POINT: Should Broad-Spectrum Antibiotics Be Routinely Administered to All Patients With Sepsis as Soon as Possible? Yes

      Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
      • Singer M.
      • Deutschman C.S.
      • Seymour C.W.
      • et al.
      The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
      It affects millions of people worldwide annually, with a mortality ranging from 25% to 50%.
      • Casserly B.
      • Phillips G.S.
      • Schorr C.
      • et al.
      Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database.
      Significant improvements in patient outcomes have resulted from early identification and appropriate management in the initial hours following development of sepsis. Evidence-based guidelines currently recommend empiric broad-spectrum antibiotics with one or more antimicrobial agents within 1 h for patients with sepsis or septic shock, a strong recommendation with moderate quality of evidence.
      • Rhodes A.
      • Evans L.E.
      • Alhazzani W.
      • et al.
      Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
      However, some have voiced concern that this approach may cause indiscriminate administration of antibiotics, leading to unintended short- and long-term consequences. Despite these concerns, we believe that broad-spectrum antibiotics should be administered as soon as possible to all patients with sepsis and septic shock because withholding appropriate antibiotics is associated with a significant increase in mortality. The benefits of early and appropriate antibiotic administration clearly outweigh the risks of withholding such therapy, and we discuss a few important questions to better illustrate this point.

      Abbreviations:

      CDI ( Clostridium difficile infections), MDRO ( multidrug-resistant organism), NNT ( number-needed-to-treat)

      References

        • Singer M.
        • Deutschman C.S.
        • Seymour C.W.
        • et al.
        The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
        JAMA. 2016; 315: 801-810
        • Casserly B.
        • Phillips G.S.
        • Schorr C.
        • et al.
        Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database.
        Crit Care Med. 2015; 43: 567-573
        • Rhodes A.
        • Evans L.E.
        • Alhazzani W.
        • et al.
        Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
        Intensive Care Med. 2017; 43: 304-377
        • Kumar A.
        • Roberts D.
        • Wood K.E.
        • 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: 1589-1596
        • Seymour C.W.
        • Gesten F.
        • Prescott H.C.
        • et al.
        Time to treatment and mortality during mandated emergency care for sepsis.
        N Engl J Med. 2017; 376: 2235-2244
        • Liu V.X.
        • Fielding-Singh V.
        • Greene J.D.
        • et al.
        The timing of early antibiotics and hospital mortality in sepsis.
        Am J Respir Crit Care Med. 2017; 196: 856-863
        • Whiles B.B.
        • Deis A.S.
        • Simpson S.Q.
        Increased time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients.
        Crit Care Med. 2017; 45: 623-629
        • Kumar A.
        • Ellis P.
        • Arabi Y.
        • et al.
        Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.
        Chest. 2009; 136: 1237-1248
        • Vazquez-Guillamet C.
        • Scolari M.
        • Zilberberg M.D.
        • Shorr A.F.
        • Micek S.T.
        • Kollef M.
        Using the number needed to treat to assess appropriate antimicrobial therapy as a determinant of outcome in severe sepsis and septic shock.
        Crit Care Med. 2014; 42: 2342-2349
      1. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group.
        Lancet. 1994; 343: 311-322
        • Emberson J.
        • Lees K.R.
        • Lyden P.
        • et al.
        Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.
        Lancet. 2014; 384: 1929-1935
        • GiVi T.I.S.C.
        • Bertolini G.
        • Nattino G.
        • et al.
        Mortality attributable to different Klebsiella susceptibility patterns and to the coverage of empirical antibiotic therapy: a cohort study on patients admitted to the ICU with infection.
        Intensive Care Med. 2018; 44: 1709-1719
        • Mi M.Y.
        • Klompas M.
        • Evans L.
        Early administration of antibiotics for suspected sepsis.
        N Engl J Med. 2019; 380: 593-596
        • Peake S.L.
        • et al.
        • ARISE Investigators A
        • ANZICS Clinical Trials Group
        Goal-directed resuscitation for patients with early septic shock.
        N Engl J Med. 2014; 371: 1496-1506
        • Phua J.
        • Ngerng W.
        • See K.
        • et al.
        Characteristics and outcomes of culture-negative versus culture-positive severe sepsis.
        Crit Care. 2013; 17: R202
        • Rhee C.
        • Dantes R.
        • Epstein L.
        • et al.
        Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014.
        JAMA. 2017; 318: 1241-1249
        • Fridkin S.
        • Baggs J.
        • Fagan R.
        • et al.
        Vital signs: improving antibiotic use among hospitalized patients.
        MMWR Morb Mortal Wkly Rep. 2014; 63: 194-200
        • Fleming-Dutra K.E.
        • Hersh A.L.
        • Shapiro D.J.
        • et al.
        Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011.
        JAMA. 2016; 315: 1864-1873
        • Barlam T.F.
        • Cosgrove S.E.
        • Abbo L.M.
        • 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: e51-e77
        • Public Health Agency of Canada
        Canadian Antimicrobial Resistance Surveillance System Report, 2016.
        • US Food and Drug Administration
        Summary Report on Antimicrobials Sold or Distributed for Use in Food-Producing Animals 2017. Published December 2018.