Epidemiology and patterns of empiric antimicrobial therapy practice in patients with community-onset sepsis using data from a Japanese nationwide medical claims database-the Japan Sepsis Alliance (JaSA) study group.

Objectives: We aimed to describe empiric antimicrobial options for patients with community-onset sepsis using nationwide real-world data from Japan. Methods: This retrospective cohort study used nationwide Japanese data from a medical reimbursement system database. Patients aged ≥20 years with both presumed infections and acute organ dysfunction who were admitted to hospitals from the outpatient department or emergency department between 2010 and 2017 were enrolled. We described the initial choices of antimicrobials for patients with sepsis stratified by intensive care unit (ICU) or ward. Results: There were 1,195,741 patients with community-onset sepsis; of these, 1,068,719 and 127,022 patients were admitted to the wards and ICU, respectively. Third-generation cephalosporins and carbapenem were most commonly used for patients with community-onset sepsis. We found that 1.7% and 6.0% of patients initially used antimicrobials for methicillin-resistant Staphylococcus aureus coverage in the wards and ICU, respectively. Although half of the patients initially used antipseudomonal agents, only a few patients used a combination of antipseudomonal agents. Moreover, few patients initially used a combination of antimicrobials to treat methicillin-resistant Staphylococcus aureus and Pseudomonas sp. Conclusion: Third-generation cephalosporins and carbapenem were most frequently used for patients with sepsis. A combination therapy of antimicrobials for drug-resistant bacteria coverage was rarely provided to these patients.

Association between intra-abdominal injured organs and abdominal compartment syndrome in patients with severe blunt trauma: A propensity score matched study using nationwide trauma registry in Japan.

INTRODUCTION: Abdominal compartment syndrome (ACS) after blunt abdominal trauma is a rare complication that requires early recognition and subsequent surgical intervention for optimal outcome. We aimed to investigate how differences in injured abdominal organs affect ACS development in patients with severe blunt abdominal trauma. METHODS: This nested case-control study used a nationwide registry of trauma patients, namely, the Japan Trauma Data Bank (JTDB), and only included patients aged ≥ 18 years with blunt severe abdominal trauma, defined as an AIS score of abdomen ≥ 3, sustained between 2004 and 2017. Patients without ACS were used as control subjects and identified using propensity score (PS) matching. Characteristics and outcomes between patients with and without ACS were compared and logistic regression was used to identify specific risk factors for ACS. RESULTS: Among 294,274 patients in the JTDB, 11,220 were eligible for inclusion before PS matching, and 150 (1.3%) developed ACS after trauma. PS matching led to the inclusion of 131 and 655 patients with and without ACS, respectively. Compared to controls, patients with ACS had higher number of injured organs in the abdomen and displayed a greater frequency of vascular and pancreatic injuries, need for blood transfusion, and disseminated intravascular coagulopathy, a complication of ACS. In-hospital mortality was higher in patients with ACS than those without ACS (51.1% vs. 26.0%, p < 0.01). Logistic regression analysis revealed that a higher number of injured organs in the abdomen [odds ratio (OR) (95% confidence interval [CI]): 1.76 (1.23-2.53)] and pancreatic injury [OR (95% CI): 1.53 (1.03-2.27)] were independently associated with ACS. CONCLUSIONS: Greater number of injured organs in abdomen and pancreatic injury are independent risk factors for the development of ACS.

Impact of defibrillation with automated external defibrillator by bystander before defibrillation by emergency medical system personnel on neurological outcome of out-of-hospital cardiac arrest with non-cardiac etiology.

Aim of the study: Although defibrillation using automated external defibrillator (AED) by bystander prior to emergency medical system (EMS) arrival was associated with favorable outcomes in out-of-hospital cardiac arrest (OHCA) of cardiac cause, whether it improves outcomes of OHCA due to non-cardiac cause is not clear. We aimed to investigate the impact of defibrillation with AED by bystander before defibrillation by EMS personnel on the outcomes of OHCA of presumed non-cardiac cause. Methods: This was a retrospective cohort study using the All-Japan Utstein registry (reference period: 2013 to 2017). We included adult patients with OHCA of presumed non-cardiac cause, who had initial shockable rhythm, and who received witnessed arrest bystander cardiopulmonary resuscitation (CPR). Exposure variable was defibrillation with AED by bystander in comparison with initial defibrillation by EMS. Logistic regression analyses were conducted to assess the association between bystander AED shock and favorable neurological outcome (Cerebral Performance Category scale 1 or 2) at one month. Results: Among the 1,053 patients included for analysis, 57 (5.4%) received bystander AED shock. There was no statistically significant difference in the rate of favorable neurological outcome at one month between groups [9 (15.8%) vs 109 (10.9%), p = 0.26]. Logistic regression analysis adjusted for characteristics, intervention, and time course of CPR showed no association between bystander AED shock and favorable neurological outcome [OR (95% CI): 1.63 (0.70-3.77), p = 0.25]. Conclusion: In this study, defibrillation with AED by bystander before defibrillation by EMS personnel was not associated with the favorable outcomes of OHCA of presumed non-cardiac cause.

A nested case-control study of risk for pulmonary embolism in the general trauma population using nationwide trauma registry data in Japan.

Post-trauma patients are at great risk of pulmonary embolism (PE), however, data assessing specific risk factors for post-traumatic PE are scarce. This was a nested case-control study using the Japan Trauma Data Bank between 2004 and 2017. We enrolled patients aged ≥ 16 years, Injury Severity Score ≥ 9, and length of hospital stay ≥ 2 days, with PE and without PE, using propensity score matching. We conducted logistic regression analyses to examine risk factors for PE. We included 719 patients with PE and 3595 patients without PE. Of these patients, 1864 [43.2%] were male, and their median Interquartile Range (IQR) age was 73 [55-84] years. The major mechanism of injury was blunt (4282 [99.3%]). Median [IQR] Injury Severity Score (ISS) was 10 [9-18]. In the multivariate analysis, the variables spinal injury [odds ratio (OR), 1.40 (1.03-1.89)]; long bone open fracture in upper extremity and lower extremity [OR, 1.51 (1.06-2.15) and OR, 3.69 (2.89-4.71), respectively]; central vein catheter [OR, 2.17 (1.44-3.27)]; and any surgery [OR, 4.48 (3.46-5.81)] were independently associated with PE. Spinal injury, long bone open fracture in extremities, central vein catheter placement, and any surgery were risk factors for post-traumatic PE. Prompt initiation of prophylaxis is needed for patients with such trauma.

The impact of infection complications after trauma differs according to trauma severity.

The impact of infection on the prognosis of trauma patients according to severity remains unclear. We assessed the impact of infection complications on in-hospital mortality among patients with trauma according to severity. This retrospective cohort study used a nationwide registry of trauma patients. Patients aged ≥ 18 years with blunt or penetrating trauma who were admitted to intensive care units or general wards between 2004 and 2017 were included. We compared the baseline characteristics and outcomes between patients with and without infection and conducted a multivariable logistic regression analysis to investigate the impact of infection on in-hospital mortality according to trauma severity, which was classified as mild [Injury Severity Score (ISS) < 15], moderate (ISS 15-29), or severe (ISS ≥ 30). Among the 150,948 patients in this study, 10,338 (6.8%) developed infections. Patients with infection had greater in-hospital mortality than patients without infection [1085 (10.5%) vs. 2898 (2.1%), p < 0.01]. After adjusting for clinical characteristics, in-hospital mortality differed between trauma patients with and without infection according to trauma severity [17.1% (95% CI 15.2-18.9%) vs. 2.9% (95% CI 2.7-3.1%), p < 0.01, in patients with mild trauma; 14.8% (95% CI 13.3-16.3%) vs. 8.4% (95% CI 7.9-8.8%), p < 0.01, in patients with moderate trauma; and 13.5% (95% CI 11.2-15.7%) vs. 13.7% (95% CI 12.4-14.9%), p = 0.86, in patients with severe trauma]. In conclusion, the effect of infection complications in patients with trauma on in-hospital mortality differs by trauma severity.

Surgical mask use by healthcare personnel to prevent COVID-19 spread in a long-term care facility.

Long-term care facilities are a recognized high-risk setting for severe outcomes during the coronavirus disease 2019 (COVID-19) outbreak. This study describes a COVID-19 outbreak in a long-term care facility in Japan. The index case was a nurse who wore a surgical mask and used standard precautions. Of the 17 confirmed cases of COVID-19, 14 (14/93, 15.1%) were residents and three (3/69, 4.3%) were healthcare personnel (HCP); no visitors tested positive 0 (0/22, 0.0%). Mask utilization by HCP was not much effective in preventing COVID-19 transmission, even when interaction was not considered as being in close contact.

Assessment of blood consumption score for pediatrics predicts transfusion requirements for children with trauma.

ABSTRACT: Although transfusion is a primary life-saving technique, the assessment of transfusion requirements in children with trauma at an early stage is challenging. We aimed to develop a scoring system for predicting transfusion requirements in children with trauma.This was a case-control study that employed a nationwide registry of patients with trauma (Japan Trauma Data Bank) and included patients aged <16 years with blunt trauma between 2004 and 2015. An assessment of blood consumption score for pediatrics (ped-ABC score) was developed based on previous literatures and clinical relevance. One point was assigned for each of the following criteria: systolic blood pressure ≤90 mm Hg, heart rate ≥120/min, Glasgow coma scale (GCS) score <15, and positive focused assessment with sonography for trauma (FAST) scan. For sensitivity analysis, we assessed age-adjusted ped-ABC scores using cutoff points for different ages.Among 5943 pediatric patients with trauma, 540 patients had transfusion within 24 hours after trauma. The in-hospital mortality rate was 2.6% (145/5615). The transfusion rate increased from 7.6% (430/5631) to 35.3% (110/312) in patients with systolic blood pressure ≤90 mm Hg (1 point), from 6.1% (276/4504) to 18.3% (264/1439) in patients with heart rate ≥120/min (1 point), from 4.1% (130/3198) to 14.9% (410/2745) in patients with disturbance of consciousness with GCS score <15 (1 point), and from 7.4% (400/5380) to 24.9% (140/563) in patients with positive FAST scan (1 point). Ped-ABC scores of 0, 1, 2, 3, and 4 points were associated with transfusion rates of 2.2% (48/2210), 7.5% (198/2628), 19.8% (181/912), 53.3% (88/165), and 89.3% (25/28), respectively. After age adjustment, c-statistic was 0.76 (95% confidence interval, 0.74-0.78).The ped-ABC score using vital signs and FAST scan may be helpful in predicting the requirement for transfusion within 24 hours in children with trauma.

Risk Factors of Fat Embolism Syndrome After Trauma: A Nested Case-Control Study With the Use of a Nationwide Trauma Registry in Japan.

BACKGROUND: Fat embolism syndrome (FES) is a rare syndrome resulting from a fat embolism, which is defined by the presence of fat globules in the pulmonary microcirculation; it is associated with a wide range of symptoms. RESEARCH QUESTION: What are the specific unknown risk factors for FES after we have controlled for basic characteristics and patient's severity? STUDY DESIGN AND METHODS: This was a nested case-control study that used the Japan Trauma Data Bank database from 2004 and 2017. We included patients with FES and identified patients without FES as control subjects using a propensity score matching. The primary outcome was the presence of FES during a hospital stay. RESULTS: There were 209 (0.1%) patients with FES after trauma; they were compared with 2,090 matched patients from 168,835 candidates for this study. Patients with FES had long bone and open fractures in their extremities more frequently than those without FES. Regarding treatments, patients with FES received bone reduction and fixation more than those without FES. Among patients who received bone reduction and fixation, time to operation was not different between the groups (P = .63). The overall in-hospital mortality rate was 5.8% in patients with FES and 3.4% in those without FES (P = .11). Conditional logistic regression models to identify risk factors associated with FES shows long bone and open fractures in extremities injury were associated with FES. Primary bone reduction and fixation was not associated independently with FES (OR, 1.80; 95% CI, 0.92-3.54), but delay time to the operation was associated with FES (OR, 2.21; 95% CI, 1.16-4.23). INTERPRETATION: Long bone and open fractures in injuries to the extremities were associated with FES. Although bone reduction and fixation were not associated with FES, delay time to the operation was associated with FES.

Characteristics and outcomes of frail patients with suspected infection in intensive care units: a descriptive analysis from a multicenter cohort study.

BACKGROUND: Frailty is associated with morbidity and mortality in patients admitted to intensive care units (ICUs). However, the characteristics of frail patients with suspected infection remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs. METHODS: This is a secondary analysis of a multicenter cohort study, including 22 ICUs in Japan. Adult patients (aged ≥16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes among three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score, 1-3), vulnerable (score, 4), and frail (score, 5-9). We conducted subgroup analysis of patients with sepsis defined as per Sepsis-3 criteria. We also produced Kaplan-Meier survival curves for 90-day survival. RESULTS: We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median CFS score of 3 (interquartile range [IQR] 3-5) were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 (31.4%) were frail. The median patient age was 72 years (IQR 60-81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (IQR 4-10), 8 (IQR 5-11), and 7 (IQR 5-10), respectively (p = 0.59). The median body temperatures of fit, vulnerable, and frail patients were 37.5 °C (IQR 36.5 °C-38.5 °C), 37.5 °C (IQR 36.4 °C-38.6 °C), and 37.0 °C (IQR 36.3 °C-38.1 °C), respectively (p < 0.01). The median C-reactive protein levels of fit, vulnerable, and frail patients were 13.6 (IQR 4.6-24.5), 12.1 (IQR 3.9-24.9), 10.5 (IQR 3.0-21.0) mg/dL, respectively (p < 0.01). In-hospital mortality did not statistically differ among the patients according to frailty (p = 0.19). Kaplan-Meier survival curves showed little difference in the mortality rate during short-term follow-up. However, more vulnerable and frail patients died after 30-day than fit patients; this difference was not statistically significant (p = 0.25). Compared with the fit and vulnerable groups, the rate of home discharge was lower in the frail group. CONCLUSION: Frail and vulnerable patients with suspected infection tend to have poor disease outcomes. However, they did not show a statistically significant increase in the 90-day mortality risk.

Flux Growth and Magnetic Properties of Helimagnetic Hexagonal Ferrite Ba(Fe1-x Sc x )12O19 Single Crystals.

Fabricating large, high-crystalline-quality single-crystal samples of hexagonal ferrite Ba(Fe1-x Sc x )12O19 is the first important step to elucidating its helimagnetic structure and developing it for further applications. In this study, single crystals of Ba(Fe1-x Sc x )12O19 of various Sc concentrations x were successfully grown by the spontaneous crystallization method using Na2O-Fe2O3 flux. We determined the optimal starting composition of reagents for Ba(Fe1-x Sc x )12O19 growth as a function of x. In situ monitoring of the crystal nucleus generation accelerated the success of crystal growth. The obtained crystals comprised black and lamellate structures with a size of 13 mm × 8 mm × 2 mm and a surface of {001} orientation. X-ray diffraction and elemental analysis revealed that the obtained crystals were composed of single-phase Ba(Fe1-x Sc x )12O19 of high crystalline quality. The lattice constants a and c increased linearly with increasing x, thereby following Vegard's law. The temperature dependence of magnetization and the magnetization curves at 77 K of the x = 0.128 crystal exhibited behavior characteristics of helimagnetism. Neutron diffraction measurements of the x = 0.128 crystal exhibited magnetic satellite reflection peaks below 211 K, providing evidence that Ba(Fe1-x Sc x )12O19 behaves as a helimagnetic material.

Epidemiology of sepsis and septic shock in intensive care units between sepsis-2 and sepsis-3 populations: sepsis prognostication in intensive care unit and emergency room (SPICE-ICU).

BACKGROUND: Diagnosing sepsis remains difficult because it is not a single disease but a syndrome with various pathogen- and host factor-associated symptoms. Sepsis-3 was established to improve risk stratification among patients with infection based on organ failures, but it has been still controversial compared with previous definitions. Therefore, we aimed to describe characteristics of patients who met sepsis-2 (severe sepsis) and sepsis-3 definitions. METHODS: This was a multicenter, prospective cohort study conducted by 22 intensive care units (ICUs) in Japan. Adult patients (≥ 16 years) with newly suspected infection from December 2017 to May 2018 were included. Those without infection at final diagnosis were excluded. Patient's characteristics and outcomes were described according to whether they met each definition or not. RESULTS: In total, 618 patients with suspected infection were admitted to 22 ICUs during the study, of whom 530 (85.8%) met the sepsis-2 definition and 569 (92.1%) met the sepsis-3 definition. The two groups comprised different individuals, and 501 (81.1%) patients met both definitions. In-hospital mortality of study population was 19.1%. In-hospital mortality among patients with sepsis-2 and sepsis-3 patients was comparable (21.7% and 19.8%, respectively). Patients exclusively identified with sepsis-2 or sepsis-3 had a lower mortality (17.2% vs. 4.4%, respectively). No patients died if they did not meet any definitions. Patients who met sepsis-3 shock definition had higher in-hospital mortality than those who met sepsis-2 shock definition. CONCLUSIONS: Most patients with infection admitted to ICU meet sepsis-2 and sepsis-3 criteria. However, in-hospital mortality did not occur if patients did not meet any criteria. Better criteria might be developed by better selection and combination of elements in both definitions. TRIAL REGISTRATION: UMIN000027452.

Trauma complications and in-hospital mortality: failure-to-rescue.

BACKGROUND: Reducing medical errors and minimizing complications have become the focus of quality improvement in medicine. Failure-to-rescue (FTR) is defined as death after a surgical complication, which is an institution-level surgical safety and quality metric that is an important variable affecting mortality rates in hospitals. This study aims to examine whether complication and FTR are different across low- and high-mortality hospitals for trauma care. METHODS: This was a retrospective cohort study performed at trauma care hospitals registered at Japan Trauma Data Bank (JTDB) from 2004 to 2017. Trauma patients aged ≥ 15 years with injury severity score (ISS) of ≥ 3 and those who survived for > 48 h after hospital admission were included. The hospitals in JTDB were categorized into three groups by standardized mortality rate. We compared trauma complications, FTR, and in-hospital mortality by a standardized mortality rate (divided by the institute-level quartile). RESULTS: Among 184,214 patients that were enrolled, the rate of any complication was 12.7%. The overall mortality rate was 3.7%, and the mortality rate among trauma patients without complications was only 2.8% (non-precedented deaths). However, the mortality rate among trauma patients with any complications was 10.2% (FTR). Hospitals were categorized into high- (40 facilities with 44,773 patients), average- (72 facilities with 102,368 patients), and low- (39 facilities with 37,073 patients) mortality hospitals, using the hospital ranking of a standardized mortality rate. High-mortality hospitals showed lower ISS than low-mortality hospitals [10 (IQR, 9-18) vs. 11 (IQR, 9-20), P < 0.01]. Patients in high-mortality hospitals showed more complications (14.2% vs. 11.2%, P < 0.01), in-hospital mortality (5.1% vs. 2.5%, P < 0.01), FTR (13.6% vs. 7.4%, P < 0.01), and non-precedented deaths (3.6% vs. 1.9%, P < 0.01) than those in low-mortality hospitals. CONCLUSIONS: Unlike reports of elective surgery, complication rates and FTR are associated with in-hospital mortality rates at the center level in trauma care.

History of diabetes may delay antibiotic administration in patients with severe sepsis presenting to emergency departments.

Clinical manifestations of sepsis differ between patients with and without diabetes mellitus (DM), and these differences could influence the clinical behaviors of medical staff. Therefore, we aimed to investigate whether pre-existing DM was associated with the time to antibiotics or sepsis care protocols.This was a retrospective cohort study.It conducted at 53 intensive care units (ICUs) in Japan.Consecutive adult patients with severe sepsis admitted directly to ICUs form emergency departments from January 2016 to March 2017 were included.The primary outcome was time to antibiotics.Of the 619 eligible patients, 142 had DM and 477 did not have DM. The median times (interquartile ranges) to antibiotics in patients with and without DM were 103 minutes (60-180 minutes) and 86 minutes (45-155 minutes), respectively (P = .05). There were no significant differences in the rates of compliance with sepsis protocols or with patient-centred outcomes such as in-hospital mortality. The mortality rates of patients with and without DM were 23.9% and 21.6%, respectively (P = .55). Comparing patients with and without DM, the gamma generalized linear model-adjusted relative difference indicated that patients with DM had a delay to starting antibiotics of 26.5% (95% confidence intervals (95%CI): 4.6-52.8, P = .02). The gamma generalized linear model-adjusted relative difference with multiple imputation for missing data of sequential organ failure assessment was 19.9% (95%CI: 1.0-42.3, P = .04). The linear regression model-adjusted beta coefficient indicated that patients with DM had a delay to starting antibiotics of 29.2 minutes (95%CI: 6.8-51.7, P = .01). Logistic regression modelling showed that pre-existing DM was not associated with in-hospital mortality (odds ratio, 1.26; 95%CI: 0.72-2.19, P = .42).Pre-existing DM was associated with delayed antibiotic administration among patients with severe sepsis or septic shock; however, patient-centred outcomes and compliance with sepsis care protocols were comparable.

Risk modifiers of acute respiratory distress syndrome in patients with non-pulmonary sepsis: a retrospective analysis of the FORECAST study.

BACKGROUND: Predisposing conditions and risk modifiers instead of causes and risk factors have recently been used as alternatives to identify patients at a risk of acute respiratory distress syndrome (ARDS). However, data regarding risk modifiers among patients with non-pulmonary sepsis is rare. METHODS: We conducted a secondary analysis of the multicenter, prospective, Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) cohort study that was conducted in 59 intensive care units (ICUs) in Japan during January 2016-March 2017. Adult patients with severe sepsis caused by non-pulmonary infection were included, and the primary outcome was having ARDS, defined as meeting the Berlin definition on the first or fourth day of screening. Multivariate logistic regression modeling was used to identify risk modifiers associated with ARDS, and odds ratios (ORs) and their 95% confidence intervals were reported. The following explanatory variables were then assessed: age, sex, admission source, body mass index, smoking status, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, steroid use, statin use, infection site, septic shock, and acute physiology and chronic health evaluation (APACHE) II score. RESULTS: After applying inclusion and exclusion criteria, 594 patients with non-pulmonary sepsis were enrolled, among whom 85 (14.3%) had ARDS. Septic shock was diagnosed in 80% of patients with ARDS and 66% of those without ARDS (p = 0.01). APACHE II scores were higher in patients with ARDS [26 (22-33)] than in those without ARDS [21 (16-28), p < 0.01]. In the multivariate logistic regression model, the following were independently associated with ARDS: ICU admission source [OR, 1.89 (1.06-3.40) for emergency department compared with hospital wards], smoking status [OR, 0.18 (0.06-0.59) for current smoking compared with never smoked], infection site [OR, 2.39 (1.04-5.40) for soft tissue infection compared with abdominal infection], and APACHE II score [OR, 1.08 (1.05-1.12) for higher compared with lower score]. CONCLUSIONS: Soft tissue infection, ICU admission from an emergency department, and a higher APACHE II score appear to be the risk modifiers of ARDS in patients with non-pulmonary sepsis.

Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study.

BACKGROUND: Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. METHODS: This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0-60, 61-120, 121-180, 181-240, 241-360, and 361-1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with "hospital" as the grouping variable. RESULTS: Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55-189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48-164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39-180 min)] and longest in patients transferred from wards [120 min (62-226)]. Overall crude mortality was 23.4%, where patients in the 0-60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3-34.1%)], whereas those in the 61-120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5-26.6%)]. Differences in mortality were noted only between the 0-60 min and 61-120 min groups. CONCLUSIONS: We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.