Antimicrobial de-escalation in critically ill patients: a position statement from a task force of the European Society of Intensive Care Medicine (ESICM) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Critically Ill Patients Study Group (ESGCIP)

  • Alexis TabahEmail author
  • Matteo Bassetti
  • Marin H. Kollef
  • Jean-Ralph Zahar
  • José-Artur Paiva
  • Jean-Francois Timsit
  • Jason A. Roberts
  • Jeroen Schouten
  • Helen Giamarellou
  • Jordi Rello
  • Jan De Waele
  • Andrew F. Shorr
  • Marc Leone
  • Garyphallia Poulakou
  • Pieter Depuydt
  • Jose Garnacho-Montero
Conference Reports and Expert Panel
Part of the following topical collections:
  1. Patients Study Group (ESGCIP)



Antimicrobial de-escalation (ADE) is a strategy of antimicrobial stewardship, aiming at preventing the emergence of antimicrobial resistance (AMR) by decreasing the exposure to broad-spectrum antimicrobials. There is no high-quality research on ADE and its effects on AMR. Its definition varies and there is little evidence-based guidance for clinicians to use ADE in the intensive care unit (ICU).


A task force of 16 international experts was formed in November 2016 to provide with guidelines for clinical practice to develop questions targeted at defining ADE, its effects on the ICU population and to provide clinical guidance. Groups of 2 experts were assigned 1–2 questions each within their field of expertise to provide draft statements and rationale. A Delphi method, with 3 rounds and an agreement threshold of 70% was required to reach consensus.


We present a comprehensive document with 13 statements, reviewing the evidence on the definition of ADE, its effects in the ICU population and providing guidance for clinicians in subsets of clinical scenarios where ADE may be considered.


ADE remains a topic of controversy due to the complexity of clinical scenarios where it may be applied and the absence of evidence to the effects it may have on antimicrobial resistance.


Antimicrobial de-escalation De-escalation Antimicrobial resistance Stewardship 


Compliance with ethical standards

Conflict of interest

Dr. Tabah has nothing to disclose. Dr. Bassetti reports grants and personal fees from PFIZER, grants and personal fees from MSD, grants and personal fees from MENARINI, grants and personal fees from ANGELINI, personal fees from ASTELLAS, personal fees from NABRIVA, grants and personal fees from PARATEK, personal fees from GILEAD, personal fees from BASILEA, personal fees from CIDARA, personal fees from MOLTENI, outside the submitted work. Dr. Kollef’s efforts are supported by the Barnes-Jewish Hospital Foundation. Dr. Zahar reports personal fees from MSD, personal fees from Correvio, personal fees from Pfizer, outside the submitted work. Dr. Paiva has nothing to disclose. Dr. Timsit reports grants and personal fees from Pfizer, grants and personal fees from Merck, personal fees from Astellas, grants and personal fees from Biomerieux, personal fees from 3 M, during the conduct of the study; personal fees from Nabriva, personal fees from Bayer pharma, outside the submitted work. Dr. Roberts reports personal fees and non-financial support from Biomerieux, grants and personal fees from MSD, personal fees from Astellas, personal fees from Infectopharm, grants from The Medicines Company, outside the submitted work. Dr. Schouten has nothing to disclose. Dr. Giamarellou has received research grants from Pfizer, MSD, Angelini. Dr. Rello reports personal fees from Navriba, grants from BAYER, personal fees from Pfizer, personal fees from Anchoagen, outside the submitted work. Dr. De Waele reports grants from Research Foundation Flanders, during the conduct of the study; other from Bayer, other from Pfizer, other from MSD, other from Grifols, other from Accelerate, outside the submitted work. Dr Shorr has served as a speaker for, received research support from, or been a consultant to: Astellas, Merck, Nabriva, Paratek, Shinogi, and Tetraphase. Dr. Leone reports personal fees from MSD, personal fees from Pfizer, during the conduct of the study; grants, personal fees and non-financial support from AMOMED, personal fees from AGUETTANT, personal fees from ASPEN, personal fees from OCTAPHARMA, personal fees from ORION, outside the submitted work. Dr. Poulakou reports personal fees from Angelini, personal fees from MSD, grants and personal fees from Pfizer, grants from Roche, outside the submitted work. Dr. Depuydt has nothing to disclose. Dr. Garnacho-Montero has nothing to disclose.

Supplementary material

134_2019_5866_MOESM1_ESM.pdf (613 kb)
Supplementary material 1 (PDF 613 kb)
134_2019_5866_MOESM2_ESM.pdf (254 kb)
Supplementary material 2 (PDF 254 kb)
134_2019_5866_MOESM3_ESM.pdf (100 kb)
Supplementary material 3 (PDF 100 kb)


  1. 1.
    Rhodes A, Evans LE, Alhazzani W et al (2017) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 43:304–377. CrossRefPubMedGoogle Scholar
  2. 2.
    Liu VX, Fielding-Singh V, Greene JD et al (2017) The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 196:856–863. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bhalodi AA, van Engelen TSR, Virk HS, Wiersinga WJ (2019) Impact of antimicrobial therapy on the gut microbiome. J Antimicrob Chemother 74:i6–i15. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Armand-Lefèvre L, Angebault C, Barbier F et al (2013) Emergence of imipenem-resistant gram-negative bacilli in intestinal flora of intensive care patients. Antimicrob Agents Chemother 57:1488–1495. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Antonelli M, Mercurio G, Di Nunno S et al (2001) De-escalation antimicrobial chemotherapy in critically III patients: pros and cons. J Chemother. CrossRefPubMedGoogle Scholar
  6. 6.
    Rello J, Gallego M, Mariscal D et al (1997) The value of routine microbial investigation in ventilator-associated pneumonia. Am J Respir Crit Care Med 156:196–200. CrossRefPubMedGoogle Scholar
  7. 7.
    Kollef MH (2001) Hospital-acquired pneumonia and de-escalation of antimicrobial treatment. Crit Care Med 29:1473–1475CrossRefGoogle Scholar
  8. 8.
    Barlam TF, Cosgrove SE, Abbo LM et al (2016) Implementing an antibiotic stewardship program: guidelines by the infectious diseases society of America and the society for healthcare epidemiology of America. Clin Infect Dis 62:51–77. CrossRefGoogle Scholar
  9. 9.
    Ruiz J, Ramirez P, Gordon M et al (2018) Antimicrobial stewardship programme in critical care medicine: a prospective interventional study. Med Intensiva. CrossRefPubMedGoogle Scholar
  10. 10.
    Tabah A, Cotta MO, Garnacho-Montero J et al (2016) A systematic review of the definitions, determinants, and clinical outcomes of antimicrobial de-escalation in the intensive care unit. Clin Infect Dis 62:1009–1017. CrossRefPubMedGoogle Scholar
  11. 11.
    Guyatt GH, Oxman AD, Vist GE et al (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336:924–926. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kumar A, Roberts D, Wood KE et al (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. CrossRefPubMedGoogle Scholar
  13. 13.
    Tamma PD, Cosgrove SE, Maragakis LL (2012) Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev 25:450–470. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L (2014) Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst, RevCrossRefGoogle Scholar
  15. 15.
    Kumar A, Safdar N, Kethireddy S, Chateau D (2010) A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study. Crit Care Med 38:1651–1664. CrossRefPubMedGoogle Scholar
  16. 16.
    Woerther P-L, Lepeule R, Burdet C et al (2018) Carbapenems and alternative beta-lactams for the treatment of infections due to ESBL-producing Enterobacteriaceae: what impact on intestinal colonization resistance? Int J Antimicrob Agents. CrossRefPubMedGoogle Scholar
  17. 17.
    Álvarez-Lerma F, Alvarez B, Luque P et al (2006) Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study. Crit Care 10:1–11. CrossRefGoogle Scholar
  18. 18.
    Giantsou E, Liratzopoulos N, Efraimidou E et al (2007) De-escalation therapy rates are significantly higher by bronchoalveolar lavage than by tracheal aspirate. Intensive Care Med 33:1533–1540. CrossRefPubMedGoogle Scholar
  19. 19.
    Mokart D, Slehofer G, Lambert J et al (2014) De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. Intensive Care Med 40:41–49. CrossRefPubMedGoogle Scholar
  20. 20.
    Garnacho-Montero J, Gutiérrez-Pizarraya A, Escoresca-Ortega A et al (2014) De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med 40:32–40. CrossRefPubMedGoogle Scholar
  21. 21.
    Leone M, Bechis C, Baumstarck K et al (2014) De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med 40:1399–1408. CrossRefPubMedGoogle Scholar
  22. 22.
    Paskovaty A, Pastores SM, Gedrimaite Z et al (2015) Antimicrobial de-escalation in septic cancer patients: is it safe to back down? Intensive Care Med 41:2022–2023. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Weiss E, Zahar JR, Garrouste-Orgeas M et al (2016) De-escalation of pivotal beta-lactam in ventilator-associated pneumonia does not impact outcome and marginally affects MDR acquisition. Intensive Care Med 42:2098–2100. CrossRefPubMedGoogle Scholar
  24. 24.
    De Bus L, Denys W, Catteeuw J et al (2016) Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients: a retrospective observational study. Intensive Care Med 42:1029–1039. CrossRefPubMedGoogle Scholar
  25. 25.
    Eachempati SR, Hydo LJ, Shou J, Barie PS (2009) Does de-escalation of antibiotic therapy for ventilator- associated pneumonia affect the likelihood of recurrent pneumonia or mortality in critically III surgical patients? J Trauma Inj Infect Crit Care 66:1343–1348. CrossRefGoogle Scholar
  26. 26.
    De Waele JJ, Ravyts M, Depuydt P et al (2010) De-escalation after empirical meropenem treatment in the intensive care unit: fiction or reality? J Crit Care 25:641–646. CrossRefPubMedGoogle Scholar
  27. 27.
    Morel J, Casoetto J, Jospé R, et al (2010) De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit. Crit Care CrossRefGoogle Scholar
  28. 28.
    Joung MK, Lee JA, Youn SM et al (2011) Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia. Crit Care 15:R79. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Heenen S, Jacobs F, Vincent JL (2012) Antibiotic strategies in severe nosocomial sepsis: why do we not de-escalate more often? Crit Care Med 40:1404–1409. CrossRefPubMedGoogle Scholar
  30. 30.
    Kim JW, Chung J, Choi SH et al (2012) Early use of imipenem/cilastatin and vancomycin followed by de-escalation versus conventional antimicrobials without de-escalation for patients with hospital-acquired pneumonia in a medical ICU: a randomized clinical trial. Crit Care 16:R28. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Gonzalez L, Cravoisy A, Barraud D et al (2013) Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients. Crit Care 17:R140. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Knaak E, Cavalieri SJ, Elsasser GN et al (2013) Does antibiotic de-escalation for nosocomial pneumonia impact intensive care unit length of stay? Infect Dis Clin Pract 21:172–176. CrossRefGoogle Scholar
  33. 33.
    Leone M, Garcin F, Bouvenot J et al (2007) Ventilator-associated pneumonia: breaking the vicious circle of antibiotic overuse. Crit Care Med 35:379–385. CrossRefPubMedGoogle Scholar
  34. 34.
    Cowley MC, Ritchie DJ, Hampton N et al (2018) Outcomes associated with de-escalating anti-MRSA therapy in culture-negative nosocomial pneumonia. Chest 155:53–59. CrossRefPubMedGoogle Scholar
  35. 35.
    Madaras-Kelly K, Jones M, Remington R et al (2014) Development of an antibiotic spectrum score based on veterans affairs culture and susceptibility data for the purpose of measuring antibiotic de-escalation: a modified Delphi approach. Infect Control Hosp Epidemiol 35:1103–1113. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Weiss E, Zahar JR, Lesprit P et al (2015) Elaboration of a consensual definition of de-escalation allowing a ranking of β-lactams. Clin Microbiol Infect 21:649.e1–649.e10. CrossRefGoogle Scholar
  37. 37.
    Moraes RB, Guillén JAV, Zabaleta WJC, Borges FK (2016) De-escalation, adequacy of antibiotic therapy and culture positivity in septic patients: an observational study. Rev Bras Ter Intensiva 28:315–322. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Trupka T, Fisher K, Micek ST et al (2017) Enhanced antimicrobial de-escalation for pneumonia in mechanically ventilated patients: a cross-over study. Crit Care 21:1–8. CrossRefGoogle Scholar
  39. 39.
    Khan RA, Aziz Z (2017) A retrospective study of antibiotic de-escalation in patients with ventilator-associated pneumonia in Malaysia. Int J Clin Pharm 39:906–912. CrossRefPubMedGoogle Scholar
  40. 40.
    Jaffal K, Poissy J, Rouze A et al (2018) De - escalation of antifungal treatment in critically ill patients with suspected invasive Candida infection: incidence, associated factors, and safety. Ann Intensive Care. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Li H, Yang C-H, Huang L-O et al (2018) Antibiotics de-escalation in the treatment of ventilator-associated pneumonia in trauma patients: a retrospective study on propensity score matching method. Chin Med J (Engl) 131:1151. CrossRefGoogle Scholar
  42. 42.
    Bailly S, Leroy O, Montravers P et al (2015) Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data. Intensive Care Med. CrossRefPubMedGoogle Scholar
  43. 43.
    Paul M, Dickstein Y, Raz-Pasteur A (2016) Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis. Clin Microbiol Infect 22:960–967. CrossRefPubMedGoogle Scholar
  44. 44.
    Turza KC, Politano AD, Rosenberger LH et al (2016) De-escalation of antibiotics does not increase mortality in critically ill surgical patients. Surg Infect (Larchmt) 17:48–52. CrossRefGoogle Scholar
  45. 45.
    Chastre J (2005) Antibiotic prescribing for ventilator-associated pneumonia: get it right from the beginning but be able to rapidly deescalate. Intensive Care Med 31:1463–1465. CrossRefPubMedGoogle Scholar
  46. 46.
    Sawyer RG, Claridge JA, Nathens AB et al (2015) Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med 372:1996–2005. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Montravers P, Tubach F, Lescot T et al (2018) Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial. Intensive Care Med 44:300–310. CrossRefPubMedGoogle Scholar
  48. 48.
    Chastre J, Wolff M, Fagon JY et al (2003) Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. J Am Med Assoc 290:2588–2598. CrossRefGoogle Scholar
  49. 49.
    Harris PNA, Peleg AY, Iredell J et al (2015) Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp (the MERINO trial): study protocol for a randomised controlled trial. Trials. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Timbrook TT, Morton JB, McConeghy KW et al (2016) The effect of molecular rapid diagnostic testing on clinical outcomes in bloodstream infections: a systematic review and meta-analysis. Clin Infect Dis. CrossRefPubMedGoogle Scholar
  51. 51.
    Schlaffer K, Heil E, Leekha S et al (2017) Validation of an antimicrobial stewardship driven verigene® blood-culture gram-negative treatment algorithm to improve appropriateness of antibiotics. Open Forum Infect Dis 4:S624–S624. CrossRefPubMedCentralGoogle Scholar
  52. 52.
    Magiorakos AP, Srinivasan A, Carey RB et al (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. CrossRefPubMedGoogle Scholar
  53. 53.
    Kadri SS, Adjemian J, Lai YL et al (2018) Difficult-to-treat resistance in Gram-negative bacteremia at 173 us hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin Infect Dis. CrossRefPubMedGoogle Scholar
  54. 54.
    Joffe AR, Muscedere J, Marshall JC et al (2008) The safety of targeted antibiotic therapy for ventilator-associated pneumonia: a multicenter observational study. J Crit Care 23:82–90. CrossRefPubMedGoogle Scholar
  55. 55.
    Rello J, Vidaur L, Sandiumenge A et al (2004) De-escalation therapy in ventilator-associated pneumonia. Crit Care Med 32:2183–2190. CrossRefPubMedGoogle Scholar
  56. 56.
    Salahuddin N, Amer L, Joseph M et al (2016) Determinants of deescalation failure in critically ill patients with sepsis: a prospective cohort study. Crit Care Res Pract. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Montravers P, Augustin P, Grall N et al (2016) Characteristics and outcomes of anti-infective de-escalation during health care-associated intra-abdominal infections. Crit Care. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Souza-Oliveira AC, Cunha TM, da Passos LB et al (2016) Ventilator-associated pneumonia: the influence of bacterial resistance, prescription errors, and de-escalation of antimicrobial therapy on mortality rates. Braz J Infect Dis 20:437–443. CrossRefPubMedGoogle Scholar
  59. 59.
    Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M et al (2017) Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis 17:726–734. CrossRefPubMedGoogle Scholar
  60. 60.
    Paul M, Daikos GL, Durante-Mangoni E et al (2018) Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis. CrossRefPubMedGoogle Scholar
  61. 61.
    Dickstein Y, Lellouche J, Ben Dalak Amar M et al (2019) Treatment outcomes of colistin- and carbapenem-resistant Acinetobacter baumannii infections: an exploratory subgroup analysis of a randomized clinical trial. Clin Infect Dis 69:769–776. CrossRefPubMedGoogle Scholar
  62. 62.
    Pappas PG, Kauffman CA, Andes DR et al (2015) Clinical practice guideline for the management of candidiasis: 2016 update by the infectious Diseases Society of America. Clin Infect Dis. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Cornely OA, Bassetti M, Calandra T et al (2012) ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 18:19–37. CrossRefPubMedGoogle Scholar
  64. 64.
    Pfaller MA, Castanheira M, Lockhart SR et al (2012) Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata. J Clin Microbiol. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Vazquez J, Reboli AC, Pappas PG et al (2014) Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial. BMC Infect Dis. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Nucci M, Colombo AL, Petti M et al (2014) An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America. Mycoses. CrossRefPubMedGoogle Scholar
  67. 67.
    Mootsikapun P, Hsueh PR, Talwar D et al (2013) Intravenous anidulafungin followed optionally by oral voriconazole for the treatment of candidemia in Asian patients: results from an open-label Phase III trial. BMC Infect Dis. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Garnacho-Montero J, Diaz-Martin A, Canton-Bulnes L et al (2018) Initial antifungal strategy reduces mortality in critically ill patients with Candidemia: a propensity score-adjusted analysis of a multicenter study. Crit Care Med. CrossRefPubMedGoogle Scholar
  69. 69.
    Ferreira D, Grenouillet F, Blasco G et al (2015) Outcomes associated with routine systemic antifungal therapy in critically ill patients with Candida colonization. Intensive Care Med. CrossRefPubMedGoogle Scholar
  70. 70.
    Jensen RH, Johansen HK, Søes LM et al (2016) Posttreatment antifungal resistance among colonizing Candida isolates in candidemia patients: results from a systematic multicenter study. Antimicrob Agents Chemother. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Vallabhaneni S, Cleveland AA, Farley MM et al (2015) Epidemiology and risk factors for echinocandin nonsusceptible Candida glabrata bloodstream infections: data from a large multisite population-based candidemia surveillance program, 2008–2014. Open Forum Infect Dis. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Sinnollareddy MG, Roberts JA, Lipman J et al (2015) Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients Study. Crit Care. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Baddley JW, Patel M, Bhavnani SM et al (2008) Association of fluconazole pharmacodynamics with mortality in patients with candidemia. Antimicrob Agents Chemother 52:3022–3028. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Pfaller MA, Andes D, Diekema DJ et al (2010) Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: time for harmonization of CLSI and EUCAST broth microdilution methods. Drug Resist Updat. CrossRefPubMedGoogle Scholar
  75. 75.
    Gharibian KN, Mueller BA (2016) Fluconazole dosing predictions in critically-ill patients receiving prolonged intermittent renal replacement therapy: a Monte Carlo simulation approach. Clin Nephrol. CrossRefPubMedGoogle Scholar
  76. 76.
    Kollef MH, Morrow LE, Niederman MS et al (2006) Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Chest. CrossRefPubMedGoogle Scholar
  77. 77.
    Carlier M, Roberts JA, Stove V et al (2015) A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients. Antimicrob Agents Chemother 59:4689–4694. CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Alshukairi A, Alserehi H, El-Saed A et al (2016) A de-escalation protocol for febrile neutropenia cases and its impact on carbapenem resistance: a retrospective, quasi-experimental single-center study. J Infect Public Health. CrossRefPubMedGoogle Scholar
  79. 79.
    Kroll AL, Corrigan PA, Patel S, Hawks KG (2016) Evaluation of empiric antibiotic de-escalation in febrile neutropenia. J Oncol Pharm, PractCrossRefGoogle Scholar
  80. 80.
    Averbuch D, Orasch C, Cordonnier C, et al. (2013) European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica CrossRefGoogle Scholar
  81. 81.
    Palacios-Baena ZR, Delgado-Valverde M, Valiente Méndez A et al (2019) Impact of de-escalation on prognosis of patients with bacteremia due to Enterobacteriaceae: a post hoc analysis from a multicenter prospective cohort. Clin Infect Dis 69:956–962. CrossRefPubMedGoogle Scholar
  82. 82.
    Iankova I, Thompson-Leduc P, Kirson NY et al (2018) Efficacy and safety of procalcitonin guidance in patients with suspected or confirmed sepsis. Crit Care Med 46:691–698. CrossRefPubMedGoogle Scholar
  83. 83.
    Jensen JU, Hein L, Lundgren B et al (2011) Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med. CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Li C, Du X, Kuti JL, Nicolau DP (2007) Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections. Antimicrob Agents Chemother. CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Zelenitsky S, Rubinstein E, Ariano R et al (2013) Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock. Int J Antimicrob Agents. CrossRefPubMedGoogle Scholar
  86. 86.
    Forrest A, Nix DE, Ballow CH et al (1993) Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother. CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Roberts JA, Paul SK, Akova M et al (2014) DALI: defining antibiotic levels in intensive care unit patients: are current ß-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 58:1072–1083. CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    López-Cortés LE, Rosso-Fernández C, Núñez-Núñez M et al (2017) Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clin. BMJ Open 7:1–10. CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Intensive Care Unit, Redcliffe and Caboolture Hospitals, Faculty of MedicineUniversity of QueenslandBrisbaneAustralia
  2. 2.Infectious Diseases Division, Department of MedicineUniversity of Udine and Santa Maria Misericordia University HospitalUdineItaly
  3. 3.Division of Pulmonary and Critical Care MedicineWashington University School of MedicineSt LouisUSA
  4. 4.Hygiène Hospitalière Et Prévention du Risque Infectieux, CHU Avicenne, AP-HPBobignyFrance
  5. 5.Intensive Care Medicine DepartmentCentro Hospitalar Universitário São João, Faculty of Medicine and University of Porto, Grupo de Infecçao e SépsisPortoPortugal
  6. 6.Medical and Infectious Diseases Intensive Care UnitBichat-Claude Bernard University HospitalParisFrance
  7. 7.University of Paris, INSERM IAME, U1137, Team DesCIDParisFrance
  8. 8.University of Queensland Centre for Clinical Research, Faculty of Medicine, and Centre for Translational Anti-infective Pharmacodynamics, School of PharmacyThe University of QueenslandBrisbaneAustralia
  9. 9.Departments of Pharmacy and Intensive Care MedicineRoyal Brisbane and Women’s HospitalBrisbaneAustralia
  10. 10.Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University HospitalUniversity of MontpellierNîmesFrance
  11. 11.Department of Intensive CareRadboudumcNijmegenThe Netherlands
  12. 12.1st Department of Internal Medicine-Infectious DiseasesHygeia General HospitalAthensGreece
  13. 13.CIBERES and Vall d’Hebron Institute of ResearchBarcelonaSpain
  14. 14.Clinical Research in ICU, CHU NîmesUniversity MontpellierMontpellierFrance
  15. 15.Department of Critical Care MedicineGhent University HospitalGhentBelgium
  16. 16.Medstar Washington Hospital CenterWashington DCUSA
  17. 17.Department of Anesthesiology and Intensive Care MedicineAix Marseille Université, Assistance Publique Hôpitaux de Marseille, Hôpital NordMarseilleFrance
  18. 18.3rd Department of MedicineNational and Kapodistrian University of Athens, Medical School, Sotiria General HospitalAthensGreece
  19. 19.Intensive Care Clinical UnitHospital Universitario Virgen MacarenaSevilleSpain

Personalised recommendations