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Importance: The impact of early antibiotics on mortality in patients with suspected sepsis in the emergency department (ED) remains debated, particularly in patients with less severe presentations or before infection confirmation., Objective: To evaluate the association between time to antibiotic administration and 28-day in-hospital mortality among patients with suspected sepsis in the ED., Design, Setting, and Participants: Post hoc analysis of the 1-bundle emergency department trial, a multicenter, stepped-wedge cluster-randomized controlled trial conducted in 23 EDs in France and Spain. A total of 872 patients with suspected sepsis were included between June 2022 and September 2023. All patients with available data on antibiotic administration were analyzed, and a subgroup of patients with no hypotension was also assessed., Exposures: Time to antibiotic administration. The effect of time to fluid resuscitation was also assessed., Main Outcomes and Measures: The primary outcome was in-hospital mortality at 28 days. Secondary outcomes included all-cause 28-day mortality, ICU length of stay, number of days without vasopressors at day 28, and change in Sequential Organ Failure Assessment score at 72 h., Results: Among 872 patients (mean age 66 years; 41% female), 859 had available data on antibiotic administration (primary analysis) and 791 (92%) received antibiotics. The median time to antibiotic administration was 61 min (IQR 14-169), with 457 patients (58%) receiving antibiotics within 1 h. In-hospital mortality at 28 days was 14.7% for patients who did not received antibiotic within 1 h versus 9.6% for patients who did [adjusted odds ratio (aOR) 2.00 (1.24-3.23)]. There was an aOR of 1.06 (1.02-1.1) for each hour of delay for antibiotic administration. This effect was confirmed in patients without hypotension [aOR 2.02 (1.08-3.76) for patients who received antibiotics beyond 1 h]. Time to fluid resuscitation was not associated with 28-day in-hospital mortality., Conclusion and Relevance: In patients with suspected sepsis presenting to the ED antibiotic administration beyond 1 h was associated with a two-fold increased 28-day in-hospital mortality. This effect persisted in patients without hypotension., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: During a pandemic like COVID-19, hospital resources are constrained and accurate severity triage of the patients is required., Objective: The objective of this study is to estimate the predictive performances of candidate biomarkers for short-term worsening (STW) of COVID-19., Design: Prospective, multicenter (20 hospitals in Paris) cohort study of consecutive COVID-19 patients with systematic biobanking at admission, during the first waves of COVID-19 in France in 2020 (COVIDeF cohort)., Setting and Participants: Consecutive COVID-19 patients were screened for inclusion. They were excluded in presence of severity criteria defined by either an ICU admission, mechanical ventilation (including noninvasive ventilation), acute respiratory distress, or in-hospital death before sampling. Routine blood tests measured during usual care and centralized systematic measurement of creatine kinase, C-reactive protein (CRP), procalcitonin, soluble urokinase plasminogen activator receptor (suPAR), high-sensitive troponin T (TnT-hs), N terminal pro-B natriuretic peptide (NT-proBNP), calprotectin, platelet factor 4, mid-regional pro-adrenomedullin (MR-proADM), and proendothelin were performed., Outcome Measures and Analyses: The primary outcome was STW, defined by a severity criteria within 7 days. A backward stepwise logistic regression model and a 'best subset' approach were used to identify independent association, and the area under the receiving operator characteristics (AUROC) was computed., Results: Five hundred and eleven patients were analyzed, of whom 60 (11.7%) experienced STW. Median time to occurrence of a severity criteria was 3 days. At admission, lower values of eosinophils, lymphocytes, platelets, alanine aminotransferase, and higher values of neutrophils, creatinine, urea, CRP, TnT-hs, suPAR, NT-proBNP, calprotectin, procalcitonin, MR-proADM, and proendothelin were predictive of worsening. Stepwise logistic regression identified three biomarkers significantly associated with worsening: CRP [adjusted odds ratio (aOR): 1.10, 95% confidence interval (95% CI): 1.06-1.15 for a 10-unit increase, AUROC: 0.73 (0.66-0.79)], procalcitonin [aOR: 0.42, 95% CI: 0.22-0.81, AUROC: 0.69 (0.64-0.88)], and MR-proADM [aOR: 2.85, 95% CI: 1.74-4.69, AUROC: 0.75 (0.69-0.81)]. These biomarkers outperformed clinical variables except diabetes and cancer comorbidities., Conclusion: In this multicenter prospective study that assessed a large panel of biomarkers for COVID-19 patients, CRP, procalcitonin, and MR-proADM were independently associated with the risk of STW., Trial Registration: ClinicalTrials.gov NCT04352348., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Timely recognition of sepsis in emergency department (ED) is challenging. We evaluated the impact of implementing the biomarker monocyte distribution width (MDW) at bedside, on the time to anti-infective administration., Methods: We conducted a before-and-after cohort study in the ED of an academic hospital in Paris, to compare sepsis patients care and outcomes, before and after the implementation of point of care (POC) MDW measurement in the ED. During post-implementation period (period-2), MDW was measured with complete blood count by ED nurses with results given in 2 min: if above 21.5 units, ED physicians were asked to consider sepsis and to start an anti-infectious as soon as possible. Primary endpoint was time to anti-infectious administration (TTA) from ED arrival, and secondary endpoints were TTA from sepsis onset (TTAS), length of stay, mortality, and hospitalization rates., Results: In total, 255 patients (period-1) and 180 patients (period-2) with sepsis were included. The TTA was 5.4 h (3.5-7.7) period-1 and 4.9 h (IQR 2.5-7.1) in period-2 (p = 0.06). MDW implementation significantly reduced the median TTAS from to 3.7 h (IQR 1.5-5.8) in period-1, to 2.2 h (IQR 0.5-4.5) in period-2 (p < 0.001). Mortality rates remained similar between the two periods (18% vs. 16% respectively, p = 0.4), as did hospitalization rates (93% vs. 91%, p = 0.4) and ED length of stay (7.2 h (5.3-9.8) vs 7.0 (5.4-9.4), p = 0.7)., Conclusion: Implementing POC MDW measurement in the ED protocols enhances the timeliness of anti-infective administration from sepsis onset, meeting current sepsis management guidelines., (© 2024. The Author(s).)

Purpose: The efficacy of the 1-h bundle for emergency department (ED) patients with suspected sepsis, which includes lactate measurement, blood culture, broad-spectrum antibiotics administration, administration of 30 mL/kg crystalloid fluid for hypotension or lactate ≥ 4 mmol/L, remains controversial., Methods: We carried out a pragmatic stepped-wedge cluster-randomized trial in 23 EDs in France and Spain. Adult patients with Sepsis-3 criteria or a quick sequential organ failure assessment (SOFA) score ≥ 2 or a lactate > 2 mmol/L were eligible. The intervention was the implementation of the 1-h sepsis bundle. The primary outcome was in-hospital mortality truncated at 28 days. Secondary outcomes included volume of fluid resuscitation at 24 h, acute heart failure at 24 h, SOFA score at 72 h, intensive care unit (ICU) length of stay, number of days on mechanical ventilation or renal replacement therapy, vasopressor free days, unnecessary antibiotic administration, and mortality at 28 days. 1148 patients were planned to be analysed; the study period ended after 873 patients were included., Results: 872 patients (mean age 66, 42% female) were analyzed: 387 (44.4%) in the intervention group and 485 (55.6%) in the control group. Median SOFA score was 3 [1-5]. Median time to antibiotic administration was 40 min in the intervention group vs 113 min in the control group (difference - 73 [95% confidence interval (CI) - 93 to - 53]). There was a significantly higher rate, volume, and shorter time to fluid resuscitation within 3 h in the intervention group. There were 47 (12.1%) in-hospital deaths in the intervention group compared to 61 (12.6%) in the control group (difference in percentage - 0.4 [95% CI - 5.1 to 4.2], adjusted relative risk (aRR) 0.81 [95% CI 0.48 to 1.39]). There were no differences between groups for other secondary endpoints., Conclusions: Among patients with suspected sepsis in the ED, the implementation of the 1-h sepsis bundle was not associated with significant difference in in-hospital mortality. However, this study may be underpowered to report a statistically significant difference between groups., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We aimed to show that coupling molecular syndromic respiratory panel (RP) testing with procalcitonin (PCT) measurement in the emergency department improves antibiotic (ATB) stewardship in lower respiratory tract infection., Methods: Open-label, prospective, randomized interventional trial, conducted from 2019 to 2022 in an adult emergency department. Patients with a suspicion of lower respiratory tract infection were randomized into an intervention arm (PCT measurement and point-of-care BIOFIRE RP2.1 plus testing, accompanied by a recommended ATB algorithm) or a standard of care (SOC) arm (PCT allowed as current practice). The primary endpoint was the duration of antibiotic exposure., Results: Four hundred fifty-one patients were randomized, median age 65 years (Q1-Q3: 49-77), the hospitalization rate was 59.9% (270/451), the median length of stay 5 days (Q1-Q3: 3 - 12), and the 28-day mortality rate 5.3% (23/451). The median duration of ATB exposure was 6 days (Q1-Q3: 0-9) and 5 days (Q1-Q3: 0-9) in the SOC and interventional arm respectively (p = 0.71). ATB was started in 29.6 % (67/226) and 33.8% (76/225) respectively (p = 0.54). The BIOFIRE RP2.1 plus identified at least one viral species in 112/225 patients (49.8%) of intervention arm. Two hundred twelve out of two hundred twenty-six (93.8%) SOC patients had PCT measurement. The adherence rate to algorithm in the intervention arm was 93.3 % (210/225)., Conclusion: Displaying PCT and real-time RP results to emergency physicians failed to significantly reduce ATB exposure in lower respiratory tract infection suspicions. However, the median ATB duration and rate of initiation were already low in the SOC arm using PCT measurement routinely., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Acute infectious diarrhoea is one of the most common diseases worldwide. Procalcitonin (PCT) is useful for antibiotic stewardship in lower respiratory tract infections but has been poorly studied in infectious diarrhoea. Our objective is to describe the PCT concentrations according to diarrhoea aetiology., Methods: This is a single-center prospective cohort study involving adults consulting the emergency department (ED) for an acute diarrhoea or colitis. Serum PCT was measured and a stool sample was tested with FilmArray® Gastro-Intestinal Panel. The primary endpoint is the PCT concentration according to each type of pathogen identified using Gastro-Intestinal-panel and/or stool cultures at ED admission., Results: 125 patients were included: 80 had an acute infectious diarrhoea, 21 an acute colitis and 24 another illness causing diarrhoea. The median (interquartile ranges) PCT values (ng/ml) were 0.13 (0.08-0.28), 0.07 (0.06-0.54), 0.13 (0.09-0.26) and 0.05 (0.03-0.17), respectively if there was a bacteria (n = 41), parasite (n = 3), virus (n = 10) or no pathogen identified and 0.34 (0.13-1.03) if the diarrhoea was due to another illness (n = 24)., Conclusion: In patients admitted to the ED with an acute infectious diarrhoea or acute colitis, PCT remained low when a bacteria was identified. It may not be informative in current practice to guide antibiotic therapy.

Background: Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP)., Methods: Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP)., Results: A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78-0.84] and 0.86 [0.84-0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79-0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84-0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83-0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2-7.1, 95% CI] and Sepsis-3 by 7.6 [5.1-11.3, 95% CI]., Conclusions: MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325).

Background: Unplanned transfer to an ICU within 48 hours of admission from the emergency department (ED) can be considered an adverse event. Screening at risk for such an event is a challenge for ED staff. Our purpose was to identify the clinical and biological variables which may be identified in the ED setting and can predict short-term unplanned secondary transfer to the intensive care setting., Methods: This was a three-year retrospective case controlled monocentric study. The cases were patients transferred to a medical ICU within 48 hours of admission to the general wards from the ED. Each case was matched to two controls (patients not transferred to the ICU) based on age, gender, year of admission, and hospital unit. A conditional logistic regression was performed., Results: Three hundred nineteen patients, including 107 cases and 212 controls, were studied. Community-acquired pneumonia (CAP) was the most frequent diagnosis (23% of cases) followed by sepsis (16%). We identified six predictive factors of an unplanned short-term transfer to the ICU. Former smoking status, fever between 38°C and 40°C, dyspnea as the chief complaint in the ED, a lower MEDS score, an elevated acute physiology age chronic health evaluation score, and the ordering of an arterial blood gas each correlate with secondary transfer to an intensive care setting., Conclusion: We report a higher risk of short-term unscheduled ICU transfer in patients meeting these criteria. These patients should be closely monitored and frequently re-evaluated before being transferred to a general ward.

Competing Interests: M. Cancella de Abreu déclare participer ou avoir participé à des interventions ponctuelles pour les entreprises bioMérieux et Beckman Coulter. P. Hausfater déclare participer ou avoir participé à des interventions ponctuelles pour les entreprises bioMérieux, Radiometer, Beckman Coulter et avoir été pris en charge à l’occasion de déplacement pour congrès par bioMérieux, Radiometer, Beckman Coulter et Thermo Fisher Scientific.

Competing Interests: M. Cancella de Abreu déclare participer ou avoir participé à des interventions ponctuelles pour les entreprises bioMérieux et Beckman Coulter. P. Hausfater déclare participer ou avoir participé à des interventions ponctuelles pour les entreprises bioMérieux, Radiometer, Beckman Coulter et avoir été pris en charge à l’occasion de déplacement pour congrès par bioMérieux, Radiometer, Beckman Coulter et Thermo Fisher Scientific.