Prevention of Vascular Access Device-Associated Hospital Onset Bacteremia and Fungemia: A Review of Emerging Perspectives and Synthesis of Technical Aspects.

Significant events impacting healthcare over the last several years have been associated with escalating rates of healthcare-associated infections. This has resulted in increased efforts to reinstitute well-established and evidence-based infection prevention practices, particularly for central line associated bloodstream infections. However, implementation of prevention initiatives beyond central lines has not received the same level of acknowledgement and response as being a considerable risk to patients. This article, authored by infection prevention, infectious disease, and vascular access professionals, provides emerging perspectives and technical aspects associated with the complete lifecycle of a vascular access device. The intent is to provide insight and perspective into enhancing current IP practices in the acute care hospital setting. This will also help prepare hospitals for upcoming broader surveillance and intervention activities aimed at reducing Hospital Onset Bacteremia and Fungemia (HOB) associated with all types of vascular access devices.

Improving Sepsis Outcomes in the Era of Pay-for-Performance and Electronic Quality Measures: A Joint IDSA/ACEP/PIDS/SHEA/SHM/SIDP Position Paper.

The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis/Septic Shock Management Bundle (SEP-1) as a pay-for-reporting measure in 2015 and is now planning to make it a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing Program. This joint IDSA/ACEP/PIDS/SHEA/SHM/SIPD position paper highlights concerns with this change. Multiple studies indicate that SEP-1 implementation was associated with increased broad-spectrum antibiotic use, lactate measurements, and aggressive fluid resuscitation for patients with suspected sepsis but not with decreased mortality rates. Increased focus on SEP-1 risks further diverting attention and resources from more effective measures and comprehensive sepsis care. We recommend retiring SEP-1 rather than using it in a payment model and shifting instead to new sepsis metrics that focus on patient outcomes. CMS is developing a community-onset sepsis 30-day mortality electronic clinical quality measure (eCQM) that is an important step in this direction. The eCQM preliminarily identifies sepsis using systemic inflammatory response syndrome (SIRS) criteria, antibiotic administrations or diagnosis codes for infection or sepsis, and clinical indicators of acute organ dysfunction. We support the eCQM but recommend removing SIRS criteria and diagnosis codes to streamline implementation, decrease variability between hospitals, maintain vigilance for patients with sepsis but without SIRS, and avoid promoting antibiotic use in uninfected patients with SIRS. We further advocate for CMS to harmonize the eCQM with the Centers for Disease Control and Prevention's (CDC) Adult Sepsis Event surveillance metric to promote unity in federal measures, decrease reporting burden for hospitals, and facilitate shared prevention initiatives. These steps will result in a more robust measure that will encourage hospitals to pay more attention to the full breadth of sepsis care, stimulate new innovations in diagnosis and treatment, and ultimately bring us closer to our shared goal of improving outcomes for patients.

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs: A Randomized Clinical Trial.

Importance: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. Objective: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. Design, Setting, and Participants: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. Intervention: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). Main Outcomes and Measures: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. Results: Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). Conclusions and Relevance: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. Trial Registration: ClinicalTrials.gov Identifier: NCT03140423.

Risk of Misleading Conclusions in Observational Studies of Time-to-Antibiotics and Mortality in Suspected Sepsis.

BACKGROUND: Influential studies conclude that each hour until antibiotics increases mortality in sepsis. However, these analyses often (1) adjusted for limited covariates, (2) included patients with long delays until antibiotics, (3) combined sepsis and septic shock, and (4) used linear models presuming each hour delay has equal impact. We evaluated the effect of these analytic choices on associations between time-to-antibiotics and mortality. METHODS: We retrospectively identified 104 248 adults admitted to 5 hospitals from 2015-2022 with suspected infection (blood culture collection and intravenous antibiotics ≤24 h of arrival), including 25 990 with suspected septic shock and 23 619 with sepsis without shock. We used multivariable regression to calculate associations between time-to-antibiotics and in-hospital mortality under successively broader confounding-adjustment, shorter maximum time-to-antibiotic intervals, stratification by illness severity, and removing assumptions of linear hourly associations. RESULTS: Changing covariates, maximum time-to-antibiotics, and severity stratification altered the magnitude, direction, and significance of observed associations between time-to-antibiotics and mortality. In a fully adjusted model of patients treated ≤6 hours, each hour was associated with higher mortality for septic shock (adjusted odds ratio [aOR]: 1.07; 95% CI: 1.04-1.11) but not sepsis without shock (aOR: 1.03; .98-1.09) or suspected infection alone (aOR: .99; .94-1.05). Modeling each hour separately confirmed that every hour of delay was associated with increased mortality for septic shock, but only delays >6 hours were associated with higher mortality for sepsis without shock. CONCLUSIONS: Associations between time-to-antibiotics and mortality in sepsis are highly sensitive to analytic choices. Failure to adequately address these issues can generate misleading conclusions.

Public Health Interventions Guided by Houston's Wastewater Surveillance Program During the COVID-19 Pandemic.

Since the start of the COVID-19 pandemic, wastewater surveillance has emerged as a powerful tool used by public health authorities to track SARS-CoV-2 infections in communities. In May 2020, the Houston Health Department began working with a coalition of municipal and academic partners to develop a wastewater monitoring and reporting system for the city of Houston, Texas. Data collected from the system are integrated with other COVID-19 surveillance data and communicated through different channels to local authorities and the general public. This information is used to shape policies and inform actions to mitigate and prevent the spread of COVID-19 at municipal, institutional, and individual levels. Based on the success of this monitoring and reporting system to drive public health protection efforts, the wastewater surveillance program is likely to become a standard part of the public health toolkit for responding to infectious diseases and, potentially, other disease-causing outbreaks.

Society for Healthcare Epidemiology of America Compendium updates 2022.

PURPOSE OF REVIEW: Healthcare-associated infections (HAIs) are a leading cause of preventable harm in US hospitals. Hospitals are required to conduct surveillance and report selected HAIs, including central line-associated bloodstream infections, catheter-associated urinary tract infections, colon and abdominal hysterectomy surgical-site infections, methicillin-resistant Staphylococcus aureus bacteremia, and Clostridioides difficile infections, to the CDC's National Healthcare Safety Network. RECENT FINDINGS: Up until the COVID-19 pandemic, there was significant progress in reducing HAIs. However, the pandemic resulted in extraordinary challenges for infection prevention in hospitals. Increases in HAIs were observed throughout 2020 and 2021. The Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals has recently been updated and provides common sense evidenced-based strategies to reduce HAIs. SUMMARY: The purpose of this review is to highlight important changes since the 2014 Compendium.

The impact of surgical volume on hospital ranking using the standardized infection ratio.

The Centers for Medicare and Medicaid Services require hospitals to report on quality metrics which are used to financially penalize those that perform in the lowest quartile. Surgical site infections (SSIs) are a critical component of the quality metrics that target healthcare-associated infections. However, the accuracy of such hospital profiling is highly affected by small surgical volumes which lead to a large amount of uncertainty in estimating standardized hospital-specific infection rates. Currently, hospitals with less than one expected SSI are excluded from rankings, but the effectiveness of this exclusion criterion is unknown. Tools that can quantify the classification accuracy and can determine the minimal surgical volume required for a desired level of accuracy are lacking. We investigate the effect of surgical volume on the accuracy of identifying poorly performing hospitals based on the standardized infection ratio and develop simulation-based algorithms for quantifying the classification accuracy. We apply our proposed method to data from HCA Healthcare (2014-2016) on SSIs in colon surgery patients. We estimate that for a procedure like colon surgery with an overall SSI rate of 3%, to rank hospitals in the HCA colon SSI dataset, hospitals that perform less than 200 procedures have a greater than 10% chance of being incorrectly assigned to the worst performing quartile. Minimum surgical volumes and predicted events criteria are required to make evaluating hospitals reliable, and these criteria vary by overall prevalence and between-hospital variability.

Development of the invasive candidiasis discharge [I Can discharge] model: a mixed methods analysis.

Patients with invasive candidiasis (IC) have complex medical and infectious disease problems that often require continued care after discharge. This study aimed to assess echinocandin use at hospital discharge and develop a transition of care (TOC) model to facilitate discharge for patients with IC. This was a mixed method study design that used epidemiologic assessment to better understand echinocandin use at hospital discharge TOC. Using grounded theory methodology focused on patients given echinocandins during their last day of hospitalization, a TOC model for patients with IC, the invasive candidiasis [I Can] discharge model was developed to better understand discharge barriers. A total of 33% (1405/4211) echinocandin courses were continued until the last day of hospitalization. Of 536 patients chosen for in-depth review, 220 (41%) were discharged home, 109 (20%) were transferred, and 207 (39%) died prior to discharge. Almost half (46%, 151/329) of patients discharged alive received outpatient echinocandin therapy. Independent predictors for outpatient echinocandin use were osteomyelitis (OR, 4.1; 95% CI, 1.1-15.7; p = 0.04), other deep-seated infection (OR, 4.4; 95% CI, 1.7-12.0; p = 0.003), and non-home discharge location (OR, 3.9, 95% CI, 2.0-7.7; p < 0.001). The I Can discharge model was developed encompassing four distinct themes which was used to identify potential barriers to discharge. Significant echinocadin use occurs at hospital discharge TOC. The I Can discharge model may help clinical, policy, and research decision-making processes to facilitate smoother and earlier hospital discharges.

Recommendations for change in infection prevention programs and practice.

Fifty years of evolution in infection prevention and control programs have involved significant accomplishments related to clinical practices, methodologies, and technology. However, regulatory mandates, and resource and research limitations, coupled with emerging infection threats such as the COVID-19 pandemic, present considerable challenges for infection preventionists. This article provides guidance and recommendations in 14 key areas. These interventions should be considered for implementation by United States health care facilities in the near future.

The Impact of Coronavirus Disease 2019 (COVID-19) on Healthcare-Associated Infections.

BACKGROUND: The profound changes wrought by coronavirus disease 2019 (COVID-19) on routine hospital operations may have influenced performance on hospital measures, including healthcare-associated infections (HAIs). We aimed to evaluate the association between COVID-19 surges and HAI and cluster rates. METHODS: In 148 HCA Healthcare-affiliated hospitals, from 1 March 2020 to 30 September 2020, and a subset of hospitals with microbiology and cluster data through 31 December 2020, we evaluated the association between COVID-19 surges and HAIs, hospital-onset pathogens, and cluster rates using negative binomial mixed models. To account for local variation in COVID-19 pandemic surge timing, we included the number of discharges with a laboratory-confirmed COVID-19 diagnosis per staffed bed per month. RESULTS: Central line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as COVID-19 burden increased. There were 60% (95% confidence interval [CI]: 23-108%) more CLABSI, 43% (95% CI: 8-90%) more CAUTI, and 44% (95% CI: 10-88%) more cases of MRSA bacteremia than expected over 7 months based on predicted HAIs had there not been COVID-19 cases. Clostridioides difficile infection was not significantly associated with COVID-19 burden. Microbiology data from 81 of the hospitals corroborated the findings. Notably, rates of hospital-onset bloodstream infections and multidrug resistant organisms, including MRSA, vancomycin-resistant enterococcus, and Gram-negative organisms, were each significantly associated with COVID-19 surges. Finally, clusters of hospital-onset pathogens increased as the COVID-19 burden increased. CONCLUSIONS: COVID-19 surges adversely impact HAI rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention.

Epidemiology, Outcomes, and Trends of Patients With Sepsis and Opioid-Related Hospitalizations in U.S. Hospitals.

OBJECTIVES: Widespread use and misuse of prescription and illicit opioids have exposed millions to health risks including serious infectious complications. Little is known, however, about the association between opioid use and sepsis. DESIGN: Retrospective cohort study. SETTING: About 373 U.S. hospitals. PATIENTS: Adults hospitalized between January 2009 and September 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was identified by clinical indicators of concurrent infection and organ dysfunction. Opioid-related hospitalizations were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes and/or inpatient orders for buprenorphine. Clinical characteristics and outcomes were compared by sepsis and opioid-related hospitalization status. The association between opioid-related hospitalization and all-cause, in-hospital mortality in patients with sepsis was assessed using mixed-effects logistic models to adjust for baseline characteristics and severity of illness.The cohort included 6,715,286 hospitalizations; 375,479 (5.6%) had sepsis, 130,399 (1.9%) had opioid-related hospitalizations, and 8,764 (0.1%) had both. Compared with sepsis patients without opioid-related hospitalizations (n = 366,715), sepsis patients with opioid-related hospitalizations (n = 8,764) were younger (mean 52.3 vs 66.9 yr) and healthier (mean Elixhauser score 5.4 vs 10.5), had more bloodstream infections from Gram-positive and fungal pathogens (68.9% vs 47.0% and 10.6% vs 6.4%, respectively), and had lower in-hospital mortality rates (10.6% vs 16.2%; adjusted odds ratio, 0.73; 95% CI, 0.60-0.79; p < 0.001 for all comparisons). Of 1,803 patients with opioid-related hospitalizations who died in-hospital, 928 (51.5%) had sepsis. Opioid-related hospitalizations accounted for 1.5% of all sepsis-associated deaths, including 5.7% of sepsis deaths among patients less than 50 years old. From 2009 to 2015, the proportion of sepsis hospitalizations that were opioid-related increased by 77% (95% CI, 40.7-123.5%). CONCLUSIONS: Sepsis is an important cause of morbidity and mortality in patients with opioid-related hospitalizations, and opioid-related hospitalizations contribute disproportionately to sepsis-associated deaths among younger patients. In addition to ongoing efforts to combat the opioid crisis, public health agencies should focus on raising awareness about sepsis among patients who use opioids and their providers.

Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure.

The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

Impact of Risk Adjustment Using Clinical vs Administrative Data on Hospital Sepsis Mortality Comparisons.

BACKGROUND: A reliable risk-adjusted sepsis outcome measure could complement current national process metrics by identifying outlier hospitals and catalyzing additional improvements in care. However, it is unclear whether integrating clinical data into risk adjustment models identifies similar high- and low-performing hospitals compared with administrative data alone, which are simpler to acquire and analyze. METHODS: We ranked 200 US hospitals by their Centers for Disease Control and Prevention Adult Sepsis Event (ASE) mortality rates and assessed how rankings changed after applying (1) an administrative risk adjustment model incorporating demographics, comorbidities, and codes for severe illness and (2) an integrated clinical and administrative model replacing severity-of-illness codes with laboratory results, vasopressors, and mechanical ventilation. We assessed agreement between hospitals' risk-adjusted ASE mortality rates when ranked into quartiles using weighted kappa statistics (к). RESULTS: The cohort included 4 009 631 hospitalizations, of which 245 808 met ASE criteria. Risk-adjustment had a large effect on rankings: 22/50 hospitals (44%) in the worst quartile using crude mortality rates shifted into better quartiles after administrative risk adjustment, and a further 21/50 (42%) of hospitals in the worst quartile using administrative risk adjustment shifted to better quartiles after incorporating clinical data. Conversely, 14/50 (28%) hospitals in the best quartile using administrative risk adjustment shifted to worse quartiles with clinical data. Overall agreement between hospital quartile rankings when risk-adjusted using administrative vs clinical data was moderate (к = 0.55). CONCLUSIONS: Incorporating clinical data into risk adjustment substantially changes rankings of hospitals' sepsis mortality rates compared with using administrative data alone. Comprehensive risk adjustment using both administrative and clinical data is necessary before comparing hospitals by sepsis mortality rates.

Nasal decolonization: What antimicrobials are most effective prior to surgery?

BACKGROUND: Surgical site infection (SSI) is one of the most common health care-associated infections. Staphylococcus aureus remains the most common etiologic agent causing SSIs. Studies confirm S aureus carriage increases the risk of S aureus SSIs. The purpose of this article is to review the strategies to reduce SSIs due to S aureus focusing on nasal decolonization. RESULTS: Published studies indicate screening patients for S aureus nasal carriage and decolonizing carriers during the preoperative period decreases the risk of S aureus SSIs in cardiac and orthopedic surgery. Mupirocin remains the best topical agent at eradicating nasal S aureus however, concerns over resistance have led to development of alternative agents. Nasal povidone-iodine, alcohol-based nasal antiseptic, and photodynamic therapy are promising new interventions, but more studies are needed. CONCLUSIONS: Short term nasal mupirocin is still the most studied and effective topical agent in eradicating S aureus nasal colonization. However, increasing mupirocin resistance remains an ongoing concern and newer agents are needed. Currently, preoperative S aureus decolonization often uses combination chlorhexidine gluconate bathing and nasal mupirocin considering that colonization of multiple body sites is commonly seen.

Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Electronic Clinical Data and Impact on Hospital Outcome Comparisons.

OBJECTIVES: Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices for sepsis and organ dysfunction may confound efforts to estimate sepsis rates, compare outcomes, and perform risk adjustment. We evaluated hospital variation in the sensitivity of claims data relative to clinical data from electronic health records and its impact on outcome comparisons. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 4.3 million adult encounters at 193 U.S. hospitals in 2013-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was defined using electronic health record-derived clinical indicators of presumed infection (blood culture draws and antibiotic administrations) and concurrent organ dysfunction (vasopressors, mechanical ventilation, doubling in creatinine, doubling in bilirubin to ≥ 2.0 mg/dL, decrease in platelets to < 100 cells/µL, or lactate ≥ 2.0 mmol/L). We compared claims for sepsis prevalence and mortality rates between both methods. All estimates were reliability adjusted to account for random variation using hierarchical logistic regression modeling. The sensitivity of hospitals' claims data was low and variable: median 30% (range, 5-54%) for sepsis, 66% (range, 26-84%) for acute kidney injury, 39% (range, 16-60%) for thrombocytopenia, 36% (range, 29-44%) for hepatic injury, and 66% (range, 29-84%) for shock. Correlation between claims and clinical data was moderate for sepsis prevalence (Pearson coefficient, 0.64) and mortality (0.61). Among hospitals in the lowest sepsis mortality quartile by claims, 46% shifted to higher mortality quartiles using clinical data. Using implicit sepsis criteria based on infection and organ dysfunction codes also yielded major differences versus clinical data. CONCLUSIONS: Variation in the accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospitals' sepsis rates and outcomes. Using objective clinical data may facilitate more meaningful hospital comparisons.

Risk Adjustment for Sepsis Mortality to Facilitate Hospital Comparisons Using Centers for Disease Control and Prevention's Adult Sepsis Event Criteria and Routine Electronic Clinical Data.

Variability in hospital-level sepsis mortality rates may be due to differences in case mix, quality of care, or diagnosis and coding practices. Centers for Disease Control and Prevention's Adult Sepsis Event definition could facilitate objective comparisons of sepsis mortality rates between hospitals but requires rigorous risk-adjustment tools. We developed risk-adjustment models for Adult Sepsis Events using administrative and electronic health record data. DESIGN: Retrospective cohort study. SETTING: One hundred thirty-six U.S. hospitals in Cerner HealthFacts (derivation dataset) and 137 HCA Healthcare hospitals (validation dataset). PATIENTS: A total of 95,154 hospitalized adult patients (derivation) and 201,997 patients (validation) meeting Centers for Disease Control and Prevention Adult Sepsis Event criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We created logistic regression models of increasing complexity using administrative and electronic health record data to predict in-hospital mortality. An administrative model using demographics, comorbidities, and coded markers of severity of illness at admission achieved an area under the receiver operating curve of 0.776 (95% CI, 0.770-0.783) in the Cerner cohort, with diminishing calibration at higher baseline risk deciles. An electronic health record-based model that integrated administrative data with laboratory results, vasopressors, and mechanical ventilation achieved an area under the receiver operating curve of 0.826 (95% CI, 0.820-0.831) in the derivation cohort and 0.827 (95% CI, 0.824-0.829) in the validation cohort, with better calibration than the administrative model. Adding vital signs and Glasgow Coma Score minimally improved performance. CONCLUSIONS: Models incorporating electronic health record data accurately predict hospital mortality for patients with Adult Sepsis Events and outperform models using administrative data alone. Utilizing laboratory test results, vasopressors, and mechanical ventilation without vital signs may achieve a good balance between data collection needs and model performance, but electronic health record-based models must be attentive to potential variability in data quality and availability. With ongoing testing and refinement of these risk-adjustment models, Adult Sepsis Event surveillance may enable more meaningful comparisons of hospital sepsis outcomes and provide an important window into quality of care.