The association between influenza vaccine effectiveness and egg-based manufacturing technology: literature review and US expert consensus.

BACKGROUND: Influenza is associated with significant disease burden in the US and is currently best controlled by vaccination programs. Influenza vaccine effectiveness (VE) is low and may be reduced by several factors, including egg adaptations. Although non-egg-based influenza vaccines reportedly have greater VE in egg-adapted seasons, evidence for egg adaptations' reduction of VE is indirect and dissociated, apart from two previous European consensuses. METHODS: This study replicated the methodology used in a 2020 literature review and European consensus, providing an updated review and consensus opinion of 10 US experts on the evidence for a mechanistic basis for reduction of VE due to egg-based manufacturing methods. A mechanistic basis was assumed if sufficient evidence was found for underlying principles proposed to give rise to such an effect. Evidence for each principle was brought forward from the 2020 review and identified here by structured literature review and expert panel. Experts rated the strength of support for each principle and a mechanistic basis for reduction of VE due to egg-based influenza vaccine manufacture in a consensus method (consensus for strong/very strong evidence = ≥ 3.5 on 5-point Likert scale). RESULTS: Experts assessed 251 references (from previous study: 185; this study: 66). The majority of references for all underlying principles were rated as strong or very strong supporting evidence (52-86%). Global surveillance, WHO candidate vaccine virus selection, and manufacturing stages involving eggs were identified as most likely to impact influenza VE. CONCLUSION: After review of extensive evidence for reduction of VE due to egg-based influenza vaccine manufacture, influenza experts in the US joined those in Europe in unanimous agreement for a mechanistic basis for the effect. Vaccine providers and administrators should consider use of non-egg-based influenza vaccine manufacture to reduce the risk of egg adaptations and likely impact on VE.

Assessment of the impact of centralized bioMérieux BACT/ALERT® VIRTUO® blood culture system (VIRTUO) implementation on outcomes in patients with gram-negative bacteremia.

BACKGROUND: We evaluated pre- and postimplementation of Virtuo on outcome in patients with gram-negative bacteremia using a quasiexperimental time-in-motion design. METHODS: Becton Dickinson BACTEC™ 9000 series (Bactec) (2018) and Virtuo system (2020) were utilized in a decentralized and centralized process, respectively. Data collected in August-December in 2018 and 2020 were analyzed with SPSS (ver 28). RESULTS: For 185 patients in each time period, patient age, gender, length of hospitalization were not different. However, blood culture (BC) volume was significantly lower in 2020 (7.1 ± 2.6 mL) compared to 2018 (8.9 ± 1.9 mL). Time from BC draw and time from pathogen identification (ID) to treatment change were both significantly faster in 2020 (52.9 ± 38.3 hours; 15.1 ± 27.4 hours), compared to 2018 (65.0 ± 46.3 hours; 23.8 ± 33.8), respectively. CONCLUSIONS: Replacement of decentralized Bactec with centralized Virtuo, resulted in significant improvement in management of patients gram-negative bacteremia.

Discharge disposition and clinical outcomes of patients hospitalized with COVID-19.

OBJECTIVES: By better understanding the long-term effects of COVID-19 and assessing rehabilitation placement among the patients in our study, we hope to determine the predictors of rehabilitation needs in individuals suffering from the long-term sequelae of COVID-19. METHODS: A retrospective chart review was performed of adult patients with a positive COVID-19 polymerase chain reaction test among multiple hospitals in a regional health system. The main outcomes measured were discharge disposition, total length of hospital stay, and overall all-cause mortality and readmission rates within 30 and 90 days of discharge. RESULTS: Of the 2502 patients included in the study, we found that 65.2% were discharged to home, while the remaining patients were discharged to home healthcare (33.6%), skilled nursing facilities (31.7%), or long-term acute rehabilitation centers (11.6%). The overall all-cause mortality rate at 30 and 90 days were 2.7% and 4.4%, respectively. The overall all-cause 30-day and 90-day readmission rates were 7.0% and 7.6%, respectively. CONCLUSION: Younger age and shorter hospitalization stays were the most important predictors of home discharge. Discharge to home was also significantly associated with lower all-cause mortality rates at 30 and 90 days after discharge.

Improving understanding and utilization of the antibiogram among medical residents.

In this quality improvement project, we sought to increase the understanding and utilization of the antibiogram among physicians in family medicine, internal medicine, and surgery residency programs at a Midwest Academic Healthcare institution. Through simple, inexpensive measures the comfort with, access to, and utilization of the antibiogram can be improved.

COVID-19 Mortality and Therapeutics in Nebraska and Southwest Iowa during Early Pandemic.

Different pharmacotherapeutics have been introduced, and then stopped or continued, for the treatment of SARS-CoV-2. We evaluated the risks associated with mortality from SARS-CoV-2 infection. METHODS: Data was concurrently or retrospectively captured on COVID-19 hospitalized patients from 6 regional hospitals within the health system. Demographic details, the source of SARS-CoV-2 infection, concomitant disease status, as well as the therapeutic agents used for treating SARS-CoV-2 (e.g., antimicrobials, dexamethasone, convalescent plasma, tocilizumab, and remdesivir) were recorded. Discrete and continuous variables were analyzed using SPSS (ver. 27). Logistic regression identified variables significantly correlated with mortality. RESULTS: 471 patients (admitted from 1 March 2020 through 15 July 2020) were reviewed. Mean (±SD) age and body weight (kg) were 62.5 ± 17.7 years and 86.3 ± 27.1 kg, respectively. Patients were Caucasian (50%), Hispanic (34%), African-American (10%), or Asian (5%). Females accounted for 52% of patients. Therapeutic modalities used for COVID-19 illness included remdesivir (16%), dexamethasone (35%), convalescent plasma (17.8%), and tocilizumab (5.8%). The majority of patients returned home (62%) or were transferred to a skilled nursing facility (23%). The overall mortality from SARS-CoV-2 was 14%. Logistic regression identified variables significantly correlated with mortality. Intubation, receipt of dexamethasone, African-American or Asian ethnicity, and being a patient from a nursing home were significantly associated with mortality (x2 = 86.36 (13) p < 0.0005). CONCLUSIONS: SARS-CoV-2 infected hospitalized patients had significant mortality risk if they were intubated, received dexamethasone, were of African-American or Asian ethnicity, or occupied a nursing home bed prior to hospital admission.

Bamlanivimab use in mild-to-moderate COVID-19 disease: A matched cohort design.

STUDY OBJECTIVE: Our objective was to determine if bamlanivimab (LY-CoV555; BAM), a monoclonal antibody for mild-to-moderate Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co-V-2, prevented emergency department (ED) visits, hospitalizations for SARS-CoV-2, or death within 60 days of a positive SARS-CoV-2 viral test. DESIGN: Patient propensity matching was performed for BAM administration to get two discrete groups of patients; those who received BAM (N = 117) and those who did not (N = 117). SETTING: Outpatients (N = 2107) eligible to receive BAM from November 1 to December 31, 2020, were identified. PATIENTS: A total of 144 of 2107 patients with mild-to-moderate SARS-CoV-2 received BAM INTERVENTION: Eligible patients had mild-to-moderate SARS-CoV-2 disease, a positive SARS-CoV-2 test, and risk factor(s) for progression to severe SARS-CoV-2 infection. All patients were reviewed for subsequent ED visits, subsequent hospitalization, and death. MEASUREMENTS AND MAIN RESULTS: Patients (N = 234) were matched, 117 in each group. Median (interquartile range) age was 72 (65-80) years. Forty-seven percent of patients were male. Twenty-one patients who received BAM were subsequently seen in the ED compared to 34 untreated patients (18.0% vs. 29.1%; p = 0.045). Fourteen BAM-treated patients were subsequently hospitalized post-BAM infusion compared to 27 untreated patients (12.0% vs. 23.1%; p = 0.025). Finally, there were no mortalities in the BAM group, however, eleven patients in the untreated group died (0.0% vs. 9.4%; p < 0.001). The number needed to treat (NNT) is 11 patients to prevent one mortality event. CONCLUSIONS: BAM infusion for mild-to-moderate SARS-CoV-2 infection in outpatients significantly prevented subsequent ED visits, hospitalizations, and death from SARS-CoV-2.

Multisystem inflammatory syndrome in adults: A rare sequela of SARS-CoV-2 infection.

Multisystem inflammatory syndrome in adults (MIS-A) came to attention back in June 2020, when the United States Center for Disease Control and Prevention (CDC) received initial reports regarding patients who had presented delayed and multisystem involvement of the disease, with clinical course resembling multisystem inflammatory syndrome in children (MIS-C). This study introduces a case of MIS-A, where the patient presented 3 weeks after initial COVID-19 exposure. His clinical course was consistent with the working definition of MIS-A as specified by the CDC. Aggressive supportive care in the intensive care unit, utilization of advanced heart failure devices, and immunomodulatory therapeutics (high-dose steroids, anakinra, intravenous immunoglobulin) led to clinical recovery. Management of MIS-A is a topic of ongoing research and needs more studies to elaborate on treatment modalities and clinical predictors.

Implementation of a Health-System Wide Antimicrobial Stewardship Program in Omaha, NE.

The Centers for Medicare and Medicaid Services (CMS) have mandated that acute care and critical access hospitals implement an Antimicrobial Stewardship (AMS) Program. This manuscript describes the process that was implemented to ensure CMS compliance for AMS, across a 14-member health system (eight community hospitals, five critical access hospitals, and an academic medical center) in the Omaha metro area, and surrounding cities. The addition of the AMS program to the 14-member health system increased personnel, with a 0.5 full-time equivalent (FTE) infectious diseases (ID) physician, and 2.5 FTE infectious diseases trained clinical pharmacists to support daily AMS activities. Clinical decision support software had previously been implemented across the health system, which was also key to the success of the program. Overall, in its first year, the AMS program demonstrated a $1.2 million normalized reduction (21% total reduction in antimicrobial purchases) in antimicrobial expenses. The ability to review charts daily for antimicrobial optimization with ID pharmacist and physician support, identify facility specific needs and opportunities, and to collect available data endpoints to determine program effectiveness helped to ensure the success of the program.

A rare case of Shewanella septicemia: risk factors, environmental associations and management.

Shewanella species are Gram-negative, saprophytic, motile bacilli. Exposure to aquatic environment and raw fish ingestion have been defined as significant associated risk factors. The two species most commonly associated with human infections are Shewanella algae and Shewanella putrefaciens and major portion of infections (80%) caused by the former. Herein, we report a case of Shewanella septicaemia in a 70-year-old man in Omaha, NE who had no exposure to aquatic environment. To date, no defined treatment guidelines are present due to rarity of Shewanella infections, which is contributing to emerging antibiotic resistance.

Trends in the use of echocardiography in patients with Staphylococcus aureus bacteremia: an analysis using the Nationwide Inpatient Sample data.

BACKGROUND: Infective endocarditis occurs in approximately 10%-30% of patients with Staphylococcus aureus bacteremia (SaB). Guidelines recommend echocardiography in patients with SaB and risk factors for infective endocarditis in the absence of any obvious source of infection. Herein, we explored the trends in the use of echocardiography in patients with SaB and its relationship to outcomes using a large national database. METHOD: All patients with a principal discharge diagnosis of SaB were identified using the National Inpatient Sample database from 2001 to 2014. Procedure code 88.72 was used to identify echocardiography. Logistic regression models were estimated to identify the year-over-year trends in echocardiogram, predictors of use, and association with mortality. RESULTS: From 2001 to 2014, there were 668 423 hospitalizations with SaB diagnosis and 86 387 (12.9%) had echocardiogram. The rate of echocardiography increased from 10.7% in 2001 to 15.2% in 2014 (ptrend  < 0.001). Major predictors of echocardiogram usage were younger age, male gender, presence of sepsis, valvular or congenital heart disease, prosthetic heart valve (PHV), cardiac implantable electronic device (CIED), hemodialysis, and drug abuse. The adjusted rates of echocardiography increased from approximately 10% to 15% in hospitalizations without risk factors for IE while for high-risk groups like PHV and CIED it remained constant at 30% and 19%, respectively. Echocardiography was associated with 31% lower odds of in-hospital mortality. CONCLUSION: The increase in echocardiography rate was largely attributable to increased use in those without risk factors while usage in those with PHV and CIED remained much lower than expected. Echocardiography use was associated with lower risk-adjusted mortality. These findings require further study and confirmation.

Effect of antimicrobial stewardship with rapid MALDI-TOF identification and Vitek 2 antimicrobial susceptibility testing on hospitalization outcome.

We sought to evaluate time for bacterial culture and initiation of appropriate therapy for patients, from 2017 (without rapid diagnostic test (RDT) and Antimicrobial Stewardship Program (ASP)) and 2018 (with RDT and ASP). Time to identification (ID) was significantly faster in 2018 (2018 24.9 ±â€¯14.4, 2017 33.8 ±â€¯17 h, P = 0.001). Time to antimicrobial susceptibility test (AST) results was significantly faster for patients in 2018 compared to 2017 (18.2 ±â€¯14 h compared to 28.5 ±â€¯14.9 h, P < 0.001). Length of hospital stay for enrolled patients was significantly shorter in 2018 compared to 2017 (2018 10.7 ±â€¯11.1 days and 2017 15.5 ±â€¯18.1 days, P = 0.05). Length of antimicrobial therapy for enrolled patients was significantly shorter for 2018 (2018 6.7 ±â€¯3.8 d vs. 2017 8.8 ±â€¯7.8 d, P = 0.036). These results demonstrate MALDI-TOF/Vitek 2 leads to an average 21.5 h faster ID and AST results that can be acted upon by ASP for antimicrobial recommendations.

Correction to: Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model.

There are errors in the published article (Volume 34, Number 12, pp. 2749-2755). The errors occurred in pharmacokinetic study design of materials and methods section on page 2750-51.

Postpartum Invasive Group A Streptococcus Infection: Case Report and Mini-review.

The overall incidence of postpartum invasive group A streptococcal (GAS) disease is low in the United States. However, postpartum women are much more likely to develop GAS disease than nonpregnant women. Additionally, postpartum GAS has the potential to develop into a severe disease and a delay in diagnosis can have deadly consequences. This case describes a patient with invasive postpartum endometritis in the setting of diastases of the pubic symphysis. Sepsis secondary to the endometritis develops along with bilateral pneumonia. This case characterizes some of the typical and atypical symptoms a patient with invasive postpartum GAS can present with. Further, it outlines the timely identification of the disease and its appropriate treatment to prevent a potentially disastrous outcome.

Maxillary Teeth Abscesses Result in Atypical Liver Abscesses.

Hepatic liver abscesses are often misdiagnosed on initial presentation because pyogenic liver lesions are a rare occurrence in the United States. This leads to a delay in proper treatment and results in increasing morbidity and mortality. Our case report demonstrates the atypical presentation of a hepatic liver abscess in the elderly. The source of infection was found to be periapical abscesses of the teeth, which subsequently seeded the portal blood stream of our patient. Our findings validate the potential hazard of Viridans streptococci and illustrate how untreated dental infections can serve as a reservoir for a systemic infection.

Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model.

PURPOSE: Non-adherence to the antiretroviral (ARV) regimen is a critical factor in determining efficacy of ARV drugs for pre-exposure prophylaxis (PrEP). A long-acting parenteral formulation may be an effective alternative to daily oral dosing. A pharmacokinetic and tissue distribution study of drug-loaded nanoparticle (NP) was performed in female humanized CD34+-NSG mice. METHODS: Mice received 200 mg/kg each of tenofovir alafenamide (TAF) and elvitegravir (EVG) as free drugs (TAF + EVG solution) or as drug loaded NP (TAF + EVG NP) formulation by subcutaneous (SubQ) administration. Plasma and tissue were collected to determine tenofovir (TFV) and EVG concentrations using LC-MS/MS. Non-compartmental analysis was performed using WinNonlin. RESULTS: SubQ administration of TAF + EVG NP formulation resulted in long residence time and exposure for both drugs. The AUC(0-72h) of TFV and EVG was 14.1 ± 2.0, 7.2 ± 1.8 µg × hr./mL from drugs in solution (free) and the AUC(0-14day) for the same drugs was 23.1 ± 4.4, 39.7 ± 6.7 µg × hr./mL from NPs. The observed elimination half-life (t1/2) for TFV of free and NPs were 14.2 h, 5.1 days and for EVG 10.8 h, 3.3 days, respectively. CONCLUSION: This study documents that a TAF + EVG NP provides sustained release, which can overcome patient non-adherence to dosing and may facilitate prediction of appropriate protective drug concentration for HIV prophylaxis.

Evaluation of Staphylococcus aureus Bacteremia: Academic and Community-Based Management Within the Same Health System.

A nonrandomized, retrospective comparison of Staphylococcus aureus bacteremia between an academic hospital setting (n=53) and a community hospital setting (n=245) within a single healthcare system was performed. Despite infectious disease consultations, S. aureus bacteremia management recommendations based on Infectious Diseases Society of America (IDSA) guidelines were not followed as closely in the community hospital setting. The community hospital setting requires management standardization for patients with S. aureus bacteremia. Infect Control Hosp Epidemiol 2017;38:740-742.

Rare Multidrug-Resistant Pulmonary Nocardiosis in AIDS.

Nocardiosis is an opportunistic infection in patients with depressed cell-mediated immunity. Inhalation is the primary route for exposure via dust particles. Patients with acquired immune deficiency syndrome (AIDS) are at increased risk of disseminated disease. A challenge in the diagnosis of pulmonary nocardiosis is that it can mimic other pulmonary diseases. Nocardia farcinica tends to be a more virulent, multidrug-resistant strain with an increased tendency to disseminate. This report describes a 64-year-old man with AIDS found to have pulmonary nocardiosis that did not respond to standard antibiotic therapy. Further evaluation revealed the virulent, multidrug-resistant Nocardia farcinica species. Targeted antibiotic therapy was initiated, after which the patient had an improvement in pulmonary symptoms. It is important to suspect pulmonary nocardiosis in immunocompromised patients who fail to respond to standard antimicrobial therapy. Susceptibilities should be obtained so that appropriate therapy can be promptly initiated as Nocardia farcinica is highly resistant to multiple antimicrobials.

Education and Communication in an Interprofessional Antimicrobial Stewardship Program.

CONTEXT: Interprofessional education/interprofessional practice (IPE/IPP) is an essential component in medical education and training. A collaborative interprofessional team environment ensures optimal patient-centered care. OBJECTIVE: To describe the implementation of 2 interprofessional antimicrobial stewardship program (ASP) teams using IPE/IPP and to assess the acceptance rate by the primary medical and surgical teams of ASP recommendations for antimicrobial interventions. METHODS: A business plan for the ASP was approved at 2 academic medical centers used for the present study. During a 3-year study period, 2 interprofessional ASP teams included an attending physician specializing in infectious disease (ID), an ID physician fellow, an ASP pharmacist, physician residents, medical students, pharmacy residents, and pharmacy students. Educational seminars were presented for all adult-admitting physicians to discuss the need for the ASP and the prospective audit and feedback process. Cases were presented for discussion during ASP/ID rounds and recommendations were agreed upon by the ASP team. A motivational interviewing face-to-face technique was frequently used to convey the ASP team recommendation to the primary medical or surgical team in a noncoercive and educational manner. The ASP team recommendations for ASP interventions were documented in the medical records. RESULTS: The overall acceptance rate of recommendations by the primary medical and surgical teams were greater than 90% (2051 of 2266). The most frequent interventions provided were streamline therapy (601), route of administration change (452), bug-drug mismatch (190), and discontinuation of therapy (179). Route of administration change was also the most frequently accepted intervention (96%). CONCLUSIONS: The motivational face-to-face communication technique was particularly useful in conveying ASP team member recommendations to the primary medical or surgical teams. Communicating recommendations as a multidisciplinary team in an educational manner seems to have resulted in to greater acceptance of recommendations.