The Timing of Early Antibiotics and Hospital Mortality in Sepsis

Vincent, Jean‐Louis; Fielding‐Singh, Vikram; Greene, J; Baker, Jennifer M.; Iwashyna, Theodore J.; Bhattacharya, Jay; Escobar, Gabriel J.

doi:10.1164/rccm.201609-1848oc

Cited by 627 publications

(511 citation statements)

References 50 publications

(60 reference statements)

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“…5,15,16 A recent meta-analysis of 11 observational studies, however, showed no significant mortality benefit of the administration of antibiotics within 3 hours, as compared with after 3 hours, after triage in the emergency department (odds ratio, 1.16; 95% CI, 0.92 to 1.46) or within 1 hour after the recognition of shock (odds ratio, 1.46; 95% CI, 0.89 to 2.40). 6 The odds ratios we report are similar, but the confidence intervals are narrower given the much larger sample size that was included in our study.…”

Section: Discussionmentioning

confidence: 99%

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

Seymour¹,

et al. 2017

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BACKGROUND In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. METHODS We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. RESULTS Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted inhospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). CONCLUSIONS More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality.

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Section: Discussionmentioning

confidence: 99%

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

Seymour¹,

et al. 2017

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“…It is essential to become aware of the pathogen and potential antibiotic resistances [1, 2]. Sufficient diagnostic with BC can reduce mortality, length of stay on the intensive care unit and furthermore hospital expense [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Nudge to better care - blood cultures and catheter-related bloodstream infections in Germany at two points in time (2006, 2015)

Salm

Schwab

Behnke

et al. 2018

Antimicrob Resist Infect Control

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BackgroundBlood cultures (BCs) are the gold standard for diagnosing sepsis and are prerequisite for a targeted antibiotic treatment and essential for patient outcomes. Aim of the study was to analyze the frequency of BCs, the rate of central line-associated bloodstream infections (CLABSIs) and to study the association between both parameters on intensive care units in Germany over time.MethodsCross-sectional studies at two points in time (2006, 2015) on ICUs participating in the German hospital infection surveillance system. CLABSIs were defined according to the Center for Disease Control and Prevention (CDC). Univariable and multivariable analyses were performed using generalized linear models.ResultsA total of 639 ICUs participated in 2006 or 2015 and 90 ICUs (“core group”) in both years. Overall, 2,427,921 patient days from 644,575 patients were analyzed. In the ICU core group the frequency of BCs per 1000 patient days doubled from 57.8 (interquartile range [IQR] 29.8–101.2; 2006) to 128.2 (IQR 71.6–183.2; 2015). In the same time, the pooled median CLABSI rate decreased from 0.8 (IQR 0–1.9; 2006) per 1000 central-line catheter days to 0.2 (IQR 0–0.9; 2015).ConclusionsFrom 2006 to 2015 the frequency of BCs increased on ICUs in Germany and is now within the recommended 100 to 200 BCs sets per 1000 patient days.

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“…Simulated clinical trajectories apply the first dose of antibiotics at 6 hours post initial infection, reflecting a recognition that nearly always the actual T 0 of clinical infection happens some hours prior to encounter with the medical system but with the goal of administering antibiotics as early as possible. This timeframe is within the range of the ongoing controversy/investigation regarding the optimal timing of antibiotics for sepsis [14, 15]. The selected duration of antibiotic therapy is 10 days, a clinically common treatment duration for sepsis.…”

Section: Methodsmentioning

confidence: 99%

Sepsis reconsidered: Identifying novel metrics for behavioral landscape characterization with a high-performance computing implementation of an agent-based model

Cockrell

2017

Journal of Theoretical Biology

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Objectives Sepsis affects nearly 1 million people in the United States per year, has a mortality rate of 28–50% and requires more than $20 billion a year in hospital costs. Over a quarter century of research has not yielded a single reliable diagnostic test or a directed therapeutic agent for sepsis. Central to this insufficiency is the fact that sepsis remains a clinical/physiological diagnosis representing a multitude of molecularly heterogeneous pathological trajectories. Advances in computational capabilities offered by High Performance Computing (HPC) platforms call for an evolution in the investigation of sepsis to attempt to define the boundaries of traditional research (bench, clinical and computational) through the use of computational proxy models. We present a novel investigatory and analytical approach, derived from how HPC resources and simulation are used in the physical sciences, to identify the epistemic boundary conditions of the study of clinical sepsis via the use of a proxy agent-based model of systemic inflammation. Design Current predictive models for sepsis use correlative methods that are limited by patient heterogeneity and data sparseness. We address this issue by using an HPC version of a system-level validated agent-based model of sepsis, the Innate Immune Response ABM (IIRBM), as a proxy system in order to identify boundary conditions for the possible behavioral space for sepsis. We then apply advanced analysis derived from the study of Random Dynamical Systems (RDS) to identify novel means for characterizing system behavior and providing insight into the tractability of traditional investigatory methods. Results The behavior space of the IIRABM was examined by simulating over 70 million sepsis patients for up to 90 days in a sweep across the following parameters: cardio-respiratory-metabolic resilience; microbial invasiveness; microbial toxigenesis; and degree of nosocomial exposure. In addition to using established methods for describing parameter space, we developed two novel methods for characterizing the behavior of a RDS: Probabilistic Basins of Attraction (PBoA) and Stochastic Trajectory Analysis (STA). Computationally generated behavioral landscapes demonstrated attractor structures around stochastic regions of behavior that could be described in a complementary fashion through use of PBoA and STA. The stochasticity of the boundaries of the attractors highlights the challenge for correlative attempts to characterize and classify clinical sepsis. Conclusions HPC simulations of models like the IIRABM can be used to generate approximations of the behavior space of sepsis to both establish “boundaries of futility” with respect to existing investigatory approaches and apply system engineering principles to investigate the general dynamic properties of sepsis to provide a pathway for developing control strategies. The issues that bedevil the study and treatment of sepsis, namely clinical data sparseness and inadequate experimental sampling of system behavior space, are funda...

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The Timing of Early Antibiotics and Hospital Mortality in Sepsis

Cited by 627 publications

References 50 publications

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

Nudge to better care - blood cultures and catheter-related bloodstream infections in Germany at two points in time (2006, 2015)

Sepsis reconsidered: Identifying novel metrics for behavioral landscape characterization with a high-performance computing implementation of an agent-based model

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