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Review Article| Volume 36, ISSUE 4, P719-733, December 2022

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Timing and Spectrum of Antibiotic Treatment for Suspected Sepsis and Septic Shock

Why so Controversial?
  • Theodore R. Pak
    Affiliations
    Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Cox Building, Suite #515, Boston, MA 02114, USA

    Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, 401 Park Drive, Suite 401 East, Boston, MA 02215, USA
    Search for articles by this author
  • Chanu Rhee
    Affiliations
    Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, 401 Park Drive, Suite 401 East, Boston, MA 02215, USA

    Division of Infectious Diseases, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
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  • Michael Klompas
    Correspondence
    Corresponding author. 401 Park Drive, Suite 401 East, Boston, MA 02215.
    Affiliations
    Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, 401 Park Drive, Suite 401 East, Boston, MA 02215, USA

    Division of Infectious Diseases, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Search for articles by this author

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      References

        • Wang H.E.
        • Jones A.R.
        • Donnelly J.P.
        Revised National Estimates of Emergency Department Visits for Sepsis in the United States.
        Crit Care Med. 2017; 45: 1443-1449
        • 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
        • 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
        • Sterling S.A.
        • Miller W.R.
        • Pryor J.
        • et al.
        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: 1907-1915
      1. Door-to-Antibiotic Time and Long-term Mortality in Sepsis.
        Chest. 2019; 155: 938-946
        • 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: 1749-1755
        • 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
        • Centers for Medicare & Medicaid Services
        Hospital Inpatient Specifications Manuals.
        (Available at:) (Accessed February 8, 2022)
        • 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
        • Rhodes A.
        • Evans L.E.
        • Alhazzani W.
        • et al.
        Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
        Crit Care Med. 2017; 45: 486-552
        • Dwyer J.
        One boy’s death moves state to action to prevent others.
        The New York Times, 2012 (Available at:) (Accessed February 13, 2022)
        • Seymour C.W.
        • Liu V.X.
        • Iwashyna T.J.
        • et al.
        Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
        JAMA. 2016; 315: 762-774
        • Dellinger R.P.
        • Levy M.M.
        • Rhodes A.
        • et al.
        Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock, 2012.
        Intensive Care Med. 2013; 39: 165-228
        • Pepper D.J.
        • Jaswal D.
        • Sun J.
        • et al.
        Evidence underpinning the centers for medicare & medicaid services’ severe sepsis and septic shock management bundle (SEP-1) a systematic review.
        Ann Intern Med. 2018; 168: 1-11
        • Kalil A.C.
        • Gilbert D.N.
        • Winslow D.L.
        • et al.
        • 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: 1631-1635
        • Klein Klouwenberg P.M.C.
        • Cremer O.L.
        • van Vught L.A.
        • 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: 1-8
        • Shappell C.N.
        • Klompas M.
        • Ochoa A.
        • et al.
        Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department.
        Crit Care Med. 2021; 49: e1144-e1150
        • Rhee C.
        • Kadri S.S.
        • Dekker J.P.
        • et al.
        Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated With Inadequate and Broad-Spectrum Empiric Antibiotic Use.
        JAMA Netw Open. 2020; 3: e202899
        • Tamma P.D.
        • Avdic E.
        • Li D.X.
        • et al.
        Association of Adverse Events With Antibiotic Use in Hospitalized Patients.
        JAMA Intern Med. 2017; 177: 1308-1315
        • Ong D.S.Y.
        • Frencken J.F.
        • Klein Klouwenberg P.M.C.
        • et al.
        Short-Course Adjunctive Gentamicin as Empirical Therapy in Patients With Severe Sepsis and Septic Shock: A Prospective Observational Cohort Study.
        Clin Infect Dis. 2017; 64: 1731-1736
        • Weinberger J.
        • Rhee C.
        • Klompas M.
        A critical analysis of the literature on time-to-antibiotics in suspected sepsis.
        J Infect Dis. 2021; 222: S110-S118
        • Rhee C.
        • Chiotos K.
        • Cosgrove S.E.
        • et al.
        Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure.
        Clin Infect Dis. 2021; 72: 541-552
        • Alam N.
        • Oskam E.
        • Stassen P.M.
        • et al.
        Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial.
        Lancet Respir Med. 2018; 6: 40-50
        • Bloos F.
        • Rüddel H.
        • Thomas-Rüddel D.
        • et al.
        Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial.
        Intensive Care Med. 2017; 43: 1602-1612
        • Bisarya R.
        • Song X.
        • Salle J.
        • et al.
        Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection.
        Chest. 2022; 161: 112-120
        • Umemura Y.
        • Abe T.
        • Ogura H.
        • et al.
        Hour-1 bundle adherence was associated with reduction of in-hospital mortality among patients with sepsis in Japan.
        PLoS One. 2022; 17: 1-12
        • Rüddel H.
        • Thomas-Rüddel D.O.
        • Reinhart K.
        • et al.
        Adverse effects of delayed antimicrobial treatment and surgical source control in adults with sepsis: results of a planned secondary analysis of a cluster-randomized controlled trial.
        Crit Care. 2022; 26: 51
        • Filbin M.R.
        • Lynch J.
        • Gillingham T.D.
        • et al.
        Presenting symptoms independently predict mortality in septic shock: Importance of a previously unmeasured confounder.
        Crit Care Med. 2018; 46: 1592-1599
        • Henning D.J.
        • Carey J.R.
        • Oedorf K.
        • et al.
        The absence of fever is associated with higher mortality and decreased antibiotic and IV fluid administration in emergency department patients with suspected septic shock.
        Crit Care Med. 2017; 45: e575-e582
        • Van Walraven C.
        • Austin P.C.
        • Jennings A.
        • et al.
        A modification of the elixhauser comorbidity measures into a point system for hospital death using administrative data.
        Med Care. 2009; 47: 626-633
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • et al.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
      2. Agency for Healthcare Research and Quality. Elixhauser comorbidity software refined for ICD-10-CM reference file, v2022.1.
        (Available at:) (Accessed March 13, 2022)
        • Alrawashdeh M.
        • Klompas M.
        • Simpson S.Q.Q.
        • et al.
        Prevalence and Outcomes of Previously Healthy Adults Among Patients Hospitalized With Community-Onset Sepsis.
        Chest. 2022; : 1-10https://doi.org/10.1016/j.chest.2022.01.016
        • 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
        • Levy M.M.
        • Evans L.E.
        • Rhodes A.
        The Surviving Sepsis Campaign Bundle: 2018 update.
        Intensive Care Med. 2018; 44: 925-928
        • Marik P.E.
        • Farkas J.D.
        • Spiegel R.
        • et al.
        POINT: Should the Surviving Sepsis Campaign Guidelines Be Retired?.
        Yes Chest. 2019; 155: 12-14
        • Kalantari A.
        • Rezaie S.R.
        Challenging the one-hour sepsis bundle.
        West J Emerg Med. 2019; 20: 185-190
        • Talan D.A.
        • Yealy D.M.
        Challenging the One-Hour Bundle Goal for Sepsis Antibiotics.
        Ann Emerg Med. 2019; 73: 359-362
        • Levy M.M.
        • Rhodes A.
        • Evans L.E.
        Steering and Executive Committee of the Surviving Sepsis Campaign. COUNTERPOINT: Should the Surviving Sepsis Campaign Guidelines Be Retired? No.
        Chest. 2019; 155: 14-17
        • Brunkhorst F.M.
        • Oppert M.
        • Marx G.
        • 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.
        JAMA. 2012; 307: 2390-2399
        • Heyland D.K.
        • Dodek P.
        • Muscedere J.
        • et al.
        Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia.
        Crit Care Med. 2008; 36: 737-744
        • Sjövall F.
        • Perner A.
        • Hylander Møller M.
        Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis – A systematic review with meta-analysis and trial sequential analysis.
        J Infect. 2017; 74: 331-344
        • Arulkumaran N.
        • Routledge M.
        • Schlebusch S.
        • et al.
        Antimicrobial-associated harm in critical care: a narrative review.
        Intensive Care Med. 2020; 46: 225-235
        • Jones B.E.
        • Ying J.
        • Stevens V.
        • et al.
        Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality in Patients Hospitalized for Pneumonia.
        JAMA Intern Med. 2020; 180: 552-560
        • Webb B.J.
        • Sorensen J.
        • Jephson A.
        • et al.
        Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: A cohort study.
        Eur Respir J. 2019; 54: 1-9
        • Attridge R.T.
        • Frei C.R.
        • Restrepo M.I.
        • et al.
        Guideline-concordant therapy and outcomes in healthcare-associated pneumonia.
        Eur Respir J. 2011; 38: 878-887
        • Kett D.H.
        • Cano E.
        • Quartin A.A.
        • et al.
        Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: An observational, multicentre cohort study.
        Lancet Infect Dis. 2011; 11: 181-189
        • Hranjec T.
        • Rosenberger L.H.
        • 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: 774-780
        • Kadri S.S.
        • Lai Y.L.
        • Warner S.
        • et al.
        Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals.
        Lancet Infect Dis. 2021; 21: 241-251
        • Leisman D.E.
        The Goldilocks Effect in the ICU—When the Data Speak, but Not the Truth.
        Crit Care Med. 2020; 48: 1887-1889
        • Yealy D.M.
        • Mohr N.M.
        • Shapiro N.I.
        • et al.
        Early Care of Adults With Suspected Sepsis in the Emergency Department and Out-of-Hospital Environment: A Consensus-Based Task Force Report.
        Ann Emerg Med. 2021; 78: 1-19
        • Evans L.
        • Rhodes A.
        • Alhazzani W.
        • et al.
        Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.
        Crit Care Med. 2021; 49: e1063-e1143
        • Evans L.
        • Rhodes A.
        • Alhazzani W.
        • et al.
        Executive Summary: Surviving Sepsis Campaign: International Guidelines for the Management of Sepsis and Septic Shock 2021.
        Crit Care Med. 2021; 49: 1974-1982
        • Rhee C.
        • Brown S.R.
        • Jones T.M.
        • et al.
        Variability in determining sepsis time zero and bundle compliance rates for the centers for medicare and medicaid services SEP-1 measure.
        Infect Control Hosp Epidemiol. 2018; 39: 994-996
        • Zhang Z.
        • Zhang G.
        • Goyal H.
        • et al.
        Identification of subclasses of sepsis that showed different clinical outcomes and responses to amount of fluid resuscitation: a latent profile analysis.
        Crit Care. 2018; 22: 347
        • Gårdlund B.
        • Dmitrieva N.O.
        • Pieper C.F.
        • et al.
        Six subphenotypes in septic shock: Latent class analysis of the PROWESS Shock study.
        J Crit Care. 2018; 47: 70-79
        • Han X.
        • Spicer A.
        • Carey K.A.
        • et al.
        Identifying High-Risk Subphenotypes and Associated Harms From Delayed Antibiotic Orders and Delivery.
        Crit Care Med. 2021; 49: 1694-1705
        • Seymour C.W.
        • Kennedy J.N.
        • Wang S.
        • et al.
        Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis.
        JAMA. 2019; 321: 2003-2017
        • Ibrahim Z.M.
        • Wu H.
        • Hamoud A.
        • et al.
        On classifying sepsis heterogeneity in the ICU: Insight using machine learning.
        J Am Med Inform Assoc. 2020; 27: 437-443
        • Stanski N.L.
        • Wong H.R.
        Prognostic and predictive enrichment in sepsis.
        Nat Rev Nephrol. 2020; 16: 20-31
        • Bone R.C.
        • Balk R.A.
        • Cerra F.B.
        • et al.
        Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.
        Chest. 1992; 101: 1644-1655
        • Pierrakos C.
        • Velissaris D.
        • Bisdorff M.
        • et al.
        Biomarkers of sepsis: Time for a reappraisal.
        Crit Care. 2020; 24: 1-15
        • Pepper D.J.
        • Sun J.
        • Rhee C.
        • et al.
        Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis.
        Chest. 2019; 155: 1109-1118
        • Elnajdy D.
        • El-Dahiyat F.
        Antibiotics duration guided by biomarkers in hospitalized adult patients; a systematic review and meta-analysis.
        Infect Dis (Auckl). 2022; 0: 1-16
        • Järvinen A.K.K.
        • Laakso S.
        • Piiparinen P.
        • et al.
        Rapid identification of bacterial pathogens using a PCR- and microarray-based assay.
        BMC Microbiol. 2009; 9https://doi.org/10.1186/1471-2180-9-161
        • Shang S.
        • Chen G.
        • Wu Y.
        • et al.
        Rapid diagnosis of bacterial sepsis with PCR amplification and microarray hybridization in 16S rRNA gene.
        Pediatr Res. 2005; 58: 143-148
        • Altun O.
        • Botero-Kleiven S.
        • Carlsson S.
        • et al.
        Rapid identification of bacteria from positive blood culture bottles by MALDI-TOF MS following short-term incubation on solid media.
        J Med Microbiol. 2015; 64: 1346-1352
        • Watanabe N.
        • Koyama S.
        • Taji Y.
        • et al.
        Direct microorganism species identification and antimicrobial susceptibility tests from positive blood culture bottles using rapid Sepsityper Kit.
        J Infect Chemother. 2022; 2021https://doi.org/10.1016/j.jiac.2021.12.030
        • Lin J.F.F.
        • Ge M.C.C.
        • Liu T.P.P.
        • et al.
        A simple method for rapid microbial identification from positive monomicrobial blood culture bottles through matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
        J Microbiol Immunol Infect. 2018; 51: 659-665
        • Pak T.R.
        • Kasarskis A.
        How Next-Generation Sequencing and Multiscale Data Analysis Will Transform Infectious Disease Management.
        Clin Infect Dis. 2015; 61: 1695-1702
        • Sweeney T.E.
        • Azad T.D.
        • Donato M.
        • et al.
        Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters.
        Crit Care Med. 2018; 46: 915-925
        • Reyes M.
        • Filbin M.R.
        • Bhattacharyya R.P.
        • et al.
        An immune-cell signature of bacterial sepsis.
        Nat Med. 2020; 26: 333-340