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Cited by 434Sepsis Diagnosis and TreatmentAntibiotics Pharmacokinetics and EfficacyAntibiotic Use and Resistance

The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-Analysis*

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Sterling, Sarah A., Miller, W. Ryan, Pryor, Jason, Puskarich, Michael A., Jones, Alan E.·2015·Critical Care Medicine
DOI 10.1097/ccm.0000000000001142PMC PMC4597314
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Abstract

OBJECTIVES: We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. DATA SOURCES: A comprehensive search criteria was performed using a predefined protocol. INCLUSION CRITERIA: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to emergency department triage and/or shock recognition, and mortality. EXCLUSION CRITERIA: immunosuppressed populations, review article, editorial, or nonhuman studies. DATA EXTRACTION: Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of emergency department triage and 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds ratios were calculated using a random effect model. The primary outcome was mortality. DATA SYNTHESIS: A total of 1,123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from emergency department triage. Patients who received antibiotics more than 3 hours after emergency department triage (< 3 hr reference) had a pooled odds ratio for mortality of 1.16 (0.92-1.46; p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hr reference) had a pooled odds ratio for mortality of 1.46 (0.89-2.40; p = 0.13). There was no increased mortality in the pooled odds ratios for each hourly delay from less than 1 to more than 5 hours in antibiotic administration from severe sepsis/shock recognition. CONCLUSION: Using the available pooled data, we found no significant mortality benefit of administering antibiotics within 3 hours of emergency department triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence.

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Crossref · 10.1097/ccm.0000000000001142

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  • Diagnostic delays in BSIs contribute to longer hospital stays and higher healthcare burdens.

    “These diagnostic delays not only exacerbate the risk of multiorgan failure but also contribute to longer hospital stays and higher healthcare burdens [8, 9].”

    From Early prediction of bloodstream infections in ICU patients using machine learning methods based on routine laboratory parameters (2025) · cites this paper as [9]

    The Introduction says severe sepsis and septic shock are associated with health care costs, but does not link those costs to diagnostic delays. The Discussion addresses delayed recognition and antibiotic timing; neither it nor the searched passages report that diagnostic delays in bloodstream infections lengthen hospital stays or increase healthcare burden (searched: diagnostic delays, length of stay, hospital costs). (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Diagnostic delays in BSIs exacerbate the risk of multiorgan failure.

    “These diagnostic delays not only exacerbate the risk of multiorgan failure but also contribute to longer hospital stays and higher healthcare burdens [8, 9].”

    From Early prediction of bloodstream infections in ICU patients using machine learning methods based on routine laboratory parameters (2025) · cites this paper as [9]

    The Introduction and Discussion address delays in antibiotic administration for severe sepsis and septic shock, not delays in diagnosing bloodstream infections. The Discussion mentions organ dysfunction but does not link diagnostic delay to an increased risk of multiorgan failure. Searches for diagnostic delay, bloodstream infection, and organ failure found no passage making that link. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 21

  1. [1]Angus DC Linde-Zwirble WT Lidicker J Clermont G Carcillo J Pinsky MR Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care Crit Care Med 2001 7 29 7 1303 10 11445675
  2. [2]Wang HE Shapiro NI Angus DC Yealy DM National estimates of severe sepsis in United States emergency departments Crit Care Med 2007 8 35 8 1928 36 17581480
  3. [3]Rivers E Nguyen B Havstad S Ressler J Muzzin A Knoblich B Peterson E Tomlanovich M Early goal-directed therapy in the treatment of severe sepsis and septic shock N Engl J Med 2001 11 8 345 19 1368 77 11794169
  4. [4]Jones AE Focht A Horton JM Kline JA Prospective external validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock Chest 2007 8 132 2 425 32 17573521 PMC2703721
  5. [5]Jones AE Brown MD Trzeciak S Shapiro NI Garrett JS Heffner AC Kline JA The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: a meta-analysis Crit Care Med 2008 10 36 10 2734 9 18766093 PMC2737059
  6. [6]Nguyen HB Corbett SW Steele R Banta J Clark RT Hayes SR Edwards J Cho TW Wittlake WA Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality Crit Care Med 2007 4 35 4 1105 12 17334251
  7. [7]Puskarich MA Marchick MR Kline JA Steuerwald MT Jones AE One year mortality of patients treated with an emergency department based early goal directed therapy protocol for severe sepsis and septic shock: a before and after study Crit Care 2009 13 5 R167 19845956 PMC2784398
  8. [8]Ferrer R Martin-Loeches I Phillips G Osborn TM Townsend S Dellinger RP Artigas A Schorr C Levy MM 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 8 42 8 1749 55 24717459
  9. [12]Venkatesh AK Avula U Bartimus H Reif J Schmidt MJ Powell ES Time to antibiotics for septic shock: evaluating a proposed performance measure Am J Emerg Med 2013 4 31 4 680 3 23380106
  10. [13]Dellinger RP Levy MM Rhodes A Annane D Gerlach H Opal SM Sevransky JE Sprung CL Douglas IS Jaeschke R Osborn TM Nunnally ME Townsend SR Reinhart K Kleinpell RM Angus DC Deutschman CS Machado FR Rubenfeld GD Webb SA Beale RJ Vincent JL Moreno R Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012 Crit Care Med 2013 2 41 2 580 637 23353941
  11. [14]Vilella AL Seifert CF Timing and appropriateness of initial antibiotic therapy in newly presenting septic patients Am J Emerg Med 2014 1 32 1 7 13 24139996
  12. [18]Borenstein M Hedges LV Higgines JPT Rothstein HR Fixed-Effect Versus Random-Effects Models Introduction to Meta-Analysis John Wiley & Sons, Ltd 2009
  13. [19]Hutchison RW Govathoti DA Fehlis K Zheng Q Cottrell JH Franklin N Montgomery GM Improving severe sepsis outcomes: cost and time to first antibiotic dose Dimens Crit Care Nurs 2011 9 30 5 277 82 21841424
  14. [20]Siddiqui S Razzak J Early versus late pre-intensive care unit admission broad spectrum antibiotics for severe sepsis in adults Cochrane Database Syst Rev 2010 10 CD007081 20927754 PMC6516895
  15. [22]Shenep JL Mogan KA Kinetics of endotoxin release during antibiotic therapy for experimental gram-negative bacterial sepsis J Infect Dis 1984 9 150 3 380 8 6384378
  16. [23]Peng ZY Wang HZ Srisawat N Wen X Rimmele T Bishop J Singbartl K Murugan R Kellum JA Bactericidal antibiotics temporarily increase inflammation and worsen acute kidney injury in experimental sepsis Crit Care Med 2012 2 40 2 538 43 21926582 PMC3254710
  17. [24]Lepper PM Held TK Schneider EM Bolke E Gerlach H Trautmann M Clinical implications of antibiotic-induced endotoxin release in septic shock Intensive Care Med 2002 7 28 7 824 33 12122518
  18. [25]Mignon F Piagnerelli M Van N M Vincent JL Effect of empiric antibiotic treatment on plasma endotoxin activity in septic patients Infection 2014 6 42 3 521 8 24470321
  19. [26]Villar J Clement JP Stotts J Linnen D Rubin DJ Thompson D Gomez A Fee C Many emergency department patients with severe sepsis and septic shock do not meet diagnostic criteria within 3 hours of arrival Ann Emerg Med 2014 7 64 1 48 54 24680548
  20. [27]Kirn TJ Weinstein MP Update on blood cultures: how to obtain, process, report, and interpret Clin Microbiol Infect 2013 6 19 6 513 20 23490046
  21. [28]Kerremans JJ Verboom P Stijnen T Hakkaart-van RL Goessens W Verbrugh HA Vos MC Rapid identification and antimicrobial susceptibility testing reduce antibiotic use and accelerate pathogen-directed antibiotic use J Antimicrob Chemother 2008 2 61 2 428 35 18156278

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Authors
Sterling, S. A., Miller, W. R., Pryor, J., Puskarich, M. A., & Jones, A. E.
Affiliations
University of Mississippi Medical Center (US)
ORCID
Venue
Critical Care Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-09
Volume
43
Issue
9
Pages
1907-1915
ISSN
0090-3493 (ISSN-L)
DOI
10.1097/ccm.0000000000001142
PMC
PMC4597314
OpenAlex
W854296307
Cited by
434
References
6
Citations by year
2026: 20 · 2025: 28 · 2024: 34 · 2023: 38 · 2022: 34 · 2021: 43 · 2020: 52 · 2019: 58 · 2018: 40 · 2017: 45 · 2016: 34 · 2015: 7
FWCI
5.46
Type
journal article
Language
en
Open access
Locations
  • Critical Care Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (4r01gm103799-05)
  • National Institute of General Medical Sciences ((R01 GM103799), K23GM113041)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
Keywords
timing of antibiotic administration, severe sepsis, septic shock, mortality, emergency department triage, shock recognition, quality of care metrics, guideline recommendations
MeSH terms
Anti-Bacterial Agents, Emergency Service, Hospital, Humans, Length of Stay, Shock, Septic, Triage, Hospital Mortality, Sepsis

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