A5011598437- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- SARS-CoV-2 and COVID-19 Research
- Antibiotics Pharmacokinetics and Efficacy
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Accounting and Organizational Management
- Antibiotic Resistance in Bacteria
- Respiratory viral infections research
- Animal Virus Infections Studies
- Neutropenia and Cancer Infections
- Nail Diseases and Treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- Infectious Diseases and Mycology
- Fusion materials and technologies
- Drug Transport and Resistance Mechanisms
- Peptidase Inhibition and Analysis
- Pharmacological Effects and Toxicity Studies
- Influenza Virus Research Studies
- Accounting Education and Careers
- Vector-Borne Animal Diseases
- Ion-surface interactions and analysis
- Transport and Economic Policies
- Advanced Materials Characterization Techniques
- Advanced Drug Delivery Systems
University of Liverpool
2012-2025
University of Huddersfield
2024
Liverpool Hospital
2021
Evotec (United Kingdom)
2018-2020
Spring Hill College
2014-2019
University of Manchester
2002-2013
Manchester Academic Health Science Centre
2009-2013
National Health Service
2011-2013
National Institute for Health Research
2011-2013
Southwestern Oklahoma State University
2004
Abstract Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2) 1 , could represent a new chemoprophylactic approach for COVID-19 that complements vaccination 2,3 . However, the mechanisms control expression of ACE2 remain unclear. Here we show farnesoid X receptor (FXR) is direct regulator transcription in several tissues affected COVID-19, including gastrointestinal and respiratory systems. We then use over-the-counter compound...
COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence SARS-CoV-2 seasonal respiratory viruses, particularly influenza global health concern. To understand this, transgenic mice expressing the human ACE2 receptor (K18-hACE2) were infected A virus (IAV) followed and host response effect on biology was compared to K18-hACE2 IAV or alone. sequentially showed reduced RNA synthesis, yet exhibited more rapid weight loss, severe lung damage...
Background. Posaconazole is a triazole with anti-Aspergillus activity. However, little known about the utility of posaconazole as primary therapy for invasive pulmonary aspergillosis. Methods. An in vitro model human alveolus was used to study impact minimum inhibitory concentrations (MIC) on exposure-response relationships. The pharmacokinetic-pharmacodynamic relationships were examined an inhalational murine A mathematical fitted entire data set. This then describe relationship between...
Management of nosocomial pneumonia is frequently complicated by bacterial resistance. Extended infusions beta-lactams are increasingly being used to improve clinical outcomes. However, the impact this strategy on emergence antimicrobial resistance not known. A hollow-fiber infection model with Pseudomonas aeruginosa (PAO1) was used. Pharmacokinetic (PK) profiles piperacillin-tazobactam similar those in humans were simulated over 5 days. Three dosages administered 0.5 h or 4 h, redosing every...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic and urgent treatment prevention strategies are needed. Nitazoxanide, an anthelmintic drug, shown to exhibit in vitro activity against SARS-CoV-2. The present study used physiologically based pharmacokinetic (PBPK) modelling inform optimal doses of nitazoxanide capable maintaining plasma lung tizoxanide exposures above the reported SARS-CoV-2 EC
Objectives: BAL4815 is the active component of antifungal triazole agent BAL8557 (the water-soluble prodrug). We compared in vitro activity with that itraconazole, voriconazole, caspofungin and amphotericin B against 118 isolates Aspergillus comprising four different species (fumigatus, terreus, flavus niger); were pre-selected to include 16 demonstrating resistance other agents.
ABSTRACT Isavuconazole is a triazole with broad-spectrum activity against medically important fungal pathogens. We investigated the pharmacokinetics and pharmacodynamics of isavuconazole in murine model disseminated candidiasis. determined both plasma kidney. The relationship between tissue concentrations resultant antifungal effect was described using mathematical model. pharmacodynamic parameter that optimally links drug exposure dose fractionation studies. impact immune status mice...
Fluconazole is frequently the only antifungal agent that available for induction therapy cryptococcal meningitis. There relatively little understanding of pharmacokinetics and pharmacodynamics (PK-PD) fluconazole in this setting. PK-PD relationships were estimated with 4 clinical isolates Cryptococcus neoformans. MICs determined using Clinical Laboratory Standards Institute (CLSI) methodology. A nonimmunosuppressed murine model meningitis was used. Mice received two different doses (125...
Pharmaceutical excipients are no longer considered inert and have been shown to influence the activity of metabolic enzymes transporters, resulting in altered pharmacokinetics substrate drugs. In this study, effect 25 commonly used drug formulations were investigated for their on P-glycoprotein (P-gp) activity. The P-gp assessed by measuring change cellular accumulation a substrate, digoxin, MDCK-MDR1 (Madin Darby canine kidney transfected with multidrug resistance 1 gene) cells. cells...
BackgroundThere is growing interest in utilizing structured extended periods of simulation as partial replacement for clinical placement (PRCP) due to workforce demands and COVID-19 impact. This project aimed identify the extent which stakeholders felt that simulated placements could reduce overall time requirement health care students.MethodParticipants included a range nurses Allied Health Professionals including managers, clinicians lecturers. A three-round Delphi study was conducted with...
COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines drug-like advantages both. Bicycles are entropically constrained peptides stabilized by central chemical scaffold into bi-cyclic structure. Rapid screening diverse bacteriophage libraries against Spike yielded unique Bicycle binders across entire protein. Exploiting Bicycles' inherent combinability, converted...
BAL8557 (WSA) is the water-soluble prodrug of triazole BAL4815 with in vitro anti-Aspergillus activity. We compared activity oral itraconazole, voriconazole and intravenous caspofungin a temporarily neutropenic murine model disseminated Aspergillus flavus.Mice were immunosuppressed using cyclophosphamide, then infected. Mice treated either 2 h pre-infection (PRE), or 4 24 post-infection (4POST 24POST, respectively). Treatment was for 10 days followed by observation. Surviving mice killed...
A randomised double-blind controlled trial compared three-day and 10-day courses of amoxycillin (25 mg/kg daily) in children with otitis media. Seventeen doctors from five centres admitted 84 between the ages 2 10 years. Symptoms signs were measured on admission to trial, day 3, 15. Mother9s observations recorded daily for days. Audiograms performed at four 12 weeks after end trial. The treatment groups showed little difference speed resolution symptoms signs, numbers primary failures, or...
The aim of this study was to assess the dose–response isavuconazole, voriconazole and fluconazole in disseminated Candidatropicalis Candidakrusei infections. Mice were immunosuppressed using either one dose [temporarily neutropenic (TN)] or two doses [persistently (PN)] cyclophosphamide. Treatment started 5 h after infection with oral isavuconazole (6, 15, 30, 60, 90, 120 150 mg/kg equivalent active compound), intravenous (5, 20 40 plus grapefruit gavage twice daily) (15, 50 mg/kg) all...
Background Despite advances in the treatment, morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70–90%) immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic broad spectrum antifungal activity appears to be choice of treatment but is available only as an intravenous formulation; development oral formulation would beneficial well economical. Methodology Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs)...
The clinical utility of the echinocandins is potentially compromised by emergence drug resistance. We investigated whether Candida albicans with amino acid substitutions at position Ser645 in Fks1 can be treated either a conventional or an elevated dosage micafungin. studied (wild-type SC5314; MIC, 0.06 mg/liter) and four fks1 mutants (one FKS1/fks1 heterozygote mutant [MIC, 0.5 mg/liter] three fks1/fks1 homozygous [MICs for all, 2 mg/liter]) variety Ser645. pharmacokinetic pharmacodynamic...
Cryptococcal meningoencephalitis is a lethal infection with relatively few therapeutic options. The optimal dosage of liposomal amphotericin B (LAmB) alone or in combination flucytosine not known.A murine model cryptococcal was used. fungal density the brain determined using quantitative cultures. Pharmacokinetic-pharmacodynamic relationships were for LAmB and administered alone. effect described Greco mathematical model. results bridged to humans.Inoculation resulted hematogenous...
Candida glabrata is a leading cause of disseminated candidiasis. The echinocandins are increasingly used as first-line agents for the treatment patients with this syndrome, although optimal regimen invasive infections in neutropenic not known. We studied pharmacokinetics (PK) and pharmacodynamics (PD) micafungin, anidulafungin, caspofungin murine model infection to gain further insight into therapeutic options syndrome. A mathematical was fitted data bridge experimental results humans....
ABSTRACT Immunocompromised individuals are susceptible to severe coronavirus disease 2019 and potentially contribute the emergence of variants with altered pathogenicity due persistent infection. This study investigated impact immunosuppression on acute respiratory syndrome 2 (SARS-CoV-2) infection in K18-hACE2 mice effectiveness antiviral treatments this context during first 7 days Mice were immunosuppressed using cyclophosphamide infected a B lineage SARS-CoV-2. Molnupiravir nirmatrelvir,...
ABSTRACT Hematogenous Candida meningoencephalitis (HCME) is a serious infection in premature neonates. Anidulafungin an echinocandin antifungal agent with potent activity against spp., but its efficacy and optimal regimens for human neonates HCME are not known. A well-validated rabbit model of was used to define pharmacokinetic-pharmacodynamic (PK-PD) relationships anidulafungin. mathematical fitted the entire data set. The experimental were bridged humans. population PK from receiving...
Annual global deaths from cryptococcal meningitis (CM) are estimated at 180 000 and mortality is as high 30%, even with optimal therapy. VT-1598 a novel fungal CYP51 inhibitor potent intrinsic antifungal activity against Cryptococcus. We report here VT-1598's in vivo murine model of CM.Single-dose plasma brain pharmacokinetics mice MIC for Cryptococcus neoformans H99 were determined prior to efficacy studies. Short-course monotherapy combination doses explored the endpoint burden. A survival...