Trends and geographical variations in outpatient antimicrobial consumption in Ireland in relation to socio-economic deprivation.

Background: Different factors have been associated with changes in antimicrobial consumption rates in Ireland, however the relationship between socio-economic deprivation and antimicrobial consumption has not been explored. The presented ecological analysis explores the temporal and geographical variation in outpatient antimicrobial consumption and socio-economic deprivation in Ireland from January 2015 to March 2022. Method: Deprivation index (DI) was used as a socio-economic proxy. A multilevel mixed model was applied to explore temporal variation and analyse the longitudinal antimicrobial consumption (DID) in relation to DI. Furthermore, maps were generated based on antimicrobial consumption rates, and spatial autocorrelation analyses were carried out to study geographical variation in antimicrobial consumption rates. Results: The antimicrobial consumption rates per month varied from 26.2 DID (January 2015) to 22.1 DID (March 2022) showing an overall reduction of 16 %. Overall, total antimicrobial consumption in the multilevel model showed a consistent correlation with higher DI score (6.6 (95%CI 3.9 to 9.3)), and winter season (3.6 (95%CI 3.2 to 3.9)). In contrast, before COVID-19 showed significant lower antimicrobial consumption rates compared to during COVID-19 (-4.0 (95%CI -4.7 to -3.23)). No consistent trends were observed for geographical variation between areas. Conclusion: Antimicrobial consumption rates decreased from 2015 to 2021 in Ireland. No geographical patterns were observed in antimicrobial consumption rates but associations between deprivation and antimicrobial consumption rates were observed.

A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients.

Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem's activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study's primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP.

First Vesicular Self-assembly of an Apocarotenoid Bixin in Aqueous Liquids and its Antibacterial Activity.

Bixin1 is the major constituent of the reddish carotenoids present in the seed-coat of Bixa orellana.  The use of the extract of the seed-coat of Bixa orellana in food, cosmetics and garments is well known. The nano-sized long 24C chain molecule has nine conjugated double bonds having extended conjugation with the '-COOH' and '-COOMe' groups present at the two ends of the molecule.  Herein, we report the first self-assembly of bixin in several aqueous liquids. The molecule undergoes spontaneous self-assembly in several liquids yielding vesicular self-assembly.  Characterizations of the self-assemblies of bixinwere carried out by various microscopic techniques, X-ray diffraction and FTIR studies. The critical vesicular concentrations (CVCs) of the compound carried out in DMSO-water in three different solvent ratios as 2: 1 (v/v), 1: 1 (v/v) and 1: 4 (v/v) were determined to be 100 mM, 90 mM and 60 mM respectively indicating lower CVC values at higher proportion of water. Utilization of the vesicular self-assemblies of bixin have been demonstrated in the entrapment and release of fluorophores including the anticancer drugs doxorubicin and curcumin.  Self-assembled bixin and curcumin loaded self-assembled bixin showed significant antibacterial activity with both Gram positive as well as Gram negative bacteria.

Hybrid Zinc Oxide Nanocoating on Titanium Implants: Controlled Drug Release for Enhanced Antibacterial and Osteogenic Performance in Infectious Conditions.

Implant-associated bacterial infections are a primary cause of complications in orthopedic implants, and localized drug delivery represents an effective mitigation strategy. Drawing inspiration from the morphology of desiccated soil, our group has developed an advanced drug-delivery system augmented onto titanium (Ti) plates. This system integrates zinc oxide (ZnO) nanorod arrays with a vancomycin drug layer along with a protective Poly(lactic-co-glycolic acid) (PLGA) coating. The binding between the ZnO nanorods and the drug results in attached drug blocks, isolated by desiccation-like cracks, which are then encapsulated by PLGA to enable sustained drug release. Additionally, the release of zinc ions and the generation of reactive oxygen species (ROS) from the ZnO nanorods enhance the antibacterial efficacy. The antibacterial properties of ZnO nanorod-drug-PLGA system have been validated through both in vitro and in vivo studies. Comprehensive investigations were conducted on the impact of bacterial infections on bone defect regeneration and the role of this drug-delivery system in the healing process. Furthermore, the local immune response was analyzed and the immunomodulatory function of the system was demonstrated. Overall, the findings underscore the superior performance of the ZnO nanorod-drug-PLGA system as an efficient and safe approach to combat implant-associated bacterial infections. STATEMENT OF SIGNIFICANCE: Implant-associated bacterial infections pose a significant clinical challenge, particularly in orthopedic procedures. To address this, we developed an innovative ZnO nanorod-drug-PLGA system for local antibiotic delivery on conventional titanium implants. This system is biodegradable and features a unique desiccation-like structure that enables sustained drug release, along with the active substances released from the ZnO nanorods. In a rat calvarial defect model challenged with S. aureus, our system demonstrated remarkable antibacterial efficacy, significantly enhanced bone defect regeneration, and exhibited local immunomodulatory effects that support both infection control and osteogenesis. These breakthrough findings highlight the substantial clinical potential of this novel drug delivery system and introduce a transformative coating strategy to enhance the functionality of traditional metallic biomaterials.

Biodiversity in nutrients and biological activities of 14 highbush blueberry (Vaccinium corymbosum L.) cultivars.

The present study aimed to identify nutrients (UPLC-PDA-ESI-MS/MS, HPLC-RI method) and biological activities (antioxidant activity to reduce Fe3+ and ABTS·+, pancreatic lipase inhibitory effect, α-amylase, and α-glucosidase, anti-bacterial) of 14 highbush blueberries (Vaccinium corymbosum L.) cultivars (Northern type) as well as a principal component analysis (PCA) to assess the variation of these properties in the context of biodiversity. Most of the cultivars in this research have been first presented in this paper. Phytochemical profiling of the tested highbush blueberry fruit revealed 75 bioactive compounds, including 5 macroelements, 7 microelements, 7 monophosphate nucleotides, 15 anthocyanins, 1 phenolic acid, 14 flavonols, 11 essential amino acids, 8 non-essential amino acids, 2 sugars, 7 organic acids. The PCA showed that the profile and contents of the analyzed compounds as well as their anti-bacterial, antioxidant, anti-diabetic, and anti-obesity potentials depended significantly on the tested cultivars. Thus, the study provides comprehensive data on cultivar-specific biodiversity and correlations that can be used to design novel extracts rich in polyphenolic, amino acids, and/or minerals extracts from the selected cultivars of highbush blueberry as natural and alternative sources to fulfill the growing industry demand for supplements, pharmaceuticals, and nutraceutical products.

Nanorod inside hollow-nanosphere structured magnetoelectric nanocatalyst for remotely controlled electrocatalysis assisted environmental remediation.

We introduce a highly efficient method for the catalytic breakdown of organic compounds using nanorods embedded within hollow nanospheres structured magnetoelectric nanocatalyst (MENC). MENCs were fabricated through a single-step process utilizing the ultrasonic spray pyrolysis technique. The dynamic electric dipole generation capability due to synergistic interaction between nanorods at the core and the hollow nanosphere shell creates a nanoscale magnetoelectric device capable of electrocatalysis-assisted water purification through advanced oxidation processes under remotely applied magnetic field excitation. Our study examines the electrocatalytic degradation of organic pollutants by MENCs under magnetic field excitation, achieving an unprecedented 90% removal efficiency for synthetic dyes. This remarkable efficiency is a result of surface redox reactions facilitated by electron and hole transfer, resulting in the production of Reactive oxygen species (ROS) such as O2•- and •OH. Additionally, antioxidant experiments were performed to confirm the ROS generation capability of MENCs under magnetic field excitation. Furthermore, trapping experiments performed employing specific scavengers for individual reactive species reveal the mechanism responsible for the magnetic field-driven catalytic breakdown of organic contaminants by MENCs. Interestingly, the MENCs exhibit >95% reduction in Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria, respectively, within 90 min of exposure to a (20 mT& 1.9 kHz) AC magnetic field.

Spectroscopic, anti-cancer, anti-bacterial and theoretical studies of new bivalent Schiff base complexes derived from 4-bromo-2,6-dichloroaniline.

In this paper, four new mono-nuclear Ni(II), Pd(II), Pt(II) and Zn(II) complexes were prepared by using a bi-dentate Schiff base ligand, (E)-2-(((4-bromo-2,6-dichlorophenyl)imino)methyl)-5-chlorophenol (BrcOH), with bivalent ions in a methanol and distil water mixture as solvent in presence of NaOH as base. The structures of the prepared compounds were characterized by spectroscopic techniques (IR and 1H NMR), CHN analysis, and molar conductivity. The M(II) (Ni, Pd and Pt) ions are four-coordinated by a bi-dentate N2O2 donor ligand, forming square planar geometry, whereas the Zn(II) is coordinated as a tetrahedral geometry. The newly synthesized compounds, which include the Schiff base ligand and its complexes, underwent antibacterial screening against E. coli and S. aureus. The results demonstrated a remarkable and noteworthy biological activity of these compounds against these pathogenic bacterial strains. Different binding energies showed good correlation, with Pd showing the strongest binding. Small energy differences indicated high reactivity, with Ni and Pd complexes being the most reactive. Electrophilicity index exhibited electron-accepting properties, with Zn showing the highest reactivity. The dipole moments showed polarity and charge separation, with Pt having the highest polarity. We evaluated the pharmacokinetic properties (ADME) of a ligand and its metal complexes using the Swiss ADME website. The results of the in-silico prediction of physicochemical properties revealed that ten compounds in total adhered to Lipinski's rule.

Cost comparison analysis of continuous versus intermittent antimicrobial therapy infusions in inpatient and outpatient care: real-world data from Finland.

OBJECTIVE: This study compared the costs and nursing time associated with the delivery of continuous infusion of antibiotics via elastomeric infusion pumps (EIP) versus conventional intermittent infusion (CII) across different care pathways. DESIGN: Retrospective real-world data informed a cost comparison analysis that compared costs and nursing hours between infusion of antibiotics via EIP versus CII across eight care pathways in inpatient or outpatient care during infection episodes. Real-world data were obtained from patients treated within a year with parenteral antimicrobial therapy in Päijät-Häme Region, Finland. SETTING: Inpatient care with hospital admission and outpatient care at hospital at home in Päijät-Häme Region in Finland. PARTICIPANTS: 3778 patients with a total of 4214 infection episodes treated with intravenous antimicrobial therapy. INTERVENTIONS: Eight treatment strategies with various combinations of EIP and CII administered in inpatient or outpatient care. PRIMARY AND SECONDARY OUTCOME MEASURES: Direct costs and nursing time. RESULTS: Skin and soft tissue infections accounted for the highest number of episodes treated with EIP overall (30.8%; 74 out of 240 episodes) and in outpatient care specifically (53.3%; 128 out of 240 episodes). Compared with inpatient care costs with CII (€4590 per episode), treating skin and soft tissue infections in outpatient care with EIP or CII incurred only 24% (€1104) and 35% (€1620) of the costs, respectively. Across all treatment strategies and infections studied, the use of EIP consistently required less nursing time. The highest nursing time in the outpatient care was observed in sepsis episodes treated with CII (37 hours with CII vs 7 hours with EIP per episode). CONCLUSION: Delivery of antimicrobial therapy using continuous infusions with EIP instead of CII can significantly decrease the nursing time and cost in both inpatient and outpatient care. For skin and soft tissue infections and sepsis, the utilisation of EIP is a cost-saving option in outpatient care compared with the use of CII.

Dysregulation and impaired anti-bacterial potential of mucosal-associated invariant T cells in autoimmune liver diseases.

Autoimmune liver diseases (AILD) encompass a group of conditions in which the immune system mistakenly attacks the liver tissue. Mucosal-associated invariant T (MAIT) cells are enriched in the liver, where they play crucial roles in antibacterial defense and inflammation regulation. Compared to other autoimmune conditions affecting the synovium of the joints, MAIT cells from AILD exhibited a greater deficiency in ratio, elevated activation markers, increased apoptosis, and higher pro-inflammatory cytokines production. However, the frequency of MAIT cells in AILD was negatively correlated with anti-bacterial indexes, and their impaired responsiveness and weakened anti-bacterial potential were evidenced by reduced expansion ability, lower maximal IFN-γ production, and diminished E. coli-induced cytotoxic mediators release. Similar shifts in MAIT cell ratios and phenotypes were observed in both primary biliary cirrhosis and autoimmune hepatitis, linked to upregulation of bile acid components in the affected tissue. Specifically, ursodeoxycholic acid, a metabolic intermediate and traditional anti-primary biliary cirrhosis drug, inhibited TCR-mediated expansion and downregulated pro-inflammatory cytokines and anti-bacterial-related mediators in MAIT cells. These findings underscore the intricate interplay between hepatic pathology and MAIT cells, and highlight the importance of antibacterial monitoring during ursodeoxycholic acid treatment in AILD.

Retrospective Study on Penicillin Allergy Delabeling and Evaluation of an Antibiotic Allergy Assessment Tool.

BACKGROUND: It has been reported that 95% of patients labeled as penicillin-allergic may be mislabeled. However, the process of delabeling has not advanced due to a shortage of allergy specialists capable of conducting accurate assessments. To address this issue, The Antibiotics Allergy Assessment Tool (AAAT) has been proposed as a tool to evaluate patients who can be delabeled by non-specialists. OBJECTIVE: This study aims to identify patients who can be delabeled and to evaluate patients who are likely to be delabeled using AAAT. METHODS: Patients admitted to the hospital between January 1, 2017, and December 31, 2021, with documented penicillin allergy labels were included in the study. Patients who demonstrated tolerance to labeled antibiotics or were labeled without explicit allergy declarations were defined as delabeling. Subsequently, patients who did not meet the criteria for delabeling were evaluated for their potential to be delabeled using the AAAT, retrospectively. RESULTS: 530 patients were selected, of which 62 (11.7%) were delabeled. The AAAT evaluation of the remaining patients indicated that at least an additional 137 (25.8%) patients could potentially be delabeled. CONCLUSION: The use of AAAT demonstrated the potential to delabel approximately third as many patients without the need for specialist evaluation. To promote broader delabeling efforts in the future, prospective studies should investigate the safety and effectiveness of evaluation tools such as the AAAT.

A multi-functional coating on cotton fabric to incorporate electro-conductive, anti-bacterial, and flame-retardant properties.

Multi-functional textiles have become a growing trend among smart customers who dream of having multiple functionalities in a single product. Thus, this study aimed to develop a multi-functional textile from a common textile substrate like cotton equipped with electrically conductive, anti-bacterial, and flame-retardant properties. Herein, a bunch of compounds from various sources like petro-based poly-aniline (PANI), phosphoric acid (H3PO4), inorganic silver nanoparticles (Ag-NPs), and biomass-sourced fish scale protein (FSP) were used. The coating was prepared via in-situ polymerization of PANI with the cotton substrate, followed by the dipping in AGNPs solution, layer-by-layer deposition of FSP and sodium alginate, and finally, a dip-dry-cure technique after immersing the modified cotton substrate into the H3PO4 and citric acid solution. The key results indicated that the fabric treated with PANI/Ag-NPs/FSP/P-compound exhibited a balanced improvement in all three desired properties as the electrical resistance was reduced by 44.44 % while showing superior bacterial inhibition against gram-positive bacteria (S. aureus) and gram-negative bacteria (E. coli), and produced dense-black carbonaceous char residues, indicating its flame retardant properties as well. Thus, such amicable developments made the cotton textile substrate a multi-functional textile, which showed potential to be used in medical textiles, wearable electronics, fire-fighter suits, etc.

The synthesis and bioactivity of Apigenin derivatives.

BACKGROUND: Apigenin, a naturally occurring compound with a flavone core structure, is known for its diverse bioactivities, including anti-inflammation, anti-toxicant, anti-cancer and so on. There has been significant interest in the medicinal chemistry community. To address these challenges, researchers have developed various derivatives of apigenin to address challenges such as poor water-solubility and low intestinal absorption, aiming to enhance the pharmacological activities and pharmacokinetic properties of this compound. OBJECTIVE: In recent years, there has been a proliferation of apigenin derivatives with enhanced bioactivity. However, there is a lack of comprehensive reviews on the function-based modification of these derivatives. In this paper, we provide an overview of the apigenin derivatives with varying bioactivities and explored their structure activity relationships. And the functions of different groups of apigenin derivatives were also analyzed. CONCLUSION: This review summarized the current achievements that could provide some clues for further study of apigenin-based drugs.

Anti-bacterial effects, and metabolites derived from bifidobacterial fermentation of an exopolysaccharide of Cs-HK1 medicinal fungus.

This study was to investigate the antibacterial effects and metabolites derived from bifidobacterial fermentation of an exopolysaccharide EPS-LM produced by a medicinal fungus Cordyceps sinensis, Cs-HK1. EPS-LM was a partially purified polysaccharide fraction which was mainly composed of Man, Glc and Gal at 7.31:12.95:1.00 mol ratio with a maximum molecular weight of 360 kDa. After fermentation of EPS-LM in two bifidobacterial cultures, B. breve and B. longum, the culture digesta showed significant antibacterial activities, inhibiting the proliferation and biofilm formation of Escherichia coli. Based on untargeted metabolomic profiling of the digesta, the levels of short chain fatty acids, carboxylic acids, benzenoids and their derivatives were all increased significantly (p < 0.01), which probably contributed to the enhanced antibacterial activity by EPS-LM. Since EPS-LM was only slightly consumed for the bifidobacterial growth, it mainly stimulated the biosynthesis of bioactive metabolites in the bifidobacterial cells. The results also suggested that EPS-LM polysaccharide may have a regulatory function on the bifidobacterial metabolism leading to production of antibacterial metabolites, which may be of significance for further exploration.

Clinical outcome of ampicillin or ampicillin/sulbactam versus glycopeptides in ampicillin-susceptible Enterococcus faecalis/faecium bacteremia: a 10-year retrospective cohort study.

BACKGROUND: Glycopeptides for ampicillin-susceptible Enterococcus faecalis/faecium bacteremia are readily prescribed depending on the severity of the condition. However, there is limited data on the outcomes of glycopeptide use compared to ampicillin-containing regimens for ampicillin-susceptible E. faecalis/faecium bacteremia. From an antibiotic stewardship perspective, it is important to determine whether the use of glycopeptides is associated with improved clinical outcomes in patients with ampicillin-susceptible E. faecalis/faecium bacteremia. METHODS: This retrospective cohort study was conducted at a university-affiliated hospital between January 2010 and September 2019. We collected data from patients with positive blood cultures for Enterococcus species isolates. The clinical data of patients who received ampicillin-containing regimens or glycopeptides as definitive therapy for ampicillin-susceptible E. faecalis/faecium bacteremia were reviewed. Multivariate logistic regression analysis was performed to identify risk factors for 28-day mortality. RESULTS: Ampicillin-susceptible E. faecalis/faecium accounted for 41.2% (557/1,353) of enterococcal bacteremia cases during the study period. A total of 127 patients who received ampicillin-containing regimens (N = 56) or glycopeptides (N = 71) as definitive therapy were included in the analysis. The 28-day mortality rate was higher in patients treated with glycopeptides (19.7%) than in those treated with ampicillin-containing regimens (3.6%) (p = 0.006). However, in the multivariate model, antibiotic choice was not an independent predictor of 28-day mortality (adjusted OR, 3.7; 95% CI, 0.6-23.6). CONCLUSIONS: Glycopeptide use was not associated with improved mortality in patients with ampicillin-susceptible E. faecalis/faecium bacteremia. This study provides insights to reduce the inappropriate use of glycopeptides in ampicillin-susceptible E. faecalis/faecium bacteremia treatment and promote antimicrobial stewardship.

ATP synthase of E. coli: F1-ATPase activity is functionally decoupled from the proton-transporting complex (FO) by tributyltin.

The F-type ATP synthase/ATPase (FOF1) is important for cellular bioenergetics in eukaryotes and bacteria. We recently showed that venturicidins, a class of macrolides that inhibit the proton transporting complex (FO), can also induce time-dependent functional decoupling of F1-ATPase from FO on membranes from Escherichia coli and Pseudomonas aeruginosa. This dysregulated ATPase activity could deplete bacterial ATP levels and contribute to venturicidin's capacity to enhance the bactericidal action of aminoglycosides antibiotics. We now show that a distinct type of FO inhibitor, tributyltin, also can decouple FOF1-ATPase activity of E. coli membranes. In contrast to the action of venturicidins, decoupling by tributyltin is not dependent on ATP, indicating mechanistic differences. Tributyltin disrupts the coupling role of the ε subunit of F1 but does not induce dissociation of the F1-ATPase complex from membrane-embedded FO. Understanding such decoupling mechanisms could support development of novel antibacterial compounds that target dysregulation of FOF1 functions.

Antimicrobial spectrum against wound pathogens and cytotoxicity of star-arranged poly-l-lysine-based antimicrobial peptide polymers.

Introduction. As growing numbers of patients are at higher risk of infection, novel topical broad-spectrum antimicrobials are urgently required for wound infection management. Robust pre-clinical studies should support the development of such novel antimicrobials.Gap statement. To date, evidence of robust investigation of the cytotoxicity and antimicrobial spectrum of activity of antimicrobial peptides (AMP)s is lacking in published literature. Using a more clinical lens, we address this gap in experimental approach, building on our experience with poly-l-lysine (PLL)-based AMP polymers.Aim. To evaluate the in vitro bactericidal activity and cytotoxicity of a PLL-based 16-armed star AMP polymer, designated 16-PLL10, as a novel candidate antimicrobial.Methods. Antimicrobial susceptibilities of clinical isolates and reference strains of ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) pathogens, to 16-PLL10 were investigated. Human erythrocyte haemolysis and keratinocyte viability assays were used to assess toxicity. Modifications were made to 16-PLL10 and re-evaluated for improvement.Results. Minimum bactericidal concentration of 16-PLL10 ranged from 1.25 µM to ≥25 µM. At 2.5 µM, 16-PLL10 was broadly bactericidal against ESKAPE strains/wound isolates. Log-reduction in colony forming units (c.f.u.) per millilitre after 1 h, ranged from 0.3 (E. cloacae) to 5.6 (K. pneumoniae). At bactericidal concentrations, 16-PLL10 was toxic to human keratinocyte and erythrocytes. Conjugates of 16-PLL10, Trifluoroacetylated (TFA)-16-PLL10, and Poly-ethylene glycol (PEG)ylated 16-PLL10, synthesised to address toxicity, only moderately reduced cytotoxicity and haemolysis.Conclusions. Due to poor selectivity indices, further development of 16-PLL10 is unlikely warranted. However, considering the unmet need for novel topical antimicrobials, the ease of AMP polymer synthesises/modification is attractive. To support more rational development, prioritising clinically relevant pathogens and human cells, to establish selective toxicity profiles in vitro, is critical. Further characterisation and discovery utilising artificial intelligence and computational screening approaches can accelerate future AMP nanomaterial development.

Ethical and Practical Issues with the Use of Antimicrobial Agents during the End of Life.

The use of antimicrobials in patients receiving end-of-life (EOL) care, which is generally defined as supportive care provided to patients anticipated to live less than 1 year, has been actively debated in the realm of palliative care medicine due to the nebulous nature of the topic. In this article, we explore the use of antimicrobial use near EOL as it relates to both the ethical and practical issues that face physicians. We also discuss the reasons underlying the scarcity of prospective studies on this topic.

Purified L-glutaminase effects against multidrug-resistant Pseudomonas aeruginosa in experimental vaginosis model: An immunological and histopathological observation.

The antimicrobial activity of crude and purified L-glutaminase (EC 3.5.1.2), obtained from Lactobacillus gasseri, was evaluated against multidrug-resistant Pseudomonas aeruginosa in the in vivo vaginosis condition. The L-glutaminase possessed significant antimicrobial and anti-biofilm formation activity against multi-drug resistance P. aeruginosa, which were confirmed in the BALBc rat vaginosis model, together with its effects on the immunological and histopathological aspects. The untreated animals showed heavy vaginitis, characterized by sub-epithelial edema and infiltration of mononuclear leukocytes, perivascular heavy inflammatory cells infiltration in the vaginal tissue, and moderate stromal edema. However, the L-glutaminase treatment exhibited no changes in vaginal tissue structure with normal appearance of the epithelium and lamina propria with marked repair of the vaginal section when compared with normal, uninfected, control group A. The immunomodulatory actions of the L-glutaminase were confirmed by observance of higher concentrations of tumor necrosis factor-γ (TNF-γ), and interleukin -12 (IL-12) in treated animals, while the interleukin-10 (IL-10) was higher in the infected, untreated animals' sera samples. Therefore, the L-glutaminase showed corrective and healing actions, which were observed through histopathological observations of the vaginal tissue. The investigations led to imply that L-glutaminase may have the potential to be an effective antimicrobial agent for preventing and inhibiting bacterial growth, as well as inhibiting the biofilm formation in the P. aeruginosa-originated vaginosis. The observations may be of promising value for future clinical use.

Long-Lasting, Transparent Antibacterial Shield: A Durable, Broad-Spectrum Anti-Bacterial, Non-Cytotoxic, Transparent Nanocoating for Extended Wear Contact Lenses.

The increasing incidence of serious bacterial keratitis, a sight-threatening condition often exacerbated by inadequate contact lens (CLs) care, highlights the need for innovative protective technology. This study introduces a long-lasting antibacterial, non-cytotoxic, transparent nanocoating for CLs via a solvent-free polymer deposition method, aiming to prevent bacterial keratitis. The nanocoating comprises stacked polymer films, with poly(dimethylaminomethyl styrene-co-ethylene glycol dimethacrylate) (pDE) as a biocompatible, antibacterial layer atop poly(2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane) (pV4D4) as an adhesion-promoting layer. The pD6E1-grafted (g)-pV4D4 film shows non-cytotoxicity toward two human cell lines and antibacterial activity of >99% against four bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacteria and Pseudomonas aeruginosa, which causes ocular diseases. Additionally, the film demonstrates long-lasting antibacterial activity greater than 96% against MRSA for 9 weeks in phosphate-buffered saline. To the best knowledge, this duration represents the longest reported long-term stability with less than 5% decay of antibacterial performance among contact-killing antibacterial coatings. The film exhibits exceptional mechanical durability, retaining its antibacterial activity even after 15 washing cycles. The pD6E1-g-pV4D4-coated CL maintains full optical transmittance compared to that of pristine CL. It is expected that the unprecedentedly prolonged antibacterial performance of the coating will significantly alleviate the risk of infection for long-term CL users.

The impact of the COVID-19 pandemic on antibiotic prescription rates in out-of-hours primary care - a register-based study in Denmark.

BACKGROUND: Antibiotic prescription rates can be affected by pandemic measures such as lockdowns, social distancing, and remote consultations in general practice. Therefore, such emergency states may negatively affect antimicrobial stewardship, specifically in out-of-hours (OOH) primary care. As contact patterns changed in the COVID-19 pandemic, it would be relevant to explore the impact on antimicrobial stewardship. AIM: To study the impact of the pandemic on antibiotic prescription rates in OOH primary care, overall and per age group. METHODS: This cross-sectional register-based study used routine data from OOH primary care in the Central Denmark Region. We included all patient contacts in two equivalent time periods: pre-pandemic and pandemic period. The main outcome measure was defined as the number of antibiotic prescriptions per contact (antibiotic prescription rate). RESULTS: The overall antibiotic prescription rate decreased during the first year of the pandemic compared to the pre-pandemic period (RR = 0.97, 95%CI: 0.96-0.98). Likewise, the rate decreased for clinic consultations (RR = 0.63, 95%CI: 0.62-0.64). However, an increase was seen for telephone consultations (RR = 1.73, 95%CI: 1.70-1.76). The decline in clinic consultations was largest for consultations involving children aged 0-10 years (RR = 0.53, 95%CI: 0.51-0.56). CONCLUSION: Antibiotic prescription rates in Danish OOH primary care decreased during the first year of the COVID-19 pandemic, especially for young children. Prescription rates decreased in clinic consultations, whereas the rates increased in telephone consultations. Further research should explore if antibiotic prescription rates have returned to pre-pandemic levels, and if the introduction of video consultations has affected antibiotic prescription patterns in OOH primary care.