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Semin Respir Crit Care Med 2021; 42(05): 689-697
DOI: 10.1055/s-0041-1733987
Review Article

How Antibiotics Stewardship Can Be Safely Implemented in Patients with Septic Shock?

Etienne de Montmollin
1   Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat Claude Bernard University Hospital, Paris, France
2   INSERM IAME UMR 1137, University of Paris, Sorbonne Paris Cite, Paris, France
,
Jean-François Timsit
1   Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat Claude Bernard University Hospital, Paris, France
2   INSERM IAME UMR 1137, University of Paris, Sorbonne Paris Cite, Paris, France
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Abstract

In critically ill patients with sepsis and septic shock, the need for prompt and adequate antibiotic therapy is balanced by the risk of excessive antibiotic exposure that leads to emergence of multidrug-resistant pathogens. As such, antibiotic stewardship programs propose a set of operating rules from antibiotic treatment initiation to de-escalation and finally cessation. In this review, we will describe the rationale for early antibiotic treatment in septic patients, how to optimize initial antibiotic treatment, rules for early treatment discontinuation in pathogen-negative sepsis, and optimal duration of antimicrobial therapy.

Keywords

septic shock - sepsis - antimicrobials - pharmacokinetics - antimicrobial stewardship


Publikationsverlauf

Artikel online veröffentlicht:
20. September 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 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
    CrossrefPubMedGoogle Scholar
  • 2 Dellinger RP, Levy MM, Rhodes A. et al; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013; 39 (02) 165-228
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Seymour CW, Gesten F, Prescott HC. et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017; 376 (23) 2235-2244
    CrossrefPubMedGoogle Scholar
  • 5 Levy MM, Dellinger RP, Townsend SR. et al; Surviving Sepsis Campaign. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010; 38 (02) 367-374
    CrossrefPubMedGoogle Scholar
  • 6 Puskarich MA, Trzeciak S, Shapiro NI. et al; Emergency Medicine Shock Research Network (EMSHOCKNET). Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med 2011; 39 (09) 2066-2071
    CrossrefPubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 IDSA Sepsis Task Force. Infectious Diseases Society of America (IDSA) POSITION STATEMENT: why IDSA did not endorse the surviving sepsis campaign guidelines. Clin Infect Dis 2018; 66 (10) 1631-1635
    CrossrefPubMedGoogle Scholar
  • 10 Heffner AC, Horton JM, Marchick MR, Jones AE. Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department. Clin Infect Dis 2010; 50 (06) 814-820
    CrossrefPubMedGoogle Scholar
  • 11 Klein Klouwenberg PMC, Cremer OL, van Vught LA. et al. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care 2015; 19: 319
    CrossrefPubMedGoogle Scholar
  • 12 Turnbull IR, Javadi P, Buchman TG, Hotchkiss RS, Karl IE, Coopersmith CM. Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels. Shock 2004; 21 (02) 121-125
    CrossrefPubMedGoogle Scholar
  • 13 Kumar A, Haery C, Paladugu B. et al. The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels. J Infect Dis 2006; 193 (02) 251-258
    CrossrefPubMedGoogle Scholar
  • 14 Bloos F, Rüddel H, Thomas-Rüddel D. et al; MEDUSA study group. Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial. Intensive Care Med 2017; 43 (11) 1602-1612
    CrossrefPubMedGoogle Scholar
  • 15 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
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 Amaral ACKB, Holder MW. Timing of antimicrobial therapy after identification of ventilator-associated condition is not associated with mortality in patients with ventilator-associated pneumonia: a cohort study. PLoS One 2014; 9 (05) e97575
    CrossrefPubMedGoogle Scholar
  • 18 van Vught LA, Klein Klouwenberg PMC, 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
    CrossrefPubMedGoogle Scholar
  • 19 Bretonnière C, Leone M, Milési C. et al; Société de Réanimation de Langue Française (SRLF), Société Française d'Anesthésie et de Réanimation (SFAR). Strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric). Intensive Care Med 2015; 41 (07) 1181-1196
    CrossrefPubMedGoogle Scholar
  • 20 Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev 2014; (01) CD003344
    PubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Ripa M, Rodríguez-Núñez O, Cardozo C. et al. Influence of empirical double-active combination antimicrobial therapy compared with active monotherapy on mortality in patients with septic shock: a propensity score-adjusted and matched analysis. J Antimicrob Chemother 2017; 72 (12) 3443-3452
    CrossrefPubMedGoogle Scholar
  • 23 Roberts JA, Taccone FS, Lipman J. Understanding PK/PD. Intensive Care Med 2016; 42 (11) 1797-1800
    CrossrefPubMedGoogle Scholar
  • 24 Roberts JA, Abdul-Aziz MH, Lipman J. et al; International Society of Anti-Infective Pharmacology and the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014; 14 (06) 498-509
    CrossrefPubMedGoogle Scholar
  • 25 Pea F, Viale P, Furlanut M. Antimicrobial therapy in critically ill patients: a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability. Clin Pharmacokinet 2005; 44 (10) 1009-1034
    CrossrefPubMedGoogle Scholar
  • 26 Ulldemolins M, Roberts JA, Rello J, Paterson DL, Lipman J. The effects of hypoalbuminaemia on optimizing antibacterial dosing in critically ill patients. Clin Pharmacokinet 2011; 50 (02) 99-110
    CrossrefPubMedGoogle Scholar
  • 27 Roberts JA, Paul SK, Akova M. et al; DALI Study. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients?. Clin Infect Dis 2014; 58 (08) 1072-1083
    CrossrefPubMedGoogle Scholar
  • 28 de Montmollin E, Bouadma L, Gault N. et al. Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen. Intensive Care Med 2014; 40 (07) 998-1005
    CrossrefPubMedGoogle Scholar
  • 29 Meng L, Mui E, Holubar MK, Deresinski SC. Comprehensive guidance for antibiotic dosing in obese adults. Pharmacotherapy 2017; 37 (11) 1415-1431
    CrossrefPubMedGoogle Scholar
  • 30 Jung B, Mahul M, Breilh D. et al. Repeated piperacillin-tazobactam plasma concentration measurements in severely obese versus nonobese critically ill septic patients and the risk of under- and overdosing. Crit Care Med 2017; 45 (05) e470-e478
    CrossrefPubMedGoogle Scholar
  • 31 Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 2010; 49 (02) 71-87
    CrossrefPubMedGoogle Scholar
  • 32 Shekar K, Fraser JF, Smith MT, Roberts JA. Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation. J Crit Care 2012; 27 (06) 741.e9-741.e18
    CrossrefPubMedGoogle Scholar
  • 33 Leisman D, Huang V, Zhou Q. et al. Delayed second dose antibiotics for patients admitted from the emergency department with sepsis: prevalence, risk factors, and outcomes. Crit Care Med 2017; 45 (06) 956-965
    CrossrefPubMedGoogle Scholar
  • 34 Vardakas KZ, Voulgaris GL, Maliaros A, Samonis G, Falagas ME. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis 2018; 18 (01) 108-120
    CrossrefPubMedGoogle Scholar
  • 35 Taccone FS, Laupland KB, Montravers P. Continuous infusion of β-lactam antibiotics for all critically ill patients?. Intensive Care Med 2016; 42 (10) 1604-1606
    CrossrefPubMedGoogle Scholar
  • 36 Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillo N. Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. J Antimicrob Chemother 2012; 67 (01) 17-24
    CrossrefPubMedGoogle Scholar
  • 37 Ambrose PG, Bhavnani SM, Rubino CM. et al. Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it's not just for mice anymore. Clin Infect Dis 2007; 44 (01) 79-86
    CrossrefPubMedGoogle Scholar
  • 38 Abdul-Aziz MH, Alffenaar JC, Bassetti M. et al; Infection Section of European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Group of International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), Infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy (ISAC). Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper. Intensive Care Med 2020; 46 (06) 1127-1153
    CrossrefPubMedGoogle Scholar
  • 39 Gupta S, Sakhuja A, Kumar G, McGrath E, Nanchal RS, Kashani KB. Culture-negative severe sepsis: nationwide trends and outcomes. Chest 2016; 150 (06) 1251-1259
    CrossrefPubMedGoogle Scholar
  • 40 De Bus L, Depuydt P, Steen J. et al; DIANA study group. Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study. Intensive Care Med 2020; 46 (07) 1404-1417
    CrossrefPubMedGoogle Scholar
  • 41 Salahuddin N, Amer L, Joseph M, El Hazmi A, Hawa H, Maghrabi K. Determinants of deescalation failure in critically ill patients with sepsis: a prospective cohort study. Crit Care Res Pract 2016; 2016: 6794861
    PubMedGoogle Scholar
  • 42 Al-Qahtani SM, Baffoe-Bonnie H, El-Saed A. et al. Appropriateness of antimicrobial use among septic patients managed by the critical care response team: an opportunity for improvement through de-escalation. Antimicrob Resist Infect Control 2019; 8: 186
    CrossrefPubMedGoogle Scholar
  • 43 Lockhart GC, Hanin J, Micek ST, Kollef MH. Pathogen-negative sepsis-an opportunity for antimicrobial stewardship. Open Forum Infect Dis 2019; 6 (10) ofz397
    CrossrefPubMedGoogle Scholar
  • 44 Tabah A, Bassetti M, Kollef MH. et al. 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). Intensive Care Med 2020; 46 (02) 245-265
    CrossrefPubMedGoogle Scholar
  • 45 Cheng MP, Stenstrom R, Paquette K. et al; FABLED Investigators. Blood culture results before and after antimicrobial administration in patients with severe manifestations of sepsis: a diagnostic study. Ann Intern Med 2019; 171 (08) 547-554
    CrossrefPubMedGoogle Scholar
  • 46 Timsit J-F, Ruppé E, Barbier F, Tabah A, Bassetti M. Bloodstream infections in critically ill patients: an expert statement. Intensive Care Med 2020; 46 (02) 266-284
    CrossrefPubMedGoogle Scholar
  • 47 Sinha M, Jupe J, Mack H, Coleman TP, Lawrence SM, Fraley SI. Emerging technologies for molecular diagnosis of sepsis. Clin Microbiol Rev 2018; 31 (02) e00089-e17
    CrossrefPubMedGoogle Scholar
  • 48 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
    CrossrefPubMedGoogle Scholar
  • 49 Teshome BF, Vouri SM, Hampton N, Kollef MH, Micek ST. Duration of exposure to antipseudomonal β-lactam antibiotics in the critically ill and development of new resistance. Pharmacotherapy 2019; 39 (03) 261-270
    CrossrefPubMedGoogle Scholar
  • 50 Capellier G, Mockly H, Charpentier C. et al. Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment. PLoS One 2012; 7 (08) e41290
    CrossrefPubMedGoogle Scholar
  • 51 Dimopoulos G, Poulakou G, Pneumatikos IA, Armaganidis A, Kollef MH, Matthaiou DK. Short- vs long-duration antibiotic regimens for ventilator-associated pneumonia: a systematic review and meta-analysis. Chest 2013; 144 (06) 1759-1767
    CrossrefPubMedGoogle Scholar
  • 52 Pugh R, Grant C, Cooke RPD, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev 2015; (08) CD007577
    PubMedGoogle Scholar
  • 53 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
    CrossrefPubMedGoogle Scholar
  • 54 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
    CrossrefPubMedGoogle Scholar
  • 55 Stolz D, Papakonstantinou E, Grize L. et al. Time-course of upper respiratory tract viral infection and COPD exacerbation. Eur Respir J 2019; 54 (04) 1900407
    CrossrefPubMedGoogle Scholar
  • 56 Planquette B, Timsit J-F, Misset BY. et al; OUTCOMEREA Study Group. Pseudomonas aeruginosa ventilator-associated pneumonia. predictive factors of treatment failure. Am J Respir Crit Care Med 2013; 188 (01) 69-76
    CrossrefPubMedGoogle Scholar
  • 57 Bouadma L, Luyt C-E, Tubach F. et al; PRORATA trial group. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375 (9713): 463-474
    CrossrefPubMedGoogle Scholar
  • 58 Beye F, Vigneron C, Dargent A. et al. Adhering to the procalcitonin algorithm allows antibiotic therapy to be shortened in patients with ventilator-associated pneumonia. J Crit Care 2019; 53: 125-131
    CrossrefPubMedGoogle Scholar
  • 59 Kyriazopoulou E, Liaskou-Antoniou L, Adamis G. et al. Procalcitonin to reduce long-term infection-associated adverse events in sepsis. a randomized trial. Am J Respir Crit Care Med 2021; 203 (02) 202-210
    CrossrefPubMedGoogle Scholar
  • 60 Regimbeau JM, Fuks D, Pautrat K. et al; FRENCH Study Group. Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis: a randomized clinical trial. JAMA 2014; 312 (02) 145-154
    CrossrefPubMedGoogle Scholar
  • 61 Hussain MI, Alam MK, Al-Qahatani HH, Al-Akeely MH. Role of postoperative antibiotics after appendectomy in non-perforated appendicitis. J Coll Physicians Surg Pak 2012; 22 (12) 756-759
    PubMedGoogle Scholar
  • 62 Miura F, Okamoto K, Takada T. et al. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci 2018; 25 (01) 31-40
    CrossrefPubMedGoogle Scholar
  • 63 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
    CrossrefPubMedGoogle Scholar
  • 64 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
    CrossrefPubMedGoogle Scholar
  • 65 Daneman N, Rishu AH, Xiong W. et al; Canadian Critical Care Trials Group. Duration of antimicrobial treatment for bacteremia in Canadian critically ill patients. Crit Care Med 2016; 44 (02) 256-264
    CrossrefPubMedGoogle Scholar
  • 66 Yahav D, Franceschini E, Koppel F. et al; Bacteremia Duration Study Group. Seven versus 14 days of antibiotic therapy for uncomplicated gram-negative bacteremia: a noninferiority randomized controlled trial. Clin Infect Dis 2019; 69 (07) 1091-1098
    CrossrefPubMedGoogle Scholar
  • 67 Sartelli M, Labricciosa FM, Barbadoro P. et al. The Global Alliance for Infections in Surgery: defining a model for antimicrobial stewardship-results from an international cross-sectional survey. World J Emerg Surg 2017; 12: 34
    CrossrefPubMedGoogle Scholar
  • 68 Buetti N, Timsit J-F. Management and prevention of central venous catheter-related infections in the ICU. Semin Respir Crit Care Med 2019; 40 (04) 508-523
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 69 Fabre V, Amoah J, Cosgrove SE, Tamma PD. Antibiotic therapy for pseudomonas aeruginosa bloodstream infections: how long is long enough?. Clin Infect Dis 2019; 69 (11) 2011-2014
    CrossrefPubMedGoogle Scholar
  • 70 Doi Y. Treatment options for carbapenem-resistant gram-negative bacterial infections. Clin Infect Dis 2019; 69 (Suppl. 07) S565-S575
    CrossrefPubMedGoogle Scholar
  • 71 von Dach E, Albrich WC, Brunel A-S. et al. Effect of C-reactive protein-guided antibiotic treatment duration, 7-day treatment, or 14-day treatment on 30-day clinical failure rate in patients with uncomplicated gram-negative bacteremia: a randomized clinical trial. JAMA 2020; 323 (21) 2160-2169
    CrossrefPubMedGoogle Scholar
  • 72 Stolz D, Smyrnios N, Eggimann P. et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J 2009; 34 (06) 1364-1375
    CrossrefPubMedGoogle Scholar
  • 73 Le Fevre L, Timsit J-F. Duration of antimicrobial therapy for Gram-negative infections. Curr Opin Infect Dis 2020; 33 (06) 511-516
    CrossrefPubMedGoogle Scholar