Semin Respir Crit Care Med 2019; 40(04): 435-446
DOI: 10.1055/s-0039-1693995
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Practical Approach to Clinical Antibiotic Stewardship in the ICU Patient with Severe Infection

Jan Fierens
1   Department of Intensive Care, University Hospital Ghent, Ghent, Belgium
,
Pieter O. Depuydt
1   Department of Intensive Care, University Hospital Ghent, Ghent, Belgium
,
Jan J. De Waele
1   Department of Intensive Care, University Hospital Ghent, Ghent, Belgium
› Author Affiliations
Further Information

Publication History

Publication Date:
04 October 2019 (online)

Abstract

Patients with severe infections are often treated with multiple courses of antibiotics in the intensive care unit (ICU), making the ICU a true antibiotic hotspot. The increasing incidence of multidrug resistance worldwide emphasizes the need for continued efforts in developing and implementing antibiotic stewardship programs. Using a pragmatic approach for the bedside clinical team, this review will highlight different key moments for antibiotic decision making throughout the course of the antibiotic treatment in patients with severe infections. We will focus especially on the importance of adequate empirical therapy, source control in infections, assessment of immune status, and two separate antibiotic time-out moments early in the course, as well as the moment of stopping antibiotics. Additionally, the importance of a team-based approach and clinical decision support systems will be highlighted.

Financial Support and Sponsorship

Jan De Waele is Senior Clinical Investigator at the Research Foundation—Flanders (Belgium) (FWO).


 
  • References

  • 1 Vincent J-L, Rello J, Marshall J. , et al; EPIC II Group of Investigators. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302 (21) 2323-2329
  • 2 van Vught LA, Klein Klouwenberg PM, Spitoni C. , et al; MARS Consortium. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA 2016; 315 (14) 1469-1479
  • 3 Rhodes A, Evans LE, Alhazzani W. , et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med 2017; 43 (03) 304-377
  • 4 Luyt C-E, Bréchot N, Trouillet J-L, Chastre J. Antibiotic stewardship in the intensive care unit. Crit Care 2014; 18 (05) 480
  • 5 Irek EO, Amupitan AA, Obadare TO, Aboderin AO. A systematic review of healthcare-associated infections in Africa: an antimicrobial resistance perspective. Afr J Lab Med 2018; 7 (02) 796
  • 6 Bell JM, Gottlieb T, Daley DA, Coombs GW. ; Australian Group on Antimicrobial Resistance. Australian Group on Antimicrobial Resistance (AGAR) Australian Gram-negative Sepsis Outcome Programme (GNSOP) Annual Report 2015. Commun Dis Intell 2018; 42 (18) 22
  • 7 Coombs GW, Daley DA, Lee YT, Pang S, Bell JM, Turnidge JD. ; Australian Group on Antimicrobial Resistance. Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2015. Commun Dis Intell (2018) 2018; 42 (18) 16-17
  • 8 World Health Organization. Antimicrobial Resistance: Global Report on Surveillance. 1st ed. Geneva: World Health Organization; 2014
  • 9 Boucher HW, Talbot GH, Bradley JS. , et al. Bad bugs, no drugs: no ESKAPE! an update from the Infectious Diseases Society of America. Clin Infect Dis 2009; 48 (01) 1-12
  • 10 Rosenthal VD, Bijie H, Maki DG. , et al; INICC members. International Nosocomial Infection Control Consortium (INICC) report, data summary of 36 countries, for 2004-2009. Am J Infect Control 2012; 40 (05) 396-407
  • 11 Hu F-P, Guo Y, Zhu D-M. , et al. Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014. Clin Microbiol Infect 2016; 22 (Suppl. 01) S9-S14
  • 12 Timsit J-F, Bassetti M, Cremer O. , et al. Rationalizing antimicrobial therapy in the ICU: a narrative review. Intensive Care Med 2019; 45 (02) 172-189
  • 13 Arnold HM, Micek ST, Skrupky LP, Kollef MH. Antibiotic stewardship in the intensive care unit. Semin Respir Crit Care Med 2011; 32 (02) 215-227
  • 14 Kumar A, Roberts D, Wood KE. , et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34 (06) 1589-1596
  • 15 Ferrer R, Martin-Loeches I, Phillips G. , et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 2014; 42 (08) 1749-1755
  • 16 Sterling SA, Miller WR, Pryor J, Puskarich MA, Jones AE. The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis. Crit Care Med 2015; 43 (09) 1907-1915
  • 17 Depuydt PO, De Bus L, De Waele JJ. Reducing antibiotic use in the ICU: a time-based approach to rational antimicrobial use. In: Vincent J-L. , ed. Annual Update in Intensive Care and Emergency Medicine 2016. Cham: Springer International Publishing; 2016: 15-23
  • 18 Niven DJ, Laupland KB. Pyrexia: aetiology in the ICU. Crit Care 2016; 20 (01) 247
  • 19 Hranjec T, Rosenberger LH, Swenson B. , et al. Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study. Lancet Infect Dis 2012; 12 (10) 774-780
  • 20 Torres A, Niederman MS, Chastre J. , et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J 2017; 50 (03) 1700582
  • 21 Golan Y. Empiric therapy for hospital-acquired, Gram-negative complicated intra-abdominal infection and complicated urinary tract infections: a systematic literature review of current and emerging treatment options. BMC Infect Dis 2015; 15 (01) 313
  • 22 Kalil AC, Metersky ML, Klompas M. , et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63 (05) e61-e111
  • 23 Hawkey PM, Warren RE, Livermore DM. , et al. Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party. J Antimicrob Chemother 2018; 73 (03) (Suppl. 03) iii2-iii78
  • 24 Bernal NP, Latenser BA, Born JM, Liao J. Trends in 393 necrotizing acute soft tissue infection patients 2000-2008. Burns 2012; 38 (02) 252-260
  • 25 Das DK, Baker MG, Venugopal K. Risk factors, microbiological findings and outcomes of necrotizing fasciitis in New Zealand: a retrospective chart review. BMC Infect Dis 2012; 12 (01) 348
  • 26 Simonetti AF, Garcia-Vidal C, Viasus D. , et al. Declining mortality among hospitalized patients with community-acquired pneumonia. Clin Microbiol Infect 2016; 22 (06) 567.e1-567.e7
  • 27 Postma DF, van Werkhoven CH, van Elden LJR. , et al; CAP-START Study Group. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med 2015; 372 (14) 1312-1323
  • 28 Webb BJ, Dascomb K, Stenehjem E, Dean N. Predicting risk of drug-resistant organisms in pneumonia: moving beyond the HCAP model. Respir Med 2015; 109 (01) 1-10
  • 29 Zilberberg MD, Nathanson BH, Sulham K, Fan W, Shorr AF. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis. BMC Infect Dis 2017; 17 (01) 279
  • 30 Beardsley JR, Williamson JC, Johnson JW, Ohl CA, Karchmer TB, Bowton DL. Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia. Chest 2006; 130 (03) 787-793
  • 31 Becher RD, Hoth JJ, Rebo JJ, Kendall JL, Miller PR. Locally derived versus guideline-based approach to treatment of hospital-acquired pneumonia in the trauma intensive care unit. Surg Infect (Larchmt) 2012; 13 (06) 352-359
  • 32 De Bus L, Saerens L, Gadeyne B. , et al. Development of antibiotic treatment algorithms based on local ecology and respiratory surveillance cultures to restrict the use of broad-spectrum antimicrobial drugs in the treatment of hospital-acquired pneumonia in the intensive care unit: a retrospective analysis. Crit Care 2014; 18 (04) R152
  • 33 Bassetti M, Righi E, Vena A, Graziano E, Russo A, Peghin M. Risk stratification and treatment of ICU-acquired pneumonia caused by multidrug- resistant/extensively drug-resistant/pandrug-resistant bacteria. Curr Opin Crit Care 2018; 24 (05) 385-393
  • 34 Trinh TD, Zasowski EJ, Claeys KC. , et al. Multidrug-resistant Pseudomonas aeruginosa lower respiratory tract infections in the intensive care unit: prevalence and risk factors. Diagn Microbiol Infect Dis 2017; 89 (01) 61-66
  • 35 Blanco N, Harris AD, Rock C. , et al; the CDC Epicenters Program. Risk factors and outcomes associated with multidrug-resistant Acinetobacter baumannii upon intensive care unit admission. Antimicrob Agents Chemother 2017; 62 (01) e01631-17
  • 36 Masse J, Elkalioubie A, Blazejewski C. , et al. Colonization pressure as a risk factor of ICU-acquired multidrug resistant bacteria: a prospective observational study. Eur J Clin Microbiol Infect Dis 2017; 36 (05) 797-805
  • 37 Kett DH, Cano E, Quartin AA. , et al; Improving Medicine through Pathway Assessment of Critical Therapy of Hospital-Acquired Pneumonia (IMPACT-HAP) Investigators. Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study. Lancet Infect Dis 2011; 11 (03) 181-189
  • 38 Mehta KC, Dargad RR, Borade DM, Swami OC. Burden of antibiotic resistance in common infectious diseases: role of antibiotic combination therapy. J Clin Diagn Res 2014; 8 (06) ME05-ME08
  • 39 Versporten A, Zarb P, Caniaux I. , et al; Global-PPS network. Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: results of an internet-based global point prevalence survey. Lancet Glob Health 2018; 6 (06) e619-e629
  • 40 Yusuf E, Versporten A, Goossens H. Is there any difference in quality of prescribing between antibacterials and antifungals? Results from the first global point prevalence study (Global PPS) of antimicrobial consumption and resistance from 53 countries. J Antimicrob Chemother 2017; 72 (10) 2906-2909
  • 41 Zusman O, Altunin S, Koppel F, Dishon Benattar Y, Gedik H, Paul M. Polymyxin monotherapy or in combination against carbapenem-resistant bacteria: systematic review and meta-analysis. J Antimicrob Chemother 2017; 72 (01) 29-39
  • 42 Tschudin-Sutter S, Fosse N, Frei R, Widmer AF. Combination therapy for treatment of Pseudomonas aeruginosa bloodstream infections. PLoS One 2018; 13 (09) e0203295
  • 43 Brunkhorst FM, Oppert M, Marx G. , et al; German Study Group Competence Network Sepsis (SepNet). Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA 2012; 307 (22) 2390-2399
  • 44 Garin N, Genné D, Carballo S. , et al. β-Lactam monotherapy vs β-lactam-macrolide combination treatment in moderately severe community-acquired pneumonia: a randomized noninferiority trial. JAMA Intern Med 2014; 174 (12) 1894-1901
  • 45 Tamma PD, Cosgrove SE, Maragakis LL. Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev 2012; 25 (03) 450-470
  • 46 Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L. β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 2004; 328 (7441): 668
  • 47 Vardakas KZ, Tansarli GS, Bliziotis IA, Falagas ME. β-Lactam plus aminoglycoside or fluoroquinolone combination versus β-lactam monotherapy for Pseudomonas aeruginosa infections: a meta-analysis. Int J Antimicrob Agents 2013; 41 (04) 301-310
  • 48 Martin-Loeches I, Lisboa T, Rodriguez A. , et al. Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia. Intensive Care Med 2010; 36 (04) 612-620
  • 49 Kumar A, Safdar N, Kethireddy S, Chateau D. 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 2010; 38 (08) 1651-1664
  • 50 Falzon D, Schünemann HJ, Harausz E. , et al. World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update. Eur Respir J 2017; 49 (03) 1602308
  • 51 Habib G, Lancellotti P, Antunes MJ. , et al; ESC Scientific Document Group. 2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015; 36 (44) 3075-3128
  • 52 Nie W, Li B, Xiu Q. β-Lactam/macrolide dual therapy versus β-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis. J Antimicrob Chemother 2014; 69 (06) 1441-1446
  • 53 Majhail NS, Farnia SH, Carpenter PA. , et al. Indications for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2015; 21 (11) 1863-1869
  • 54 Gómez MP, Pérez B, Manyalich M. International Registry in Organ Donation and Transplantation--2013. Transplant Proc 2014; 46 (04) 1044-1048
  • 55 Fishman JA. Infection in organ transplantation. Am J Transplant 2017; 17 (04) 856-879
  • 56 Dorschner P, McElroy LM, Ison MG. Nosocomial infections within the first month of solid organ transplantation. Transpl Infect Dis 2014; 16 (02) 171-187
  • 57 Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357 (25) 2601-2614
  • 58 Seggewiss R, Einsele H. Immune reconstitution after allogeneic transplantation and expanding options for immunomodulation: an update. Blood 2010; 115 (19) 3861-3868
  • 59 Averbuch D, Orasch C, Cordonnier C. , et al; ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. 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 2013; 98 (12) 1826-1835
  • 60 Freifeld AG, Bow EJ, Sepkowitz KA. , et al; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52 (04) e56-e93
  • 61 Patterson TF, Thompson III GR, Denning DW. , et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63 (04) e1-e60
  • 62 Klastersky J, de Naurois J, Rolston K. , et al; ESMO Guidelines Committee. Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol 2016; 27 (05) (Suppl. 05) v111-v118
  • 63 De Waele J, De Bus L. How to treat infections in a surgical intensive care unit. BMC Infect Dis 2014; 14 (01) 193
  • 64 Mulier S, Penninckx F, Verwaest C. , et al. Factors affecting mortality in generalized postoperative peritonitis: multivariate analysis in 96 patients. World J Surg 2003; 27 (04) 379-384
  • 65 Tellor B, Skrupky LP, Symons W, High E, Micek ST, Mazuski JE. Inadequate source control and inappropriate antibiotics are key determinants of mortality in patients with intra-abdominal sepsis and associated bacteremia. Surg Infect (Larchmt) 2015; 16 (06) 785-793
  • 66 Bassetti M, Righi E, Ansaldi F. , et al. A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality. Intensive Care Med 2015; 41 (09) 1601-1610
  • 67 Wacha H, Hau T, Dittmer R, Ohmann C. ; Peritonitis Study Group. Risk factors associated with intraabdominal infections: a prospective multicenter study. Langenbecks Arch Surg 1999; 384 (01) 24-32
  • 68 Bloos F, Thomas-Rüddel D, Rüddel H. , et al; MEDUSA Study Group. Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study. Crit Care 2014; 18 (02) R42
  • 69 van Santvoort HC, Besselink MG, Bakker OJ. , et al; Dutch Pancreatitis Study Group. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med 2010; 362 (16) 1491-1502
  • 70 Sawyer RG, Claridge JA, Nathens AB. , et al; STOP-IT Trial Investigators. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med 2015; 372 (21) 1996-2005
  • 71 Solomkin JS, Mazuski JE, Bradley JS. , et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt) 2010; 11 (01) 79-109
  • 72 Pollack LA, Srinivasan A. Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis 2014; 59 (03) (Suppl. 03) S97-S100
  • 73 Borgatta B, Rello J. How to approach and treat VAP in ICU patients. BMC Infect Dis 2014; 14: 211
  • 74 Garnacho-Montero J, Corcia-Palomo Y, Amaya-Villar R, Martin-Villen L. How to treat VAP due to MDR pathogens in ICU patients. BMC Infect Dis 2014; 14 (01) 135
  • 75 Cercenado E, Cercenado S, Marín M, Rico M-V, Vicente T, Bouza E. Evaluation of direct E-test on lower respiratory tract samples: a rapid and accurate procedure for antimicrobial susceptibility testing. Diagn Microbiol Infect Dis 2007; 58 (02) 211-216
  • 76 Kontopidou F, Galani I, Panagea T. , et al. Comparison of direct antimicrobial susceptibility testing methods for rapid analysis of bronchial secretion samples in ventilator-associated pneumonia. Int J Antimicrob Agents 2011; 38 (02) 130-134
  • 77 Boyer A, Medrano J, Mzali F. , et al. Direct testing of bronchoalveolar lavages from ventilator-associated pneumonia patients. Diagn Microbiol Infect Dis 2012; 73 (02) 107-110
  • 78 Le Dorze M, Gault N, Foucrier A. , et al. 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 2015; 21 (05) 468.e1-468.e6
  • 79 Dark P, Blackwood B, Gates S. , et al. Accuracy of LightCycler(®) SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review and meta-analysis. Intensive Care Med 2015; 41 (01) 21-33
  • 80 Vincent J-L, Brealey D, Libert N. , et al; Rapid Diagnosis of Infections in the Critically Ill Team. Rapid diagnosis of infection in the critically ill, a multicenter study of molecular detection in bloodstream infections, pneumonia, and sterile site infections. Crit Care Med 2015; 43 (11) 2283-2291
  • 81 Vogne C, Prod'hom G, Jaton K, Decosterd LA, Greub G. A simple, robust and rapid approach to detect carbapenemases in Gram-negative isolates by MALDI-TOF mass spectrometry: validation with triple quadripole tandem mass spectrometry, microarray and PCR. Clin Microbiol Infect 2014; 20 (12) O1106-O1112
  • 82 Rhoads DD, Wang H, Karichu J, Richter SS. The presence of a single MALDI-TOF mass spectral peak predicts methicillin resistance in staphylococci. Diagn Microbiol Infect Dis 2016; 86 (03) 257-261
  • 83 Sakarikou C, Ciotti M, Dolfa C, Angeletti S, Favalli C. Rapid detection of carbapenemase-producing Klebsiella pneumoniae strains derived from blood cultures by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). BMC Microbiol 2017; 17 (01) 54
  • 84 Lau AF, Wang H, Weingarten RA. , et al. A rapid matrix-assisted laser desorption ionization-time of flight mass spectrometry-based method for single-plasmid tracking in an outbreak of carbapenem-resistant Enterobacteriaceae. J Clin Microbiol 2014; 52 (08) 2804-2812
  • 85 Buchan BW, Ledeboer NA. Emerging technologies for the clinical microbiology laboratory. Clin Microbiol Rev 2014; 27 (04) 783-822
  • 86 Deurenberg RH, Bathoorn E, Chlebowicz MA. , et al. Application of next generation sequencing in clinical microbiology and infection prevention. J Biotechnol 2017; 243: 16-24
  • 87 Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000; 162 (2, Pt 1): 505-511
  • 88 Tabah A, Cotta MO, Garnacho-Montero J. , et al. A systematic review of the definitions, determinants, and clinical outcomes of antimicrobial de-escalation in the intensive care unit. Clin Infect Dis 2016; 62 (08) 1009-1017
  • 89 Bassetti M, De Waele JJ, Eggimann P. , et al. Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Intensive Care Med 2015; 41 (05) 776-795
  • 90 Harris PNA, Tambyah PA, Lye DC. , et al; MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN). Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: a randomized clinical trial. JAMA 2018; 320 (10) 984-994
  • 91 Morel J, Casoetto J, Jospé R. , et al. De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit. Crit Care 2010; 14 (06) R225
  • 92 Heenen S, Jacobs F, Vincent J-L. Antibiotic strategies in severe nosocomial sepsis: why do we not de-escalate more often?. Crit Care Med 2012; 40 (05) 1404-1409
  • 93 Garnacho-Montero J, Gutiérrez-Pizarraya A, Escoresca-Ortega A. , et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med 2014; 40 (01) 32-40
  • 94 Gonzalez L, Cravoisy A, Barraud D. , et al. Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients. Crit Care 2013; 17 (04) R140
  • 95 Garnacho-Montero J, Escoresca-Ortega A, Fernández-Delgado E. Antibiotic de-escalation in the ICU: how is it best done?. Curr Opin Infect Dis 2015; 28 (02) 193-198
  • 96 Guo Y, Gao W, Yang H, Ma C, Sui S. De-escalation of empiric antibiotics in patients with severe sepsis or septic shock: a meta-analysis. Heart Lung 2016; 45 (05) 454-459
  • 97 Joung MK, Lee JA, Moon SY. , et al. Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia. Crit Care 2011; 15 (02) R79
  • 98 Paskovaty A, Pastores SM, Gedrimaite Z, Kostelecky N, Riedel ER, Seo SK. Antimicrobial de-escalation in septic cancer patients: is it safe to back down?. Intensive Care Med 2015; 41 (11) 2022-2023
  • 99 Knaak E, Cavalieri SJ, Elsasser GN, Preheim LC, Gonitzke A, Destache CJ. Does antibiotic de-escalation for nosocomial pneumonia impact intensive care unit length of stay?. Infect Dis Clin Pract 2013; 21 (03) 172-176
  • 100 Paul M, Dickstein Y, Raz-Pasteur A. Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis. Clin Microbiol Infect 2016; 22 (12) 960-967
  • 101 Mokart D, Slehofer G, Lambert J. , et al. De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. Intensive Care Med 2014; 40 (01) 41-49
  • 102 Leone M, Bechis C, Baumstarck K. , et al; AZUREA Network Investigators. De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med 2014; 40 (10) 1399-1408
  • 103 Kritsotakis EI, Tsioutis C, Roumbelaki M, Christidou A, Gikas A. Antibiotic use and the risk of carbapenem-resistant extended-spectrum-β-lactamase-producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case-control study. J Antimicrob Chemother 2011; 66 (06) 1383-1391
  • 104 Tansarli GS, Andreatos N, Pliakos EE, Mylonakis E. A systematic review and meta-analysis of antibiotic treatment duration for bacteremia due to Enterobacteriaceae . Antimicrob Agents Chemother 2019; 63 (05) e02495-18
  • 105 Havey TC, Fowler RA, Daneman N. Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis. Crit Care 2011; 15 (06) R267
  • 106 Martin-Loeches I, Torres A. A week seems to be weak: tailoring duration of antibiotic treatment in Gram-negative ventilator-associated pneumonia. Crit Care 2013; 17 (01) 106
  • 107 Thomas Z, Bandali F, Sankaranarayanan J, Reardon T, Olsen KM. ; Critical Care Pharmacotherapy Trials Network. A multicenter evaluation of prolonged empiric antibiotic therapy in adult ICUs in the United States. Crit Care Med 2015; 43 (12) 2527-2534
  • 108 Chastre J, Wolff M, Fagon J-Y. , et al; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290 (19) 2588-2598
  • 109 Montravers P, Tubach F, Lescot T. , et al; DURAPOP Trial Group. Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial. Intensive Care Med 2018; 44 (03) 300-310
  • 110 Tansarli GS, Mylonakis E. Systematic review and meta-analysis of the efficacy of short-course antibiotic treatments for community-acquired pneumonia in adults. Antimicrob Agents Chemother 2018; 62 (09) e00635-18
  • 111 Fabre V, Amoah J, Cosgrove SE, Tamma PD. Antibiotic therapy for Pseudomonas aeruginosa bloodstream infections: how long is long enough?. Clin Infect Dis 2019; 18: ciz223
  • 112 Bernard L, Dinh A, Ghout I. , et al; Duration of Treatment for Spondylodiscitis (DTS) study group. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial. Lancet 2015; 385 (9971): 875-882
  • 113 Barlam TF, Cosgrove SE, Abbo LM. , et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016; 62 (10) e51-e77
  • 114 CoBaTrICE Collaboration. International standards for programmes of training in intensive care medicine in Europe. Intensive Care Med 2011; 37 (03) 385-393
  • 115 Laub RR, Knudsen JD. Clinical consequences of using PNA-FISH in Staphylococcal bacteraemia. Eur J Clin Microbiol Infect Dis 2014; 33 (04) 599-601
  • 116 Morency-Potvin P, Schwartz DN, Weinstein RA. Antimicrobial stewardship: how the microbiology laboratory can right the ship. Clin Microbiol Rev 2016; 30 (01) 381-407
  • 117 Buehler SS, Madison B, Snyder SR. , et al. Effectiveness of practices to increase timeliness of providing targeted therapy for inpatients with bloodstream infections: a laboratory medicine best practices systematic review and meta-analysis. Clin Microbiol Rev 2016; 29 (01) 59-103
  • 118 Carver PL, Lin S-W, DePestel DD, Newton DW. Impact of mecA gene testing and intervention by infectious disease clinical pharmacists on time to optimal antimicrobial therapy for Staphylococcus aureus bacteremia at a University Hospital. J Clin Microbiol 2008; 46 (07) 2381-2383
  • 119 Gentry CA, Greenfield RA, Slater LN, Wack M, Huycke MM. Outcomes of an antimicrobial control program in a teaching hospital. Am J Health Syst Pharm 2000; 57 (03) 268-274
  • 120 Cappelletty D, Jacobs D. Evaluating the impact of a pharmacist's absence from an antimicrobial stewardship team. Am J Health Syst Pharm 2013; 70 (12) 1065-1069
  • 121 MacLaren R, Bond CA, Martin SJ, Fike D. Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections. Crit Care Med 2008; 36 (12) 3184-3189
  • 122 Olans RN, Olans RD, DeMaria Jr A. The critical role of the staff nurse in antimicrobial stewardship--unrecognized, but already there. Clin Infect Dis 2016; 62 (01) 84-89
  • 123 Furuya EY, Dick A, Perencevich EN, Pogorzelska M, Goldmann D, Stone PW. Central line bundle implementation in US intensive care units and impact on bloodstream infections. PLoS One 2011; 6 (01) e15452
  • 124 Huang W-C, Wann S-R, Lin S-L. , et al. Catheter-associated urinary tract infections in intensive care units can be reduced by prompting physicians to remove unnecessary catheters. Infect Control Hosp Epidemiol 2004; 25 (11) 974-978
  • 125 Parry MF, Grant B, Sestovic M. Successful reduction in catheter-associated urinary tract infections: focus on nurse-directed catheter removal. Am J Infect Control 2013; 41 (12) 1178-1181
  • 126 Paskovaty A, Pflomm JM, Myke N, Seo SK. A multidisciplinary approach to antimicrobial stewardship: evolution into the 21st century. Int J Antimicrob Agents 2005; 25 (01) 1-10
  • 127 Hulscher MEJL, Prins JM. Antibiotic stewardship: does it work in hospital practice? A review of the evidence base. Clin Microbiol Infect 2017; 23 (11) 799-805
  • 128 Kannampallil TG, Franklin A, Mishra R, Almoosa KF, Cohen T, Patel VL. Understanding the nature of information seeking behavior in critical care: implications for the design of health information technology. Artif Intell Med 2013; 57 (01) 21-29
  • 129 Davey P, Marwick CA, Scott CL. , et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2017; 2 (02) CD003543
  • 130 Grol R. Personal paper. Beliefs and evidence in changing clinical practice. BMJ 1997; 315 (7105): 418-421
  • 131 Luz C, Berends M, Dik J-W. , et al. Rapid analysis of diagnostic and antimicrobial patterns in R (RadaR): interactive open-source software app for infection management and antimicrobial stewardship. J Med Internet Res 2019; 21 (06) 12843
  • 132 Steurbaut K, Colpaert K, Gadeyne B. , et al. COSARA: integrated service platform for infection surveillance and antibiotic management in the ICU. J Med Syst 2012; 36 (06) 3765-3775
  • 133 Forrest GN, Van Schooneveld TC, Kullar R, Schulz LT, Duong P, Postelnick M. Use of electronic health records and clinical decision support systems for antimicrobial stewardship. Clin Infect Dis 2014; 59 (03) (Suppl. 03) S122-S133
  • 134 De Bus L, Gadeyne B, Steen J. , et al. A complete and multifaceted overview of antibiotic use and infection diagnosis in the intensive care unit: results from a prospective four-year registration. Crit Care 2018; 22 (01) 241
  • 135 Sintchenko V, Iredell JR, Gilbert GL, Coiera E. Handheld computer-based decision support reduces patient length of stay and antibiotic prescribing in critical care. J Am Med Inform Assoc 2005; 12 (04) 398-402
  • 136 Thursky KA, Buising KL, Bak N. , et al. Reduction of broad-spectrum antibiotic use with computerized decision support in an intensive care unit. Int J Qual Health Care 2006; 18 (03) 224-231
  • 137 Tafelski S, Nachtigall I, Deja M. , et al. Computer-assisted decision support for changing practice in severe sepsis and septic shock. J Int Med Res 2010; 38 (05) 1605-1616
  • 138 Yong MK, Buising KL, Cheng AC, Thursky KA. Improved susceptibility of Gram-negative bacteria in an intensive care unit following implementation of a computerized antibiotic decision support system. J Antimicrob Chemother 2010; 65 (05) 1062-1069
  • 139 Nachtigall I, Tafelski S, Deja M. , et al. Long-term effect of computer-assisted decision support for antibiotic treatment in critically ill patients: a prospective ‘before/after’ cohort study. BMJ Open 2014; 4 (12) e005370