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Anales de Pediatria May 2019Influenza is a generally a benign disease, but occasionally it can cause serious complications. There is controversy about the benefits of antiviral treatment. (Review)
Review
INTRODUCTION
Influenza is a generally a benign disease, but occasionally it can cause serious complications. There is controversy about the benefits of antiviral treatment.
OBJECTIVES
To provide some recommendations on the treatment with oseltamivir in paediatric patients with influenza, based on the best data available and valid in our environment.
METHODS
The Respiratory Infections Group of the Spanish Society of Paediatric Infectious Diseases carried out a review of the literature. The findings were analysed using the GRADE methodology, and recommendations were made.
RESULTS
The systematic use of diagnostic tests for influenza in the outpatient setting, or in the emergency room, in immunocompetent patients with a compatible clinical picture is not recommended. If the aim is to prevent serious events, the use of antivirals is not recommended for the vast majority of healthy and asthmatic patients with influenza or suspected seasonal flu. The systematic use of oseltamivir in patients admitted to hospital with influenza is not recommended. Oseltamivir treatment is recommended in any patients with influenza and pneumonia or severe illness, and critically ill patients, especially during the first 48hours of illness. The treatment of patients with risk factors is recommended, considering their underlying disease. Influenza vaccination, together with basic isolation measures, continue to be the main tool in the prevention of influenza.
CONCLUSION
In some situations, there are sufficient data to issue clear recommendations. In other situations, the data are incomplete, and only allows weak recommendations.
Topics: Adolescent; Age Factors; Antiviral Agents; Child; Critical Illness; Humans; Influenza, Human; Oseltamivir; Risk Factors; Time Factors
PubMed: 30797703
DOI: 10.1016/j.anpedi.2019.01.009 -
Antiviral Research Feb 2023Effective antivirals provide crucial benefits during the early phase of an influenza pandemic, when vaccines are still being developed and manufactured. Currently, two... (Review)
Review
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.
Topics: Humans; Antiviral Agents; Drug Resistance, Viral; Enzyme Inhibitors; Influenza, Human; Neuraminidase; Oseltamivir; Pandemics
PubMed: 36567025
DOI: 10.1016/j.antiviral.2022.105499 -
JAMA Internal Medicine Jan 2024Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when given to outpatients. Several large investigator-initiated randomized clinical trials have not yet been meta-analyzed.
OBJECTIVE
To assess the efficacy and safety of oseltamivir in preventing hospitalization among influenza-infected adult and adolescent outpatients.
DATA SOURCES
PubMed, Ovid MEDLINE, Embase, Europe PubMed Central, Web of Science, Cochrane Central, ClinicalTrials.gov, and WHO International Clinical Trials Registry were searched from inception to January 4, 2022.
STUDY SELECTION
Included studies were randomized clinical trials comparing oseltamivir vs placebo or nonactive controls in outpatients with confirmed influenza infection.
DATA EXTRACTION AND SYNTHESIS
In this systematic review and meta-analysis, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two independent reviewers (R.H. and É.B.C.) extracted data and assessed risk of bias using the Cochrane Risk of Bias Tool 2.0. Each effect size was pooled using a restricted maximum likelihood random effects model. The quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.
MAIN OUTCOMES AND MEASURES
Hospitalization was pooled as risk ratio (RR) and risk difference (RD) estimates with 95% CIs.
RESULTS
Of 2352 studies identified, 15 were included. The intention-to-treat infected (ITTi) population was comprised of 6166 individuals with 54.7% prescribed oseltamivir. Across study populations, 53.9% (5610 of 10 471) were female and the mean age was 45.3 (14.5) years. Overall, oseltamivir was not associated with reduced risk of hospitalization within the ITTi population (RR, 0.79; 95% CI, 0.48 to 1.29; RD, -0.17%; 95% CI, -0.23% to 0.48%). Oseltamivir was also not associated with reduced hospitalization in older populations (mean age ≥65 years: RR, 1.01; 95% CI, 0.21 to 4.90) or in patients considered at greater risk of hospitalization (RR, 0.65; 0.33 to 1.28). Within the safety population, oseltamivir was associated with increased nausea (RR, 1.43; 95% CI, 1.13 to 1.82) and vomiting (RR, 1.83; 95% CI, 1.28 to 2.63) but not serious adverse events (RR, 0.71; 95% CI, 0.46 to1.08).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis among influenza-infected outpatients, oseltamivir was not associated with a reduced risk of hospitalization but was associated with increased gastrointestinal adverse events. To justify continued use for this purpose, an adequately powered trial in a suitably high-risk population is justified.
Topics: Adult; Adolescent; Humans; Female; Aged; Middle Aged; Male; Oseltamivir; Influenza, Human; Outpatients; Hospitalization; Europe
PubMed: 37306992
DOI: 10.1001/jamainternmed.2023.0699 -
JAMA Pediatrics Nov 2022Oseltamivir is recommended for all children hospitalized with influenza, despite limited evidence supporting its use in the inpatient setting.
IMPORTANCE
Oseltamivir is recommended for all children hospitalized with influenza, despite limited evidence supporting its use in the inpatient setting.
OBJECTIVE
To determine whether early oseltamivir use is associated with improved outcomes in children hospitalized with influenza.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter retrospective study included 55 799 children younger than 18 years who were hospitalized with influenza from October 1, 2007, to March 31, 2020, in 36 tertiary care pediatric hospitals who participate in the Pediatric Health Information System database. Data were analyzed from January 2021 to March 2022.
EXPOSURES
Early oseltamivir treatment, defined as use of oseltamivir on hospital day 0 or 1.
MAIN OUTCOMES AND MEASURES
The primary outcome was hospital length of stay (LOS) in calendar days. Secondary outcomes included 7-day hospital readmission, late (hospital day 2 or later) intensive care unit (ICU) transfer, and a composite outcome of in-hospital death or use of extracorporeal membrane oxygenation (ECMO). Inverse probability treatment weighting (IPTW) based on propensity scoring was used to address confounding by indication. Mixed-effects models were used to compare outcomes between children who did and did not receive early oseltamivir treatment. Outcomes were also compared within high-risk subgroups based on age, presence of a complex chronic condition, early critical illness, and history of asthma.
RESULTS
The analysis included 55 799 encounters from 36 hospitals. The median (IQR) age of the cohort was 3.61 years (1.03-8.27); 56% were male, and 44% were female. A total of 33 207 patients (59.5%) received early oseltamivir. In propensity score-weighted models, we found that children treated with early oseltamivir had shorter LOS (median 3 vs 4 days; IPTW model ratio, 0.52; 95% CI, 0.52-0.53) and lower odds of all-cause 7-day hospital readmission (3.5% vs 4.8%; adjusted odds ratio [aOR], 0.72; 95% CI, 0.66-0.77), late ICU transfer (2.4% vs 5.5%; aOR, 0.41; 95% CI, 0.37-0.46), and the composite outcome of death or ECMO use (0.9% vs 1.4%; aOR, 0.63; 95% CI, 0.54-0.73).
CONCLUSIONS AND RELEVANCE
Early use of oseltamivir in hospitalized children was associated with shorter hospital stay and lower odds of 7-day readmission, ICU transfer, ECMO use, and death. These findings support the current recommendations for oseltamivir use in children hospitalized with influenza.
Topics: Humans; Male; Female; Child; Child, Preschool; Oseltamivir; Influenza, Human; Child, Hospitalized; Retrospective Studies; Hospital Mortality; Antiviral Agents; Length of Stay; Hospitalization
PubMed: 36121673
DOI: 10.1001/jamapediatrics.2022.3261 -
Cold Spring Harbor Perspectives in... Jan 2022The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic)... (Review)
Review
The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired under selective pressure, have been shown to reduce drug binding, thereby affecting the effectiveness of NA inhibitors. Drug resistance and other drawbacks have prompted the search for the next-generation NA-targeting therapeutics. One of the promising approaches is the identification of monoclonal antibodies (mAbs) targeting the conserved NA epitopes. Anti-NA mAbs demonstrate Fab-based antiviral activity supplemented with Fc-mediated immune effector functions. Antiviral Fc-conjugates offer another cutting-edge strategy that is based on a multimodal mechanism of action. These novel antiviral agents are composed of a small-molecule NA inhibitor and an Fc-region that simultaneously engages the immune system. The significant advancements made in recent years further support the value of NA as an attractive target for the antiviral development.
Topics: Antibodies, Monoclonal; Antiviral Agents; Drug Resistance, Viral; Enzyme Inhibitors; Humans; Influenza, Human; Neuraminidase; Oseltamivir; Zanamivir
PubMed: 32152244
DOI: 10.1101/cshperspect.a038455 -
FEBS Open Bio Jun 2022Influenza A and B viruses are among the most prominent human respiratory pathogens. About 3-5 million severe cases of influenza are associated with 300 000-650 000... (Review)
Review
Influenza A and B viruses are among the most prominent human respiratory pathogens. About 3-5 million severe cases of influenza are associated with 300 000-650 000 deaths per year globally. Antivirals effective at reducing morbidity and mortality are part of the first line of defense against influenza. FDA-approved antiviral drugs currently include adamantanes (rimantadine and amantadine), neuraminidase inhibitors (NAI; peramivir, zanamivir, and oseltamivir), and the PA endonuclease inhibitor (baloxavir). Mutations associated with antiviral resistance are common and highlight the need for further improvement and development of novel anti-influenza drugs. A summary is provided for the current knowledge of the approved influenza antivirals and antivirals strategies under evaluation in clinical trials. Preclinical evaluations of novel compounds effective against influenza in different animal models are also discussed.
Topics: Animals; Antiviral Agents; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Models, Animal; Oseltamivir
PubMed: 35451200
DOI: 10.1002/2211-5463.13416 -
Journal of Medicinal Chemistry Oct 2022Sialidases, or neuraminidases, are enzymes that catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly removal of the terminal Sia (desialylation). By... (Review)
Review
Sialidases, or neuraminidases, are enzymes that catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly removal of the terminal Sia (desialylation). By desialylation, sialidase can modulate the functionality of the target compound and is thus often involved in biological pathways. Inhibition of sialidases with inhibitors is an important approach for understanding sialidase function and the underlying mechanisms and could serve as a therapeutic approach as well. Transition-state analogues, such as anti-influenza drugs oseltamivir and zanamivir, are major sialidase inhibitors. In addition, difluoro-sialic acids were developed as mechanism-based sialidase inhibitors. Further, fluorinated quinone methide-based suicide substrates were reported. Sialidase product analogue inhibitors were also explored. Finally, natural products have shown competitive inhibiton against viral, bacterial, and human sialidases. This Perspective describes sialidase inhibitors with different mechanisms and their activities and future potential, which include transition-state analogue inhibitors, mechanism-based inhibitors, suicide substrate inhibitors, product analogue inhibitors, and natural product inhibitors.
Topics: Humans; Neuraminidase; Zanamivir; Oseltamivir; N-Acetylneuraminic Acid; Enzyme Inhibitors; Sialic Acids; Antiviral Agents; Biological Products
PubMed: 36252951
DOI: 10.1021/acs.jmedchem.2c01258 -
Seminars in Perinatology Dec 2014Pregnancy predisposes women to disproportionate morbidity and mortality from influenza infections. This is true for both seasonal epidemics as well as occasional... (Review)
Review
Pregnancy predisposes women to disproportionate morbidity and mortality from influenza infections. This is true for both seasonal epidemics as well as occasional pandemics. Inactivated yearly influenza vaccines are the best available method of disease prevention and are recommended for all pregnant women in any trimester of pregnancy and postpartum. Oseltamivir (Tamiflu(®)) is currently the first-line recommended and most commonly used pharmaceutical agent for influenza prophylaxis and treatment. Oseltamivir has been demonstrated to prevent disease among exposed individuals, as well as to shorten the duration of illness and lessen the likelihood of complications among those infected. The physiologic adaptations of pregnancy may alter the pharmacokinetics and pharmacodynamics of this important drug. Updated evidence regarding these potential alterations, current knowledge gaps, and future investigative directions is discussed.
Topics: Antiviral Agents; Female; Humans; Influenza, Human; Oseltamivir; Pregnancy; Pregnancy Complications, Infectious
PubMed: 25281358
DOI: 10.1053/j.semperi.2014.08.015 -
The American Journal of Managed Care Mar 2022To determine whether baloxavir use is associated with lower health care resource utilization (HCRU) and costs for secondary influenza complications post treatment...
OBJECTIVES
To determine whether baloxavir use is associated with lower health care resource utilization (HCRU) and costs for secondary influenza complications post treatment compared with oseltamivir.
STUDY DESIGN
Retrospective cohort study.
METHODS
Patients filling a prescription for baloxavir or oseltamivir within 48 hours following an influenza-related outpatient visit were identified in the 2018-2019 influenza season from the US Truven MarketScan Research Databases and propensity matched 1:2 (baloxavir:oseltamivir). Outcomes were assessed 15 and 30 days after antiviral treatment and included all-cause, all respiratory-related, and select respiratory-related (influenza, asthma, chronic obstructive pulmonary disease, or infection) HCRU and costs.
RESULTS
The study included 5080 baloxavir-treated and 10,160 matched oseltamivir-treated patients. All-cause emergency department (ED) visits and inpatient hospitalizations were lower in baloxavir-treated patients, with a statistically significant difference in the percentage hospitalized at 30 days (0.3% vs 0.5%; P = .04). ED visits for all or select respiratory-related conditions were significantly reduced with baloxavir (P < .01 for all comparisons). Mean per-patient cost savings at day 30 for all-cause, all respiratory-related, and select respiratory-related conditions were $79, $50, and $51, respectively, despite slightly higher prescription costs for baloxavir. In high-risk patients (baloxavir: n = 1958; oseltamivir: n = 3949), the incidence of ED visits was significantly lower for all respiratory-related and select respiratory-related conditions (P < .01); cost savings with baloxavir in the high-risk cohort were substantially greater than in the overall cohort.
CONCLUSIONS
Treatment of patients with influenza with single-dose baloxavir was generally associated with lower HCRU and costs post treatment compared with oseltamivir, particularly in high-risk patients.
Topics: Antiviral Agents; Dibenzothiepins; Humans; Influenza, Human; Morpholines; Oseltamivir; Pyridones; Retrospective Studies; Triazines
PubMed: 35404552
DOI: 10.37765/ajmc.2022.88786 -
Pharmacological Reports : PR Dec 2021The global spread of COVID-19 has imparted significant economic, medical, and social burdens. Like adults, children are affected by this pandemic. However, milder... (Review)
Review
The global spread of COVID-19 has imparted significant economic, medical, and social burdens. Like adults, children are affected by this pandemic. However, milder clinical symptoms are often experienced by them. Only a minimal proportion of the affected patients may develop severe and complicated COVID-19. Supportive treatment is recommended in all patients. Antiviral and immunomodulatory medications are spared for hospitalized children with respiratory distress or severe to critical disease. Up till now, remdesivir is the only USFDA-approved anti-COVID-19 medication indicated in the majority of symptomatic patients with moderate to severe disease. Dexamethasone is solely recommended in patients with respiratory distress maintained on oxygen or ventilatory support. The use of these medications in pediatric patients is founded on evidence deriving from adult studies. No randomized controlled trials (RCTs) involving pediatric COVID-19 patients have assessed these medications' efficacy and safety, among others. Similarly, three novel monoclonal anti-SARS-CoV-2 spike protein antibodies, bamlanivimab, casirivimab and imdevimab, have been recently authorized by the USFDA. Nonetheless, their efficacy has not been demonstrated by multiple RCTs. In this review, we aim to dissect the various potential therapeutics used in children with COVID-19. We aspire to provide a comprehensive review of the available evidence and display the mechanisms of action and the pharmacokinetic properties of the studied therapeutics. Our review offers an efficient and practical guide for treating children with COVID-19.
Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Child; Dexamethasone; Humans; Hydroxychloroquine; Ivermectin; Lopinavir; Oseltamivir; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19 Drug Treatment
PubMed: 34458951
DOI: 10.1007/s43440-021-00316-1