Características del almacenamiento de antibióticos en una población suburbana de México

Objetivo: Determinar las características de almacenamiento de los antibióticos de las familias en una población suburbana en México. Metodología: El enfoque del estudio es cuantitativo, observacional, de corte transversal y alcance descriptivo. La unidad de estudio fueron las familias que vivían en el área de estudio de una zona suburbana en México. Resultados: Se encuestaron un total de 235 familias, dentro de las cuales existen diversos grupos etarios, de los cuales predominaron las edades de entre 36 a 64 años en 153 familias. Se obtuvo que más del 70 % presentaban enfermedades y, respecto a la posibilidad de que tuviesen almacenados medicamentos antibióticos caducados o próximos a caducar, el 68.1 % mencionó que no era probable. Conclusiones: El importante número de población adulta, la amplia presencia de comorbilidades y diversos factores sociodemográficos impactan en las prácticas y actitudes en relación con las formas en que las familias obtienen, usan, almacenan y desechan los medicamentos dentro de sus hogares. Esta investigación busca contribuir a la concientización y creación de diversos programas para la adopción de medidas de seguridad para el almacenamiento de medicamentos dentro del hogar, así como servir de guía en la identificación de procedimientos óptimos, eficientes y eficaces para tratar este fenómeno.

Objetivo: Determinar as características do armazenamento de antibióticos das famílias em uma população suburbana no México. Metodologia: A abordagem do estudo é quantitativa, observacional, transversal e de escopo descritivo. A unidade de estudo foram as famílias que viviam na área de estudo de uma zona suburbana no México. Resultados: Foram pesquisadas 235 famílias, de diversas faixas etárias, das quais predominaram as idades de 36 a 64 anos em 153 famílias. Verificou-se que mais de 70% apresentavam enfermidades, e com relação à possibilidade de terem medicamentos antibióticos vencidos ou prestes a vencer armazenados, 68,1 % mencionaram que não era provável. Conclusões: O significativo número de população adulta, a ampla presença de comorbidades e vários fatores sociodemográficos impactam nas práticas e atitudes relativas às formas como as famílias obtêm, usam, armazenam e descartam medicamentos em suas residências. Esta pesquisa busca contribuir para a conscientização e a criação de vários programas para a adoção de medidas de segurança para o armazenamento de medicamentos em casa, bem como servir de guia na identificação de procedimentos ideais, eficientes e eficazes para lidar com esse fenômeno.

Objective: To determine the antibiotic storage characteristics of families in a suburban population in Mexico. Methodology: The study approach is quantitative, observational, cross-sectional and descriptive in scope. The unit of study was families living in the area under study in a suburban zone of Mexico. Results: A total of 235 families were surveyed, within which there are different age groups, with 153 families predominantly aged between 36 and 64 years old. It was obtained that more than 70 % presented illnesses and, regarding the possibility that they had stored expired or soon to expire antibiotic drugs, 68.1 % mentioned that it was not likely. Conclusions: The significant number of adult population, the wide presence of comorbidities and various sociodemographic factors impact practices and attitudes regarding the ways in which families obtain, use, store and dispose of medications within their homes. This research seeks to contribute to the awareness and creation of various programs for the adoption of safety measures for the storage of medicines within the home, as well as to serve as a guide in the identification of optimal, efficient and effective procedures to deal with this phenomenon.

Intraosseous regional antibiotic prophylaxis in total joint arthroplasty (TJA): Systematic review and meta-analysis.

Background: A major catastrophic adverse event after total joint arthroplasty surgery (TJA) is the periprosthetic joint infection (PJI). In the recent years, regional antibiotic prophylaxis has gained momentum as a novel infection control strategy in total knee arthroplasty (TKA), with different purported benefits over systemic administration. The current article was planned to comprehensively review the available evidence in literature; as well as compare the safety and effectiveness of intraosseous (IO) antibiotic prophylaxis with systemic prophylaxis in patients undergoing TJA. Methods: An independent database (5 databases: Pubmed, Scopus, Embase, Web of science and Cochrane library) search was performed (on January 1, 2024) using suitable key words [PROSPERO (registration number: CRD42023458219)]. All randomised controlled trials (RCT), prospective or retrospective studies reporting data on intraosseous vancomycin or other antibiotics during arthroplasty for prophylaxis of PJI were considered. Studies not pertaining to the topic of interest or non-clinical trials were excluded. The evaluated outcome parameters included PJI incidence, systemic antibiotic levels, minimal inhibitory concentrations, local antibiotic concentrations achieved in soft tissues (or fat) and bone; and associated complications. While the "risk of bias" was evaluated using ROB-2 tool and MINORS criteria; LibreOffice version (v)7.5.6 was utilized for data management. OpenMeta-analyst v5.26.14 and RevMan v5.4 software were employed for meta-analysis. Results: Following our literature search, 11 studies (1 prospective series, 6 RCT and 4 retrospective studies) were finally identified. Based on our meta-analysis, there was statistically higher antibiotic concentration in the bone [mean difference (MD):25.12 µg/g;95%CI:10.32,39.91;z=3.33,p = 0.0009] and local fat tissues [MD:22.01 µg/g;95%CI:1.71,32.30;z=4.19,p < 0.0001) following IO prophylaxis, as compared with the systemic drug administration. IO prophylaxis was also associated with a significant reduction in prosthetic joint infections (PJI; April 1633 and 25/2213 patients developed PJI in IO and systemic prophylaxis groups, respectively; p = 0.006). There was significant difference in gram-positive infections between IO and systemic prophylaxis groups (2/1123 and 13/1753 g + ve infections in IO and systemic prophylaxis groups, respectively; p = 0.05). Our review and meta-analysis revealed no substantial difference in complications amongst the groups (p = 0.66). Conclusion: IO antibiotic prophylaxis appears to be an effective and safe strategy in patients undergoing TJA. IO access provides substantially enhanced antibiotic elution into the local tissues (bone and soft tissues); and consequently, results in reduced of PJI rates after TJA (in comparison with conventional systemic antibiotic prophylaxis).

A Sr@Ag-based spatiotemporal and step-release scaffold against chronic osteomyelitis, fabricated by coaxial 3D-printing.

Chronic osteomyelitis (OM) represents a severe and persistent infectious bone disease. Effective treatment requires controlled anti-inflammatory releases and bone regeneration across disease phases. A Sr@Ag-based scaffold was successfully printed, featuring micron-scale coaxial fibers containing Ag-doped hydroxyapatite (HA) in the outer layer of PLLA and Sr-doped HA in the inner layer of PLLA, facilitating the spatiotemporal and sequential release of Ag and Sr ions during OM treatment. Most antibacterial agent (Ag) was released during the first 20 days, followed by a slow-release plateau over the next 40 days in phosphate-buffered saline solution (PBS). Meanwhile, the pro-angiogenic agent (Sr) was released in minimal amounts during the initial 20 days, followed by a rapid and considerable release in the following 40 days. The coaxial design effectively inhibited the growth of Staphylococcus aureus and Escherichia coli while preserving the viability of bone cells. The ion-based scaffold exhibited broad-spectrum antibacterial effects and enhanced bone-regenerating gene expression in a complex air-bacteria environment. The Sr@Ag-based coaxial scaffold demonstrated effective antibacterial activity during the early stage and exhibited excellent non-toxic bone regeneration results during the middle and late stages in vivo. This work offered a promising treatment strategy through sequential anti-inflammatory and pro-osteogenic effects for infectious bone-defect diseases.

Investigation on taxonomy, secondary metabolites and antibacterial activity of Streptomyces sediminicola sp. nov., a novel marine sediment-derived Actinobacteria.

BACKGROUND: Marine actinomycetes, especially Streptomyces, are recognized as excellent producers of diverse and bioactive secondary metabolites on account of the multiplicity of marine habitations and unique ecological conditions, which are yet to be explored in terms of taxonomy, ecology, and functional activity. Isolation, culture and genome analysis of novel species of Streptomyces to explore their potential for discovering bioactive compounds is an important approach in natural product research. RESULTS: A marine actinobacteria, designated strain SCSIO 75703 T, was isolated, and the potential for bioactive natural product discovery was evaluated based on genome mining, compound detection, and antimicrobial activity assays. The phylogenetic, phenotypic and chemotaxonomic analyses indicate that strain SCSIO 75703 T represents a novel species in genus Streptomyces, for which the name Streptomyces sediminicola sp. nov. is proposed. Genome analysis revealed the presence of 25 secondary metabolite biosynthetic gene clusters. The screening for antibacterial activity reveals the potential to produce bioactive metabolites, highlighting its value for in-depth exploration of chemical constituents. Seven compounds (1-7) were separated from the fractions guided by antibacterial activities, including three indole alkaloids (1-3), three polyketide derivatives (4-6), and 4-(dimethylamino)benzoic acid (7). These primarily antibacterial components were identified as anthracimycin (4), 2-epi-anthracimycin (5) and ß-rubromycin (6), presenting strong antibacterial activities against Gram-positive bacteria with the MIC value ranged from 0.125 to 16 µg/mL. Additionally,, monaprenylindole A (1) and 3-cyanomethyl-6-prenylindole (2) displayed moderate inhibitory activities against α-glucosidase with the IC50 values of 83.27 and 86.21 µg/mL, respectively. CONCLUSION: Strain SCSIO 75703 T was isolated from marine sediment and identified as a novel species within the genus Streptomyces. Based on genomic analysis, compounds isolation and bioactivity studies, seven compounds were identified, with anthracimycin and ß-rubromycin showing significant biological activity and promising potential for further applications.

Renal Function and Its Impact on the Concentration of Ceftazidime-Avibactam: A cross-sectional study.

OBJECTIVES: This study measured the effect of renal function on the plasma concentrations of ceftazidime and avibactam in critically ill patients. We also sought to measure the concentration ratio of ceftazidime to avibactam. METHODS: This was a cohort study at a tertiary referral centre in Italy, on patients treated with continuous infusion of ceftazidime-avibactam (CAZ-AVI) between November 2019 and December 2023. The association between creatine clearance (CrCl) and free plasma ceftazidime and avibactam concentration, as well as CAZ-AVI ratio was explored to assess correlation and potential risk to fail to achieve target therapeutic concentration. RESULTS: 52 patients, predominantly male (75%), with a median age of 68.5 years were included. Our analyses provided strong evidence for inverse correlation between CrCl and both free-CAZ (r=-0.627; R2=0.3936; P<0.001) and free-AVI plasma concentration (r=-0.619; R2=0.3832; P<0.001). Overall CrCl alone could explain about 40% of overall variation of either free-CAZ and free-AVI. Linear models suggest that free-CAZ and free-AVI concentration drop of about 7.31% and 9.23% for each 10 point increase of CrCl, respectively. . Assessment of the CAZ-AVI ratio supports a direct linear association with CrCl suggesting that free-AVI concetration is more affected by CrCl variation than free-CAZ concentration. Patients with CrCl ≥130 mL/min showed a significantly higher risk of suboptimal drug exposure (i.e. less than 4 times the MIC) both to CAZ and AVI. CONCLUSION: The findings emphasize the need for individualized dosing strategies of CAZ-AVI based on renal function, for antibiotics used in critically ill patients. The study suggests that underdosing in patients with high CrCl is likely to be common and as such could affect drug effectiveness.

Rising trend of dentist-prescribed antibiotics in Brazil: 2011-2021.

OBJECTIVES: To describe the trends in antibiotic prescribing by dental practitioners and to investigate the relationship between these trends and some factors of public oral health services in Minas Gerais (MG), Brazil. METHODS: This was a time-series analysis of antibiotics prescribed by dental practitioners between January 2011 and December 2021. The outcome variables were number of defined daily doses (DDD) and DDD/1000 population/year in a sample of cities in MG. Covariates were public oral healthcare factors, such as coverage, estimates of dental procedures, and frequency of dental pain. Linear time-series regression models were used to examine trends and the influence of covariates on antibiotic prescribing. RESULTS: Overall, the number of prescriptions increased by 334.69% between 2011 and 2021, with amoxicillin being the most commonly prescribed drug (78.53%). The number of DDD for all antibiotics increased from 17,147.13 to 77,346.67 and the average DDD/1000 inhabitants/year was 126.66 (SD: 130.28). The linear time-series regression model showed that for each one-year increase, the average log DDD/1000 inhabitants increased by 0.35 (standard error = 0.07, p < 0.001). No covariates were found to be associated with the outcome. CONCLUSIONS: In Minas Gerais, Brazil, a significant upward trend was observed in the number of prescriptions and the number of DDD of antibiotics prescribed by dental practitioners. No influence of factors related to public oral healthcare services on the outcome was observed, thereby emphasizing the need for further research on factors influencing medication use in dental practice.

Primary Caregiver Knowledge about Self-Medication of Antibiotics in Children Aged 0-12 Years.

Globally, it is estimated that more than 50% of antibiotics are obtained without a prescription. The main purpose of this study is to determine the knowledge and practice of primary caregivers about self-medication in children with antibiotics, as studies on self-medication is lacking in India, also, it will help is assessing parents' knowledge and attitude towards self medication. This cross-sectional study conducted in the urban community of Shastri Nagar, Patna, aimed to evaluated antibiotic use in children aged 0-12. From January 2023 to March 2023, 173 caregivers were randomly selected through house visits. Data collection used a pre-tested questionnaire, ensuring confidentiality. In this study of 173 participants, caregivers in an urban community demonstrated varying knowledge regarding antibiotic use in children. Mothers and post-graduates possessed better awareness of antibiotic consequences. Fathers exhibited better understanding of side effects. Knowledge on antibiotics' action was seen among mothers, those aged 30-39, with family income of Rs. 20,000-40,000 and those with family members in medical field. Fathers had more incorrect beliefs about antibiotics treating viral infections. Common conditions for self-medication included cough/cold, fever and diarrhea, with hospitals being the primary source of antibiotics. Majority obtained information from pharmacies but awareness about antibiotic course completion and versatility was limited. Caregivers' antibiotic knowledge varied; mothers and post-graduates were more aware, while fathers understood side effects better.

Tuning Interfacial Molecular Asymmetry to Engineer Protective Coatings with Superior Surface Anchoring, Antifouling and Antibacterial Properties.

Multifunctional robust protective coatings that combine biocompatibility, antifouling and antimicrobial properties play an essential role in reducing host reactions and infection on invasive medical devices. However, developing these protective coatings generally faces a paradox: coating materials capable of achieving robust adhesion to substrates via spontaneous deposition inevitably initiate continuous biofoulant adsorption, while those employing strong hydration capability to resist biofoulant attachment have limited substrate binding ability and durability under wear. Herein, we designed a multifunctional terpolymer of poly(dopamine methyacrylamide-co-2-methacryloyloxyethyl phoasphorylcholine-co-2-(dimethylamino)-ethyl methacrylate) (P(DMA-co-MPC-co-DMAEMA)), which integrates desired yet traditionally incompatible functions (i.e., robust adhesion, antifouling, lubrication, and antimicrobial properties). Direct normal and lateral force measurements, dynamic adsorption tests, surface ion conductance mapping were applied to comprehensively investigate the nanomechanics of coating-biofloulant interactions. Catechol groups of DMA act as basal anchors for robust substrate deposition, while the highly hydrated zwitterion of MPC provides apical protection to resist biofouling and wear. Moreover, the antimicrobial property is conferred through the protonation of tertiary amine groups on DMAEMA, inhibiting infections under physiological conditions. This work provides an effective strategy for harmonizing demanded yet incompatible properties in one coating material, with significant implications for the development of multifunctional surfaces towards the advancement of invasive biomedical devices. STATEMENT OF SIGNIFICANCE: Multifunctional robust protective coatings have been widely utilized in invasive medical devices to mitigate host responses and infection. However, modified surface coatings often encounter a trade-off between robust adhesion to substrates and strong hydration capability for antifouling and antimicrobial properties. We propose a universal strategy for surface modification by dopamine-assisted co-deposition with a multifunctional terpolymer of P(DMA-co-MPC-co-DMAEMA) that simultaneously achieves robust adhesion, antifouling, and antimicrobial properties. Through elucidating the nanomechanics with fundamentally understanding the interactions between the coating and biomacromolecules, we highlight the role of DMA for substrate adhesion, MPC for biofouling resistance, and DMAEMA for antimicrobial activity. This approach presents a promising strategy for constructing multifunctional coatings on minimally invasive medical devices by tuning interfacial molecular asymmetricity to reconcile incompatible properties within one coating.

Biosynthesis of antimicrobial nanoparticle from Swertia spp. (Chirayita) against bacterial pathogens of Poultry- A way forward to Green Nanotechnology and Nano-medicines.

The increasing prevalence of multidrug-resistant microorganisms in poultry has led to a rise in bacterial infections, causing significant economic loss. Green nanotechnology, such as silver nanoparticles (AgNPs), has the potential to address this issue by providing potent antifungal, antiviral, and antibacterial properties. This study explored the combined potential of AgNPs and the local herb Swertia chirayita against established poultry pathogens, employing a non-factorial Central Composite Design (CCD) to evaluate the factors affecting the production of nanoparticles induced by silver nitrate from the selected herb. The optimal values for temperature, wavelength, silver nitrate concentration, incubation duration, and pH were found to produce the highest nanoparticles. The functional groups in Swertia chirayita stimulated nanoparticles were confirmed using FTIR spectroscopy, and the stability of ScNPs was elucidated using zeta potential. The crystalline structure of ScNPs was confirmed using diffraction intensity patterns. Silver nanoparticles demonstrated antibacterial activity against Salmonella spp. and Escherichia coli (E.coli), both known as significant poultry pathogens, using the agar well diffusion method, with inhibition zones of 25.0 mm and 35.0 mm, respectively.This study explored the green manufacturing of silver nanoparticles by using plants and microorganisms, focusing on their antibacterial properties. The exact mechanism of synthesis and action in AgNPs is still poorly understood. Researchers should prioritize the use of accessible, easy-to-extract plants or bacteria, especially non-pathogenic and fast-growing microorganisms for safe handling. Analyzing biomolecules in plant extract, microbial biomass, or culture supernatants, including probiotic bacteria, is crucial for creating and stabilizing AgNPs, which could be effective synthetic agents. It is crucial to optimize conditions for rapid, stable, and large-scale synthesis. Based on this research, Sc-NPs may be proposed as nanomedicine for treating infections in poultry caused by E. coli and Salmonella spp.

Synthesis and characterization of aniline-based azo molecules: In vitro pharmacological and emission studies.

The present work involves the synthesis of novel dispersed mono-azo dyes using different coupling components and 2-methoxy-5-nitro aniline as amine through a simple and convenient diazo-coupling method. The structures of the newly synthesized mono azo dyes were confirmed by using various spectral techniques such as 1H NMR, Fourier transform infrared, and high-resolution mass spectrometry. At room temperature, the electronic absorption spectra and fluorescence spectra of the synthesized mono azo dyes were recorded with different solvents. The global reactive parameters for the synthesized azo molecules were evaluated by performing density functional theory through the 6-311++G (d, p) basis set. The anti-microbial activities for the synthesized azo compounds were carried out, and the compounds G1 and G2 exhibited good antibacterial and anti-fungal activities. The in silico molecular docking studies of the azo molecules revealed that all the compounds exhibited extraordinary binding affinity as that of the standard drug. Further, the anti-tuberculosis study against the Mycobacterium tuberculosis for the synthesized azo dyes was evaluated, and from the results, it was revealed that the compound G4 showed good sensitivity among the other synthesized azo compounds.

Non-fused Pyrimidine Derivatives as Potential Pharmacological Entities: A Review.

Non-fused pyrimidine scaffold is a significant component for designing new drugs. The review emphasizes the pharmacological importance of non-fused pyrimidine-containing moieties based on the broad spectrum of activities such as antiprotozoal, antibacterial, antimycobacterial, anticancer, anti-inflammatory activity, and CNS depressant. Pyrimidine derivatives are fascinating entities that display biological activities for the treatment of cancer. It also highlights the tendency of non-fused pyrimidine derivatives to suppress cell growth by obstructing the activity of VCP, CDK-2, EGFR, ATR, EphB4 & EphA2, PDGF as well as inhibitory action towards different cell lines such as MCF-7, HeLa, NCI/ADR-RES, NCIH23, HOP-92, HCT-116, OV-3, MOLT-4, PC-3, MDA-MB-231, MALME-3M, K562 and Bcr-Abl. The review details the importance of morpholine, piperidine, and pyrrolidine ring substitutions on pyrimidine moiety as well as the role of H-bonding and amino linkage along with antibacterial activity due to the presence of pleuromutilin and tetrazole molecules. Researchers were motivated to develop and enhance the non-fused pyrimidine scaffold to uncover novel medicines by reading this review article.

[When should shortterm antibiotic therapy be chosen?] / Quand choisir une antibiothérapie de courte durée ?

WHEN SHOULD SHORT-TERM ANTIBIOTIC THERAPY BE CHOSEN? Reducing antibiotic exposure by shortening treatment duration is a public health priority that could mitigate the emergence of bacterial resistance, minimize adverse effects, and lower costs. Additionally, a short yet effective antibiotic regimen is associated with improved patient compliance and satisfaction. Several trials in recent years have confirmed the efficacy of shorter treatment durations. For instance, five days of antibiotics are sufficient for uncomplicated pyelonephritis, while seven days suffice for non-febrile urinary tract infections in males. However, a 14-day regimen appears necessary for febrile urinary tract infections in men. A study examining a five-day treatment period found no difference compared to a 10-day regimen for skin and soft tissue infections. In acute community-acquired pneumonia, two randomized trials found three days of beta-lactam therapy to be effective. In intra-abdominal infections, durations ranging from four to eight days were found to be non-inferior to 15-day courses in two trials. Regarding osteoarticular infections, six weeks are adequate for spondylodiscitis, whereas 12 weeks are required for prosthetic joint infections. These findings validate shorter treatment durations across many clinical scenarios. However, in rare conditions such as febrile male urinary tract infections and prosthetic joint infections, shortening the duration may not be feasible. It is imperative to prescribe the shortest effective antibiotic duration possible in routine medical practice to combat antibiotic resistance.

QUAND CHOISIR UNE ANTIBIOTHÉRAPIE DE COURTE DURÉE ? Réduire l'exposition antibiotique en diminuant la durée de traitement est un enjeu de santé publique qui permettrait de limiter l'émergence des résistances bactériennes, réduire les effets indésirables, les coûts. En outre, une durée courte et efficace de traitement antibiotique est associée à une meilleure observance et satisfaction du patient. Ces dernières années, plusieurs essais ont permis de valider l'efficacité de durées de traitement court. Cinq jours d'antibiotique suffisent au cours des pyélonéphrites simples et sept jours au cours des infections urinaires masculines non fébriles. En revanche, un traitement de quatorze jours semble nécessaire au cours des infections urinaires fébriles de l'homme. Une étude portant sur cinq jours de traitement n'a pas retrouvé de différence avec un traitement de dix jours au cours des infections de la peau et des tissus mous. Dans les pneumonies aiguës communautaires, deux essais randomisés ont prouvé l'efficacité d'un traitement de trois jours par bêtalactamines. Au cours des infections intra- abdominales, deux essais ont montré que des durées d'antibiothérapie de quatre à huit jours étaient non inférieures à des traitements de quinze jours. Concernant les infections ostéoarticulaires, une durée de six semaines suffit au cours des spondylodiscites alors que douze semaines restent nécessaires lors des infections sur prothèse ostéoarticulaire. Ces données permettent de valider des durées de traitement courtes dans un grand nombre de situations cliniques. Cependant, dans de rares pathologies comme les infections urinaires masculines fébriles et les infections sur prothèses ostéoarticulaires, la durée ne semble pas pouvoir être raccourcie. Il convient de prescrire la durée de traitement antibiotique efficace la plus courte possible en pratique médicale courante afin de lutter contre l'antibiorésistance.

Discovery of sulfone containing metallo-ß-lactamase inhibitors with reduced bacterial cell efflux and histamine release issues.

The design, syntheses and antibacterial evaluation of sulfone analogues of previously disclosed metallo-ß-lactamase inhibitors (MBLis) are described. The novel derivatives were overall more effective in gram-negative bacterial cell-based assays when combined with imipenem and relebactam. The major contributors to the improved anti-bacterial activity are enhanced enzyme-inhibitor interactions and reduced bacterial cell efflux monitored via an efflux assay involving isogenic Pseudomonas aeruginosa efflux + and efflux - tool strains.

Synthesis and Anti-bacterial Activity of New Substituted 2-trifluoromethyl-4-quinolinylhydrazone Analogs against Mycobacterium tuberculosis Strains.

BACKGROUND: Tuberculosis (TB) is a serious disease that still affects humanity, despite being old, caused by the bacterium Mycobacterium tuberculosis (Mtb). The emergence of drug-resistant strains has alarmed governments and international organizations, such as the World Health Organization (WHO). The need for research on new drugs that are effective in a shorter treatment time and active against resistant strains still persists. OBJECTIVE: The objective of this study is to synthesize and evaluate forty-four substituted 2-trifluoromethyl-4-quinolinylhydrazone analogs, as probable inhibitors of Mycobacterium tuberculosis growth. METHODS: The anti-mycobacterial activities of all tested compounds against Mycobacterium tuberculosis strains, as well as the cytotoxicity test, were evaluated using the in vitro microplate procedure with broth microdilution assay. RESULTS: Thirteen compounds exhibited some activity against sensitive strain ATCC 27294, six of which were the most active: 4a, 4c, 6a, 6b, 6c, and 6g; with MIC around 7 - 8 µM, close to that presented by ethambutol (15.9 µM), a drug used in the treatment of tuberculosis. These same compounds also were active against a resistant strain of Mtb (T113), with MIC around 7 - 8 µM. Three of these compounds 4a, 6a, and 6c were not cytotoxic against Vero cells at concentrations near the MIC. CONCLUSION: This study indicates the importance of the hydrazone function to obtain promising anti-TB compounds and open new perspectives for drug development.

Niosome-loaded Tet-Amp against S. aureus, K. pneumoniae, and P. aeruginosa.

Biofilm-associated disorders contribute to elevated morbidity and death rates among patients. We propose synthesizing niosomal structures containing the antibiotics tetracycline and ampicillin ((Tet/Amp)-Nio) and investigating their impact on standard strains of S. aureus, K. pneumoniae, and P. aeruginosa. The antibacterial and anti-biofilm effects of synthesized niosomes against standard pathogenic bacterial strains were studied, and also its cytotoxic activity was investigated against human foreskin fibroblast (HFF) cell line. The optimal formulation (F2) had an average particle size of 196.90 ± 4.57 nm, a PDI of 0.223 ± 0.013, a Zeta-potential of -19.25 ± 1.19 mV, a %EE of 70.92 ± 1.75% for Tet and 58.34 ± 1.85% for Amp, and a %Release rate of 49.34 ± 1.78% for Tet and 62.67 ± 1.19% for Amp. The release of Tet and Amp drugs over 48 h was 47% and 61%, respectively, from the (Tet/Amp)-Nio formulation. Also, our findings demonstrated that the Tet/Amp)-Nio have potent antibacterial, anti-biofilm, and lower cytotoxic activity compared to the Tet + Amp. In addition, (Tet/Amp)-Nio can upregulate the expression level of matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) genes, which shows their great activity in the wound healing process. The findings of the current investigation suggest that (Tet/Amp)-Nio enhances its antibacterial and antibiofilm effects against S. aureus, P. aeruginosa, and K. pneumoniae isolates. These formulations may serve as a novel approach for targeted drug delivery.

How nanomaterials act against bacterial structures? a narrative review focusing on nanoparticle molecular mechanisms.

OBJECTIVE: In recent years, significant progress has been made in the field of nanotechnology for the treatment and prevention of biofilm formation and Multidrug-resistant bacteria (MDR). MDR bacteria challenges is hazardous when microorganisms induce the formation of biofilms, which amplify resistance to antibiotics and promote the development of multidrug-resistant conditions. The unique physicochemical properties of certain nanomaterials make nanotechnology a promising option for combating MDR infections. Several studies have introduced nanomaterials with different antibacterial mechanisms that can effectively destroy MDR bacteria and their biofilms. This study reviews the research results, focusing on the various nanoparticle mechanisms that target bacterial structures. METHOD: To accomplish this study, we conducted investigations to gather articles and relevant studies from validated medical databases such as Scopus, PubMed, Google Scholar, and Web of Science. The selected publications from 2007 to 2023. In this review, we provide a brief overview of nanoparticles, their mechanisms, and how they function against the structure of bacteria. Furthermore, we discuss the recent advancements in using certain nanoparticles to combat infection-induced biofilms and complications caused by multidrug resistance. FINDING: Our findings demonstrate that various nanoparticles have the potential to effectively overcome bacterial infectious diseases by targeting biofilms and antibiotic-resistant strains. Additionally, the development of a new drug delivery approach based on nanosystems shows promise in overcoming antibiotic resistance and biofilms.

Disrupting Mycobacterium smegmatis biofilm using enzyme-immobilized rifampicin loaded silk fibroin nanoparticles for dual anti-bacterial and anti-biofilm action.

Biofilm formation is a major challenge in the treatment of tuberculosis, leading to poor treatment outcomes and latent infections. The complex and dense extracellular polymeric substances (EPS) of the biofilm provides safe harbour for bacterium enabling persistence against anti-TB antibiotics. In this study, we demonstrated that rifampicin-encapsulated silk fibroin nanoparticles immobilized with antibiofilm enzymes can disrupt the Mycobacterium smegmatis biofilm and facilitate the anti-bacterial action of Rifampicin (RIF). The EPS of M.smegmatis biofilm predominantly comprised of lipids (48.8 ± 1.32 %) and carbohydrates (34.8 ± 4.70 %), similar to tuberculosis biofilms. Pre-formed biofilm eradication screening revealed that hydrolytic enzymes such as ß-Glucosidase, Glucose oxidase, ɑ-Amylase, Acylase, and Phytase can exhibit biofilm eradication of M.smegmatis biofilms. The enzyme-mediated biofilm disruption was associated with a decrease in hydrophobicity of biofilm surfaces. Treatment with ß-glucosidase and Phytase demonstrated a putative biofilm eradication by reducing the total carbohydrates and lipid composition without causing any significant bactericidal activity. Further, Phytase (250 µg/ml) and ß-Glucosidase (112.5 ± 17.6 µg/ml) conjugated rifampicin-loaded silk fibroin nanoparticles (R-SFNs) exhibited an enhanced anti-bacterial activity against pre-formed M.smegmatis biofilms, compared to free rifampicin (32.5±7 µg/ml). Notably, treatment with ß-glucosidase, Phytase and ɑ-amylase immobilized SFNs decreased the biofilm thickness by ∼98.84 % at 6h, compared to control. Thus, the study highlights that coupling anti-mycobacterial drugs with biofilm-eradicating enzymes such as amylase, phytase or ß-glucosidase can be a potential strategy to improve the TB therapeutic outcomes.

A new antibacterial with anti-inflammatory properties promotes wound healing through inhibiting cGAS/STING/NF-κB/IRF3 pathway.

Benzothiazole-urea hybrid 8l was found to be a potent anti-bacterial agent against methicillin-resistant Staphylococcus aureus (MRSA2858) (MIC = 0.78 µM, Eur J Med Chem. 2022,236:114333). Herein, 8l was further evaluated to remedy the MRSA-infected scald with bacterial infection and severe inflammation. In scalded skin model with MRSA infection, 8l not only effectively reduced bacterial load, but also decreased pro-inflammatory cytokines secretion and promoted collagen deposition to effectively reverse the progression of wound infection and inflammation by blocking cGAS/STING/NF-κB/IRF3 signaling pathway. In vitro model of RAW264.7 cells verified that 8l can inhibit MRSA-induced inflammation via regulating this pathway. All in all, dual anti-bacterial and anti-inflammatory agent 8l could heal MRSA-infected refractory scald by regulating cGAS/STING/NF-κB/IRF3 pathway.

Antimicrobial Prescription Practices and Stewardship in Washington State Small and Mixed Animal Veterinary Medicine.

INTRODUCTION: Judicious antimicrobial use is essential for the continued treatment of infections in small and mixed animal veterinary medicine. To better support Washington (WA) State veterinarians in antimicrobial stewardship, we surveyed licensed small and mixed animal veterinarians and led group conversations regarding antimicrobial prescription practices. METHODS: Survey questions included demographic information, factors influencing prescription practices and clinical cases. Responses were summarised and logistic regressions were performed to identify factors associated with antibiotic treatment choices. Group conversations, led by a licensed veterinarian, focused on resource gaps for veterinarians, management of clinical scenarios and interpretation of minimum inhibitory concentrations (MICs) and breakpoints. A systematic qualitative analysis of conversation transcripts identified key themes such as common barriers to stewardship. RESULTS: Among 53 responses to clinical scenarios, veterinarians selected the most appropriate treatment choice, according to a veterinary microbiologist, 62% of the time. Variability was observed in culture and susceptibility practices and antibiotic choices. Survey respondents reported an influence of the client ability to medicate (92%), considerations of resistance (91%), client finances (75%) and availability of antimicrobials (75%) on their prescription decisions. There were no significant associations between opinions about contributing factors to antimicrobial resistance (AMR) or guidelines used and treatment choices in clinical scenarios. Among 15 veterinarians interviewed in group conversations, a systematic qualitative analysis of conversation transcripts revealed key themes, including reliance on human medicine as a resource and a lack of support for veterinarians in interpreting MICs and breakpoints. CONCLUSIONS: The variability in veterinary antibiotic treatment decisions in this study suggests a need for further dissemination of standardised antimicrobial stewardship resources for veterinarians. Client-related challenges and the cost of culture and susceptibility are major barriers to stewardship. To address these barriers, it is necessary to provide standardised, easy-to-access guidance for veterinarians in interpreting MICs and breakpoints, as well as develop antimicrobial use resources for clients.