Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department.

OBJECTIVES: Best practice guidelines and quality metrics recommend immediate antibiotic treatment for all patients with suspected sepsis. However, little is known about how many patients given IV antibiotics in the emergency department are ultimately confirmed to have bacterial infection. DESIGN, SETTING, AND PATIENTS: We performed a retrospective study of adult patients who presented to four Massachusetts emergency departments between June 2015 and June 2018 with suspected serious bacterial infection, defined as blood cultures drawn and broad-spectrum IV antibiotics administered. Structured medical record reviews were performed on a random sample of 300 cases to determine the post hoc likelihood of bacterial infection, categorized as definite, likely, unlikely, or definitely none. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 300 patients with suspected serious bacterial infections, mean age was 68 years (sd 18), median hospital length of stay was 5 days (interquartile range, 3-8 d), 45 (15%) were admitted directly to ICU, and 14 (5%) died in hospital. Overall, 196 (65%) had definite (n = 115; 38%) or likely (n = 81; 27%) bacterial infection, whereas 104 (35%) were unlikely (n = 55; 18%) or definitely not infected (n = 49; 16%). Antibiotic treatment durations differed by likelihood of infection (median 15 days for definite, 9 for likely, 7 for unlikely, and 3 for definitely not infected). The most frequent post hoc diagnoses in patients with unlikely or definitely no bacterial infection included viral infections (28%), volume overload or cardiac disease (9%), drug effects (9%), and hypovolemia (7%). The likelihoods of infection were similar in the subset of 96 cases in whom emergency department providers explicitly documented possible or suspected sepsis and in the 45 patients admitted from the emergency department to the ICU. CONCLUSIONS: One third of patients empirically treated with broad-spectrum antibiotics in the emergency department are ultimately diagnosed with noninfectious or viral conditions. These findings underscore the difficulty diagnosing serious infections in the emergency department and have important implications for guidelines and quality measures that compel immediate empiric antibiotics for all patients with possible sepsis.

Surveillance Strategies for Tracking Sepsis Incidence and Outcomes.

Sepsis is a leading cause of death and the target of intense efforts to improve recognition, management and outcomes. Accurate sepsis surveillance is essential to properly interpreting the impact of quality improvement initiatives, making meaningful comparisons across hospitals and geographic regions, and guiding future research and resource investments. However, it is challenging to reliably track sepsis incidence and outcomes because sepsis is a heterogeneous clinical syndrome without a pathologic reference standard, allowing for subjectivity and broad discretion in assigning diagnoses. Most epidemiologic studies of sepsis to date have used hospital discharge codes and have suggested dramatic increases in sepsis incidence and decreases in mortality rates over time. However, diagnosis and coding practices vary widely between hospitals and are changing over time, complicating the interpretation of absolute rates and trends. Other surveillance approaches include death records, prospective clinical registries, retrospective medical record reviews, and analyses of the usual care arms of randomized controlled trials. Each of these strategies, however, has substantial limitations. Recently, the US Centers for Disease Control and Prevention released an "Adult Sepsis Event" definition that uses objective clinical indicators of infection and organ dysfunction that can be extracted from most hospitals' electronic health record systems. Emerging data suggest that electronic health record-based clinical surveillance, such as surveillance of Adult Sepsis Event, is accurate, can be applied uniformly across diverse hospitals, and generates more credible estimates of sepsis trends than administrative data. In this review, we discuss the advantages and limitations of different sepsis surveillance strategies and consider future directions.

Trends in Empiric Broad-Spectrum Antibiotic Use for Suspected Community-Onset Sepsis in US Hospitals.

Importance: Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time. Objective: To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis. Design, Setting, and Participants: This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission. Exposures: Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal ß-lactam agent use. Main Outcomes and Measures: Annual rates of empiric anti-MRSA and/or antipseudomonal ß-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of ß-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics. Results: Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal ß-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal ß-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13). Conclusions and Relevance: In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.

Impact of changing case definitions for coronavirus disease 2019 (COVID-19) hospitalization on pandemic metrics.

OBJECTIVE: To examine the impact of commonly used case definitions for coronavirus disease 2019 (COVID-19) hospitalizations on case counts and outcomes. DESIGN, PATIENTS, AND SETTING: Retrospective analysis of all adults hospitalized between March 1, 2020, and March 1, 2022, at 5 Massachusetts acute-care hospitals. INTERVENTIONS: We applied 6 commonly used definitions of COVID-19 hospitalization: positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) assay within 14 days of admission, PCR plus dexamethasone administration, PCR plus remdesivir, PCR plus hypoxemia, institutional COVID-19 flag, or COVID-19 International Classification of Disease, Tenth Revision (ICD-10) codes. Outcomes included case counts and in-hospital mortality. Overall, 100 PCR-positive cases were reviewed to determine each definition's accuracy for distinguishing primary or contributing versus incidental COVID-19 hospitalizations. RESULTS: Of 306,387 hospital encounters, 15,436 (5.0%) met the PCR-based definition. COVID-19 hospitalization counts varied substantially between definitions: 4,628 (1.5% of all encounters) for PCR plus dexamethasone, 5,757 (1.9%) for PCR plus remdesivir, 11,801 (3.9%) for PCR plus hypoxemia, 15,673 (5.1%) for institutional flags, and 15,868 (5.2%) for ICD-10 codes. Definitions requiring dexamethasone, hypoxemia, or remdesivir selected sicker patients compared to PCR alone (mortality rates 12.2%, 10.7%, and 8.8% vs 8.3%, respectively). Definitions requiring PCR plus remdesivir or dexamethasone did not detect a reduction in in-hospital mortality associated with the SARS-CoV-2 Omicron variant. ICD-10 codes had the highest sensitivity (98.4%) but low specificity (39.5%) for distinguishing primary or contributing versus incidental COVID-19 hospitalizations. PCR plus dexamethasone had the highest specificity (92.1%) but low sensitivity (35.5%). CONCLUSIONS: Commonly used definitions for COVID-19 hospitalizations generate variable case counts and outcomes and differentiate poorly between primary or contributing versus incidental COVID-19 hospitalizations. Surveillance definitions that better capture and delineate COVID-19-associated hospitalizations are needed.

Use of Electronic Clinical Data to Track Incidence and Mortality for SARS-CoV-2-Associated Sepsis.

Importance: Efforts to quantify the burden of SARS-CoV-2-associated sepsis have been limited by inconsistent definitions and underrecognition of viral sepsis. Objective: To describe the incidence and outcomes of SARS-CoV-2-associated sepsis vs presumed bacterial sepsis using objective electronic clinical criteria. Design, Setting, and Participants: This retrospective cohort study included adults hospitalized at 5 Massachusetts hospitals between March 2020 and November 2022. Exposures: SARS-CoV-2-associated sepsis was defined as a positive SARS-CoV-2 polymerase chain reaction test and concurrent organ dysfunction (ie, oxygen support above simple nasal cannula, vasopressors, elevated lactate level, rise in creatine or bilirubin level, and/or decline in platelets). Presumed bacterial sepsis was defined by modified US Centers for Disease Control and Prevention adult sepsis event criteria (ie, blood culture order, sustained treatment with antibiotics, and organ dysfunction using identical thresholds as for SARS-CoV-2-associated sepsis). Main Outcomes and Measures: Trends in the quarterly incidence (ie, proportion of hospitalizations) and in-hospital mortality for SARS-CoV-2-associated and presumed bacterial sepsis were assessed using negative binomial and logistic regression models. Results: This study included 431 017 hospital encounters from 261 595 individuals (mean [SD] age 57.9 [19.8] years, 241 131 (55.9%) females, 286 397 [66.5%] from academic hospital site). Of these encounters, 23 276 (5.4%) were from SARS-CoV-2, 6558 (1.5%) had SARS-CoV-2-associated sepsis, and 30 604 patients (7.1%) had presumed bacterial sepsis without SARS-CoV-2 infection. Crude in-hospital mortality for SARS-CoV-2-associated sepsis declined from 490 of 1469 (33.4%) in the first quarter to 67 of 450 (14.9%) in the last (adjusted odds ratio [aOR], 0.88 [95% CI, 0.85-0.90] per quarter). Crude mortality for presumed bacterial sepsis was 4451 of 30 604 patients (14.5%) and stable across quarters (aOR, 1.00 [95% CI, 0.99-1.01]). Medical record reviews of 200 SARS-CoV-2-positive hospitalizations confirmed electronic health record (EHR)-based SARS-CoV-2-associated sepsis criteria performed well relative to sepsis-3 criteria (90.6% [95% CI, 80.7%-96.5%] sensitivity; 91.2% [95% CI, 85.1%-95.4%] specificity). Conclusions and Relevance: In this retrospective cohort study of hospitalized adults, SARS-CoV-2 accounted for approximately 1 in 6 cases of sepsis during the first 33 months of the COVID-19 pandemic. In-hospital mortality rates for SARS-CoV-2-associated sepsis were high but declined over time and ultimately were similar to presumed bacterial sepsis. These findings highlight the high burden of SARS-CoV-2-associated sepsis and demonstrate the utility of EHR-based algorithms to conduct surveillance for viral and bacterial sepsis.

Prevalence, Clinical Characteristics, and Outcomes of Sepsis Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Versus Other Pathogens in Hospitalized Patients With COVID-19.

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.

Practice variability in brain death determination: a call to action.

OBJECTIVE: To characterize the present state of brain death (BD) determination in actual practice relative to contemporary American Academy of Neurology (AAN) guidelines. METHODS: We reviewed the charts of all adult (16 years and older) BD organ donors during 2011 from 68 heterogeneous hospitals in the Midwest United States. Data were collected across 5 categories: guideline performance, preclinical testing, clinical examination, apnea testing, and use of ancillary tests. Practice within categories and overall adherence to AAN guidelines were assessed. RESULTS: Two hundred twenty-six BD organ donors were included. Practice exceeded recommendations in guideline performance but varied widely and deviated from AAN guidelines in all other categories. One hundred two (45.1%) had complete documentation of brainstem areflexia and absent motor response. One hundred sixty-six (73.5%) had completed apnea testing. Of the 60 without completed apnea testing, 56 (93.3%) had ancillary tests consistent with BD. Overall, 101 (44.7%) strictly and 84 (37.2%) loosely adhered to contemporary AAN guidelines. CONCLUSIONS: There is wide variability in the documentation of BD determination, likely reflecting similar variability in practice. This is a call for improved documentation, better uniformity of policies, and comprehensive and strategically targeted educational initiatives to ensure consistently contemporary approaches to BD determination in every patient.