Household Influenza Transmission and Healthcare Resource Utilization Among Patients Treated with Baloxavir vs Oseltamivir: A United States Outpatient Prospective Survey.

INTRODUCTION: Influenza is a common, seasonal infectious disease with broad medical, economic, and social consequences. Real-world evidence on the effect of influenza treatment on household transmission and healthcare resource utilization is limited in outpatient settings in the USA. This study examined the real-world effectiveness of baloxavir vs oseltamivir in reducing influenza household transmission and healthcare resource utilization. METHODS: This prospective electronic survey on patient-reported outcomes was conducted between October 2022 and May 2023 via CVS Pharmacy in the USA. Adult participants (≥ 18 years old) were eligible if they filled a prescription for baloxavir or oseltamivir at a CVS Pharmacy within 2 days of influenza symptom onset. Participant demographics, household transmission, and all-cause healthcare resource utilization were collected. Transmission and utilization outcomes were assessed using χ2 and Fisher exact tests. RESULTS: Of 87,871 unique patients contacted, 1346 (1.5%) consented. Of 374 eligible patients, 286 (90 baloxavir- and 196 oseltamivir-treated patients) completed the survey and were included in the analysis. Mean age of participants was 45.4 years, 65.6% were female, and 86.7% were White. Lower household transmission was observed with baloxavir compared with oseltamivir therapy (17.8% vs 26.5%; relative risk = 0.67; 95% CI 0.41-1.11). Healthcare resource utilization, particularly emergency department visits (0.0% vs 4.6%), was also numerically lower in the baloxavir-treated group; no hospitalizations were reported in either cohort. CONCLUSIONS: The findings from this real-world study suggest that antiviral treatment of influenza with baloxavir may decrease household transmission and reduce healthcare resource utilization compared with oseltamivir.

Control of SARS-CoV-2 infection in skilled nursing facilities in Detroit, Michigan: a model for emerging infectious diseases.

An infection prevention bundle that consisted of the development of a response team, public-academic partnership, daily assessment, regular testing, isolation, and environmental controls was implemented in 26 skilled nursing facilities in Detroit, Michigan (March 2020-April 2021). This intervention was associated with sustained control of severe acute respiratory coronavirus virus 2 infection among residents and staff.

Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT).

BACKGROUND: Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics. METHODS: In DISRUPT, a superiority-design phase 3 study, patients with S. aureus bacteremia/endocarditis were randomly assigned to receive a single dose of IV exebacase or placebo in addition to standard-of-care antibiotics. The primary efficacy outcome was clinical response at Day 14 in the MRSA population. RESULTS: A total of 259 patients were randomized before the study was stopped for futility based on the recommendation of the unblinded Data Safety Monitoring Board. Clinical response rates at Day 14 in the MRSA population (n = 97) were 50.0% (exebacase + antibiotics; 32/64) vs. 60.6% (antibiotics alone; 20/33) (P = 0.392). Overall, rates of adverse events were similar across groups. No adverse events of hypersensitivity related to exebacase were reported. CONCLUSIONS: Exebacase + antibiotics failed to improve clinical response at Day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of Day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis.

LiaX is a surrogate marker for cell envelope stress and daptomycin non-susceptibility in Enterococcus faecium.

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistant Enterococcus faecium infections, but emergence of DAP non-susceptibility threatens the effectiveness of this antibiotic. Moreover, current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility and accuracy. In enterococci, DAP resistance is mediated by the LiaFSR cell membrane stress response system, and deletion of liaR encoding the response regulator results in hypersusceptibility to DAP and antimicrobial peptides. The main genes regulated by LiaR are a cluster of three genes, designated liaXYZ. In Enterococcus faecalis, LiaX is surface-exposed with a C-terminus that functions as a negative regulator of cell membrane remodeling and an N-terminal domain that is released to the extracellular medium where it binds DAP. Thus, in E. faecalis, LiaX functions as a sentinel molecule recognizing DAP and controlling the cell membrane response, but less is known about LiaX in E. faecium. Here, we found that liaX is essential in E. faecium with an activated LiaFSR system. Unlike E. faecalis, E. faecium LiaX is not detected in the extracellular milieu and does not appear to alter phospholipid architecture. We further postulated that LiaX could be used as a surrogate marker for cell envelope activation and non-susceptibility to DAP. For this purpose, we developed and optimized a LiaX enzyme-linked immunosorbent assay (ELISA). We then assessed 86 clinical E. faecium bloodstream isolates for DAP MICs and used whole genome sequencing to assess for substitutions in LiaX. All DAP-resistant clinical strains of E. faecium exhibited elevated LiaX levels. Strikingly, 73% of DAP-susceptible isolates by standard MIC determination also had elevated LiaX ELISAs compared to a well-characterized DAP-susceptible strain. Phylogenetic analyses of predicted amino acid substitutions showed 12 different variants of LiaX without a specific association with DAP MIC or LiaX ELISA values. Our findings also suggest that many E. faecium isolates that test DAP susceptible by standard MIC determination are likely to have an activated cell stress response that may predispose to DAP failure. As LiaX appears to be essential for the cell envelope response to DAP, its detection could prove useful to improve the accuracy of susceptibility testing by anticipating therapeutic failure.

Lessons from the field: Supporting infection prevention and control and antimicrobial stewardship in Amman, Jordan.

BACKGROUND: To reduce antimicrobial resistance (AMR), appropriate antimicrobial prescribing is critical. In conjunction with Infection Prevention & Control (IPC) programs, Antimicrobial Stewardship Programs (ASP) have been shown to improve prescribing practices and patient outcomes. Low- and middle-income countries (LMIC) face challenges related to inadequate ASP policies and guidelines at both the national and healthcare facility (HCF) levels. METHODS: To address this challenge, the World Health Organization (WHO) created a policy guidance and practical toolkit for implementation of ASPs in LMIC. We utilized this document to support a situational analysis and two-day ASP-focused workshop. In follow-up, we invited these attendees, additional HCF and hospital directors to attend a workshop focused on the benefits of supporting these programs. RESULTS: Over the course of a total three days, we recruited hospital directors, ASP team members, and IPC officers from fifteen different healthcare facilities in Jordan. We describe the courses and coordination, feedback from participants, and lessons learned for future implementation. CONCLUSIONS: Future efforts will include more time for panel-type discussion. which will assist in further delineating enablers and barriers. Also planned is a total three-day workshop; with the first two days being with ASP/IPC teams, and the final third day being with hospital directors and leadership. The WHO policy guidance and toolkit are useful tools to address overuse of antimicrobial agents. Strong leadership support is needed for successful implementation of ASP and IPC. Discussions on quality/safety, as well as cost analyses, are important to generate interest of stakeholders.

Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Hospitalized Patients in Peru.

There is a knowledge gap in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) causing bloodstream infections (BSIs) in Peru. Through a surveillance study in 13 hospitals of 10 Peruvian regions (2017-2019), we assessed the proportion of MRSA among S. aureus BSIs as well as the molecular typing of the isolates. A total of 166 S. aureus isolates were collected, and 36.1% of them were MRSA. Of note, MRSA isolates with phenotypic and genetic characteristics of the hospital-associated Chilean-Cordobes clone (multidrug-resistant SCCmec I, non-Panton-Valentine leukocidin [PVL] producers) were most commonly found (70%), five isolates with genetic characteristics of community-associated MRSA (CA-MRSA)-SCCmec IV, PVL-producer-(8.3%) were seen in three separate regions. These results demonstrate that hospital-associated MRSA is the most frequent MRSA found in patients with BSIs in Peru. They also show the emergence of S. aureus with genetic characteristics of CA-MRSA. Further studies are needed to evaluate the extension of CA-MRSA dissemination in Peru.

LiaX is a surrogate marker for cell-envelope stress and daptomycin non-susceptibility in Enterococcus faecium.

Daptomycin (DAP) is often used as a first line therapy to treat vancomycin-resistant Enterococcus faecium (VR Efm ) infections but emergence of DAP non-susceptibility threatens the effectiveness of this antibiotic. Moreover, current methods to determine DAP MICs have poor reproducibility and accuracy. In enterococci, DAP resistance is mediated by the LiaFSR cell membrane stress response system and deletion of liaR encoding the response regulator results in hypersusceptibility to DAP and antimicrobial peptides. The main genes regulated by LiaR are a cluster of three genes, designated liaXYZ . In Enterococcus faecalis , LiaX is surface exposed with a C-terminus that functions as a negative regulator of cell membrane remodeling and an N-terminal domain that is released to the extracellular medium where it binds DAP. Thus, in E. faecalis , LiaX functions as a sentinel molecule recognizing DAP and controlling the cell membrane response, but less is known about LiaX in E. faecium . Here, we found that liaX is essential in E. faecium ( Efm ) with an activated LiaFSR system. Unlike E. faecalis , Efm LiaX is not detected in the extracellular milieu and does not appear to alter phospholipid architecture. We further postulated that LiaX could be used as a surrogate marker for cell envelope activation and non-susceptibility to DAP. For this purpose, we developed and optimized a LiaX ELISA. We then assessed 86 clinical E. faecium BSI isolates for DAP MICs and used whole genome sequencing to assess for substitutions in LiaX. All DAP-R clinical strains of E. faecium exhibited elevated LiaX levels. Strikingly, 73% of DAP-S isolates by standard MIC determination had elevated LiaX ELISAs above the established cut-off. Phylogenetic analyses of predicted amino acid substitutions showed 12 different variants of LiaX without a specific association with DAP MIC or LiaX ELISA values. Our findings also suggest that many Efm isolates that test DAP susceptible by standard MIC determination are likely to have an activated cell stress response that may predispose to DAP failure. As LiaX appears to be essential for the cell envelope response to DAP, its detection could prove useful to improve the accuracy of susceptibility testing by anticipating therapeutic failure.

Aminopenicillins vs non-aminopenicillins for treatment of enterococcal lower urinary tract infections.

Aminopenicillins (APs) achieve urinary concentrations that exceed typical minimum inhibitory concentrations for enterococcal lower urinary tract infection (UTI). The local clinical microbiology laboratory discontinued routine susceptibilities on enterococcal urine isolates, and reports that 'APs are predictably reliable for uncomplicated enterococcal UTI'. The objective of this study was to compare outcomes of APs with non-APs (NAPs) for enterococcal lower UTIs. This was an institutional-review-board-approved, retrospective cohort of adults hospitalized with symptomatic enterococcal lower UTIs from 2013 to 2021. The primary endpoint was composite clinical success at 14 days, defined as resolution of symptoms without new symptoms and no repeat culture growth of the index organism. A non-inferiority analysis was utilized with a 15% margin, and logistic regression evaluated characteristics associated with 14-day failure. In total, 178 subjects were included: 89 AP patients and 89 NAP patients. Vancomycin-resistant enterococci (VRE) were identified in 73 (82%) AP patients and 76 (85%) NAP patients (P=0.54); in total, 34 (38.2%) AP patients and 66 (74.2%) NAP patients had confirmed Enterococcus faecium (P<0.001). Amoxicillin (n=36, 40.5%) and ampicillin (n=36, 40.5%) were the most commonly used APs, and linezolid (n=41, 46%) and fosfomycin (n=30, 34%) were the most commonly used NAPs. Fourteen-day clinical success rates for APs and NAPs were 83.1% and 82.0%, respectively [1.1% difference, 97.5% confidence interval (CI) -0.117 to 0.139]. Among the E. faecium subgroup, 14-day clinical success was observed in 27/34 (79.4%) AP patients and 53/66 (80.3%) NAP patients (P=0.916). On logistic regression, APs were not associated with 14-day clinical failure (adjusted odds ratio 0.84, 95% CI 0.38-1.86). APs were non-inferior to NAPs for treating enterococcal lower UTIs, and may be considered irrespective of susceptibility results.

COVID-19 vaccination up-take in three districts of Nepal.

Vaccine hesitancy during the COVID-19 pandemic continues to be an issue in terms of global efforts to decrease transmission rates. Despite high demand for the vaccines in Nepal, the country still contends with challenges related to vaccine accessibility, equitable vaccine distribution, and vaccine hesitancy. Study objectives were to identify: 1) up-take and intention for use of COVID-19 vaccines, 2) factors associated with vaccine up-take, and 3) trusted communication strategies about COVID-19 and the vaccines. A quantitative survey was implemented in August and September 2021 through an initiative at the Nepali Ministry of Health and Population Department of Health Services, Family Welfare Division. Data were collected from 865 respondents in three provinces (Bagmati, Lumbini, and Province 1). Ordinal multivariate logistic regression was utilized to determine relationships between vaccination status and associated factors. Overall, 62% (537) respondents were fully vaccinated and 18% (159) were partially vaccinated. Those respondents with higher education (p < .001) and higher household income (p < .001) were more likely vaccinated. There were also significant differences in vaccine up-take across the three provinces (p < .001). Respondents who were vaccinated were significantly more likely to perceive vaccines as efficacious in terms of preventing COVID-19 (p = .004) and preventing serious outcomes (p = .010). Among both vaccinated and unvaccinated individuals, there was a high level of trust in information about COVID-19 vaccines provided through local health-care workers [e.g. nurses and physicians]. These results are consistent with other findings within the South Asia region. Targeted advocacy and outreach efforts are needed to support ongoing COVID-19 vaccination campaigns throughout Nepal.

Pandemic response gaps: Infection prevention and control lessons learned during coronavirus disease 2019 (COVID-19) outbreaks in skilled nursing facilities in Detroit, Michigan.

BACKGROUND: Hospitalizations among skilled nursing facility (SNF) residents in Detroit increased in mid-March 2020 due to the coronavirus disease 2019 (COVID-19) pandemic. Outbreak response teams were deployed from local healthcare systems, the Centers for Disease Control and Prevention (CDC), and the Detroit Health Department (DHD) to understand the infection prevention and control (IPC) gaps in SNFs that may have accelerated the outbreak. METHODS: We conducted 2 point-prevalence surveys (PPS-1 and PPS-2) at 13 Detroit SNFs from April 8 to May 8, 2020. The DHD and partners conducted facility-wide severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing of all residents and staff and collected information regarding resident cohorting, staff cohorting, and personnel protective equipment (PPE) utilized during that time. RESULTS: Resident cohorting had been implemented in 7 of 13 (58.3%) SNFs prior to point-prevalence survey 1 (PPS-1), and other facilities initiated cohorting after obtaining PPS-1 results. Cohorting protocols of healthcare practitioners and environmental service staff were not established in 4 (31%) of 13 facilities, and in 3 facilities (23.1%) the ancillary staff were not assigned to cohorts. Also, 2 SNFs (15%) had an observation unit prior to PPS-1, 2 (15%) had an observation unit after PPS-1, 4 (31%) could not establish an observation unit due to inadequate space, and 5 (38.4%) created an observation unit after PPS-2. CONCLUSION: On-site consultations identified gaps in IPC knowledge and cohorting that may have contributed to ongoing transmission of SARS-CoV-2 among SNF residents despite aggressive testing measures. Infection preventionists (IPs) are critical in guiding ongoing IPC practices in SNFs to reduce spread of COVID-19 through response and prevention.

A Formative Assessment of Antibiotic Dispensing/Prescribing Practices and Knowledge and Perceptions of Antimicrobial Resistance (AMR) among Healthcare Workers in Lahore Pakistan.

(1) Background: Antimicrobial resistance causes significant disease burden in low- and middle-income countries. The objective of this paper is to describe antibiotic dispensing/prescribing practices and underlying factors associated with these practices among community-based healthcare workers. (2) Methods: Cross-sectional survey data were collected from private and public health facilities in 14 union councils, Lahore Pakistan. Respondents included physicians, nurses, lady health workers/volunteers, midwives, pharmacy and medicine shop employees, and medical technicians. Descriptive and bivariate analysis are used to present the data; (3) Results: 177 respondents completed the survey. In terms of weekly dispensing of antibiotics, the most common were Amoxicillin/Augmentin (2.3 [SD 1.5]), Cefixine (2.4 [SD 1.6]), and Azithromycin (2.5 [SD 2.1]). For children, antibiotics were more likely to be prescribed/dispensed for sore throat (54.3%/95) and diarrhea (48.9%/86). For adults, antibiotics were more likely to be prescribed/dispensed for sore throat (67.0%/118), diarrhea (59.7%/105) and burning sensation when urinating (55.7%/176). In total, 55.4% of respondents stated that they have sold partial antibiotic courses to patients/customers. A total of 44.6% of respondents incorrectly answered that antibiotics could be used for viral infections; (4) Conclusions: Data from this study and similar research emphasize the urgent need to implement community-based stewardship programs for all healthcare workers.

Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

A Case of Malaria-Associated Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory syndrome of inappropriate and excessive immune system activation. It often occurs in the setting of viral, bacterial, fungal, and parasitic infections. HLH associated with malaria is very rare, and literature on this association is limited. Significant overlap exists between these two conditions, which makes the diagnosis of HLH superimposed on malaria difficult. We present a case of a patient who recently traveled from Djibouti and was diagnosed with Plasmodium falciparum malaria. She had a transient improvement in response to antimalarial therapy followed by clinical deterioration. This prompted further investigations that revealed the diagnosis of HLH, which was confirmed by an elevated soluble interleukin-2 receptor CD25 (sCD25) level, a specific marker of HLH. Most patients recover with antimalarial therapy, supportive care, and monitoring, whereas some patients require immunosuppressive therapy. Maintaining a high index of suspicion for HLH-associated malaria in at-risk patients allows for early identification and management.

PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts.

Background: The prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population. Methods: Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and Drug Administration guidance and a subset potentially eligible for antibacterial trial enrollment. We compared patient characteristics, treatment exposures, and pneumonia incidence in a European cohort and a previously described US cohort. Results: Of 888 high-risk patients, 211/888 (24%) were treated for possible pneumonia, and 150/888 (17%) met the Food and Drug Administration definition for hospital-acquired/ventilator-associated bacterial pneumonia. A higher proportion of European patients treated for possible pneumonia met the pneumonia definition (150/211 [71%] vs 537/1464 [37%]; P < .001). Among patients developing pneumonia, a higher proportion of European patients met antibacterial trial eligibility criteria (124/150 [83%] vs 371/537 [69%]; P < .001). Conclusions: Clinical criteria prospectively identified high-risk patients with high rates of pneumonia in the European cohort. Despite higher rates of established risk factors and incident pneumonia, European patients were significantly less likely to receive antibiotics for possible pneumonia than US patients. Different treatment practices may contribute to lower rates of antibacterial trial enrollment in the United States.

Antibiotic Stewardship in Disaster Situations: Lessons Learned in Lebanon.

A post-prescription review and feedback program was implemented as an antimicrobial stewardship intervention in Lebanon as the country grappled with complete economic collapse, the COVID-19 pandemic, and a large blast in Beirut. We describe the implications of antimicrobial use in disaster preparedness and crisis situations, the sequelae related to increasing antimicrobial resistance, and our lessons learned in Lebanon. We explore opportunities and potential solutions for future disaster preparedness.

The Impact of a Post-Prescription Review and Feedback Antimicrobial Stewardship Program in Lebanon.

Antimicrobial stewardship programs (ASPs) are effective means to optimize prescribing practices. They are under-utilized in the Middle East where many challenges exist for ASP implementation. We assessed the effectiveness of infectious disease physician-driven post-prescription review and feedback as an ASP in Lebanon. This prospective cohort study was conducted over an 18-month period in the medical, surgical, and intensive care units of a tertiary care hospital. It consisted of three phases: the baseline, intervention, and follow-up. There was a washout period of two months between each phase. Patients aged ≥16 years receiving 48 h of antibiotics were included. During the intervention phase, the AMS team reviewed antimicrobial use within 72 h post-prescription and gave alternate recommendations based on the guidelines for use. The acceptance of the recommendations was measured at 72 h. The primary outcome of the study was days of therapy per 1000 study patient days. A total of 328 patients were recruited in the baseline phase (August−October 2020), 467 patients in the intervention phase (January−June 2021), and 301 patients in the post-intervention phase (September−December 2021). The total days of therapy decreased from 11.46 during the baseline phase to 8.64 during the intervention phase (p < 0.001). Intervention acceptance occurred 88.5% of the time. The infectious disease physician-driven implementation of an ASP was successful in reducing antibiotic utilization in an acute care setting in Lebanon.

Pharmacist-Driven Transitions of Care Practice Model for Prescribing Oral Antimicrobials at Hospital Discharge.

Importance: Although prescribers face numerous patient-centered challenges during transitions of care (TOC) at hospital discharge, prolonged duration of antimicrobial therapy for common infections remains problematic, and resources are needed for antimicrobial stewardship throughout this period. Objective: To evaluate a pharmacist-driven intervention designed to improve selection and duration of oral antimicrobial therapy prescribed at hospital discharge for common infections. Design, Setting, and Participants: This quality improvement study used a nonrandomized stepped-wedge design with 3 study phases from September 1, 2018, to August 31, 2019. Seventeen distinct medicine, surgery, and specialty units from a health system in Southeast Michigan participated, including 1 academic tertiary hospital and 4 community hospitals. Hospitalized adults who had urinary, respiratory, skin and/or soft tissue, and intra-abdominal infections and were prescribed antimicrobials at discharge were included in the analysis. Data were analyzed from February 18, 2020, to February 28, 2022. Interventions: Clinical pharmacists engaged in a new standard of care for antimicrobial stewardship practices during TOC by identifying patients to be discharged with a prescription for oral antimicrobials and collaborating with primary teams to prescribe optimal therapy. Academic and community hospitals used both antimicrobial stewardship and clinical pharmacists in a multidisciplinary rounding model to discuss, document, and facilitate order entry of the antimicrobial prescription at discharge. Main Outcomes and Measures: The primary end point was frequency of optimized antimicrobial prescription at discharge. Health system guidelines developed from national guidelines and best practices for short-course therapies were used to evaluate optimal therapy. Results: A total of 800 patients prescribed oral antimicrobials at hospital discharge were included in the analysis (441 women [55.1%]; mean [SD] age, 66.8 [17.3] years): 400 in the preintervention period and 400 in the postintervention period. The most common diagnoses were pneumonia (264 [33.0%]), upper respiratory tract infection and/or acute exacerbation of chronic obstructive pulmonary disease (214 [26.8%]), and urinary tract infection (203 [25.4%]). Patients in the postintervention group were more likely to have an optimal antimicrobial prescription (time-adjusted generalized estimating equation odds ratio, 5.63 [95% CI, 3.69-8.60]). The absolute increase in optimal prescribing in the postintervention group was consistent in both academic (37.4% [95% CI, 27.5%-46.7%]) and community (43.2% [95% CI, 32.4%-52.8%]) TOC models. There were no differences in clinical resolution or mortality. Fewer severe antimicrobial-related adverse effects (time-adjusted generalized estimating equation odds ratio, 0.40 [95% CI, 0.18-0.88]) were identified in the postintervention (13 [3.2%]) compared with the preintervention (36 [9.0%]) groups. Conclusions and Relevance: The findings of this quality improvement study suggest that targeted antimicrobial stewardship interventions during TOC were associated with increased optimal, guideline-concordant antimicrobial prescriptions at discharge.

COVID-19 Vaccine Hesitancy among Arab Americans.

(1) Background: Coronavirus disease-2019 (COVID-19) vaccines have a significant impact on reducing morbidity and mortality from infection. However, vaccine hesitancy remains an obstacle in combating the pandemic. The Arab American (AA) population is understudied; thus, we aimed to explore COVID-19 attitudes within this community. (2) Methods: This was a cross-sectional study. An anonymous online survey was distributed to members of different AA associations and to the community through the snowball method. (3) Results: A total of 1746 participants completed the survey. A total of 92% of respondents reported having received at least one dose of a COVID-19 vaccine. A total of 73% reported willingness to receive a booster, and 72% plan to give their children the vaccine. On multivariate analysis, respondents were more likely to be vaccine-hesitant if they were hesitant about receiving any vaccine in general. They were less likely to be vaccine-hesitant if they were immigrants, over the age of 40, up to date on their general vaccination and if they believed that COVID-19 vaccines are safe and effective in preventing an infection. The belief that all vaccines are effective at preventing diseases was also associated with lower hesitancy. (4) Conclusions: This sample of AAs have higher vaccination rates and are more willing to vaccinate their children against COVID-19 when compared to the rest of the population. However, a reemergence of hesitancy might be arising towards the boosters.

Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I).

BACKGROUND: Vancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking. METHODS: The Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals. We included patients with Enterococcus faecalis or Enterococcus faecium BSI with ≥1 follow-up blood culture(s) within 7 days and availability of isolate(s) for further characterization. The primary study outcome was in-hospital mortality. Secondary outcomes were mortality at days 4, 7, 10, 12, and 15 after index blood culture. A desirability of outcome ranking was constructed to assess the association of vancomycin resistance with outcomes. All index isolates were subjected to whole genome sequencing. RESULTS: Forty-two of 232 (18%) patients died in hospital and 39 (17%) exhibited microbiological failure (lack of clearance in the first 4 days). Neutropenia (hazard ratio [HR], 3.13), microbiological failure (HR, 2.4), VRE BSI (HR, 2.13), use of urinary catheter (HR, 1.85), and Pitt BSI score ≥2 (HR, 1.83) were significant predictors of in-hospital mortality. Microbiological failure was the strongest predictor of in-hospital mortality in patients with E faecium bacteremia (HR, 5.03). The impact of vancomycin resistance on mortality in our cohort changed throughout the course of hospitalization. Enterococcus faecalis sequence type 6 was a predominant multidrug-resistant lineage, whereas a heterogeneous genomic population of E faecium was identified. CONCLUSIONS: Failure of early eradication of VRE from the bloodstream is a major factor associated with poor outcomes.