Search

Background: In this work, we represent synthesis, in silico analysis and biological activity of 1,4 diazepine linked piperidine derivatives (6a–6o). All the derivatives were screened for their anti-microbial activity against gram-positive (Staphylococcus aureus, Bacillus Subtills, Bacillus megaterium) and gram-negative (Escherichia coli, Pseudonymous, Shigella sp.) bacteria. Compounds were synthesized from reaction of tert-butyl 1,4-diazepane-1-carboxylic, butyryl chloride and varied aromatic aldehyde, further characterized by 1H NMR and LCMS spectral techniques. Result: Using ampicillin as a positive control, the synthetic compounds 6a–6o were tested for their in-silico study and experimental anti-microbial activity against gram-positive (Staphylococcus aureus, Bacillus Subtills, Bacillus megaterium) and gram-negative (Escherichia coli, Pseudonymous, Shigella sp.) bacteria. According to in vitro assay compound 6a, compound 6c, compound 6d, compound 6m and compound 6I showed higher activity against all the tested strains. Molecule 6i, compound 6j, compound 6k, compound 6f has good to moderate antibacterial activity. DFT computations were used to optimize the molecular geometry at the B3LYP/6-31G (d, p) theoretical level. The corresponding energy values of molecular orbitals were visualized using optimized geometries. Moreover, Auto Dock Vina 1.2.0 is used to assess molecular docking against two target proteins, Bacillus subtilis (PDB ID: 6UF6) and Protease Vulgaris (PDB ID: 5HXW). The target molecule 6b displayed the best binding energies for both. Additionally, we calculated the ADME for each molecule (6a–6o). Conclusion: All fifteen synthesized compounds were screened for their in vitro and in silico analysis. In vitro analysis for anti-microbial activity was carried out against gram-positive (Staphylococcus aureus, Bacillus Subtills, Bacillus megaterium) and gram-negative (Escherichia coli, Pseudonymous, Shigella sp.) bacteria and compound 6a, compound 6c, compound 6d, compound 6m and compound 6I exhibits more potent activity towards all tested strains. Molecular docking is performed against target proteins, L-amino acid deaminase from Proteus Vulgaris and LcpA ligase from Bacillus subtilis, representing the Gram-negative bacterium and Gram-positive bacterium, respectively. Compound 6b showed the highest no. of interaction with protein according to molecular docking. With the advent of innovative techniques like ADME, we select their hit compounds early on and anticipate future pharmacokinetic and pharmacodynamic benefits and drawbacks of these promising therapeutic candidates. [ABSTRACT FROM AUTHOR]

AbstractA series of quinoline-thiazole appended 1,4-disubstituted 1,2,3-triazole were synthesized by performing Cu(I) catalyzed 1,3-dipolar cycloaddition reaction (“Click” reaction) and fully characterized by various spectral techniques like FTIR, NMR and HRMS. These compounds were evaluated for in vitro antimalarial activity against plasmodium falciparum. All the compounds (7a–7y) exhibited moderate to good activity in comparison to standard drug Quinine. Compound 7r (IC50 0.19 µg/mL) displayed appreciable activity comparable to Quinine (IC50 0.268 µg/mL). Further antimicrobial screening of the synthesized substituted triazoles were also carried out against two gram (+) bacteria (Staphylococcus aureus, Bacillus subtilis), two gram (–) bacteria (Escherichia coli, Klebsiella pneumonia) and two fungi (Candida albicans, Aspergillus niger). Results revealed that compound 7r reflected promising antimicrobial activity among the synthesized library of molecules. Molecular docking studies of broadly active antimalarial disubstituted triazoles 7m and 7r were explored in the active site of enzyme dihydroorotate dehydrogenase (DHODH) to have the probable mode of action. [ABSTRACT FROM AUTHOR]

Silver compounds are mainly studied as antimicrobial agents, but they also have anticancer properties, with the latter, in some cases, being better than their gold counterparts. Herein, we analyse the first example of a new Ag(I)-biscarbene that can bind non-canonical structures of DNA, more precisely G-quadruplexes (G4), with different binding signatures depending on the type of G4. Moreover, we show that this Ag-based carbene binds the i-motif DNA structure. Alternatively, its Au(I) counterpart, which was investigated for comparison, stabilises mitochondrial G4. Theoretical in silico studies elucidated the details of different binding modes depending on the geometry of G4. The two complexes showed increased cytotoxic activity compared to cisplatin, overcoming its resistance in ovarian cancer. The binding of these new drug candidates with other relevant biosubstrates was studied to afford a more complete picture of their possible targets. In particular, the Ag(I) complex preferentially binds DNA structures over RNA structures, with higher binding constants for the non-canonical nucleic acids with respect to natural calf thymus DNA. Regarding possible protein targets, its interaction with the albumin model protein BSA was also tested. [ABSTRACT FROM AUTHOR]

AbstractA new cladosporol derivative xylophilum A (1), together with 10 known compounds (2–11), were isolated from the rice fermentation of the fungus Cladosporium xylophilum. Their structures were established by extensive spectroscopic methods and comparison of their NMR data with literatures. The antimicrobial activity of compound 1 against 11 kinds of pathogenic microbial was evaluated, but no significant activity was found (MIC >100 μg/ml). [ABSTRACT FROM AUTHOR]

A set of thymol‐based derivatives (3 a–d) was synthesized and characterized. Quantum chemical calculations were performed to explain the nature of the transitions in the absorption spectra. These new compounds were tested as anticancer agents on human liver (HepG2), lung (A549), and colon (DLD‐1) cancer cell lines using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide method showing in some cases higher antiproliferative properties than the reference drug cisplatin. All synthesized compounds were also screened for their antimicrobial activity against a representative panel of Gram‐positive and Gram‐negative bacteria plus a pathogenic yeast species (Candida albicans ATCC90028) using agar disc diffusion and broth microdilution assays. Furthermore, we determined the antioxidant activity of these compounds by the DPPH free radical scavenging test. According to the minimum bactericidal concentration, minimum fungicidal concentration, and IC50 values, compound 3 c showed the highest antimicrobial activity, compound 3 d exhibited the highest antioxidant activity, while compounds 3 b and 3 c displayed higher cytotoxic activity than cisplatin against HepG2 and DLD‐1 cell lines albeit no selectivity towards healthy cells (HEK‐293T). Furthermore, docking simulations of the compounds towards two potential molecular targets, namely caspase‐3 protein (PDB ID: 3KJF) and Escherichia coli glucosamine‐6‐phosphate synthase (PDB ID: 2VF5), were performed in order to validate the anticancer and antimicrobial activities, respectively. [ABSTRACT FROM AUTHOR]

Phenolic acids still gain significant attention due to their potential antimicrobial and cytotoxic properties. In this study, we have investigated the antimicrobial of six phenolic acids, namely chlorogenic, caffeic, p-coumaric, rosmarinic, gallic and tannic acids in the concentration range 0.5–500 μM, against Escherichia coli and Lactobacillus rhamnosus. The antimicrobial activity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Additionally, the cytotoxic effects of these phenolic acids on two cancer cell lines, the colorectal adenocarcinoma Caco-2 cell line and Dukes' type C colorectal adenocarcinoma DLD-1 cell line was examined. To further understand the molecular properties of these phenolic acids, quantum chemical calculations were performed using the Gaussian 09W program. Parameters such as ionization potential, electron affinity, electronegativity, chemical hardness, chemical softness, dipole moment, and electrophilicity index were obtained. The lipophilicity properties represented by logP parameter was also discussed. This study provides a comprehensive evaluation of the antimicrobial and cytotoxic activity of six phenolic acids, compounds deliberately selected due to their chemical structure. They are derivatives of benzoic or cinnamic acids with the increasing number of hydroxyl groups in the aromatic ring. The integration of experimental and computational methodologies provides a knowledge of the molecular characteristics of bioactive compounds and partial explanation of the relationship between the molecular structure and biological properties. This knowledge aids in guiding the development of bioactive components for use in dietary supplements, functional foods and pharmaceutical drugs. [ABSTRACT FROM AUTHOR]

Background Streptococcal bacteremia is associated with high mortality. Thia study aims to identify predictors of mortality among patients with streptococcal bacteremia. Methods This retrospective study was conducted at the Lausanne University Hospital, Switzerland, and included episodes of streptococcal bacteremia among adult patients from 2015 to 2023. Results During the study period, 861 episodes of streptococcal bacteremia were included. The majority of episodes were categorized in the Mitis group (348 episodes; 40%), followed by the Pyogenic group (215; 25%). Endocarditis was the most common source of bacteremia (164; 19%). The overall 14-day mortality rate was 8% (65 episodes). The results from the Cox multivariable regression model showed that a Charlson comorbidity index >4 (P.001; hazard ratio [HR], 2.87; confidence interval [CI]: 1.58–5.22), Streptococcus pyogenes (P =.011; HR, 2.54;CI: 1.24–5.21), sepsis (P <.001; HR, 7.48; CI: 3.86–14.47), lower respiratory tract infection (P =.002; HR, 2.62; CI: 1.42–4.81), and absence of source control interventions within 48 hours despite being warranted (P =.002; HR, 2.62; CI: 1.43–4.80) were associated with 14-day mortality. Conversely, interventions performed within 48 hours of bacteremia onset, such as infectious diseases consultation (P <.001; HR, 0.29; CI:.17–.48) and appropriate antimicrobial treatment (P <.001; HR,.28; CI:.14–.57), were associated with improved outcome. Conclusions Our findings underscore the pivotal role of infectious diseases consultation in guiding antimicrobial treatment and recommending source control interventions for patients with streptococcal bacteremia. [ABSTRACT FROM AUTHOR]

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision making for challenging presentations. This review will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta. [ABSTRACT FROM AUTHOR]

Background The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations. Methods We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood–brain barrier). Results The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%–95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid. Conclusions Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy. [ABSTRACT FROM AUTHOR]

Background Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. Methods In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. Results Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: −4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: −14.1%, −4.5%; P =.0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. Conclusions Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration. Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566. [ABSTRACT FROM AUTHOR]

The early administration of appropriate antibiotic therapy is crucial for the survival of patients with bacteremia. Current research focuses on improving analytical times through technology, whereas there have been very few efforts to improve postanalytical times even though they represent 40% of the time between blood taking and appropriate treatment administration. One of the clues is the efficiency and appropriateness of the result communication system. Here, we review all delays in the entire process with the aim of improving time to appropriate treatment administration. We discuss causes for long times to adjust treatment once microbiological results are released. We argue that the pervasive health information system in this organization serves as both a bottleneck and a rigid framework. Finally, we explore how next-generation hospital information systems should be designed to effectively assist the doctors in treating patients with bacteremia. [ABSTRACT FROM AUTHOR]

Ten novel 4-esterchalcones, licochalcone analogues, were strategically synthesized to study the effect of electro-donating or electro-withdrawing substituents in the aryl enone moiety on their pharmacological and photoprotective properties. 4-Esterchalcones had their drug-like character evaluated, which demonstrated positive characteristics for the development of novel drug candidates. In the in vitro antimicrobial evaluation, isovaleryl 4-esterchalcones showed activity against strains of Staphylococcus aureus, Candida albicans and C. tropicalis with minimum inhibitory concentration (MIC) in the range of 2.64-3.32 µmol mL−1, and the isobutyryl 4-esterchalcone 5d (4'-Br) presented antimicrobial activity against all strains tested, with a MIC of 2.74 µmol mL−1. In the UV-Vis study, λmax were observed at 312-327 nm, the UVB range, mainly. The best SPF-UVB results ranged from 18.04 to 21.06, with high εmax values, indicating that 4-esterchalcones have the potential to act as sunscreens. Furthermore, along with the environmental concern, halogenated compounds demonstrated slightly toxic on Artemia salina. [ABSTRACT FROM AUTHOR]

Detergent chemistry enables applications in the world today while harming safe operating spaces that humanity needs for survival. Aim of this review is to support a holistic thought process in the design of detergent chemistry. We harness the planetary boundary concept as a framework for literature survey to identify progresses and knowledge gaps in context with detergent chemistry and five planetary boundaries that are currently transgressed, i.e. climate, freshwater, land system, novel entities, biosphere integrity. Our survey unveils the status of three critical challenges to be addressed in the years to come, including (i) the implementation of a holistically, climate‐friendly detergent industry; (ii) the alignment of materialistic and social aspects in creating technical solutions by means of sustainable chemistry; (iii) the development of detergents that serve the purpose of applications but do not harm the biosphere in their role as novel entities. Specifically, medically relevant case reports revealed that even the most sophisticated detergent design cannot sufficiently accelerate drug discovery to outperform the antibiotic resistance development that detergents simultaneously promote as novel entities. Safe operating spaces that humanity needs for its survival may be secured by directing future efforts beyond sustainable chemistry, resource efficiency, and net zero emission targets. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the major health problems associated with patient care. In this context, researchers are interested in developing novel, effective and sustainable therapeutic nanoformulations. It has been observed that chitosan, polyvinyl alcohol, copper oxide and Acalypha indica (AI) extract have proven antimicrobial efficacy either individually or in combination. The presented study was focused on development of chitosan/PVA/CuO-AI nanocomposite for antimicrobial activity. In addition, hemolytic activity of the nanocomposite was also determined. Scanning electron microscopy, Fourier-transform infrared spectroscopy and X-ray crystallography confirmed the preparation of the nanocomposite. In addition, the chitosan/PVA/CuO-AI nanocomposite demonstrated effective antimicrobial activity and it was not hemolytic on human blood samples. Moreover, the cytotoxicity assay performed on Danio rerio gill cell line recorded 85% cells viability and no significant morphological alterations were observed. [ABSTRACT FROM AUTHOR]

Four neutral Rh1–Rh4 complexes of the general formula [Rh2(CH3COO)4L2], where L is an N-alkylimidazole ligand, were synthesized and characterized using various spectroscopic techniques, and in the case of Rh4 the crystal structure was confirmed. Investigation of the interactions of these complexes with HSA by fluorescence spectroscopy revealed that the binding constants Kb are moderately strong (∼104 M−1), and site-marker competition experiments showed that the complexes bind to Heme site III (subdomain IB). Competitive binding studies for CT DNA using EB and HOE showed that the complexes bind to the minor groove, which was also confirmed by viscosity experiments. Molecular docking confirmed the experimental data for HSA and CT DNA. Antimicrobial tests showed that the Rh2–Rh4 complexes exerted a strong inhibitory effect on G+ bacteria B. cereus and G− bacteria V. parahaemolyticus as well as on the yeast C. tropicalis, which showed a higher sensitivity compared to fluconazole. The cytotoxic activity of Rh1–Rh4 complexes tested on three cancer cell lines (HeLa, HCT116 and MDA-MB-231) and on healthy MRC-5 cells showed that all investigated complexes elicited more efficient cytotoxicity on all tested tumor cells than on control cells. Investigation of the mechanism of action revealed that the Rh1–Rh4 complexes inhibit cell proliferation via different mechanisms of action, namely apoptosis (increase in expression of the pro-apoptotic Bax protein and caspase-3 protein in HeLa and HCT116 cells; changes in mitochondrial potential and mitochondrial damage; release of cytochrome c from the mitochondria; cell cycle arrest in G2/M phase in both HeLa and HCT116 cells together with a decrease in the expression of cyclin A and cyclin B) and autophagy (reduction in the expression of the protein p62 in HeLa and HCT116 cells). [ABSTRACT FROM AUTHOR]

A new series of daidzein‐based short peptidomimetic compounds were developed. In this study, we incorporated an alkyl chain with different chain lengths as hydrophobic groups, various amino acids and their respective guanidinium salts as hydrophilic groups. The most potent compound 9 a showed excellent antibacterial activity with minimum inhibitory concentration (MIC) of 8 μM against S. aureus and 32 μM against Escherichia coli. Furthermore, 9 a inhibited more than 65 % S. aureus biofilm formation at sub‐MIC, it also disrupted 69 % pre‐established S. aureus at 64 μM. The cytoplasmic membrane permeability study of 9 a revealed that the depolarization of membrane could be the possible mechanism of action. However, 9 a exhibited moderate toxicity against human erythrocytes. [ABSTRACT FROM AUTHOR]

The investigation involved examining the binding of two lanthanide complexes, specifically those containing Holmium (Ho) and Dysprosium (Dy), with a ligand called 1, 10-phenanthroline (phen), and bovine serum albumin (BSA). The evaluation was carried out utilizing fluorescence measurements, Förster theory, and docking studies. The findings indicated that both the Ho-complex and Dycomplex possessed a significant ability to quench the emission of the protein. Furthermore, the primary mechanism of interaction was identified as a static process. The Kb values indicate a strong tendency of these complexes for binding with BSA. The Kb values show the strangely high affinity of BSA to complexes and the following order for binding affinity: Ho-complex > Dy-complex. The thermodynamic parameters were found to be negative, affirming that the main forces driving the interaction between BSA and the lanthanide complexes are van der Waals engagement and hydrogen bonds. Additionally, the investigation included the examination of competition site markers, and molecular docking proposed that the engagement sites of the Ho-complex and Dy-complex with BSA were predominantly located in site 3 (specifically, subdomain IB). Moreover, the Ho-complex and Dy-complex were specifically chosen for their potential anticancer and antimicrobial properties. Consequently, these complexes could present promising prospects as novel candidates for anti-tumor and antibacterial applications. [ABSTRACT FROM AUTHOR]

Background: Antibiotic consumption is a driver for the increase of antimicrobial resistance. The objective of this study is to analyze variations in antibiotic consumption and its appropriate use in Brazil from 2014 to 2019. Methods: We conducted a time series study using the surveillance information system database (SNGPC) from the Brazilian Health Regulatory Agency. Antimicrobials sold in retail pharmacies were evaluated. All antimicrobials recorded for systemic use identified by the active ingredient were eligible. Compounded products and formulations for topic use (dermatological, gynecological, and eye/ear treatments) were excluded. The number of defined daily doses (DDDs)/1,000 inhabitants/day for each antibiotic was attributed. The number of DDDs per 1,000 inhabitants per day (DDIs) was used as a proxy for consumption. Results were stratified by regions and the average annual percentage change in the whole period studied was estimated. We used the WHO Access, Watch, and Reserve (AWaRe) framework to categorize antimicrobial drugs. Results: An overall increase of 30% in consumption from 2014 to 2019 was observed in all Brazilian regions. Amoxicillin, azithromycin and cephalexin were the antimicrobials more consumed, with the Southeast region responsible for more than 50% of the antibiotic utilization. Among all antimicrobials analyzed 45.0% were classified as watch group in all Brazilian regions. Conclusion: We observed a significant increase in antibiotics consumption from 2014 to 2019 in Brazil restricted to the Northeast and Central West regions. Almost half of the antibiotics consumed in Brazil were classified as watch group, highlighting the importance to promote rational use in this country. [ABSTRACT FROM AUTHOR]

Background: In the region of Piedmont, in Northern Italy, formal monitoring of antimicrobial stewardship (AMS) programs has been in place since 2012. The objective of our study was to provide an updated assessment of AMS programs operating in our region, and to assess the impact of the COVID-19 pandemic on stewardship activities. Methods: A retrospective observational study was conducted to investigate AMS programs implemented in acute-care trusts participating in a broader healthcare-associated infections and antimicrobial resistance (AMR) prevention and control program, promoted by the regional health department. Within this program, structure, process, and outcome indicators of AMS programs were investigated, using a previously developed scoring system. Differences between scores prior to (2019) and during the pandemic (2021) were assessed. Linear regression was used to assess whether the 5-year trends (2017–2021) in outcome measures in relation to structure and process scores were statistically significant. Compound annual growth rates (CAGR) for each outcome were calculated to illustrate changes in outcome rates over time. Results: All public trusts in the Region (20) and a small number of private institutions (3) provided data for this study. A modest, non-significant improvement was found for 2021 structure, process, and total scores compared to respective 2019 scores. A significant improvement was found concerning the definition of a formal mission statement, whereas significantly less trusts included monitoring adherence to antimicrobial policy or treatment guidelines in their programs. Overall consumption of antibiotics for systemic use saw an increase in 2021, with 2021 recording the highest median overall consumption compared to all previous years considered in this study. Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant enterobacteria (CRE) rates decreased over the 5-year period. Significant downwards trends in MRSA rates were identified for high-outlier structure and process groups. Conclusions: Results of this study suggest AMS programs in Piedmont were not set back following the pandemic. This outcome was possible thanks to well-established programs, coordinated within a regional framework. Continued efforts should be dedicated to supporting AMS programs and contrasting AMR, even when the focus is shifted towards other public health emergencies. [ABSTRACT FROM AUTHOR]

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery. [ABSTRACT FROM AUTHOR]

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs. [ABSTRACT FROM AUTHOR]

Oral antiretroviral therapy (ART) is extremely effective, allowing people living with HIV to have a normal life expectancy. Most treatments consist of oral tablets that must be taken at the same time every day for the rest of an individual's life. For a variety of reasons, some people cannot adhere to a daily regimen, resulting in a deterioration in their health. The introduction in 2021 of long-acting injectable ART has provided an alternative option for those who would prefer not to take oral therapy. This article provides an overview of the practicalities and challenges of setting up nurse clinics to administer these injections. It also highlights how this type of treatment has improved the quality of life for people receiving them. HIV nurse specialists are leading the way in delivering this innovative new treatment, and the article concludes by discussing which patients may benefit from injectables in the future. This guide is aimed at nurses who work within the HIV field or are supporting this treatment in other settings, for example in outpatient parenteral antimicrobial therapy (OPAT) services. [ABSTRACT FROM AUTHOR]

To learn more about the chemotherapeutic and pharmacokinetic properties of a neodymium complex containing 1,10-phenanthroline (dafone), In vitro binding was investigated with bovine serum albumin and fish-salmon DNA, using a variety of molecular modeling research and biophysical approaches. A variety of spectroscopic techniques including fluorescence and absorption were used to investigate the interplay between DNA/BSA and the neodymium complex. The findings revealed that the Nd complex had a high affinity for BSA and DNA interplays through van der Waals powers. In addition, the binding of the Nd complex to FS-DNA mainly in the groove binding mode clearly reflects with iodide quenching studies, ethidium bromide (EtBr) exclusion assay, ionic strength effect, and viscosity studies. It was observed that the Nd complex binds to FS-DNA through a minor groove with 3.81 × 105 (M-1). Also, Kb for BSA at 298 K was 5.19×105 (M-1), indicating a relatively high affinity of the Nd complex for DNA and BSA. In addition, a competitive study of a docking investigation revealed that the neodymium complex interacts at BSA site III. The results obtained from the binding calculations are well consistent with the experimental findings. Also, cytotoxicity studies of Nd complex were performed in MCF-7 and A-549 cell lines and the results show that this new complex has a selective inhibitory effect on the growth of various cancer cells. [ABSTRACT FROM AUTHOR]

The article focuses on an unusual case of cutaneous anthrax in a Texas rancher during winter, prompting an investigation into anthrax outbreak dynamics and diagnostic challenges. It highlights the importance of considering anthrax as a differential diagnosis, utilizing advanced diagnostic techniques like real-time PCR and mass spectrometry, and emphasizes the need for proper antimicrobial treatment despite challenges in culturing the bacterium.

This study reports the antibacterial and antibiofilm activities of Magnesium ferrite nanoparticles (MgFe2O4) against gram-positive and gram-negative bacteria. The photocatalytic degradation of Carbol Fuchsin (CF) dye (a class of dyestuffs that are resistant to biodegradation) under the influence of UV-light irradiation is also studied. The crystalline magnesium ferrite (MgFe2O4) nanoparticles were synthesized using the co-precipitation method. The morphology of the resulting nanocomposite was examined using scanning electron microscopy (SEM), while transmission electron microscopy (TEM) was employed for further characterization of particle morphology and size. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) were utilized to analyze the crystalline structure, chemical composition, and surface area, respectively. Optical properties were evaluated using UV–Vis spectroscopy. The UV-assisted photocatalytic performance of MgFe2O4 nanoparticles was assessed by studying the decolorization of Carbol fuchsin (CF) azo dye. The crystallite size of the MgFe2O4 nanoparticles at the (311) plane, the most prominent peak, was determined to be 28.5 nm. The photocatalytic degradation of 10 ppm CF using 15 mg of MgFe2O4 nanoparticles resulted in a significant 96% reduction after 135 min at ambient temperature (25 °C) and a pH value of 9. Additionally, MgFe2O4 nanoparticles exhibited potent antibacterial activity against E. coli and S. aureus in a dose dependent manner with maximum utilized concentration of 30 µg/ml. Specifically, MgFe2O4 nanoparticles demonstrated substantial antibacterial activity via disk diffusion and microbroth dilution tests with zones of inhibition and minimum inhibitory concentrations (MIC) for E. coli (26.0 mm, 1.25 µg/ml) and S. aureus (23.0 mm, 2.5 µg/ml), respectively. Moreover, 10.0 µg/ml of MgFe2O4 nanoparticles elicited marked percent reduction in biofilm formation by E. coli (89%) followed by S. aureus (78.5%) after treatment. In conclusion, MgFe2O4 nanoparticles demonstrated efficient dye removal capabilities along with significant antimicrobial and antibiofilm activity against gram-positive and gram-negative bacterial strains suggesting their potential as promising antimicrobial and detoxifying agents. [ABSTRACT FROM AUTHOR]

Background: Treatment of carbapenem-resistant Enterobacterales (CRE) infections in low-resource settings is challenging particularly due to limited treatment options. Colistin is the mainstay drug for treatment; however, nephrotoxicity and neurotoxicity make this drug less desirable. Thus, mortality may be higher among patients treated with alternative antimicrobials that are potentially less efficacious than colistin. We assessed mortality in patients with CRE bacteremia treated with colistin-based therapy compared to colistin-sparing therapy. Methods: We conducted a cross-sectional study using secondary data from a South African national laboratory-based CRE bacteremia surveillance system from January 2015 to December 2020. Patients hospitalized at surveillance sentinel sites with CRE isolated from blood cultures were included. Multivariable logistic regression modeling, with multiple imputations to account for missing data, was conducted to determine the association between in-hospital mortality and colistin-based therapy versus colistin-sparing therapy. Results: We included 1 607 case-patients with a median age of 29 years (interquartile range [IQR], 0–52 years) and 53% (857/1 607) male. Klebsiella pneumoniae caused most of the infections (82%, n=1 247), and the most common carbapenemase genes detected were blaOXA-48-like (61%, n=551), and blaNDM (37%, n=333). The overall in-hospital mortality was 31% (504/1 607). Patients treated with colistin-based combination therapy had a lower case fatality ratio (29% [152/521]) compared to those treated with colistin-sparing therapy 32% [352/1 086]) (p=0.18). In our imputed model, compared to colistin-sparing therapy, colistin-based therapy was associated with similar odds of mortality (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 0.78-1.33, p=0.873). Conclusion: In our resource-limited setting, the mortality risk in patients treated with colistin-based therapy was comparable to that of patients treated with colistin-sparing therapy. Given the challenges with colistin treatment and the increasing resistance to alternative agents, further investigations into the benefit of newer antimicrobials for managing CRE infections are needed. [ABSTRACT FROM AUTHOR]

The objective of this study was to synthesize a novel antibacterial and anticancer nanoformulation using aloe vera-derived carbon quantum dots (Cdot) and chromium-doped alumina nanoparticles (Al2O3:Cr/Cdot NPs) via a sol–gel method. X-ray diffraction (XRD) analysis confirmed crystalline NPs with a size range of 10–12 nm, while energy-dispersive X-ray spectroscopy (EDS) revealed their elemental composition without impurities. Fourier-transform infrared spectroscopy (FT-IR) indicated strong interactions between Cdot and Al2O3:Cr NPs, forming a robust heterostructure. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images provided visual confirmation of monodisperse, spherical NPs, ensuring uniformity for further applications. Evaluation of reactive oxygen species (ROS) demonstrated superior generation of singlet oxygen and hydroxyl radicals by Al2O3:Cr/Cdot NPs, essential for photodynamic therapy. Minimum inhibitory concentration (MIC) tests revealed potent antibacterial activity against drug-resistant bacteria, inhibiting biofilm formation by 89% and 95% for MRSA and P. aeruginosa PAO1, respectively. Furthermore, the anticancer activity of Al2O3:Cr/Cdot NPs was assessed using C26 cells, demonstrating enhanced cytotoxicity upon UVA exposure. The NPs exhibited an inhibitory concentration (IC50) of 20 μg/mL without UVA exposure, decreasing to 10 μg/mL with UVA exposure, highlighting the synergistic effect of UVA light in enhancing cytotoxicity. Overall, these findings underscore the significant potential of Al2O3:Cr/Cdot NPs as multifunctional agents for addressing drug-resistant bacteria and advancing cancer therapy, offering promising avenues for nanomedicine research and development. [ABSTRACT FROM AUTHOR]

We have begun a series of publications on studies related to the optimization of the antimicrobial product protection effectiveness of multifunctional cosmetic ingredients. Previously, we reported studies on the impact of pH even within a narrow range most relevant to cosmetic products [1]. Powerful combinations with organic acids were also examined as part of our technology platform Symshield®, which explores the concept of barrier technology or hurdle technology in the interest of empowering multifunctionals. In this article, we report studies with two additional parameters, chelating agents and water activity [ABSTRACT FROM AUTHOR]

This study proposes an innovative strategy to enhance the pharmacophore model of antimicrobial bismuth thiolato complex drugs by substituting hydrocarbon ligand structures with boron clusters, particularly icosahedral closo‐dicarbadodecaborane (C2B10H12, carboranes). The hetero‐ and homoleptic mercaptocarborane complexes BiPh2L (1) and BiL3 (2) (L=9‐S‐1,2‐C2B10H11) were prepared from 9‐mercaptocarborane (HL) and triphenylbismuth. Comprehensive characterization using NMR, IR, MS, and XRD techniques confirmed their successful synthesis. Evaluation of antimicrobial activity in a liquid broth microdilution assay demonstrated micromolar to submicromolar minimum inhibitory concentrations (MIC) suggesting high effectiveness against S. aureus and limited efficacy against E. coli. This study highlights the potential of boron‐containing bismuth complexes as promising antimicrobial agents, especially targeting Gram‐positive bacteria, thus contributing to the advancement of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Melaleuca polandii, commonly known as "Gold-tipped Bottlebrush", is widely grown in Indian gardens and parks as an ornamental plant. In the present study, the chemical composition, antioxidant, antimicrobial and cytotoxic activities of M. polandii leaf essential oil (MPLEO) have been investigated. GC-MS analysis of MPLEO isolated from plants grown along the coastal plains of Eastern India revealed the presence of 50 constituents with α-pinene (46.17%), 3Z-hexenyl acetate (10.10 %), α-terpineol (5.43%), limonene (3.63%) and ρ-cymene (2.44 %) as the major constituents. MPLEO exhibited moderate antioxidant capacity in DPPH, ABTS and Reducing ability assays with IC50 values of 7.94 ± 0.34 μg/mL, 5.71 ± 0.21 μg/mL and EC50 7.09 ± 0.35 μg/mL, respectively. Of the 5 bacterial strains tested, the EO exhibited highest sensitivity against Bacillus subtilis with the ZOI of 12.66 ± 0.57 mm and strong antimicrobial activity against Staphylococcus saprophyticus with MIC value of 6.25 μg/mL. MPLEO exhibited significant cytotoxic effects against Human alveolar lung adenocarcinoma (A549), Human hepato-cellular carcinoma (HepG2), Human cervix adenocarcinoma (HeLa) and normal Human Embryonic Kidney cell (HEK-293) as evaluated through MTT assay with IC50 values of 9.5 ± 0.38 μg/mL, 22.73 ± 0.95 μg/mL, 20.41 ± 0.82 μg/mL and 237.68 ± 9.26 μg/mL, respectively. The findings of the present study demonstrated that MPLEO could be considered as a potential bioresource having applications in pharmaceutical industries as an antibacterial and antiproliferative agent. [ABSTRACT FROM AUTHOR]

Essential oils isolated from leaves, twigs, fruit bark and seeds of Michelia tonkinensis collected in Muong Nhe Nature Reserve, Dien Bien province were obtained by hydrodistillation with yields of 1.5, 0.42, 0.16 and 4.6% respectively (v/w on dry weight basis). After analysis through GC, GC-MS and 13C NMR, 30, 34, 31 and 13 compounds (representing 96.4%, 96.8%, 97.1% and 99.9% of the whole composition, respectively) were identified in the leave, twig, fruit bark and seed essential oils. The main components were limonene (43.2%) and germacrene D (32.7%) in the leaf oil; limonene (67.1%) and germacrene D (10.4%) in the twig oil; limonene (66%) in the fruit bark oil; and safrole (90%) in the seed oil. Essential oils from the leaves and twigs showed strong inhibition against Staphyloccocus aureus. The fruit bark essential oil exhibited greater antibacterial potential against all 3 tested microorganisms (S. aureus, Escherichia coli and Candida albicans). The essential oil from seed displayed weak antibacterial activity against the three tested microorganisms. [ABSTRACT FROM AUTHOR]

The chemical characterization of the essential oil of the endemic Moroccan species, Calendula maroccana, was achieved by GC and GC-MS methods. The antioxidant, antimicrobial and antibiofilm activities of this essential oil were also studied. Eighty-one compounds were identified in the essential oil, representing 94.82% of the total. Sesquiterpenes predominate in the essential oil; 2-Methoxy-4-vinylphenol (16.13%), δ-amorphene (13.56%), α-cedrene (6.23%), γ-curcumene (5.10%) and α-bisabolol (4.94%) were the main constituents. The antioxidant potential was evaluated by DPPH, FRAP and ABTS assays: the essential oil exhibited antioxidant effectiveness with IC50 values of 0.92, 0.3 and 1.7 mg/mL, respectively. Moreover, the essential oil showed potent antimicrobial activity as revealed by inhibition zone values against selected clinically important pathogenic microorganisms. Inhibition zone values of 15.33 ± 0.19, 23 ± 0.05 and 15.33 ± 0.33 mm were observed against Staphylococcus aureus, Candida albicans and C. tropicalis, respectively. The maximal and minimal inhibition concentration values were in the range of 0.25 ± 0.17 - 4.68 ± 0.10 mg/mL for bacteria and 0.06 ± 0.03 - 0.12 ± 0.14 mg/mL, for Candida. The essential oil showed potent anti-biofilm activity with dual actions, inhibiting (69 - 88%) and eradicating (75 - 92%) the biofilms formed by the three tested bacteria strains. Based on these results, this essential oil can be considered as a natural antioxidant, antibacterial and antibiofilm agent that could be applied in phytotherapy, pharmaceutical and food sectors. [ABSTRACT FROM AUTHOR]

Dialium guineense essential oil possesses various biological and biochemical activities. The present study is based on determination of antimicrobial, anti-diabetic, anti-cholinesterase, anti-biofim, anti-antibiotic resistance modifying activities and anti-quorum sensing potential of essential oil. Chemical compounds in essential oil were recognised by retention indices using gas chromatograph-mass spectroscopy (GC-MS). A total of 45 compounds were present in the essential oil of which 12 are most active. Essential oil of D. guineense showed highest anti-bacterial activity in the form of zone of inhibition, produced 23 mm zone against Staphylococcus aureus and 15 mm against Escherichia coli. D. guineense oil at various concentrations showed excellent anti-diabetic and anti-cholinesterase activities. Since many active compounds were present in D. guineense oil so authors of this study planned to observe effect of D. guineense oil on quorum sensing regulated virulence factors and thus bio-film formation in pathogens Essential oil reduced bio-film formation considerably at all concentrations against E. coli, Staphylococcus aureus and Pseudomonas aeruginosa. Determination of quorum sensing (QS) inhibitory activity was demonstrated by reduction in pyocyanin (73.93%), total protease (68.59%) and chitinase activity (66.18%) in Pseudomonas aeruginosa at 1 mg/mL of D. guineense oil compared to control. Essential oil at all concentrations tested showed synergistic effect. Since essential oil showed anti-microbial, anti-biofilm and quorum sensing regulated anti-pathogenic activities. Based on results mentioned above, it is concluded that bioactive chemicals from D. guineense oil can act as an anti-infective agent by controlling growth, bio-film formation and signalling pathways of pathogenic microbes as well as other diseases. [ABSTRACT FROM AUTHOR]

The development of antimicrobial drugs with novel structures and clear mechanisms of action that are active against drug-resistant bacteria has become an urgent need of safeguarding human health due to the rise of bacterial drug resistance. The discovery of AMPs and the development of amphipathic peptidomimetics have lay the foundation for novel antimicrobial agents to combat drug resistance due to their overall strong antimicrobial activities and unique membrane-active mechanisms. To break the limitation of AMPs, researchers have invested in great endeavors through various approaches in the past years. This review summarized the recent advances including the development of antibacterial small molecule peptidomimetics and peptide-mimic cationic oligomers/polymers, as well as mechanism-of-action studies. As this exciting interdisciplinary field is continuously expanding and growing, we hope this review will benefit researchers in the rational design of novel antimicrobial peptidomimetics in the future. [ABSTRACT FROM AUTHOR]

Diarrhoea remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diarrhoeic infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of plant-based compounds) was evaluated in vitro against selected diarrhoeic bacteria (Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Shigella flexneri, Vibrio parahaemolyticus, and Yersinia enterocolitica). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combination of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline–nitroxoline combinations produced the greatest synergistic action against S. flexneri at a FICI value of 0.086. The combinations of the agents tested in this study can thus be used for the development of new anti-diarrhoeic medications. However, studies focusing on their in vivo anti-diarrhoeic activity and safety are required before any consideration for utilization in human medicine. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a menace to public health on a global scale. In this regard, nanomaterials exhibiting antimicrobial properties represent a promising solution. Both metal and metal oxide nanomaterials are suitable candidates, even though their mechanisms of action vary. Multiple antimicrobial mechanisms can occur simultaneously or independently; this includes either direct contact with the pathogens, nanomaterial uptake, oxidative stress, ion release, or any of their combinations. However, due to their specific properties and more particularly fast settling, existing methods to study the antimicrobial properties of nanoparticles have not been specifically adapted in some cases. The development of methodologies that can assess the antimicrobial properties of metallic nanomaterials accurately is necessary. A cost-effective methodology with a straightforward set-up that enables the easy and quick assessment of the antimicrobial properties of metal nanoparticles with high accuracy has been developed. The methodology is also capable of confirming whether the killing mechanism involves ionic diffusion. Finally, Aloe Vera gel showed good properties for use as a medium for the development of antimicrobial ointment. [ABSTRACT FROM AUTHOR]

Titanium (Ti), as a hard tissue implant, is facing a big challenge for rapid and stable osseointegration owing to its intrinsic bio-inertness. Meanwile, surface-related infection is also a serious threat. In this study, large-scale quasi-vertically aligned sodium titanate nanowire (SNW) arrayed coatings incorporated with bioactive Cu2+ ions were fabricated through a compound process involving acid etching, hydrothermal treatment (HT), and ion exchange (IE). A novel coating based on sustained ion release and a shape-preserving design is successfully obtained. Cu2+ substituted Na+ in sodium titanate lattice to generate Cu-doped SNW (CNW), which maintains the micro-structure and phase components of the original SNW, and can be efficiently released from the structure by immersing them in physiological saline (PS) solutions, ensuring superior long-term structural stability. The synergistic effects of the acid etching, bidirectional cogrowth, and solution-strengthening mechanisms endow the coating with higher bonding strengths. In vitro antibacterial tests demonstrated that the CNW coatings exhibited effective good antibacterial properties against both Gram-positive and Gram-negative bacteria based on the continuous slow release of copper ions. This is an exciting attempt to achieve topographic, hydrophilic, and antibacterial activation of metal implants, demonstrating a paradigm for the activation of coatings without dissolution and providing new insights into insoluble ceramic-coated implants with high bonding strengths. [ABSTRACT FROM AUTHOR]

2-Azetidinones (β-lactams) possess broad and potent bioactivity owing to the presence of lactam rings. As evidence has shown, it is one of the most critical biological frameworks. Some new 2- azetidinones have been synthesized from corresponding Schiff bases using different amines and aldehydes. All compounds (Schiff bases and β- lactams) were synthesized for comparison research using conventional and microwave techniques. The microwave approach has been found to reduce reaction time and boost yield drastically. Analysis combining elemental (C, H, and N) and spectroscopic approaches (NMR, IR, and UV) have been applied to ensure the Schiff bases constitution and corresponding β-lactams constitution. The newly synthesized compound's antibacterial action was estimated opposite to one gram-positive and one gram-negative bacteria. One compound (A-03) among synthesized 2-azitidinones was shown significant activity against the gram-positive bacteria. The other synthesized compounds had no substantial activity on either of the microorganisms. [ABSTRACT FROM AUTHOR]

Coriander (Coriandrum sativum L.) is an annual herb belonging to the Apiaceae family that is grown worldwide. This aromatic herb has been used for its nutritional value and biological properties. In this study, we compared the essential oil composition and antibacterial activity of coriander seeds from nine Iranian and Iraqi populations for the first time. The seed oils were extracted using a Clevenger‐type apparatus, and their chemical composition was determined using GC and GC/MS Agilent apparatuses. The antimicrobial activity of the oils was tested against three infectious bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) using the agar well diffusion method. The experiments were repeated three times, and the results were analyzed using PAST, SAS, and SPSS software. The results showed that oxygenated monoterpenes, especially linalool, were the major compounds in the oils, followed by α‐pinene, γ‐terpinene, and geranyl acetate. The proportions of these compounds varied among the populations. Trace amounts of other compounds were also detected, some of which were only found in certain populations. The populations were detected as linalool chemotype, and classified into four groups based on their chemical constituents in the UPGMA tree. The PCA‐Biplot showed that these groups were characterized by the presence and percentage of specific compounds. The essential oils showed bacterial growth inhibitory properties only at 100% concentration. S. aureus was the most sensitive bacterium to the coriander essential oil, while the essential oils of all populations inhibited the growth of this bacterium. Additionally, the essential oils were more effective than antibiotics against E. coli. These findings contribute to our understanding of coriander seed essential oil by providing data on antibacterial activity and chemical characteristics. Furthermore, the study highlights the importance of selecting populations based on their specific essential oil profiles for antibacterial applications. [ABSTRACT FROM AUTHOR]

This study reports the design, synthesis, and antibacterial evaluation of a library of novel polyheterocyclic derivatives featuring a unique fused pyrimidopyridopyrazole moiety. A cyclocondensation reaction between an amino−pyrazolopyridopyrimidine precursor and malonates afforded a series of pyrimidopyridopyrazolopyrimidine derivatives. Further diversification was achieved through nucleophilic cyclocondensation, yielding a collection of complex polyheterocyclic systems encompassing various ring structures. All synthesized compounds were rigorously characterized using spectroscopic techniques and elemental analysis. The antibacterial activity of the newly synthesized compounds was assessed against a panel of Gram‐positive and Gram‐negative bacteria. Notably, several compounds exhibited promising antibacterial activity, highlighting their potential as leads for the development of novel antibiotics. [ABSTRACT FROM AUTHOR]

Problem: In Australia, inappropriate prescribing of antimicrobials is higher in rural and regional areas than in major city hospitals. Inappropriate prescribing is defined as the prescription of antimicrobial agents that do not adhere to guidelines in terms of type of antimicrobial chosen, dose and/or duration or are deemed unnecessary. A review of antimicrobial prescribing in a Queensland rural Hospital and Health Service (HHS) identified that respiratory infections were an area for potential improvement. Setting: The study was performed in a rural HHS in Queensland. Key Measures for Improvement: Appropriateness of antimicrobial prescribing for baseline and post‐implementation phases of the study was evaluated according to Therapeutic Guidelines: antibiotic recommendations for community acquired pneumonia (CAP). Strategies for Change: Quality improvement strategy to implement a multifaceted package of interventions for CAP. Effects of Change: Post‐implementation, overall appropriateness of antimicrobial prescribing improved and there was a decrease in duration of antimicrobial therapy. Lessons Learnt: A quality improvement strategy to implement a multifaceted package of interventions for CAP has shown to be acceptable and effective in improving the antimicrobial prescribing in a rural setting. Our findings highlight the importance of utilising a multifaceted package of interventions which can be tailored to the prescribers and the patients at hand. It is also valuable to engage with local clinicians to promote the optimal management of common infections in the rural setting. [ABSTRACT FROM AUTHOR]

The use of antibiotics against a range of pathogenic bacteria has increased in recent years, leading to the development of drug resistance, which makes disease control challenging. Thus, the need for the development of new antibacterial medications is critical. Natural resources, such as entomopathogenic bacteria (EPB), provide a rich source of metabolites with well-known antibacterial properties. The present study aimed to investigate the antibacterial activity of symbiotic (n = 1) and non-symbiotic (n = 8) entomopathogenic bacterial species associated with the entomopathogenic nematode (EPN) Steinernema feltiae against four multidrug-resistant bacterial species. Bacterial cells and filtrates from Xenorhabdus bovienii strongly inhibited the growth of Staphylococcus aureus (33.3 and 28.9 mm) and Escherichia coli (24.6 and 21.6 mm) in disk diffusion, minimum inhibitory concentration (MIC) (2 and 8 µl/ml) and minimal bactericidal concentration (MBC) (4 and 12.5 µl/ml) assays. In conclusion, the direct application of endogenous S. feltiae-associated EPB, especially X. bovienii, appears promising as an antibacterial agent against multidrug-resistant bacteria (MRBs). [ABSTRACT FROM AUTHOR]

In this work, Azadirachta indica leaf extract and the ultrasonic method were applied for the fabrication of a CuO/Ag-based nanocomposite. The CuO/Ag was characterised using different analytical methods such as FTIR, SEM, EDX, and XRD. The well diffusion method was used to evaluate the antibacterial activity of non-calcined and calcined CuO/Ag against some hazardous bacterial strains. After the incubation period, remarkable zones of inhibition were observed around the loaded CuO/Ag. The maximum zones of inhibition were found to be 17.9 (± 0.39), 20 (± 0.17), and 14.3 (± 0.31) mm for E. coli, S. aureus, and S. enterica, respectively. Experimental findings indicated that non-calcined CuO/Ag was a more effective antibacterial agent as compared to calcined CuO/Ag. [ABSTRACT FROM AUTHOR]

The escalation of environmental pathogenic microorganisms and disregard of public hygiene practices have resulted in the emergence of various skin infections within communities. Recent investigations have proposed that diverse snail mucus compositions may possess antimicrobial properties. Therefore, it is imperative to conduct further research to elucidate specific antibacterial characteristics inherent in the mucus of White Garden snail (Theba pisana). This study aimed to evaluate antibacterial activity of Theba pisana mucus extract against selected ATCC bacterial strains being Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and MRSA. The assessment involved comparing antimicrobial activity of the mucus extract to various broad-spectrum antibiotics. The susceptibility of bacterial isolates to snail mucus secretions was assessed using agar well diffusion method on Muller Hilton Agar plates. After incubation at 37°C for 24 hours, various concentrations of snail slime including 100%, 75%, 50%, and 25% were applied. The findings reported that E. faecalis exhibited highest activity, with zone of inhibition measuring 24 mm, followed by K. pneumonia and S. aureus (16 mm), MRSA (14 mm), and E. coli (12 mm). However, at concentration of 25%, mucus extract exhibited effect only against E. faecalis. Moreover, the antimicrobial activity of several tested antibiotics demonstrated similarity to that of the mucus extract. Therefore, it revealed that secretions of T. pisana mucus may possess the potential to act as a source of antibacterial agents. This may become as an alternative agent to costly synthetic antibacterial compounds. However, further studies are required to exploit the mucus secretion in addressing the issue of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Objective: The tandem Knoevenagel-cyclocondensation reaction of aromatic aldehydes, malonitrile, and phenylhydrazine in water and ethanol at room temperature is described as an effective, one-pot, threecomponent synthesis of many scientifically relevant heterocyclic compounds. Methods: As a part of our efforts, we have synthesized pyrazole-4-carbonitriles and characterized using various spectroscopic methods and subjected for antimicrobial analysis. Results and Discussion: From our analysis, we observed best in vitro candidate as 5-amino-3-(2,5-difluorophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile. The molecular docking analysis on common bacterial target suggested the involvement of 2,2-dialkylglycine decarboxylase (PDB ID: 1D7U) as a target for compound (IVi) (docking score: –9.32 kcal/mol). Furthermore, a molecular dynamic simulation of 100 ns resulted in the stability of best docked candidate, (IVi): 1D7U. Conclusions: We propose that best docked candidate, (IVi) as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]

Species of the genus Allium across the world have several biological activities among which the antimicrobial activity. Among these species, we can find around the world: A. ursinum, A. sativum, A. roseum, A. kastambulense, A. stipitatum, A. hirtifolium, A. ascalonicum, A. cepa, A. fistulosum, A. tuberosum Rottler, A. orientale, A. triquetrum, A. hookeri, A. subhirsutum, and A. staticiform. Antimicrobial activities of raw juices, essential oils, aqueous extracts and extracts prepared with various solvents (ethanolic, methanolic, chloformic, dichloro methane, ethyl acetate) have been studied using bulbs, flowers, stems and leaves from different species. The fine analysis by LC-MS/MS and by GC-MS is indicative of the presence of bioactive sulfur and phenolic compounds in most of the extracts. The latter are responsible of their antimicrobial activities. The modes of action of these active compounds on microrganisms have been studied very thouroughly using scanning and transmission electron microscopies, and by mass spectophotometry MALDI-TOF as well as molecular docking. [ABSTRACT FROM AUTHOR]

Objectives To determine the frequencies and clonal distributions of putative genetic determinants of resistance to antimicrobials applied for treatment of Clostridioides difficile infection (CDI), as documented in the genomic record. Methods We scanned 26 557 C. difficile genome sequences publicly available from the EnteroBase platform for plasmids, point mutations and gene truncations previously reported to reduce susceptibility to vancomycin, fidaxomicin or metronidazole, respectively. We measured the antimicrobial susceptibility of 143 selected C. difficile isolates. Results The frequency of mutations causing reduced susceptibility to vancomycin and metronidazole, respectively, increased strongly after 2000, peaking at up to 52% of all sequenced C. difficile genomes. However, both mutations declined sharply more recently, reflecting major changes in CDI epidemiology. We detected mutations associated with fidaxomicin resistance in several major genotypes, but found no evidence of international spread of resistant clones. The pCD-METRO plasmid, conferring metronidazole resistance, was detected in a single previously unreported C. difficile isolate, recovered from a hospital patient in Germany in 2008. The pX18-498 plasmid, putatively associated with decreased vancomycin susceptibility, was confined to related, recent isolates from the USA. Phenotype measurements confirmed that most of those genetic features were useful predictors of antibiotic susceptibility, even though ranges of MICs typically overlapped among isolates with and without specific mutations. Conclusions Genomic data suggested that resistance to therapeutic antimicrobial drugs is rare in C. difficile. Public antimicrobial resistance marker databases were not equipped to detect most of the genetic determinants relevant to antibiotic therapy of CDI. [ABSTRACT FROM AUTHOR]

Poor-quality antimicrobial medicines continue to proliferate across supply chains, threatening patients' health and safety, especially in lowand middle-income regions. This article discusses consequences and risks of antimicrobial resistance and other ways in which antimicrobial medicines can be of poor quality and recommends regulatory and policy reforms to help maintain supply chain resilience and quality of antimicrobial medicines. [ABSTRACT FROM AUTHOR]