Treatment Of Influenza Research Articles

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Simulation of Influenza Polymerase PB2 Inhibitors

The PB2 subunit of the influenza RNA-dependent RNA polymerase (RdRp) has been identified as a promising target for the treatment of influenza. To expand the chemical space of the known influenza polymerase PB2 inhibitor-pimodivir (formerly VX-787) and improve its pharmacokinetic profile, two pimodivir analogs containing 2,3-dihydro-imidazopyridine fragment (comp. I and comp. II) were designed, synthesized, and evaluated for anti-influenza virus activity. In the cytopathic effect (CPE) inhibition assay, comp. I and comp. II showed IC50 values of 0.07 and 0.09 μM for A/Puerto Rico/8/34 (H1N1) and 0.04 and 0.07 μM for A/Hong Kong/8/68 (H3N2), respectively. Protein-binding affinity assay results showed a concentration-dependent association and dissociation pattern, with KD values of 1.398 and 1.670 μM, respectively. In vitro metabolic stability assays showed that comp. I and comp. II exhibited good stability to liver microsomes and considerably less sensitivity to aldehyde oxidase compared to pimodivir. The binding modes of comp. I and comp. II were similar to those of VX-787; however, comp. I and comp. II had lower structural adaptability to PB2 than VX-787. Our results provide helpful information regarding the structure-activity relationship for the design of novel PB2 inhibitors and a reference for the development of drugs containing 2,3-dihydro-imidazopyridine fragments.

IN VITRO ANTI-DIABETIC ACTIVITY PUNICA GRANATUM LINN LEAF EXTRACT

Objective: The present investigation deals with the study of in vitro anti-diabetic activity by inhibition of intestinal absorption of glucose by alpha-amylase method. Punica granatum L plant is a fruit-bearing deciduous shrub. It is used in the treatment of pneumonia as a bitter tonic also used in the treatment of flu, mouth and lip infection, antifungal, and immunosuppressant which used to treat heart disorders, stomach disorders, dental care, anemia, osteoarthritis, and anti-diabetic. The intestinal digestive enzymes such as alpha-glucosidase and alpha-amylase have played a vital role in carbohydrate digestion that these can be an important approach in managing of blood glucose. Methods: The air-dried powder of P. granatum Linn (leaf part) was extracted using a Soxhlet apparatus with ethanol extract of Psidium guajava (EEPG) and water aqueous extract of P. granatum (AEPG) as solvent. The extracts were concentrated under reduced pressure. The activities were carried out using the following concentration (10, 20, 30, 40, and 50 μg/mL) and compared with Acarbose as standard drug. It has significant in vitro anti-diabetic in alpha-amylase method. Results: The extract of P. granatum possessed significant anti-diabetic property in EEPG than compared to AEPG. Conclusion: Activity may be due to the presence of chemical profile such as glycosides, flavonoids, and terpenoids. The results of the study have suggested in the use of P. granatum Linn. as a potent anti-diabetic in several applications.

High Light Intensity Triggered Abscisic Acid Biosynthesis Mediates Anthocyanin Accumulation in Young Leaves of Tea Plant (Camellia sinensis)

There is increasing interest in the production and consumption of tea (Camellia sinensis L.) processed from purple-leaved cultivar due to their high anthocyanin content and health benefits. However, how and why seasonal changes affect anthocyanin accumulation in young tea leaves still remains obscured. In this study, anthocyanin and abscisic acid (ABA) contents in young leaves of Zifuxing 1 (ZFX1), a cultivar with new shoots turning to purple in Wuyi Mountain, a key tea production region in China, were monitored over four seasons. Young leaves produced in September were highly purplish, which was accompanied with higher anthocyanin and ABA contents. Among the environmental factors, the light intensity in particular was closely correlated with anthocyanin and ABA contents. A shade experiment also indicated that anthocyanin content significantly decreased after 168 h growth under 75% shade, but ABA treatment under the shade conditions sustained anthocyanin content. To confirm the involvement of ABA in the modulation of anthocyanin accumulation, anthocyanin, carotenoids, chlorophyll, ABA, jasmonic acid (JA), and salicylic acid (SA) in the young leaves of four cultivars, including ZFX1, Zijuan (ZJ), wherein leaves are completely purple, Rougui (RG) and Fudingdabaicha (FDDB) wherein leaves are green, were analyzed, and antioxidant activities of the leaf extracts were tested. Results showed that ABA, not other tested hormones, was significantly correlated with anthocyanin accumulation in the purple-leaved cultivars. Cultivars with higher anthocyanin contents exhibited higher antioxidant activities. Subsequently, ZFX1 plants were grown under full sun and treated with ABA and fluridone (Flu), an ABA inhibitor. ABA treatment elevated anthocyanin level but decreased chlorophyll contents. The reverse was true to those treated with Flu. To pursue a better understanding of ABA involvement in anthocyanin accumulation, RNA-Seq was used to analyze transcript differences among ABA- or Flu-treated and untreated ZFX1 plants. Results indicated that the differentially expressed genes in ABA or Flu treatment were mainly ABA signal sensing and metabolism-related genes, anthocyanin accumulation-related genes, light-responsive genes, and key regulatory MYB transcription factors. Taking all the results into account, a model for anthocyanin accumulation in ZFX1 cultivar was proposed: high light intensity caused reactive oxygen stress, which triggered the biosynthesis of ABA; ABA interactions with transcription factors, such as MYB-enhanced anthocyanin biosynthesis limited chlorophyll and carotenoid accumulation; and transport of anthocyanin to vacuoles resulting in the young leaves of ZFX1 with purplish coloration. Further research is warranted to test this model.

Inhibitory effects of Patchouli alcohol on the early lifecycle stages of influenza A virus.

The antiviral activity and underlying mechanism of Patchouli alcohol remain unclear. This study evaluated the cytotoxicity, optimal methods for drug administration, anti-influenza A activity of Patchouli alcohol. The antiviral mechanism of Patchouli alcohol was also assessed via qRT-PCR, western blot, hemagglutination inhibiting (HAI) assay, and hemolysis inhibiting assay. Patchouli alcohol was shown to have low cytotoxicity and its strongest antiviral effect was associated with premixed administration. Patchouli alcohol inhibited virus replication during the early lifecycle stages of influenza A virus infection and specifically prevented expression of the viral proteins, HA and NP. In both the HAI and hemolysis inhibiting assays, Patchouli alcohol was able to block HA2-mediated membrane fusion under low pH conditions. Patchouli alcohol had lower binding energy with HA2 than HA1. These findings suggest that Patchouli alcohol could be a promising membrane fusion inhibitor for the treatment of influenza A infection.

Baloxavir marboxil as a new specific anti-influenza drug

Baloxavir marboxil is the first antiviral drug with a unique single dose, registered in Russia in September 2020 under the trade name Xoflusa, for treating infection caused by influenza A and B viruses.
 This article presents an overview of studies on the anti-influenza activity of baloxavir marboxil by foreign colleagues. Data from scientific articles by different authors were analyzed and in vitro results and clinical data were considered, which can help in making recommendations for the use of the drug for the treatment and postexposure prophylaxis of influenza.
 Baloxavir marboxil acts as a selective low-molecular-weight inhibitor of an enzyme specific to the influenza virus in the viral RNA polymerase complex and is effective against strains resistant to oseltamivir. In the combined phenotypic analysis and analysis based on the sequence in the polymerase acidic (PA) protein, the frequency of viruses showing reduced susceptibility to the drug remains low.
 Numerous studies have demonstrated the safety profile and productivity of influenza treatment in various groups (without risk factors and high-risk patients). Baloxavir marboxil stops the replication of the influenza virus in the early stages, which terminates its release during the first day and significantly relieves the patients condition on the second day. Monitoring of the antiviral activity of the drug, especially in children aged 12 years and people with weakened immunity, should be closely monitored to develop clinical recommendations and prevent the formation of substitutions I38(T/F/M/S/L/V) in the PA of influenza A and B viruses that reduce their sensitivity to the drug.

Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy.

Influenza infection is serious and debilitating for humans and animals. The influenza virus undergoes incessant mutation, segment recombination, and genome reassortment. As a result, new epidemics and pandemics are expected to emerge, making the elimination challenging of the disease. Antiviral therapy has been used for the treatment of influenza since the development of amantadine in the 1960s; however, its use is hampered by the emergence of novel strains and the development of drug resistance. Thus, combinational therapy with two or more antivirals or immunomodulators with different modes of action is the optimal strategy for the effective treatment of influenza infection. In this review, we describe current options for combination therapy, their performance, and constraints imposed by resistance, calling attention to the advantages of combination therapy against severe influenza infections. We also discuss the challenges of influenza therapy and the limitations of approved antiviral drugs.

Better design leads to better results - Importance of virological outcome design in clinical trials for antiviral treatment of coronavirus disease 2019.

Better design leads to better results - Importance of virological outcome design in clinical trials for antiviral treatment of coronavirus disease 2019.

Successful Treatment of Complicated Influenza A(H3N2) Virus Infection and Rhabdomyolysis with Compassionate Use of IV Zanamivir

In 2019, EMA licensed intravenous (IV) zanamivir for severe influenza virus infection in children over 6 months as well as adults. Prior to that, it was possible via a compassionate use program. We present successful compassionate use of IV zanamivir in a 14-year-old female with severe influenza A(H3N2) and multi-organ failure, who had failed oral oseltamivir. Her illness was complicated by acute respiratory distress syndrome and rhabdomyolysis requiring extracorporeal membrane oxygenation and hemofiltration. Considering the broad safety margins with neuraminidase inhibitors, an adult dose of 600 mg IV BID was administered in this 60 kg patient. Influenza virus was cleared rapidly and undetectable on day 13. Creatine kinase (CK) values were dropping from 38,000 to 500 within nine days. Given the recent licensure of IV zanamivir, multi-center prospective observational studies in pediatric Intensive Care Unit patients would be beneficial to guide the most appropriate use of IV zanamivir in this vulnerable age group.

Comparative effectiveness of oseltamivir versus peramivir for hospitalized children (aged 0-5 years) with influenza infection

ObjectivesThe effectiveness of oseltamivir versus peramivir in children infected with influenza remains unclear. This study aimed to evaluate their effectiveness in young children (aged 0-5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV). MethodsWe analyzed a cohort of 1662 young children with either IAV (N = 1095) or IBV (N = 567) who received oseltamivir or peramivir treatment from January 1, 2018 to March 31, 2022. Propensity score matching methods were applied to match children who were oseltamivir-treated versus peramivir-treated. ResultsChildren who were IAV-infected and IBV-infected shared similar features, such as influenza-associated symptoms and comorbidities at baseline. Among children infected with IAV with bacterial coinfection, the recovery rate was significantly greater in children treated with oseltamivir than in children treated with peramivir (15.6% vs 4.4%, P = 0.01). The median duration of hospitalization was also shorter in children treated with oseltamivir. Among children infected with IAV without bacterial coinfection, the recovery rate was greater in children treated with oseltamivir than in children treated with peramivir (21.1% vs 3.7%, P = 0.002). However, oseltamivir and peramivir offered similar recovery rates and duration of hospitalization (P >0.05 for both) among children infected with IBV. ConclusionOseltamivir and peramivir exhibit similar effectiveness in young children with severe influenza B, whereas oseltamivir demonstrated improved recovery and shorter hospitalization in the treatment of severe influenza A in hospitalized children.

Influenza in Pregnancy

Pregnant women should avoid places with too many people during a influenza epidemic and people who already have influenza. The immune system of pregnant women is very sensitive and prone to attacks by viruses and bacteria, and the treatment of flu during pregnancy takes longer than usual. Influenza during pregnancy can increase the duration of the infection and can lead to more serious complications, such as pneumonia. More severe cases of influenza in pregnant women can end up in hospitalization of pregnant women. As the influenza has a bad effect on the health of the pregnant woman herself, it can unfortunately also affect the fetus and can lead to the birth of a child with a low birth weight and premature birth.

The Therapeutic Efficacy of Lianhua Qingwen Granule Combined with Peramivir Sodium Chloride Injection in Treating Influenza and Serum Inflammatory Factors

To examine the therapeutic efficacy of Lianhua Qingwen granule combined with peramivir sodium chloride injection in treating influenza and level changes of serum inflammatory factors. The clinical data of 100 influenza sufferers enrolled in our infirmary from January 2018 to January 2020 retrospectively analyzed and they were randomized in the contrast group (n=50) and the experience group (n=50). The former was provided with peramivir sodium chloride injection, while the latter was medicated with Lianhua Qingwen granule after peramivir sodium chloride injection. The clinical efficacy, serum inflammatory factor, C-reactive protein, interleukin-6 level and procalcitonin level of both groups of sufferers were compared. The overall response rate of the injected group was 80 %, lower compared with 96 % of the injected and medicated group (p<0.05). The antipyretic time and sore throat disappearance time, cough disappearance time and general ache disappearance duration in the medicated group were remarkably shorter than those without Lianhua Qingwen powder (p<0.05). The differences in interleukin-6, C-reactive protein and procalcitonin levels before treatment between both groups were not statistically remarkable (p>0.05) and the levels of interleukin-6, C-reactive protein and procalcitonin of both groups of sufferers decreased after treatment. The levels of interleukin-6, C-reactive protein and procalcitonin of patients got injection and took medicine were remarkably lower than those who had no granule (p<0.05). Lianhua Qingwen granule combined with peramivir sodium chloride injection shows a remarkable potency in the treatment of influenza. It can shorten the treatment time and reduce the level of serum inflammatory factors. It is worthy of clinical promotion and application.

Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virus-induced oxidative stress.

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Эффективность нового режима дозирования препарата Виферон® в терапии гриппа и других ОРВИ у детей разного возраста с нарушениями в состоянии здоровья

Purpose. To study the efficacy and safety of a new dosing regimen of Viferon®, rectal suppositories, in the treatment of influenza and other acute respiratory viral infections (ARVI) in children from 1 month of age. up to 18 years of age with deviations in the state of health (related to II–IV health groups). Patients and methods. Conducted a double-blind placebo-controlled study involving 260 children aged 1 month up to 18 years of health groups II–IV, patients with influenza and other acute respiratory viral infections, who were randomized into 2 groups: 129 people group 1 received Viferon®, rectal suppositories, 131 people group 2 – placebo according to one of the three treatment regimens in accordance with the age of the children. All patients received standard therapy: antipyretics, anticongestants, mucolytics, if necessary, antihistamines and antibacterials. Clinical and laboratory observation was carried out within 10 days of therapy and then 1, 3 and 6 months after the start of treatment. Statistical processing was carried out using the statistical software Statistica 13.0. Null hypotheses were rejected at p &lt; 0.05. Results. The inclusion of the drug Viferon®, rectal suppositories, in the complex therapy of influenza and other acute respiratory viral infections in children of II–IV health groups, compared with Placebo, significantly reduces the period of improvement by 2.82 days (p = 0.0001, Tukey's test), by 2.85 days of recovery (p = 0.0001, Tukey's test), contributes to a 3.5-fold decrease in the proportion of patients with complications (p &lt; 0.001), and also allows a significant reduction in the number of episodes of influenza and other acute respiratory viral infections during the follow-up period after 1, 3 and 6 months after therapy. Conclusion. Complex therapy of influenza and other acute respiratory viral infections in children with functional and morphofunctional deviations in health status (II–IV health groups) using the drug Viferon®, rectal suppositories, according to a modified scheme using higher doses and with a longer duration of therapy, can reduce the onset improvement and overall recovery of patients, reduce the number of complications of influenza and other acute respiratory viral infections, reduce the number of recurrent episodes of the disease during the follow-up period 1, 3 and 6 months after treatment. Key words: Viferon®, children, immunity, interferon, influenza, acute respiratory viral infections

Distribution characteristics of traditional Chinese medicine syndromes in 4 367 adult influenza patients: a Meta-analysis

To systematically evaluate the distribution characteristics of traditional Chinese medicine (TCM) syndromes in adult influenza patients and to provide a basis for the TCM syndrome differentiation of influenza. The CNKI, CBM, Wanfang, VIP, PubMed, Embase, Cochrane Library databases were searched to collect cross-sectional studies on the distribution pattern of TCM syndromes in adult patients with influenza. The risk of bias assessment tool for cross-sectional studies developed by the Joanna Briggs Institute (JBI) evidence-based health care center was used to evaluate the literature quality, and the Stata 15.1 software was used to conduct a Meta-analysis of the pooled effect sizes of the included studies. A total of 11 studies with 4 367 influenza patients were included. Quality assessment results of JBI showed that the risk bias was higher in the sample size calculation, and the description of sampling modalities and response rate was unclear. There were 17 influenza syndromes after specification, and a single group rate Meta-analysis was performed of the syndromes with ≥ 50 incident cases showed that there were 9 syndromes with an incidence ≥ 10% and statistical significance, the top 5 syndromes were syndrome of wind and heat invading the defense [n = 1 583, RATE = 34.3%, 95% confidence interval (95%CI) was 22.2%-46.3%], syndrome of exterior cold and interior heat (n = 1 122, RATE = 36.1%, 95%CI was 21.2%-51.1%), syndrome of wind-cold fettering the exterior (n = 860, RATE = 19.4%, 95%CI was 10.7%-28.0%), syndrome of heat and toxin in the lung (n = 217, RATE = 17.1%, 95%CI was 9.1%-25.0%), and syndrome of disease involving both defense phase and qi phase (n = 184, RATE = 38.8%, 95%CI was 14.2%-63.5%). The results of the subgroup analysis in different geographical regions showed that the frequency of distribution of syndrome of wind and heat invading the defense and heat and toxin in the lung was higher in the South (RATE: 36.5%, 18.6%) than in the North (RATE: 30.9%, 15.4%), and the frequency of distribution of syndrome of wind-cold fettering the exterior and exterior cold and interior heat in the North (RATE: 23.8%, 40.1%) was higher than that in the South (RATE: 15.7%, 32.3%). There are 9 common TCM syndromes of influenza, including wind and heat invading the defense syndrome, exterior cold and interior heat syndrome, wind-cold fettering the exterior syndrome, heat and toxin in the lung syndrome, disease involving both defense phase and qi phase syndrome, wind and heat complicated by dampnessinvading the surface syndrome, wind and cold complicated by dampnessinvading the surface syndrome, defense phase syndrome and dampness and heatinvading the surface syndrome, which can provide a reference for the TCM syndrome differentiation and treatment of influenza.

Safety and efficacy of favipiravir in COVID-19: a comprehensive literature review

The severe acute respiratory syndrome coronavirus 2 virus spread fast around the globe. The medical community is actively searching for an antiviral that could be effective against it. An antiviral drug called favipiravir, created for the treatment of influenza, may work well for coronavirus disease 2019 (COVID-19). Therefore, this study evaluated the safety and efficacy of favipiravir in COVID-19 by reviewing published articles. We found favipiravir is effective, safe, and tolerated against COVID-19. More information is needed to determine long-term consequences, such as QT prolongation, hyperuricemia, and teratogenicity. Favipiravir interacts with other medications such as repaglinide, pyrazinamide, theophylline, acyclovir, warfarin, and methotrexate. Physicians should be aware when prescribing it.

Alloferon and Zanamivir Show Effective Antiviral Activity against Influenza A Virus (H1N1) Infection In Vitro and In Vivo

The use of vaccines is the most effective and reliable method for the prevention of viral infections. However, research on evaluation of effective therapeutic agents for use in treatment after infection is necessary. Zanamivir was administered through inhalation for treatment of pandemic influenza A/H1N1 in 2009. However, the emergence of drug-resistant strains can occur rapidly. Alloferon, an immunomodulatory drug developed as an NK cell activator, exerts antiviral effects against various viruses, particularly influenza viruses. Therefore, alloferon and zanamivir were administered in combination in an effort to improve the antiviral effect of zanamivir by reducing H1N1 resistance. First, we confirmed that administration of combined treatment would result in effective inhibition of viral proliferation in MDCK and A549 cells infected with H1N1. Production of IL-6 and MIP-1α in these cells and the activity of p38 MAPK and c-Jun that are increased by H1N1 were inhibited by combined treatment. Mice were then infected intranasally with H1N1, and examination of the antiviral efficacy of the alloferon/zanamivir combination was performed. The results showed that combined treatment after infection with H1N1 prevented weight loss, increased the survival rate, and improved lung fibrosis. Combined treatment also resulted in reduced infiltration of neutrophils and macrophages into the lungs. Combined treatment effectively inhibited the activity of p38 MAPK and c-Jun in lung tissue, which was increased by infection with H1N1. Therefore, the combination of alloferon/zanamivir effectively prevents the development of H1N1-mediated inflammation in the lungs by inhibiting the production of inflammatory mediators and migration of inflammatory cells into lung tissue.

Influenza antivirals and their role in pandemic preparedness

Effective antivirals provide crucial benefits during the early phase of an influenza pandemic, when vaccines are still being developed and manufactured. Currently, two classes of viral protein–targeting drugs, neuraminidase inhibitors and polymerase inhibitors, are approved for influenza treatment and post-exposure prophylaxis. Resistance to both classes has been documented, highlighting the need to develop novel antiviral options that may include both viral and host-targeted inhibitors. Such efforts will form the basis of management of seasonal influenza infections and of strategic planning for future influenza pandemics. This review focuses on the two classes of approved antivirals, their drawbacks, and ongoing work to characterize novel agents or combination therapy approaches to address these shortcomings. The importance of these topics in the ongoing process of influenza pandemic planning is also discussed.

1471. Treatment of Influenza with Baloxavir was Associated with Reduced Absenteeism Compared with Oseltamivir in a Patient-Generated Health Data Study

Abstract Background Lost productivity from workplace absenteeism is a significant component of the economic burden of influenza [1]. Antiviral treatment together with influenza vaccination may help reduce work time lost from influenza illness [2]. In clinical trials, baloxavir, an oral single dose treatment for influenza, demonstrated comparable symptom resolution to oseltamivir taken twice daily for 5 days [3]. We examined baloxavir real-world outcomes using patient generated health data (PGHD) to investigate the association between antiviral use and workplace absenteeism. Methods Using data from a participatory influenza-like illness (ILI) surveillance program (ISP), we identified participants who self-reported ILI using the online Evidation platform during the 2019-2020 influenza season in the United States. Participants who self-reported treatment with baloxavir or oseltamivir were included. We conducted an ordinal logistic regression to estimate the odds of missing work due to ILI, while adjusting for use of over-the-counter (OTC) medication, age, number of symptoms, US region, and comorbidities. Results Of 3658 participants eligible for inclusion in the analysis, 3285 (89.8%) were prescribed oseltamivir and 373 (10.2%) were prescribed baloxavir. A majority of participants (81.7%) reported missing at least one day of work. In the ordinal logistic regression, use of baloxavir was associated with lower odds of absenteeism, compared to oseltamivir (odds ratio [OR]: 0.748, 95% confidence interval [CI]: 0.616, 0.907). In addition, a higher number of symptoms (OR 2.922, 95% CI: 2.454, 3.481), older age (OR: 1.425, 95% CI: 1.162, 1.747), and use of OTC medication (OR: 1.242, 95% CI: 1.086, 1.420) were associated with higher odds of absenteeism. Due to a high rate of missing data on the timing of antiviral use (24.5% missing), its association with absenteeism could not be adequately assessed. Conclusion Treatment of patients with ILI with single dose baloxavir was associated with reduced workplace absenteeism compared to oseltamivir after adjusting for measured confounders. This study provides useful insight into factors associated with ILI-related workplace absenteeism and the potential real-world utility of baloxavir. Disclosures Hao Xu, MSc, Hoffmann-La Roche Limited: Employee Vincent Ukachukwu, n/a, Roche Products Ltd: Employee Devika Chawla, PhD, Genentech: Employee.

2188. A Quality Improvement Initiative for Influenza Diagnosis and Treatment within Health Systems Serving American Indian/Alaskan Native Patients

Abstract Background This project aimed to identify practices, knowledge and confidence in diagnosing and treating influenza in health systems serving American Indian/Alaskan Native communities and to provide education to support alignment with IDSA guidelines. Methods Anonymous baseline surveys were completed electronically by healthcare professionals (HCPs) from Cherokee Nation Health Services (CNHS) and the Northwest Portland Area Indian Health Board’s teleECHO program. Responses informed a 2-part series of live virtual educational trainings featuring pre- and post-program surveys and team-based action planning. Results Baseline surveys were completed by 247 HCPs. 149 attended the 1st meeting, and 90 attended the 2nd. For outpatient influenza diagnosis, 72% of baseline survey respondents reported primarily using rapid antigen testing, and 11% reported using molecular testing. Similarly, 15% of learners in the live meetings correctly identified rapid molecular assay as the guideline-recommended test, which improved to 72% afterwards. All 9 CNHS outpatient health centers switched from rapid antigen to molecular testing for influenza diagnosis after the training. Influenza treatment decision-making was assessed using a case vignette. For a patient at high risk for complications with flu-like symptoms but stable for outpatient care, 23% of learners in the live meetings correctly chose to start antiviral treatment immediately, which improved to 54% after the program, and more learners felt confident applying diagnostic test results to treatment, from 31% before to 68% after the training. Learner confidence also improved from 19% feeling confident in selecting antiviral treatment and 33% feeling confident in identifying high risk patients before the program to 60% and 70% afterwards, respectively. Action plans prioritized by the HCPs included: patient engagement (61%), reviewing guidelines and data (57%), improving patient adherence to treatment (50%), and developing criteria for immediate antiviral treatment (50%). Conclusion Knowledge and confidence in influenza management improved after the training, as did system-wide alignment with IDSA-recommended diagnostic testing. Studies evaluating the clinical impact of this activity is warranted. Disclosures Jorge Mera, MD, FACP, Abbvie: Grant/Research Support|Gilead Sciences: Grant/Research Support|Gilead Sciences: Received one time honorarium for participating as a panelist in a COVID-19 Webinar|Merck: Grant/Research Support.

882. Systematic Underdosing of Oseltamivir in Hospitalized Patients with Influenza

Abstract Background Oseltamivir remains the primary treatment for seasonal influenza syndromes and early administration has been shown to increase the clinical benefit of treatment; we studied current practice and describe patient and system variables influencing dosing decisions. Methods We reviewed oseltamivir dosing in 135 adult patients in our community hospital admitted with acute influenza over two northern Hemisphere influenza seasons (2016-2017 and 2017-2018) and for whom pharmacy dosing protocols were invoked. We reviewed admitting symptoms for factors suggesting possible dehydration, the timing of treatment in relation to testing for influenza, the estimated creatinine clearance at the time of dose determination for oseltamivir, the initial dose of drug, and dose-adjustment over time. Results Patients ranged in age from 27-96 years (mean 74), with 83 males and 52 females among the 135 patients over these two seasons. Testing results were available for 131 patients and 75 (57%) were positive, while 56 (43%) were negative, and therefore treated empirically based on presenting symptoms. Ninety patients (67%) received an initial dose of 30 mg of oseltamivir, while 45 patients (33%) received an initial dose of 75 mg. Of the 90 patients who were dose-adjusted by the pharmacist to 30 mg for the initial dose, 24 (27%) had a creatinine clearance &amp;gt; 60 mL/min, and it is not clear what factors influenced those decisions. Of the 90 patients with an initial creatinine clearance of &amp;lt; 60 mL/min, 22 (24%) showed a clinically significant improvement to &amp;gt; 60 mL/min within the first 24 hours of hospitalization yet only 8 patients had their dose adjusted. Presenting symptoms did not predict patients who had rapid improvement of creatinine clearance. Of the 45 patients receiving an initial dose of 75 mg of oseltamivir, 19 (42%) had creatinine clearance values of &amp;lt; 60mL/min, and were therefore given a loading dose, followed by dose adjustment. Conclusion We found a significant percentage of patients were underdosed initially and dosing was not adjusted for changes in renal function. Reviewing and revising dosing protocols and guidelines may lead to more effective treatment for influenza and may serve as a model for future test-to-treat options for therapies for other acute viral respiratory infections in the future. Disclosures All Authors: No reported disclosures.