Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge: A Cohort Study and Randomized Comparative Effectiveness Trial.

Importance: The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant. Objective: To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab. Design, Setting, and Participants: This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria. Exposure: For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. Main Outcomes and Measures: For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. Results: A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence. Conclusions and Relevance: In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant. Trial Registration: ClinicalTrials.gov Identifier: NCT04790786.

The comparative effectiveness of COVID-19 monoclonal antibodies: A learning health system randomized clinical trial.

BACKGROUND: Monoclonal antibodies (mAb) that neutralize SARS-CoV-2 decrease hospitalization and death compared to placebo in patients with mild to moderate COVID-19; however, comparative effectiveness is unknown. We report the comparative effectiveness of bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab. METHODS: A learning health system platform trial in a U.S. health system enrolled patients meeting mAb Emergency Use Authorization criteria. An electronic health record-embedded application linked local mAb inventory to patient encounters and provided random mAb allocation. Primary outcome was hospital-free days to day 28. Primary analysis was a Bayesian model adjusting for treatment location, age, sex, and time. Inferiority was defined as 99% posterior probability of an odds ratio < 1. Equivalence was defined as 95% posterior probability the odds ratio is within a given bound. FINDINGS: Between March 10 and June 25, 2021, 1935 patients received treatment. Median hospital-free days were 28 (IQR 28, 28) for each mAb. Mortality was 0.8% (1/128), 0.8% (7/885), and 0.7% (6/922) for bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab, respectively. Relative to casirivimab-imdevimab (n = 922), median adjusted odds ratios were 0.58 (95% credible interval [CI] 0.30-1.16) and 0.94 (95% CI 0.72-1.24) for bamlanivimab (n = 128) and bamlanivimab-etesevimab (n = 885), respectively. These odds ratios yielded 91% and 94% probabilities of inferiority of bamlanivimab versus bamlanivimab-etesevimab and casirivimab-imdevimab, and an 86% probability of equivalence between bamlanivimab-etesevimab and casirivimab-imdevimab. INTERPRETATION: Among patients with mild to moderate COVID-19, bamlanivimab-etesevimab or casirivimab-imdevimab treatment resulted in 86% probability of equivalence. No treatment met prespecified criteria for statistical equivalence. Median hospital-free days to day 28 were 28 (IQR 28, 28) for each mAb. FUNDING AND REGISTRATION: This work received no external funding. The U.S. government provided the reported mAb. This trial is registered at ClinicalTrials.gov, NCT04790786.

Launching a comparative effectiveness adaptive platform trial of monoclonal antibodies for COVID-19 in 21 days.

Outpatient treatments that limit progression to severe coronavirus disease 2019 (COVID-19) are of vital importance to optimise patient outcomes and public health. Monoclonal antibodies (mAb) demonstrated ability to decrease hospitalizations in randomized, clinical trials. However, there are many barriers to mAb treatment such as patient access and clinician education. There are no data comparing efficacy or safety of available mAbs. We sought to rapidly launch an adaptive platform trial with the goals of enhancing access to treatment, regardless of geography and socioeconomic status, and evaluating comparative efficacy and safety of available mAbs. Within 21 days from idea genesis, we allocated mAb treatment to all patients within the context of this clinical trial. Within 2 months, we closed the gap of the likelihood of receiving mAb, conditional on background positivity rate, between Black and White patients (Black patients 0.238; White patients 0.241). We describe trial infrastructure, lessons learned, and future directions for a culture of learning while doing.

Reliability of nonlocalizing signs and symptoms as indicators of the presence of infection in nursing-home residents.

Antibiotics are among the most common medications prescribed in nursing homes. The annual prevalence of antibiotic use in residents of nursing homes ranges from 47% to 79%, and more than half of antibiotic courses initiated in nursing-home settings are unnecessary or prescribed inappropriately (wrong drug, dose, or duration). Inappropriate antibiotic use is associated with a variety of negative consequences including Clostridioides difficile infection (CDI), adverse drug effects, drug-drug interactions, and antimicrobial resistance. In response to this problem, public health authorities have called for efforts to improve the quality of antibiotic prescribing in nursing homes.

Impact of Bamlanivimab Monoclonal Antibody Treatment on Hospitalization and Mortality Among Nonhospitalized Adults With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Monoclonal antibody treatment may prevent complications of coronavirus disease 2019 (COVID-19). We sought to quantify the impact of bamlanivimab monoclonal antibody monotherapy on hospitalization and mortality among outpatients at high risk of COVID-19 complications. METHODS: In this observational study we compared outpatients who received bamlanivimab monoclonal antibody from December 9, 2020 to March 3, 2021 to nontreated patients with a positive polymerase chain reaction or antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the same period who were eligible for monoclonal antibody treatment. The primary outcome was 28-day hospitalization or all-cause mortality, and the secondary outcome was hospitalization or emergency department visit without hospitalization. The risk-adjusted odds of study outcomes comparing bamlanivimab treated and untreated patients was determined using 1:5 propensity matching and multivariable logistic regression. RESULTS: Among 232 patients receiving bamlanivimab matched with 1160 comparator patients, the mean age was 67 years, 56% were female, and 196 (14%) of patients experienced hospitalization or mortality. After adjustment for propensity to receive treatment, bamlanivimab treatment was associated with a significantly reduced risk-adjusted odds of hospitalization or mortality within 28 days (odds ratio [OR], 0.40; 95% confidence interval [95% CI], 0.24-0.69; P < .001). Bamlanivimab treatment was also associated with a significantly lower risk adjusted odds of hospitalization or emergency department visit without hospitalization (OR, 0.54; 95% CI, 0.35-0.82; P = .004). The results were most strongly associated with patients age 65 years and older. CONCLUSIONS: Bamlanivimab monoclonal antibody monotherapy was associated with reduced hospitalizations and mortality within 28 days among outpatients with mild to moderate COVID-19.Use of bamlanivimab monotherapy for outpatients with mild to moderate COVID-19 infection was associated with reductions in hospitalizations and mortality within 28 days. Benefit was strongest in those age 65 years or older.

Establishing a Distribution Network for COVID-19 Monoclonal Antibody Therapy Across a Large Health System During a Global Pandemic.

Emergency authorized coronavirus disease 2019 (COVID-19)-neutralizing monoclonal antibodies can aid outpatients with mild to moderate COVID-19 infection. Many report barriers to adequate distribution and uptake. We present our model for distribution in a large health system as well as early lessons learned.

Antibody Responses After mRNA-Based COVID-19 Vaccination in Residential Older Adults: Implications for Reopening.

OBJECTIVE: COVID-19 disproportionately impacts residents in long-term care facilities. Our objective was to quantify the presence and magnitude of antibody response in vaccinated, older adult residents at assisted living, personal care, and independent living communities. DESIGN: A cross-sectional quality improvement study was conducted March 15 - April 1, 2021 in the greater Pittsburgh region. SETTING AND POPULATION: Participants were older adult residents at assisted living, personal care, and independent living communities, who received mRNA-based COVID-19 vaccine. Conditions that impair immune responses were exclusionary criteria. METHODS: Sera were collected to measure IgG anti-SARS-CoV-2 antibody level with reflex to total anti-SARS-CoV-2 immunoglobulin levels, and blinded evaluation of SARS-CoV-2 pseudovirus neutralization titers. Descriptive statistics, Pearson correlation coefficients, and multiple linear regression analysis evaluated relationships between factors potentially associated with antibody levels. Spearman correlations were calculated between antibody levels and neutralization titers. RESULTS: All participants (N = 70) had received two rounds of vaccination and were found to have antibodies with wide variation in relative levels. Antibody levels trended lower in males, advanced age, current use of steroids, and longer length of time from vaccination. Pseudovirus neutralization titer levels were strongly correlated (P < .001) with Beckman Coulter antibody levels [D614 G NT50, rs = 0.91; B.1.1.7 (UK) NT50, rs = 0.91]. CONCLUSIONS AND IMPLICATIONS: Higher functioning, healthier, residential older adults mounted detectable antibody responses when vaccinated with mRNA-based COVID-19 vaccines. Data suggests some degree of immunity is present during the immediate period following vaccination. However, protective effects remain to be determined in larger studies as clinical protection is afforded by ongoing adaptive immunity, which is known to be decreased in older adults. This study provides important preliminary results on level of population risk in older adult residents at assisted living, personal care, and independent living communities to inform reopening strategies, but are not likely to be translatable for residents in nursing homes.

The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization.

OBJECTIVES: The primary objective is to evaluate the comparative effectiveness of COVID-19 specific monoclonal antibodies (mABs) with US Food and Drug Administration (FDA) Emergency Use Authorization (EUA), alongside UPMC Health System efforts to increase patient access to these mABs. TRIAL DESIGN: Open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization PARTICIPANTS: We will evaluate patients who meet the eligibility criteria stipulated by the COVID-19 mAB EUAs who receive mABs within the UPMC Health System, including infusion centers and emergency departments. EUA eligibility criteria include patients with mild to moderate COVID-19, <10 days of symptoms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization (elderly, obese, and/or with specific comorbidities). The EUA criteria exclude patients who require oxygen for the treatment of COVID-19 and patients already hospitalized for the treatment of COVID-19. We will use data collected for routine clinical care, including data entered into the electronic medical record and from follow-up calls. INTERVENTION AND COMPARATOR: The interventions are the COVID-19 specific mABs authorized by the EUAs. All aspects of mAB treatment, including eligibility criteria, dosing, and post-infusion monitoring, are as per the EUAs. As a comparative effectiveness trial, all patients receive mAB treatment, and the interventions are compared against each other. When U.S. government mAB policies change (e.g., FDA grants or revokes EUAs), UPMC Health System policies and the evaluated mAB interventions will accordingly change. From November 2020 to February 2021, FDA issued EUAs for three mAB treatments (bamlanivimab; bamlanivimab and etesevimab; and casirivimab and imdevimab), and at trial launch on March 10, 2021 we evaluated all three. Due to a sustained increase in SARS-CoV-2 variants in the United States resistant to bamlanivimab administered alone, on March 24, 2021 the U.S. Government halted distribution of bamlanivimab alone, and UPMC accordingly halted bamlanivimab monotherapy on March 31, 2021. On April 16, 2021, FDA revoked the EUA for bamlanivimab monotherapy. At the time of manuscript submission, we are therefore evaluating the two mAB treatments authorized by EUAs (bamlanivimab and etesevimab; and casirivimab and imdevimab). MAIN OUTCOMES: The primary outcome is total hospital free days (HFD) at 28 days after mAB administration, calculated as 28 minus the number of days during the index stay (if applicable - e.g., for patients admitted to hospital after mAB administration in the emergency department) minus the number of days readmitted during the 28 days after treatment. This composite endpoint captures the number of days from the day of mAB administration to the 28 days thereafter, during which the patient is alive and free of hospitalization. Death within 28 days is recorded as -1 HFD, as the worst outcome. RANDOMISATION: We will start with equal allocation. Due to uncertainty in sample size, we will use a Bayesian adaptive design and response adaptive randomization to ensure ability to provide statistical inference despite variable sample size. When mABs are ordered by UPMC physicians as a generic referral order, the order is filled by UPMC pharmacy via therapeutic interchange. OPTIMISE-C19 provides the therapeutic interchange via random allocation. Infusion center operations teams and pharmacists use a mAB assignment application embedded in the electronic medical record to determine the random allocation. BLINDING (MASKING): This trial is open-label. However, outcome assessors conducting follow-up calls at day 28 are blinded to mAB assignment, and investigators are blinded to by-mAB aggregate outcome data until a statistical platform trial conclusion is reached. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size will be determined by case volume throughout the course of the pandemic, supply of FDA authorized mABs, and by that needed to reach a platform trial conclusion of inferiority, superiority, or futility of a given mAB. The trial will continue as long as more than one mAB type is available under EUA, and their comparative effectiveness is uncertain. TRIAL STATUS: Protocol Version 1.0, February 24, 2021. Recruitment began March 10, 2021 and is ongoing at the time of manuscript submission. The estimated recruitment end date is February 22, 2022, though the final end date is dependent on how the pandemic evolves, mAB availability, and when final platform trial conclusions are reached. As noted above, due to U.S. Government decisions, UPMC Health System halted bamlanivimab monotherapy on March 31, 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04790786 . Registered March 10, 2021 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Improvements in Antibiotic Appropriateness for Cystitis in Older Nursing Home Residents: A Quality Improvement Study With Randomized Assignment.

OBJECTIVE: To determine the impact of an educational quality improvement initiative on the appropriateness of antibiotic prescribing restricted to uncomplicated cystitis in older noncatheterized nursing home residents. DESIGN: Quality improvement study with randomized assignment. SETTINGS AND PARTICIPANTS: Twenty-five nursing homes in United States were randomized to the intervention or usual care group by strata that included state, urban/rural status, bed size, and geographic separation. METHODS: A 12-month trial of a low-intensity multifaceted antimicrobial stewardship intervention focused on uncomplicated cystitis in nursing home residents vs usual care. The outcome was the modified Medication Appropriateness Index as assessed by a blinded geriatric clinical pharmacist and consisted of an assessment of antibiotic effectiveness, dosage, drug-drug interactions, and duration. RESULTS: There were 75 cases (0.15/1000 resident days) in intervention and 92 (0.22/1000 resident days) in control groups with a probable cystitis per consensus guidelines. Compared with controls, there was a statistically nonsignificant 21% reduction in the risk of inappropriate antibiotic prescribing (nonzero Medication Appropriateness Index score rate 0.13 vs 0.21/1000 person days; adjusted incident rate ratio 0.79; 95% confidence interval 0.45‒1.38). There was a favorable comparison in inappropriateness of duration (77% vs 89% for intervention vs control groups, respectively; P = .0394). However, the intervention group had more problems with drug-drug interactions than the control group (8% vs 1%, respectively; P = .0463). Similarly, the intervention group had a nonsignificant trend toward more problems with dosage (primarily because of the lack of adjustment for decreased renal function) than the control group (32% vs 25%, respectively; P = .3170). Both groups had similar rates of problems with choice/effectiveness (44% vs 45%; P = .9417). The most common class of antibiotics prescribed inappropriately was quinolones (25% vs 23% for intervention versus control groups, respectively; P = .7057). CONCLUSIONS AND IMPLICATIONS: A low-intensity intervention showed a trend toward improved appropriate antibiotic prescribing in nursing home residents with likely uncomplicated cystitis. Efforts to improve antibiotic prescribing in addition to the low-intensity intervention might include a consultant pharmacist in a nursing home to identify inappropriate prescribing practices.

Transforming the Medication Regimen Review Process Using Telemedicine to Prevent Adverse Events.

BACKGROUND/OBJECTIVES: Federally-mandated consultant pharmacist-conducted retrospective medication regimen reviews (MRRs) are designed to improve medication safety in nursing homes (NH). However, MRRs are potentially ineffective. A new model of care that improves access to and efficiency of consultant pharmacists is needed. The objective of this study was to determine the impact of pharmacist-led telemedicine services on reducing high-risk medication adverse drug events (ADEs) for NH residents using medication reconciliation and prospective MRR on admission plus ongoing clinical decision support alerts throughout the residents' stay. DESIGN: Quality improvement study using a stepped-wedge design comparing the novel service to usual care in a one-year evaluation from November 2016 to October 2017. SETTING: Four NHs (two urban, two suburban) in Southwestern Pennsylvania. PARTICIPANTS: All residents in the four NHs were screened. There were 2,127 residents admitted having 652 alerts in the active period. INTERVENTION: Upon admission, pharmacists conducted medication reconciliation and prospective MRR for residents and also used telemedicine for communication with cognitively-intact residents. Post-admission, pharmacists received clinical decision support alerts to conduct targeted concurrent MRRs and telemedicine. MEASUREMENT: Main outcome was incidence of high-risk medication, alert-specific ADEs. Secondary outcomes included all-cause hospitalization, 30-day readmission rates, and consultant pharmacists' recommendations. RESULTS: Consultant pharmacists provided 769 recommendations. The intervention group had a 92% lower incidence of alert-specific ADEs than usual care (9 vs 31; 0.14 vs 0.61/1,000-resident-days; adjusted incident rate ratio (AIRR) = 0.08 (95% confidence interval (CI) = 0.01-0.40]; P = .002). All-cause hospitalization was similar between groups (149 vs 138; 2.33 vs 2.70/1,000-resident-days; AIRR = 1.06 (95% CI = 0.72-1.58); P = .75), as were 30-day readmissions (110 vs 102; 1.72 vs 2.00/1,000-resident-days; AIRR = 1.21 (95% CI = 0.76-1.93); P = .42). CONCLUSIONS: This is the first evaluation of the impact of pharmacist-led patient-centered telemedicine services to manage high-risk medications during transitional care and throughout the resident's NH stay, supporting a new model of patient care.

Does Universal Testing for COVID-19 Work for Everyone?

The Coronavirus disease 2019 (COVID-19) pandemic has been especially devastating among nursing home residents, with both the health circumstances of individual residents as well as communal living settings contributing to increased morbidity and mortality. Preventing the spread of COVID-19 infection requires a multipronged approach that includes early identification of infected residents and health care personnel, compliance with infection prevention and control measures, cohorting infected residents, and furlough of infected staff. Strategies to address COVID-19 infections among nursing home residents vary based on the availability for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests, the incorporation of tests into broader surveillance efforts, and using results to help mitigate the spread of COVID-19 by identifying asymptomatic and presymptomatic infections. We review the tests available to diagnose COVID-19 infections, the implications of universal testing for nursing home staff and residents, interpretation of test results, issues around repeat testing, and incorporation of test results as part of a long-term response to the COVID-19 pandemic. We propose a structured approach for facility-wide testing of residents and staff and provide alternatives if testing capacity is limited, emphasizing contact tracing. Nursing homes with strong screening protocols for residents and staff, that engage in contact tracing for new cases, and that continue to remain vigilant about infection prevent and control practices, may better serve their residents and staff by thoughtful use of symptom- and risk-based testing strategies.

Solving the COVID-19 Crisis in Post-Acute and Long-Term Care.

Our nation's nursing home industry has been in need of overhaul for decades-a situation made all the more evident by COVID-19. AMDA-The Society for Post-Acute and Long-Term Care Medicine is dedicated to quality in post-acute and long-term care process and outcomes. This special article presents 5 keys to solving the COVID-19 crisis in post-acute and long-term care, related to policy, collaboration, individualization, leadership, and reorganization. Taking action during this crisis may prevent sinking back into the complacency and habits of our pre-COVID-19 lives.

A Structured Tool for Communication and Care Planning in the Era of the COVID-19 Pandemic.

Residents in long-term care settings are particularly vulnerable to COVID-19 infections and, compared to younger adults, are at higher risk of poor outcomes and death. Given the poor prognosis of resuscitation outcomes for COVID-19 in general, the specter of COVID-19 in long-term care residents should prompt revisiting goals of care. Visitor restriction policies enacted to reduce the risk of transmission of COVID-19 to long-term care residents requires advance care planning discussions to be conducted remotely. A structured approach can help guide discussions regarding the diagnosis, expected course, and care of individuals with COVID-19 in long-term care settings. Information should be shared in a transparent and comprehensive manner to allay the increased anxiety that families may feel during this time. To achieve this, we propose an evidence-based COVID-19 Communication and Care Planning Tool that allows for an informed consent process and shared decision making between the clinician, resident, and their family.

Workflow Barriers and Strategies to Reduce Antibiotic Overuse in Nursing Homes.

OBJECTIVES: Antibiotic overuse is a significant problem in nursing homes (NHs). Strategies to improve antibiotic prescribing practices in NHs are a critical need. In this study, we analyzed antibiotic prescribing workflows to identify strategies for improving antibiotic prescribing in NHs. DESIGN: Qualitative descriptive study using prospective field-based assessment of workflows. SETTING: Six NHs in Wisconsin (n = 3) and Pennsylvania (n = 3). PARTICIPANTS: A total of 44 interviews with 68 NH professionals, including leadership, nurses, and prescribers. MEASUREMENTS: During a 1-day field visit in each NH, we conducted semistructured interviews with NH professionals, collected artifacts (policies, procedures, and documentation and communication tools), and observed clinical meetings. Study participants were interviewed (30-60 minutes) about antibiotic prescribing workflows in their facility. Information collected during site visits was used to create a representative workflow map of NH antibiotic prescribing. The workflow map guided thematic analysis to identify barriers corresponding to workflow steps across multiple NHs. RESULTS: The representative antibiotic preprescribing workflow map included 17 steps, beginning with resident change in condition and ending with the decision to prescribe an antibiotic. Thematic analysis identified common step-specific barriers to antibiotic stewardship centering on three themes: (A) information barriers, comprising (A1) inconsistent nurse assessment report and (A2) misalignment between the work and tools of information sharing within the facility, (B) communication barriers, comprising (B1) mismatched perception of prescriber information needs and (B2) difficulty reaching prescribers for direct interaction, and (C) professional barriers, comprising (C1) low prescriber confidence in nurse assessment report and (C2) nurse reluctance to express their professional opinions. CONCLUSION: Strategies addressing workflow barriers are important targets for antibiotic stewardship. Such strategies include structured information tools, nurse and prescriber education, and organizational improvement. Future research can build on combinations of existing and new strategies to measure their effects in improving antibiotic prescribing. J Am Geriatr Soc 68:2222-2231, 2020.

A Multifaceted Antimicrobial Stewardship Program for the Treatment of Uncomplicated Cystitis in Nursing Home Residents.

Importance: Urinary tract infections are the most common infections in nursing home residents. However, most antibiotic use is for unlikely cystitis (ie, nonspecific symptoms and positive culture results secondary to asymptomatic bacteriuria or a urine sample improperly collected for culture) that is unnecessary and inappropriate. This antibiotic use is associated with an increased risk of antimicrobial resistance, adverse drug events, and Clostridioides difficile (formerly Clostridium difficile) infections. Objective: To determine the association of a multifaceted antimicrobial stewardship and quality improvement intervention with the reduction in unnecessary antimicrobial use for unlikely cystitis among noncatheterized nursing home residents. Design, Setting, and Participants: A quality improvement intervention evaluation was conducted to target antimicrobial use among residents with unlikely cystitis in 25 nursing homes across the United States. Baseline data were collected between February 1, 2017, and April 30, 2017. The intervention was conducted from May 1, 2017, to April 30, 2018. Interventions: Intervention nursing homes (n = 12) were randomized to receive a 1-hour introductory webinar, pocket-sized educational cards, tools for system change, and educational clinical vignettes addressing the diagnosis and treatment of suspected uncomplicated cystitis. Monthly web-based coaching calls were held for staff of intervention nursing homes. All facilities received quarterly feedback reports regarding the management of uncomplicated cystitis. Control group nursing homes (n = 13) received usual care. Main Outcomes and Measures: The primary outcome was the incidence of antibiotic treatment for unlikely cystitis cases, defined using published criteria. Secondary outcomes included overall antibiotic use for any urinary tract infection and the safety outcomes of C difficile infections, as well as all-cause hospitalizations and death. Results: Among the 25 nursing homes participating in this quality improvement study, including 512 408 intervention facility resident-days and 443 912 control facility resident-days, fewer unlikely cystitis cases were treated with antibiotics in intervention facilities compared with control facilities (adjusted incident rate ratio [AIRR], 0.73 [95% CI, 0.59-0.91]); C difficile infection rates were also lower in intervention nursing homes vs control nursing homes (AIRR, 0.35 [95% CI, 0.19-0.64]). Overall antibiotic use for any type of urinary tract infection was 17% lower in the intervention facilities than the control facilities (AIRR, 0.83 [95% CI, 0.70-0.99]; P = .04). There was no increase in all-cause hospitalizations or deaths due to the intervention (all-cause hospitalizations: AIRR, 0.95 [95% CI, 0.75-1.19]; all-cause death: AIRR, 0.92 [95% CI, 0.73-1.16]). Conclusions and Relevance: This study suggests that a low-intensity, multifaceted intervention was associated with improved antibiotic prescribing for uncomplicated cystitis in a cohort of nursing homes without an adverse association with other safety outcomes. Although promising, further study is needed to determine whether the intervention could be widely implemented to assist facilities in meeting new federal nursing home requirements for antimicrobial stewardship and quality assurance performance improvement programs.

Early changes in bone turnover predict longer-term changes in bone mineral density but not trabecular bone score in frail older women.

Clinicians and patients want to know if therapy is working early in their course of treatment. We found that early changes in bone turnover markers at 6 months were associated with long-term changes in bone mineral density but not trabecular bone score at 12 and 24 months. PURPOSE: We sought to examine the association between shorter-term changes in markers of bone turnover and longer-term changes in bone mineral density (BMD) and microstructure in a cohort of frail elderly women with multiple comorbid conditions including osteoporosis. METHODS: We performed a secondary analysis of a 2-year zoledronic acid trial for osteoporosis in 155 women residents of long-term care communities (mean age 86.9 years). We examined the association of the 6-month change in serum C-terminal crosslinking telopeptide of type I collagen (CTX) and serum intact procollagen type I N propeptide (PINP) with the 12- and 24-month changes in BMD at the spine and hip and the trabecular bone score (TBS), an indirect measure of bone microstructure. RESULTS: For every 0.2-ng/ml 6-month CTX decrease, the corresponding increase in spine BMD at 12 and 24 months was 0.2% (p = 0.7210) and 1.1% (p = 0.0396), respectively; total hip BMD 1.1% (p = 0.0279) and 0.9% (p = 0.0716); and femoral neck BMD 1.7% (p = 0.0079) and 0.9% (p = 0.1698). Similarly, for every 20-ng/ml 6-month PINP decrease, the corresponding increase in spine BMD at 12 and 24 months was 0.9% (p = 0.0286) and 1.4% (p = 0.0012), respectively; total hip BMD 1.4% (p = 0.0005) and 1.4% (p = 0.0006); and femoral neck BMD 2.3% (p < 0.0001) and 2.0% (p < 0.0001). Bone marker changes were not consistently associated with TBS changes. CONCLUSION: Shorter-term 6-month changes in bone turnover markers are associated with the long-term changes in BMD over 1-2 years in the spine and hip but not with TBS.

Effect of antibiotic time-outs on modification of antibiotic prescriptions in nursing homes.

BACKGROUND: Antibiotic overuse and misuse is a common problem in nursing homes. Antibiotic time-out (ATO) interventions have led to improvements in antibiotic uses in hospitals, but their impact in nursing homes remain understudied. OBJECTIVE: To evaluate the impact of a stewardship intervention, promoting use of ATOs on the frequency and types of antibiotic change events (ACEs) in nursing homes. DESIGN: Controlled before-and-after intervention study. SETTING: Nursing homes in Wisconsin and Pennsylvania. METHOD: Data on antibiotic prescriptions in 11 nursing homes were collected for 25 months. We categorized ACEs as (1) early discontinuation, (2) class modification, or (3) administration modification. Class modification ACEs were further classified based on whether the change narrowed, expanded, or had no effect on bacterial spectrum coverage. Analyses were performed using a difference-in-difference (DiD) approach. RESULT: Of 2,647 antibiotic events initiated in study nursing homes, 376 (14.2%) were associated with an ACE. The overall proportion of ACEs did not significantly differ between intervention and control nursing homes. Early discontinuation ACEs increased in intervention nursing homes (DiD, 2.5%; P = .01), primarily affecting residents initiated on broad-spectrum antibiotics (DiD, 2.9%; P < .01). Class modification ACEs decreased in intervention nursing homes but remained unchanged in control nursing homes. CONCLUSION: The impact of an ATO intervention in study nursing homes was mixed with increases in early discontinuation ACEs offset by reductions in class modification ACEs. More research on the potential value of ATO interventions in nursing homes is warranted.

Recommendations for Mandatory Influenza Vaccinations for Health Care Personnel From AMDA's Infection Advisory Subcommittee.

Preventing influenza infections is a national health priority, particularly among geriatric and adults with frailty who reside in post-acute and long-term care (PALTC) settings. Older adults account for more than 70% of deaths from influenza, a reflection of decreased vaccine effectiveness in that age group. Annually vaccinating health care personnel (HCP) working with these patients against influenza is critical to reducing influenza morbidity and mortality among patients. PALTC HCP have the lowest influenza vaccination rate when compared to HCP in other settings. The Advisory Committee on Immunization Practices recommends that all HCP receive an annual influenza vaccination, including those who do not have direct patient care responsibilities. Here, we discuss the importance of influenza vaccination for HCP, detail recommendations for influenza vaccination practice and procedures for PALTC settings, and offer support to PALTC settings and their staff on influenza vaccinations.