Reignier
    • 11
  • Michaël Darmon
    • 5
  • Jean-Ralph Zahar
    • 12
  • Dany Goldgran-Toledano
    • 13
  • Étienne de Montmollin
    • 14
  • Bertrand Souweine
    • 15
  • Bruno Mourvillier
    • 16
  • Jean-François Timsit
    • 2
    • 16
  • for the OUTCOMEREA Study Group
  1. 1.Medical ICU, La Source HospitalCHR OrléansOrléansFrance
  2. 2.UMR 1137, IAME Team 5, DeSCID: Decision SCiences in Infectious Diseases, Control and Care, INSERM, Paris DiderotSorbonne Paris Cité UniversityParisFrance
  3. 3.Medical ICUAlbert Michallon University HospitalGrenobleFrance
  4. 4.Respiratory and Infectious Diseases ICUNorth HospitalMarseilleFrance
  5. 5.Medical ICUSaint-Louis Hospital, APHPParisFrance
  6. 6.Medical Surgical ICUAndrée Rosemon HospitalCayenneFrance
  7. 7.Medical Surgical ICUCorbeil-Essone HospitalCorbeil-EssoneFrance
  8. 8.Medical ICUEdouard-Herriot University HospitalLyonFrance
  9. 9.Surgical ICUEdouard-Herriot University HospitalLyonFrance
  10. 10.Medical ICUCharles Nicolle University HospitalRouenFrance
  11. 11.Medical ICUHôtel-Dieu University HospitalNantesFrance
  12. 12.Infection Control UnitAvicenne HospitalBobignyFrance
  13. 13.Medical-Surgical ICUGeneral HospitalMontfermeilFrance
  14. 14.Medical-Surgical ICUDelafontaine HospitalSaint-DenisFrance
  15. 15.Medical ICUGabriel Montpied HospitalClermont-FerrandFrance
  16. 16.Medical and Infectious Diseases ICUBichat-Claude Bernard Hospital, APHPParis Cedex 18France

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