P45 Antimicrobial activity of ruthenium-based metallo-therapeutics against Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that is highly resistant to antibiotics and biocidal products used in both medical and industrial environments respectively. Metal-based compounds have been used as antimicrobial agents throughout history for a broad range of applications. More recently, it has been shown that ruthenium (Ru)-based compounds have potent antimicrobial properties and, in contrast to traditional antibiotics, these are thought to elicit antibacterial activity at multiple sites within the bacterial cell, which will undoubtedly reduce the possibility of resistance evolution. Methods: MIC and MBC assays coupled with disc diffusion assays were used to screen a library of Ru-based compounds. Results: One lead compound was identified that was highly active at inhibiting growth of multiple strains of P. aeruginosa at ≤32 mg/L. Crystal violet biofilm assays were performed, which showed a decrease in biomass following exposure over a 24 h period. Scanning electron microscopy was used to reveal morphological changes in the bacterial cell ultrastructure when exposed to the Ru-based compound, with evidence of membrane perturbation that supported a proposed mechanism of antimicrobial activity. Conclusions: These findings make a significant contribution towards the search for novel bactericidal agents and further research is now focused on determining the potential for use as novel adjuvants within medicinal applications such as wound care management

Natural Antimicrobial Nano Composite Fibres Manufactured from a Combination of Alginate and Oregano Essential Oil

Alginate is a linear biodegradable polysaccharide polymer, which is bio-renewable and widely used for various biomedical applications. For the next generation of medical textiles, alginate nanofibres are desirable for their use in wound dressings that are biocompatible, sustainable, and abundantly available. This study has developed a unique manufacturing process for producing alginate nanofibres with exceptional antimicrobial properties of oregano essential oil (OEO) as a natural antimicrobial agent. OEO with varying degrees of concentration was incorporated in an aqueous alginate solution. Appropriate materials and electrospinning process parameter selection allowed us to manufacture alginate fibres with a range of diameters between 38 and 105 nm. A unique crosslinking process for alginate nanofibres using extended water soaking was developed. Mechanical characterisation using micro-mechanical testing of nonwoven electrospun alginate/oregano composite nanofibres revealed that it was durable. An extensive antimicrobial study was carried out on alginate/oregano composite nanofibres using a range of Gram-positive (methicillin-resistant Staphylococcus aureus (MRSA) and Listeria monocytogenes) and Gram-negative bacteria (Klebsiella pneumoniae and Salmonella enterica), which are common wound and food pathogens. The results indicated that increasing the concentration of OEO from 2 to 3 wt % showed improved antimicrobial activity against all pathogens, and activity was significantly improved against MRSA compared to a non-alginate-based control disk containing OEO. Therefore, our research suggests that all-natural alginate/oregano nanofibre composite textiles offer a new generation of medical textiles for advanced wound dressing technology as well as for food packaging applications

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Additional file 1 of The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling

Supplementary Material