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Background: For each of the COVID-19 pandemic waves, hospitals have had to plan for deploying surge capacity and resources to manage large but transient increases in COVID-19 admissions. While a lot of effort has gone into predicting regional trends in COVID-19 cases and hospitalizations, there are far fewer successful tools for creating accurate hospital-level forecasts., Methods: Large-scale, anonymized mobile phone data has been shown to correlate with regional case counts during the first two waves of the pandemic (spring 2020, and fall/winter 2021). Building off this success, we developed a multi-step, recursive forecasting model to predict individual hospital admissions; this model incorporates the following data: (i) hospital-level COVID-19 admissions, (ii) statewide test positivity data, and (iii) aggregate measures of large-scale human mobility, contact patterns, and commuting volume., Results: Incorporating large-scale, aggregate mobility data as exogenous variables in prediction models allows us to make hospital-specific COVID-19 admission forecasts 21 days ahead. We show this through highly accurate predictions of hospital admissions for five hospitals in Massachusetts during the first year of the COVID-19 pandemic., Conclusions: The high predictive capability of the model was achieved by combining anonymized, aggregated mobile device data about users' contact patterns, commuting volume, and mobility range with COVID hospitalizations and test-positivity data. Mobility-informed forecasting models can increase the lead-time of accurate predictions for individual hospitals, giving managers valuable time to strategize how best to allocate resources to manage forthcoming surges., (© 2023. The Author(s).)

Background: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis., Methods: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics., Results: Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47-.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88-1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar., Conclusions: An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm., Clinical Trials Registration: NCT03517007., Competing Interests: Potential conflicts of interest. E. D. A. reports grants or contracts from the University of Maryland (paid to author), University of Chicago (paid to author), CDC Prevention Epicenter Program (paid to institution), Oxford University Clinical Research Unit (paid to author), CDC (paid to institution), and DASON Member Hospital Contracts (paid to institution); royalties or licenses from UpToDate (paid to author); consulting fees from the American College of Clinical Pharmacy (paid to author), Hospital Association of New York State (paid to author), Sarah Moreland Russel Consulting (paid to author), and HealthTrackRX (paid to author); and support for attending meetings and/or travel from the American Society of Microbiology (paid to author), Pew Charitable Trusts (paid to author), and Oxford University Clinical Research Unit (paid to institution). A. E. D. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck & Co (paid to author). M. Z. D. reports grants or contracts from the National Institutes of Health, GSK, Johnson & Johnson, and Contrafect (paid to institution); support for attending meetings and/or travel from GSK; and participation on a data and safety monitoring board or advisory board for GSK (paid to author). D. J. A. reports grants or contracts from Agency for Healthcare Research and Quality (to institution), royalties or licenses from UpToDate Online (paid to author), and other financial or nonfinancial interests from Infection Control Education for Major Sports, LLC (owner). M. K. reports grants or contracts from Agency for Healthcare Research and Quality (paid to institution) and the Massachusetts Department of Public Health (paid to institution) and royalties or licenses from UpToDate (paid to author). R. W. M. reports grants or contracts from the CDC (paid to institution) and the Agency for Healthcare Research and Quality (paid to institution), royalties or licenses from UpToDate, Inc. (paid to author), speaker honoraria for the North Carolina Statewide Program for Infection Control and Epidemiology (paid to author), support for attending meetings and/or travel from the Society for Healthcare Epidemiology of America, and is on the Society for Healthcare Epidemiology of America Board of Trustees. A. P. reports grants from Clinical and Translational Science Award (to Biostatistics, Epidemiology, and Research Design Core, within the Biostatistics and Bioinformatics Department at Duke University). J. C. P. reports serving on the advisory boards for Shionogi, Inc, and Gilead Sciences, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Suspected pneumonia is the most common indication for antibiotics in hospitalized patients but is frequently overdiagnosed. We explored whether normal oxygenation could be used as an indicator to support early discontinuation of antibiotics., Methods: We retrospectively identified all patients started on antibiotics for pneumonia in 4 hospitals with oxygen saturations ≥95% on ambient air, May 2017-February 2021. We propensity-matched patients treated 1-2 days vs 5-8 days and compared hospital mortality and time to discharge using subdistribution hazard ratios (SHRs). Secondary outcomes included readmissions, 30-day mortality, Clostridioides difficile infections, hospital-free days, and antibiotic-free days., Results: Among 39 752 patients treated for possible pneumonia, 10 012 had median oxygen saturations ≥95% without supplemental oxygen. Of these, 2871 were treated 1-2 days and 2891 for 5-8 days; 4478 patients were propensity-matched. Patients treated 1-2 vs 5-8 days had similar hospital mortality (2.1% vs 2.8%; SHR, 0.75 [95% confidence interval {CI}, .51-1.09]) but less time to discharge (6.1 vs 6.6 days; SHR, 1.13 [95% CI, 1.07-1.19]) and more 30-day hospital-free days (23.1 vs 22.7; mean difference, 0.44 [95% CI, .09-.78]). There were no significant differences in 30-day readmissions (16.0% vs 15.8%; odds ratio [OR], 1.01 [95% CI, .86-1.19]), 30-day mortality (4.6% vs 5.1%; OR, 0.91 [95% CI, .69-1.19]), or 90-day C. difficile infections (1.3% vs 0.8%; OR, 1.67 [95% CI, .94-2.99])., Conclusions: One-quarter of hospitalized patients treated for pneumonia had oxygenation saturations ≥95% on ambient air. Outcomes were similar with 1-2 vs 5-8 days of antibiotics. Normal oxygenation levels may help identify candidates for early antibiotic discontinuation. Prospective trials are warranted., Competing Interests: Potential conflicts of interest. M. K. has received royalties from UpToDate for articles on pneumonia and has also received grants from the Agency for Healthcare Research and Quality. C. R. has received royalties from UpToDate for articles on procalcitonin; payments for consulting related to sepsis diagnostics from Cytovale; and payments from Pfizer for consulting related to Lyme disease surveillance. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Timely and accurate data on the epidemiology of sepsis is essential to inform public policy, clinical practice, and research priorities. Recent studies have illuminated several ongoing questions about sepsis epidemiology, including the incidence and outcomes of sepsis in non-Western countries and in specialized populations such as surgical patients, patients with cancer, and the elderly. There have also been new insights into the limitations of current surveillance methods using administrative data and increasing experience tracking sepsis incidence and outcomes using "big data" approaches that take advantage of detailed electronic health record data. The COVID-19 pandemic, however, has fundamentally changed the landscape of sepsis epidemiology. It has increased sepsis rates, helped highlight ongoing controversies about how to define sepsis, and intensified debate about the possible unintended consequences of overly rigid sepsis care bundles. Despite these controversies, there is a growing consensus that severe COVID-19 causing organ dysfunction is appropriate to label as sepsis, even though it is treated very differently from bacterial sepsis, and that surveillance strategies need to be modified to reliably identify these cases to fully capture and delineate the current burden of sepsis. This review will summarize recent insights into the epidemiology of sepsis and highlight several urgent questions and priorities catalyzed by COVID-19., Competing Interests: None declared., (Thieme. All rights reserved.)

Management of critically ill coronavirus disease 2019 (COVID-19) patients has evolved considerably during the pandemic. We investigated rates and causes of ventilator-associated events (VAEs) in COVID-19 patients in the late versus early waves in 4 Massachusetts hospitals. VAE rates per episode decreased, rates per ventilator day were stable, and most cases were caused by acute respiratory distress syndrome (ARDS).

We assessed the extent to which healthcare workers report more favorable hand hygiene rates when observing members of their own professional group versus other groups' observations of them. Healthcare workers consistently reported higher compliance rates for their own group compared to others' observations of them (97 vs 92%; P ≤ .001).

Sepsis guidelines and mandates encourage increasingly aggressive time-to-antibiotic targets for broad-spectrum antimicrobials for suspected sepsis and septic shock. This has caused considerable controversy due to weaknesses in the underlying evidence and fear that overly strict antibiotic deadlines may harm patients by perpetuating or escalating overtreatment. Indeed, a third or more of patients currently treated for sepsis and septic shock have noninfectious or nonbacterial conditions. These patients risk all the potential harms of antibiotics without their possible benefits. Updated Surviving Sepsis Campaign guidelines now emphasize the importance of tailoring antibiotics to each patient's likelihood of infection, risk for drug-resistant pathogens, and severity-of-illness., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We report on probable factory-based contamination of portable water heaters with waterborne pathogens and 2 bloodstream infections potentially attributable to off-label use of these water heaters to warm extracorporeal membrane oxygenation circuits. Great caution is warranted when using water-based devices to care for critically ill patients., Competing Interests: Potential conflicts of interest. M. B., C. R., and M. K. have received grant funding from the Centers for Disease Control and Prevention within the past 3 years for research on severe acute respiratory syndrome coronavirus 2 prevention and transmission and currently receive grant funding for research on unrelated topics. C. R. and M. K. also have grant funding from AHRQ. M. K. receives funding from the Massachusetts Department of Public Health to support public health surveillance. M. K. has received royalties from UpToDate, Inc., for chapters on preventing nosocomial pneumonia and other unrelated topics. C. R. has received royalties from UpToDate, Inc., for chapters related to procalcitonin use. M. H. H. and M. R. S. are employees of Day Zero Diagnostics. A. S. received consulting fees from Inspira Technologies. R. S. reports consulting fees from BD. C. R. reports consulting fees from Pfizer and Cytovale. M. B. reports holding a leadership or fiduciary role on the SHEA Guidelines Committee. All other authors report no potential conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate the effectiveness of a daily attestation system used by employees of a multi-institutional academic medical center, which comprised of symptom-screening, self-referrals to the Occupational Health Services team, and/or a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test., Design: We conducted a retrospective cohort study of all employee attestations and SARS-CoV-2 tests performed between March and June 2020., Setting: A large multi-institutional academic medical center, including both inpatient and ambulatory settings., Participants: All employees who worked at the study site., Methods: Data were combined from the attestation system (COVIDPass), the employee database, and the electronic health records and were analyzed using descriptive statistics including χ 2 , Wilcoxon, and Kruskal-Wallis tests. We investigated whether an association existed between symptomatic attestations by the employees and the employee testing positive for SARS-CoV-2., Results: After data linkage and cleaning, there were 2,117,298 attestations submitted by 65,422 employees between March and June 2020. Most attestations were asymptomatic (99.9%). The most commonly reported symptoms were sore throat (n = 910), runny nose (n = 637), and cough (n = 570). Among the 2,026 employees who ever attested that they were symptomatic, 905 employees were tested within 14 days of a symptomatic attestation, and 114 (13%) of these tests were positive. The most common symptoms associated with a positive SARS-CoV-2 test were anosmia (23% vs 4%) and fever (46% vs 19%)., Conclusions: Daily symptom attestations among healthcare workers identified a handful of employees with COVID-19. Although the number of positive tests was low, attestations may help keep unwell employees off campus to prevent transmissions.

Background: Burkholderia cepacia complex is a group of potential nosocomial pathogens often linked to contaminated water. We report on a cluster of 8 B. cepacia complex infections in cardiothoracic intensive care unit patients, which were attributed to contaminated extracorporeal membrane oxygenation (ECMO) water heaters., Methods: In December 2020, we identified an increase in B. cepacia complex infections in the cardiothoracic intensive care unit at Brigham and Women's Hospital. We sought commonalities, sequenced isolates, obtained environmental specimens, and enacted mitigation measures., Results: Whole-genome sequencing of 13 B. cepacia complex clinical specimens between November 2020 and February 2021 identified 6 clonally related isolates, speciated as Burkholderia contaminans. All 6 occurred in patients on ECMO. Microbiology review identified 2 additional B. contaminans cases from June 2020 that may have also been cluster related, including 1 in a patient receiving ECMO. All 8 definite or probable cluster cases required treatment; 3 patients died, and 3 experienced recurrent infections. After ECMO was identified as the major commonality, all 9 of the hospital's ECMO water heaters were cultured, and B. contaminans grew in all cultures. Cultures from air sampled adjacent to the water heaters were negative. Water heater touch screens were culture positive for B. contaminans, and the sink drain in the ECMO heater reprocessing room also grew clonal B. contaminans. Observations of reprocessing revealed opportunities for cross-contamination between devices through splashing from the contaminated sink. The cluster was aborted by removing all water heaters from clinical service., Conclusions: We identified a cluster of 8 B. cepacia complex infections associated with contaminated ECMO water heaters. This cluster underscores the potential risks associated with water-based ECMO heaters and, more broadly, water-based care for vulnerable patients., Competing Interests: Potential conflicts of interest. C. R. and M. K. report grants or contracts outside the scope of this work from the Centers for Disease Control and Prevention and the Agency for Healthcare Quality and Research and royalties from UpToDate. M. A. B. reports a leadership or fiduciary role on the Guidelines Committee of the Society for Healthcare Epidemiology of America. M. S. and M. Huntley report stock or stock options and other financial or nonfinancial interests in their employer, Day Zero Diagnostics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose of Review: Sepsis guidelines and quality measures set aggressive deadlines for administering antibiotics to patients with possible sepsis or septic shock. However, the diagnosis of sepsis is often uncertain, particularly upon initial presentation, and pressure to treat more rapidly may harm some patients by exposing them to unnecessary or inappropriate broad-spectrum antibiotics., Recent Findings: Observational studies that report that each hour until antibiotics increases mortality often fail to adequately adjust for comorbidities and severity of illness, fail to account for antibiotics given to uninfected patients, and inappropriately blend the effects of long delays with short delays. Accounting for these factors weakens or eliminates the association between time-to-antibiotics and mortality, especially for patients without shock. These findings are underscored by analyses of the Centers for Medicaid and Medicare Services SEP-1 measure: it has increased sepsis diagnoses and broad-spectrum antibiotic use but has not improved outcomes., Summary: Clinicians are advised to tailor the urgency of antibiotics to their certainty of infection and patients' severity of illness. Immediate antibiotics are warranted for patients with possible septic shock or high likelihood of infection. Antibiotics can safely be withheld to allow for more investigation, however, in most patients with less severe illnesses if the diagnosis of infection is uncertain., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Influenza is a leading cause of community-acquired pneumonia (CAP), and results of influenza tests can direct therapy. However, among adults hospitalized with CAP, little is known about the frequency and timing of influenza testing, treatment, and their associations with outcomes., Research Question: In patients with CAP, is testing for influenza associated with antiviral treatment and shorter antibiotic courses, and is early treatment associated with better clinical outcomes?, Study Design and Methods: This study included adults admitted with pneumonia in 2010 to 2015 to 179 US hospitals contributing to the Premier database. We assessed influenza testing and compared antimicrobial utilization and the outcomes of test-positive, test-negative, and untested patients. Associations of early antiviral treatment (oseltamivir) with 14-day in-hospital mortality, hospital length of stay, and cost were studied., Results: Among 166,268 patients with CAP, 38,703 (23.3%) were tested for influenza, of whom 11.5% tested positive. Testing increased from 15.4% to 35.6% from 2010 to 2015 and was 28.9% during flu season (October-May) vs 8.2% in June to September. Patients testing positive for influenza received antiviral agents more often and antibacterial agents less often and for shorter courses than patients testing negative (5.3 vs 6.4 days; P < .001). Influenza-positive patients receiving oseltamivir on hospital day 1 (n = 2,585) experienced lower 14-day in-hospital mortality (adjusted OR, 0.75; 95% CI, 0.59-0.96), lower costs (adjusted ratio of means, 0.88; 95% CI, 0.81-0.95), and shorter length of stay (adjusted ratio of means, 0.88; 95% CI, 0.84-0.93) vs patients receiving oseltamivir later or not at all (n = 1,742)., Interpretation: Even during flu season, most patients with CAP in this study went untested for influenza. A positive influenza test result was associated with antiviral treatment, and early treatment was associated with lower mortality, suggesting that more widespread testing might improve patient outcomes., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The highly contagious severe acute respiratory syndrome coronavirus 2 Omicron variant increases risk for nosocomial transmission despite universal masking, admission testing, and symptom screening. We report large increases in hospital-onset infections and 2 unit-based clusters. The clusters rapidly abated after instituting universal N95 respirators and daily testing. Broader use of these strategies may prevent nosocomial transmissions., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Electronic Health Record (EHR) data are increasingly being used to monitor population health on account of their timeliness, granularity, and large sample sizes. While EHR data are often sufficient to estimate disease prevalence and trends for large geographic areas, the same accuracy and precision may not carry over for smaller areas that are sparsely represented by non-random samples., Methods: We developed small-area estimation models using a combination of EHR data drawn from MDPHnet, an EHR-based public health surveillance network in Massachusetts, the American Community Survey, and state hospitalization data. We estimated municipality-specific prevalence rates of asthma, diabetes, hypertension, obesity, and smoking in each of the 351 municipalities in Massachusetts in 2016. Models were compared against Behavioral Risk Factor Surveillance System (BRFSS) state and small area estimates for 2016., Results: Integrating progressively more variables into prediction models generally reduced mean absolute error (MAE) relative to municipality-level BRFSS small area estimates: asthma (2.24% MAE crude, 1.02% MAE modeled), diabetes (3.13% MAE crude, 3.48% MAE modeled), hypertension (2.60% MAE crude, 1.48% MAE modeled), obesity (4.92% MAE crude, 4.07% MAE modeled), and smoking (5.33% MAE crude, 2.99% MAE modeled). Correlation between modeled estimates and BRFSS estimates for the 13 municipalities in Massachusetts covered by BRFSS's 500 Cities ranged from 81.9% (obesity) to 96.7% (diabetes)., Conclusions: Small-area estimation using EHR data is feasible and generates estimates comparable to BRFSS state and small-area estimates. Integrating EHR data with survey data can provide timely and accurate disease monitoring tools for areas with sparse data coverage., (© 2022. The Author(s).)

Purpose of Review: COVID-19 has catalyzed a wealth of new data on the science of respiratory pathogen transmission and revealed opportunities to enhance infection prevention practices in healthcare settings., Recent Findings: New data refute the traditional division between droplet vs airborne transmission and clarify the central role of aerosols in spreading all respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), even in the absence of so-called 'aerosol-generating procedures' (AGPs). Indeed, most AGPs generate fewer aerosols than talking, labored breathing, or coughing. Risk factors for transmission include high viral loads, symptoms, proximity, prolonged exposure, lack of masking, and poor ventilation. Testing all patients on admission and thereafter can identify early occult infections and prevent hospital-based clusters. Additional prevention strategies include universal masking, encouraging universal vaccination, preferential use of N95 respirators when community rates are high, improving native ventilation, utilizing portable high-efficiency particulate air filters when ventilation is limited, and minimizing room sharing when possible., Summary: Multifaceted infection prevention programs that include universal testing, masking, vaccination, and enhanced ventilation can minimize nosocomial SARS-CoV-2 infections in patients and workplace infections in healthcare personnel. Extending these insights to other respiratory viruses may further increase the safety of healthcare and ready hospitals for novel respiratory viruses that may emerge in the future., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

We compared healthcare worker severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates between March and August 2020 in 2 similar hospitals with high vs low airborne infection isolation room utilization rates but otherwise identical infection control policies. We found no difference in healthcare worker infection rates between the 2 hospitals, nor between patient-facing vs non-patient-facing providers., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Devastating cases of sepsis in previously healthy patients have received widespread attention and have helped to catalyze state and national mandates to improve sepsis detection and care. However, it is unclear what proportion of patients hospitalized with sepsis previously were healthy and how their outcomes compare with those of patients with comorbidities., Research Question: Among adults hospitalized with community-onset sepsis, how many previously were healthy and how do their outcomes compare with those of patients with comorbidities?, Study Design and Methods: We retrospectively identified all adults with community-onset sepsis hospitalized in 373 US hospitals from 2009 through 2015 using clinical indicators of presumed infection and organ dysfunction (Centers for Disease Control and Prevention's Adult Sepsis Event criteria). Comorbidities were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. We applied generalized linear mixed models to measure the associations between the presence or absence of comorbidities and short-term mortality (in-hospital death or discharge to hospice), adjusting for severity of illness on admission., Results: Of 6,715,286 hospitalized patients, 337,983 (5.0%) were hospitalized with community-onset sepsis. Most patients with sepsis (329,052 [97.4%]) had received a diagnosis of at least one comorbidity; only 2.6% previously were healthy. Patients with sepsis who previously were healthy were younger than those with comorbidities (mean age, 58.0 ± 19.8 years vs 67.0 ± 16.5 years), were less likely to require ICU care on admission (37.9% vs 50.5%), and were more likely to be discharged home (57.9% vs 45.6%), rather than to subacute facilities (16.3% vs 30.8%), but showed higher short-term mortality rates (22.8% vs 20.8%; P < .001 for all). The association between previously healthy status and higher short-term mortality persisted after risk adjustment (adjusted OR, 1.99; 95% CI, 1.87-2.13)., Interpretation: The vast majority of patients hospitalized with community-onset sepsis harbor pre-existing comorbidities. However, previously healthy patients may be more likely to die when they seek treatment at the hospital with sepsis compared with patients with comorbidities. These findings underscore the importance of early sepsis recognition and treatment for all patients., (Copyright © 2022. Published by Elsevier Inc.)

Patients in intensive care units (ICUs) are at high risk for healthcare-acquired infections (HAI) due to the high prevalence of invasive procedures and devices, induced immunosuppression, comorbidity, frailty and increased age. Over the past decade we have seen a successful reduction in the incidence of HAI related to invasive procedures and devices. However, the rate of ICU-acquired infections remains high. Within this context, the ongoing emergence of new pathogens, further complicates treatment and threatens patient outcomes. Additionally, the SARS-CoV-2 (COVID-19) pandemic highlighted the challenge that an emerging pathogen provides in adapting prevention measures regarding both the risk of exposure to caregivers and the need to maintain quality of care. ICU nurses hold a special place in the prevention and management of HAI as they are involved in basic hygienic care, steering and implementing quality improvement initiatives, correct microbiological sampling, and aspects antibiotic stewardship. The emergence of more sensitive microbiological techniques and our increased knowledge about interactions between critically ill patients and their microbiota are leading us to rethink how we define HAIs and best strategies to diagnose, treat and prevent these infections in the ICU. This multidisciplinary expert review, focused on the ICU setting, will summarise the recent epidemiology of ICU-HAI, discuss the place of modern microbiological techniques in their diagnosis, review operational and epidemiological definitions and redefine the place of several controversial preventive measures including antimicrobial-impregnated medical devices, chlorhexidine-impregnated washcloths, catheter dressings and chlorhexidine-based mouthwashes. Finally, general guidance is suggested that may reduce HAI incidence and especially outbreaks in ICUs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The purpose of this document is to highlight practical recommendations to assist acute care hospitals to prioritize and implement strategies to prevent ventilator-associated pneumonia (VAP), ventilator-associated events (VAE), and non-ventilator hospital-acquired pneumonia (NV-HAP) in adults, children, and neonates. This document updates the Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA), and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the American Hospital Association, the Association for Professionals in Infection Control and Epidemiology, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

The prevalence and causes of sepsis in patients hospitalized with COVID-19 are poorly characterized., Objectives: To investigate the prevalence, clinical characteristics, and outcomes of sepsis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus other pathogens in patients hospitalized with COVID-19., Design Setting and Participants: Cross-sectional, retrospective chart review of 200 randomly selected patients hospitalized with COVID-19 at four Massachusetts hospitals between March 2020 and March 2021., Main Outcomes and Measures: The presence or absence of sepsis was determined per Sepsis-3 criteria (infection leading to an increase in Sequential Organ Failure Assessment score by ≥ 2 points above baseline). Sepsis episodes were assessed as caused by SARS-CoV-2, other pathogens, or both. Rates of organ dysfunction and in-hospital death were also assessed., Results: Sepsis was present in 65 of 200 COVID-19 hospitalizations (32.5%), of which 46 of 65 sepsis episodes (70.8%) were due to SARS-CoV-2 alone, 17 of 65 (26.2%) were due to both SARS-CoV-2 and non-SARS-CoV-2 infections, and two of 65 (3.1%) were due to bacterial infection alone. SARS-CoV-2-related organ dysfunction in patients with sepsis occurred a median of 1 day after admission (interquartile range, 0-2 d) and most often presented as respiratory (93.7%), neurologic (46.0%), and/or renal (39.7%) dysfunctions. In-hospital death occurred in 28 of 200 COVID-19 hospitalizations (14.0%), including two of 135 patients without sepsis (1.5%), 16 of 46 patients with sepsis (34.8%) due to SARS-CoV-2 alone, and 10 of 17 patients with sepsis (58.8%) due to both SARS-CoV-2 and bacterial pathogens., Conclusions: Sepsis occurred in one in three patients hospitalized with COVID-19 and was primarily caused by SARS-CoV-2 itself, although bacterial infection also contributed in a quarter of sepsis cases. Mortality in COVID-19 patients with sepsis was high, especially in patients with mixed SARS-CoV-2 and bacterial sepsis. These findings affirm SARS-CoV-2 as an important cause of sepsis and highlight the need to improve surveillance, recognition, prevention, and treatment of both viral and bacterial sepsis in hospitalized patients with COVID-19., Competing Interests: Drs. Klompas and Rhee report royalties from UpToDate. Dr. Rhee also reports consulting fees from Pfizer and Cytovale for work unrelated to this topic. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

In a retrospective cohort study, among 131 773 patients with previous coronavirus disease 2019 (COVID-19), reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) was suspected in 253 patients (0.2%) at 238 US healthcare facilities between 1 June 2020 and 28 February 2021. Women displayed a higher cumulative reinfection risk. Healthcare burden and illness severity were similar between index and reinfection encounters., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Non-communicable diseases (NCDs) remain the largest global public health threat. The emerging field of precision public health (PPH) offers a transformative opportunity to capitalize on digital health data to create an agile, responsive and data-driven public health system to actively prevent NCDs. Using learnings from digital health, our aim is to propose a vision toward PPH for NCDs across three horizons of digital health transformation: Horizon 1-digital public health workflows; Horizon 2-population health data and analytics; Horizon 3-precision public health. This perspective provides a high-level strategic roadmap for public health practitioners and policymakers, health system stakeholders and researchers to achieving PPH for NCDs. Two multinational use cases are presented to contextualize our roadmap in pragmatic action: ESP and RiskScape (USA), a mature PPH platform for multiple NCDs, and PopHQ (Australia), a proof-of-concept population health informatics tool to monitor and prevent obesity. Our intent is to provide a strategic foundation to guide new health policy, investment and research in the rapidly emerging but nascent area of PPH to reduce the public health burden of NCDs., Competing Interests: BZ was employed by Commonwealth Informatics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Canfell, Davidson, Woods, Sullivan, Cocoros, Klompas, Zambarano, Eakin, Littlewood and Burton-Jones.)

A fifth or more of hospital-acquired pneumonias may be attributable to respiratory viruses. The SARS-CoV-2 pandemic has clearly demonstrated the potential morbidity and mortality of respiratory viruses and the constant threat of nosocomial transmission and hospital-based clusters. Data from before the pandemic suggest the same can be true of influenza, respiratory syncytial virus, and other respiratory viruses. The pandemic has also helped clarify the primary mechanisms and risk factors for viral transmission. Respiratory viruses are primarily transmitted by respiratory aerosols that are routinely emitted when people exhale, talk, and cough. Labored breathing and coughing increase aerosol generation to a much greater extent than intubation, extubation, positive pressure ventilation, and other so-called aerosol-generating procedures. Transmission risk is proportional to the amount of viral exposure. Most transmissions take place over short distances because respiratory emissions are densest immediately adjacent to the source but then rapidly dilute and diffuse with distance leading to less viral exposure. The primary risk factors for transmission then are high viral loads, proximity, sustained exposure, and poor ventilation as these all increase net viral exposure. Poor ventilation increases the risk of long-distance transmission by allowing aerosol-borne viruses to accumulate over time leading to higher levels of exposure throughout an enclosed space. Surgical and procedural masks reduce viral exposure but do not eradicate it and thus lower but do not eliminate transmission risk. Most hospital-based clusters have been attributed to delayed diagnoses, transmission between roommates, and staff-to-patient infections. Strategies to prevent nosocomial respiratory viral infections include testing all patients upon admission, preventing healthcare providers from working while sick, assuring adequate ventilation, universal masking, and vaccinating both patients and healthcare workers., Competing Interests: None declared., (Thieme. All rights reserved.)

We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission between patients in shared rooms in an academic hospital between September 2020 and April 2021. In total, 11 290 patients were admitted to shared rooms, of whom 25 tested positive. Among 31 exposed roommates, 12 (39%) tested positive within 14 days. Transmission was associated with polymerase chain reaction (PCR) cycle thresholds ≤21., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The Centers for Disease Control and Prevention recommends N95 respirators for all providers who see patients with possible or confirmed coronavirus disease 2019 (COVID-19). We suggest that N95 respirators may be just as important for the care of patients without suspected COVID-19 when community incidence rates are high. This is because severe acute respiratory syndrome coronavirus 2 is most contagious before symptom onset. Ironically, by the time patients are sick enough to be admitted to the hospital with COVID-19, they tend to be less contagious. The greatest threat of transmission in healthcare facilities may therefore be patients and healthcare workers with early occult infection. N95 respirators' superior fit and filtration provide superior exposure protection for healthcare providers seeing patients with early undiagnosed infection and superior source control to protect patients from healthcare workers with early undiagnosed infection. The probability of occult infection in patients and healthcare workers is greatest when community incidence rates are high. Universal use of N95 respirators may help decrease nosocomial transmission at such times., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Fluid therapy is an important component of intensive care management, however, optimal fluid management is unknown. The relationship between fluid balance and ventilator-associated events has not been well established. This study investigated the dose-response relationship between fluid balance and ventilator-associated events., Design: Nested case-control study., Setting: The study was based on a well-established, research-oriented registry of healthcare-associated infections at ICUs of West China Hospital system (Chengdu, China)., Patients: A total of 1,528 ventilator-associated event cases with 3,038 matched controls, who consistently underwent mechanical ventilation for at least 4 days from April 1, 2015, to December 31, 2018, were included., Interventions: None., Measurements and Main Results: We calculated cumulative fluid balance within 4 days prior to ventilator-associated event occurrence. A weighted Cox proportional hazards model with restricted cubic splines was used to evaluate the dose-response relationship. A nonlinear relationship between fluid balance and all three tiers of ventilator-associated events, patients with fluid balance between -1 and 0 L had the lowest risk (p < 0.05 for nonlinear test). The risk of ventilator-associated event was significantly higher in patients with positive fluid balance (4 d cumulative fluid balance: 1 L: 1.19; 3 L: 1.92; 5 L: 2.58; 7 L: 3.24), but not in those with negative fluid balance (-5 L: 1.34; -3 L: 1.14; -1 L: 0.98)., Conclusions: There was nonlinear relationship between fluid balance and all three tiers of ventilator-associated event, with an fluid balance between -1 and 0 L corresponding to the lowest risk. Positive but not negative fluid balance increased the risk of ventilator-associated events, with higher positive fluid balance more likely to lead to ventilator-associated events., Competing Interests: Dr. Wang received support from National Key Research and Development Program (Grant No. 2020YFC2009003). Dr. Sun received support for article research from the Sichuan Youth Science and Technology Innovation Research Team (Grant No. 2020JDTD0015), and the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant No. ZYYC08003). Dr. Zong received support from the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant No. ZYYC08006). Drs. Zou and Zong received support for article research from the National Natural Science Foundation of China. Dr. Klompas’ institution received funding from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and the Massachusetts Department of Public Health; he received funding from UpToDate. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Purpose of Review: We conducted a systematic literature review to summarize the available evidence regarding the incidence, risk factors, and clinical characteristics of ventilator-associated pneumonia (VAP) in patients undergoing mechanical ventilation because of acute respiratory distress syndrome secondary to SARS-CoV-2 infection (C-ARDS)., Recent Findings: Sixteen studies (6484 patients) were identified. Bacterial coinfection was uncommon at baseline (<15%) but a high proportion of patients developed positive bacterial cultures thereafter leading to a VAP diagnosis (range 21-64%, weighted average 50%). Diagnostic criteria varied between studies but most signs of VAP have substantial overlap with the signs of C-ARDS making it difficult to differentiate between bacterial colonization versus superinfection. Most episodes of VAP were associated with Gram-negative bacteria. Occasional cases were also attributed to herpes virus reactivations and pulmonary aspergillosis. Potential factors driving high VAP incidence rates include immunoparalysis, prolonged ventilation, exposure to immunosuppressants, understaffing, lapses in prevention processes, and overdiagnosis., Summary: Covid-19 patients who require mechanical ventilation for ARDS have a high risk (>50%) of developing VAP, most commonly because of Gram-negative bacteria. Further work is needed to elucidate the disease-specific risk factors for VAP, strategies for prevention, and how best to differentiate between bacterial colonization versus superinfection., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection., Methods: We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost., Results: Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17-4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98-4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59-1.96)., Conclusions: In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.

Rationale: Ventilator-associated event (VAE) surveillance provides an objective means to measure and compare complications that develop during mechanical ventilation by identifying patients with sustained increases in ventilator settings after a period of stable or decreasing ventilator settings. The impact of the coronavirus disease (COVID-19) pandemic on VAE rates and characteristics is unknown. Objectives: To compare the incidence, causes, and outcomes of VAE during the COVID-19 pandemic year versus prepandemic years and among ventilated patients with and without COVID-19. Methods: In this retrospective cohort study of mechanically ventilated adults at four academic and community hospitals in Massachusetts, we compared VAE incidence rates between March 1 and August 31 for each year from 2017 to 2020 (corresponding to the time frame of the pandemic first wave in 2020) and among COVID-19-positive and COVID-19-negative patients in 2020. The medical records of 200 randomly selected patients with VAEs in 2020 (100 with COVID-19 and 100 without COVID-19) were analyzed to compare conditions precipitating VAEs in patients with versus without COVID-19. Results: VAEs per 100 episodes of mechanical ventilation were more common in 2020 than in prior years (11.2 vs. 6.7; P  < 0.01) but the rate of VAEs per 1,000 ventilator-days was similar (14.2 vs. 12.7; P  = 0.08). VAEs were more frequent in COVID-19-positive patients than in COVID-19-negative patients in 2020 (29.0 vs. 7.1 per 100 ventilator episodes [ P  < 0.01] and 17.2 vs. 12.2 per 1,000 ventilator-days [ P  < 0.01]). Compared with patients without COVID-19 with VAEs, patients with COVID-19 and VAEs had similar rates of infection-related ventilator-associated complications, longer median durations of mechanical ventilation (22 vs. 14 d; P  < 0.01), and similar in-hospital mortality (30% vs. 38%; P  = 0.15). Progressive acute respiratory distress syndrome (ARDS) accounted for 53% of VAEs in patients with COVID-19, whereas it accounted for 14% of VAEs among patients without COVID-19. Conclusions: VAE rates per 100 episodes of mechanical ventilation and per 1,000 ventilator-days were higher among COVID-19-positive patients than among COVID-19-negative patients. Over 50% of VAEs in patients with COVID-19 were caused by progressive ARDS, whereas less than 15% of VAEs in patients without COVID-19 were caused by progressive ARDS. These findings provide insight into the natural history of COVID-19 in ventilated patients and may inform targeted strategies to mitigate complications in this population.

We interviewed 1,208 healthcare workers with positive SARS-CoV-2 tests between October 2020 and June 2021 to determine likely exposure sources. Overall, 689 (57.0%) had community exposures (479 from household members), 76 (6.3%) had hospital exposures (64 from other employees including 49 despite masking), 11 (0.9%) had community and hospital exposures, and 432 (35.8%) had no identifiable source of exposure., (© The Author(s) 2021.)

The Centers for Disease Control and Prevention shifted the focus of safety surveillance in mechanically ventilated patients from ventilator-associated pneumonia to ventilator-associated events in 2013 to increase the objectivity and reproducibility of surveillance and to encourage quality improvement programs to focus on preventing a broader array of complications. Ventilator-associated events are associated with a doubling of the risk of dying. Prospective studies have found that minimizing sedation, increasing spontaneous awakening and breathing trials, and conservative fluid management can decrease event rates and the duration of ventilation. Multifaceted interventions to enhance these practices can decrease ventilator-associated event rates., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: In October 2015, the Centers for Medicare & Medicaid Services began requiring US hospitals to report adherence to the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1)., Objective: To evaluate the association of SEP-1 implementation with sepsis treatment patterns and outcomes in diverse hospitals., Design, Setting, and Participants: This retrospective cohort study with interrupted time-series analysis and logistic regression models was conducted among adults admitted to 114 hospitals from October 2013 to December 2017 with suspected sepsis (blood culture orders, ≥2 systemic inflammatory response syndrome criteria, and acute organ dysfunction) within 24 hours of hospital arrival. Data analysis was conducted from September 2020 to September 2021., Exposures: SEP-1 implementation in the fourth quarter (Q4) of 2015., Main Outcomes and Measures: The primary outcome was quarterly rates of risk-adjusted short-term mortality (in-hospital death or discharge to hospice). Secondary outcomes included lactate testing and administration of anti-methicillin-resistant Staphylococcus aureus (MRSA) or antipseudomonal β-lactam antibiotics within 24 hours of hospital arrival. Generalized estimating equations with robust sandwich variances were used to fit logistic regression models to assess for changes in level or trends in these outcomes, adjusting for baseline characteristics and severity of illness., Results: The cohort included 117 510 patients (median [IQR] age, 67 years [55-78] years; 60 530 [51.5%] men and 56 980 [48.5%] women) with suspected sepsis. Lactate testing rates increased from 55.1% (95% CI, 53.9%-56.2%) in Q4 of 2013 to 76.7% (95% CI, 75.4%-78.0%) in Q4 of 2017, with a significant level change following SEP-1 implementation (odds ratio [OR], 1.34; 95% CI, 1.04-1.74). There were increases in use of anti-MRSA antibiotics (19.8% [95% CI, 18.9%-20.7%] in Q4 of 2013 to 26.3% [95% CI, 24.9%-27.7%] in Q4 of 2017) and antipseudomonal antibiotics (27.7% [95% CI, 26.7%-28.8%] in Q4 of 2013 to 40.5% [95% CI, 38.9%-42.0%] in Q4 of 2017), but these trends preceded SEP-1 and did not change with SEP-1 implementation. Unadjusted short-term mortality rates were similar in the pre-SEP-1 period (Q4 of 2013 through Q3 of 2015) vs the post-SEP-1 period (Q1 of 2016 through Q4 of 2017) (20.3% [95% CI, 20.0%-20.6%] vs 20.4% [95% CI, 20.1%-20.7%]), and SEP-1 implementation was not associated with changes in level (OR, 0.94; 95% CI, 0.68-1.29) or trend (OR, 1.00; 95% CI, 0.97-1.04) for risk-adjusted short-term mortality rates., Conclusions and Relevance: In this cohort study, SEP-1 implementation was associated with an immediate increase in lactate testing rates, no change in already-increasing rates of broad-spectrum antibiotic use, and no change in short-term mortality rates for patients with suspected sepsis. Other approaches to decrease sepsis mortality may be warranted.

Policies to prevent respiratory virus transmission in health care settings have traditionally divided organisms into Droplet versus Airborne categories. Droplet organisms (for example, influenza) are said to be transmitted via large respiratory secretions that rapidly fall to the ground within 1 to 2 meters and are adequately blocked by surgical masks. Airborne pathogens (for example, measles), by contrast, are transmitted by aerosols that are small enough and light enough to carry beyond 2 meters and to penetrate the gaps between masks and faces; health care workers are advised to wear N95 respirators and to place these patients in negative-pressure rooms. Respirators and negative-pressure rooms are also recommended when caring for patients with influenza or SARS-CoV-2 who are undergoing "aerosol-generating procedures," such as intubation. An increasing body of evidence, however, questions this framework. People routinely emit respiratory particles in a range of sizes, but most are aerosols, and most procedures do not generate meaningfully more aerosols than ordinary breathing, and far fewer than coughing, exercise, or labored breathing. Most transmission nonetheless occurs at close range because virus-laden aerosols are most concentrated at the source; they then diffuse and dilute with distance, making long-distance transmission rare in well-ventilated spaces. The primary risk factors for nosocomial transmission are community incidence rates, viral load, symptoms, proximity, duration of exposure, and poor ventilation. Failure to appreciate these factors may lead to underappreciation of some risks (for example, overestimation of the protection provided by medical masks, insufficient attention to ventilation) or misallocation of limited resources (for example, reserving N95 respirators and negative-pressure rooms only for aerosol-generating procedures or requiring negative-pressure rooms for all patients with SARS-CoV-2 infection regardless of stage of illness). Enhanced understanding of the factors governing respiratory pathogen transmission may inform the development of more effective policies to prevent nosocomial transmission of respiratory pathogens.

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., Competing Interests: Drs. Alrawashdeh’s, Klompas’s, Larochelle’s, and Rhee’s institutions received funding from the Centers for Disease Control and Prevention (CDC; U54CK000484). Drs. Alrawashdeh’s, Klompas, and Rhee’s institutions received funding from the Agency for Healthcare Research and Quality (AHRQ; K08HS025008). Drs. Alrawashdeh’s and Larochelle’s institutions received funding from the National Institutes of Health (NIH). Drs. Alrawashdeh, Kimmel, and Kadri received support for article research from the NIH. Dr. Klompas’ institution received funding from the Massachusetts Department of Public Health. Drs. Klompas and Rhee received funding from UpToDate. Dr. Kimmel received funding from Abt Associates on a Department of Public Health–funded project. Dr. Larochelle’s institution received funding from the National Institute on Drug Abuse and the Robert Wood Johnson Foundation; he received funding from the University of Baltimore, the Office of National Drug Control Policy, and OptumLabs. Drs. Gokhale, Hoots, Hatfield, Reddy, and Fiore received support for article research from the government. Drs. Reddy and Rhee received support for article research from the CDC. Dr. Rhee received support for article research from the AHRQ. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)