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



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).


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.


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).


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.


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



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)


  1. 1.
    Bassetti M, De Waele JJ, Eggimann P, Garnacho-Montero J, Kahlmeter G, Menichetti F, Nicolau DP, Paiva JA, Tumbarello M, Welte T, Wilcox M, Zahar JR, Poulakou G (2015) Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Intensive Care Med 41(5):776–795CrossRefPubMedGoogle Scholar
  2. 2.
    Ruppé E, Woerther PL, Barbier F (2015) Mechanisms of antimicrobial resistance in Gram-negative bacilli. Ann Intensive Care 5:21CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Detsis M, Karanika S, Mylonakis E (2017) ICU acquisition rate, risk factors, and clinical significance of digestive tract colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae: a systematic review and meta-analysis. Crit Care Med 45(4):705–714CrossRefPubMedGoogle Scholar
  4. 4.
    Bretonniere C, Leone M, Milesi C, Allaouchiche B, Armand-Lefevre L, Baldesi O, Bouadma L, Decre D, Figueiredo S, Gauzit R, Guery B, Joram N, Jung B, Lasocki S, Lepape A, Lesage F, Pajot O, Philippart F, Souweine B, Tattevin P, Timsit JF, Vialet R, Zahar JR, Misset B, Bedos JP (2015) Strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric). Intensive Care Med 41(7):1181–1196CrossRefPubMedGoogle Scholar
  5. 5.
    Barbier F, Pommier C, Essaied W, Garrouste-Orgeas M, Schwebel C, Ruckly S, Dumenil AS, Lemiale V, Mourvillier B, Clec’h C, Darmon M, Laurent V, Marcotte G, Lucet JC, Souweine B, Zahar JR, Timsit JF (2016) Colonization and infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae in ICU patients: what impact on outcomes and carbapenem exposure? J Antimicrob Chemother 71(4):1088–1097CrossRefPubMedGoogle Scholar
  6. 6.
    Armand-Lefevre L, Angebault C, Barbier F, Hamelet E, Defrance G, Ruppé E, Bronchard R, Lepeule R, Lucet JC, El Mniai A, Wolff M, Montravers P, Plesiat P, Andremont A (2013) Emergence of imipenem-resistant Gram-negative bacilli in intestinal flora of intensive care patients. Antimicrob Agents Chemother 57(3):1488–1495CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Razazi K, Mekontso Dessap A, Carteaux G, Jansen C, Decousser JW, de Prost N, Brun-Buisson C (2017) Frequency, associated factors and outcome of multi-drug-resistant intensive care unit-acquired pneumonia among patients colonized with extended-spectrum beta-lactamase-producing Enterobacteriaceae. Ann Intensive Care 7(1):61CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gauzit R, Pean Y, Alfandari S, Bru JP, Bedos JP, Rabaud C, Robert J (2015) Carbapenem use in French hospitals: a nationwide survey at the patient level. Int J Antimicrob Agents 46(6):707–712CrossRefPubMedGoogle Scholar
  9. 9.
    Bassi GL, Ferrer M, Marti JD, Comaru T, Torres A (2014) Ventilator-associated pneumonia. Semin Respir Crit Care Med 35(4):469–481CrossRefPubMedGoogle Scholar
  10. 10.
    Nussenblatt V, Avdic E, Berenholtz S, Daugherty E, Hadhazy E, Lipsett PA, Maragakis LL, Perl TM, Speck K, Swoboda SM, Ziai W, Cosgrove SE (2014) Ventilator-associated pneumonia: overdiagnosis and treatment are common in medical and surgical intensive care units. Infect Control Hosp Epidemiol 35(3):278–284CrossRefPubMedGoogle Scholar
  11. 11.
    Magill SS, Klompas M, Balk R, Burns SM, Deutschman CS, Diekema D, Fridkin S, Greene L, Guh A, Gutterman D, Hammer B, Henderson D, Hess D, Hill NS, Horan T, Kollef M, Levy M, Septimus E, Vanantwerpen C, Wright D, Lipsett P (2013) Developing a new, national approach to surveillance for ventilator-associated events: executive summary. Clin Infect Dis 57(12):1742–1746CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    O’Horo JC, Kashyap R, Sevilla Berrios R, Herasevich V, Sampathkumar P (2016) Differentiating infectious and noninfectious ventilator-associated complications: a new challenge. Am J Infect Control 44(6):661–665CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Bouadma L, Sonneville R, Garrouste-Orgeas M, Darmon M, Souweine B, Voiriot G, Kallel H, Schwebel C, Goldgran-Toledano D, Dumenil AS, Argaud L, Ruckly S, Jamali S, Planquette B, Adrie C, Lucet JC, Azoulay E, Timsit JF (2015) Ventilator-associated events: prevalence, outcome, and relationship with ventilator-associated pneumonia. Crit Care Med 43(9):1798–1806CrossRefPubMedGoogle Scholar
  14. 14.
    Boyer AF, Schoenberg N, Babcock H, McMullen KM, Micek ST, Kollef MH (2015) A prospective evaluation of ventilator-associated conditions and infection-related ventilator-associated conditions. Chest 147(1):68–81CrossRefPubMedGoogle Scholar
  15. 15.
    Barbier F, Bailly S, Schwebel C, Forel JM, Azoulay E, Misset B, Mourvillier B, Reignier J, Darmon M, Zahar JR, Goldgran-Toledano D, de Montmollin E, Souweine B, Timsit JF, OUTCOMEREA Study Group. Infection-related ventilator-associated complications in critically ill patients colonized with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE): correlation with ventilator-associated pneumonia due to ESBLE and impact on carbapenem exposure (abstract #0944). In: Lives 2017—annuel conference of the European Society of Intensive Care Medicine, Vienna, Austria; 2017.Google Scholar
  16. 16.
    Chastre J, Luyt CE (2016) Does this patient have VAP? Intensive Care Med 42(7):1159–1163CrossRefPubMedGoogle Scholar
  17. 17.
    Weiss E, Zahar JR, Lesprit P, Ruppe E, Leone M, Chastre J, Lucet JC, Paugam-Burtz C, Brun-Buisson C, Timsit JF (2015) Elaboration of a consensual definition of de-escalation allowing a ranking of beta-lactams. Clin Microbiol Infect 21(7):649 (e1–10) CrossRefPubMedGoogle Scholar
  18. 18.
    Razazi K, Derde LP, Verachten M, Legrand P, Lesprit P, Brun-Buisson C (2012) Clinical impact and risk factors for colonization with extended-spectrum beta-lactamase-producing bacteria in the intensive care unit. Intensive Care Med 38(11):1769–1778CrossRefPubMedGoogle Scholar
  19. 19.
    Grohs P, Podglajen I, Guerot E, Bellenfant F, Caumont-Prim A, Kac G, Tillecovidin B, Carbonnelle E, Chatellier G, Meyer G, Fagon JY, Gutmann L (2014) Assessment of five screening strategies for optimal detection of carriers of third-generation cephalosporin-resistant Enterobacteriaceae in intensive care units using daily sampling. Clin Microbiol Infect 20(11):O879–O886CrossRefPubMedGoogle Scholar
  20. 20.
    Carbonne H, Le Dorze M, Bourrel AS, Poupet H, Poyart C, Cambau E, Mira JP, Charpentier J, Amarsy R (2017) Relation between presence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in systematic rectal swabs and respiratory tract specimens in ICU patients. Ann Intensive Care 7(1):13CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Woerther PL, Burdet C, Chachaty E, Andremont A (2013) Trends in human fecal carriage of extended-spectrum beta-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev 26(4):744–758CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Masse J, Elkalioubie A, Blazejewski C, Ledoux G, Wallet F, Poissy J, Preau S, Nseir S (2017) Colonization pressure as a risk factor of ICU-acquired multidrug resistant bacteria: a prospective observational study. Eur J Clin Microbiol Infect Dis 36(5):797–805CrossRefPubMedGoogle Scholar
  23. 23.
    Gurieva T, Dautzenberg MJD, Gniadkowski M, Derde LPJ, Bonten MJM, Bootsma MCJ (2017) The transmissibility of antibiotic-resistant Enterobacteriaceae in intensive care units. Clin Infect Dis. PubMedCentralGoogle Scholar
  24. 24.
    Rottier WC, Ammerlaan HS, Bonten MJM (2012) Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis. J Antimicrob Chemother 67(6):1311–1320CrossRefPubMedGoogle Scholar
  25. 25.
    Schwaber MJ, Carmeli Y (2007) Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother 60(5):913–920CrossRefPubMedGoogle Scholar
  26. 26.
    de Kraker ME, Wolkewitz M, Davey PG, Koller W, Berger J, Nagler J, Icket C, Kalenic S, Horvatic J, Seifert H, Kaasch A, Paniara O, Argyropoulou A, Bompola M, Smyth E, Skally M, Raglio A, Dumpis U, Melbarde Kelmere A, Borg M, Xuereb D, Ghita MC, Noble M, Kolman J, Grabljevec S, Turner D, Lansbury L, Grundmann H (2011) Burden of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay associated with bloodstream infections due to Escherichia coli resistant to third-generation cephalosporins. J Antimicrob Chemother 66(2):398–407CrossRefPubMedGoogle Scholar
  27. 27.
    Bruyere R, Vigneron C, Bador J, Aho S, Toitot A, Quenot JP, Prin S, Emmanuel Charles P (2016) Significance of prior digestive colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae in patients with ventilator-associated pneumonia. Crit Care Med 44(4):699–706PubMedGoogle Scholar
  28. 28.
    Fan Y, Gao F, Wu Y, Zhang J, Zhu M, Xiong L (2016) Does ventilator-associated event surveillance detect ventilator-associated pneumonia in intensive care units? A systematic review and meta-analysis. Crit Care 20(1):338CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Vodovar D, Marcadié G, Rousseau H, Raskine L, Vicaut E, Deye N, Baud FJ, Mégarbane B (2014) Predictive factors for extended-spectrum beta-lactamase producing Enterobacteriaceae causing infection among ICU patients with prior colonization. Infection 42(4):743–748CrossRefPubMedGoogle Scholar
  30. 30.
    Miliani K, L’Heriteau F, Lacave L, Carbonne A, Astagneau P (2011) Imipenem and ciprofloxacin consumption as factors associated with high incidence rates of resistant Pseudomonas aeruginosa in hospitals in northern France. J Hosp Infect 77(4):343–347CrossRefPubMedGoogle Scholar
  31. 31.
    Cohen J, Vincent JL, Adhikari NK, Machado FR, Angus DC, Calandra T, Jaton K, Giulieri S, Delaloye J, Opal S, Tracey K, van der Poll T, Pelfrene E (2015) Sepsis: a roadmap for future research. Lancet Infect Dis 15(5):581–614CrossRefPubMedGoogle Scholar
  32. 32.
    Le Dorze M, Gault N, Foucrier A, Ruppe E, Mourvillier B, Woerther PL, Birgand G, Montravers P, Dilly MP, Tubach F, Andremont A, Timsit JF, Wolff M, Armand-Lefevre L (2015) Performance and impact of a rapid method combining mass spectrometry and direct antimicrobial susceptibility testing on treatment adequacy of patients with ventilator-associated pneumonia. Clin Microbiol Infect 21(5):468 (e1–6) CrossRefPubMedGoogle Scholar
  33. 33.
    Kollef MH, Burnham CD (2017) Ventilator-associated pneumonia: the role of emerging diagnostic technologies. Semin Respir Crit Care Med 38(3):253–263CrossRefPubMedGoogle Scholar
  34. 34.
    Ruppé E, Lixandru B, Cojocaru R, Buke C, Paramythiotou E, Angebault C, Visseaux C, Djuikoue I, Erdem E, Burduniuc O, El Mniai A, Marcel C, Perrier M, Kesteman T, Clermont O, Denamur E, Armand-Lefevre L, Andremont A (2013) Relative fecal abundance of extended-spectrum-beta-lactamase-producing Escherichia coli strains and their occurrence in urinary tract infections in women. Antimicrob Agents Chemother 57(9):4512–4517CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Harris PN, Tambyah PA, Paterson DL (2015) Beta-lactam and beta-lactamase inhibitor combinations in the treatment of extended-spectrum beta-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? Lancet Infect Dis 15(4):475–485CrossRefPubMedGoogle Scholar
  36. 36.
    Gutierrez-Gutierrez B, Perez-Galera S, Salamanca E, de Cueto M, Calbo E, Almirante B, Viale P, Oliver A, Pintado V, Gasch O, Martinez-Martinez L, Pitout J, Akova M, Pena C, Molina J, Hernandez A, Venditti M, Prim N, Origuen J, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Giamarellou H, Almela M, Perez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Mora-Rillo M, Natera C, Souli M, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodriguez-Bano J (2016) A multinational, preregistered cohort study of beta-lactam/beta-lactamase inhibitor combinations for treatment of bloodstream infections due to extended-spectrum-beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 60(7):4159–4169CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Guet-Revillet H, Tomini E, Emirian A, Join-Lambert O, Lecuyer H, Zahar JR, Jullien V (2017) Piperacillin/tazobactam as an alternative antibiotic therapy to carbapenems in the treatment of urinary tract infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae: an in silico pharmacokinetic study. Int J Antimicrob Agents 49(1):62–66CrossRefPubMedGoogle Scholar
  38. 38.
    Timsit JF, Pilmis B, Zahar JR (2017) How should we treat hospital-acquired and ventilator-associated pneumonia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae? Semin Respir Crit Care Med 38(3):287–300CrossRefPubMedGoogle Scholar
  39. 39.
    Torres A, Zhong N, Pachl J, Timsit JF, Kollef M, Chen Z, Song J, Taylor D, Laud PJ, Stone GG, Chow JW (2017) Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. PubMedGoogle Scholar
  40. 40.
    Wright H, Bonomo RA, Paterson DL (2017) New agents for the treatment of infections with Gram-negative bacteria: restoring the miracle or false dawn? Clin Microbiol Infect 23(10):704–712CrossRefPubMedGoogle Scholar

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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