Oseltamivir Treatment Research Articles

Influenza clinical testing and oseltamivir treatment in hospitalized children with acute respiratory illness, 2015-2016.

BackgroundAntiviral treatment is recommended for all hospitalized children with suspected or confirmed influenza, regardless of their risk profile. Few data exist on adherence to these recommendations, so we sought to determine factors associated with influenza testing and antiviral treatment in children.MethodsHospitalized children <18 years of age with acute respiratory illness (ARI) were enrolled through active surveillance at pediatric medical centers in seven cities between 11/1/2015 and 6/30/2016; clinical information was obtained from parent interview and chart review. We used generalized linear mixed‐effects models to identify factors associated with influenza testing and antiviral treatment.ResultsOf the 2299 hospitalized children with ARI enrolled during one influenza season, 51% (n = 1183) were tested clinically for influenza. Clinicians provided antiviral treatment for 61 of 117 (52%) patients with a positive influenza test versus 66 of 1066 (6%) with a negative or unknown test result. In multivariable analyses, factors associated with testing included neuromuscular disease (aOR = 5.35, 95% CI [3.58–8.01]), immunocompromised status (aOR = 2.88, 95% CI [1.66–5.01]), age (aOR = 0.93, 95% CI [0.91–0.96]), private only versus public only insurance (aOR = 0.78, 95% CI [0.63–0.98]), and chronic lung disease (aOR = 0.64, 95% CI [0.51–0.81]). Factors associated with antiviral treatment included neuromuscular disease (aOR = 1.86, 95% CI [1.04, 3.31]), immunocompromised state (aOR = 2.63, 95% CI [1.38, 4.99]), duration of illness (aOR = 0.92, 95% CI [0.84, 0.99]), and chronic lung disease (aOR = 0.60, 95% CI [0.38, 0.95]).ConclusionApproximately half of children hospitalized with influenza during the 2015–2016 influenza season were treated with antivirals. Because antiviral treatment for influenza is associated with better health outcomes, further studies of subsequent seasons would help evaluate current use of antivirals among children and better understand barriers for treatment.

Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis

Objective Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. Design Secondary analysis of randomized controlled trial data. Setting Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016–2018. Subjects A total of 277 ILI patients aged one year or older and symptom duration of ≤72 h. Main outcome measures Capillary blood CRP concentration at baseline, and ILI recovery time defined as having ‘returned to usual daily activity’ with residual symptoms minimally interfering. Results At baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0–210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50–1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37–1.3; p = 0.23). Conclusion There was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment. Key Points Predicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians. • There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care. • There was no association between CRP concentration at baseline and benefit from oseltamivir treatment. • We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

Early oseltamivir reduces risk for influenza-associated aspergillosis in a double-hit murine model

ABSTRACT Invasive pulmonary aspergillosis (IPA) is a life-threatening fungal infection occurring mainly in immunocompromised patients. We recently identified IPA as an emerging co-infection with high mortality in critically ill, but otherwise immunocompetent influenza patients. The neuraminidase inhibitor oseltamivir is the current standard-of-care treatment in hospitalized influenza patients; however, its efficacy in influenza-associated pulmonary aspergillosis (IAPA) is not known. Therefore, we have established an imaging-supported double-hit mouse model to investigate the therapeutic effect of oseltamivir on the development of IAPA. Immunocompetent mice received intranasal instillation influenza A or PBS followed by orotracheal inoculation with Aspergillus fumigatus 4 days later. Oseltamivir treatment or placebo was started at day 0, day 2, or day 4. Daily monitoring included micro-computed tomography and bioluminescence imaging of pneumonia and fungal burden. Non-invasive biomarkers were complemented with imaging, molecular, immunological, and pathological analysis. Influenza virus-infected immunocompetent mice developed proven airway IPA upon co-infection with Aspergillus fumigatus, whereas non-influenza-infected mice fully cleared Aspergillus, confirming influenza as a risk factor for developing IPA. Longitudinal micro-CT showed pulmonary lesions after influenza infection worsening after Aspergillus co-infection, congruent with bioluminescence imaging and histology confirming Aspergillus pneumonia. Early oseltamivir treatment prevented severe influenza pneumonia and mitigated the development of IPA and associated mortality. A time-dependent treatment effect was consistently observed with imaging, molecular, and pathological analyses. Hence, our findings underscore the importance of initiating oseltamivir as soon as possible, to suppress influenza infection and mitigate the risk of potentially lethal IAPA disease.

Risk Factors Associated with 30-Day Mortality in Older Patients with Influenza.

Background: Influenza is a common viral condition, but factors related to short-term mortality have not been fully studied in older adults. Our objective was to determine whether there is an association between geriatric factors and 30-day mortality. Methods: This was a retrospective cohort design. All patients aged 75 years and over, with a diagnosis of influenza confirmed by a positive RT-PCR, were included. The primary endpoint was death within the 30 days after diagnosis. Results: 114 patients were included; 14 (12.3%) patients died within 30 days. In multivariate analysis these patients were older (OR: 1.37 95% CI (1.05, 1.79), p = 0.021), and had a lower ADL score (OR: 0.36 95% CI (0, 17; 0.75), p = 0.006), and a higher SOFA score (OR: 2.30 95% CI (1.07, 4.94), p = 0.03). Oseltamivir treatment, initiated within the first 48 h, was independently associated with survival (OR: 0.04 95% CI (0.002, 0.78), p = 0.034). Conclusions: Identification of mortality risk factors makes it possible to consider specific secondary prevention measures such as the rapid introduction of antiviral treatment. Combined with primary prevention, these measures could help to limit the mortality associated with influenza in older patients.

Efficacy and Safety of Chinese Patent Medicine Combined With Oseltamivir in Treatment of Children With Influenza: A meta-Analysis.

Background: Recently, Chinese patent medicines (CPMs) have been widely used to treat children with influenza in China, with curative effects. Therefore, the efficacy and safety of such treatment require further evaluation. The present meta-analysis integrated data from several independent studies to determine overall treatment trends in children with influenza.Methods: The following databases were searched for randomized controlled trials (RCTs) published from their inception to December 12, 2020: CNKI, Wanfang, SinoMed, PubMed, Cochrane library, and Embase. Two researchers independently extracted the data, assessed the methodological quality of the studies, and conducted a meta-analysis of the results using Review Manager 5.2. The results were assessed using forest plots, and publication bias was evaluated using a funnel plot.Results: A total of 21 RCTs involving 2960 cases were included. Compared to oseltamivir alone, CPMs combined with oseltamivir reduced the duration of symptoms, including that of fever (mean difference [MD] = −0.64, 95% confidence interval [CI]: −0.86 to −0.41, P < 0.00001), cough (MD = −0.82, 95% CI: −1.02 to −0.62, P < 0.00001), nasal obstruction (MD = −0.88, 95% CI: −1.15 to −0.61, P < 0.00001), and sore throat (MD = −0.92, 95% CI: −1.26 to −0.57, P < 0.00001). Combined therapy also reduced the time of viral shedding (MD = −0.53, 95% CI: −0.70 to −0.36, P < 0.00001) and the occurrence of adverse drug reactions (ADRs) (RR=0.53, 95% CI: 0.34 to 0.83, P = 0.005).Conclusions: CPMs combined with oseltamivir reduced the duration of symptoms, shortened the time of viral shedding, and reduced the number of ADRs. However, these results should be considered with caution because there was marked heterogeneity and publication bias in the research data. More rigorous RCTs should be designed to verify the effect of CPMs in children with influenza.

Complications and Outcome of H1N1 Influenza in a Tertiary Care Hospital in South India A Retrospective Study

Background: Influenza virus causes a highly contagious febrile illness ranging from mild symptoms to acute respiratory distress syndrome, respiratory failure and death. The H1N1 influenza pandemic caused a worldwide public health challenge. Objectives: This study aimed to record the clinical outcomes and factors associated with poorer outcomes in hospitalized patients. Materials and Methods: Patients with laboratory-confirmed H1N1 infection by real-time polymerase chain reaction were included in this retrospective study. Data regarding the demographics, medical comorbidities, complications, treatment details and outcome were obtained. Statistical analysis was performed using SPSS version 16. Results: Among 295 patients, 143 (48.5%) were males and 152 (51.5%) were females. The majority were in the age group of 18 to 49 years. Pneumonia (8.1%) and respiratory failure (9.2%) were the most frequent complications. A majority (71%) required hospitalization of fewer than 5 days and 32 (10.8%) required ventilatory support. There were no deaths reported in this group. Elderly patients (age&gt;50 years) (P= 0.002) with the presence of comorbidities (P= 0.000) had greater complications. Elderly patients (P= 0.011) with the presence of co-morbidities (P= 0.000) required a longer duration of Oseltamivir treatment. Female patients (P= 0.015) and patients with comorbidities (P= 0.001) had greater ventilator requirements. Elderly (P= 0.002), female patients (P= 0.018), and those with comorbidities (P= 0.000) required a longer hospital stay. Patients with cardiovascular diseases and pre-existing lung diseases had overall poorer outcomes. Conclusion: The main risk factors were old age, female sex, cardiovascular diseases, Chronic Obstructive Pulmonary Disease, and asthma. These parameters were significantly associated with increased Oseltamivir treatment duration, greater complications, prolonged hospital stay and ventilatory support.

In Non-Selected Patients Treated for Influenza, Oseltamivir, a Glycosialidase Inhibitor, Demonstrates Improvement in Platelet Counts Compared to Time of Dosing, but Not over Baseline Levels

Background:Severe thrombocytopenia can cause morbidity or mortality in many patients, especially those with hematologic cancers or who are treated with chemotherapy. Safer and more rational treatment options are critically needed. Platelet aging and clearance, and therefore the quantity of circulating platelets, is intimately tied to the loss of sialic acid on the platelet surface. Platelets lose surface sialic acid gradually as they circulate and age through cleavage by sialidases. In vitro desialylation of the platelet could be circumvented with a sialidase inhibitor. Oseltamivir phosphate (Tamiflu) is an FDA-approved antiviral sialidase inhibitor and has been prescribed worldwide for the treatment of patients with influenza. Multiple case reports have shown a significant improvement in platelet quantity in patients with thrombocytopenia who were treated with oseltamivir. We here investigated the in vivo effect of oseltamivir treatment on platelet counts in a historical cohort.Methods:We performed a retrospective observational study in 52 patients treated at the Medical College of Wisconsin. All patients received one treatment course of 75 mg oseltamivir phosphate between October 2004 and February 2017 due to suspicion of influenza. Excluded patients included those who received a different dose of oseltamivir and those who received multiple treatment courses during this time. Constraints in patient platelet count availability at various time-points around dosing led us to divide our two time-point comparison analysis into four groups: (1) baseline (defined as 30 days prior to dosing) vs. 30 days post-treatment, (2) baseline vs. 100 days post-treatment, (3) first day of treatment vs. 30 days post-treatment and (4) first day of treatment vs. 100 days post-treatment. Data were analyzed using paired t-testing after normalizing with a logarithmic scale. Statistical analyses were done with significance level of p<0.05.Results:The mean patient age was 61 years old (range 25-88 years old) and 59.6% were male. Treatment courses ranged from 1 to 15 doses over 1 to 14 days with an average treatment course of 4.3 doses over 3.9 days (median of 4 doses over 3 days). There were a total of 26 patients in Group 1, 24 patients in Group 2, 32 patients in Group 3, and 32 patients in Group 4. Some patients had data for multiple time-points and are therefore represented in more than one group.In Groups 3 and 4, the difference in platelet count was statistically significant (p<0.05) between the first day of oseltamivir administration and 30 days or 100 days after the last dose. About 72% of patients (23 out of 32) in Group 3 experienced a 2-fold increase in platelet count at 30 days following termination of treatment and 84% of patients (27 out of 32) in Group 4 experienced a 2.1-fold increase in platelet count at 100 days following termination of treatment.In Groups 1 and 2, where end-points were compared to 30 days prior to oseltamivir administration (baseline), platelet counts were also increased, but were not found to be statistically significant. About 65% of patients (17 out of 26) in Group 1 experienced a 1.1-fold increase in platelet count 30 days following termination of treatment. About 63% of patients (15 out of 24) in Group 2 experienced a 2.5-fold increase in platelet count 100 days following termination of treatment.Conclusions:Multiple published case reports have pointed to improvements in thromobocytopenia following dosing of oseltamivir for the treatment of influenza. Our data also shows significant increases in platelet counts when 30 day and 100 day post-treatment levels are compared to levels on the first day of treatment. However, our analysis does not indicate that treatment with oseltamivir significantly increases a patient's platelet count over baseline (defined as 30 days prior to dosing). To our knowledge, this is the only data to look at platelet counts both at the time of drug administration as well as at baseline to assess effect. Platelet counts may be decreased at the time of drug dosing due to concomitant illness, in particular, influenza. Whether there is an independent effect of oseltamivir on platelet clearance will require a controlled study. We plan further research to clarify potential therapeutic application of this commonly available sialidase inhibitor in patients with chronically low platelets. DisclosuresMichaelis:Incyte: Other: consultation for product; Celgene: Speakers Bureau; Novartis: Other: Consultation for New Product.

Virological and clinical outcomes in outpatients treated with baloxavir or oseltamivir: A Japanese multicenter study in the 2019–2020 influenza season

Although the virological and clinical efficacies of baloxavir for influenza and the post-treatment emergence of variant viruses have been reported in clinical trials, its efficacies have not been fully investigated in clinical settings. This prospective, observational investigator-initiated study was conducted during the 2019–2020 Japanese influenza season. In outpatients receiving baloxavir or oseltamivir, nasopharyngeal samples were obtained on day 1 before treatment and on the scheduled days 5 and 10 after treatment. RT-PCR and sequencing were performed to detect polymerase acidic protein (PA) E23X/I38X and neuraminidase (NA) H275Y variants in clinical and cultivated samples. Fever and illness-related symptoms were recorded using self-reporting diaries. Overall, 116 outpatients, 76 treated with baloxavir (34 under 12 years) and 40 with oseltamivir (32 under 12 years), were eligible. Of these, 91 were infected with A (H1N1)pdm09 (78.4%), of which 58 received baloxavir and 33 received oseltamivir. PA variants were detected in clinical (1.7%, 1/58; 3.8%, 1/26 for children under 12 years) and isolated (3.4%, 2/58; 3.8%, 1/26 for children under 12 years) samples obtained on day 5 after baloxavir treatment, but not on day 10. The isolation frequencies of A (H1N1)pdm09 on days 5 and 10 after baloxavir treatment were 5.2% (3/58) and 0.0% (0/58), respectively. Of the three viruses isolated on day 5, two (66.7%, 2/3) were PA I38 T/F variants with reduced baloxavir susceptibility. The isolation frequencies of A (H1N1)pdm09 on days 5 and 10 after oseltamivir treatment were 30.3% (10/33) and 6.1% (2/33), respectively. Only the two viruses isolated on day 10 were NA H275Y variants. The median duration of fever in baloxavir and oseltamivir recipients was 22.3 and 27.5 h, respectively. No patients with PA or NA variants showed prolonged durations of fever. Baloxavir was virologically effective for influenza in the clinical setting of the 2019–2020 Japanese season. Variant emergence after baloxavir treatment was limited to the early post-treatment stage.

Oseltamivir treatment of influenza A and B infections in infants.

BackgroundOseltamivir treatment is currently the only way of managing influenza in young infants for whom influenza vaccines are not licensed, but little data exist on the effectiveness of the treatment in this age group.MethodsIn a prospective study, we enrolled 431 newborn infants and followed them up for 10 months during their first respiratory season (September 2017‐June 2018). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for determination of the viral etiology. Infants with influenza were re‐examined at short intervals, and additional nasopharyngeal specimens were obtained at each visit for measuring the viral load. All infants with symptoms <48 hours received oseltamivir treatment. The parents filled out daily symptom diaries.ResultsAmong 23 infants with influenza A, the mean total duration of illness in oseltamivir recipients was 82.1 hours, compared with 253.5 hours in infants without treatment (P = .0003). For infants with influenza B, the corresponding durations were 110.0 and 173.9 hours, respectively (P = .03). In infants with influenza A, total symptom scores were significantly lower in oseltamivir‐treated infants at all time points between days 3 and 11 after the onset of therapy. In most children with either influenza A or B, viral antigen concentrations declined rapidly within 1‐2 days after the initiation of oseltamivir treatment.ConclusionsOseltamivir treatment of infants with influenza rapidly decreased the viral load in nasopharyngeal secretions and shortened the duration and severity of symptoms. The clinical effectiveness of oseltamivir appeared to be greater against influenza A than against influenza B infections.

Neuraminidase inhibitors for treatment of influenza.

Neuraminidase inhibitors (NAIs) are commonly used in the prevention and treatment of influenza. Previous studies and reviews have demonstrated a questionable and modest benefit of their use while demonstrating potential adverse effects.1,2.

P0256 / #1971: MANAGEMENT OF MULTIORGAN FAILURE SECONDARY TO INFLUENZA VIRUS

Aims & Objectives: It was aimed to present a severe case with multiorgan failure secondary to influenza virus. Methods: A four-year and five-month-old girl presented with a runny nose and fever. She was hypotensive and lethargic at admission and intubated because of respiratory failure. Adrenaline and milrinone infusion was because of hypotension. Clinical findings and labarotory parameters were consistent with multiple organ failure (PELOD score 51). Plasma exchange was performed by considering cytokine storm with detection of high ferritin level (3288 µg/L). Intravenous immunoglobulin was given to influenza infection by considering secondary myocarditis due to elevated cardiac markers and decreased cardiac contraction (ejection fraction 40%). Results: On the second day, continuous venovenous hemodiafiltration was started because of oliguria. After detection of influenza A (H1N1) in nasopharyngeal aspirate, oseltamivir treatment was extended to ten days. Plasma exchange was performed five times. After plasma exchange sessions ferritin level decreased to 597 µg/L and PELOD score decreased to 10. She was extubated on the eighth day. In lymphocyte subgroups, “natural killer” cells were found to be low (0%), and central ‘memory ‘T cell ratio was found to be low in lymphocyte proliferation test. A new generation sequencing panel was studied for agent-specific immune deficiency. On the 32nd day of hospitalization, she was transferred to the pediatric ward. Conclusions: In hyperferritinemic sepsis and multiorgan failure caused by influenza virus, plasma exchange and venovenous hemodiafiltration minimize mortality and morbidity.

Efficacy of tocilizumab treatment in COVID-19 patients with cytokine release syndrome

Background/Aim: Cytokine release syndrome, a potentially life-threatening condition in SARS‐CoV‐2 (COVID-19) patients, plays a critical role that may lead to the prioritization of tocilizumab (TCZ) in the treatment of this disease. We aimed to present our TCZ-treated SARS‐CoV‐2 patients’ data that might help and guide clinicians in dealing with this infectious disease in their daily practice and research. Methods: This is a retrospective multicenter cohort study from two Turkish pandemic centers. A total of 5165 patients’ data who were hospitalized due to SARS‐CoV‐2 pneumonia from March 16 to May 20, 2020 were screened and 72 patients treated with TCZ were included in the study. We evaluated patients' demographic data, laboratory and imaging studies, and clinical outcomes and the effect of TCZ treatment on patients' laboratory and clinical results. Results: O2 saturation levels significantly increased, and fever significantly decreased on the 5th day after TCZ therapy compared to before its initiation (P=0.001, P=0.010, respectively). The decrease in troponin-I, creatinine, LDH, fibrinogen, CRP, procalcitonin, CK, and ferritin levels after TCZ therapy were significant (P0.05 for all). Importantly, we found a significant increase in mortality rates in patients who received azithromycin, oseltamivir, and ascorbic acid treatments compared to those who did not receive those treatments (P

Impact of Oseltamivir Treatment on Influenza A and B Virus Dynamics in Human Volunteers.

Influenza viruses infect millions of humans every year causing an estimated 400,000 deaths globally. Due to continuous virus evolution current vaccines provide only limited protection against the flu. Several antiviral drugs are available to treat influenza infection, and one of the most commonly used drugs is oseltamivir (Tamiflu). While the mechanism of action of oseltamivir as a neuraminidase inhibitor is well-understood, the impact of oseltamivir on influenza virus dynamics in humans has been controversial. Many clinical trials with oseltamivir have been done by pharmaceutical companies such as Roche but the results of these trials until recently have been provided as summary reports or papers. Typically, such reports included median virus shedding curves for placebo and drug-treated influenza virus infected volunteers often indicating high efficacy of the early treatment. However, median shedding curves may be not accurately representing drug impact in individual volunteers. Importantly, due to public pressure clinical trials data testing oseltamivir efficacy has been recently released in the form of redacted PDF documents. We digitized and re-analyzed experimental data on influenza virus shedding in human volunteers from three previously published trials: on influenza A (1 trial) or B viruses (2 trials). Given that not all volunteers exposed to influenza viruses actually start virus shedding we found that impact of oseltamivir on the virus shedding dynamics was dependent on (i) selection of volunteers that were infected with the virus, and (ii) the detection limit in the measurement assay; both of these details were not well-articulated in the published studies. By assuming that any non-zero viral measurement is above the limit of detection we could match previously published data on median influenza A virus (flu A study) shedding but not on influenza B virus shedding (flu B study B) in human volunteers. Additional analyses confirmed that oseltamivir had an impact on the duration of shedding and overall shedding (defined as area under the curve) but this result varied by the trial. Interestingly, treatment had no impact on the rates at which shedding increased or declined with time in individual volunteers. Additional analyses showed that oseltamivir impacted the kinetics of the end of viral shedding, and in about 20–40% of volunteers that shed the virus treatment had no impact on viral shedding duration. Our results suggest an unusual impact of oseltamivir on influenza viruses shedding kinetics and caution about the use of published median data or data from a few individuals for inferences. Furthermore, we call for the need to publish raw data from critical clinical trials that can be independently analyzed.

Early oseltamivir treatment improves survival in critically ill patients with influenza pneumonia.

BackgroundThe relationship between early oseltamivir treatment (within 48 h of symptom onset) and mortality in patients admitted to intensive care units (ICUs) with severe influenza is disputed. This study aimed to investigate the association between early oseltamivir treatment and ICU mortality in critically ill patients with influenza pneumonia.MethodsThis was an observational study of patients with influenza pneumonia admitted to 184 ICUs in Spain during 2009–2018. The primary outcome was to evaluate the association between early oseltamivir treatment and ICU mortality compared with later treatment. Secondary outcomes were to compare the duration of mechanical ventilation and ICU length of stay between the early and later oseltamivir treatment groups. To reduce biases related to observational studies, propensity score matching and a competing risk analysis were performed.ResultsDuring the study period, 2124 patients met the inclusion criteria. All patients had influenza pneumonia and received oseltamivir before ICU admission. Of these, 529 (24.9%) received early oseltamivir treatment. In the multivariate analysis, early treatment was associated with reduced ICU mortality (OR 0.69, 95% CI 0.51–0.95). After propensity score matching, early oseltamivir treatment was associated with improved survival rates in the Cox regression (hazard ratio 0.77, 95% CI 0.61–0.99) and competing risk (subdistribution hazard ratio 0.67, 95% CI 0.53–0.85) analyses. The ICU length of stay and duration of mechanical ventilation were shorter in patients receiving early treatment.ConclusionsEarly oseltamivir treatment is associated with improved survival rates in critically ill patients with influenza pneumonia, and may decrease ICU length of stay and mechanical ventilation duration.

1518. Real-World Comparative Effectiveness of Baloxavir Marboxil versus Oseltamivir on Influenza-Related Complication and Resource Utilization

BackgroundIn the 2018-19 season, there were an estimated 490,500 hospitalizations and 24,000 deaths from influenza in the US. Understanding how antiviral use affects rates and severity of complications is crucial to inform clinical practice. The objective of this study was to compare the frequency and costs of complications in influenza patients treated with baloxavir compared with oseltamivir-treated patients. This is one of the first analyses to examine comparative effectiveness of baloxavir in a real-world setting.MethodsThis retrospective cohort study used IBM MarketScan US administrative claims data from the 2018–19 influenza season. Patients were required to have an outpatient visit for influenza followed by a prescription for baloxavir or oseltamivir within 2 days. Baloxavir- and oseltamivir-treated patients were propensity score matched based on key baseline clinical and demographic characteristics. All-cause, all respiratory-related, and select respiratory-related (infection, asthma, and COPD) HRU in the 15 and 30 days following prescription fill were assessed using chi-square and Fisher’s exact tests for categorical measures and Wilcoxon signed-rank tests for counts and costs.ResultsWe included 5,080 baloxavir-treated patients and 10,160 matched oseltamivir-treated patients in the analysis. Statistically significantly lower HRU was associated with baloxavir compared with oseltamivir therapy (15-day: respiratory-related ED visits, select respiratory-related ED visits and outpatient visits; 30-day: all-cause hospitalization, respiratory-related ED visits, select respiratory-related ED visits and outpatient visits (Table 1). Similarly, associated costs were generally lower in the baloxavir-treated group. Baloxavir-treated patients had lower mean per-patient all-cause 15-day costs (ED visits: $30 [95% CI: $21–$39] vs $42 [95% CI: $32–$51]; hospitalizations: $31 [95% CI: $6–$55] vs $74 [95% CI: $43–$104]) and 30-day costs (ED visits: $46 [95% CI: $35–$57] vs $67 [95% CI: $55–$79]; hospitalizations: $47 [95% CI: $15–$80] vs $119 [95% CI: $78–$161]).Table 1. Proportion of patients with at least one event ConclusionThese findings suggest that treatment of influenza with baloxavir may improve outcomes and lower HRU costs compared with oseltamivir treatment.DisclosuresEddie Neuberger, PharmD, Genentech, Inc. (Employee) Chris Wallick, PharmD, MS, Genentech, Inc. (Employee) Devika Chawla, PhD MSPH, Genentech, Inc. (Employee) Rita de Cassia Castro, MD, Genentech, Inc. (Employee)

Association between oseltamivir use and neuropsychiatric adverse events in influenza patients: a nationwide population-based cohort study

ABSTRACT Background: A potential risk of neuropsychiatric adverse events (NPAEs) of oseltamivir has remained controversial by retrospective cohort studies. This nationwide population-based cohort study aimed to assess the risk of NPAEs in influenza patients undergoing oseltamivir treatment (users) compared with a propensity score-matched cohort of patients not receiving oseltamivir (non-users). Research design and methods: Using the Korean National Health Service–Sample Cohort Database, patients diagnosed with incident influenza during 2003–2013 were divided into two cohorts: oseltamivir users and non-users. We calculated adjusted hazard ratios (aHRs) for the 5-day treatment course with oseltamivir using Cox regression analysis. Results: The incidence rate of NPAEs during 5-day oseltamivir treatment was 0.0029 and 0.0023 in oseltamivir users and non-users, respectively. The risk of NPAEs was different according to age, with an increased risk in patients aged 10–19 years (aHR 2.69, 95% CI 1.05–6.93) and a decreased risk in patients aged 0–9 years (aHR 0.46, 95% CI 0.24–0.88). The non-significant positive associations were observed in patients aged 20–64 years and those aged greater than 65 years. Conclusions: Although the reason for the inverse association in children aged 0–9 years is unknown, oseltamivir could increase the risk of NPAEs for children or adolescents aged greater than 10 years.

Epidemiological and clinical characteristics of community-acquired and nosocomial influenza cases and risk factors associated with complications: A four season analysis of all adult patients admitted in a tertiary hospital.

BackgroundInformation on the characteristics of patients with nosocomial influenza and associated complications is scarce. This study compared epidemiological and clinical characteristics of patients admitted with hospital‐acquired influenza (HAI) to those with community‐acquired influenza (CAI) and analyzed risk factors associated with complications.MethodsThis retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during the influenza season in Spain (October to May) from 2012‐2013 to 2015‐2016. Symptom onset before admission was included as CAI, and 2 days after admission or within 48 hours after previous discharge were considered as HAI.ResultsOverall, 666 patients with laboratory‐confirmed influenza were included; 590 (88.6%) and 76 (11.4%) had CAI and HAI, respectively. Baseline characteristics and vaccination rates were similar in both groups. Patients with HAI had significantly fewer symptoms, less radiological alterations, and earlier microbiological diagnosis than those with CAI. Eighty‐five (14.4%) and 20 (27.6%) CAI and HAI patients, respectively, experienced at least one complication, including septic shock, admission to the intensive care unit, mechanical ventilation or evolution to death (any one, P = .003). Univariate and multivariate binary logistic regression was performed to assess independent risk factors associated with the occurrence of complications: nosocomial infection, diabetes, oseltamivir treatment, having received no vaccination, microbiological delay, dyspnea, and the state of confusion were the most important significant factors.ConclusionsOur study shows the need to implement microbiological diagnostic measures in the first 48 hours to reduce HAI frequency and associated complications.

Dexamethasone and remdesivir: finding method in the COVID-19 madness

Dexamethasone and remdesivir: finding method in the COVID-19 madness

Duration of fever and symptoms in children after treatment with baloxavir marboxil and oseltamivir during the 2018–2019 season and detection of variant influenza a viruses with polymerase acidic subunit substitutions

We conducted a prospective, multicenter, non-randomized observational study to assess the duration of fever and symptoms of influenza A/H1N1pdm09 and A/H3N2 infected children < 19 years old treated with either baloxavir or oseltamivir. Additionally, these symptoms were investigated in association with pre- and post-baloxavir treatment-emergent polymerase acidic unit (PA) variants as compared to non-substituted viruses. Following receipt of informed consent, baloxavir was administered to 102 influenza A patients, and oseltamivir to 52 patients during the 2018–2019 influenza season in Japan. The average age was higher in the baloxavir treatment group compared to the oseltamivir treatment group (10.6 ± 2.7 versus 6.9 ± 2.9 years old, p < 0.01). The duration of fever and symptoms in baloxavir-treated A/H1N1pdm09 and A/H3N2-infected children did not differ from those in oseltamivir-treated groups (median 22.0, 11.8, 23.0, and 21.0 h, and median 114.5, 121.0, 123.0, and 122.0 h, respectively). One (1.2%) of 83 A/H3N2 patients possessed a PA/I38T substituted virus prior to treatment. The frequency of PA variants in post-treatment samples obtained 2–11 days after beginning of baloxavir was 12.5% (4/32) for A/H1N1pdm09 and 14.1% (9/64) for A/H3N2 when the total number of cases was used as the denominator, however, were 57.1% (4/7) and 33.3% (9/27) when PCR-positive cases at the time of second sampling was used as the denominator. The most frequent PA substitution was I38T (9), with E23K (1), I38K (1), I38M (1), and PA/I38S (1) also observed. The duration of fever and overall symptoms did not differ significantly following baloxavir treatment in individuals with PA variant viruses, non-substituted virus, or in those that were PCR negative at the second sampling (median 20, 24 and 11 h, and median 121, 115 and 121 h, respectively). Rebound of viral RNA load was observed in 13.5% (2/13) of PA variants but it was not associated with recurrence of fever and symptoms. Hence, prolonged fever or symptoms were not observed in children treated with baloxavir following emergence of PA variants, however, further studies are needed to evaluate the clinical impact of PA variants.

Effectiveness of oseltamivir in reduction of complications and 30-day mortality in severe seasonal influenza infection

The benefit of oseltamivir treatment in patients admitted with influenza virus infection and the design of studies addressing this issue have been questioned extensively. As the burden of influenza disease is substantial and oseltamivir treatment is biologically plausible, this study assessed the clinical benefit of oseltamivir treatment in adult patients admitted with severe seasonal influenza virus infection in daily practice. A multi-centre, retrospective cohort study was conducted to compare the effectiveness of treatment with and without oseltamivir <48 h after admission in patients admitted with laboratory-confirmed influenza virus infection in three large hospitals in the Netherlands. Propensity score matching was used to compare clinically relevant outcome variables. In total, 390 patients were included in this study, of whom 80% had comorbidities. Thirty-day mortality, as well as the composite endpoint of 30-day mortality or intensive care unit admission >48 h after admission, were reduced by 9% (P=0.04) and 11% (P=0.02), respectively. Length of hospital stay and in-hospital mortality rates all showed a trend towards reduction. The median duration between symptom onset and initiation of treatment was 3 days. This study supports that, in daily practice, patients admitted with influenza virus infection should be treated with oseltamivir within 48 h of admission, even if they have had complaints for >48 h.