Novel diarylated tacrine derivatives: Synthesis, characterization, anticancer, antiepileptic, antibacterial, and antifungal activities.

In this study, our goal was to synthesize novel aryl tacrine derivatives and assess their potential as anticancer, antibacterial agents, and enzyme inhibitors. We adopted a two-step approach, initiating with the synthesis of dibromotacrine derivatives 3 and 4 through the Friedlander reaction. These intermediates underwent further transformation into diarylated tacrine derivatives 3a-e and 4a-e using a Suzuki-Miyaura cross-coupling reaction. Thorough characterization of these novel diarylated tacrines was achieved using various spectroscopic techniques. Our findings highlighted the potent anticancer effects of these innovative compounds across a range of cancer cell lines, including lung, gynecologic, bone, colon, and breast cancers, while demonstrating low cytotoxicity against normal cells. Notably, these compounds surpassed the control drug, 5-Fluorouracil, in terms of antiproliferative activity in numerous cancer cell lines. Moreover, our investigation included an analysis of the inhibitory properties of these novel compounds against various microorganisms and cytosolic carbonic anhydrase enzymes. The results suggest their potential for further exploration as cancer-specific, enzyme inhibitory, and antibacterial therapeutic agents. Notably, four compounds, namely, 5,7-bis(4-(methylthio)phenyl)tacrine (3d), 5,7-bis(4-(trifluoromethoxy)phenyl)tacrine (3e), 2,4-bis(4-(trifluoromethoxy)phenyl)-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-amine (4e), and 6,8-dibromotacrine (3), emerged as the most promising candidates for preclinical studies.

An update on antibacterial AlkylGuanidino Ureas: Design of new derivatives, synergism with colistin and data analysis of the whole library.

Antimicrobial resistance (AMR) represents one of the most challenging global Public Health issues, with an alarmingly increasing rate of attributable mortality. This scenario highlights the urgent need for innovative medicinal strategies showing activity on resistant isolates (especially, carbapenem-resistant Gram-negative bacteria, methicillin-resistant S. aureus, and vancomycin-resistant enterococci) yielding new approaches for the treatment of bacterial infections. We previously reported AlkylGuanidino Ureas (AGUs) with broad-spectrum antibacterial activity and a putative membrane-based mechanism of action. Herein, new tetra- and mono-guanidino derivatives were designed and synthesized to expand the structure-activity relationships (SARs) and, thereby, tested on the same panel of Gram-positive and Gram-negative bacteria. The membrane-active mechanism of selected compounds was then investigated through molecular dynamics (MD) on simulated bacterial membranes. In the end, the newly synthesized series, along with the whole library of compounds (more than 70) developed in the last decade, was tested in combination with subinhibitory concentrations of the last resort antibiotic colistin to assess putative synergistic or additive effects. Moreover, all the AGUs were subjected to cheminformatic and machine learning analyses to gain a deeper knowledge of the key features required for bioactivity.

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights.

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%-95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (-7.55 kcal/mol) with the active site of serine protease, better than compound 4c (-6.90 kcal/mol) as well as indole-based control compound 5 (-7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 µg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 µg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 µg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 µg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

Production of kojic acid by Aspergillus flavus OL314748 using box-Behnken statistical design and its antibacterial and anticancer applications using molecular docking technique.

Kojic acid is a wonderful fungal secondary metabolite that has several applications in the food, medical, and agriculture sectors. Many human diseases become resistant to normal antibiotics and normal treatments. We need to search for alternative treatment sources and understand their mode of action. Aspergillus flavus ASU45 (OL314748) was isolated from the caraway rhizosphere as a non-aflatoxin producer and identified genetically using 18S rRNA gene sequencing. After applying the Box-Behnken statistical design to maximize KA production, the production raised from 39.96 to 81.59 g/l utilizing (g/l) glucose 150, yeast extract 5, KH2PO4 1, MgSO4.7H2O 2, and medium pH 3 with a coefficient (R2) of 98.45%. Extracted KA was characterized using FTIR, XRD, and a scanning electron microscope. Crystalized KA was an effective antibacterial agent against six human pathogenic bacteria (Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Serratia marcescens, and Serratia plymuthica). KA achieves high inhibition activity against Bacillus cereus, K. pneumonia, and S. plymuthica at 100 µg/ml concentration by 2.75, 2.85, and 2.85 compared with chloramphenicol which gives inhibition zones 1, 1.1, and 1.6, respectively. Crystalized KA had anticancer activity versus three types of cancer cell lines (Mcf-7, HepG2, and Huh7) and demonstrated high cytotoxic capabilities on HepG-2 cells that propose strong antitumor potent of KA versus hepatocellular carcinoma. The antibacterial and anticancer modes of action were illustrated using the molecular docking technique. Crystalized kojic acid from a biological source represented a promising microbial metabolite that could be utilized as an alternative antibacterial and anticancer agent effectively.

Antibiotic Prescribing Patterns for Urinary Tract Infections and Pneumonia by Prescriber Type and Specialty in Nursing Home Care, 2016-2018.

OBJECTIVE: To identify whether differences in antibiotic prescribing practices by prescriber type and specialization in nursing home (NH) care exist for urinary tract infection (UTI) and pneumonia. DESIGN: Retrospective cohort. SETTING AND PARTICIPANTS: This national study included antibiotic dispensings to traditional Medicare beneficiaries aged ≥65 years with UTI or pneumonia infections residing long-term (≥100 days) in US NHs between 2016 and 2018. METHODS: Minimum Data Set assessment data were linked to Medicare data [Part D prescription drug, inpatient hospital (MedPAR), prescriber characteristics, and enrollment]. We compared antibiotic prescribing patterns by prescriber type [physician vs advanced practice practitioner (AP)] and NH specialization (≥90% vs <90% of all associated medication dispensings to NH residents). Antibiotic dispensing measures included the total number of dispensings and duration of therapy (median number of days supplied) by antibiotic class. RESULTS: There were 264,735 antibiotic dispensings prescribed by 32,437 prescribers for 140,360 residents in 14,035 NHs. NH specialists were less likely to prescribe fluoroquinolones for UTI (22.9% NH specialist physician, 23.9% non-NH specialist physician, 21.3% NH specialist AP, 24.2% non-NH specialist AP), but more likely to prescribe fluoroquinolones for pneumonia (38.9%, 37.8%, 38.8%, 37.3%, respectively). Over time, NH specialists reduced fluoroquinolone prescribing for pneumonia to a greater extent than non-NH specialists. The duration of therapy was similar across prescriber groups for UTI, but longer among non-NH specialist APs for several antibiotic classes for pneumonia, including tetracyclines, glycopeptides and lipoglycopeptides, and metronidazole. CONCLUSIONS AND IMPLICATIONS: There were differences in antibiotic prescribing patterns by prescriber type and specialization in NH care between 2016 and 2018. Understanding how antibiotic prescribing differs based on prescriber characteristics is essential to inform antibiotic stewardship efforts. Tailoring antibiotic stewardship efforts to prescribers by NH specialization is rational given differences in antibiotic prescribing patterns based on NH specialization.

Polypyridyl ruthenium complexes with benzothiazole moiety as membrane disruptors and anti-resistance agents for Staphylococcus aureus.

Developing new antimicrobials to combat drug-resistant bacterial infections is necessary due to the increasing problem of bacterial resistance. In this study, four metallic ruthenium complexes modified with benzothiazoles were designed, synthesized and subjected to bio-evaluated. Among them, Ru-2 displayed remarkable inhibitory activity against Staphylococcus aureus (S. aureus) with a minimum inhibitory concentration (MIC) of 1.56 µg/mL. Additionally, it showcased low hemolytic toxicity (HC50 > 200 µg/mL) and the ability to effectively eradicate S. aureus without fostering drug resistance. Further investigation into the antibacterial mechanism suggested that Ru-2 may target the phospholipid component of S. aureus, leading to the disruption of the bacterial cell membrane and subsequent leakage of cell contents (nucleic acid, protein, and ONPG), ultimately resulting in the death of the bacterial cell. In vivo studies, both the G. mellonella larvae and the mouse skin infection models were conducted, indicated that Ru-2 could potentially serve as a viable candidate for the treatment of S. aureus infection. It exhibited no toxic or side effects on normal tissues. The results suggest that benzothiazole-modified ruthenium complexes may have potential as membrane-active antimicrobials against drug-resistant bacterial infections.

Clinical and Radiographic Outcomes of Adjunctive Phototherapy Versus Antibiotic Therapy Against Peri-Implant Diseases: A Systematic Review and Meta-Analysis.

Background: Peri-implantitis, an inflammatory condition in implant tissues, requires bacterial eradication and implant surface decontamination, with aPDT as a helpful surgical adjunct. Objective:This project was designed to investigate the effect of antibiotic therapy versus aPDT, as adjuncts to conventional mechanical debridement (MD), on the peri-implant clinical and/or radiographic parameters among patients with peri-implant diseases. Methods: A comprehensive search was conducted across electronic databases, including PubMed, Scopus, and Web of Science, up to and including April 2023, without any restriction on the language and year of publication, focusing the following research question: "Does adjunctive aPDT improve the peri-implant clinical and/or radiographic parameters in treating peri-implant diseases compared to antibiotic therapy?" Statistical analysis was performed on peri-implant clinical [plaque index (PI), probing depth (PD), and bleeding on probing (BOP)] and radiographic parameters [marginal bone loss (MBL)]. The study included six randomized controlled trials and one clinical (nonrandomized) study. Results: The systematic review findings indicate that the application of aPDT as an adjunct to MD is equally effective as adjunctive antibiotic therapy in improving peri-implant clinical parameters and radiographic parameters in patients with peri-implant diseases. Only two studies were classified as having a low risk of bias (RoB), two were assessed as having an unclear RoB, and the remaining three studies were determined to have a high RoB. However, the meta-analysis results revealed no statistically significant difference in peri-implant PI, PD, and MBL scores between patients treated with adjunct aPDT or adjunct antibiotic therapy. Notably, there was a statistically significant difference favoring adjunct aPDT in peri-implant BOP values compared to the control group. Conclusions: Despite the limited number of included studies and the significant heterogeneity among them, the findings suggest that aPDT yields comparable peri-implant clinical and radiographic outcomes to adjunctive antibiotic therapy, as adjuncts to MD, for the potential treatment of peri-implant diseases.

Peptide Dendrimer-Based Antibacterial Agents: Synthesis and Applications.

Pathogenic bacteria cause the deaths of millions of people every year. With the development of antibiotics, hundreds and thousands of people's lives have been saved. Nevertheless, bacteria can develop resistance to antibiotics, rendering them insensitive to antibiotics over time. Peptides containing specific amino acids can be used as antibacterial agents; however, they can be easily degraded by proteases in vivo. To address these issues, branched peptide dendrimers are now being considered as good antibacterial agents due to their high efficacy, resistance to protease degradation, and low cytotoxicity. The ease with which peptide dendrimers can be synthesized and modified makes them accessible for use in various biological and nonbiological fields. That is, peptide dendrimers hold a promising future as antibacterial agents with prolonged efficacy without bacterial resistance development. Their in vivo stability and multivalence allow them to effectively target multi-drug-resistant strains and prevent biofilm formation. Thus, it is interesting to have an overview of the development and applications of peptide dendrimers in antibacterial research, including the possibility of employing machine learning approaches for the design of AMPs and dendrimers. This review summarizes the synthesis and applications of peptide dendrimers as antibacterial agents. The challenges and perspectives of using peptide dendrimers as the antibacterial agents are also discussed.

Injectable Phage-Loaded Microparticles Effectively Release Phages to Kill Methicillin-Resistant Staphylococcus aureus.

The increasing prevalence of bacterial multidrug antibiotic resistance has led to a serious threat to public health, emphasizing the urgent need for alternative antibacterial therapeutics. Lytic phages, a class of viruses that selectively infect and kill bacteria, offer promising potential as alternatives to antibiotics. However, injectable carriers with a desired release profile remain to be developed to deliver them to infection sites. To address this challenge, phage-loaded microparticles (Phage-MPs) have been developed to deliver phages to the infection site and release phages for an optimal therapeutic effect. The Phage-MPs are synthesized by allowing phages to be electrostatically attached onto the porous polyethylenimine-modified silk fibroin microparticles (SF-MPs). The high specific surface area of SF-MPs allows them to efficiently load phages, reaching about 1.25 × 1010 pfu per mg of microparticles. The Phage-MPs could release phages in a controlled manner to achieve potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Unlike the diffuse biodistribution of free phages post-intraperitoneal injection, Phage-MPs could continuously release phages to effectively boost the local phage concentration at the bacterial infection site after they are intraperitoneally injected into an abdominal MRSA-infected mouse model. In a mouse abdominal MRSA infection model, Phage-MPs significantly reduce the bacterial load in major organs, achieving an efficient therapeutic effect. Furthermore, Phage-MPs demonstrate outstanding biocompatibility both in vitro and in vivo. Overall, our research lays the foundation for a new generation of phage-based therapies to combat antibiotic-resistant bacterial infections.

Application of Nanotechnology to Develop Carrageenan-based Films and Coatings as Carriers for Essential Oils.

This review highlights the effect of combining bioactive agents, especially nanoparticles, in carrageenan coating to increase the quality and stability of foods. This study is designed based on a review of previous studies. Biopolymer coatings and films are suitable for food and non-food packaging due to their degradability, renewable and edible nature. Edible coatings and films are based on polysaccharides, proteins, and lipids. They confer some beneficial effects on foods, such as improvement of appearance and texture, reducing the amount of moisture loss and oxidation, prevention of the release of gases and control of microbial growth, delaying ripening and adverse changes in color and taste, improvement of nutritional value, and increasing the shelf life of the product. These improvements lead to the prevention of food spoilage and increase the shelf life of various foods. In addition, nanomaterials and food additives such as antimicrobial and antioxidant agents, flavorings, and colors can be incorporated into food coatings and films to expand their applications. Nanotechnology can be applied in coatings and food films using nanoparticles. However, more research is still needed to gather information about coating formulations, especially when new materials are incorporated into them.

Sulfur (Sâ ¥)-containing heterocyclic hybrids as antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) and its SAR.

The discovery of new small molecule-based inhibitors is an attractive field in medicinal chemistry. Structurally diversified heterocyclic derivatives have been investigated to combat multi-drug resistant bacterial infections and they offers several mechanism of action. Methicillin-resistant Staphylococcus aureus (MRSA) is becoming more and more deadly to humans because of its simple method of transmission, quick development of antibiotic resistance, and ability to cause hard-to-treat skin and filmy diseases. The sulfur (SVI) particularly sulfonyl and sulfonamide based heterocyclic moieties, have found to be good anti-MRSA agents. The development of new nontoxic, economical and highly active sulfur (SVI) containing derivatives has become hot research topics in drug discovery research. Presently, more than 150 FDA approved Sulfur (SVI)-based drugs are available in the market, and they are widely used to treat various types of diseases with different therapeutic potential. The present collective data provides the latest advancements in Sulfur (SVI)-hybrid compounds as antibacterial agents against MRSA. It also examines the outcomes of in-vitro and in-vivo investigations, exploring potential mechanisms of action and offering alternative perspectives on the structure-activity relationship (SAR). Sulfur (SVI)-hybrids exhibits synergistic effects with existing drugs to provide antibacterial action against MRSA.

Effect of Perioperative Prophylactic Intravenous Antibiotic Use in Immediate Implant-Based Breast Reconstruction: A Retrospective Matched Cohort Study.

Background Among breast reconstruction methods, implant-based breast reconstruction has become the mainstream. However, periprosthetic infection is still an unresolved problem. Although published articles have revealed that limited use of antibiotics is sufficient to reduce infection rates, the number of surgeons still preferring elongated usage of antibiotics is not less. The aim of our study is to validate the appropriate duration of antibiotic use to reduce infection rate after implant-based breast reconstruction. Methods A retrospective study reviewed medical record of 235 patients (274 implants for reconstruction) who underwent prepectoral direct to implant breast reconstruction using acellular dermal matrix wrapping technique. Infection rates were analyzed for the patients administered postoperative prophylactic antibiotics until drain removal and those who received only perioperative prophylactic antibiotics for 24 hours. Results Of the 274 implants, 98 who were administered prophylactic antibiotics until drain removal had an infection rate of 3.06% (three implants) and 176 who received prophylactic antibiotics no longer than 24 hours postoperatively had an infection rate of 4.49% (eight implants). A total of 11 patients diagnosed with postoperative infection clinically, 8 were salvaged by antibiotic treatment, and 3 had implant removal and replacement with autologous flap. Postoperative antibiotic prophylaxis duration had no statistically significant effects in the risk of infection ( p = 0.549). Conclusion The duration of prophylactic antibiotics after surgery was not related to infection risk. Further study with a large number of patients, randomized control study, and route of antibiotics is needed.

A journey into the regulatory secrets of the de novo purine nucleotide biosynthesis.

De novo purine nucleotide biosynthesis (DNPNB) consists of sequential reactions that are majorly conserved in living organisms. Several regulation events take place to maintain physiological concentrations of adenylate and guanylate nucleotides in cells and to fine-tune the production of purine nucleotides in response to changing cellular demands. Recent years have seen a renewed interest in the DNPNB enzymes, with some being highlighted as promising targets for therapeutic molecules. Herein, a review of two newly revealed modes of regulation of the DNPNB pathway has been carried out: i) the unprecedent allosteric regulation of one of the limiting enzymes of the pathway named inosine 5'-monophosphate dehydrogenase (IMPDH), and ii) the supramolecular assembly of DNPNB enzymes. Moreover, recent advances that revealed the therapeutic potential of DNPNB enzymes in bacteria could open the road for the pharmacological development of novel antibiotics.

Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options.

SUMMARYClostridioides difficile infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for C. difficile infection.

Development and evaluation of 2,4-disubstituted-5-aryl pyrimidine derivatives as antibacterial agents.

Designing novel candidates as potential antibacterial scaffolds has become crucial due to the lack of new antibiotics entering the market and the persistent rise in multidrug resistance. Here, we describe a new class of potent antibacterial agents based on a 5-aryl-N2,N4-dibutylpyrimidine-2,4-diamine scaffold. Structural optimization focused on the 5-aryl moiety and the bioisosteric replacement of the side chain linker atom. Screening of the synthesized compounds focused on a panel of bacterial strains, including gram-positive Staphylococcus aureus strains (Newman MSSA, methicillin- and vancomycin-resistant), and the gram-negative Escherichia coli (ΔAcrB strain). Several compounds showed broad-spectrum antibacterial activity with compound 12, bearing a 4-chlorophenyl substituent, being the most potent among this series of compounds. This frontrunner compound revealed a minimum inhibitory concentration (MIC) value of 1 µg/mL against the S. aureus strain (Mu50 methicillin-resistant S. aureus/vancomycin-intermediate S. aureus) and an MIC of 2 µg/mL against other tested strains. The most potent derivatives were further tested against a wider panel of bacteria and evaluated for their cytotoxicity, revealing further potent activities toward Streptococcus pneumoniae, Enterococcus faecium, and Enterococcus faecalis. To explore the mode of action, compound 12 was tested in a macromolecule inhibition assay. The obtained data were supported by the safety profile of compound 12, which possessed an IC50 of 12.3 µg/mL against HepG2 cells. The current results hold good potential for a new class of extended-spectrum antibacterial agents.

Organo-Ptii Complexes for Potent Photodynamic Inactivation of Multi-Drug Resistant Bacteria and the Influence of Configuration.

PtII based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few PtII PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure-activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis-BODIPY (4,4-difluoro-boradizaindacene) embedded PtII PSs. The cis-isomer (cis-BBP) displayed enhanced 1O2 generation and better bacterial membrane anchoring capability as compared to the trans-isomer (trans-BBP). The effective PDI concentrations (efficiency > 99.9%) for cis-BBP in Acinetobacter baumannii (multi-drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm-2) and 100 nM (18 J cm-2), respectively; corresponding concentrations and light doses for trans-BBP in the two bacteria are 2.50 µM (30 J cm-2) and 1.50 µM (18 J cm-2), respectively. The 50% and 90% minimum inhibitory concentration (MIC50 and MIC90) ratio of trans-BBP to cis-BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis-BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis-BBP is a robust light-assisted antibacterial reagent at sub-micromolecular concentrations. More importantly, configuration of PtII PSs should be an important issue to be considered in further PDI reagents design.

Design, synthesis and biological evaluation of thiazolyl-halogenated pyrroles or pyrazoles as novel antibacterial and antibiofilm agents.

The formation of biofilm is one of the important factors for bacteria to develop drug-resistant. A series of halogenated-pyrroles or pyrazoles containing thiazole groups as antibacterial agents were designed and synthesized to target biofilms. Among them, compound 8c showed antibacterial activity against various Gram-positive bacteria, particularly against vancomycin-resistant Enterococcus faecalis (MIC ≤0.125 µg/mL). Additionally, this compound significantly inhibited biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa at sub-MIC doses. Furthermore, compound 8c exhibited significantly lower mammalian cell toxicity compared to pyrrolomycin C and its hepatic microsomal metabolic stability in various species was also evaluated. Further experiment on the infection model of Galleria mellonella proved that the compound was effective in vivo.

Epidemiology and patterns of empiric antimicrobial therapy practice in patients with community-onset sepsis using data from a Japanese nationwide medical claims database-the Japan Sepsis Alliance (JaSA) study group.

Objectives: We aimed to describe empiric antimicrobial options for patients with community-onset sepsis using nationwide real-world data from Japan. Methods: This retrospective cohort study used nationwide Japanese data from a medical reimbursement system database. Patients aged ≥20 years with both presumed infections and acute organ dysfunction who were admitted to hospitals from the outpatient department or emergency department between 2010 and 2017 were enrolled. We described the initial choices of antimicrobials for patients with sepsis stratified by intensive care unit (ICU) or ward. Results: There were 1,195,741 patients with community-onset sepsis; of these, 1,068,719 and 127,022 patients were admitted to the wards and ICU, respectively. Third-generation cephalosporins and carbapenem were most commonly used for patients with community-onset sepsis. We found that 1.7% and 6.0% of patients initially used antimicrobials for methicillin-resistant Staphylococcus aureus coverage in the wards and ICU, respectively. Although half of the patients initially used antipseudomonal agents, only a few patients used a combination of antipseudomonal agents. Moreover, few patients initially used a combination of antimicrobials to treat methicillin-resistant Staphylococcus aureus and Pseudomonas sp. Conclusion: Third-generation cephalosporins and carbapenem were most frequently used for patients with sepsis. A combination therapy of antimicrobials for drug-resistant bacteria coverage was rarely provided to these patients.

Antimicrobial activity of carvacrol and its derivatives on Mycobacterium spp.: systematic review of preclinical studies.

Background: The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the Mycobacterium genus. Materials & methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, four databases (PubMed, Web of Science, SCOPUS and EMBASE) were searched. Results: The search retrieved 392 records, of which 11 papers were selected. Heterogeneity in the techniques and mycobacterial targets was observed. Carvacrol demonstrated synergistic antimycobacterial activity with rifampicin against multidrug-resistant Mycobacterium tuberculosis on membranes and biofilms. In silico approaches showed specific targets in mycobacteria, by inhibition and molecular docking assays, on the enzyme chorismate mutase and the heat shock protein 16.3. Conclusion: Carvacrol has been shown to be a scaffold candidate for future molecules with activity against mycobacteria.

Addressing Antimicrobial Properties in Guided Tissue/Bone Regeneration Membrane: Enhancing Effectiveness in Periodontitis Treatment.

Guided tissue regeneration (GTR) and guided bone regeneration (GBR) are the two surgical techniques generally used for periodontitis disease treatment. These techniques are based on a barrier membrane to direct the growth of new bone and gingival tissue at sites with insufficient volumes or dimensions of bone or gingiva for proper function, esthetics, or prosthetic restoration. Numerous studies have highlighted biocompatibility, space-creation, cell-blocking, bioactivity, and proper handling as essential characteristics of a membrane's performance. Given that bacterial infection is the primary cause of periodontitis, we strongly believe that addressing the antimicrobial properties of these membranes is of utmost importance. Indeed, the absence of effective inhibition of periodontal pathogens has been recognized as a primary factor contributing to the failure of GTR/GBR membranes. Therefore, we suggest considering antimicrobial properties as one of the key factors in the design of GTR/GBR membranes. Antibiotics are potent medications frequently administered systemically to combat microbes and mitigate bacterial infections. Nevertheless, the excessive use of antibiotics has resulted in a surge in bacterial resistance. To overcome this challenge, alternative antibacterial substances have been developed. In this review, we explore the utilization of alternative substances with antimicrobial properties for topical application in membranes. The use of antibacterial nanoparticles, phytochemical compounds, and antimicrobial peptides in this context was investigated. By carefully selecting and integrating antimicrobial agents into GTR/GBR membranes, we can significantly enhance their effectiveness in combating periodontitis. These antibacterial substances not only act as barriers against pathogenic bacteria but also promote the process of periodontal healing.