Protocol for a parallel cluster randomized trial of a participatory tailored approach to reduce overuse of antibiotics at hospital discharge: the ROAD home trial.

BACKGROUND: Antibiotic overuse at hospital discharge is common, costly, and harmful. While discharge-specific antibiotic stewardship interventions are effective, they are resource-intensive and often infeasible for hospitals with resource constraints. This weakness impacts generalizability of stewardship interventions and has health equity implications as not all patients have access to the benefits of stewardship based on where they receive care. There may be different pathways to improve discharge antibiotic prescribing that vary widely in feasibility. Supporting hospitals in selecting interventions tailored to their context may be an effective approach to feasibly reduce antibiotic overuse at discharge across diverse hospitals. The objective of this study is to evaluate the effectiveness of the Reducing Overuse of Antibiotics at Discharge Home multicomponent implementation strategy ("ROAD Home") on antibiotic overuse at discharge for community-acquired pneumonia and urinary tract infection. METHODS: This 4-year two-arm parallel cluster-randomized trial will include three phases: baseline (23 months), intervention (12 months), and postintervention (12 months). Forty hospitals recruited from the Michigan Hospital Medicine Safety Consortium will undergo covariate-constrained randomization with half randomized to the ROAD Home implementation strategy and half to a "stewardship as usual" control. ROAD Home is informed by the integrated-Promoting Action on Research Implementation in Health Services Framework and includes (1) a baseline needs assessment to create a tailored suite of potential stewardship interventions, (2) supported decision-making in selecting interventions to implement, and (3) external facilitation following an implementation blueprint. The primary outcome is baseline-adjusted days of antibiotic overuse at discharge. Secondary outcomes include 30-day patient outcomes and antibiotic-associated adverse events. A mixed-methods concurrent process evaluation will identify contextual factors influencing the implementation of tailored interventions, and assess implementation outcomes including acceptability, feasibility, fidelity, and sustainment. DISCUSSION: Reducing antibiotic overuse at discharge across hospitals with varied resources requires tailoring of interventions. This trial will assess whether a multicomponent implementation strategy that supports hospitals in selecting evidence-based stewardship interventions tailored to local context leads to reduced overuse of antibiotics at discharge. Knowledge gained during this study could inform future efforts to implement stewardship in diverse hospitals and promote equity in access to the benefits of quality improvement initiatives. TRIAL REGISTRATION: Clinicaltrials.gov NCT06106204 on 10/30/23.

Inappropriate Diagnosis of Pneumonia Among Hospitalized Adults.

Importance: Little is known about incidence of, risk factors for, and harms associated with inappropriate diagnosis of community-acquired pneumonia (CAP). Objective: To characterize inappropriate diagnosis of CAP in hospitalized patients. Design, Setting, and Participants: This prospective cohort study, including medical record review and patient telephone calls, took place across 48 Michigan hospitals. Trained abstractors retrospectively assessed hospitalized patients treated for CAP between July 1, 2017, and March 31, 2020. Patients were eligible for inclusion if they were adults admitted to general care with a discharge diagnostic code of pneumonia who received antibiotics on day 1 or 2 of hospitalization. Data were analyzed from February to December 2023. Main Outcomes and Measures: Inappropriate diagnosis of CAP was defined using a National Quality Forum-endorsed metric as CAP-directed antibiotic therapy in patients with fewer than 2 signs or symptoms of CAP or negative chest imaging. Risk factors for inappropriate diagnosis were assessed and, for those inappropriately diagnosed, 30-day composite outcomes (mortality, readmission, emergency department visit, Clostridioides difficile infection, and antibiotic-associated adverse events) were documented and stratified by full course (>3 days) vs brief (≤3 days) antibiotic treatment using generalized estimating equation models adjusting for confounders and propensity for treatment. Results: Of the 17 290 hospitalized patients treated for CAP, 2079 (12.0%) met criteria for inappropriate diagnosis (median [IQR] age, 71.8 [60.1-82.8] years; 1045 [50.3%] female), of whom 1821 (87.6%) received full antibiotic courses. Compared with patients with CAP, patients inappropriately diagnosed were older (adjusted odds ratio [AOR], 1.08; 95% CI, 1.05-1.11 per decade) and more likely to have dementia (AOR, 1.79; 95% CI, 1.55-2.08) or altered mental status on presentation (AOR, 1.75; 95% CI, 1.39-2.19). Among those inappropriately diagnosed, 30-day composite outcomes for full vs brief treatment did not differ (25.8% vs 25.6%; AOR, 0.98; 95% CI, 0.79-1.23). Full vs brief duration of antibiotic treatment among patients was associated with antibiotic-associated adverse events (31 of 1821 [2.1%] vs 1 of 258 [0.4%]; P = .03). Conclusions and Relevance: In this cohort study, inappropriate diagnosis of CAP among hospitalized adults was common, particularly among older adults, those with dementia, and those presenting with altered mental status. Full-course antibiotic treatment of those inappropriately diagnosed with CAP may be harmful.

Bacteremia From a Presumed Urinary Source in Hospitalized Adults With Asymptomatic Bacteriuria.

Importance: Guidelines recommend withholding antibiotics in asymptomatic bacteriuria (ASB), including among patients with altered mental status (AMS) and no systemic signs of infection. However, ASB treatment remains common. Objectives: To determine prevalence and factors associated with bacteremia from a presumed urinary source in inpatients with ASB with or without AMS and estimate antibiotics avoided if a 2% risk of bacteremia were used as a threshold to prompt empiric antibiotic treatment of ASB. Design, Setting, and Participants: This cohort study assessed patients hospitalized to nonintensive care with ASB (no immune compromise or concomitant infections) in 68 Michigan hospitals from July 1, 2017, to June 30, 2022. Data were analyzed from August 2022 to January 2023. Main Outcomes and Measures: The primary outcome was prevalence of bacteremia from a presumed urinary source (ie, positive blood culture with matching organisms within 3 days of urine culture). To determine factors associated with bacteremia, we used multivariable logistic regression models. We estimated each patient's risk of bacteremia and determined what percentage of patients empirically treated with antibiotics had less than 2% estimated risk of bacteremia. Results: Of 11 590 hospitalized patients with ASB (median [IQR] age, 78.2 [67.7-86.6] years; 8595 female patients [74.2%]; 2235 African American or Black patients [19.3%], 184 Hispanic patients [1.6%], and 8897 White patients [76.8%]), 8364 (72.2%) received antimicrobial treatment for UTI, and 161 (1.4%) had bacteremia from a presumed urinary source. Only 17 of 2126 patients with AMS but no systemic signs of infection (0.7%) developed bacteremia. On multivariable analysis, male sex (adjusted odds ratio [aOR], 1.45; 95% CI, 1.02-2.05), hypotension (aOR, 1.86; 95% CI, 1.18-2.93), 2 or more systemic inflammatory response criteria (aOR, 1.72; 95% CI, 1.21-2.46), urinary retention (aOR, 1.87; 95% CI, 1.18-2.96), fatigue (aOR, 1.53; 95% CI, 1.08-2.17), log of serum leukocytosis (aOR, 3.38; 95% CI, 2.48-4.61), and pyuria (aOR, 3.31; 95% CI, 2.10-5.21) were associated with bacteremia. No single factor was associated with more than 2% risk of bacteremia. If 2% or higher risk of bacteremia were used as a cutoff for empiric antibiotics, antibiotic exposure would have been avoided in 78.4% (6323 of 8064) of empirically treated patients with low risk of bacteremia. Conclusions and Relevance: In patients with ASB, bacteremia from a presumed urinary source was rare, occurring in less than 1% of patients with AMS. A personalized, risk-based approach to empiric therapy could decrease unnecessary ASB treatment.

Development of patient safety measures to identify inappropriate diagnosis of common infections.

BACKGROUND: Inappropriate diagnosis of infections results in antibiotic overuse and may delay diagnosis of underlying conditions. Here, we describe the development and characteristics of two safety measures of inappropriate diagnosis of urinary tract infection (UTI) and community-acquired pneumonia (CAP), the most common inpatient infections on general medicine services. METHODS: Measures were developed from guidelines and literature and adapted based on data from patients hospitalized with UTI and CAP in 49 Michigan hospitals and feedback from end-users, a technical expert panel (TEP), and a patient focus group. Each measure was assessed for reliability, validity, feasibility, and usability. RESULTS: Two measures, now endorsed by the National Quality Forum (NQF), were developed. Measure reliability (derived from 24,483 patients) was excellent (0.90 for UTI; 0.91 for CAP). Both measures had strong validity demonstrated through a) face validity by hospital users, the TEPs, and patient focus group, b) implicit case review (ĸ 0.72 for UTI; ĸ 0.72 for CAP), and c) rare case misclassification (4% for UTI; 0% for CAP) due to data errors (<2% for UTI; 6.3% for CAP). Measure implementation through hospital peer comparison in Michigan hospitals (2017 to 2020) demonstrated significant decreases in inappropriate diagnosis of UTI and CAP (37% and 32%, respectively, p < 0.001), supporting usability. CONCLUSIONS: We developed highly reliable, valid, and usable measures of inappropriate diagnosis of UTI and CAP for hospitalized patients. Hospitals seeking to improve diagnostic safety, antibiotic use, and patient care should consider using these measures to reduce inappropriate diagnosis of CAP and UTI.

Excellence in Antibiotic Stewardship: A mixed methods study comparing High, Medium, and Low Performing Hospitals.

BACKGROUND: Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood. METHODS: We conducted an explanatory, sequential mixed methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse. For each hospital, we conducted surveys, document analysis, and semi-structured interviews with antibiotic stewardship and clinical stakeholders. Data were analyzed separately and mixed during the interpretation phase, where each hospital was examined as a case, with findings organized across cases using a strengths, weaknesses, opportunities, and threats framework to identify factors accounting for differences in antibiotic overuse across hospitals. RESULTS: Surveys included 85 respondents. Interviews included 90 respondents (31 hospitalists, 33 clinical pharmacists, 14 stewardship leaders, 12 hospital leaders). On surveys, clinical pharmacists at hospitals with lower antibiotic overuse were more likely to report feeling: respected by hospitalist colleagues (p=0.001), considered valuable team members (p=0.001), comfortable recommending antibiotic changes (p=0.02). Based on mixed-methods analysis, hospitals with low antibiotic overuse had four distinguishing characteristics: a) robust knowledge of and access to antibiotic stewardship guidance, b) high quality clinical pharmacist-physician relationships, c) tools and infrastructure to support stewardship, and d) highly engaged Infectious Diseases physicians who advocated stewardship principles. CONCLUSION: This mixed-method study demonstrates the importance of organizational context for high performance in stewardship and suggests improving antimicrobial stewardship requires attention to knowledge, interactions, and relationships between clinical teams and infrastructure that supports stewardship and team interactions.

A Statewide Quality Initiative to Reduce Unnecessary Antibiotic Treatment of Asymptomatic Bacteriuria.

Importance: Hospitalized patients with asymptomatic bacteriuria (ASB) often receive unnecessary antibiotic treatment, which increases antibiotic resistance and adverse events. Objective: To determine whether diagnostic stewardship (avoiding unnecessary urine cultures) or antibiotic stewardship (reducing unnecessary antibiotic treatment after an unnecessary culture) is associated with better outcomes in reducing antibiotic use for ASB. Design, Setting, and Participants: This 3-year, prospective quality improvement study included hospitalized general care medicine patients with a positive urine culture among 46 hospitals participating in a collaborative quality initiative, the Michigan Hospital Medicine Safety Consortium. Data were collected from July 1, 2017, through March 31, 2020, and analyzed from February to October 2022. Exposure: Participation in the Michigan Hospital Medicine Safety Consortium with antibiotic and diagnostic stewardship strategies at hospital discretion. Main Outcomes and Measures: Overall improvement in ASB-related antibiotic use was estimated as change in percentage of patients treated with antibiotics who had ASB. Effect of diagnostic stewardship was estimated as change in percentage of patients with a positive urine culture who had ASB. Effect of antibiotic stewardship was estimated as change in percentage of patients with ASB who received antibiotics and antibiotic duration. Results: Of the 14 572 patients with a positive urine culture included in the study (median [IQR] age, 75.8 [64.2-85.1] years; 70.5% female); 28.4% (n = 4134) had ASB, of whom 76.8% (n = 3175) received antibiotics. Over the study period, the percentage of patients treated with antibiotics who had ASB (overall ASB-related antibiotic use) declined from 29.1% (95% CI, 26.2%-32.2%) to 17.1% (95% CI, 14.3%-20.2%) (adjusted odds ratio [aOR], 0.94 per quarter; 95% CI, 0.92-0.96). The percentage of patients with a positive urine culture who had ASB (diagnostic stewardship metric) declined from 34.1% (95% CI, 31.0%-37.3%) to 22.5% (95% CI, 19.7%-25.6%) (aOR, 0.95 per quarter; 95% CI, 0.93-0.97). The percentage of patients with ASB who received antibiotics (antibiotic stewardship metric) remained stable, from 82.0% (95% CI, 77.7%-85.6%) to 76.3% (95% CI, 68.5%-82.6%) (aOR, 0.97 per quarter; 95% CI, 0.94-1.01), as did adjusted mean antibiotic duration, from 6.38 (95% CI, 6.00-6.78) days to 5.93 (95% CI, 5.54-6.35) days (adjusted incidence rate ratio, 0.99 per quarter; 95% CI, 0.99-1.00). Conclusions and Relevance: This quality improvement study showed that over 3 years, ASB-related antibiotic use decreased and was associated with a decline in unnecessary urine cultures. Hospitals should prioritize reducing unnecessary urine cultures (ie, diagnostic stewardship) to reduce antibiotic treatment related to ASB.

Antibiotic Stewardship Strategies and Their Association With Antibiotic Overuse After Hospital Discharge: An Analysis of the Reducing Overuse of Antibiotics at Discharge (Road) Home Framework.

BACKGROUND: Strategies to optimize antibiotic prescribing at discharge are not well understood. METHODS: In fall 2019, we surveyed 39 Michigan hospitals on their antibiotic stewardship strategies. The association of reported strategies with discharge antibiotic overuse (unnecessary, excess, suboptimal fluoroquinolones) for community-acquired pneumonia (CAP) and urinary tract infection (UTI) was evaluated in 2 ways: (1) all strategies assumed equal weight and (2) strategies were weighted based on the ROAD (Reducing Overuse of Antibiotics at Discharge) Home Framework (ie, Tier 1-Critical infrastructure, Tier 2-Broad inpatient interventions, Tier 3-Discharge-specific strategies) with Tier 3 strategies receiving the highest weight. RESULTS: Between 1 July 2017 and 30 July 2019, 39 hospitals with 20 444 patients (56.5% CAP; 43.5% UTI) were included. Survey response was 100%. Hospitals reported a median (interquartile range [IQR]) 12 (9-14) of 34 possible stewardship strategies. On analyses of individual stewardship strategies, the Tier 3 intervention, review of antibiotics prior to discharge, was the only strategy consistently associated with lower antibiotic overuse at discharge (adjusted incident rate ratio [aIRR] 0.543, 95% confidence interval [CI]: .335-.878). On multivariable analysis, weighting by ROAD Home tier predicted antibiotic overuse at discharge for both CAP and UTI. For diseases combined, having more weighted strategies was associated with lower antibiotic overuse at discharge (aIRR 0.957, 95% CI: .927-.987, per weighted intervention); discharge-specific stewardship strategies were associated with a 12.4% relative decrease in antibiotic overuse days at discharge. CONCLUSIONS: The more stewardship strategies a hospital reported, the lower its antibiotic overuse at discharge. However, Tier 3, or discharge-specific strategies, appeared to have the largest effect on antibiotic prescribing at discharge.

Improving antibiotic use for sinusitis and upper respiratory tract infections: A virtual-visit antibiotic stewardship initiative.

BACKGROUND: Asynchronous virtual patient care is increasingly used; however, the effectiveness of virtually delivering guideline-concordant care in conjunction with antibiotic stewardship initiatives remains uncertain. We developed a bundled stewardship intervention to improve antibiotic use in E-visits for upper respiratory tract infections (URTIs). METHODS: In this before-and-after study, adult patients who completed E-visits for "cough," "flu," or "sinus symptoms" at Michigan Medicine between January 1, 2018, and September 30, 2020, were included. Patient demographics, diagnoses, and antibiotic details were collected. The multifaceted intervention occurred over 6 months. Segmented linear regression was performed to estimate the effect of the intervention on appropriate antibiotic use for URTI diagnoses (defined as no antibiotic prescribed) and sinusitis (defined as guideline-concordant antibiotic selection and duration). Regression lines were fit to data before the bundled intervention (January 2019) and after the bundled intervention (May 2019). RESULTS: In total, 5,151 E-visits were included. The intervention decreased the number of visits for flu, cough, or sinus symptoms prescribed antibiotics from 43.2% to 28.9% (P < .001). Guideline concordance of antibiotic prescriptions improved following the intervention: first-line amoxicillin-clavulanate rose from 37.9% of prescriptions to 66.1% of prescriptions (P < .001), second-line doxycycline rose from 13.8% to 22.7% (P < .001); and median duration of antibiotics decreased from 10 days to 5 days (P < .001). CONCLUSIONS: A multifaceted stewardship bundle for E-visits involving both changes in the EMR and audit and feedback improved guideline-concordant antibiotic use for URTIs. This approach can aid stewardship efforts in the ambulatory care setting with regard to telemedicine.

A Statewide Collaborative Quality Initiative to Improve Antibiotic Duration and Outcomes in Patients Hospitalized With Uncomplicated Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a common cause for hospitalization and antibiotic overuse. We aimed to improve antibiotic duration for CAP across 41 hospitals participating in the Michigan Hospital Medicine Safety Consortium (HMS). METHODS: This prospective collaborative quality initiative included patients hospitalized with uncomplicated CAP who qualified for a 5-day antibiotic duration. Between 23 February 2017 and 5 February 2020, HMS targeted appropriate 5-day antibiotic treatment through benchmarking, sharing best practices, and pay-for-performance incentives. Changes in outcomes, including appropriate receipt of 5 ± 1-day antibiotic treatment and 30-day postdischarge composite adverse events (ie, deaths, readmissions, urgent visits, and antibiotic-associated adverse events), were assessed over time (per 3-month quarter), using logistic regression and controlling for hospital clustering. RESULTS: A total of 41 hospitals and 6553 patients were included. The percentage of patients treated with an appropriate 5 ±â€…1-day duration increased from 22.1% (predicted probability, 20.9% [95% confidence interval: 17.2%-25.0%]) to 45.9% (predicted probability, 43.9% [36.8%-51.2%]; adjusted odds ratio [aOR] per quarter, 1.10 [1.07-1.14]). Thirty-day composite adverse events occurred in 18.5% of patients (1166 of 6319) and decreased over time (aOR per quarter, 0.98 [95% confidence interval: .96-.99]) owing to a decrease in antibiotic-associated adverse events (aOR per quarter, 0.91 [.87-.95]). CONCLUSIONS: Across diverse hospitals, HMS participation was associated with more appropriate use of short-course therapy and fewer adverse events in hospitalized patients with uncomplicated CAP. Establishment of national or regional collaborative quality initiatives with data collection and benchmarking, sharing of best practices, and pay-for-performance incentives may improve antibiotic use and outcomes for patients hospitalized with uncomplicated CAP.

Monoclonal Antibodies for Early Treatment of COVID-19 in a World of Evolving SARS-CoV-2 Mutations and Variants.

Monoclonal antibodies targeting the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 spike protein are important outpatient treatment options in coronavirus disease 2019 to mitigate progression of disease and prevent hospitalization. The impact of different RBD mutations on the efficacy of the available monoclonal antibodies and processes for incorporating this impact into treatment algorithms are ill defined. Herein, we synthesize the data surrounding the impact of key RBD mutations on the efficacy of US Food and Drug Administration Emergency Use Authorized monoclonal antibodies and describe our approach at Michigan Medicine at monitoring mutation frequency in circulating virus and developing an algorithm that incorporates these data into outpatient treatment pathways.

Empiric Antibacterial Therapy and Community-onset Bacterial Coinfection in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19): A Multi-hospital Cohort Study.

BACKGROUND: Antibacterials may be initiated out of concern for bacterial coinfection in coronavirus disease 2019 (COVID-19). We determined prevalence and predictors of empiric antibacterial therapy and community-onset bacterial coinfections in hospitalized patients with COVID-19. METHODS: A randomly sampled cohort of 1705 patients hospitalized with COVID-19 in 38 Michigan hospitals between 3/13/2020 and 6/18/2020. Data were collected on early (within 2 days of hospitalization) empiric antibacterial therapy and community-onset bacterial coinfections (positive microbiologic test ≤3 days). Poisson generalized estimating equation models were used to assess predictors. RESULTS: Of 1705 patients with COVID-19, 56.6% were prescribed early empiric antibacterial therapy; 3.5% (59/1705) had a confirmed community-onset bacterial infection. Across hospitals, early empiric antibacterial use varied from 27% to 84%. Patients were more likely to receive early empiric antibacterial therapy if they were older (adjusted rate ratio [ARR]: 1.04 [1.00-1.08] per 10 years); had a lower body mass index (ARR: 0.99 [0.99-1.00] per kg/m2), more severe illness (eg, severe sepsis; ARR: 1.16 [1.07-1.27]), a lobar infiltrate (ARR: 1.21 [1.04-1.42]); or were admitted to a for-profit hospital (ARR: 1.30 [1.15-1.47]). Over time, COVID-19 test turnaround time (returned ≤1 day in March [54.2%, 461/850] vs April [85.2%, 628/737], P < .001) and empiric antibacterial use (ARR: 0.71 [0.63-0.81] April vs March) decreased. CONCLUSIONS: The prevalence of confirmed community-onset bacterial coinfections was low. Despite this, half of patients received early empiric antibacterial therapy. Antibacterial use varied widely by hospital. Reducing COVID-19 test turnaround time and supporting stewardship could improve antibacterial use.

Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.

Antibiotic Overuse After Hospital Discharge: A Multi-hospital Cohort Study.

BACKGROUND: Antibiotics are commonly prescribed to patients as they leave the hospital. We aimed to create a comprehensive metric to characterize antibiotic overuse after discharge among hospitalized patients treated for pneumonia or urinary tract infection (UTI), and to determine whether overuse varied across hospitals and conditions. METHODS: In a retrospective cohort study of hospitalized patients treated for pneumonia or UTI in 46 hospitals between 1 July 2017-30 July 2019, we quantified the proportion of patients discharged with antibiotic overuse, defined as unnecessary antibiotic use, excess antibiotic duration, or suboptimal fluoroquinolone use. Using linear regression, we assessed hospital-level associations between antibiotic overuse after discharge in patients treated for pneumonia versus a UTI. RESULTS: Of 21 825 patients treated for infection (12 445 with pneumonia; 9380 with a UTI), nearly half (49.1%) had antibiotic overuse after discharge (56.9% with pneumonia; 38.7% with a UTI). For pneumonia, 63.1% of overuse days after discharge were due to excess duration; for UTIs, 43.9% were due to treatment of asymptomatic bacteriuria. The percentage of patients discharged with antibiotic overuse varied 5-fold among hospitals (from 15.9% [95% confidence interval, 8.7%-24.6%] to 80.6% [95% confidence interval, 69.4%-88.1%]) and was strongly correlated between conditions (regression coefficient = 0.85; P < .001). CONCLUSIONS: Antibiotic overuse after discharge was common and varied widely between hospitals. Antibiotic overuse after discharge was associated between conditions, suggesting that the prescribing culture, physician behavior, or organizational processes contribute to overprescribing at discharge. Multifaceted efforts focusing on all 3 types of overuse and multiple conditions should be considered to improve antibiotic prescribing at discharge.

Impact of a Best Practice Advisory for Pediatric Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: Infectious diseases (ID) consultation and optimal antibiotic therapy improve outcomes in Staphylococcus aureus bacteremia (SAB). Data on strategies to improve adherence to these practices in children are limited. METHODS: This was a quasi-experimental study evaluating the impact of an electronic medical record (EMR)-based best practice advisory (BPA) for SAB, recommending ID consult and optimal antibiotic therapy based on rapid mecA gene detection. Inpatients < 21 years old with SAB before (January 2015-July 2017) and after (August 2017-December 2018) BPA implementation were included. Primary outcome was receipt of ID consult. Secondary outcomes included receipt of optimal therapy, time to ID consult and optimal therapy, recurrent SAB, and 30-day all-cause mortality. ID consultation rates pre- and postimplementation were compared using interrupted time series (ITS) analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to optimal therapy were calculated using Cox regression. RESULTS: We included 99 SAB episodes (70 preintervention, 29 postintervention). Preintervention, 48 (68.6%) patients received an ID consult compared to 27 (93.1%) postintervention, but this was not statistically significant on ITS analysis due to a preexisting trend of increasing consultation. Median hours to optimal therapy decreased from 26.1 to 5.5 (P = .03), most notably in patients with methicillin-sensitive S. aureus (MSSA) (42.2 to 10.8; P < .01). On Cox regression, BPA implementation was associated with faster time to optimal therapy (HR, 3.22 [95% CI, 1.04-10.01]). CONCLUSIONS: Implementation of an EMR-based BPA for SAB resulted in faster time to optimal antibiotic therapy, particularly for patients with MSSA. ID consultation increased throughout the study period and was not significantly impacted by the BPA.

Assessment of Testing and Treatment of Asymptomatic Bacteriuria Initiated in the Emergency Department.

BACKGROUND: Reducing antibiotic use in patients with asymptomatic bacteriuria (ASB) has been inpatient focused. However, testing and treatment is often started in the emergency department (ED). Thus, for hospitalized patients with ASB, we sought to identify patterns of testing and treatment initiated by emergency medicine (EM) clinicians and the association of treatment with outcomes. METHODS: We conducted a 43-hospital, cohort study of adults admitted through the ED with ASB (February 2018-February 2020). Using generalized estimating equation models, we assessed for (1) factors associated with antibiotic treatment by EM clinicians and, after inverse probability of treatment weighting, (2) the effect of treatment on outcomes. RESULTS: Of 2461 patients with ASB, 74.4% (N = 1830) received antibiotics. The EM clinicians ordered urine cultures in 80.0% (N = 1970) of patients and initiated treatment in 68.5% (1253 of 1830). Predictors of EM clinician treatment of ASB versus no treatment included dementia, spinal cord injury, incontinence, urinary catheter, altered mental status, leukocytosis, and abnormal urinalysis. Once initiated by EM clinicians, 79% (993 of 1253) of patients remained on antibiotics for at least 3 days. Antibiotic treatment was associated with a longer length of hospitalization (mean 5.1 vs 4.2 days; relative risk = 1.16; 95% confidence interval, 1.08-1.23) and Clostridioides difficile infection (CDI) (0.9% [N = 11] vs 0% [N = 0]; P = .02). CONCLUSIONS: Among hospitalized patients ultimately diagnosed with ASB, EM clinicians commonly initiated testing and treatment; most antibiotics were continued by inpatient clinicians. Antibiotic treatment was not associated with improved outcomes, whereas it was associated with prolonged hospitalization and CDI. For best impact, stewardship interventions must expand to the ED.

Association of Infectious Disease Physician Approval of Peripherally Inserted Central Catheter With Appropriateness and Complications.

Importance: Peripherally inserted central catheters (PICCs) are frequently used to deliver intravenous antimicrobial therapy. However, inappropriate PICC use may lead to patient harm. Objective: To evaluate whether infectious disease physician approval prior to PICC placement for intravenous antimicrobials is associated with more appropriate device use and fewer complications. Design, Setting, and Participants: This cohort study of 21 653 PICCs placed for a primary indication of intravenous antimicrobial therapy between January 1, 2015, and July 26, 2019, was conducted in 42 hospitals participating in a quality collaborative across Michigan among hospitalized medical patients. Main Outcomes and Measures: Appropriateness of PICCs was defined according to the Michigan Appropriateness Guide for Intravenous Catheters as a composite measure of (1) single-lumen catheter use, (2) avoiding use of PICCs for 5 days or less, and (3) avoiding use of PICCs for patients with chronic kidney disease (defined as an estimated glomerular filtration rate <45 mL/min/1.73 m2). Complications related to PICCs included catheter occlusion, deep vein thrombosis, and central line-associated bloodstream infection. The association between infectious disease physician approval, device appropriateness, and catheter complications was assessed using multivariable models, adjusted for patient comorbidities and hospital clustering. Results were expressed as odds ratios with 95% CIs. Results: A total of 21 653 PICCs were placed for intravenous antimicrobials (11 960 PICCs were placed in men [55.2%]; median age, 64.5 years [interquartile range, 53.4-75.4 years]); 10 238 PICCs (47.3%) were approved by an infectious disease physician prior to placement. Compared with PICCs with no documented approval, PICCs with approval by an infectious disease physician were more likely to be appropriately used (72.7% [7446 of 10 238] appropriate with approval vs 45.4% [5180 of 11 415] appropriate without approval; odds ratio, 3.53; 95% CI, 3.29-3.79; P < .001). Furthermore, approval was associated with lower odds of a PICC-related complication (6.5% [665 of 10 238] with approval vs 11.3% [1292 of 11 415] without approval; odds ratio, 0.55; 95% CI, 0.50-0.61). Conclusions and Relevance: This cohort study suggests that, when PICCs were placed for intravenous antimicrobial therapy, infectious disease physician approval of PICC insertion was associated with more appropriate device use and fewer complications. Policies aimed at ensuring infectious disease physician approval prior to PICC placement for antimicrobials may improve patient safety.

Tocilizumab for treatment of mechanically ventilated patients with COVID-19.

BACKGROUND: Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). FINDINGS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. INTERPRETATION: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings.