The association between time to antibiotics and relevant clinical outcomes in emergency department patients with various stages of sepsis: a prospective multi-center study

Abstract

IntroductionIn early sepsis stages, optimal treatment could contribute to prevention of progression to severe sepsis. Therefore, we investigated if there was an association between time to antibiotics and relevant clinical outcomes in hospitalized emergency department (ED) patients with mild to severe sepsis stages.MethodsThis is a prospective multicenter study in three Dutch EDs. Patients were stratified into three categories of illness severity, as assessed by the predisposition, infection, response, and organ failure (PIRO) score: PIRO score 1 to 7, 8 to 14 and >14 points, reflected low, intermediate, and high illness severity, respectively. Consecutive hospitalized ED patients with a suspected infection who were treated with intravenous antibiotics were eligible to participate in the study. The primary outcome measure was the number of surviving days outside the hospital at day 28 which was used as an inverse measure of hospital length of stay (LOS). The secondary outcome measure was 28-day mortality, taking into account the time to mortality.Multivariable Cox regression analysis was used to estimate the association between time to antibiotics and the primary and secondary outcome measures corrected for confounders, including appropriateness of antibiotics and initial ED resuscitation, in three categories of illness severity.ResultsOf the 1,168 included patients, 112 died (10%), while 85% and 95% received antibiotics within three and six hours, respectively. No association between time to antibiotics and surviving days outside the hospital or mortality was found. Only in PIRO group 1 to 7 was delayed administration of antibiotics (>3 hours) associated with an increase in surviving days outside the hospital at day 28 (hazard ratio: 1.46, 95% confidence interval: 1.05 to 2.02 after correction for potential confounders).ConclusionsIn ED patients with mild to severe sepsis who received antibiotics within six hours after ED presentation, a reduction in time to antibiotics was not found to be associated with an improvement in relevant clinical outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0936-3) contains supplementary material, which is available to authorized users.

Empirical antimicrobial therapy for probable v. directed therapy for possible ventilator-associated pneumonia in critically injured patients

“…In fact, evidence to the contrary has been presented. [11] In the absence of haemodynamic instability or worsening organ function, there is no reported relationship between the timing of treatment and outcome. Moreover, the unwarranted use of broad-spectrum empirical antimicrobials in sepsis without organ dysfunction or hypotension may potentiate bacterial resistance without conferring benefit.…”

Inclusion of emergency department patients in early stages of sepsis in a quality improvement programme has the potential to improve survival: a prospective dual-centre study

“…However, the impact of individual performance measures on mortality may differ across EDs and healthcare systems. For example, it was recently shown in the participating EDs of the present study that a further reduction of time to antibiotic infusion did not improve the survival of ED patients with sepsis,10 probably because antibiotics had already been administered very early. If we would like to improve the survival in these EDs, we should focus on the aforementioned other aspects of ED sepsis management.…”

“…As described in detail previously,10 the ED visit data collected included patient demographic characteristics and comorbidities, time points for start of oxygen and fluid therapy and antibiotic administration, laboratory values, triage categories and vital signs, treatment administered (including antibiotics, intravenous fluids and oxygen), and disposition from the ED. In addition to these data, we reviewed charts for do not resuscitate (DNR) status as indicated by their previous medical files or decided during their ED stay or hospital admission, and determined the presence or absence of acute-onset organ failure as described by Dellinger et al 9 We also calculated illness severity using the patient’s initial Predisposition, Infection, Response and Organ failure (PIRO) score.…”

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“…Nevertheless, the evidence base that 'every hour counts', that combination therapy is beneficial, and that long courses of therapy are needed to better eradicate microorganisms is weak and conflicting (e.g. [54,55]). Emerging data suggest harm from antibiotic load, be it from longer courses and/or multiple agents.…”