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Antibiotics development during the last century permitted unprecedent medical advances. However, it is undeniable that there has been an abuse and misuse of antimicrobials in medicine and cosmetics, food production and food processing, in the last decades. The pay toll for human development and consumism is the emergence of extended antimicrobial resistance and omnipresent contamination of the biosphere. The One Health concept recognizes the interconnection of human, environmental and animal health, being impossible alter one without affecting the others. In this context, antibiotic decontamination from water-sources is of upmost importance, with new and more efficient strategies needed. In this framework, light-driven antibiotic degradation has gained interest in the last few years, strongly relying in semiconductor photocatalysts. To improve the semiconductor properties (i.e., efficiency, recovery, bandgap width, dispersibility, wavelength excitation, etc.), bio-based supporting material as photocatalysts matrices have been thoroughly studied, exploring synergetic effects as operating parameters that could improve the photodegradation of antibiotics. The present work describes some of the most relevant advances of the last 5 years on photodegradation of antibiotics and other antimicrobial molecules. It presents the conjugation of semiconductor photocatalysts to different organic scaffolds (biochar and biopolymers), then to describe hybrid systems based on g-C 3 N 4 and finally addressing the emerging use of organic photocatalysts. These systems were developed for the degradation of several antibiotics and antimicrobials, and tested under different conditions, which are analyzed and thoroughly discussed along the work., (© 2024. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Background: Antimicrobial stewardship (AMS) aims to optimize antimicrobial use. Auditing and reporting of antimicrobial prescribing are essential. Auditing tools for solid organ transplant (SOT) patients should tailor to their needs., Methods: We reviewed published data describing auditing tools in the general and SOT population., Results: We focused on three internationally or nationally available auditing tools. The National Antimicrobial Prescribing Survey (NAPS) is web-based tool to report antimicrobial consumption and assess appropriateness using standardized definitions based on consensus guidelines. In the absence of guidelines, adjudication is based on AMS principles. An automated dashboard, analyses by indication or antimicrobial, and benchmarking reports are available. The National Healthcare Safety Network Antimicrobial Use/Resistance module was developed by the Centers for Disease Control and Prevention for hospitals to upload monthly data, which are standardized for benchmarking. It does not assess appropriateness or address SOT wards. The Global-Point Prevalence Survey from bioMérieux collects data on antimicrobial regimen, indication and microbial resistance. Variables unique to SOT include comorbidities and devices. Assessment of appropriateness is limited to guideline adherence, and benchmarking may require prearrangement with bioMérieux. Benchmarking requires prearrangement. Advances in electronic health record systems and clinical decision support tools can improve the efficiency of the auditing process., Conclusion: Each AMS auditing tool has unique features for SOT patients. Capturing immunosuppression, source control, organ dysfunction, donor-derived infection, serology, and colonization status will enhance their applicability., (© 2022 Wiley Periodicals LLC.)

India at present is one of the leading countries in antimicrobial drug production and use, leading to increasing antimicrobial resistance (AMR) and public health problems. Attention has mainly been focused on the human and food animals' contribution to AMR neglecting the potential contribution of the perceptibly degraded aquatic environment in India. The paper reviews the available published literature in India on the prevalence of antimicrobial residues and their dissemination pathways in wastewater of pharmaceutical industries, sewage treatment plants, hospitals, riverine, community pond water, and groundwater. The prevalence of antimicrobial residue concentration, pathogenic and non-pathogenic bacteria antimicrobial resistant bacteria (ARB), their drug resistance levels, and their specific antimicrobial resistant genes (ARGs) occurring in various water matrices of India have been comprehensively depicted from existing literature. The concentration of some widely used antimicrobials recorded from the sewage treatment plants and hospital wastewater and rivers in India has been compared with other countries. The ecotoxicological risk posed by these antimicrobials in the various water matrices in India indicated high hazard quotient (HQ) values for pharmaceutical effluents, hospital effluents, and river water. The degraded aquatic environment exhibited the selection of a wide array of co-existent resistant genes for antibiotics and metals. The review revealed improper use of antibiotics and inadequate wastewater treatment as major drivers of AMR contaminating water bodies in India and suggestion for containing the challenges posed by AMR in India has been proposed., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Drug dosing in obese patients continues to be challenging due to a lack of high-quality evidence to guide dosing recommendations. We first published guidance for antibiotic dosing in obese adults in 2017, in which we critically reviewed articles identified from a broad search strategy to develop dosing recommendations for 35 antimicrobials. In this updated narrative review, we searched Pubmed, Web of Science, and the Cochrane Library using Medical Subject Headings including anti-infectives, specific generic antimicrobial names, obese, pharmacokinetics, and others. We reviewed 393 articles, cross-referenced select cited references, and when applicable, referenced drug databases, package inserts, and clinical trial data to update dosing recommendations for 41 antimicrobials. Most included articles were pharmacokinetic studies, other less frequently included articles were clinical studies (mostly small, retrospective), case reports, and very rarely, guidelines. Pharmacokinetic changes are frequently reported, can be variable, and sometimes conflicting in this population, and do not always translate to a documented difference in clinical outcomes, yet are used to inform dosing strategies. Extended infusions, high doses, and therapeutic drug monitoring remain important strategies to optimize dosing in this population. Additional studies are needed to clinically validate proposed dosing strategies, clarify optimal body size descriptors, dosing weight scalars, and estimation method of renal function in obese patients., (© 2023 Pharmacotherapy Publications, Inc.)

Background: Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses., Objectives: To compute PK/PD cut-offs (PK/PD CO ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation., Study Design: A meta-analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings., Methods: Horses (n = 131) received MBX intravenously at doses of either 2 or 10 mg/kg BW. They were richly sampled (five or six samples per horse). A population model was built to generate a virtual population of 5000 MBX disposition curves by Monte Carlo simulations (MCS) over 24 hours. The selected PK/PD index was the ratio of Area Under the free plasma concentration-time Curve divided by the MIC (fAUC/MIC). The PK/PD CO , which is the highest MIC for which 90% of horses can achieve an a priori selected critical value for the numerical value of the PK/PD index, was established for Gram-positive and Gram-negative bacteria for a dose of 2 mg/kg., Results: The PK/PD CO of MBX in horses was 0.125 mg/L for Gram-positive pathogens and 0.0625 mg/L for Gram-negative pathogens. MBX MICs determined by broth microdilution for 54 Escherichia coli and 189 Streptococcus equi isolates are reported., Main Limitation: No clinical data are taken into account in the determination of a PK/PD co ., Conclusion: The computed PK/PD co predicts that MBX may be efficacious in horses to treat infections associated with Enterobacteriaceae but unlikely to those involving Staphylococcus aureus or Streptococcus equi., (© 2020 EVJ Ltd.)

In this study, five earth-friendly spectrophotometric methods using multivariate techniques were developed to analyze levofloxacin, linezolid, and meropenem, which are utilized in critical care units as combination therapies. These techniques were used to determine the mentioned medications in laboratory-prepared mixtures, pharmaceutical products and spiked human plasma that had not been separated before handling. These methods were named classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), genetic algorithm partial least squares (GA-PLS), and artificial neural network (ANN). The methods used a five-level, three-factor experimental design to make different concentrations of the antibiotics mentioned (based on how much of them are found in the plasma of critical care patients and their linearity ranges). The approaches used for levofloxacin, linezolid, and meropenem were in the ranges of 3-15, 8-20, and 5-25 µg/mL, respectively. Several analytical tools were used to test the proposed methods' performance. These included the root mean square error of prediction, the root mean square error of cross-validation, percentage recoveries, standard deviations, and correlation coefficients. The outcome was highly satisfactory. The study found that the root mean square errors of prediction for levofloxacin were 0.090, 0.079, 0.065, 0.027, and 0.001 for the CLS, PCR, PLS, GA-PLS, and ANN models, respectively. The corresponding values for linezolid were 0.127, 0.122, 0.108, 0.05, and 0.114, respectively. For meropenem, the values were 0.230, 0.222, 0.179, 0.097, and 0.099 for the same models, respectively. These results indicate that the developed models were highly accurate and precise. This study compared the efficiency of artificial neural networks and classical chemometric models in enhancing spectral data selectivity for quickly identifying three antimicrobials. The results from these five models were subjected to statistical analysis and compared with each other and with the previously published ones. Finally, the whiteness of the methods was assessed by the recently published white analytical chemistry (WAC) RGB 12, and the greenness of the proposed methods was assessed using AGREE, GAPI, NEMI, Raynie and Driver, and eco-scale, which showed that the suggested approaches had the least negative environmental impact. Furthermore, to demonstrate solvent sustainability, a greenness index using a spider chart methodology was employed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Clinical treatments ofgastric infections using antibiotics suffer from the undesired killing of commensal bacteria and emergence of antibiotic resistance. It is desirable to develop pH-responsive antimicrobial peptides (AMPs) that kill pathogenic bacteria such as H. pyloriand resistant E. coli under acidic environment with minimal impact to commensal bacteria whilst not causing antibiotic resistance., Experiments: Using a combined approach of cell assays, molecular dynamics (MD) simulations and membrane models facilitating biophysical and biochemical measurements including small angle neutron scattering (SANS), we have characterized the pH-responsive physiochemical properties and antimicrobial performance of two amphiphilic AMPs, GIIKDIIKDIIKDI-NH 2 and GIIKKIIDDIIKKI-NH 2 (denoted as 3D and 2D, respectively), that were designed by selective substitutions of cationic residues of Lys (K) in the extensively studied AMP G(IIKK) 3 I-NH 2 with anionic residue Asp (D)., Findings: Whilst 2D kept non-ordered coils across the entire pH range studied, 3D displayed a range of secondary structures when pH was shifted from basic to acidic, with distinct self-assembly into nanofibers in aqueous environment. Further experimental and modeling studies revealed that the AMPs interacted differently with the inner and outer membranes of Gram-negative bacteria in a pH-responsive manner and that the structural features characterized by membrane leakage and intramembrane nanoaggregates revealed from fluorescence spectroscopy and SANS were well linked to antimicrobial actions. Different antimicrobial efficacies of 2D and 3D were underlined by the interplay between their ability to bind to the outer membrane lipid LPS (lipopolysaccharide), outer membrane permeability change and inner membrane depolarization and leakage. Furthermore, AMP's binding with the inner membrane under acidic condition caused both the dissipation of membrane potential (Δψ) and the continuous dissipation of transmembrane ΔpH, with Δψ and ΔpH being the key components of the proton motive force. Combinations of antibiotic (Minocycline) with the pH-responsive AMP generated the synergistic effects against Gram-negative bacteria only under acidic condition. These features are crucial to target applications to gastric infections, anti-acne and wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

The use of outpatient parenteral antimicrobial therapy (OPAT) for children has several advantages, including reduced length of hospital stay and costs. A reliable vascular access is key to delivering safe and effective pediatric OPAT. In recent years, midline catheters (MC) have been increasingly used for short-term intravenous antibiotic therapy in children. However, there are no studies investigating the use of MCs in the OPAT setting. The main aim of this paper was to evaluate the success and complications of using MCs for pediatric OPAT. This was a retrospective cohort study from a tertiary academic pediatric hospital. All MCs inserted at the hospital and used for OPAT were eligible for study inclusion. The primary objective was to describe the percentage of patients able to complete OPAT without the need for additional venous access. Forty-one MCs were included in the study. Patient mean (SD) age was 5.9 (4.9) years. In 31 cases (76%, 95% CI 62-86%), the iv therapy could be successfully completed using only the MC. Imbalances between the groups suggested unfavorable outcome for saphenous vein catheters as well as for shorter and smaller-sized catheters. Fourteen patients (34%) were subjected to a MC-related complication. Pain on injection in the MC was the most frequent complication (n = 10, 24%).    Conclusion: Midline catheters could be an alternative to central venous access for pediatric OPAT. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase MC success rate. No severe MC-related complication was found. Further randomized studies comparing different catheter types are needed. What is Known: • For selected patients, pediatric outpatient parenteral antimicrobial therapy (OPAT) is safe and provides health-economic, psychosocial, and medical advantages compared to in-hospital care. • A reliable venous access is one of the key factors to the success of OPAT, but this can be a challenge in children. What is New: • Using midline catheters, 76% of patients could complete their intended iv therapy without the need for additional venous access. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase the success rate. • Thirty-four percent of catheters were subject to some kind of complication, the most common being pain on injection in the catheter., (© 2024. The Author(s).)

This year we commemorate the centennial of the birth of the mature concept of bacteriostasis by John W. Churchman at Cornell University Medical School. The term bacteriostasis has primarily been applied to antibiotics (bacteriostatic antibiotics). In this Opinion paper, we are revisiting this concept by suggesting that bacteriostasis essentially reflects a distinct cellular status (or "cell variant") characterized by the inability to be killed as a consequence of an antibiotic-induced stress impacting on bacterial physiology/metabolism (growth). Note that the term "bacteriostasis" should not be associated only with antimicrobials but with many stressful conditions. In that respect, the drug promotion of bacteriostasis might resemble other types of stress-induced cellular differentiation, such as sporulation, in which spores can be considered "bacteriostatic cells" or perhaps as persister bacteria, which can become "normal cells" again when the stressful conditions have abated.IMPORTANCEThis year we commemorate the centennial of the birth of the mature concept of bacteriostasis by John W. Churchman at Cornell University Medical School. The term bacteriostasis has primarily been applied to antibiotics (bacteriostatic antibiotics). In this Opinion paper, we are revisiting this concept by suggesting that some antibiotics are drugs that induce bacteria to become bacteriostatic. Cells that are unable to multiply, thereby preventing the antibiotic from exerting major lethal effects on them, are a variant ("different") type of cells, bacteriostatic cells. Note that the term "bacteriostasis" should not be associated only with antimicrobials but with many stressful conditions. In that respect, the drug promotion of bacteriostasis might resemble other types of stress-induced cellular differentiation, such as sporulation, in which spores can be considered "bacteriostatic cells" or perhaps as persister bacteria, which can become "normal cells" again when the stressful conditions have abated., Competing Interests: The authors declare no conflict of interest.

Antimicrobial resistance (AMR) is an urgent and growing global health concern, and a clear understanding of existing capacities to address AMR, particularly in low-income and middle-income countries (LMICs), is needed to inform national priorities, investment targets and development activities. Across LMICs, there are limited data regarding existing mechanisms to address AMR, including national AMR policies, current infection prevention and antimicrobial prescribing practices, antimicrobial use in animals, and microbiological testing capacity for AMR. Despite the development of numerous individual tools designed to inform policy formulation and implementation or surveillance interventions to address AMR, there is an unmet need for easy-to-use instruments that together provide a detailed overview of AMR policy, practice and capacity. This paper describes the development of a framework comprising five assessment tools which provide a detailed assessment of country capacity to address AMR within both the human and animal health sectors. The framework is flexible to meet the needs of implementers, as tools can be used separately to assess the capacity of individual institutions or as a whole to align priority-setting and capacity-building with AMR National Action Plans (NAPs) or national policies. Development of the tools was conducted by a multidisciplinary team across three phases: (1) review of existing tools; (2) adaptation of existing tools; and (3) piloting, refinement and finalisation. The framework may be best used by projects which aim to build capacity and foster cross-sectoral collaborations towards the surveillance of AMR, and by LMICs wishing to conduct their own assessments to better understand capacity and capabilities to inform future investments or the implementation of NAPs for AMR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The incidence of infections caused by drug-resistant bacteria has been one of the most serious health threats in the past and is substantially increasing in an alarming rate. Therefore, the development of new antimicrobial agents to combat bacterial resistance effectively is urgent. This study focused on the design and synthesis of 40 novel tetrahydrobenzothiophene amide/sulfonamide derivatives and their antibacterial activities were evaluated. Compounds 2p, 6p, and 6 s exhibited significant inhibitory effects on the growth of bacteria. To assess their safety, the cytotoxicity of the compounds was assessed using human normal liver cells, revealing that compound 6p has lower cytotoxicity. A mouse wound healing experiment demonstrated that compound 6p effectively improved wound infection induced by trauma and accelerated the healing process. Compound 6p holds promise as a potential therapeutic agent for combating bacterial infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this study, novel fibers were designed based on ethylcellulose (EC), loaded with different concentrations of gallic acid (GA) using the electrospinning technique, in order to investigate the potential of these materials as wound dressings. The chemical structure and morphology, along with the antimicrobial and biocompatibility tests of the EC_GA fibers were investigated. To observe the chemical interactions between the components, fourier transform infrared spectroscopy (FTIR) was used. The morphological analyzes were performed using scanning electron microscope (SEM). The uniaxial tensile test machine was used to obtain mechanical performance of the fibers. MTT assay was applied to get the biocompatibility properties of the fibers and antimicrobial test was applied to obtain the antimicrobial activity of the fibers. Based on the obtained results, the highest viability value of 67.4 % was obtained for 10%EC_100GA on the third day of incubation, demonstrating that with the addition of a higher concentration of GA, the cell viability increases. The antimicrobial tests, evaluated against Staphylococcus (S.) aureus, Escherichia (E.) coli, Pseudomonas (Ps.) aeruginosa and Candida (C.) albicans, showed a >90 % microbial reduction capacity correlated with a logarithmic reduction ranging from 0.63 to 1, for 10%EC_100 GA. In vitro release tests of GA from the fibers showed that GA was totally released from 10%EC_100 GA fibers after 2880 min, demonstrating a controlled release profile. These findings demonstrated that EC_GA fibers may be suitable for application in biomedical fields such as wound dressing materials. However, further studies should be performed to increase the biocompatibility properties of the fibers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Filth flies at wet markets can be a vector harbouring multiple antimicrobial-resistant (MAR) nontyphoidal Salmonella (NTS), and such strains are a significant threat to public health as they may cause severe infections in humans. This study aims to investigate the prevalence of antimicrobial-resistant NTS, especially Salmonella Enteritidis and S. Typhimurium harboured by filth flies at wet markets, and investigate their survival in the simulated gastric fluid (SGF). Filth flies (n = 90) were captured from wet markets in Klang, Malaysia, and processed to isolate Salmonella spp. The isolates (n = 16) were identified using the multiplex-touchdown PCR and assessed their antimicrobial susceptibility against 11 antimicrobial agents. Finally, three isolates with the highest MAR index were subjected to SGF survival tests. It was observed that 17.8 % of flies (n = 16/90) harbouring Salmonella, out of which 10 % (n = 9/90) was S. Enteritidis, 2.2 % (n = 2/90) was S. Typhimurium, and 5.6 % was unidentified serotypes of Salmonella enterica subsp. I. 43.8 % (n = 7/16) were confirmed as MAR, and they were observed to be resistant against ampicillin, chloramphenicol, kanamycin, streptomycin, and nalidixic acid. Three strains, F35, F75, and F85 demonstrated the highest MAR index and were able to survive (>6-log 10 ) in the SGF (180 min), indicating their potential virulence and invasiveness. This study provides significant insights into the prevalence and severity of MAR nontyphoidal Salmonella harboured by filth flies in wet markets, which may help inform strategies for controlling the spread and outbreak of foodborne disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Antibiotics are gradually becoming less effective against bacteria worldwide, and this issue is of particular concern in economically-developing nations like Pakistan. We undertook a scoping review in order to review the literature on antimicrobial use, prescribing, dispensing and the challenges associated with antimicrobial resistance in primary care (PC) settings in Pakistan. Furthermore, this review aims to identify potential solutions to promote appropriate use of antimicrobials in Pakistan. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) checklist, a comprehensive scoping review was conducted to review the literature of antimicrobials used, prescribed and dispensed in PC settings in Pakistan. Google Scholar and Pub-Med were searched for the period 2000-2023. Papers were analyzed on the basis of eligibility i.e., included antimicrobial use, prescribing and dispensing practices by general population at homes, by prescribers in outpatient departments of hospitals and by pharmacists/dispensers in community pharmacies, respectively. Two researchers analyzed the articles thoroughly and disagreements were resolved through discussion with a third reviewer. Both quantitative and qualitative research studies were eligible for inclusion. Additionally, the selected papers were grouped into different themes. We identified 4070 papers out of which 46 studies satisfied our eligibility criteria. The findings revealed limited understanding of antimicrobial resistance (AMR) by physicians and community pharmacists along with inappropriate practices in prescribing and dispensing antibiotics. Moreover, a notable prevalence of self-medication with antibiotics was observed among the general population, underscoring a lack of awareness and knowledge concerning proper antibiotic usage. Given the clinical and public health implications of AMR, Pakistan must prioritize its policies in PC settings. Healthcare professionals (HCPs) need to reduce inappropriate antibiotic prescribing and dispensing, improve their understanding of the AWaRe (access, watch and reserve antibiotics) classification and guidance, monitor current usage and resistance trends, as well as implement antimicrobial stewardship (ASP) activities starting in targeted locations., Competing Interests: Declaration of Competing Interest The authors confirm that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: point prevalence surveys have been used as a standardized tool to monitor antibiotic consumption to inform antimicrobial stewardship interventions in many countries. The 2021 WHO model list of Essential Medicines has classified antibiotics into three groups: access, watch and reserve. The aim of this paper is to describe the antibiotics used within a space of three years between 2018 and 2021 at the University of Uyo Teaching Hospital based on WHO AWaRe classification., Methods: three point-prevalence surveys were conducted in the wards in our 500-bed tertiary hospital in 2018, 2019 and 2021. Each ward was surveyed on a particular day within a four-week period. The wards were grouped into medical and surgical for comparison. Antibiotics were classified as access, watch, and reserve. Validated data were analyzed with IBM SPSS Statistics for Windows, Version 20.0 (Armonk, NY: IBM Corp.)., Results: a total of 526 patients were surveyed out of which 344 were on antimicrobial therapy with a total of 687 antibiotic prescriptions. The overall prevalence of patients who received at least one antimicrobial was 65.4% (62.4 -72.8%). The Access group of antibiotics made up 48.2% of prescriptions while the watch group made up 50.5% of prescriptions. More watch Antibiotics were prescribed by surgical wards (49.7%) than by medical wards (43.7%)., Conclusion: the use of Access group antibiotics in our hospital falls below the WHO target level in both medical and surgical wards. There is a need for strengthening antibiotic stewardship activities to reduce the use of watch group antibiotics and limit antimicrobial resistance., Competing Interests: The authors declare no competing interests., (Copyright: Agantem Ekuma et al.)

The overuse of antibiotics has led to a rise in infections caused by multidrug-resistant bacteria, resulting in a need for new antibacterial compounds with different modes of action. In this paper, we describe a new class of compounds called lipooligoureas, which are foldamer-based mimetics of antimicrobial lipopeptides. The lipooligoureas consist of an acyl chain connected to the N-terminus of an oligourea head group that exhibits a well-defined 2.5-helix secondary structure, which is further stabilized by the attachment of the lipophilic chain to the oligourea moiety. These compounds meet the established criteria for membranolytic compounds by possessing an amphiphilic structure that promotes the internalization and partitioning of the molecules into the lipid membrane. The presence of positively charged urea residues promotes electrostatic interactions with the negatively charged bacterial membrane. The subtle structural differences in oligourea head group influence the compounds' aggregation behavior, with the number and position of positively charged urea residues correlating with their aggregation ability. The biological activity of these compounds in inhibiting bacterial growth is correlated with their ability to aggregate, with stronger antibacterial properties exhibited by those that aggregate more easily. However, the concentration inhibiting bacterial growth is significantly lower than the critical aggregation concentration values, suggesting that the mechanism of action involves the monomeric forms of lipooligoureas. Nonetheless, a mechanism based on membrane-induced aggregation cannot be ruled out. The lipooligoureas exhibit higher activity towards Gram-positive bacteria than against Gram-negative bacteria, which is indicative of certain selectivity of these compounds. It is also demonstrated that lipooligoureas exhibit increased stability against proteolytic degradation in human blood serum., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Slawomir Sek has patent Lipooligomoczniki, kompozycja farmaceutyczna, oraz lipooligomoczniki do zastosowania jako lek pending to University of Warsaw., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

To tackle antimicrobial resistance, a global threat identified by the United Nations, is a common cause of healthcare-associated infections (HAI) and is responsible for significant costs on healthcare systems, a substantial amount of research has been devoted to developing polysaccharide-based strategies that prevent bacterial attachment and biofilm formation on surfaces. Polysaccharides are essential building blocks for life and an abundant renewable resource that have attracted much attention due to their intrinsic remarkable biological potential antibacterial activities. If converted into efficient antibacterial coatings that could be applied to a broad range of surfaces and applications, polysaccharide-based coatings could have a significant potential global impact. However, the ultimate success of polysaccharide-based antibacterial materials will be determined by their potential for use in manufacturing processes that are scalable, versatile, and affordable. Therefore, in this review we focus on recent advances in polysaccharide-based antibacterial coatings from the perspective of fabrication methods. We first provide an overview of strategies for designing polysaccharide-based antimicrobial formulations and methods to assess the antibacterial properties of coatings. Recent advances on manufacturing polysaccharide-based coatings using some of the most common polysaccharides and fabrication methods are then detailed, followed by a critical comparative overview of associated challenges and opportunities for future developments. STATEMENT OF SIGNIFICANCE: Our review presents a timely perspective by being the first review in the field to focus on advances on polysaccharide-based antibacterial coatings from the perspective of fabrication methods along with an overview of strategies for designing polysaccharide-based antimicrobial formulations, methods to assess the antibacterial properties of coatings as well as a critical comparative overview of associated challenges and opportunities for future developments. Meanwhile this work is specifically targeted at an audience focused on featuring critical information and guidelines for developing polysaccharide-based coatings. Including such a complementary work in the journal could lead to further developments on polysaccharide antibacterial applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Salmonella represents one of the most common foodborne pathogens, frequently associated with the contamination of poultry products, constituting a prominent worldwide public health concern. This study determined the prevalence and antimicrobial resistance of Salmonella spp. in chilled chicken meat (115 samples) commercialized at retail in the Federal District, Brazil. Microbiological tests were performed to screen for Salmonella spp. in the chicken meat samples, and the isolated strains were confirmed by the invA gene presence (PCR technique). The strains were evaluated for antimicrobial susceptibility by the disk diffusion technique (Kirby-Bauer method) and tested for the presence of the sul2, blaCTX, and tetB antimicrobial resistance genes. The Salmonella spp. prevalence in chilled chicken meat sold at retail in the Federal District, Brazil, was 46.1% (53 of 115 chicken meat samples analyzed had invA gene-positive strains). Seventy-eight strains of Salmonella spp. isolated from the 53 contaminated samples showed higher resistance to amoxicillin/clavulanic acid (83.3%), followed by sulfonamide (64.1%) and tetracycline (46.2%); 53.8% of the isolates were multidrug-resistant (MDR). The sul2 gene that confers resistance to sulfonamide was found in 53 strains (68.0%), the blaCTX gene that confers resistance to beta-lactams was identified in 39 strains (50.0%), and the tetB gene that confers resistance to tetracycline was identified in 29 strains (37.2%). The high percentage of Salmonella contamination in chicken meat can pose a risk to consumers' health due to the possibility of causing salmonellosis. In addition, many isolates were MDR and carried antimicrobial resistance genes. Public agencies can use these results to develop effective public health policies and strategies to ensure the safety of these food products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The spread of new strains of antibiotic-resistant pathogenic microorganisms has led to the urgent need to discover and develop new antimicrobial systems. The antibacterial effects of fatty acids have been well-known and recognized since the first experiments of Robert Koch in 1881, and they are now used in diverse fields. Fatty acids can prevent the growth and directly kill bacteria by insertion into their membrane. For that, a sufficient amount of fatty acid molecules has to be solubilized in water to transfer from the aqueous phase to the cell membrane. Due to conflicting results in the literature and lack of standardization methods, it is very difficult to draw clear conclusions on the antibacterial effect of fatty acids. Most of the current studies link fatty acids' effectiveness against bacteria to their chemical structure, notably the alkyl chain length and the presence of double bonds in their chain. Furthermore, the solubility of fatty acids and their critical aggregation concentration is not only related to their structure, but also influenced by medium conditions (pH, temperature, ionic strength, etc.). There is a possibility that the antibacterial activity of saturated long chain fatty acids (LCFA) may be underestimated due to the lack of water solubility and the use of unsuitable methods to assess their antibacterial activity. Thus, enhancing the solubility of these long chain saturated fatty acids is the main goal before examining their antibacterial properties. To increase their water solubility and thereby improve their antibacterial efficacy, novel alternatives may be considered, including the use of organic positively charged counter-ions instead of the conventional sodium and potassium soaps, the formation of catanionic systems, the mixture with co-surfactants, and solubilization in emulsion systems. This review summarizes the latest findings on fatty acids as antibacterial agents, with a focus on long chain saturated fatty acids. Additionally, it highlights the different ways to improve their water solubility, which may be a crucial factor in increasing their antibacterial efficacy. We finish with a discussion on the challenges, strategies and opportunities for the formulation of LCFAs as antibacterial agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The environment is an important component in the emergence and transmission of antimicrobial resistance (AMR). Despite that, little effort has been made to monitor AMR outside of clinical and veterinary settings. Partially, this is caused by a lack of comprehensive reference data for the vast majority of environments. To enable monitoring to detect deviations from the normal background resistance levels in the environment, it is necessary to establish a baseline of AMR in a variety of settings. In an attempt to establish this baseline level, we here performed a comprehensive literature survey, identifying 150 scientific papers containing relevant qPCR data on antimicrobial resistance genes (ARGs) in environments associated with potential routes for AMR dissemination. The collected data included 1594 samples distributed across 30 different countries and 12 sample types, in a time span from 2001 to 2020. We found that for most ARGs, the typically reported abundances in human impacted environments fell in an interval from 10 -5 to 10 -3 copies per 16S rRNA, roughly corresponding to one ARG copy in a thousand bacteria. Altogether these data represent a comprehensive overview of the occurrence and levels of ARGs in different environments, providing background data for risk assessment models within current and future AMR monitoring frameworks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This paper employs an assemblage lens to generate analyses of general public narratives on antimicrobial resistance (AMR). Global efforts to reduce AMR include communications aiming to promote general public awareness, provide knowledge, encourage careful antibiotics use, and discourage demands for them. These efforts are somewhat compromised by the assumptions they make of individual lack of knowledge and motivation and the manner in which the AMR problem is framed in isolation from the biological, social and economic structures that produce it. Conceptualising AMR as an effect of antimicrobial assemblages of which publics are but one part, we analysed interviews with the general public on the lived experience of infections, antibiotic treatments and AMR. Far from science and policy discourse on AMR, these narratives showed antibiotics to be partly solutions to the social and biomedical challenges of infection, framed by self-defensive immunity and hygiene, the affective benefits of 'immune boosting', and the imperative to sustain the moral standing of the healthy citizen. Failing public awareness and action on AMR can be attributed to public health messages that overlook the social, affective and moral dimensions of infection care and separate AMR from its socio-economic drivers.

In recent years significant efforts have been made to develop new materials for wound dressing with improved healing properties. However, the synthesis methods usually employed to this end are often complex or require several steps. We describe here the synthesis and characterization of antimicrobial reusable dermatological wound dressings based on N-isopropylacrylamide co-polymerized with [2-(Methacryloyloxy) ethyl] trimethylammonium chloride hydrogels (NIPAM-co-METAC). The dressings were obtained with a very efficient single-step synthesis procedure based on visible light (455 nm) by photopolymerization. To this end, F8BT nanoparticles of the conjugated polymer (poly(9,9-dioctylfluorene-alt-benzothiadiazole) - F8BT) were used as macro-photoinitiators, and a modified silsesquioxane was employed as crosslinker. Dressings obtained by this simple and gentle method show antimicrobial and wound healing properties, without the incorporation of antibiotics or any other additives. The physical and mechanical properties of these hydrogel-based dressings were evaluated, as well as their microbiological properties, through in vitro experiments. Results show that dressings with a molar ratio of METAC of 0.5 or higher exhibit high swelling capacity, appropriate water vapor transmission rate values, stability and thermal response, high ductility and adhesiveness. In addition, biological tests showed that the dressings have significant antimicrobial capacity. The best inactivation performance was found for hydrogels synthesized with the highest METAC content. The dressings were tested several times with fresh bacterial cultures, showing a bacterial kill efficiency of 99.99 % even after three repetitions in a row, employing the same dressing, demonstrating the intrinsic bactericidal property of the materials and their reusability. In addition, the gels show low hemolytic effect, high dermal biocompatibility and noticeable wound healing effects. Overall results demonstrate that some specific hydrogel formulations have potential application as dermatological dressings for wound healing and disinfection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The alarming increase in the resistance of bacteria to the currently available antibiotics necessitates the development of new effective antimicrobial agents that are active against bacterial pathogens causing major public health problems. For this purpose, our in-house libraries were screened against a wide panel of clinically relevant Gram-positive and Gram-negative bacteria, based on which compound I was selected for further optimization. Synthetic efforts in a group of arylurea derivatives of aryloxy(1-phenylpropyl) alicyclic diamines, followed with an in vitro evaluation of the activity against multidrug-resistant strains identified compound 44 (1-(3-chlorophenyl)-3-(1-{3-phenyl-3-[3-(trifluoromethyl)phenoxy] propyl}piperidin-4-yl)urea). Compound 44 showed antibacterial activity against Gram-positive bacteria including fatal drug-resistant strains i.e., Staphylococcus aureus (methicillin-resistant, MRSA; vancomycin-intermediate, VISA) and Enterococcus faecium (vancomycin-resistant, VREfm) at low concentrations (0.78-3.125 μg/mL) comparable to last resort antibiotics (i.e., vancomycin and linezolid). It is also potent against biofilm-forming S. aureus and Staphylococcus epidermidis (including linezolid-resistant, LRSE) strains, but with no activity against Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa). Compound 44 showed strong bactericidal properties against susceptible and drug-resistant Gram-positive bacteria. Depolarization of the bacterial cytoplasmic membrane induced by compound 44 suggests a dissipation of the bacterial membrane potential as its mechanism of antibacterial action. The high antimicrobial activity of compound 44, along with its selectivity over mammalian cells (lung MCR-5 and skin BJ fibroblast cell lines) and no hemolytic properties toward horse erythrocytes, proposes arylurea derivatives of aryloxy(1-phenylpropyl) alicyclic diamines for development of novel antibacterial agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

Monitoring antimicrobial use (AMU) and antimicrobial resistance (AMR) on farms is recognised as an important component of antimicrobial stewardship, yet the process can be resource intensive. This paper describes a subset of findings from the first year of a collaboration across government, academia and a private sector veterinary practice focused on swine production in the Midwestern United States. The work is supported by participating farmers and the greater swine industry. Twice-annual collection of samples from pigs along with AMU monitoring occurred on 138 swine farms. Detection and resistance of Escherichia coli from pig tissues was assessed, and associations between AMU and AMR were evaluated. This paper describes the methods utilised and the first-year E. coli-related results from this project. Higher minimum inhibitory concentrations (MIC) for enrofloxacin and danofloxacin in E. coli from swine tissues were associated with the purchase of fluoroquinolones. There were no other significant associations between MIC and AMU combinations in E. coli isolated from pig tissues. This project represents one of the first attempts to monitor AMU as well as AMR in E. coli in a large-scale commercial swine system in the United States of America.

The medical literature is replete with articles in which there is confusion between "free concentration" and "unbound fraction" (f u ), which is the ratio of free to total plasma concentration. The lack of clarity in distinguishing between these two terms has led to biased computations, erroneous interpretations, and misleading recommendations. The problems are highlighted in this paper, taking the example of calculation of Probability of Target Attainment (PTA). This metric is used to propose pharmacokinetic/pharmacodynamic (PK/PD) breakpoints required for the interpretation of Antimicrobial Susceptibility Testing. Based on Monte Carlo simulations of the PK/PD index, area under the unbound concentration time curve/minimum inhibitory concentration (fAUC/MIC), computation of PTA from total plasma concentrations scaled by f u ineluctably leads to biased estimates. The bias is greater if the variability associated with f u is added, instead of removing it during this scaling. The explanation for the bias is that total plasma drug concentrations are intrinsically more variable than the corresponding free concentrations. This is due to the variability of antimicrobial binding for total, but not for free plasma concentrations. In consequence, the greater variability always leads to underestimation of the PK/PD cutoff (i.e., the critical MIC that is guaranteed for a given percentile of the population). A further consequence is an increase in calculated dosage required to attain the targeted quantile. This erroneous approach, of using free antimicrobial drug fraction, is not limited to the derivation of PK/PD cutoff, but may also have consequences for antimicrobials drug safety in clinical patients., (© 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Antimicrobial resistance (AMR) and pathogens derived from food animals and their associated environments have emerged as challenging threats to humans from a health perspective, but our understanding of these risks and their key prevention and control points in the current intensive breeding industry remains poor. By creating an integral composition and risk profile of the resistome and microbiome through metagenomics in feces, flies, dust, sewage, and soil along the four-stage laying hen production chain, we found that the whole production chain is a hotspot for antimicrobial resistance genes (ARGs) with 374 known subtypes and pathogens, including 157 human pathogenic bacteria (HPB). Feces and flies were identified as major risk sources for these contaminations. Also, we confirmed a twin-risk of AMR and pathogenicity prevailing throughout the chain, but with different frequencies in each stage; thus, high-risk ARGs in the young chicken stage and highly prioritized HPB in the chick stage contributed 37.33 % to the total AMR risk and 36.36 % to the pathogenic risks, respectively, thus rendering the two stages to be the key prevention points. Moreover, the prevalence of 112 binned ARG supercarriers (for example, Klebsiella pneumoniae harboring 20 ARGs) was unraveled along the production chain, especially in feces, flies, and dust, and 87 potential hosts exhibited high pathogenic risk, high-risk AMR, or both, with 262 ARGs and 816 virulence factor genes. Overall, this study provides first-hand comprehensive data on high-risk ARGs and their pathogenic hosts in the intensive laying hen production chain, and thus is fundamentally important for developing new measures to help control the global AMR crisis induced through the animal-environment-human pathway., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The development, and in some cases increasing prevalence, of resistance to antimicrobials used in clinical and veterinary settings has long been recognised. In recent years, the concept of 'One Health' has added recognition of the role that the environment plays in health protection along with the need for protection of the health of the environment itself. Organisations including the World Health Organization, United Nations Environment Programme, and national governments have identified a need for surveillance of antimicrobial resistance in the environment to sit alongside the surveillance carried out in clinical, veterinary and food sectors. However, having recognised the need for environmental surveillance there are multiple challenges in deciding what this should entail. For example, what pathogens or genes to monitor, who or what we wish to protect and what measures we wish to enable to decrease infection risks. That might include sampling near a source of resistant organisms entering the environment or conversely sampling where the exposure actually occurs. Choices need to be made at both policy and technical levels based on the detailed purposes of surveillance. This paper discusses these issues from the perspective of a national environmental regulator.

New efficient antimicrobial agents are urgently needed to combat invasive multidrug-resistant pathogens infections. Structurally unique benzenesulfonyl thiazoloimines (BSTIs) were exploited as novel potential antibacterial victors to confront terrific drug resistance. Some developed BSTIs exerted effectively antimicrobial efficacy against the tested strains. Notably, 2-pyridyl BSTI 14d exhibited good antibacterial activity against E. faecalis with MIC value of 1 μg/mL, which was superior to sulfathiazole and norfloxacin. The most active compound 14d not only showed rapid bactericidal properties and impeded E. faecalis biofilm formation to effectually relieve the development of drug resistance, but also performed low toxicity toward human red blood cells, human normal squamous epithelial cells and human non-neoplastic colon epithelial cells. Mechanistic investigation demonstrated that molecule 14d could exert efficient membrane destruction leading to the leakage of intracellular materials and metabolism inhibition, cause oxidative damage of E. faecalis through accumulation of excess reactive oxygen species and reduction of glutathione activity, and intercalate into DNA to hinder replication of DNA. Molecular docking indicated that the formation of 14d-dihydrofolate synthetase supramolecular complex could hinder the function of this enzyme. ADME analysis displayed that compound 14d possessed promising pharmacokinetic properties. These findings suggested that the newly developed benzenesulfonyl thiazoloimines with multitargeting antibacterial potential provided a new possibility for evading resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Agricultural application contributes major consumption of antibiotics worldwide. As veterinary antibiotics are poorly metabolized by animals, most of them end up in agricultural waste, which is increasingly subject to thermal treatment, such as torrefaction, pyrolysis, etc. However, there is a lack of research on their thermal decomposition mechanisms and products elucidation. Therefore, this study investigated the thermal decomposition of four major veterinary antibiotics groups (β-lactams, tetracyclines, fluoroquinolones, sulfonamides) with emphasis on their thermal stability, structural transformation and antibacterial activity. Results show that thermal treatment can remove the parent antibiotics with their antibacterial activity except for gatifloxacin (GAT). Although the parent form of GAT was fully removed at 200 °C, its products showed significant antibacterial activity against E. coli. We present novel evidence that the PhO-CH 3 chemical bond on GAT preferentially brake to generate methyl radical, which underwent a substitution reaction at the para position of phenol. This reaction also occurred during the thermal decomposition of antibiotic analogues, balofloxacin and moxifloxacin, whose thermolysis products also showed significant antibacterial activity. Furthermore, these thermolysis products may present potentially cardiotoxic and pose higher risks to human health than their parent forms, based on the comparison with a group of drugs withdrawn from the market., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The combination of two compounds with known antimicrobial activity may, in some cases, be an effective way to limit the resistance to antibiotics of specific pathogens. Molecules carrying pyrazole moiety are well known for their bioactive properties and have wide applicability in the medical and pharmaceutical field. Surfactants have, among other useful properties, the ability to affect the growth of microorganisms. The paper reports on the effect of the combination of two pyrazole derivatives, (1H-pyrazol-1-yl) methanol 1-hydroxymethylpyrazole (SAM1) and 1,1'methandiylbis (1H-pyrazol) (AM1), with sorbitan monolaurate (polysorbate 21, Tween 21, T21) on the growth of Gram-positive and Gram-negative bacteria. The results demonstrated a different ability of this combination to inhibit Staphylococcus aureus and Escherichia coli . T21 intensified the inhibitory activity of the pyrazoles to a greater extent in the Gram-negative bacteria compared to the Gram-positive ones, a fact confirmed by time-kill experiments. The experimental data showed that the association of T21 with the pyrazoles led to the increased release of intracellular material and a more intense uptake of crystal violet, which indicates that the potentiation of the antibacterial effect was based on the modification of the normal permeability of bacterial cells. T21 acted as a modulating factor and increased the permeability of the membrane, allowing the accelerated penetration of the pyrazoles inside the bacterial cells. This fact is important in controlling the global increase in microbial resistance to antibiotics and antimicrobials and finding viable solutions to overcome the antibiotic crisis. The paper highlights the possibility of using non-toxic surfactant molecules in antimicrobial combinations with practical applications. This could widen the range of adjuvants in applications which would be useful in the control of resistant microorganisms.

Objectives: The use of antibiotics in human medicine and livestock production has contributed to the widespread occurrence of Antimicrobial Resistance (AMR). Recognizing the relevance of AMR to human and livestock health, it is important to assess the occurrence of genetic determinants of resistance in medical, veterinary, and public health settings in order to understand risks of transmission and treatment failure. Advances in next-generation sequencing technologies have had a significant impact on research in microbial genetics and microbiome analyses. The aim of the present study was to compare the Illumina MiSeq and Ion Torrent S5 Plus sequencing platforms for the analysis of AMR genes in a veterinary/public health setting., Methods: All samples were processed in parallel for the two sequencing technologies, subsequently following a common bioinformatics workflow to define the occurrence and abundance of AMR gene sequences. The Comprehensive Antibiotic Resistance Database (CARD), QIAGEN Microbial Insight - Antimicrobial Resistance, Antimicrobial resistance database, and Comprehensive Antibiotic Resistance Database developed by CLC bio (CARD-CLC) databases were compared for analysis, with the most genes identified using CARD., Results: Drawing on these results, we described an end-to-end workflow for the analysis of AMR genes a using advances in next-generation sequencing. No statistically significant differences were observed among any other genes except the tet-(40) gene between two sequencing platforms, which may be due to the short amplicon length., Conclusions: Irrespective of sequencing chemistry and platform used, comparative analysis of AMR genes and candidate host organism suggest that the Illumina MiSeq and Ion Torrent platforms performed almost equally. Regardless of sequencing platform, the results were closely comparable with minor differences., Competing Interests: Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nanotechnology is an interdisciplinary study that has been developing worldwide in recent years and has a serious impact on human life. The fact that the nanoparticles of plant origin are clean, non-toxic, and biocompatible has enabled new fields of study. The Hibiscus sabdariffa (H. sabdariffa) plant has been attracted by scientists because of its impact on health and many other areas. The lipid peroxidation inhibiting activity, antioxidant properties, and antimicrobial properties of H. sabdariffa plant with Ag-Pd metal was ditermined. For the total phenolic component, gallic acid was used as the standard and quarcetin was used for the total flavonoid. The lipid peroxidation inhibition activity of Ag-Pd NPs in ethanol extract was found to be very well compared to the positive control (BHA). The lowest and highest concentrations of DPPH radical scavenging activity were 82.178-97.357%, whereas for BHA these values were found to be 84.142-94.142%. The highest concentration of Ag-Pd NPs at 200 μg/mL the DPPH radical quenching activity was higher than BHA. Ag-Pd NPs showed a good antimicrobial activity against certain pathogenic microorganisms such as Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, which are the causative agents of various diseases in humans. The photodegradation activity of Ag-Pd NPs also investigated against Methyl orange dye (MO) under sunlight irradiation for 120 min and was found to be as 67.88., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this paper, we report on the design and synthesis of a novel series of quinazoline-2,4(1 H ,3 H )-dione derivatives as fluoroquinolone-like inhibitors of bacterial gyrase and DNA topoisomerase IV to identify and develop antimicrobial agents to prevent bacterial resistance problems. Their structures were confirmed using spectroscopic analyses (IR, NMR, and EI-MS). The novel quinazoline-2,4(1 H ,3 H )-dione derivatives were evaluated for their antimicrobial activities against Gram-positive and Gram-negative bacterial strains using the Agar well diffusion method to study the antimicrobial activities and compared them with the standard drugs. Most compounds displayed moderate activity. Among the tested compounds, the most promising compounds 13 and 15 provided broad bioactive spectrum against Gram-positive and Gram-negative strains compared to the standard drugs.

Antimicrobial susceptibility testing (AST) is a key measure in clinical microbiology laboratories to enable appropriate antimicrobial administration. During an AST, the determination of the minimum inhibitory concentration (MIC) is an important step in which the bacterial responses to an antibiotic at a series of concentrations obtained in separate bacterial growth chambers or sites are compared. However, the preparation of different antibiotic concentrations is time-consuming and labor-intensive. In this paper, we present a microfluidic device that generates a concentration gradient for antibiotics that is produced by diffusion in the laminar flow regime along a series of lateral microwells to encapsulate bacteria for antibiotic treatment. All the AST preparation steps (including bacterium loading, antibiotic concentration generation, buffer washing, and isolated bacterial growth with an antibiotic) can be performed in a single chip. The viable bacterial cells in each microwell after the antibiotic treatment are then quantified by their surface-enhanced Raman scattering (SERS) signals that are acquired after placing a uniform SERS-active substrate in contact with all the microwells. For proof-of-concept, we demonstrated the AST performance of this system on ampicillin (AMP)-susceptible and -resistant E. coli strains. Compared with the parameters for conventional AST methods, the AST procedure based on this chip requires only 20 μL of bacteria solution and 5 h of operation time. This result indicates that this integrated system can greatly shorten and simplify the tedious and labor-intensive procedures required for current standard AST methods.

The environmental implications of antimicrobial resistance arising from food animal farm practice are still a knowledge gap. This study investigates the fate and transport of antimicrobial resistance genes related to the use of antibiotics on a dairy farm in Michigan. Manure, soil, animal feed, animal drinking water, surface and groundwater samples were taken and the abundance of antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) were subsequently measured using high parallel quantitative PCR targeting 136 genes. The total abundance and detected numbers of ARGs were found to be highest in the stagnant lagoon. Up to 44 ARG subtypes with high abundance were found in drinking water in pen which was very close to those in manure compost. The ARGs pattern clustered by soil depth although they were treated by different manure. ARGs and MGEs were detected in surface and groundwater surrounded by dairy farmlands, with the occurrence of carbapenemase-encoding KPC gene in two waters, which may be due to transport of ARGs through runoff or other sources. Overall, the results of the study suggest high prevalence of ARGs both inside and outside the animal raising area and their potential contribution to environmental ARGs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Determining antimicrobial utilization patterns in hospitals can be a challenge given personnel and resource constraints with paper-based systems. A web-based application (APP) was developed in South Africa to address this, building on a recent point prevalence survey (PPS) using a paper-based system. Consequently, there was a need to test and evaluate the ease of use of a newly developed app and potential time saving versus paper-based methods for PPS. The findings can be used to further refine the APP., Methods: The developed app was tested in a large academic public hospital in a PPS in South Africa. During data collection, the app was evaluated for functionality on 35 variables and subsequently refined. After data collection, the app was evaluated in terms of its time-saving potential and ease of use., Results: 181 patient's files were surveyed across 13 wards in the hospital, with the antimicrobial usage findings similar to the previous paper-based study in the same hospital. The median age for males was 45.5 years and 42 years for females. Overall 80 out of 181 (44%) patients received antibiotics. Whilst 38% (12 out of 31) of patients in the adult surgical ward received antimicrobials, the prevalence was the highest (78%) in the pediatric medical wards. All the data collectors were confident in using the app after training and found the tool is not complex at all to use. In addition, the time taken to plan for the study and to collect data was considerably reduced. Reduced time spent in data collection and analysis is important for timely instigation of quality improvement programs in resource limited settings., Conclusions: All data collectors would recommend the app for future PPSs. Several concerns with data entry were identified, which have now been addressed. The app development has been successful and is now being deployed across South Africa as part of a national PPS as well as wider.

Background: The treatment of infection caused by pathogenic bacteria becomes one of the serious concerns globally. The failure in the treatment was found due to the exhibition of multiple resistance mechanisms against the antimicrobial agents. The emergence of resistant bacterial species has also been observed due to prolong treatment using conventional antibiotics. To combat these problems, several alternative strategies have been employed using biological and chemically synthesized compounds as antibacterial agents. Marine organisms are considered as one of the potential sources for the isolation of bioactive compounds due to the easily available, cost-effective, and eco-friendly., Methods: The online search methodology was adapted for the collection of information related to the antimicrobial properties of marine-derived compounds. These compound has been isolated and purified by different purification techniques, and their structure also characterized. Furthermore, the antibacterial activities have been reported by using broth microdilution as well as disc diffusion assays., Results: The present review paper describes the antimicrobial effect of diverse secondary metabolites which are isolated and purified from the different marine organisms. The structural elucidation of each secondary metabolite has also been done in the present paper, which will help for the in silico designing of the novel and potent antimicrobial compounds., Conclusion: A thorough literature search has been made and summarizes the list of antimicrobial compounds that are isolated from both prokaryotic and eukaryotic marine organisms. The information obtained from the present paper will be helpful for the application of marine compounds as antimicrobial agents against different antibiotic-resistant human pathogenic bacteria., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The global surge of antimicrobial resistance (AMR) is a major concern for public health and proving to be a key challenge in modern disease treatment, requiring action plans at all levels. Microorganisms regularly and rapidly acquire resistance to antibiotic treatments and new drugs are continuously required. However, the inherent cost and risk to develop such molecules has resulted in a drying of the pipeline with very few compounds currently in development. Over the last two decades, efforts have been made to tackle the main sources of AMR. Nevertheless, these require the involvement of large governmental bodies, further increasing the complexity of the problem. As a group with a long innovation history, the biomaterials community is perfectly situated to push forward novel antimicrobial technologies to combat AMR. Although this involvement has been felt, it is necessary to ensure that the field offers a united front with special focus in areas that will facilitate the development and implementation of such systems. This paper reviews state of the art biomaterials strategies striving to limit AMR. Promising broad-spectrum antimicrobials and device modifications are showcased through two case studies for different applications, namely topical and implantables, demonstrating the potential for a highly efficacious physical and chemical approach. Finally, a critical review on barriers and limitations of these methods has been developed to provide a list of short and long-term focus areas in order to ensure the full potential of the biomaterials community is directed to helping tackle the AMR pandemic.

This Full Paper reports the formation of silver (Ag) NPs within spatially resolved two-component hydrogel beads, which combine a low-molecular-weight gelator (LMWG) DBS-CONHNH 2 and a polymer gelator (PG) calcium alginate. The AgNPs are formed through in situ reduction of Ag I , with the resulting nanoparticle-loaded gels being characterised in detail. The antibacterial activity of the nanocomposite gel beads was tested against two drug-resistant bacterial strains, often associated with hospital-acquired infections: vancomycin-resistant Enterococcus faecium (VRE) and Pseudomonas aeruginosa (PA14), and the AgNP-loaded gels showed good antimicrobial properties against both types of bacteria. It is suggested that the gel bead format of these AgNP-loaded hybrid hydrogels makes them promising versatile materials for potential applications in orthopaedics or wound healing., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Soft surfaces, including textiles are found throughout healthcare settings. Pathogens can survive for long periods of time on textiles, and can be transferred to and from the skin. Antimicrobial fabrics are used as an engineering control to prevent infection. Efficacy testing standards have limitations, including single microorganism challenges, multiple fabric plies tested, and lengthy contact times. We developed a novel method that better models in-use conditions through testing standardized mixtures of pathogens and normal skin microorganisms, artificial soils, and a 15-min contact time. Reproducible growth of all microorganisms from frozen stocks was achieved using this method. A novel rechargeable, monitorable N-halamine cotton cellulose fabric, containing 5885 ± 98 ppm of active chlorine, was evaluated with the new method using PBS, artificial sweat, and artificial sweat plus 5% serum as soil. Pathogens tested included Acinetobacter baumannii, Candida albicans, Escherichia coli, vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, methicillin-susceptible Staphylococcus aureus, and Pseudomonas aeruginosa. Each was tested singly and in the presence of a representative normal skin flora mixture, including: Acinetobacter lwoffii, Corynebacterium striatum, Micrococcus luteus, and Staphylococcus epidermidis. When tested singly, all microorganisms were reduced by 3.00 log 10 or greater, regardless of artificial soil. In mixture, 4.00 log 10 or greater reductions were achieved for all microorganisms. These results suggest that the novel testing method can be used to provide more comprehensive and realistic efficacy information for antimicrobial textiles intended for use in healthcare. Furthermore, the N-halamine fabric demonstrated efficacy against multiple pathogens, singly and in mixtures, regardless of the presence of artificial soils., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Amphiphilic polymers bearing cationic moieties are an emerging alternative to traditional antibiotics given their broad-spectrum activity and low susceptibility to the development of resistance. To date, however, much remains unclear regarding their mechanism of action. Using functional assays (ATP leakage, cell viability, DNA binding) and super-high resolution structured illumination microscopy (OMX-SR) of fluorescently tagged polymers, we present evidence for a complex mechanism, involving membrane permeation as well as cellular uptake, interaction with intracellular targets and possible complexation with bacterial DNA. STATEMENT OF SIGNIFICANCE: This manuscript details the first study to systematically and directly investigate the mechanism of action of antimicrobial polymers, using super-resolution fluorescence imaging as well as functional assays. While many in the field cite membrane permeation as the sole mechanism underlying the activity of such polymers, we present evidence for multimodal actions including high cellular uptake and interaction with intracellular targets. It is also the first report to show competitive binding of antimicrobial polymers with bacterial DNA in a dose-dependent manner., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

In this paper, we aimed to exploit and combine in the same molecule the carbazole and the 1,3,4-oxadiazole pharmacophores, to obtain novel carprofen derivatives, by using two synthesis pathways. For the first route, the following steps have been followed: (i) ( RS )-2-(6-chloro-9 H -carbazol-2-yl)propanonic acid (carprofen) treatment with methanol, yielding methyl ( RS )-2-(6-chloro-9 H -carbazol-2-yl)propanoate; (ii) the resulted methylic ester was converted to ( RS )-2-(6-chloro-9 H -carbazol-2-yl)propane hydrazide (carprofen hydrazide) by treatment with hydrazine hydrate; (iii) reaction of the hydrazide derivative with acyl chlorides led to N -[(2 RS )-2-(6-chloro-9 H -carbazol-2-yl)propanoil]- N '- R -substituted-benzoylhydrazine formation, which; (iv) in reaction with phosphorus oxychloride gave the ( RS )-1-(6-chloro-9 H -carbazol-2-yl)-1-(1,3,4-oxadiazol-2-yl)ethane derivatives. In the second synthesis pathway, new 1,3,4-oxadiazole ring compounds were obtained starting from carprofen which was reacted with isoniazid, in the presence of phosphorus oxychloride to form ( RS )-1-(6-chloro-9 H -carbazol-2-yl)-1-[5-(4-pyridyl)-1,3,4-oxadiazol-2-yl]ethane. The synthesized compounds were characterized by IR, 1 H-NMR and 13 C-NMR, screened for their drug-like properties and evaluated for in vitro cytotoxicity and antimicrobial activity. The obtained compounds exhibited a good antimicrobial activity, some of the compounds being particularly active on E. coli , while others on C. albicans . The most significant result is represented by their exceptional anti-biofilm activity, particularly against the P. aeruginosa biofilm. The cytotoxicity assay revealed that at concentrations lower than 100 μg/mL, the tested compounds do not induce cytotoxicity and do not alter the mammalian cell cycle. The new synthesized compounds show good drug-like properties. The ADME-Tox profiles indicate a good oral absorption and average permeability through the blood brain barrier. However, further research is needed to reduce the predicted mutagenic potential and the hepatotoxicity.

Bacteria within biofilms are more resistant to antibiotics and chemical agents than planktonic bacteria in suspension. Treatment of biofilm-associated infections inevitably involves high dosages and prolonged courses of antimicrobial agents; therefore, there is a potential risk of the development of antimicrobial resistance (AMR). Due to the high prevalence of AMR and its association with biofilm formation, investigation of more effective anti-biofilm agents is required. From ancient times, herbs and spices have been used to preserve foods, and their antimicrobial, anti-biofilm and anti-quorum sensing properties are well known. Moreover, phytochemicals exert their anti-biofilm properties at sub-inhibitory concentrations without providing the opportunity for the emergence of resistant bacteria or harming the host microbiota. With increasing scientific attention to natural phytotherapeutic agents, numerous experimental investigations have been conducted in recent years. The present paper aims to review the articles published in the last decade in order to summarize a) our current understanding of AMR in correlation with biofilm formation and b) the evidence of phytotherapeutic agents against bacterial biofilms and their mechanisms of action. The main focus has been put on herbal anti-biofilm compounds tested to date in association with Staphylococcus aureus, Pseudomonas aeruginosa and food-borne pathogens (Salmonella spp., Campylobacter spp., Listeria monocytogenes and Escherichia coli)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Data sources The following electronic databases were searched with no language restrictions: MEDLINE, EMBASE and Cochrane library. Reference lists of included studies were searched, alongside the Open Grey database and hand searches in Journal of Dental Research, Journal of Periodontology, Journal of Clinical Periodontology and Journal of Periodontal Research. The editor of each journal was contacted to enquire about relevant accepted and forthcoming articles.Study selection Two independent reviewers screened for randomised controlled trials (RCTs) with a follow-up of at least six months. The main outcome was the change in periodontal pocket depths (PPD) and clinical attachment level (CAL) six months after treatment, where patients were divided according to adjunctive treatment (antimicrobial vs placebo) as well as the pre-treatment detection of periodontopathogenic bacteria.Data extraction and synthesis Data was extracted from all selected papers using a standardised form, including treatment methods, antimicrobial regime and bacterial detection methods. The Cochrane Collaborations tool was used to assess risk of bias. The weighted mean difference (WMD) of treatment effects between bacterial detection groups was obtained and pooled. A two-stage, fixed-effects meta-analysis was performed, and statistical heterogeneity was described using the Q-statistic and I2 index.Results Following the screening of 643 papers and author contact, five placebo-controlled studies were included in the systematic review. All had a low risk of bias. They varied in patient sample sizes, periodontal diagnoses, subgingival debridement protocols, antimicrobial regimes, as well as baseline microbial analysis methods. The meta-analysis of four studies, using amoxicillin and metronidazole as adjuncts, revealed a significant increase in the reduction of PPDs compared to placebo. It also showed no significant difference in the clinical effect on PPDs ≥5 mm when prescribing adjunctive amoxicillin and metronidazole based on the pre-treatment detection of A. actinomycetemcomitans (WMD = 1.16, 95% CI [-5.37, 7.68], I2 = 37.8%).Conclusions Although data on baseline periodontopathogenic bacteria was limited to A. actinomycetemcomitans, this systematic review suggests that there is not enough evidence to support the use of pre-treatment analysis of subgingival bacteria as a criterion for prescribing adjunctive antibiotics.

Several studies of antimicrobial photodynamic therapy (aPDT) have been performed to verify the efficiency of this treatment against caries-related microorganisms. Thus, the aim of this study is to describe the characteristics of aPDT and to review the literature regarding its effects on cariogenic microorganisms organized in biofilms and/or caries lesions. The literature was searched for reviews and original papers about aPDT and its outcomes against Streptococcus mutans as well as other caries-associated microorganisms or caries lesions. Moreover, research on photosensitizers and light sources are also reviewed. The publications were selected using PubMed, Web of Science, and manual search of references cited in key papers. The descriptors used were "dental caries" and "photodynamic therapy". The relative efficacy of aPDT to reduce the population of cariogenic bacteria in in vitro biofilms is demonstrated by large number of laboratory studies. Preclinical (in situ models) and clinical studies show a less pronounced bacterial reduction for aPDT than for in vitro models, especially in dentin carious lesions, since the bacteria in dentin caries may be less susceptible to this therapy due to the limited photosensitizer penetration as well as reduced diffusion of light along dentin structures. Although aPDT may be an efficient and less invasive complementary approach to disinfect deep caries lesions, there is insufficient scientific evidence of its efficacy to warrant a clinical recommendation for its use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The paper describes the basic sources and principles of antibiotic therapy in contemporary medicine in which the ability to treat bacterial infections may be lost. The main reason for that is the increasing resistance of bacterial pathogens to antibiotics. A possible solution is to implement a comprehensive program of antibiotic stewardship incorporating adequate consideration of indication and selection of antimicrobial agents including appropriate duration and way of administration. Another important component of the comprehensive approach to bacterial resistance and antibiotic therapy is adequately applied antibiotic prophylaxis in surgery.