Antimicrobial Products Research Articles

The Molecular Mechanisms and Therapeutic Potential of Cranberry, D-Mannose, and Flavonoids against Infectious Diseases: The Example of Urinary Tract Infections.

The treatment of infectious diseases typically includes the administration of anti-infectives; however, the increasing rates of antimicrobial resistance (AMR) have led to attempts to develop other modalities, such as antimicrobial peptides, nanotechnology, bacteriophages, and natural products. Natural products offer a viable alternative due to their potential affordability, ease of access, and diverse biological activities. Flavonoids, a class of natural polyphenols, demonstrate broad anti-infective properties against viruses, bacteria, fungi, and parasites. Their mechanisms of action include disruption of microbial membranes, inhibition of nucleic acid synthesis, and interference with bacterial enzymes. This review explores the potential of natural compounds, such as flavonoids, as an alternative therapeutic approach to combat infectious diseases. Moreover, it discusses some commonly used natural products, such as cranberry and D-mannose, to manage urinary tract infections (UTIs). Cranberry products and D-mannose both, yet differently, inhibit the adhesion of uropathogenic bacteria to the urothelium, thus reducing the likelihood of UTI occurrence. Some studies, with methodological limitations and small patient samples, provide some encouraging results suggesting the use of these substances in the prevention of recurrent UTIs. While further research is needed to determine optimal dosages, bioavailability, and potential side effects, natural compounds hold promise as a complementary or alternative therapeutic strategy in the fight against infectious diseases.

Osteopontin Depletion in Non-haematopoietic Cells Improves Outcomes in Septic Mice by Enhancing Antimicrobial Peptide Production.

Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that non-haematopoietic but not haematopoietic Opn depletion improved septic outcomes. Compared to wild-type (WT) mice, co-housed Opn-/- mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation (FMT) and OPN neutralization assay showed that Opn depletion could reduce the bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in WT organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes.

Antioxidant and antimicrobial activity of extracts from selected Mediterranean agro-food by-products, their mutual interaction and interaction with phenolic compounds

The by-products of Mediterranean agriculture that remain after the production of fruit wines, juices and extracts represent a large source of raw materials rich in phenolic compounds. As a contribution to the current state of knowledge, this study investigated the biological activity and phenolic composition of extracts obtained from blackberry, chokeberry and juniper by-products, as well as the interactions of the extracts in mixtures. The total phenolic content of the samples ranged from 44.42 to 250.28 mg gallic acid equivalents (GAE)/g dry extract, with the extracts from blackberry leaves and juniper needles being the highest. The highest concentration of phenolics detected by high performance liquid chromatography (HPLC) was also found in blackberry leaves (41.30 mg/g dry extract), with rutin dominating. The antioxidant activity of the samples, as measured by ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, ranged from 3.4 to 26.8 mM Trolox equivalents (TE), 15.8–58.4 mM TE and 80.1%–91.8%, respectively. Among the extract mixtures, the highest synergistic interaction was observed between blackberry leaves and juniper by-products extracts at 1:2 and 2:1 ratios. The antimicrobial activity of the extracts was tested against Gram-positive and Gram-negative foodborne pathogens and spoilage bacteria, with the lowest minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values against Staphylococcus aureus, Listeria innocua, Bacillus cereus, Campylobacter jejuni, Pseudomonas spp. and Shewanella spp. On the other hand, the antimicrobial activity of blackberry leaf extract in combination with selected phenolic compounds (vanillic acid, catechin, rutin and apigenin) showed no synergy against the tested microorganisms. Overall, the results suggest that the tested by-products extracts could be utilized for the production of natural antioxidants and antimicrobials for further use in the food industry.

Facile Halogenation of Antimicrobial Peptides As Demonstrated by Producing Bromotryptophan-Labeled Nisin Variants with Enhanced Antimicrobial Activity.

Antimicrobial peptides (AMPs) have raised significant interest, forming a potential new class of antibiotics in the fight against multi-drug-resistant bacteria. Various AMPs are ribosomally synthesized and post-translationally modified peptides (RiPPs). One post-translational modification found in AMPs is the halogenation of Trp residues. This modification has, for example, been shown to be critical for the activity of the potent AMP NAI-107 from Actinoallomurus. Due to the importance of organohalogens, establishing methods for facile and selective halogen atom installation into AMPs is highly desirable. In this study, we introduce an expression system utilizing the food-grade strain Lactococcus lactis, facilitating the efficient incorporation of bromo-Trp (BrTrp) into (modified) peptides, exemplified by the lantibiotic nisin with a single Trp residue or analogue incorporated at position 1. This provides an alternative to the challenges posed by halogenase enzymes, such as poor substrate selectivity. Our method yields expression levels comparable to that of wild-type nisin, while BrTrp incorporation does not interfere with the post-translational modifications of nisin (dehydration and cyclization). One brominated nisin variant exhibits a 2-fold improvement in antimicrobial activity against two tested pathogens, including a WHO priority pathogen, while maintaining the same lipid II binding and bactericidal activity as wild-type nisin. The work presented here demonstrates the potential of this methodology for peptide halogenation, offering a new avenue for the development of diverse antimicrobial products labeled with BrTrp.

A roadmap towards safe and sustainable by design nanotechnology: Implementation for nano-silver-based antimicrobial textile coatings production by ASINA project

This report demonstrates a case study within the ASINA project, aimed at instantiating a roadmap with quantitative metrics for Safe(r) and (more) Sustainable by Design (SSbD) options. We begin with a description of ASINA’s methodology across the product lifecycle, outlining the quantitative elements within: Physical-Chemical Features (PCFs), Key Decision Factors (KDFs), and Key Performance Indicators (KPIs). Subsequently, we delve in a proposed decision support tool for implementing the SSbD objectives across various dimensions—functionality, cost, environment, and human health safety—within a broader European context. We then provide an overview of the technical processes involved, including design rationales, experimental procedures, and tools/models developed within ASINA in delivering nano-silver-based antimicrobial textile coatings. The result is pragmatic, actionable metrics intended to be estimated and assessed in future SSbD applications and to be adopted in a common SSbD roadmap aligned with the EU’s Green Deal objectives. The methodological approach is transparently and thoroughly described to inform similar projects through the integration of KPIs into SSbD and foster data-driven decision-making. Specific results and project data are beyond this work’s scope, which is to demonstrate the ASINA roadmap and thus foster SSbD-oriented innovation in nanotechnology.

The Effect of Salt Stress on Antimicrobial Activity and Potential Production of Anthocyanin and Total Phenolic of Salicornia in Hydroponic Culture

The Effect of Salt Stress on Antimicrobial Activity and Potential Production of Anthocyanin and Total Phenolic of Salicornia in Hydroponic Culture

Antimicrobial and Membrane Stabilization Activity of Plant Extracts Against Pathogenic Bacteria and Fungi

The use and search for antimicrobial drugs derived from plants have accelerated in recent years. The present study was aimed to determine the antimicrobial, antibiofilm and membrane stabilization activities of plant extracts. Crude extracts of four plants namely, Mikania scandens (L.), Mimosa pudica (L.), Murraya paniculata (L.), and Syzygium aromaticum (L.) were tested against eleven human pathogens including four biofilm producing bacterial strains Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus, and one fungal strain Candida albicans. The antimicrobial activities as well as minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extracts were evaluated using disc diffusion and macro-broth dilution methods respectively. Among the plant extracts, ethanol extract of S. aromaticum exhibited the largest zone of inhibition 35 mm in diameter against Bacillus subtilis at 500 µg/disc concentrations. The lowest MIC (1000 µg/ml) and MBC (2500 µg/ml) were determined against P. aeruginosa with the same extract of S. aromaticum. In case of time kill assay, S. aromaticum extract showed the lowest optical density (OD600) 0.2 against E coli in 3h at MBC concentration. Moreover, the same extract of S. aromaticum displayed the strong antibiofilm activity, inhibiting 100% biofilm formation of E. coli at 2×MIC concentration. Furthermore, in vitro experiment was performed to evaluate membrane stabilization activity of plant extracts and S. aromaticum showed 100% activity in stabilizing cell membranes, preventing hemolysis of red blood cells. Therefore, this study provides valuable insight for designing antimicrobial products to efficiently eliminating human infections, and the plant extracts could be the potential antimicrobial agent. Bangladesh J Microbiol, Volume 40, Number 2, December 2023, pp 76-85

Exploring the Potential of Halotolerant Actinomycetes from Rann of Kutch, India: A Study on the Synthesis, Characterization, and Biomedical Applications of Silver Nanoparticles.

A tremendous increase in the green synthesis of metallic nanoparticles has been noticed in the last decades, which is due to their unique properties at the nano dimension. The present research work deals with synthesis mediated by the actinomycete Streptomyces tendae of silver nanoparticles (AgNPs), isolated from Little and Greater Rann of Kutch, India. The confirmation of the formation of AgNPs by the actinomycetes was carried out by using a UV-Vis spectrophotometer where an absorbance peak was obtained at 420 nm. The X-ray diffraction pattern demonstrated five characteristic diffraction peaks indexed at the lattice plane (111), (200), (231), (222), and (220). Fourier transform infrared showed typical bands at 531 to 1635, 2111, and 3328 cm-1. Scanning electron microscopy shows that the spherical-shaped AgNPs particles have diameters in the range of 40 to 90 nm. The particle size analysis displayed the mean particle size of AgNPs in aqueous medium, which was about 55 nm (±27 nm), bearing a negative charge on their surfaces. The potential of the S. tendae-mediated synthesized AgNPs was evaluated for their antimicrobial, anti-methicillin-resistant Staphylococcus aureus (MRSA), anti-biofilm, and anti-oxidant activity. The maximum inhibitory effect was observed against Pseudomonas aeruginosa at (8 µg/mL), followed by Escherichia coli and Aspergillus niger at (32 µg/mL), and against Candida albicans (64 µg/mL), whereas Bacillus subtilis (128 µg/mL) and Staphylococcus aureus (256 µg/mL) were much less sensitive to AgNPs. The biosynthesized AgNPs displayed activity against MRSA, and the free radical scavenging activity was observed with an increase in the dosage of AgNPs from 25 to 200 µg/mL. AgNPs in combination with ampicillin displayed inhibition of the development of biofilm in Pseudomonas aeruginosa and Streptococcus pneumoniae at 98% and 83%, respectively. AgNPs were also successfully coated on the surface of cotton to prepare antimicrobial surgical cotton, which demonstrated inhibitory action against Bacillus subtilis (15 mm) and Escherichia coli (12 mm). The present research integrates microbiology, nanotechnology, and biomedical science to formulate environmentally friendly antimicrobial materials using halotolerant actinomycetes, evolving green nanotechnology in the biomedical field. Moreover, this study broadens the understanding of halotolerant actinomycetes and their potential and opens possibilities for formulating new antimicrobial products and therapies.

Research progress on the driving factors and mechanisms of antimicrobial resistance production and spread from the perspective of One Health

Antimicrobial resistance poses a serious threat to public health and is one of the major challenges worldwide. As global social, economic, and environmental changes lead to increased exposure of populations to antimicrobials, the antimicrobial resistance of pathogens has accelerated and resulted in weakened clinical infection treatment effects. This article reviews the main mechanisms and driving factors of the production and spread of antimicrobial resistance from the perspective of "One Health"and discusses methods and strategies for controlling antimicrobial resistance from multiple dimensions. It also looks forward to the prospects of research and prevention of drug resistance to explore antimicrobial resistance prevention and control strategies based on "One Health".

Genomic insights into an endophytic Streptomyces sp. VITGV156 for antimicrobial compounds.

Endophytic Streptomyces sp. are recognized as a potential resource for valuable natural products but are less explored. This study focused on exploring endophytic Streptomyces species residing within tomato plants (Solanum lycopersicum) harboring genes for the production of a novel class of antibiotics. Our research involved the isolation and characterization of Streptomyces sp. VITGV156, a newly identified endophytic Streptomyces species that produces antimicrobial products. VITGV156 harbors a genome of 8.18 mb and codes 6,512 proteins, of which 4,993 are of known function (76.67%) and 1,519 are of unknown function (23.32%). By employing genomic analysis, we elucidate the genome landscape of this microbial strain and shed light on various BGCs responsible for producing polyketide antimicrobial compounds, with particular emphasis on the antibiotic kendomycin. We extended our study by evaluating the antibacterial properties of kendomycin. Overall, this study provides valuable insights into the genome of endophytic Streptomyces species, particularly Streptomyces sp. VITGV156, which are prolific producers of antimicrobial agents. These findings hold promise for further research and exploitation of pharmaceutical compounds, offering opportunities for the development of novel antimicrobial drugs.

Optimization of Culturing Conditions for the Production of Antimicrobial Metabolite by Bacillus Carotarum

Forest soil antagonistic bacteria Bacillus carotarum was isolated and tested for optimum antimicrobial metabolite production. Maximum antimicrobial metabolite production was found at temperature 30°C and pH 7.0 and on Ist day of incubation at stationary condition. The medium consisting of beef extract - 0.3%, peptone - 0.5% and NaCl - 0.05%, was screened out as a suitable medium for maximum antimicrobial production supplemented individually with four carbon sources of which starch was found as the best carbon source. The active agent was best extracted with petroleum ether. Homogeneity of the crude bioactive metabolites were also tested by paper chromatographic analysis where a single type of bioactive metabolite was found with a Rf value of 0.94 in the solvent system n- butanol: acetic acid : water = 4 : 1 : 5 . The antimicrobial spectrum of the metabolite was wide and showed activity against Shigella dysenteriae (AE14612), Salmonella typhi(AE14296), Vibrio cholerae (A214748), Pseudomonas aeruginosa (CRL, ICDDR’ B), Bacillus cereus (BTCC19), and Bacillus subtilis (BTTC17). The Chittagong Univ. J. B. Sci. 8(1&2): 01-10, 2013

Оптимизация технологии фагового дисплея для получения антител, специфичных к тетрациклину

Large-scale production and use of antimicrobials in human, veterinary and agricultural applications has led to antibiotic contamination of water resources. Therefore, it is relevant to develop methods for monitoring the content of antibiotics, especially in water resources. Biosensor methods are successful for the analysis of antibiotics. One of the main elements of a biosensor system is the selection of a recognition element. An alternative tool for selecting a sensitive element (recognition element) is phage display of antibodies, which makes it possible to obtain antibodies to low molecular weight antigens. The purpose of the work was to conduct research to develop and optimize the methodology for obtaining antibodies specific to tetracycline by using phage display technology, and to evaluate the possibility of their use for the indication of tetracycline. The work included studies of optimization of conditions for the production of phage antibodies specific to tetracycline, as well as the preservation of their activity during storage. The promise of using phage display technology for the production of anti-tetracycline antibodies has been shown. Using the dot immunoassay method, the possibility of using the obtained phage antibodies for tetracycline detection was shown.

Multidrug-resistance and extended-spectrum beta-lactamase-producing lactose-fermenting enterobacteriaceae in the human-dairy interface in northwest Ethiopia.

Antimicrobial resistance (AMR) is among the top public health concerns in the globe. Estimating the prevalence of multidrug resistance (MDR), MDR index (MDR-I) and extended-spectrum beta-lactamase (ESBL)-producing lactose fermenting Enterobacteriaceae (LFE) is important in designing strategies to combat AMR. Thus, this study was designed to determine the status of MDR, MDR-I and ESBL-producing LFE isolated from the human-dairy interface in the northwestern part of Ethiopia, where such information is lacking. A cross-sectional study was conducted from June 2022 to August 2023 by analyzing 362 samples consisting of raw pooled milk (58), milk container swabs (58), milker's hand swabs (58), farm sewage (57), milker's stool (47), and cow's feces (84). The samples were analyzed using standard bacteriological methods. The antimicrobial susceptibility patterns and ESBL production ability of the LFE isolates were screened using the Kirby-Bauer disk diffusion method, and candidate isolates passing the screening criteria were phenotypically confirmed by using cefotaxime (30 μg) and cefotaxime /clavulanic acid (30 μg/10 μg) combined-disk diffusion test. The isolates were further characterized genotypically using multiplex polymerase chain reaction targeting the three ESBL-encoding- genes namely blaTEM, blaSHV, and blaCTX-M. A total of 375 bacterial isolates were identified and the proportion of MDR and ESBL-producing bacterial isolates were 70.7 and 21.3%, respectively. The MDR-I varied from 0.0 to 0.81 with an average of 0.30. The ESBL production was detected in all sample types. Genotypically, the majority of the isolates (97.5%), which were positive on the phenotypic test, were carrying one or more of the three genes. A high proportion of the bacterial isolates were MDR; had high MDR-I and were positive for ESBL production. The findings provide evidence that the human-dairy interface is one of the important reservoirs of AMR traits. Therefore, the implementation of AMR mitigation strategies is highly needed in the area.

SAFETY OF TETRACYCLINES FOR PUBLIC HEALTH AND THE ENVIRONMENT

Antimicrobial veterinary medicinal products of the tetracycline class have been most widely used for many years in the veterinary practice, both in Ukraine and in European countries, the USA, Canada, etc. Teteracyclynes have a wide-spectrum activity against gram-positive and gram-negative microorganisms, rickettsia, mycoplasma, chlamydia and protozoan parasites and are successfully used for the treatment of infectious diseases of the gastrointestinal tract, respiratory organs, skin and urogenital infections. Antimicrobial veterinary medicinal products of this class belong to AMEG category D, which is the safest in terms of impact on public health. Tetracyclines are low cost agents, are not high toxic when used in animals, which justifies their frequent choice for empirical treatment. During the monitoring of sales volumes for 2016-2021, antimicrobial veterinary medicinal products of the tetracycline class occupied the largest share among all antimicrobials entering the market in Ukraine (25.9-39.4)%. Most frequently, these veterinary medicinal products are intended for oral administration, but since their low bioavailability (5-15)%, they are excreted from the body almost unchanged. However, there is a danger of the development of tetracyclines resistance and a hazard to the environment and public health, which is explained by the frequent use of this class substances, the permission of large amounts into the soil with manure and water following drinkers washing after the treatment. Tetracyclines are poorly metabolized, and their long-term use in veterinary practice contributes to the bioaccumulation of significant amounts in soil and water. The main goal of this study were the analysis of veterinary medicinal products containing tetracyclines which were authorized in Ukraine by the category of active substances and route of administration. Another problem of this article was to substantiate the impact of tetracycline class antibiotics on the environment and the acquired antimicrobial resistance in the view of the necessity of their reasonable and safety use for the animals treatment, taking into account the requirements of the current legislation in Ukraine and EU member states. The results of the study proved that antimicrobial veterinary medicinal products containing chlortetracycline, mainly for oral administration, prevail in Ukraine. The bias of this monitoring is the lack information on the volumes of their use in farms and for individual animal species. Although the tetracycline class antibiotics do not belong to persistent bio accumulative toxic substances (PBT), their long-term and widespread use causes concern in view of the possible acquiring antimicrobial resistance and harmful effects on the environment, which will have an impact on public health. It is necessary to introduce regulatory measures to limitation and optimal use of these compounds in veterinary medicine. It is also necessary to deliver information among stakeholders about the possible negative impact on the environment and plan activities to prevent the development of acquired antimicrobial resistance to the tetracycline class antibiotics.

Revision of pharmaceutical legislation in the context of antimicrobial resistance and challenges facing the introduction of innovative antimicrobial medical products in Europe

The presented article provides a systematic review of the pharmaceutical legislation (EU Pharmaceutical Package) – the current proposal of the European Commission for a new Directive, repealing and replacing Directives and modifying Regulations of the European Parliament and of the Council, incorporating the relevant parts of the Regulation concerning medicinal products for pediatrics, Regulation for orphan drugs and others, aiming at revision of the pharmaceutical legislation in the context of antimicrobial resistance and challenges facing the introduction of innovative antimicrobial medicines in Europe. It outlines a critical analysis on the impact of the changes in the context of introduction of innovative antimicrobial medicinal products with an emphasis on unsatisfied medical demands of the European population. The revision of the pharmaceutical legislation provides an argument to consider that the proposed Pharmaceutical Package could resolve some of the issues associated with the access to novel antibiotic medicines. It is necessary to find a consensus and a balance between, on the one hand, meeting the need for antibiotics for the citizens of the European Union and, on the other hand, providing timely access to generic medicines to meet the needs of the population.

Milk residue depletion of two dry-cow intramammary antimicrobials in dairy goats

There are currently no intramammary antimicrobial products labeled for use in goats in the United States. However, both clin­ical and subclinical mastitis impart heavy production losses to this growing sector of American agriculture annually. Subclini­cal mastitis can be particularly insidious by causing unreal­ized production losses and dry off is an ideal time to detect and manage cases using long-acting intramammary antimicrobial therapy. The goal of this study was to determine milk residue depletion times for 2 such antimicrobials in dairy goats in the immediate post-fresh period.

Functionalization of silver nanoparticles coating cotton fabrics through hydrothermal synthesis for improved antimicrobial properties

Deposition of silver nanoparticles (AgNPs) on the surfaces of cotton fabric (CF) is an approach for producing antimicrobial textile products. CF-AgNPs composites were fabricated ex situ using a simple hydrothermal synthesis of AgNPs, while the fabric was surface modified using a plasma to improve adhesion prior to coating. The morphology and chemical composition of CF-AgNPs nanocomposites were examined using UV–vis spectrophotometry (UV–vis), x-ray diffraction (XRD), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM). Study results show uniform deposition of AgNPs on cotton fabrics. The CF-AgNPs composite material exhibits excellent laundering durability and antimicrobial performance against Gram-positive, Staphylococcus aureus and Gram-negative, Escherichia coli pathogens. These findings indicate that the developed fabric can be used in a wide range of biomedical applications, health care and various packaging systems.

Optimized production of antimicrobial compounds by endophytic Aspergillus niger CBMAI 2766

Fungi can adapt their metabolism to different cultivation conditions, which may accompany changes in secondary metabolites, but few cost-effective approaches were presented. Therefore, Aspergillus niger CBMAI 2766 was studied aiming at the obtention of antibacterial compounds using KBr, an innocuous and inexpensive salt. The addition of this salt to culture medium was an interesting strategy for obtention of natural products at higher concentrations, as observed by the increased extract mass that favored the isolation of biologically active compounds. Furthermore, an experimental design with temperature, pH, and KBr concentration was performed to maximize the obtained products. Seven compounds were isolated: the phenylalanine derivatives Aspernigrin A 1 and Pestalamide B 2, the polyketides RF-3192C 3, Foncesinone A 6 and Aurasperone A 7, and the bicoumarins Orlandin 4 and Kotanin 5. The bactericidal activity of 5 against Gram-positive bacteria was observed for the first time in this study. Furthermore, antimicrobial activities of the isolated metabolites 3–7 were described in the literature. In summary, the employed experimental design showed that 34 °C and 10 g.L−1 KBr were optimal conditions for producing the bioactive compounds 5-7, employing this inexpensive salt as medium modifier. Thus, indicating that this proposal presents potential for enhancing antimicrobials production.

Antimicrobial resistance and ESBL production in uropathogenic Escherichia coli: a systematic review and meta-analysis in Ethiopia.

Antimicrobial resistance (AMR) is a serious threat to global health systems. Escherichia coli is a major cause of urinary tract infections (UTIs). Understanding the AMR patterns of uropathogenic E. coli (UPEC) is crucial for effective public health interventions worldwide. This systematic review and meta-analysis aimed to consolidate existing research and provide a comprehensive information on AMR UPEC in Ethiopia. We systematically searched databases such as PubMed, Web of Science, and Science Direct, along with including articles from Google Scholar. Data were extracted into Microsoft Excel and analysed using STATA 17.0. Cohen's kappa was computed to assess reviewer agreement, while the I2 statistic evaluated heterogeneity. Egger's tests were conducted to detect publication bias, and random-effects models were utilized to estimate the pooled resistance, with AMR rates for each antibiotic pooled separately. UPEC showed resistance rates, ranging from 3.64% (95% CI: -4.38% to 11.67%) for amikacin to 85.32% (95% CI: 78.6%-92.04%) for ampicillin. Highest resistance was to ampicillin (85.32%), followed by amoxicillin at 82.52% (95% CI: 74.3%-90.74%), tetracycline at 60.67% (95% CI: 51.53%-69.81%) and trimethoprim/sulfamethoxazole at 57.17% (95% CI: 49.93%-64.42%). Conversely, resistance rates were lower for amikacin at 3.64% and meropenem at 5.26% (95% CI: 2.64%-7.88%). UPEC demonstrated a pooled MDR rate of 79.17% (95% CI: 70.32%-88.01%) and a pooled ESBL production rate of 29.16% (95% CI: 22.36%-38.55%). High levels of AMR were observed in UPEC strains, highlighting a critical public health issue requiring urgent action through robust antimicrobial stewardship and surveillance to preserve effective UTI treatment options.

An injectable chitosan-based hydrogel incorporating carbon dots with dual enzyme-mimic activities for synergistically treatment of bacteria infected wounds

Bacterial infections pose a serious threat to human health, and the emergence of superbugs and the growing antibiotic resistance phenomenon have made the development of novel antimicrobial products. In this paper, an ultrasmall Cu, N co-doped carbon dots (CDs-Cu-N) with excellent peroxidase mimic activity and enhanced catalase mimic activity was successfully prepared and anchored to an injectable chitosan (CS)-based hybrid hydrogel. As expected, the CDs-Cu-N-H2O2-CS hybrid hydrogel maintains the excellent enzyme-mimicking properties of CDs-Cu-N and shows superior antibacterial property, which has been proven to effectively promote the healing of S. aureus-infected wounds with good biocompatibility. Benefitting from the dual-enzyme-mimic activity of CDs-Cu-N, the hybrid hydrogel not only can catalyze the generation of highly toxic ROS from low concentration of H2O2 to inhibit the bacterial infections, but also can significantly promote the wound tissue repair and regeneration by improving the anoxic microenvironment and promoting neovascularization. In addition, this hybrid hydrogel also possessed excellent injectability and moldability. It can adapt to various the irregular shapes of acute wounds, maintaining a moist and safe microenvironment while prolonging the action time of nanozyme on wounds, thus promoting wound healing. This injectable hybrid hydrogel shows great potential applications in the field of wound infection management.