Consistent Effects of Early Remdesivir on Symptoms and Disease Progression Across At-Risk Outpatient Subgroups: Treatment Effect Heterogeneity in PINETREE Study.

INTRODUCTION: In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day 28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs). METHODS: PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7 days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60 years, obesity [body mass index ≥ 30], or certain coexisting medical conditions). Patients received remdesivir intravenously (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. RESULTS: In this subgroup analysis, HTE of remdesivir by time from symptom onset at treatment initiation and number of baseline RFs was not detected. Treatment with remdesivir reduced COVID-19-related hospitalizations independent of stratification by time from symptom onset to randomization. Of patients enrolled ≤ 5 days from symptom onset, 1/201 (0.5%) receiving remdesivir and 9/194 (4.6%) receiving placebo were hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.82). Of those enrolled at > 5 days from symptom onset, 1/78 (1.3%) receiving remdesivir and 6/89 (6.7%) receiving placebo were hospitalized (HR 0.19; 95% CI 0.02-1.61). Remdesivir was also effective in reducing COVID-19-related hospitalizations when stratified by number of baseline RFs for severe disease. Of patients with ≤ 2 RFs, 0/159 (0.0%) receiving remdesivir and 4/164 (2.4%) receiving placebo were hospitalized; of those with ≥ 3 RFs, 2/120 (1.7%) receiving remdesivir and 11/119 (9.2%) receiving placebo were hospitalized (HR 0.16; 95% CI 0.04-0.73). CONCLUSIONS: In the outpatient setting, benefit of remdesivir initiated within 7 days of symptoms appeared to be consistent across patients with RFs. Therefore, it may be reasonable to broadly treat patients with remdesivir regardless of comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov number NCT04501952.

Implementation of an Antibiotic Stewardship Program in Long-term Care Facilities Across the US.

IMPORTANCE: Antibiotic overuse in long-term care (LTC) is common, prompting calls for antibiotic stewardship programs (ASPs) designed for specific use in these settings. The optimal approach to establish robust, sustainable ASPs in LTC facilities is unknown. OBJECTIVES: To determine if the Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use, an educational initiative to establish ASPs focusing on patient safety, is associated with reductions in antibiotic use in LTC settings. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study including 439 LTC facilities in the US assessed antibiotic therapy data following a pragmatic quality-improvement program, which was implemented to assist facilities in establishing ASPs and with antibiotic decision-making. Training was conducted between December 2018 and November 2019. Data were analyzed from January 2019 to December 2019. INTERVENTIONS: Fifteen webinars occurred over 12 months (December 2018 to November 2019), accompanied by additional tools, activities, posters, and pocket cards. All clinical staff were encouraged to participate. MAIN OUTCOMES AND MEASURES: The primary outcome was antibiotic starts per 1000 resident-days. Secondary outcomes included days of antibiotic therapy (DOT) per 1000 resident-days, the number of urine cultures per 1000 resident-days, and Clostridioides difficile laboratory-identified events per 10 000 resident-days. All outcomes compared data from the baseline (January-February 2019) to the completion of the program (November-December 2019). Generalized linear mixed models with random intercepts at the site level assessed changes over time. RESULTS: Of a total 523 eligible LTC facilities, 439 (83.9%) completed the safety program. The mean difference for antibiotic starts from baseline to study completion per 1000 resident-days was -0.41 (95% CI, -0.76 to -0.07; P = .02), with fluoroquinolones showing the greatest decrease at -0.21 starts per 1000 resident-days (95% CI, -0.35 to -0.08; P = .002). The mean difference for antibiotic DOT per 1000 resident-days was not significant (-3.05; 95% CI, -6.34 to 0.23; P = .07). Reductions in antibiotic starts and use were greater in facilities with greater program engagement (as measured by webinar attendance). While antibiotic starts and DOT in these facilities decreased by 1.12 per 1000 resident-days (95% CI, -1.75 to -0.49; P < .001) and 9.97 per 1000 resident-days (95% CI, -15.4 to -4.6; P < .001), respectively, no significant reductions occurred in low engagement facilities. Urine cultures per 1000 resident-days decreased by 0.38 (95% CI, -0.61 to -0.15; P = .001). There was no significant change in facility-onset C difficile laboratory-identified events. CONCLUSIONS AND RELEVANCE: Participation in the AHRQ safety program was associated with the development of ASPs that actively engaged clinical staff in the decision-making processes around antibiotic prescriptions in participating LTC facilities. The reduction in antibiotic DOT and starts, which was more pronounced in more engaged facilities, indicates that implementation of this multifaceted program may support successful ASPs in LTC settings.

Evaluating immunity to SARS-CoV-2 in nursing home residents using saliva IgG.

BACKGROUND: SARS-CoV-2 circulating variants coupled with waning immunity pose a significant threat to the long-term care (LTC) population. Our objective was to measure salivary IgG antibodies in residents and staff of an LTC facility to (1) evaluate IgG response in saliva post-natural infection and vaccination and (2) assess its feasibility to describe the seroprevalence over time. METHODS: We performed salivary IgG sampling of all residents and staff who agreed to test in a 150-bed skilled nursing facility during three seroprevalence surveys between October 2020 and February 2021. The facility had SARS-CoV-2 outbreaks in May 2020 and November 2020, when 45 of 138 and 37 of 125 residents were infected, respectively; they offered two Federal vaccine clinics in January 2021. We evaluated quantitative IgG in saliva to the Nucleocapsid (N), Spike (S), and Receptor-binding domain (RBD) Antigens of SARS-CoV-2 over time post-infection and post-vaccination. RESULTS: One hundred twenty-four residents and 28 staff underwent saliva serologic testing on one or more survey visits. Over three surveys, the SARS-CoV-2 seroprevalence at the facility was 49%, 64%, and 81%, respectively. IgG to S, RBD, and N Antigens all increased post infection. Post vaccination, the infection naïve group did not have a detectable N IgG level, and N IgG levels for the previously infected did not increase post vaccination (p < 0.001). Fully vaccinated subjects with prior COVID-19 infection had significantly higher RBD and S IgG responses compared with those who were infection-naïve prior to vaccination (p < 0.001 for both). CONCLUSIONS: Positive SARS-COV-2 IgG in saliva was concordant with prior infection (Anti N, S, RBD) and vaccination (Anti S, RBD) and remained above positivity threshold for up to 9 months from infection. Salivary sampling is a non-invasive method of tracking immunity and differentiating between prior infection and vaccination to inform the need for boosters in LTC residents and staff.

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

Outcomes of Nursing Home COVID-19 Patients by Initial Symptoms and Comorbidity: Results of Universal Testing of 1970 Residents.

OBJECTIVE: Clinical implications of asymptomatic cases of the novel coronavirus disease 2019 (COVID-19) in nursing homes remain poorly understood. We assessed the association of symptom status and medical comorbidities on mortality and hospitalization risk associated with COVID-19 in residents across 15 nursing homes in Maryland. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 1970 residents from 15 nursing home facilities with universal COVID-19 testing in Maryland. METHODS: We used descriptive statistics to compare baseline characteristics, logistic regression to assess the association of comorbidities with COVID-19, and Cox regression to assess the association of asymptomatic and symptomatic COVID-19 with mortality and hospitalization. We assessed the association of comorbidities with mortality and hospitalization risk. Symptom status was assessed at the time of the first test. Maximum follow-up was 94 days. RESULTS: Among the 1970 residents (mean age 73.8, 57% female, 68% black), 752 (38.2%) were positive on their first test. Residents who were positive for COVID-19 and had multiple symptoms at the time of testing had the highest risk of mortality [hazard ratio (HR) 4.44, 95% confidence interval (CI) 2.97, 6.65) and hospitalization (subhazard ratio 2.38, 95% CI 1.70, 3.33), even after accounting for comorbidity burden. Cases who were asymptomatic at testing had a higher risk of mortality (HR 2.92, 95% CI 1.95, 4.35) but not hospitalization (HR 1.06, 95% CI 0.82, 1.38) compared with those who were negative for COVID-19. Of 52 SARS-CoV-2-positive residents who were asymptomatic at the time of testing and were closely monitored for 14 days at one facility, only 6 (11.6%) developed symptoms. CONCLUSIONS AND IMPLICATIONS: Asymptomatic infection with SARS-CoV-2 in the nursing home setting was associated with increased risk of death, suggesting a need for closer monitoring of these residents, particularly those with underlying cardiovascular and respiratory comorbidities.

Transmission of SARS-CoV-2 Involving Residents Receiving Dialysis in a Nursing Home - Maryland, April 2020.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly in nursing homes once it is introduced (1,2). To prevent outbreaks, more data are needed to identify sources of introduction and means of transmission within nursing homes. Nursing home residents who receive hemodialysis (dialysis) might be at higher risk for SARS-CoV-2 infections because of their frequent exposures outside the nursing home to both community dialysis patients and staff members at dialysis centers (3). Investigation of a COVID-19 outbreak in a Maryland nursing home (facility A) identified a higher prevalence of infection among residents undergoing dialysis (47%; 15 of 32) than among those not receiving dialysis (16%; 22 of 138) (p<0.001). Among residents with COVID-19, the 30-day hospitalization rate among those receiving dialysis (53%) was higher than that among residents not receiving dialysis (18%) (p = 0.03); the proportion of dialysis patients who died was 40% compared with those who did not receive dialysis (27%) (p = 0.42).Careful consideration of infection control practices throughout the dialysis process (e.g., transportation, time spent in waiting areas, spacing of machines, and cohorting), clear communication between nursing homes and dialysis centers, and coordination of testing practices between these sites are critical to preventing COVID-19 outbreaks in this medically vulnerable population.

Respiratory Practices in the Long-term Care Setting: A Human Factors-Based Risk Analysis.

OBJECTIVE: To systematically assess safety risks pertaining to tracheostomy care in the long-term care (LTC) setting using a human factors engineering approach. DESIGN: We utilized a 5-part approach to complete our proactive risk assessment: (1) performed a hierarchical task analysis of the processes of tracheostomy stoma and suctioning; (2) identified failure modes where a subtask may be completed inappropriately; (3) prioritized each failure mode based on a risk priority scale; (4) identified contributing factors to and consequences for each of the prioritized failure modes; and (5) identified potential solutions to eliminate or mitigate risks. SETTING: Three high-acuity LTC facilities with ventilator units across Maryland. METHODS: The hierarchical task analysis was conducted jointly by 2 human-factors experts and an infectious disease physician based on respiratory care policies from the Centers for Disease Control and Prevention and existing policies at each LTC facility. The findings were used to guide direct observations with contextual inquiry and focus group sessions to assess safety risks for residents receiving tracheostomy care. RESULTS: Direct observations of tracheostomy care and suctioning in the LTC setting revealed significant variations in practice. Respiratory therapists working in LTC reported lack of training and ambiguity concerning recommended procedures to reduce infection transmission in daily care. Highest risk steps identified in tracheostomy care and suctioning included hand hygiene, donning gloves, and providing intermittent suctioning as the suction catheter was withdrawn. Participants identified risk mitigation strategies targeting these high-risk failure modes that addressed contributing factors related to 5 work system components: person (knowledge and competency), task (eg, urgency or time constraints), tools and technology (eg, availability of hand sanitizer), environment (eg, communal rooms), and organization (eg, patient safety culture). CONCLUSIONS AND IMPLICATIONS: Human factors analysis of the highest-risk steps in respiratory care activities in the LTC setting suggest several potential mitigation strategies to decrease the risk of infection transmission. Clear procedure guidelines with training are needed to reduce ambiguity and improve care in this setting. Involving frontline staff in patient safety issues using human factors principles and risk analysis may encourage participation and improve the infection prevention culture in LTC.

Antimicrobial Resistance of Sterile Site Infections in Sub-Saharan Africa: A Systematic Review.

Sparse data exist from sub-Saharan Africa (SSA) on the prevalence of antimicrobial resistance (AMR). A prior review of antimicrobial resistance in SSA from 1990 to 2013 showed a high prevalence of AMR to commonly used antibiotics in this setting. We reviewed the literature published since 2013. Four databases (PubMed, EMBASE, Cochrane, and African Journals Online) were searched for articles between February 2013 and March 2016 with a focus on sterile site infections (bacteremia, urinary tract infections [UTIs], and meningitis). We focused on the original World Health Organization-identified priority pathogens and antibiotics, prior to the release of the most recently updated and expanded list in 2017. There were 19 eligible studies: bacteremia (12), UTI (6), and meningitis (1). Eight studies were from Western and Central Africa, 8 from Eastern Africa, and 4 from Southern Africa. Prevalence of Escherichia coli resistance to third-generation cephalosporins ranged from 0% to 75%. No studies reported resistance to carbapenems among Klebsiella spp. Prevalence of fluoroquinolone resistance ranged from 8.3% to 100% among E. coli and 0% to 15% among Salmonella spp. Prevalence of resistance to penicillin among Streptococcus pneumoniae isolates ranged from 25% to 100%. Testing for extended-spectrum beta-lactamase was reported in 7 studies (range, 1.3-60% among tested isolates). Methods for evaluating AMR varied across studies; standardized approaches are needed in the region. Testing for mechanisms of resistance is low even in research settings, but important mechanisms of resistance such as ESBL production are present.

Implementing Antimicrobial Stewardship in Long-term Care Settings: An Integrative Review Using a Human Factors Approach.

Implementing effective antimicrobial stewardship in long-term care facilities (LTCFs) is associated with challenges distinct from those faced by hospitals. LTCFs generally care for elderly populations who are vulnerable to infection, have prescribers who are often off-site, and have limited access to timely diagnostic testing. Identification of feasible interventions in LTCFs is important, particularly given the new requirement for stewardship programs by the Centers for Medicare and Medicaid Services (CMS). In this integrative review, we analyzed published evidence in the context of a human factors engineering approach as well as educational interventions to understand aspects of multimodal interventions associated with the implementation of successful stewardship programs in LTCFs. The outcomes indicate that effective antimicrobial stewardship in long-term care is supported by incorporating multidisciplinary education, tools integrated into the workflow of nurses and prescribers that facilitate review of antibiotic use, and involvement of infectious disease consultants.

Template for an Antibiotic Stewardship Policy for Post-Acute and Long-Term Care Settings.

In response to a rising concern for multidrug resistance and Clostridium difficile infections, the Centers for Medicare and Medicaid services (CMS) will require all long-term care (LTC) facilities to establish an antibiotic stewardship program by November 2017. Thus far, limited evidence describes implementation of antibiotic stewardship in LTC facilities, mostly in academic- or hospital-affiliated settings. To support compliance with CMS requirements and aid facilities in establishing a stewardship program, the Infection Advisory Committee at AMDA-The Society for Post-Acute and Long-Term Care Medicine, has developed an antibiotic stewardship policy template tailored to the LTC setting. The intent of this policy, which can be adapted by individual facilities, is to help LTC facilities implement an antibiotic stewardship policy that will meet or exceed CMS requirements. We also briefly discuss implementation of an antibiotic stewardship program in LTC settings, including a list of free resources to support those efforts.

Healthcare-associated infections in the elderly: what's new.

PURPOSE OF REVIEW: The high-risk population and current lack of knowledge regarding appropriate infection prevention in the long-term care (LTC) setting has contributed to substantial rates of resistance and healthcare-associated infections in this arena. More evidence-based research on LTC is necessary, particularly now that the elderly population is increasing. RECENT FINDINGS: Proposed government mandates highlight the urgent need to combat antimicrobial resistance in the LTC setting. Recent studies focusing on unique strategies for the prevention of transmission and infection with multidrug-resistant organisms in nursing homes are discussed, as well as attempts to formulate clear antimicrobial stewardship programs. SUMMARY: The long-term setting has unique challenges to instituting effective infection control precautions, therefore current accepted methods used in acute-care facilities need to be modified. Recent data suggest that prevention of transmission in LTC may be achieved with focus on high-risk patients or specific care-based activities rather than colonization status. Antimicrobial stewardship and consultation with specialized physicians may be important measures to combat resistance and adverse events in LTC. The prevention of unnecessary antibiotic use in palliative care may reduce rates of resistance as well as discomfort for terminal patients.

Recurrent Aeromonas Bacteremia Due to Contaminated Well Water.

Although they are ubiquitous to aquatic environments, Aeromonas species have traditionally been considered nonvirulent; however, in the past 30 years, they have emerged as important human pathogens that can cause a wide spectrum of disease. In this study, we describe a case of recurrent Aeromonas bacteremia in an immunocompetent patient, and this exposure was linked to the patient's home well water supply.

Natural disasters and myocardial infarction: the six years after Hurricane Katrina.

OBJECTIVE: To determine the prolonged effect of Hurricane Katrina on the incidence and timing of acute myocardial infarction (AMI) in the city of New Orleans. PATIENTS AND METHODS: Our study population consisted of 1476 patients with AMI before (August 29, 1999, to August 28, 2005) and after (February 14, 2006, to February 13, 2012) Hurricane Katrina at Tulane University Health Sciences Center to determine post-Katrina alterations in the occurrence and timing of AMI. RESULTS: Compared with pre-Katrina values, there was a more than 3-fold increase in the percentage of admissions for AMI during the 6 years after Hurricane Katrina (P<.001). The percentage of admissions for AMI after Hurricane Katrina increased significantly on nights (P<.001) and weekends (P<.001) and decreased significantly on mornings (P<.001), Mondays (P<.001), and weekdays (P<.001). Patients with AMI after Hurricane Katrina also had significantly higher rates of psychiatric comorbidities (P=.01), smoking (P<.001), lack of health insurance (P<.05), and unemployment (P<.001). CONCLUSION: These results indicate that the effect of natural disasters on the occurrence of AMI may persist for at least a 6-year period and may be related to various factors including population shifts, alterations in the health care system, and the effects of chronic stress and associated behaviors.

Inferior vena cava filter migration to the right ventricle causing nonsustained ventricular tachycardia.

Inferior vena cava filters are commonly used to prevent pulmonary embolism in patients who manifest deep vein thrombosis and recurrent pulmonary embolism despite anticoagulation, or in patients with contraindications to anticoagulation. We report the case of a 69-year-old man with a structurally normal heart who experienced migration of an inferior vena cava filter to the right ventricle, which caused the abrupt onset of recurrent episodes of nonsustained ventricular tachycardia unresponsive to intravenous antiarrhythmic medication. Cardiac imaging revealed the location of the filter within the right ventricle, and the device was removed, with subsequent resolution of the arrhythmia. We anticipate that the incidence of inferior vena cava filter migration might increase in the future because of recent changes in device construction. The sudden appearance of nonsustained ventricular tachycardia in a patient with an inferior vena cava filter might indicate the occurrence of this potentially life-threatening sequela and should lead to emergent cardiac imaging.