Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Among Residents and Employees in a Veterans Affairs Community Living Center: A 42-Month Prospective Cohort Study.

Background: Understanding routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in long-term care facilities is essential for the development of effective control measures. Methods: Between March 1, 2020, and August 31, 2023, we identified coronavirus disease 2019 (COVID-19) cases among residents and employees in a Veterans Affairs community living center that conducted routine screening for asymptomatic COVID-19. Contact tracing was conducted to identify suspected transmission events, and whole genome sequencing was performed to determine the relatedness of SARS-CoV-2 samples. Results: During the 42-month study period, 269 cases of COVID-19 were diagnosed, including 199 employees and 70 residents. A total of 48 (24.1%) employees and 30 (42.9%) residents were asymptomatic. Sequencing analysis provided support for multiple events in which employees transmitted SARS-CoV-2 to co-workers and residents. There was 1 episode of likely transmission of SARS-CoV-2 from one resident to another resident, but no documented transmissions from residents to employees. Conclusions: Transmission of SARS-CoV-2 in the community living center predominantly involved transmission from employees to co-workers and residents. There is a need for improved measures to prevent transmission of SARS-CoV-2 by healthcare personnel.

Interim Estimates of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

Clinical burden of invasive Escherichia coli disease among older adult patients treated in hospitals in the United States.

BACKGROUND: Invasive extraintestinal pathogenic Escherichia coli disease (IED) can lead to severe outcomes, particularly among older adults. However, the clinical burden of IED in the U.S. has not been well characterized. METHODS: IED encounters among patients ≥ 60 years old were identified using the PINC AI™ Healthcare Database (10/01/2015-03/31/2020) by either a positive E. coli culture in blood or another normally sterile body site and ≥ 1 sign of systemic inflammatory response syndrome or signs of sepsis, or a positive E. coli culture in urine with urinary tract infection and signs of sepsis. Medical resource utilization, clinical outcomes, and E. coli isolate characteristics were descriptively reported during the first IED encounter and during the following year (observation period). RESULTS: Overall, 19,773 patients with IED were included (mean age: 76.8 years; 67.4% female; 78.5% with signs of sepsis). Most encounters involved community-onset IED (94.3%) and required hospitalization (96.5%; mean duration: 6.9 days), with 32.4% of patients being admitted to the intensive care unit (mean duration: 3.7 days). Most E. coli isolates were resistant to ≥ 1 antibiotic category (61.7%) and 34.4% were resistant to ≥ 3 antibiotic categories. Following their first IED encounter, 34.8% of patients were transferred to a skilled nursing/intermediate care facility, whereas 6.8% had died. During the observation period, 36.8% of patients were rehospitalized, 2.4% had IED recurrence, and in-hospital death increased to 10.9%. CONCLUSIONS: IED is associated with substantial clinical burden at first encounter with considerable long-term consequences. Findings demonstrate the need for increased IED awareness and highlight potential benefits of prevention.

Economic burden of invasive Escherichia coli disease among older adult patients treated in hospitals in the United States.

BACKGROUND: Although invasive Escherichia coli disease (IED) can lead to severe clinical outcomes, little is known about the associated medical resource use and cost burden of IED in US hospitals. OBJECTIVE: To comprehensively describe medical resource use and costs associated with IED during the initial IED event and over the subsequent 12 months. METHODS: Patients aged 60 years or older with 1 or more IED encounters were identified from the PINC AI Healthcare US hospital database (October 1, 2015, to March 31, 2020). The index encounter was defined as the first encounter with a positive E coli culture in a normally sterile site (group 1 IED) or positive E coli culture in urine with signs of sepsis (group 2 IED). Encounters with a positive culture from other bacteria or fungal pathogens were excluded. Outcomes were descriptively reported between admission and discharge for the index encounter and more than 1 - year post-index discharge. Medical resource use and costs included inpatient admissions and outpatient hospital services; costs were reported from a hospital's perspective (ie, charged amount) in 2021 USD. RESULTS: A total of 19,773 patients were identified (group 1 IED = 51.8%; group 2 IED = 48.2%). Mean age was 76.8 years, 67.4% were female, and 82.1% were White. Most index encounters were community-onset (94.3%) and led to hospitalization (96.5%) (mean inpatient days = 6.9 days). During the 1 - year post-index, 36.8% of patients had 1 or more all-cause hospitalizations. Mean [median] total all-cause hospital costs (as captured through the PINC AI Healthcare database) amounted to $16,760 [$11,340] during the index encounter and $10,942 [$804] during the 1 - year post-index; these costs were higher in the presence of sepsis and multidrug resistance and among hospital-onset IED. CONCLUSIONS: IED is associated with a substantial medical resource use and economic burden both during the initial encounter and over the following year in older adults. This highlights the critical need and potential benefits of preventive measures that may reduce the incidence of IED and associated economic burden. DISCLOSURES: This study was funded by Janssen Global Services, LLC. Dr Hernandez-Pastor is an employee of Janssen Pharmaceutica NV. Dr Geurtsen is an employee of Janssen Vaccines & Prevention BV. Dr Baugh is an employee of Janssen Research & Development, LLC. Dr El Khoury is an employee of Janssen Global Services, LLC. Dr Kalu and Dr Krishnarajah are employees of Janssen Scientific Affairs, LLC. Dr Gauthier-Loiselle, Ms Bungay, and Mr Cloutier are employees of Analysis Group, Inc., a consulting company that provided paid consulting services to Janssen Global Services, LLC. Dr Saade received consultation and speaker fees from Janssen.

Vaccine-Preventable Diseases in Older Adults.

Older adults are at an increased risk of vaccine-preventable diseases partly because of physiologic changes in the immune and other body systems related to age and/or accumulating comorbidities that increase the vulnerability to infections and decrease the response to vaccines. Strategies to improve the response to vaccines include using a higher antigenic dose (such as in the high-dose inactivated influenza vaccines) as well as adding adjuvants (such as MF59 in the adjuvanted inactivated influenza vaccine).

Can Electronic Clinical Decision Support Systems Improve the Diagnosis of Urinary Tract Infections? A Systematic Review and Meta-Analysis.

Background: Urinary tract infection (UTI) is a commonly misdiagnosed infectious syndrome. Diagnostic stewardship interventions can reduce rates of asymptomatic bacteriuria treatment but are often labor intensive, and thus an automated means of reducing unnecessary urine testing is preferred. In this systematic review and meta-analysis, we sought to identify studies describing interventions utilizing clinical decision support (CDS) to optimize UTI diagnosis and to characterize the effectiveness of these interventions. Methods: We conducted a comprehensive electronic search and manual reference list review for peer-reviewed articles published before July 2, 2021. Publications describing an intervention intending to enhance UTI diagnosis via CDS were included. The primary outcome was urine culture test rate. Results: The electronic search identified 5013 studies for screening. After screening and full-text review, 9 studies met criteria for inclusion, and a manual reference list review identified 5 additional studies, yielding a total of 14 studies included in the systematic review. The most common CDS intervention was urinalysis with reflex to urine culture based on prespecified urinalysis parameters. All 9 studies that provided statistical comparisons reported a decreased urine culture rate postintervention, 8 of which were statistically significant. A meta-analysis including 4 studies identified a pooled urine culture incidence rate ratio of 0.56 (95% confidence interval, .52-.60) favoring the postintervention versus preintervention group. Conclusions: In this systematic review and meta-analysis, CDS appeared to be effective in decreasing urine culture rates. Prospective trials are needed to confirm these findings and to evaluate their impact on antimicrobial prescribing, patient-relevant outcomes, and potential adverse effects.

SARS-CoV-2 Seroprevalence Among First Responders in Northeastern Ohio, 2020.

OBJECTIVES: First responders, including firefighters, emergency medical technicians (EMTs), paramedics, and law enforcement officers, are working on the front lines to fight the COVID-19 pandemic and facing an increased risk of infection. This study assessed the seroprevalence of SARS-CoV-2 infection among first responders in northeastern Ohio. METHODS: A survey and immunoglobulin G antibody test against SARS-CoV-2 nucleocapsid protein were offered to University Hospitals Health System-affiliated first-responder departments during May to September 2020. The survey contained questions about demographic characteristics and history of SARS-CoV-2 infection. A total of 3080 first responders with diverse job assignments from more than 400 fire and police departments participated in the study. RESULTS: Of 3080 participants, 73 (2.4%) were seropositive and 26 (0.8%) had previously positive real-time polymerase chain reaction results. Asymptomatic infection accounted for 46.6% (34 of 73) of seropositivity. By occupation, rates of seropositivity were highest among administration/support staff (3.8%), followed by paramedics (3.0%), EMTs (2.6%), firefighters (2.2%), and law enforcement officers (0.8%). Work-associated exposure rates to COVID-19 patients were: paramedics (48.2%), firefighters (37.1%), EMTs (32.3%), law enforcement officers (7.7%), and administration/support staff (4.4%). Self-reported community exposure was positively correlated with self-reported work-associated exposure rate (correlation coefficient = 0.99). Neither self-reported community nor work-associated exposure was correlated with SARS-CoV-2 seroprevalence. We found no significant difference in seroprevalence among sex/gender or age groups; however, Black participants had a higher positivity rate than participants of other racial groups despite reporting lower exposure. CONCLUSIONS: Despite the high work-associated exposure rate to SARS-CoV-2 infection, first responders with various roles demonstrated seroprevalence no higher than their administrative/supportive colleagues, which suggests infection control measures are effective in preventing work-related infection.

A Nanoporous 3D-Printed Scaffold for Local Antibiotic Delivery.

Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery.

Prevention and treatment of COVID-19 in patients with benign and malignant blood disorders.

Patients with moderate to severe immunosuppression, a condition that is common in many hematologic diseases because of the pathology itself or its treatment, are at high risk for COVID-19 and its complications. While empirical data are sometimes conflicting, this heightened risk has been confirmed in multiple well-done studies for patients with hematologic malignancies, particularly those with B-cell lymphoid malignancies who received lymphocytotoxic therapies, those with a history of recent hematopoietic stem cell transplant and chimeric antigen receptor T-cell therapy, and, to a lesser degree, those with hemoglobinopathies. Patients with immunosuppression need to have a lower threshold for avoiding indoor public spaces where they are unable to effectively keep a safe distance from others, and wear a high-quality well-fitting mask, especially when community levels are not low. They should receive an enhanced initial vaccine regimen and additional boosting. Therapeutic options are available and immunosuppressed patients are prioritized per the NIH.

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study.

Background: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. Methods: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. Results: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P = .079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P < .001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P < .001), and incident admission to a long-term care facility (22% vs 12%, P = .045). Conclusions: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders.

High-dose influenza vaccines for the prevention of hospitalization due to cardiovascular events in older adults in the nursing home: Post-hoc analysis of a cluster-randomized trial.

Older adults are at high risk of major acute cardiovascular events (MACE) linked to influenza illness andpreventable by influenza vaccination. It is unknown whether high-dose vaccine might incrementally reduce the risk of MACE.We conducted a post-hoc analysis of data collected from a pragmatic cluster randomized study of 823 nursing homes (NH) randomized to standard-dose (SD) or high-dose (HD) influenza vaccine in the 2013-14 season. Adults age 65 year or older who are Medicare-enrolled long-stay residents were included in the analysis.There were no statistically significant differences in hospitalization for MACE, acute coronary syndromes (ACS), stroke or heart failure between the HD and SD arms. However, in the fee-for-service group, participants in the HD arm had significantly decreased risk of hospitalization for respiratory problems, which was not observed in the Medicare Advantage group.High-dose influenza vaccine was not shown to be incrementally protective against MACE relative to standard-dose vaccine.

Seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among healthcare providers prior to the vaccine era in an integrated midwestern healthcare system.

We performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antinucleocapsid IgG testing on 5,557 healthcare providers and found a seroprevalence of 3.9%. African Americans were more likely to test positive than Whites, and HCWs with household exposure and those working on COVID-19 cohorting units were more likely to test positive than their peers.

SARS-CoV-2 antibody profile of naturally infected and vaccinated individuals detected using qualitative, semi-quantitative and multiplex immunoassays.

This study measured antibodies against different antigen targets in healthcare workers (HCW) who have been fully vaccinated with mRNA vaccines, recovered from natural infection, or patients during active infection. All vaccinated individuals were positive for anti-RBD, anti-S1, and anti-S2 antibodies. The nonvaccinated recovered cohort showed 90% seropositivity by Atellica total antibody, 73% by Atellica IgG, 84% by Bioplex anti-RBD, 77% by Bioplex anti-S1, 37% by Bioplex anti-S2, and 79% by Bioplex antinucleocapsid respectively. The active infection cohort exhibited a similar pattern as the recovered cohort. About 88% and 78% of the recovered and active infection cohort produced both anti-spike and anti-N antibodies with Anti-S1/anti-N ratios ranging from 0.07 to 16.26. In summary, fully vaccinated individuals demonstrated an average of 50-fold higher antibody levels than naturally infected unvaccinated individuals with immune reactivity strongly towards RBD/S1 and a weak response to S2. The results support vaccination regardless of previous COVID-infection status.

Microbial bioburden of inpatient and outpatient areas beyond patient hospital rooms.

OBJECTIVE: To investigate the frequency of environmental contamination in hospital areas outside patient rooms and in outpatient healthcare facilities. DESIGN: Culture survey. SETTING: This study was conducted across 4 hospitals, 4 outpatient clinics, and 1 surgery center. METHODS: We conducted 3 point-prevalence culture surveys for methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridioides difficile, Candida spp, and gram-negative bacilli including Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumanii, and Stenotrophomonas maltophilia in each facility. In hospitals, high-touch surfaces were sampled from radiology, physical therapy, and mobile equipment and in emergency departments, waiting rooms, clinics, and endoscopy facilities. In outpatient facilities, surfaces were sampled in exam rooms including patient and provider areas, patient bathrooms, and waiting rooms and from portable equipment. Fluorescent markers were placed on high-touch surfaces and removal was assessed 1 day later. RESULTS: In the hospitals, 110 (9.4%) of 1,195 sites were positive for 1 or more bacterial pathogens (range, 5.3%-13.7% for the 4 hospitals) and 70 (5.9%) were positive for Candida spp (range, 3.7%-5.9%). In outpatient facilities, 31 of 485 (6.4%) sites were positive for 1 or more bacterial pathogens (range, 2% to 14.4% for the 5 outpatient facilities) and 50 (10.3%) were positive for Candida spp (range, 3.9%-23.3%). Fluorescent markers had been removed from 33% of sites in hospitals (range, 28.4%-39.7%) and 46.3% of sites in outpatient clinics (range, 7.4%-82.8%). CONCLUSIONS: Surfaces in hospitals outside patient rooms and in outpatient facilities are frequently contaminated with healthcare-associated pathogens. Improvements in cleaning and disinfection practices are needed to reduce contamination.

Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review.

BACKGROUND: Major adverse cardiovascular events (MACE) are increasingly used as composite outcomes in randomized controlled trials (RCTs) and observational studies. However, it is unclear how observational studies most commonly define MACE in the literature when using administrative data. METHODS: We identified peer-reviewed articles published in MEDLINE and EMBASE between January 1, 2010 to October 9, 2020. Studies utilizing administrative data to assess the MACE composite outcome using International Classification of Diseases 9th or 10th Revision diagnosis codes were included. Reviews, abstracts, and studies not providing outcome code definitions were excluded. Data extracted included data source, timeframe, MACE components, code definitions, code positions, and outcome validation. RESULTS: A total of 920 articles were screened, 412 were retained for full-text review, and 58 were included. Only 8.6% (n = 5/58) matched the traditional three-point MACE RCT definition of acute myocardial infarction (AMI), stroke, or cardiovascular death. None matched four-point (+unstable angina) or five-point MACE (+unstable angina and heart failure). The most common MACE components were: AMI and stroke, 15.5% (n = 9/58); AMI, stroke, and all-cause death, 13.8% (n = 8/58); and AMI, stroke and cardiovascular death 8.6% (n = 5/58). Further, 67% (n = 39/58) did not validate outcomes or cite validation studies. Additionally, 70.7% (n = 41/58) did not report code positions of endpoints, 20.7% (n = 12/58) used the primary position, and 8.6% (n = 5/58) used any position. CONCLUSIONS: Components of MACE endpoints and diagnostic codes used varied widely across observational studies. Variability in the MACE definitions used and information reported across observational studies prohibit the comparison, replication, and aggregation of findings. Studies should transparently report the administrative codes used and code positions, as well as utilize validated outcome definitions when possible.

Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT) Reveals Improvements in the Treatment of Bloodstream Infections Caused by Escherichia coli and Klebsiella pneumoniae in Patients from the Veterans Health Administration.

BACKGROUND: Reductions in the use of broad-spectrum antibiotics is a cornerstone of antimicrobial stewardship. We aim to demonstrate use of the Desirability of Outcome Ranking Approach for the Management of Antimicrobial Therapy (DOOR MAT) to evaluate the treatment of Escherichia coli and Klebsiella pneumoniae bloodstream infections in patients from the Veterans Health Administration (VHA) across a decade. METHODS: Using electronic records, we determined empiric and definitive antibiotic treatments, clinical characteristics, and 30-day mortality of patients with monomicrobial E. coli and K. pneumoniae bloodstream infections hospitalized in VHA medical centers from 2009 to 2018. Focusing on patients treated with parenteral ß-lactams and with available antibiotic susceptibility testing results, we applied a range of DOOR MAT scores that reflect the desirability of antibiotic choices according to spectrum and activity against individual isolates. We report trends in resistance and desirability of empiric and definitive antibiotic treatments. RESULTS: During the 10-year period analyzed, resistance to expanded-spectrum cephalosporins and fluoroquinolones increased in E. coli but not in K. pneumoniae, while resistance to carbapenems and piperacillin-tazobactam remained unchanged. In 6451 cases analyzed, we observed improvements in DOOR MAT scores consistent with deescalation. Improvement in desirability of definitive treatment compared with empiric treatment occurred in 26% of cases, increasing from 16% in 2009 to 34% in 2018. Reductions in overtreatment were sustained and without negative impact on survival. CONCLUSIONS: DOOR MAT provides a framework to assess antibiotic treatment of E. coli and K. pneumoniae bloodstream infections and can be a useful metric in antimicrobial stewardship.

SARS-CoV-2 antibody detection in skilled nursing facility residents.

OBJECTIVE: To describe the frequency and timing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody detection in a convenience sample of skilled nursing facility (SNF) residents with and without confirmed SARS-CoV-2 infection. DESIGN: Retrospective analysis of SNF electronic health records. SETTING: Qualitative SARS-CoV-2 antibody test results were available from 81 SNFs in 16 states. PARTICIPANTS: Six hundred and sixty nine SNF residents who underwent both polymerase chain reaction (PCR) and antibody testing for SARS-CoV-2. MEASUREMENTS: Presence of SARS-CoV-2 antibodies following the first positive PCR test for confirmed cases, or first PCR test for non-cases. RESULTS: Among 397 residents with PCR-confirmed infection, antibodies were detected in 4 of 7 (57.1%) tested within 7-14 days of their first positive PCR test; in 44 of 47 (93.6%) tested within 15-30 days; in 182 of 219 (83.1%) tested within 31-60 days; and in 110 of 124 (88.7%) tested after 60 days. Among 272 PCR negative residents, antibodies were detected in 2 of 9 (22.2%) tested within 7-14 days of their first PCR test; in 41 of 81 (50.6%) tested within 15-30 days; in 65 of 148 (43.9%) tested within 31-60 days; and in 9 of 34 (26.5%) tested after 60 days. No significant differences in baseline resident characteristics or symptoms were observed between those with versus without antibodies. CONCLUSIONS: These findings suggest that vulnerable older adults can mount an antibody response to SARS-CoV-2, and that antibodies are most likely to be detected within 15-30 days of diagnosis. That antibodies were detected in a large proportion of residents with no confirmed SARS-CoV-2 infection highlights the complexity of identifying who is infected in real time. Frequent surveillance and diagnostic testing based on low thresholds of clinical suspicion for symptoms and/or exposure will remain critical to inform strategies designed to mitigate outbreaks in SNFs while community SARS-CoV-2 prevalence remains high.

Adjuvanted Influenza Vaccine and Influenza Outbreaks in US Nursing Homes: Results From a Pragmatic Cluster-Randomized Clinical Trial.

BACKGROUND: Influenza outbreaks in nursing homes pose a threat to frail residents and occur even in vaccinated populations. We conducted a pragmatic cluster-randomized trial comparing adjuvanted trivalent influenza vaccine (aTIV) versus trivalent influenza vaccine (TIV). We report an exploratory analysis to compare the effect of aTIV versus TIV on facility-reported influenza outbreaks. METHODS: We evaluated the impact of the intent-to-treat vaccine assignment on outbreaks reported from November 2016 to March 2017. We collected data according to standard CDC definitions for both suspected outbreaks and those with a laboratory-confirmed case and adjusted for facility-level vaccination rates and resident characteristics in nursing homes. RESULTS: Of 823 randomized nursing homes, 777 (aTIV, n = 387; TIV, n = 390) reported information on influenza outbreaks. Treatment groups had similar characteristics at baseline except for race/ethnicity: homes assigned to TIV had a higher percentage of African-American residents (18.0% vs 13.7%). There were 133 versus 162 facility-reported suspected influenza outbreaks in aTIV versus TIV facilities, respectively; of these, 115 versus 140 were laboratory confirmed. The aTIV group experienced a 17% reduction in suspected (rate ratio, .83; 95% confidence interval, .65-1.05) and laboratory-confirmed (.83; .63-1.06) influenza outbreaks. Covariate adjustment increased the estimated reduction for suspected outbreaks to 21% (.79; .61-.99) and 22% for laboratory-confirmed outbreaks (.78; .60-1.02). CONCLUSIONS: In an exploratory analysis of a cluster-randomized trial we observed 17-21% fewer outbreaks with aTIV than TIV. Clinical Trials Registration. (NCT02882100).

Cluster-randomized Trial of Adjuvanted Versus Nonadjuvanted Trivalent Influenza Vaccine in 823 US Nursing Homes.

BACKGROUND: Influenza leads in preventable infection-related hospitalization in nursing home (NH) residents. The adjuvanted trivalent influenza vaccine (aTIV) is more immunogenic than similarly dosed nonadjuvanted trivalent influenza vaccine (TIV), and observational studies suggest aTIV better prevents hospitalizations in older adults. We prospectively tested this in an NH setting. METHODS: NHs with ≥50 long-stay residents aged ≥65 years were randomized to offer aTIV or TIV for residents for the 2016-2017 influenza season. Using intent-to-treat resident-level analysis with Cox proportional hazards regression models adjusted for clustering by facility and a priori baseline covariates (eg, age, heart failure, and facility-level characteristics), we assessed relative aTIV:TIV effectiveness for hospitalization (ie, all-cause, respiratory, and pneumonia and influenza [P&I]). RESULTS: We randomized 823 NHs, housing 50 012 eligible residents, to aTIV or TIV. Residents were similar between groups by age (mean, ~79 years), heart failure, lung disease, and influenza and pneumococcal vaccine uptake, except aTIV homes housed fewer Black residents (14.5 vs 18.9%). Staff vaccine uptake was similar (~55%). P&I and all-cause resident hospitalization rates were lower (adjusted HR [aHR], .80 [95% CI, .66-.98; P = .03] and .94 [.89-.99; P = .02], respectively) for aTIV versus TIV, while the respiratory hospitalization rate was similar, in a season where vaccine effectiveness was considered poor. CONCLUSIONS: aTIV was more effective than TIV in preventing all-cause and P&I hospitalization from NHs during an A/H3N2-predominant season when TIV was relatively ineffective. CLINICAL TRIALS REGISTRATION: NCT02882100.