Repositioning of Antibiotics in the Treatment of Viral Infections

Current Microbiology, Journal Year: 2024, Volume and Issue: 81(12)

Published: Oct. 26, 2024

Drug repurposing, also known as drug repositioning, is a currently tested approach by which new uses are being assigned for already drugs. In this case there antibiotics that used to combat bacterial infections. However, among the drugs have been studied possible antiviral activities. Therefore, aim of work carry out review studies could be repositioned treatment viral Among main demonstrated activity macrolides and glycopeptides. addition, several from group tetracyclines, fluoroquinolones, cephalosporins aminoglycosides their activity. These against both RNA DNA viruses, including recent pandemic virus SARS-CoV-2. Some these were selected in addition its immunomodulatory anti-inflammatory properties. Of present activity, many cases mechanisms action not exactly known. The use infections remains controversial generally accepted, since clinical trials required prove effectiveness. no antibiotic approved therapy. Hence necessary carried on can future

Language: Английский

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The PANORAMIC study of COVID-19 treatments in primary care: a review and learning exercise

Published: Aug. 8, 2024

NIHR Clinical Research Network

The PANORAMIC study of COVID-19 treatments in primary care: a review and learning exercise
Study IRAS Number: 1004274
August 2024

Foreword

Ever since the start pandemic early 2020, care research have been undergoing unprecedented and  rapid change. The Platform Adaptive trial NOvel antiviRals for eArly treatMent In Community (PANORAMIC),  the fastest recruiting largest therapeutic agent ever care, has just closed to recruitment. It is therefore opportune reflect on lessons learned from delivery this major UK-wide that informing guidelines NHS world-wide.
perspective delivery through National Institute Health Care Network (NIHR CRN) England analogous networks Wales, Scotland Northern Ireland. includes reflections about across four UK nations, talking detail those involved, probably first its kind. considerations both successes but also challenges conducting such as environment. inevitably touches aspects design, predominantly delivery.
Professor Philip Evans, Deputy Medical Director CRN, Link PANORAMIC
Executive Summary 'Platform Community' or study, led by Professor Chris Butler at University Oxford, one flagship trials Its sister trial, PRINCIPLE, tested clinical effectiveness repurposed drugs patients with mild moderate community. While evaluated cost-effectiveness novel oral antivirals, i.e. molnupiravir (Lagevrio) nirmatrelvir-ritonavir (Paxlovid) platform delivered care.
Background Trial onset caused SARS-CoV-2 virus, Department Social (DHSC) instituted Urgent Public (UPH) Group response need UPH (NIHR) (CRN), chaired Director, aimed prioritise CRN.
RAPTOR study (PI Richard Hobbs) designed test setting, opened 2020.  To setting href="https://www.principletrial.org/">PRINCIPLE set CIs Professors Hobbs Trials Unit (CTU), Nuffield Sciences, Oxford. 
RECOVERY, href="https://www.icnarc.org/Our-Research/Studies/Remap-Cap/About">REMAP-CAP, href="https://www.agiletrial.net/">AGILE, href="https://www.camcovidtrials.net/trials/protect.htm">PROTECT-V, href="https://www.stimulate-icp.org/">STIMULATE-ICP href="https://heal-covid.net/">HEAL-COVID. adaptive (Hayward, et al., 2021) Bayesian techniques, subsequently went assess included hydroxychloroquine, colchicine (Dorward, 2022), azithromycin (PRINCIPLE Collaborative Group, 2021), inhaled budesonide (Yu, doxycycline (Butler, favipiravir ivermectin (Hayward al, 2024), master protocol investigational medicinal product (IMP)-specific appendices. only finding beneficial effect time recovery, hospitalisation or death - latter being arms.
a call care. 
'Platform (PANORAMIC) (CIs Butler, Paul Little Hobbs). NIHR-funded Antivirals Therapeutics Taskforce (ATTF)-supported endorsed CMOs sought provide evidence-base decisions deployment including cost-effectiveness. Candidate assessed Advisory Panel href="https://www.ukri.org/about-us/policies-standards-and-data/data-collection/uk-covid-19-therapeutics-advisory-panel/">(UK-CTAP) eight priority, publicly funded recommended inclusion if appropriate. drug developed href="https://www.msd-uk.com/">MSD, followed nirmatrelvir/ritonavir href="https://www.pfizer.co.uk/">Pfizer.
Population

• Positive polymerase chain reaction (PCR) lateral flow device (LFD) Covid-19.
• Clinically Vulnerable 18 years
• Anyone aged 50 over
• Symptoms max 5 days

Intervention

Oral efficacy safety data phase 2/smaller trials

Molnupiravir intended intervention

Then Paxlovid

Comparator

Standard care/usual care

Outcome

Hospitalisation death, outcomes costs, safety, viral load, variants resistance (sub-study)

By 27 26,411 usual arm, December 2022 final results analysis published The Lancet after pre-publication preliminary 2022. continued recruit Paxlovid arms until end March (the 28 2024). 29,293 participants, required sample size achieved study.
 Methodology progressed broke ground so areas stock order do stakeholder workshop held online 2 February 2023, involving CIs), Coordinating Centre, local (LCRNs), England, Digital (as was), regulatory Authority (HRA), Devolved Administration (see full list attendees below). A facilitated themed discussions undertaken and, Google-specific tool (Jamboard), enabled comments directly. After workshop, these individual analysed refined specific themes addressed individually section-by-section report. One deep-dive digital domain similar methodology, building previous feedback.
Operational Oversight, Delivery, Government Engagement support pace scale UK, small prepare planning, set-up, study, oversee progress activities. Close working DHSC, vital central messaging around prioritisation pandemic, PANORAMIC. discusses how achieved, depth.

Novel Recruitment Strategies Hub & Spoke Models
Staff Workforce: Provision, Capacity, Development, Training
Regulatory, governance, sharing considerations
Costing Payments
. This associated SoECAT studies.
Digital Solutions Support Recruitment
Equality, Diversity, Inclusion (Including Patient Involvement (PPI))
Nationwide Considerations
Best practice case successes, Based thirty environment.
Recommendations Themes
Pandemic Studies

In consideration should given reach very any to  ameliorate patients' symptoms reduce admission.

Primary infrastructure, models, agents.

Diagnostic could integrated symptomatic asymptomatic mass testing programmes maximal efficiency.

The concept encouraged pandemics widely.

Close respective taskforces, Government, regulators, funders, encouraged.  include involvement nations.

Design Studies

Having variety ability flex pressures vital. site participate operational start.

Work define enhanced homes pandemics.

Pragmatic seek mechanistic sub-studies microbiological immunological samples often collected remotely. treatment face emerging strains then determined.

Engagement Sponsors, researchers (NHSE) stage extent costs excess costs.

referrals opposed Participant Identification Centres (PIC)  should carefully considered, advantages disadvantages. Research

Centralised dispatch (i.e. products kits)  considered design.  Ways delivering medicine directly home applied deployment, proven. 

NIHR agile flexibility facilitate efficient recruitment.

Involvement appropriate language flows prevent subsequent amendments.  

A pragmatic (Schedule Events Cost Attribution Template) following substantive either amendments changing methods.

Practices engaged syndromic surveillance phenotyping, sentinel surveillance.

Inclusion co-created equality, diversity (EDI) strategy build trust relationships promote inclusion.

There broad-based, mix patient (PPIE) activities, emphasis EDI ethnicity (such living disability).

pharmacy networks, pharmacies, communities. hybrid plus way increasing people engage regardless where they live receive healthcare. translations, consider communication channels, making effective accessible. Workforce

Research trained possible, exposed remote standard, equipped remotely, agility lower risk becoming themselves diseases outbreaks.

Standardisation skills, contracts moving forward respond needs system.

Clear arrangements contracting guidance better organisational boundaries, universities.

Engagement

Future benefit option register tests system. would  assist GP facilitating 'direct patient' text highlighting opportunities.

Data mirrors journey system, stages process. 

Established streamlined processes needed enable retrieval scope Summary Record screen check eligibility record.

Informatics Environment (PRIDES) systems practices identify individuals, well-received GPs underpin type trial. Systematised Nomenclature Medicine (SNOMED) codes recording invitation participation implemented successfully, replicated practices.

Although uptake Platform WebViewer minimal sites, demonstrate proof principle alternative method identification eligible individuals.

Authorship

Writing Team
: Centre (corresponding author).
Dr Emma Tonner: Director's Fellow, Centre.
: Lead, Mark Dolman: Chief Operating Officer, Thames Valley South Midlands (Lead Network).
: Sarah E. Crawshaw: Head Ly-Mee Yu: Co-Director Unit, Oxford.
Disclaimers (Award ID: NIHR135366). views expressed author(s) necessarily Care.
Acknowledgements group gratefully acknowledges widespread productive stakeholders, contribution We sites constituent teams, leadership Special thanks go Investigators (CIs) input Julie Allen Lucy Cureton Senior Managers, process. thousands took success realised.
References Bower, P., Grigoroglou, C., Anselmi, L., Kontopantelis, E., Sutton, M., Ashworth, Lock, S., Smye, Abel, K. (2020). Is burden greatest? Observational geographical inequalities 2013-2018. BMC Med. 18(1):133.
Lancet. 401(10373):281-293.
Lancet Respir 9(9):1010-1020.
Br Gen Pract. 72(720):e446-e455.
BMJ Open. 11(6):e046799.
J Infect. 88(4):106130.
Trials. 13(3):358-66.
Key Words
COVID-19/ / Omicron/ Care/ Decentralised Molnupiravir/ PRIDES Equality, Diversity Inclusion/ Lagevrio /  Referral UK-Wide/ Antiviral Virology Hybrid

Language: Английский

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The impact of ivermectin on COVID-19 outcomes: a systematic review and meta-analysis

Annals of Medicine and Surgery, Journal Year: 2024, Volume and Issue: 87(2), P. 809 - 829

Published: Dec. 11, 2024

The COVID-19 pandemic, resulting in approximately seven million deaths globally, underscores the urgency for effective treatments. Ivermectin, among several repurposed drugs, garnered interest due to its antiviral properties. However, conflicting evidence from observational studies and randomized controlled trials raised questions about efficacy safety. This systematic review meta-analysis followed MOOSE PRISMA guidelines. Comprehensive searches were conducted databases including Scopus, Embase, PubMed, Web of Science up April 2024. Data extracted independently by two reviewers analyzed using Meta-Analysis V3 software. Across 33 encompassing 15,376 participants, ivermectin showed no significant impact on critical outcomes such as mortality [risk ratio (RR) 0.911, 95% confidence intervals (CI) 0.732-1.135], mechanical ventilation (RR 0.727, CI 0.521-1.016), polymerase chain reaction conversion 1.024, 0.936-1.120), ICU admissions 0.712, 0.274-1.850), or hospitalization rates 0.735, 0.464-1.165) compared controls. it significantly reduced time symptom alleviation (standardized mean difference -0.302, -0.587 -0.018) sustained relief 0.897, 0.873-0.921). Adverse event (AE) similar between control groups 0.896, 0.797-1.007). Meta-regression indicated older age diabetes predictors AEs. Despite observed benefits management, did not influence clinical patients. These findings highlight importance continued research identify treatments COVID-19, emphasizing need high-quality with robust methodology inform practice public health policy effectively.

Language: Английский

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