IMPORTANCE Broad-spectrum antibiotics are recommended for all patients with suspected sepsis to minimize the risk of undertreatment. However, little is known regarding the net prevalence of antibiotic-resistant pathogens across all patients with community-onset sepsis or the outcomes associated with unnecessarily broad empiric treatment. OBJECTIVE To elucidate the epidemiology of antibiotic-resistant pathogens and the outcomes associated with both undertreatment and overtreatment in patients with culture-positive communityonset sepsis. DESIGN, SETTING, AND PARTICIPANTS This cohort study included 17 430 adults admitted to 104 US hospitals between January 2009 and December 2015 with sepsis and positive clinical cultures within 2 days of admission. Data analysis took place from January 2018 to December 2019. EXPOSURES Inadequate empiric antibiotic therapy (ie, Ն1 pathogen nonsusceptible to all antibiotics administered on the first or second day of treatment) and unnecessarily broad empiric therapy (ie, active against methicillin-resistant Staphylococcus aureus [MRSA]; vancomycin-resistant Enterococcus [VRE]; ceftriaxone-resistant gram-negative [CTX-RO] organisms, including Pseudomonas aeruginosa; or extended-spectrum β-lactamase [ESBL] gram-negative organisms when none of these were isolated). MAIN OUTCOMES AND MEASURES Prevalence and empiric treatment rates for antibiotic-resistant organisms and associations of inadequate and unnecessarily broad empiric therapy with in-hospital mortality were assessed, adjusting for baseline characteristics and severity of illness. RESULTS Of 17 430 patients with culture-positive community-onset sepsis (median [interquartile range] age, 69 [57-81] years; 9737 [55.9%] women), 2865 (16.4%) died in the hospital. The most common culture-positive sites were urine (9077 [52.1%]), blood (6968 [40.0%]), and the respiratory tract (2912 [16.7%]). The most common pathogens were Escherichia coli (5873 [33.7%]), S aureus (3706 [21.3%]), and Streptococcus species (2361 [13.5%]). Among 15 183 cases in which all antibiotic-pathogen susceptibility combinations could be calculated, most (12 398 [81.6%]) received adequate empiric antibiotics. Empiric therapy targeted resistant organisms in 11 683 of 17 430 cases (67.0%; primarily vancomycin and anti-Pseudomonal β-lactams), but resistant organisms were uncommon (MRSA, 2045 [11.7%]; CTX-RO, 2278 [13.1%]; VRE, 360 [2.1%]; ESBLs, 133 [0.8%]). The net prevalence for at least 1 resistant gram-positive organism (ie, MRSA or VRE) was 13.6% (2376 patients), and for at least 1 resistant gram-negative organism (ie, CTX-RO, ESBL, or CRE), it was 13.2% (2297 patients). Both inadequate and unnecessarily broad empiric antibiotics were associated with (continued) Key Points Question What is the prevalence of antibiotic resistance in communityonset sepsis, and is there risk associated with the receipt of empiric broadspectrum antibiotics? Findings In this cohort study of 17 430 adults with culture-positive sepsis admitted to 104 US hospitals, 67.0% received empiric b...

Rationale: Observational studies suggest obesity is associated with sepsis survival, but these studies are small, fail to adjust for key confounders, measure body mass index (BMI) at inconsistent time points, and/or use administrative data to define sepsis. Objective: To estimate the relationship between BMI and sepsis mortality using detailed clinical data for case detection and risk-adjustment. Design: Retrospective cohort analysis of a large clinical data repository Setting: 139 hospitals in the United States of America Patients: Adult inpatients with sepsis meeting Sepsis-3 criteria Exposure: BMI in six categories: underweight (BMI<18.5kg/m 2), normal-weight (BMI=18.5-24.9kg/m 2), overweight (BMI=25.0-29.9kg/m 2), obese-class-I (BMI=30.0-34.9kg/m 2), obeseclass-II (BMI=35.0-39.9kg/m 2), and obese-class-III (BMI≥40kg/m 2). Measurements: Multivariate logistic regression with generalized estimating equations to estimate the effect of BMI category on short-term mortality (in-hospital death or discharge to hospice) adjusting for patient, infection, and hospital-level factors. Sensitivity analyses were

Objectives: Sepsis-3 defines organ dysfunction as an increase in the Sequential Organ Failure Assessment score by greater than or equal to 2 points. However, some Sequential Organ Failure Assessment score components are not routinely recorded in all hospitals’ electronic health record systems, limiting its utility for wide-scale sepsis surveillance. The Centers for Disease Control and Prevention recently released the Adult Sepsis Event surveillance definition that includes simplified organ dysfunction criteria optimized for electronic health records (eSOFA). We compared eSOFA versus Sequential Organ Failure Assessment with regard to sepsis prevalence, overlap, and outcomes. Design: Retrospective cohort study. Setting: One hundred eleven U.S. hospitals in the Cerner HealthFacts dataset. Patients: Adults hospitalized in 2013-2015. Interventions: None. Measurements and Main Results: We identified clinical indicators of presumed infection (blood cultures and antibiotics) concurrent with either: 1) an increase in Sequential Organ Failure Assessment score by 2 or more points (Sepsis-3) or 2) 1 or more eSOFA criteria: vasopressor initiation, mechanical ventilation initiation, lactate greater than or equal to 2.0 mmol/L, doubling in creatinine, doubling in bilirubin to greater than or equal to 2.0 mg/dL, or greater than or equal to 50% decrease in platelet count to less than 100 cells/μL (Centers for Disease Control and Prevention Adult Sepsis Event). We compared area under the receiver operating characteristic curves for discriminating in-hospital mortality, adjusting for baseline characteristics. Of 942,360 patients in the cohort, 57,242 (6.1%) had sepsis by Sequential Organ Failure Assessment versus 41,618 (4.4%) by eSOFA. Agreement between sepsis by Sequential Organ Failure Assessment and eSOFA was good (Cronbach’s alpha 0.81). Baseline characteristics and infectious diagnoses were similar, but mortality was higher with eSOFA (17.1%) versus Sequential Organ Failure Assessment (14.4%; p < 0.001) as was discrimination for mortality (area under the receiver operating characteristic curve, 0.774 vs 0.759; p < 0.001). Comparisons were consistent across subgroups of age, infectious diagnoses, and comorbidities. Conclusions: The Adult Sepsis Event’s eSOFA organ dysfunction criteria identify a smaller, more severely ill sepsis cohort compared with the Sequential Organ Failure Assessment score, but with good overlap and similar clinical characteristics. Adult Sepsis Events may facilitate wide-scale automated sepsis surveillance that tracks closely with the more complex Sepsis-3 criteria.

Objectives: Prior studies have reported that hospital-onset sepsis is associated with higher mortality rates than community-onset sepsis. Most studies, however, have used inconsistent case-finding methods and applied limited risk-adjustment for potential confounders. We used consistent sepsis criteria and detailed electronic clinical data to elucidate the epidemiology and mortality associated with hospital-onset sepsis. Design: Retrospective cohort study. Setting: 136 U.S. hospitals in the Cerner HealthFacts dataset. Patients: Adults hospitalized in 2009–2015. Interventions: None. Measurements and Main Results: We identified sepsis using Centers for Disease Control and Prevention Adult Sepsis Event criteria and estimated the risk of in-hospital death for hospital-onset sepsis versus community-onset sepsis using logistic regression models. In patients admitted without community-onset sepsis, we estimated risk of death associated with hospital-onset sepsis using Cox regression models with sepsis as a time-varying covariate. Models were adjusted for baseline characteristics and severity of illness. Among 2.2 million hospitalizations, there were 95,154 sepsis cases: 83,620 (87.9%) community-onset sepsis and 11,534 (12.1%) hospital-onset sepsis (0.5% of hospitalized cohort). Compared to community-onset sepsis, hospital-onset sepsis patients were younger (median 66 vs 68 yr) but had more comorbidities (median Elixhauser score 14 vs 11), higher Sequential Organ Failure Assessment scores (median 4 vs 3), higher ICU admission rates (61% vs 44%), longer hospital length of stay (median 19 vs 8 d), and higher in-hospital mortality (33% vs 17%) (p < 0.001 for all comparisons). On multivariate analysis, hospital-onset sepsis was associated with higher mortality versus community-onset sepsis (odds ratio, 2.1; 95% CI, 2.0–2.2) and patients admitted without sepsis (hazard ratio, 3.0; 95% CI, 2.9–3.2). Conclusions: Hospital-onset sepsis complicated one in 200 hospitalizations and accounted for one in eight sepsis cases, with one in three patients dying in-hospital. Hospital-onset sepsis preferentially afflicted ill patients but even after risk-adjustment, they were twice as likely to die as community-onset sepsis patients; in patients admitted without sepsis, hospital-onset sepsis tripled the risk of death. Hospital-onset sepsis is an important target for surveillance, prevention, and quality improvement initiatives.

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