ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023
Risk of Misleading Conclusions in Observational Studies of Time-to-Antibiotics and Mortality in Suspected Sepsis.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Appropriate timing of antibiotic initiation in patients with sepsis or septic shock: a systematic review and meta-analysis.The Korean journal of internal medicine · 2025Pooled it
- Randomized controlled diagnostic trial to assess dRAST time to result and its utility for antimicrobial stewardship recommendation in bacteremic patients.Microbiology spectrum · 2025Trial
- Effectiveness and Safety of an Emergency Department Code Sepsis Protocol: A Pragmatic Clinical Trial.Annals of the American Thoracic Society · 2024Trial
- Time to Antibiotics and Mortality in Immunocompromised Versus Non-immunocompromised Patients With Suspected Sepsis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Association of Timely Antibiotics and Fluid Resuscitation With Increased Discharge to Home After Sepsis.Chest · 2026Observational
- Rapid Microbiological Diagnostics for Sepsis: Narrative Review of Current and Prospective Approaches.Critical care explorations · 2026Review
- Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2026.Intensive care medicine · 2026Article
- SERS-Based Universal AST: Rapid Treatment Guidance for Blood-Culture Bacteria before Species Identification.Analytical chemistry · 2026Article
- Physician Variation in Early Sepsis Management.JAMA network open · 2026Article
- Time to initial glycopeptide therapy and 30-day mortality in methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study.BMC infectious diseases · 2025Article
- Syndromic Analysis of Sepsis Cohorts Using Large Language Models.JAMA network open · 2025Article
- Light scattering-based screening method for rapid evaluating antibiotic effects on bacteria using laser speckle imaging.Journal of biological engineering · 2025Article
- Infections caused by clonal spread of metallo-beta-lactamase-producingMicrobiology spectrum · 2025Article
- Association Between Delayed Broad-Spectrum Gram-negative Antibiotics and Clinical Outcomes: How Much Does Getting It Right With Empiric Antibiotics Matter?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- [Specialty-specific knowledge as prerequisite for effective treatment of critically ill patients].Chirurgie (Heidelberg, Germany) · 2025Article
- Antibiotics for suspected sepsis: who and when?Intensive care medicine · 2025Article
- Association Between the Sequence of β-Lactam and Vancomycin Administration and Mortality in Patients With Suspected Sepsis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Evaluating Potential Missed Opportunities to Prevent, Treat, or Diagnose Sepsis: A Population-Based Retrospective Study of Insurance Claims.Critical care explorations · 2025Article
- Complex Sepsis Presentations, SEP-1 Compliance, and Outcomes.JAMA network open · 2025Article
- Prehospital lactate analysis in suspected sepsis improves detection of patients with increased mortality risk: an observational study.Critical care (London, England) · 2025Observational
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Authors and funding
11 authors.
Funding
Abstract
backgroundInfluential studies conclude that each hour until antibiotics increases mortality in sepsis. However, these analyses often (1) adjusted for limited covariates, (2) included patients with long delays until antibiotics, (3) combined sepsis and septic shock, and (4) used linear models presuming each hour delay has equal impact. We evaluated the effect of these analytic choices on associations between time-to-antibiotics and mortality.
methodsWe retrospectively identified 104 248 adults admitted to 5 hospitals from 2015-2022 with suspected infection (blood culture collection and intravenous antibiotics ≤24 h of arrival), including 25 990 with suspected septic shock and 23 619 with sepsis without shock. We used multivariable regression to calculate associations between time-to-antibiotics and in-hospital mortality under successively broader confounding-adjustment, shorter maximum time-to-antibiotic intervals, stratification by illness severity, and removing assumptions of linear hourly associations.
resultsChanging covariates, maximum time-to-antibiotics, and severity stratification altered the magnitude, direction, and significance of observed associations between time-to-antibiotics and mortality. In a fully adjusted model of patients treated ≤6 hours, each hour was associated with higher mortality for septic shock (adjusted odds ratio [aOR]: 1.07; 95% CI: 1.04-1.11) but not sepsis without shock (aOR: 1.03; .98-1.09) or suspected infection alone (aOR: .99; .94-1.05). Modeling each hour separately confirmed that every hour of delay was associated with increased mortality for septic shock, but only delays >6 hours were associated with higher mortality for sepsis without shock.
conclusionsAssociations between time-to-antibiotics and mortality in sepsis are highly sensitive to analytic choices. Failure to adequately address these issues can generate misleading conclusions.
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