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International Journal of Environmental... Mar 2022Flu is a serious health, medical, and economic problem, but no therapy is yet available that has satisfactory results and reduces the occurrence of these problems.... (Review)
Review
Flu is a serious health, medical, and economic problem, but no therapy is yet available that has satisfactory results and reduces the occurrence of these problems. Nearly 20 years after the registration of the previous therapy, baloxavir marboxil, a drug with a new mechanism of action, recently appeared on the market. This is a promising step in the fight against the influenza virus. This article presents the possibilities of using all available antiviral drugs specific for influenza A and B. We compare all currently recommended anti-influenza medications, considering their mechanisms of action, administration, indications, target groups, effectiveness, and safety profiles. We demonstrate that baloxavir marboxil presents a similar safety and efficacy profile to those of drugs already used in the treatment of influenza. Further research on combination therapy is highly recommended and may have promising results.
Topics: Antiviral Agents; Enzyme Inhibitors; Humans; Influenza, Human; Neuraminidase; Pyridones
PubMed: 35270708
DOI: 10.3390/ijerph19053018 -
Frontiers in Pharmacology 2020Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide... (Review)
Review
Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide a suitable empiric antimicrobial dosing for patients receiving CRRT. Inappropriate doses of antimicrobial agents may lead to treatment failure or drug resistance of pathogens. CRRT factors, patient individual conditions and drug pharmacokinetics/pharmacodynamics are the main elements effecting the antimicrobial dosing adjustment. With the development of CRRT techniques, some antimicrobial dosing recommendations in earlier studies were no longer appropriate for clinical use now. Here, we reviewed the literatures involving in new progresses of antimicrobial dosages, and complied the updated empirical dosing strategies based on CRRT modalities and effluent flow rates. The following antimicrobial agents were included for review: flucloxacillin, piperacillin/tazobactam, ceftriaxone, ceftazidime/avibactam, cefepime, ceftolozane/tazobactam, sulbactam, meropenem, imipenem, panipenem, biapenem, ertapenem, doripenem, amikacin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, azithromycin, tigecycline, polymyxin B, colistin, vancomycin, teicoplanin, linezolid, daptomycin, sulfamethoxazole/trimethoprim, fluconazole, voriconazole, posaconzole, caspofungin, micafungin, amphotericin B, acyclovir, ganciclovir, oseltamivir, and peramivir.
PubMed: 32547394
DOI: 10.3389/fphar.2020.00786 -
Indian Journal of Pediatrics Oct 2020Influenza continues to baffle humans by its constantly changing nature. The twenty-first century has witnessed considerable advances in the understanding of the... (Review)
Review
Influenza continues to baffle humans by its constantly changing nature. The twenty-first century has witnessed considerable advances in the understanding of the influenza viral pathogenesis, its synergy with bacterial infections and diagnostic methods. However, challenges continue: to find a less expensive and more reliable point-of-care test for use in developing countries, to produce more efficacious antiviral drugs, to explore ways to combat emerging antiviral resistance and to develop vaccines that can either be produced in a shorter production time or can overcome the need for annual matching with the circulating influenza strains. Most importantly for India, as a nation that suffered the highest mortality in the influenza pandemic 1918, there is an urgent need to gear up our existing preparedness for the next pandemic which is capable to hit at any moment in time.
Topics: Drug Resistance, Viral; Humans; India; Influenza, Human
PubMed: 32048225
DOI: 10.1007/s12098-020-03214-1 -
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