Incorporating social determinants of health into transmission modeling of COVID-19 vaccine in the US: a scoping review.

During COVID-19 in the US, social determinants of health (SDH) have driven health disparities. However, the use of SDH in COVID-19 vaccine modeling is unclear. This review aimed to summarize the current landscape of incorporating SDH into COVID-19 vaccine transmission modeling in the US. Medline and Embase were searched up to October 2022. We included studies that used transmission modeling to assess the effects of COVID-19 vaccine strategies in the US. Studies' characteristics, factors incorporated into models, and approaches to incorporate these factors were extracted. Ninety-two studies were included. Of these, 11 studies incorporated SDH factors (alone or combined with demographic factors). Various sets of SDH factors were integrated, with occupation being the most common (8 studies), followed by geographical location (5 studies). The results show that few studies incorporate SDHs into their models, highlighting the need for research on SDH impact and approaches to incorporating SDH into modeling. Funding: This research was funded by the Centers for Disease Control and Prevention (CDC).

Automating detection of diagnostic error of infectious diseases using machine learning.

Diagnostic error, a cause of substantial morbidity and mortality, is largely discovered and evaluated through self-report and manual review, which is costly and not suitable to real-time intervention. Opportunities exist to leverage electronic health record data for automated detection of potential misdiagnosis, executed at scale and generalized across diseases. We propose a novel automated approach to identifying diagnostic divergence considering both diagnosis and risk of mortality. Our objective was to identify cases of emergency department infectious disease misdiagnoses by measuring the deviation between predicted diagnosis and documented diagnosis, weighted by mortality. Two machine learning models were trained for prediction of infectious disease and mortality using the first 24h of data. Charts were manually reviewed by clinicians to determine whether there could have been a more correct or timely diagnosis. The proposed approach was validated against manual reviews and compared using the Spearman rank correlation. We analyzed 6.5 million ED visits and over 700 million associated clinical features from over one hundred emergency departments. The testing set performances of the infectious disease (Macro F1 = 86.7, AUROC 90.6 to 94.7) and mortality model (Macro F1 = 97.6, AUROC 89.1 to 89.1) were in expected ranges. Human reviews and the proposed automated metric demonstrated positive correlations ranging from 0.231 to 0.358. The proposed approach for diagnostic deviation shows promise as a potential tool for clinicians to find diagnostic errors. Given the vast number of clinical features used in this analysis, further improvements likely need to either take greater account of data structure (what occurs before when) or involve natural language processing. Further work is needed to explain the potential reasons for divergence and to refine and validate the approach for implementation in real-world settings.

Development and implementation of a nationwide multidrug-resistant organism tracking and alert system for Veterans Affairs medical centers.

OBJECTIVE: Develop and implement a system in the Veterans Health Administration (VA) to alert local medical center personnel in real time when an acute- or long-term care patient/resident is admitted to their facility with a history of colonization or infection with a multidrug-resistant organism (MDRO) previously identified at any VA facility across the nation. METHODS: An algorithm was developed to extract clinical microbiology and local facility census data from the VA Corporate Data Warehouse initially targeting carbapenem-resistant Enterobacterales (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). The algorithm was validated with chart review of CRE cases from 2010-2018, trialed and refined in 24 VA healthcare systems over two years, expanded to other MDROs and implemented nationwide on 4/2022 as "VA Bug Alert" (VABA). Use through 8/2023 was assessed. RESULTS: VABA performed well for CRE with recall of 96.3%, precision of 99.8%, and F1 score of 98.0%. At the 24 trial sites, feedback was recorded for 1,011 admissions with a history of CRE (130), MRSA (814), or both (67). Among Infection Preventionists and MDRO Prevention Coordinators, 338 (33%) reported being previously unaware of the information, and of these, 271 (80%) reported they would not have otherwise known this information. By fourteen months after nationwide implementation, 113/130 (87%) VA healthcare systems had at least one VABA subscriber. CONCLUSIONS: A national system for alerting facilities in real-time of patients admitted with an MDRO history was successfully developed and implemented in VA. Next steps include understanding facilitators and barriers to use and coordination with non-VA facilities nationwide.

Treatment effectiveness of antibiotic therapy in Veterans with multidrug-resistant Acinetobacter spp. bacteremia.

Objective: To describe antimicrobial therapy used for multidrug-resistant (MDR) Acinetobacter spp. bacteremia in Veterans and impacts on mortality. Methods: This was a retrospective cohort study of hospitalized Veterans Affairs patients from 2012 to 2018 with a positive MDR Acinetobacter spp. blood culture who received antimicrobial treatment 2 days prior to through 5 days after the culture date. Only the first culture per patient was used. The association between treatment and patient characteristics was assessed using bivariate analyses. Multivariable logistic regression models examined the relationship between antibiotic regimen and in-hospital, 30-day, and 1-year mortality. Generalized linear models were used to assess cost outcomes. Results: MDR Acinetobacter spp. was identified in 184 patients. Most cultures identified were Acinetobacter baumannii (90%), 3% were Acinetobacter lwoffii, and 7% were other Acinetobacter species. Penicillins-ß-lactamase inhibitor combinations (51.1%) and carbapenems (51.6%)-were the most prescribed antibiotics. In unadjusted analysis, extended spectrum cephalosporins and penicillins-ß-lactamase inhibitor combinations-were associated with a decreased odds of 30-day mortality but were insignificant after adjustment (adjusted odds ratio (aOR) = 0.47, 95% CI, 0.21-1.05, aOR = 0.75, 95% CI, 0.37-1.53). There was no association between combination therapy vs monotherapy and 30-day mortality (aOR = 1.55, 95% CI, 0.72-3.32). Conclusion: In hospitalized Veterans with MDR Acinetobacter spp., none of the treatments were shown to be associated with in-hospital, 30-day, and 1-year mortality. Combination therapy was not associated with decreased mortality for MDR Acinetobacter spp. bacteremia.

Disparities in COVID-19 related outcomes in the United States by race and ethnicity pre-vaccination era: an umbrella review of meta-analyses.

Background: Meta-analyses have investigated associations between race and ethnicity and COVID-19 outcomes. However, there is uncertainty about these associations' existence, magnitude, and level of evidence. We, therefore, aimed to synthesize, quantify, and grade the strength of evidence of race and ethnicity and COVID-19 outcomes in the US. Methods: In this umbrella review, we searched four databases (Pubmed, Embase, the Cochrane Database of Systematic Reviews, and Epistemonikos) from database inception to April 2022. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews, version 2 (AMSTAR-2). The strength of evidence of the associations between race and ethnicity with outcomes was ranked according to established criteria as convincing, highly suggestive, suggestive, weak, or non-significant. The study protocol was registered with PROSPERO, CRD42022336805. Results: Of 880 records screened, we selected seven meta-analyses for evidence synthesis, with 42 associations examined. Overall, 10 of 42 associations were statistically significant (p ≤ 0.05). Two associations were highly suggestive, two were suggestive, and two were weak, whereas the remaining 32 associations were non-significant. The risk of COVID-19 infection was higher in Black individuals compared to White individuals (risk ratio, 2.08, 95% Confidence Interval (CI), 1.60-2.71), which was supported by highly suggestive evidence; with the conservative estimates from the sensitivity analyses, this association remained suggestive. Among those infected with COVID-19, Hispanic individuals had a higher risk of COVID-19 hospitalization than non-Hispanic White individuals (odds ratio, 2.08, 95% CI, 1.60-2.70) with highly suggestive evidence which remained after sensitivity analyses. Conclusion: Individuals of Black and Hispanic groups had a higher risk of COVID-19 infection and hospitalization compared to their White counterparts. These associations of race and ethnicity and COVID-19 outcomes existed more obviously in the pre-hospitalization stage. More consideration should be given in this stage for addressing health inequity.

Active Surveillance and Contact Precautions for Preventing Methicillin-Resistant Staphylococcus aureus Healthcare-Associated Infections During the COVID-19 Pandemic.

BACKGROUND: Statistically significant decreases in methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) occurred in Veterans Affairs (VA) hospitals from 2007 to 2019 using a national policy of active surveillance (AS) for facility admissions and contact precautions for MRSA colonized (CPC) or infected (CPI) patients, but the impact of suspending these measures to free up laboratory resources for testing and conserve personal protective equipment for coronavirus disease 2019 (COVID-19) on MRSA HAI rates is not known. METHODS: From July 2020 to June 2022 all 123 acute care VA hospitals nationwide were given the rolling option to suspend (or re-initiate) any combination of AS, CPC, or CPI each month, and MRSA HAIs in intensive care units (ICUs) and non-ICUs were tracked. RESULTS: There were 917 591 admissions, 5 225 174 patient-days, and 568 MRSA HAIs. The MRSA HAI rate/1000 patient-days in ICUs was 0.20 (95% confidence interval [CI], .15-.26) for facilities practicing "AS + CPC + CPI" compared to 0.65 (95% CI, .41-.98; P < .001) for those not practicing any of these strategies, and in non-ICUs was 0.07 (95% CI, .05-.08) and 0.12 (95% CI, .08-.19; P = .01) for the respective policies. Accounting for monthly COVID-19 facility admissions using a negative binomial regression model did not change the relationships between facility policy and MRSA HAI rates. There was no significant difference in monthly facility urinary catheter-associated infection rates, a non-equivalent dependent variable, in the policy categories in either ICUs or non-ICUs. CONCLUSIONS: Facility removal of MRSA prevention practices was associated with higher rates of MRSA HAIs in ICUs and non-ICUs.

Development and validation of a standardized blood culture contamination definition and metric dashboard for a large health care system.

OBJECTIVES: Blood culture contamination is a major problem in health care, with significant impacts on both patient safety and cost. Initiatives to reduce blood culture contamination require a reliable, consistent metric to track the success of interventions. The objective of our project was to establish a standardized definition of blood culture contamination suitable for use in a Veterans Health Administration (VHA) national data query, then to validate this definition and query. A secondary objective was to construct a national VHA data dashboard to display the data from this query that could be used in VHA quality improvement projects aimed at reducing blood culture contamination. METHODS: A VHA microbiology expert work group was formed to generate a standardized definition and oversee the validation studies. The standardized definition was used to generate data for calendar year 2021 using a Structured Query Language data query. Twelve VHA hospital microbiology laboratories compared the data from the query against their own locally derived contamination data and recorded those data in a data collection worksheet that all sites used. Data were collated and presented to the work group. RESULTS: More than 50,000 blood culture accessions were in the validation data set, with more than 1,200 contamination events. The overall blood culture contamination rate for the 12 facilities participating was 2.56% with local definitions and data and 2.43% with the standardized definitions and data query. The main differences noted between the 2 data sets were deemed to be issues in local definitions. The query and definition were then converted into a national data dashboard that all VHA facilities can now access. CONCLUSIONS: A standardized definition for blood culture contamination and a national data query were validated for enterprise-wide VHA use. To our knowledge, this represents the first reported standardized, validated, and automated approach for calculating and tracking blood culture contamination. This tool will be key in quality initiatives aimed at reducing contamination events in VHA.

Performance of infectious diseases specialists, hospitalists, and other internal medicine physicians in antimicrobial case-based scenarios: Potential impact of antimicrobial stewardship programs at 16 Veterans' Affairs medical centers.

OBJECTIVE: As part of a project to implement antimicrobial dashboards at select facilities, we assessed physician attitudes and knowledge regarding antibiotic prescribing. DESIGN: An online survey explored attitudes toward antimicrobial use and assessed respondents' management of four clinical scenarios: cellulitis, community-acquired pneumonia, non-catheter-associated asymptomatic bacteriuria, and catheter-associated asymptomatic bacteriuria. SETTING: This study was conducted across 16 Veterans' Affairs (VA) medical centers in 2017. PARTICIPANTS: Physicians working in inpatient settings specializing in infectious diseases (ID), hospital medicine, and non-ID/hospitalist internal medicine. METHODS: Scenario responses were scored by assigning +1 for answers most consistent with guidelines, 0 for less guideline-concordant but acceptable answers and -1 for guideline-discordant answers. Scores were normalized to 100% guideline concordant to 100% guideline discordant across all questions within a scenario, and mean scores were calculated across respondents by specialty. Differences in mean score per scenario were tested using analysis of variance (ANOVA). RESULTS: Overall, 139 physicians completed the survey (19 ID physicians, 62 hospitalists, and 58 other internists). Attitudes were similar across the 3 groups. We detected a significant difference in cellulitis scenario scores (concordance: ID physicians, 76%; hospitalists, 58%; other internists, 52%; P = .0087). Scores were numerically but not significantly different across groups for community-acquired pneumonia (concordance: ID physicians, 75%; hospitalists, 60%; other internists, 56%; P = .0914), for non-catheter-associated asymptomatic bacteriuria (concordance: ID physicians, 65%; hospitalists, 55%; other internists, 40%; P = .322), and for catheter-associated asymptomatic bacteriuria (concordance: ID physicians, 27% concordant; hospitalists, 8% discordant; other internists 13% discordant; P = .12). CONCLUSIONS: Significant differences in performance regarding management of cellulitis and low overall performance regarding asymptomatic bacteriuria point to these conditions as being potentially high-yield targets for stewardship interventions.

Hospital coronavirus disease 2019 (COVID-19) public health reporting: Lessons from validation of an automated surveillance tool to facilitate data collection.

A comparison of computer-extracted and facility-reported counts of hospitalized coronavirus disease 2019 (COVID-19) patients for public health reporting at 36 hospitals revealed 42% of days with matching counts between the data sources. Miscategorization of suspect cases was a primary driver of discordance. Clear reporting definitions and data validation facilitate emerging disease surveillance.

Healthcare-associated infections in Veterans Affairs acute-care and long-term healthcare facilities during the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: To assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infections (HAIs) reported from 128 acute-care and 132 long-term care Veterans Affairs (VA) facilities. METHODS: We compared central-line-associated bloodstream infections (CLABSIs), ventilator-associated events (VAEs), catheter-associated urinary tract infections (CAUTIs), methicillin-resistant Staphylococcus aureus (MRSA), and Clostridioides difficile infections and rates reported from each facility monthly to a centralized database before the pandemic (February 2019 through January 2020) and during the pandemic (July 2020 through June 2021). RESULTS: Nationwide VA COVID-19 admissions peaked in January 2021. Significant increases in the rates of CLABSIs, VAEs, and MRSA all-site HAIs (but not MRSA CLABSIs) were observed during the pandemic in acute-care facilities. There was no significant change in CAUTI rates, and C. difficile rates significantly decreased. There were no significant increases in HAIs in long-term care facilities. CONCLUSIONS: The COVID-19 pandemic had a differential impact on HAIs of various types in VA acute care, with many rates increasing. The decrease in CDI HAIs may be due, in part, to evolving diagnostic testing. The minimal impact of COVID-19 in VA long-term facilities may reflect differences in patient numbers and acuity and early recognition of the impact of the pandemic on nursing home residents leading to increased vigilance and optimization of infection prevention and control practices in that setting. These data support the need for building and sustaining conventional infection prevention and control strategies before and during a pandemic.

Lack of correlation between standardized antimicrobial administration ratios (SAARs) and healthcare-facility-onset Clostridioides difficile infection rates in Veterans Affairs medical facilities.

We detected no correlation between standardized antimicrobial administration ratios (SAARs) and healthcare facility-onset Clostridioides difficile infection (HO-CDI) rates in 102 acute-care Veterans Affairs medical centers over 16 months. SAARs may be useful for investigating trends in local antimicrobial use, but no ratio threshold demarcated HO-CDI risk.

Increased carbapenemase testing following implementation of national VA guidelines for carbapenem-resistant Enterobacterales (CRE).

Objective: To describe national trends in testing and detection of carbapenemases produced by carbapenem-resistant Enterobacterales (CRE) and associate testing with culture and facility characteristics. Design: Retrospective cohort study. Setting: Department of Veterans' Affairs medical centers (VAMCs). Participants: Patients seen at VAMCs between 2013 and 2018 with cultures positive for CRE, defined by national VA guidelines. Interventions: Microbiology and clinical data were extracted from national VA data sets. Carbapenemase testing was summarized using descriptive statistics. Characteristics associated with carbapenemase testing were assessed with bivariate analyses. Results: Of 5,778 standard cultures that grew CRE, 1,905 (33.0%) had evidence of molecular or phenotypic carbapenemase testing and 1,603 (84.1%) of these had carbapenemases detected. Among these cultures confirmed as carbapenemase-producing CRE, 1,053 (65.7%) had molecular testing for ≥1 gene. Almost all testing included KPC (n = 1,047, 99.4%), with KPC detected in 914 of 1,047 (87.3%) cultures. Testing and detection of other enzymes was less frequent. Carbapenemase testing increased over the study period from 23.5% of CRE cultures in 2013 to 58.9% in 2018. The South US Census region (38.6%) and the Northeast (37.2%) region had the highest proportion of CRE cultures with carbapenemase testing. High complexity (vs low) and urban (vs rural) facilities were significantly associated with carbapenemase testing (P < .0001). Conclusions: Between 2013 and 2018, carbapenemase testing and detection increased in the VA, largely reflecting increased testing and detection of KPC. Surveillance of other carbapenemases is important due to global spread and increasing antibiotic resistance. Efforts supporting the expansion of carbapenemase testing to low-complexity, rural healthcare facilities and standardization of reporting of carbapenemase testing are needed.

Temporal Trends in Antimicrobial Prescribing During Hospitalization for Potential Infection and Sepsis.

Importance: Some experts have cautioned that national and health system emphasis on rapid administration of antimicrobials for sepsis may increase overall antimicrobial use even among patients without sepsis. Objective: To assess whether temporal changes in antimicrobial timing for sepsis are associated with increasing antimicrobial use, days of therapy, or broadness of antimicrobial coverage among all hospitalized patients at risk for sepsis. Design, Setting, and Participants: This is an observational cohort study of hospitalized patients at 152 hospitals in 2 health care systems during 2013 to 2018, admitted via the emergency department with 2 or more systemic inflammatory response syndrome (SIRS) criteria. Data analysis was performed from June 10, 2021, to March 22, 2022. Exposures: Hospital-level temporal trends in time to first antimicrobial administration. Outcomes: Antimicrobial outcomes included antimicrobial use, days of therapy, and broadness of antibacterial coverage. Clinical outcomes included in-hospital mortality, 30-day mortality, length of hospitalization, and new multidrug-resistant (MDR) organism culture positivity. Results: Among 1 559 523 patients admitted to the hospital via the emergency department with 2 or more SIRS criteria (1 269 998 male patients [81.4%]; median [IQR] age, 67 [59-77] years), 273 255 (17.5%) met objective criteria for sepsis. In multivariable models adjusted for patient characteristics, the adjusted median (IQR) time to first antimicrobial administration to patients with sepsis decreased by 37 minutes, from 4.7 (4.1-5.3) hours in 2013 to 3.9 (3.6-4.4) hours in 2018, although the slope of decrease varied across hospitals. During the same period, antimicrobial use within 48 hours, days of antimicrobial therapy, and receipt of broad-spectrum coverage decreased among the broader cohort of patients with SIRS. In-hospital mortality, 30-day mortality, length of hospitalization, new MDR culture positivity, and new MDR blood culture positivity decreased over the study period among both patients with sepsis and those with SIRS. When examining hospital-specific trends, decreases in antimicrobial use, days of therapy, and broadness of antibacterial coverage for patients with SIRS did not differ by hospital antimicrobial timing trend for sepsis. Overall, there was no evidence that accelerating antimicrobial timing for sepsis was associated with increasing antimicrobial use or impaired antimicrobial stewardship. Conclusions and Relevance: In this multihospital cohort study, the time to first antimicrobial for sepsis decreased over time, but this trend was not associated with increasing antimicrobial use, days of therapy, or broadness of antimicrobial coverage among the broader population at-risk for sepsis, which suggests that shortening the time to antibiotics for sepsis is feasible without leading to indiscriminate antimicrobial use.

Epidemiology and outcomes associated with carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa: a retrospective cohort study.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to describe CRAB and CRPA epidemiology and identify factors associated with mortality and length of stay (LOS) post-culture. METHODS: This was a national retrospective cohort study of Veterans with CRAB or CRPA positive cultures from 2013 to 2018, conducted at Hines Veterans Affairs Hospital. Carbapenem resistance was defined as non-susceptibility to imipenem, meropenem and/or doripenem. Multivariable cluster adjusted regression models were fit to assess the association of post-culture LOS among inpatient and long-term care (LTC) and to identify factors associated with 90-day and 365-day mortality after positive CRAB and CRPA cultures. RESULTS: CRAB and CRPA were identified in 1,048 and 8,204 unique patients respectively, with 90-day mortality rates of 30.3% and 24.5% and inpatient post-LOS of 26 and 27 days. Positive blood cultures were associated with an increased odds of 90-day mortality compared to urine cultures in patients with CRAB (OR 6.98, 95% CI 3.55-13.73) and CRPA (OR 2.82, 95% CI 2.04-3.90). In patients with CRAB and CRPA blood cultures, higher Charlson score was associated with increased odds of 90-day mortality. In CRAB and CRPA, among patients from inpatient care settings, blood cultures were associated with a decreased LOS compared to urine cultures. CONCLUSIONS: Positive blood cultures and more comorbidities were associated with higher odds for mortality in patients with CRAB and CRPA. Recognizing these factors would encourage clinicians to treat these patients in a timely manner to improve outcomes of patients infected with these organisms.

Trends in Illness Severity, Hospitalization, and Mortality for Community-Onset Pneumonia at 118 US Veterans Affairs Medical Centers.

BACKGROUND: Deaths from pneumonia were decreasing globally prior to the COVID-19 pandemic, but it is unclear whether this was due to changes in patient populations, illness severity, diagnosis, hospitalization thresholds, or treatment. Using clinical data from the electronic health record among a national cohort of patients initially diagnosed with pneumonia, we examined temporal trends in severity of illness, hospitalization, and short- and long-term deaths. DESIGN: Retrospective cohort PARTICIPANTS: All patients >18 years presenting to emergency departments (EDs) at 118 VA Medical Centers between 1/1/2006 and 12/31/2016 with an initial clinical diagnosis of pneumonia and confirmed by chest imaging report. EXPOSURES: Year of encounter. MAIN MEASURES: Hospitalization and 30-day and 90-day mortality. Illness severity was defined as the probability of each outcome predicted by machine learning predictive models using age, sex, comorbidities, vital signs, and laboratory data from encounters during years 2006-2007, and similar models trained on encounters from years 2015 to 2016. We estimated the changes in hospitalizations and 30-day and 90-day mortality between the first and the last 2 years of the study period accounted for by illness severity using time covariate decompositions with model estimates. RESULTS: Among 196,899 encounters across the study period, hospitalization decreased from 71 to 63%, 30-day mortality 10 to 7%, 90-day mortality 16 to 12%, and 1-year mortality 29 to 24%. Comorbidity risk increased, but illness severity decreased. Decreases in illness severity accounted for 21-31% of the decrease in hospitalizations, and 45-47%, 32-24%, and 17-19% of the decrease in 30-day, 90-day, and 1-year mortality. Findings were similar among underrepresented patients and those with only hospital discharge diagnosis codes. CONCLUSIONS: Outcomes for community-onset pneumonia have improved across the VA healthcare system after accounting for illness severity, despite an increase in cases and comorbidity burden.

Treatment of extensively-drug resistant (XDR) Acinetobacter and impact on clinical outcomes in U.S. veterans affairs (VA) medical centers.

BACKGROUND: Guidelines for treatment of resistant Acinetobacter baumannii (AB) are limited, leaving a knowledge gap in best practices for treatment. This study described treatments and outcomes of extensively-drug resistant (XDR) AB. METHODS: Retrospective cohort study including patients with XDRAB (non-susceptible to at least 1 agent in all but 2 or fewer classes) and antibiotic treatment between 2012 and 2018 at Veterans Affairs Medical Centers. Descriptive statistics summarized antibiotics; propensity score adjusted regression models were fit to compare outcomes. RESULTS: Two hundred and seventy-six patients with 439 XDRAB cultures and Gram-negative targeted antibiotic treatment were included. One hundred and eighteen (43%) patients received monotherapy while 158 (57%) received combination therapy, most commonly including a carbapenem (n = 106, 67%) and polymyxin (n = 66, 42%). One hundred and eighty-four (67%) patients received inadequate treatment. In adjusted models, combination therapy did not decrease the odds of in-hospital (aOR 1.24, 95%CI 0.60-2.59) or 30-day (aOR 1.43, 95%CI 0.86-2.38) mortality, or median postculture length of stay (aIRR 1.11, 95%CI 0.86-1.43). Likewise, receipt of inadequate treatment was not associated with poorer outcomes. CONCLUSIONS: In this national cohort of patients with XDRAB, neither combination therapy nor receipt of adequate treatment improved outcomes. Further research is needed on optimal management of this difficult-to-treat pathogen with few effective antibiotic options.

Optimal Urine Culture Diagnostic Stewardship Practice-Results from an Expert Modified-Delphi Procedure.

BACKGROUND: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship. METHODS: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed. RESULTS: One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions. CONCLUSIONS: These 18 guidance statements can optimize use of urine cultures for better patient outcomes.

Temporal Trends and Hospital Variation in Time-to-Antibiotics Among Veterans Hospitalized With Sepsis.

Importance: It is unclear whether antimicrobial timing for sepsis has changed outside of performance incentive initiatives. Objective: To examine temporal trends and variation in time-to-antibiotics for sepsis in the US Department of Veterans Affairs (VA) health care system. Design, Setting, and Participants: This observational cohort study included 130 VA hospitals from 2013 to 2018. Participants included all patients admitted to the hospital via the emergency department with sepsis from 2013 to 2018, using a definition adapted from the Centers for Disease Control and Prevention Adult Sepsis Event definition, which requires evidence of suspected infection, acute organ dysfunction, and systemic antimicrobial therapy within 12 hours of presentation. Data were analyzed from October 6, 2020, to July 1, 2021. Exposures: Time from presentation to antibiotic administration. Main Outcomes and Measures: The main outcome was differences in time-to-antibiotics across study periods, hospitals, and patient subgroups defined by presenting temperature and blood pressure. Temporal trends in time-to-antibiotics were measured overall and by subgroups. Hospital-level variation in time-to-antibiotics was quantified after adjusting for differences in patient characteristics using multilevel linear regression models. Results: A total of 111 385 hospitalizations for sepsis were identified, including 107 547 men (96.6%) men and 3838 women (3.4%) with a median (interquartile range [IQR]) age of 68 (62-77) years. A total of 7574 patients (6.8%) died in the hospital, and 13 855 patients (12.4%) died within 30 days. Median (IQR) time-to-antibiotics was 3.9 (2.4-6.5) hours but differed by presenting characteristics. Unadjusted median (IQR) time-to-antibiotics decreased over time, from 4.5 (2.7-7.1) hours during 2013 to 2014 to 3.5 (2.2-5.9) hours during 2017 to 2018 (P < .001). In multilevel models adjusted for patient characteristics, median time-to-antibiotics declined by 9.0 (95% CI, 8.8-9.2) minutes per calendar year. Temporal trends in time-to-antibiotics were similar across patient subgroups, but hospitals with faster baseline time-to-antibiotics had less change over time, with hospitals in the slowest tertile decreasing time-to-antibiotics by 16.6 minutes (23.1%) per year, while hospitals in the fastest tertile decreased time-to-antibiotics by 7.2 minutes (13.1%) per year. In the most recent years (2017-2018), median time-to-antibiotics ranged from 3.1 to 6.7 hours across hospitals (after adjustment for patient characteristics), 6.8% of variation in time-to-antibiotics was explained at the hospital level, and odds of receiving antibiotics within 3 hours increased by 65% (95% CI, 56%-77%) for the median patient if moving to a hospital with faster time-to-antibiotics. Conclusions and Relevance: This cohort study across nationwide VA hospitals found that time-to-antibiotics for sepsis has declined over time. However, there remains significant variability in time-to-antibiotics not explained by patient characteristics, suggesting potential unwarranted practice variation in sepsis treatment. Efforts to further accelerate time-to-antibiotics must be weighed against risks of overtreatment.

Computerized Mortality Prediction for Community-acquired Pneumonia at 117 Veterans Affairs Medical Centers.

Rationale: Computerized severity assessment for community-acquired pneumonia could improve consistency and reduce clinician burden. Objectives: To develop and compare 30-day mortality-prediction models using electronic health record data, including a computerized score with all variables from the original Pneumonia Severity Index (PSI) except confusion and pleural effusion ("ePSI score") versus models with additional variables. Methods: Among adults with community-acquired pneumonia presenting to emergency departments at 117 Veterans Affairs Medical Centers between January 1, 2006, and December 31, 2016, we compared an ePSI score with 10 novel models employing logistic regression, spline, and machine learning methods using PSI variables, age, sex and 26 physiologic variables as well as all 69 PSI variables. Models were trained using encounters before January 1, 2015; tested on encounters during and after January 1, 2015; and compared using the areas under the receiver operating characteristic curve, confidence intervals, and patient event rates at a threshold PSI score of 970. Results: Among 297,498 encounters, 7% resulted in death within 30 days. When compared using the ePSI score (confidence interval [CI] for the area under the receiver operating characteristic curve, 0.77-0.78), performance increased with model complexity (CI for the logistic regression PSI model, 0.79-0.80; CI for the boosted decision-tree algorithm machine learning PSI model using the Extreme Gradient Boosting algorithm [mlPSI] with the 19 original PSI factors, 0.83-0.85) and the number of variables (CI for the logistic regression PSI model using all 69 variables, 0.84-085; CI for the mlPSI with all 69 variables, 0.86-0.87). Models limited to age, sex, and physiologic variables also demonstrated high performance (CI for the mlPSI with age, sex, and 26 physiologic factors, 0.84-0.85). At an ePSI score of 970 and a mortality-risk cutoff of <2.7%, the ePSI score identified 31% of all patients as being at "low risk"; the mlPSI with age, sex, and 26 physiologic factors identified 53% of all patients as being at low risk; and the mlPSI with all 69 variables identified 56% of all patients as being at low risk, with similar rates of mortality, hospitalization, and 7-day secondary hospitalization being determined. Conclusions: Computerized versions of the PSI accurately identified patients with pneumonia who were at low risk of death. More complex models classified more patients as being at low risk of death and as having similar adverse outcomes.