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

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.

[1]  M. Hameed,et al.  Comparison of 8 VS. 15 Days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults: A Randomized Trial , 2019 .

[2]  Matthijs S. Berends,et al.  Rapid Analysis of Diagnostic and Antimicrobial Patterns in R (RadaR): Interactive Open-Source Software App for Infection Management and Antimicrobial Stewardship , 2019, Journal of medical Internet research.

[3]  S. Cosgrove,et al.  Antibiotic Therapy for Pseudomonas aeruginosa Bloodstream Infections: How Long is Long Enough? , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  E. Mylonakis,et al.  A Systematic Review and Meta-analysis of Antibiotic Treatment Duration for Bacteremia Due to Enterobacteriaceae , 2019, Antimicrobial Agents and Chemotherapy.

[5]  M. Kollef,et al.  Rationalizing antimicrobial therapy in the ICU: a narrative review , 2019, Intensive Care Medicine.

[6]  Emmanuel O Irek,et al.  A systematic review of healthcare-associated infections in Africa: An antimicrobial resistance perspective , 2018, African journal of laboratory medicine.

[7]  M. Bassetti,et al.  Risk stratification and treatment of ICU-acquired pneumonia caused by multidrug- resistant/extensively drug-resistant/pandrug-resistant bacteria , 2018, Current opinion in critical care.

[8]  Johan Decruyenaere,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 , 2018, Critical Care.

[9]  S. Tschudin-Sutter,et al.  Combination therapy for treatment of Pseudomonas aeruginosa bloodstream infections , 2018, PloS one.

[10]  S. Beatson,et al.  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 , 2018, JAMA.

[11]  E. Mylonakis,et al.  Systematic Review and Meta-analysis of the Efficacy of Short-Course Antibiotic Treatments for Community-Acquired Pneumonia in Adults , 2018, Antimicrobial Agents and Chemotherapy.

[12]  Herman Goossens,et al.  Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: results of an internet-based global point prevalence survey. , 2018, The Lancet. Global health.

[13]  C. Mcnulty,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† , 2018, The Journal of antimicrobial chemotherapy.

[14]  F. Tubach,et al.  Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial , 2018, Intensive Care Medicine.

[15]  Kerri A. Thom,et al.  Risk Factors and Outcomes Associated with Multidrug-Resistant Acinetobacter baumannii upon Intensive Care Unit Admission , 2017, Antimicrobial Agents and Chemotherapy.

[16]  M. Hulscher,et al.  Antibiotic stewardship: does it work in hospital practice? A review of the evidence base. , 2017, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[17]  H. Goossens,et al.  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 , 2017, The Journal of antimicrobial chemotherapy.

[18]  M. Rybak,et al.  Multidrug-resistant Pseudomonas aeruginosa lower respiratory tract infections in the intensive care unit: Prevalence and risk factors. , 2017, Diagnostic microbiology and infectious disease.

[19]  R. Wunderink,et al.  International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia , 2017, European Respiratory Journal.

[20]  S. Nseir,et al.  Colonization pressure as a risk factor of ICU-acquired multidrug resistant bacteria: a prospective observational study , 2017, European Journal of Clinical Microbiology & Infectious Diseases.

[21]  B. Nathanson,et al.  Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis , 2017, BMC Infectious Diseases.

[22]  J. Fishman Infection in Organ Transplantation , 2017, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[23]  M. Ciotti,et al.  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) , 2017, BMC Microbiology.

[24]  H. Schünemann,et al.  World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update , 2017, European Respiratory Journal.

[25]  Sangeeta Mehta,et al.  Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 , 2017, Intensive Care Medicine.

[26]  S. Michie,et al.  Interventions to improve antibiotic prescribing practices for hospital inpatients. , 2017, The Cochrane database of systematic reviews.

[27]  Kai Zhou,et al.  Application of next generation sequencing in clinical microbiology and infection prevention. , 2017, Journal of biotechnology.

[28]  R. Weinstein,et al.  Antimicrobial Stewardship: How the Microbiology Laboratory Can Right the Ship , 2016, Clinical Microbiology Reviews.

[29]  C. Thomson,et al.  Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia. , 2016, Annals of the American Thoracic Society.

[30]  M. Paul,et al.  Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis. , 2016, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[31]  S. Richter,et al.  The presence of a single MALDI-TOF mass spectral peak predicts methicillin resistance in staphylococci. , 2016, Diagnostic microbiology and infectious disease.

[32]  Ying Guo,et al.  De-escalation of empiric antibiotics in patients with severe sepsis or septic shock: A meta-analysis. , 2016, Heart & lung : the journal of critical care.

[33]  D. Niven,et al.  Pyrexia: aetiology in the ICU , 2016, Critical Care.

[34]  P. Fey,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. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[35]  D. Denning,et al.  Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[36]  J. Dorca,et al.  Declining mortality among hospitalized patients with community-acquired pneumonia. , 2016, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[37]  Matthew H Samore,et al.  Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[38]  J. Timsit,et al.  A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  T. van der Poll,et al.  Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis. , 2016, JAMA.

[40]  B. Jia,et al.  Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014. , 2016, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[41]  Keith M Olsen,et al.  A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States* , 2015, Critical care medicine.

[42]  S. Micek,et al.  Inadequate Source Control and Inappropriate Antibiotics are Key Determinants of Mortality in Patients with Intra-Abdominal Sepsis and Associated Bacteremia. , 2015, Surgical infections.

[43]  James H Derzon,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 , 2015, Clinical Microbiology Reviews.

[44]  B. Iung,et al.  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). , 2015, European heart journal.

[45]  S. Crawford,et al.  Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. , 2015, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[46]  D. Ecker,et al.  Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections* , 2015, Critical care medicine.

[47]  M. Puskarich,et al.  The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-Analysis* , 2015, Critical care medicine.

[48]  S. Seo,et al.  Antimicrobial de-escalation in septic cancer patients: is it safe to back down? , 2015, Intensive Care Medicine.

[49]  D. Trapani,et al.  Antibiotic treatment strategies for community-acquired pneumonia in adults , 2015, Internal and Emergency Medicine.

[50]  Y. Golan 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 , 2015, BMC Infectious Diseases.

[51]  P. Lipsett,et al.  Trial of short-course antimicrobial therapy for intraabdominal infection. , 2015, The New England journal of medicine.

[52]  M. Antonelli,et al.  A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality , 2015, Intensive Care Medicine.

[53]  F. Tubach,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. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[54]  J. Garnacho-Montero,et al.  Antibiotic de-escalation in the ICU: how is it best done? , 2015, Current opinion in infectious diseases.

[55]  W. Boersma,et al.  Antibiotic treatment strategies for community-acquired pneumonia in adults. , 2015, The New England journal of medicine.

[56]  T. Welte,et al.  Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria , 2015, Intensive Care Medicine.

[57]  M. Dupon,et al.  Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial , 2015, The Lancet.

[58]  L. Decosterd,et al.  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. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[59]  C. Spies,et al.  Long-term effect of computer-assisted decision support for antibiotic treatment in critically ill patients: a prospective ‘before/after’ cohort study , 2014, BMJ Open.

[60]  T. Perneger,et al.  β-Lactam monotherapy vs β-lactam-macrolide combination treatment in moderately severe community-acquired pneumonia: a randomized noninferiority trial. , 2014, JAMA internal medicine.

[61]  J. Garnacho-Montero,et al.  How to treat VAP due to MDR pathogens in ICU patients , 2014, BMC Infectious Diseases.

[62]  J. D. De Waele,et al.  How to treat infections in a surgical intensive care unit , 2014, BMC Infectious Diseases.

[63]  Arjun Srinivasan,et al.  Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[64]  G. Forrest,et al.  Use of electronic health records and clinical decision support systems for antimicrobial stewardship. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[65]  Blake W Buchan,et al.  Emerging Technologies for the Clinical Microbiology Laboratory , 2014, Clinical Microbiology Reviews.

[66]  J. Chastre,et al.  Antibiotic stewardship in the intensive care unit , 2014, Critical Care.

[67]  K. Baumstarck,et al.  De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial , 2014, Intensive Care Medicine.

[68]  M. Levy,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* , 2014, Critical care medicine.

[69]  B. Gadeyne,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 , 2014, Critical Care.

[70]  Bing Li,et al.  β-Lactam/macrolide dual therapy versus β-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis. , 2014, The Journal of antimicrobial chemotherapy.

[71]  K. Mehta,et al.  Burden of antibiotic resistance in common infectious diseases: role of antibiotic combination therapy. , 2014, Journal of clinical and diagnostic research : JCDR.

[72]  James J. Cimino,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 , 2014, Journal of Clinical Microbiology.

[73]  M. P. Gómez,et al.  International Registry in Organ Donation and Transplantation--2013. , 2014, Transplantation proceedings.

[74]  J. Rello,et al.  How to approach and treat VAP in ICU patients , 2014, BMC Infectious Diseases.

[75]  M. Ison,et al.  Nosocomial infections within the first month of solid organ transplantation , 2014, Transplant infectious disease : an official journal of the Transplantation Society.

[76]  J. Knudsen,et al.  Clinical consequences of using PNA-FISH in Staphylococcal bacteraemia , 2014, European Journal of Clinical Microbiology & Infectious Diseases.

[77]  J. Marshall,et al.  Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study , 2014, Critical Care.

[78]  M. F. Parry,et al.  Successful reduction in catheter-associated urinary tract infections: focus on nurse-directed catheter removal. , 2013, American journal of infection control.

[79]  D. Livermore,et al.  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 , 2013, Haematologica.

[80]  J. Knudsen,et al.  Clinical consequences of using PNA-FISH in Staphylococcal bacteraemia , 2013, European Journal of Clinical Microbiology & Infectious Diseases.

[81]  L. Nace,et al.  Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients , 2013, Critical Care.

[82]  D. Jacobs,et al.  Evaluating the impact of a pharmacist's absence from an antimicrobial stewardship team. , 2013, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[83]  C. Destache,et al.  Does Antibiotic De-escalation for Nosocomial Pneumonia Impact Intensive Care Unit Length of Stay? , 2013 .

[84]  M. Falagas,et al.  β-Lactam plus aminoglycoside or fluoroquinolone combination versus β-lactam monotherapy for Pseudomonas aeruginosa infections: a meta-analysis. , 2013, International journal of antimicrobial agents.

[85]  A. Torres,et al.  A week seems to be weak: tailoring duration of antibiotic treatment in Gram-negative ventilator-associated pneumonia , 2013, Critical Care.

[86]  J. L. Kendall,et al.  Locally derived versus guideline-based approach to treatment of hospital-acquired pneumonia in the trauma intensive care unit. , 2012, Surgical infections.

[87]  M. Baker,et al.  Risk factors, microbiological findings and outcomes of necrotizing fasciitis in New Zealand: a retrospective chart review , 2012, BMC Infectious Diseases.

[88]  Filip De Turck,et al.  COSARA: Integrated Service Platform for Infection Surveillance and Antibiotic Management in the ICU , 2012, Journal of Medical Systems.

[89]  R. Sawyer,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. , 2012, The Lancet. Infectious diseases.

[90]  Pranita D. Tamma,et al.  Combination Therapy for Treatment of Infections with Gram-Negative Bacteria , 2012, Clinical Microbiology Reviews.

[91]  M. Büchler,et al.  Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. , 2012, JAMA.

[92]  A. Boyer,et al.  Direct testing of bronchoalveolar lavages from ventilator-associated pneumonia patients. , 2012, Diagnostic microbiology and infectious disease.

[93]  Y. Mehta,et al.  International Nosocomial Infection Control Consortium (INICC) report, data summary of 36 countries, for 2004-2009. , 2012, American journal of infection control.

[94]  Frédérique Jacobs,et al.  Antibiotic strategies in severe nosocomial sepsis: Why do we not de-escalate more often?* , 2012, Critical care medicine.

[95]  B. Latenser,et al.  Trends in 393 necrotizing acute soft tissue infection patients 2000-2008. , 2012, Burns : journal of the International Society for Burn Injuries.

[96]  R. Fowler,et al.  Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis , 2011, Critical care.

[97]  A. Armaganidis,et al.  Comparison of direct antimicrobial susceptibility testing methods for rapid analysis of bronchial secretion samples in ventilator-associated pneumonia. , 2011, International journal of antimicrobial agents.

[98]  M. Kollef,et al.  Antibiotic stewardship in the intensive care unit. , 2011, Seminars in respiratory and critical care medicine.

[99]  J. Ramirez,et al.  Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study. , 2011, The Lancet. Infectious diseases.

[100]  J. Bion,et al.  International standards for programmes of training in intensive care medicine in Europe , 2011, Intensive Care Medicine.

[101]  Eli N. Perencevich,et al.  Central Line Bundle Implementation in US Intensive Care Units and Impact on Bloodstream Infections , 2011, PloS one.

[102]  J. Morel,et al.  De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit , 2010, Critical care.

[103]  C. Spies,et al.  Computer-Assisted Decision Support for Changing Practice in Severe Sepsis and Septic Shock , 2010, The Journal of international medical research.

[104]  Anand Kumar,et al.  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 , 2010, Critical care medicine.

[105]  H. Einsele,et al.  Immune reconstitution after allogeneic transplantation and expanding options for immunomodulation: an update. , 2010, Blood.

[106]  M. Aapro,et al.  Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[107]  A. Cheng,et al.  Improved susceptibility of Gram-negative bacteria in an intensive care unit following implementation of a computerized antibiotic decision support system. , 2010, The Journal of antimicrobial chemotherapy.

[108]  M. Boermeester,et al.  A step-up approach or open necrosectomy for necrotizing pancreatitis. , 2010, The New England journal of medicine.

[109]  D. Annane,et al.  Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia , 2010, Intensive Care Medicine.

[110]  J. Bartlett,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. , 2010, Surgical infections.

[111]  Jordi Rello,et al.  International study of the prevalence and outcomes of infection in intensive care units. , 2009, JAMA.

[112]  C. A. Bond,et al.  Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections* , 2008, Critical care medicine.

[113]  G. Suh,et al.  Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia , 2008, Critical care.

[114]  Shu-Wen Lin,et al.  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 , 2008, Journal of Clinical Microbiology.

[115]  J. Fishman Infection in solid-organ transplant recipients. , 2007, The New England journal of medicine.

[116]  E. Bouza,et al.  Evaluation of direct E-test on lower respiratory tract samples: a rapid and accurate procedure for antimicrobial susceptibility testing. , 2007, Diagnostic microbiology and infectious disease.

[117]  T. Karchmer,et al.  Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia. , 2006, Chest.

[118]  K. Wood,et al.  Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock* , 2006, Critical care medicine.

[119]  Karin A Thursky,et al.  Reduction of broad-spectrum antibiotic use with computerized decision support in an intensive care unit. , 2006, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[120]  E. Coiera,et al.  Application of Information Technology: Handheld Computer-based Decision Support Reduces Patient Length of Stay and Antibiotic Prescribing in Critical Care , 2005, J. Am. Medical Informatics Assoc..

[121]  Chien-Wei Hsu,et al.  Catheter-Associated Urinary Tract Infections in Intensive Care Units Can Be Reduced by Prompting Physicians to Remove Unnecessary Catheters , 2004, Infection Control & Hospital Epidemiology.

[122]  Leonard Leibovici,et al.  β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials , 2004, BMJ : British Medical Journal.

[123]  Michel Wolff,et al.  Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. , 2003, JAMA.

[124]  S. Mulier,et al.  Factors Affecting Mortality in Generalized Postoperative Peritonitis: Multivariate Analysis in 96 Patients , 2003, World Journal of Surgery.

[125]  V L Yu,et al.  Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. , 2000, American journal of respiratory and critical care medicine.

[126]  M. Huycke,et al.  Outcomes of an antimicrobial control program in a teaching hospital. , 2000, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[127]  C. Ohmann,et al.  Risk factors associated with intraabdominal infections: a prospective multicenter study , 1999, Langenbeck's Archives of Surgery.

[128]  Robert Sitton On Europe , 1992, Current History.

[129]  R A SHOOTER,et al.  Antibiotic Therapy , 1959, Proceedings of the Royal Society of Medicine.

[130]  J. Turnidge,et al.  Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2015. , 2018, Communicable diseases intelligence.

[131]  T. Gottlieb,et al.  Australian Group on Antimicrobial Resistance (AGAR) Australian Gram-negative Sepsis Outcome Programme(GNSOP) Annual Report 2015. , 2018, Communicable diseases intelligence.

[132]  T. Gottlieb,et al.  Australian Group on Antimicrobial Resistance (AGAR) Australian Gram-negative Sepsis Outcome Programme (GNSOP) Annual Report 2016. , 2018, Communicable diseases intelligence.

[133]  R. Sawyer Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection. , 2018, The New England journal of medicine.

[134]  O. Zusman,et al.  Polymyxin monotherapy or in combination against carbapenem-resistant bacteria: systematic review and meta-analysis , 2017, The Journal of antimicrobial chemotherapy.

[135]  A. DeMaria,et al.  The Critical Role of the Staff Nurse in Antimicrobial Stewardship--Unrecognized, but Already There. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[136]  J. Waele,et al.  Reducing Antibiotic Use in the ICU: A Time-Based Approach to Rational Antimicrobial Use , 2016 .

[137]  N. Dean,et al.  Predicting risk of drug-resistant organisms in pneumonia: moving beyond the HCAP model. , 2015, Respiratory medicine.

[138]  G. Perkins,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 , 2014, Intensive Care Medicine.

[139]  E. Akl,et al.  Duration of treatment , 2014 .

[140]  J. Garnacho-Montero,et al.  De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock , 2013, Intensive Care Medicine.

[141]  J. Blache,et al.  De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study , 2013, Intensive Care Medicine.

[142]  Vimla L. Patel,et al.  Understanding the nature of information seeking behavior in critical care: Implications for the design of health information technology , 2013, Artif. Intell. Medicine.

[143]  J. Bartlett,et al.  Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[144]  Jay Steingrub,et al.  International study of the prevalence and outcomes of infection in intensive care units , 2009 .

[145]  S. Seo,et al.  A multidisciplinary approach to antimicrobial stewardship: evolution into the 21st century. , 2005, International journal of antimicrobial agents.

[146]  Ruth Richardson,et al.  A Necessary Inhumanity? , 2000, Medical humanities.

[147]  K. Sepkowitz,et al.  IDSA GUIDELINES Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America , 2022 .