A pilot study investigating the effects of a manuka honey sinus rinse compared to a standard sinus rinse on sino-nasal outcome test scores in cystic fibrosis patients

Abstract: Background: People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a reservoir for these pathogens, and as part of clinical care, sinus rinses are used to alleviate symptoms in the upper airway. We have developed a sinus rinse containing manuka honey, to identify whether it can help improve symptoms or reduce the bacterial load. Methods: We will undertake a randomised controlled trial where 30 adults with CF will be recruited and randomised to either the control or intervention group. Both groups will follow a sinus rinse protocol for 30 days (± 7 days); the control group will use the standard of care rinse, and the intervention group will use a manuka honey rinse. Both groups will provide samples at day 0 and day 30. The primary outcome measure will be a change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes will include changes to quality of life (questionnaire), bacterial load/community composition, and sputum viscosity. Discussion: This trial will look at the use of a manuka honey-infused sinus rinse solution on patients diagnosed with cystic fibrosis (CF) suffering with sinusitis; it will allow us to determine the efficacy of the manuka honey sinus rinse compared to standard rinse and will allow us to determine if molecular bacterial diversity analysis will provide in-depth information beyond the usual conventional microbiological. It will allow us to determine the feasibility of recruiting participants to this type of trial, allow us to check participant compliance with the protocol, and inform future studies. Trial registration: Approval was obtained from the Research Ethics Committee Wales REC7 reference 18/WA/0319. Results of this study will be published at international conferences and in peer-reviewed journals; they will also be presented to the relevant stakeholders and research networks. Trial registration number: ClinicalTrials.gov Identifier NCT04589897 (retrospectively registered

On the antibacterial effects of manuka honey: mechanistic insights

Abstract: Antimicrobial resistance (AMR) is an increasing clinical problem precipitated by the inappropriate use of antibiotics in the later parts of the 20th Century. This problem, coupled with the lack of novel therapeutics in the development pipeline, means AMR is reaching crisis point, with an expected annual death rate of ten million people worldwide by 2050. To reduce, and to potentially remedy this problem, many researchers are looking into natural compounds with antimicrobial and/or antivirulence activity. Manuka honey is an ancient antimicrobial remedy with a good track record against a wide range of nosocomial pathogens that have increased AMR. Its inhibitory effects are the result of its constituent components, which add varying degrees of antimicrobial efficacy to the overall activity of manuka honey. The antimicrobial efficacy of manuka honey and some of its constituent components (such as methylglyoxal and leptosperin) are known to bestow some degree of antimicrobial efficacy to manuka honey. Despite growing in vitro evidence of its antimicrobial efficacy, the in vivo use of manuka honey (especially in a clinical environment) has been unexpectedly slow, partly due to the lack of mechanistic data. The mechanism by which manuka honey achieves its inhibitory efficacy has recently been identified against Staphylococcus aureus and Pseudomonas aeruginosa, with both of these contrasting organisms being inhibited through different mechanisms. Manuka honey inhibits S. aureus by interfering with the cell division process, whereas P. aeruginosa cells lyse in its presence due to the reduction of a key structural protein. In addition to these inhibitory effects, manuka honey is known to reduce virulence, motility, and biofilm formation. With this increasing in vitro dataset, we review the components and our mechanistic knowledge of manuka honey and how manuka honey could potentially be utilized in the future to impact positively on the treatment of microbial, resistant infections. Keywords: Staphylococcus aureus, Pseudomonas aeruginosa, biofilm, antibiotic resistanc

Contrasting effects of linezolid on healthy and dysfunctional human neutrophils: reducing C5a-induced injury

Background: To manage increasing demand for emergency and unscheduled care NHS England policy haspromoted services in which patients presenting to Emergency Departments (EDs) with non-urgent problems aredirected to general practitioners (GPs) and other primary care clinicians working within or alongside emergencydepartments. However, the ways that hospitals have implemented primary care services in EDs are varied. The aimof this study was to describe ED clinical leads’ experiences of implementing and delivering ‘primary care services’and ‘emergency medicine services’ where GPs were integrated into the ED team. Methods: We conducted interviews with ED clinical leads in England (n = 19) and Wales (n = 2). We usedframework analysis to analyse interview transcripts and explore differences across ‘primary care services’, ‘emergency medicine services’ and emergency departments without primary care services. Results: In EDs with separate primary care services, success was reported when having a distinct workforce ofprimary care clinicians, who improved waiting times and flow by seeing primary care-type patients in a timely way,using fewer investigations, and enabling ED doctors to focus on more acutely unwell patients. Some challengeswere: trying to align their service with the policy guidance, inconsistent demand for primary care, accessiblecommunity primary care services, difficulties in recruiting GPs, lack of funding, difficulties in agreeing governanceprotocols and establishing effective streaming pathways. Where GPs were integrated into an ED workforce successwas reported as managing the demand for both emergency and primary care and reducing admission

A review of selected bee products as potential anti-bacterial, anti-fungal, and anti-viral agents

Antimicrobial resistance (AMR) is one of the greatest medical challenges the world faces. It was estimated recently that by 2050, AMR will account for 10 million extra deaths annually with additional economic costs in the region of $100 trillion. In order to combat this, novel antimicrobial agents with a broad spectrum of activity are required. Bee products, including; honey, propolis, defensins, royal jelly, bee pollen and venom have been used to treat infectious diseases for several centuries, although they were largely disregarded by Western medicine during the antibiotic era. There has since been a resurgence in interest in their antimicrobial properties, especially due to their reported activity against multi-drug resistant pathogens displaying high levels of AMR. In this paper we review the current scientific literature of honey, propolis, honey bee, defensins, royal jelly, bee pollen and bee venom. We highlight the antimicrobial activity each of these products has displayed and potential future research directions

Antibacterial and anti-virulence activity of manuka honey against genetically diverse Staphylococcus pseudintermedius strains

Staphylococcus pseudintermedius causes opportunistic infections in dogs. It also has significant zoonotic potential, with the emergence of multidrug-resistance leading to difficulty treating both animal and human infections. Manuka honey has previously been reported to inhibit many bacterial pathogens including methicillin resistant Staphylococcus aureus and is successfully utilised in both clinical and veterinary practice. Here we evaluated the ability of manuka honey to inhibit strains of S. pseudintermedius growth alone and in combination with antibiotics, and its capacity to modulate virulence within multiple S. pseudintermedius. All 18 of the genetically diverse S. pseudintermedius strains sequenced and tested were inhibited by ≤ 12% (w/v) medical grade manuka honey, although tolerance to five clinically relevant antibiotics was observed. The susceptibility of the isolates to four of these antibiotics was significantly increased (p ≤0.05) when combined with sub lethal concentrations of honey, although sensitivity to oxacillin was decreased. Virulence (DNase, protease and haemolysin) activity was also significantly reduced (p ≤ 0.05) in over half of isolates when cultured with sub lethal concentrations of honey (13, 9 and 10 isolates respectively). These findings highlight the potential for manuka honey to be utilised against S. pseudintermedius infections. Importance: Staphylococcus pseudintermedius is an important member of the skin microbial community in animals and can cause opportunistic infections in both pets and their owners. The high incidence of antimicrobial resistance in S. pseudintermedius highlights that this opportunistic zoonotic pathogen can cause infections which require prolonged and intensive treatment to resolve. Manuka honey has proven efficacy against many bacterial pathogens and is an accepted topical treatment for infections in both veterinary and clinical practice so is a particularly appropriate antimicrobial for use with zoonotic pathogens such as S. pseudintermedius. Here we demonstrate that manuka honey is not only highly potent against novel multi-drug resistant S. pseudintermedius isolates, but also acts synergistically with clinically relevant antibiotics. In addition, manuka honey modulates S. pseudintermedius virulence activity, even at subinhibitory concentrations. In a clinical setting these attributes may assist in controlling infection, allowing a more rapid resolution and reducing antibiotic use

Impact of COVID-19 pandemic on community medication dispensing: a national cohort analysis in Wales, UK

BackgroundPopulation-level information on dispensed medication provides insight on the distribution of treated morbidities, particularly if linked to other population-scale data at an individual-level.ObjectiveTo evaluate the impact of COVID-19 on dispensing patterns of medications.MethodsRetrospective observational study using population-scale, individual-level dispensing records in Wales, UK. Total dispensed drug items for the population between 1st January 2016 and 31st December 2019 (3-years, pre-COVID-19) were compared to 2020 with follow up until 27th July 2021 (COVID-19 period). We compared trends across all years and British National Formulary (BNF) chapters and highlighted the trends in three major chapters for 2019-21: 1-Cardiovascular system (CVD); 2-Central Nervous System (CNS); 3-Immunological & Vaccine. We developed an interactive dashboard to enable monitoring of changes as the pandemic evolves.ResultAmongst all BNF chapters, 73,410,543 items were dispensed in 2020 compared to 74,121,180 items in 2019 demonstrating -0.96% relative decrease in 2020. Comparison of monthly patterns showed average difference (D) of -59,220 and average Relative Change (RC) of -0.74% between the number of dispensed items in 2020 and 2019. Maximum RC was observed in March 2020 (D= +1,224,909 and RC= +20.62%), followed by second peak in June 2020 (D= +257,920, RC= +4.50%). A third peak was observed in September 2020 (D= +264,138, RC= +4.35%). Large increases in March 2020 were observed for CVD and CNS medications across all age groups. The Immunological and Vaccine products dropped to very low levels across all age groups and all months (including the March dispensing peak).ConclusionsReconfiguration of routine clinical services during COVID-19 led to substantial changes in community pharmacy drug dispensing. This change may contribute to a long-term burden of COVID-19, raising the importance of a comprehensive and timely monitoring of changes for evaluation of the potential impact on clinical care and outcomes

A pilot study investigating the effects of a manuka honey sinus rinse compared to a standard sinus rinse on sino-nasal outcome test scores in cystic fibrosis patients

Background: People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a reservoir for these pathogens, and as part of clinical care, sinus rinses are used to alleviate symptoms in the upper airway. We have developed a sinus rinse containing manuka honey, to identify whether it can help improve symptoms or reduce the bacterial load. Methods: We will undertake a randomised controlled trial where 30 adults with CF will be recruited and randomised to either the control or intervention group. Both groups will follow a sinus rinse protocol for 30 days (± 7 days); the control group will use the standard of care rinse, and the intervention group will use a manuka honey rinse. Both groups will provide samples at day 0 and day 30. The primary outcome measure will be a change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes will include changes to quality of life (questionnaire), bacterial load/community composition, and sputum viscosity. Discussion: This trial will look at the use of a manuka honey-infused sinus rinse solution on patients diagnosed with cystic fibrosis (CF) suffering with sinusitis; it will allow us to determine the efficacy of the manuka honey sinus rinse compared to standard rinse and will allow us to determine if molecular bacterial diversity analysis will provide in-depth information beyond the usual conventional microbiological. It will allow us to determine the feasibility of recruiting participants to this type of trial, allow us to check participant compliance with the protocol, and inform future studies. Trial registration: Approval was obtained from the Research Ethics Committee Wales REC7 reference 18/WA/0319. Results of this study will be published at international conferences and in peer-reviewed journals; they will also be presented to the relevant stakeholders and research networks

Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes

Background & Aims: Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. Methods: Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. Results: HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. Conclusions: HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes