Design and synthesis of novel 1,3,4-thiadiazole thioglycosides as promising antimicrobial potent structures.

Thiosemicarbazide was used as a key starting material for the building of a diversity of novel heterocyclic moieties. The heterocyclization reaction of thiosemicarbazide derivatives with carbon disulfide in basic conditions afforded novel heterocyclic 1,3,4-thiadiazolethiolate derivatives. 1,3,4-thiadiazole-2-thiol was successfully reacted with protected α-D-gluco- and galacto-pyranosyl bromides in dimethylformamide at room temperature to give the matching 1,3,4-thiadiazole S-glycosides in good yields. The latter compounds were reacted with ammonia-methanol at room temperature for 10 min, and the deprotected derivatives were obtained in good yields. The newly synthesized compounds were characterized by basic analyses and spectral information (IR,1H NMR, and 13C NMR, X-ray). All newly produced compounds were evaluated and screened for their antibacterial activities. Compound 6f proved to be the most active antimicrobial among the investigated heterocycles.

Implementing antimicrobial stewardship: lessons and perspectives from a university-affiliated tertiary hospital in Korea.

Antimicrobial stewardship programs (ASPs) can lower antibiotic use, decrease medical expenses, prevent the emergence of resistant bacteria, and enhance treatment for infectious diseases. This study summarizes the stepwise implementation and effects of ASPs in a single university-affiliated tertiary care hospital in Korea; it also presents future directions and challenges in resource-limited settings. At the study hospital, the core elements of the ASP such as leadership commitment, accountability, and operating system were established in 2000, then strengthened by the formation of the Antimicrobial Stewardship (AMS) Team in 2018. The actions of ASPs entail key components including a computerized restrictive antibiotic prescription system, prospective audit, post-prescription review through quantitative and qualitative intervention, and pharmacy-based interventions to optimize antibiotic usage. The AMS Team regularly tracked antibiotic use, the effects of interventions, and the resistance patterns of pathogens in the hospital. The reporting system was enhanced and standardized by participation in the Korea National Antimicrobial Use Analysis System, and educational efforts are ongoing. Stepwise implementation of the ASP and the efforts of the AMS Team have led to a substantial reduction in the overall consumption of antibiotics, particularly regarding injectables, and optimization of antibiotic use. Our experience highlights the importance of leadership, accountability, institution-specific interventions, and the AMS Team.

Advances in the Synthesis of Biologically Active Quaternary Ammonium Compounds.

This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review highlights examples of quaternary ammonium compounds exhibiting activity against protozoa and herbicidal effects, as well as analgesic and anesthetic derivatives. The article also embraces the quaternary-ammonium-containing cholinesterase inhibitors and muscle relaxants. QACs, marked by their inherent permanent charge, also find widespread usage across diverse domains such as fabric softeners, hair conditioners, detergents, and disinfectants. The effectiveness of QACs hinges greatly on finding the right equilibrium between hydrophilicity and lipophilicity. The ideal length of the alkyl chain varies according to the unique structure of each QAC and its biological settings. It is expected that this review will provide comprehensive data for medicinal and industrial chemists to design and develop novel QAC-based products.

Addition of nisin to high-viscosity glass-ionomer cement: a comparative in vitro study on antibacterial and physical properties.

PURPOSE: Nisin is a lantibiotic effective against Gram-positive microorganisms such as Streptococcus mutans. The study aimed to determine the effect of the addition of nisin to high-viscosity glass-ionomer cement (HVGIC) on its antibacterial activity, setting time, surface microhardness, and compressive strength. METHODS: 1 and 3% w/w nisin were added to HVGIC before mixing. Unmodified HVGIC was the control. Agar disc diffusion, direct contact test, and scanning electron microscopy (SEM) analysis were used to evaluate antibacterial activity against S. mutans. Setting time, surface microhardness, and compressive strength were measured using Gilmore needle apparatus, digital microhardness tester, and universal testing machine, respectively. Statistical analysis included Student's t test, one-way ANOVA with Tamhane's post hoc test, and repeated-measures ANOVA. RESULTS: As evidenced by the agar disc diffusion (p < 0.001), direct contact tests (p = 0.025), and SEM analysis of the S. mutans cell count and cell surface area (p = 0.049 and 0.003), 3% nisin had the strongest antibacterial activity. There was a dose-dependent increase in setting time (p = 0.005) and surface microhardness (p = 0.006), with no significant difference in compressive strength compared to control. CONCLUSION: The addition of 3% nisin to HVGIC enhances the antibacterial action against S. mutans and surface microhardness without adversely affecting setting time and compressive strength.

Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: Retrospective, multicentre study including patients aged <20 years with PA-BSI in 4 tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multivariable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (IQR: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multidrug-resistant and 6.6% extensively drug-resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, p<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, p=0.002) than BSIs caused by carbapenem-susceptible PA. CR was associated with carbapenem treatment in the previous month (adjusted OR [aOR] 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

[Renal colic]. / Steinkolik.

INTRODUCTION: Renal colic accounts for 5-10% of all emergency department visits, making it a common condition in acute medicine. The typical clinical presentation is an early indication of urolithiasis. DIAGNOSIS: Diagnostic measures include laboratory tests, ultrasound, and low-dose noncontrast computed tomography (CT) scans. Kidney, ureter, bladder (KUB) plain film radiography has been widely replaced by low-dose noncontrast CT with similar radiation dosage. In special patient groups such as children or pregnant women, ionizing radiation should be avoided if possible. TREATMENT: General measures involve pain management (non-steroidal anti-inflammatory agents, opioids) and empirical antibiotic treatment for suspected bacterial infection. Depending on the location/size of the stone, pharmacological stone expulsion therapy may be considered. In cases of obstructive pyelonephritis or acute renal insufficiency, early urinary drainage (JJ stent/nephrostomy) is recommended. Definitive stone removal may be performed primarily in some cases (rather small and rather distal ureterolithiasis). It is common to schedule stone removal as a secondary intervention.

Effect of Dentifrice Ingredients on Volume and Vitality of a Simulated Periodontal Multispecies Biofilm.

The aim of this in vitro study was to investigate the effect of different toothpaste ingredients on biofilm volume and vitality in an established non-contact biofilm removal model. A multi-species biofilm comprising Porphyromonas gingivalis, Streptococcus sanguinis, and Fusobacterium nucleatum was grown on protein-coated titanium disks. Six disks per group were exposed to 4 seconds non-contact brushing using a sonic toothbrush. Four groups assessed slurries containing different ingredients, i.e., dexpanthenol (DP), peppermint oil (PO), cocamidopropyl betaine (CB), and sodium hydroxide (NaOH), one positive control group with the slurry of a toothpaste (POS), and a negative control group with physiological saline (NEG). Biofilm volume and vitality were measured using live-dead staining and confocal laser scanning microscopy. Statistical analysis comprised descriptive statistics and inter-group differences. In the test groups, lowest vitality and volume were found for CB (50.2 ± 11.9%) and PO (3.6 × 105 ± 1.8 × 105 µm3), respectively. Significant differences regarding biofilm vitality were found comparing CB and PO (p = 0.033), CB and NEG (p = 0.014), NaOH and NEG (p = 0.033), and POS and NEG (p = 0.037). However, no significant inter-group differences for biofilm volume were observed. These findings suggest that CB as a toothpaste ingredient had a considerable impact on biofilm vitality even in a non-contact brushing setting, while no considerable impact on biofilm volume was found.

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.

Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

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.

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.

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.

Sphingobium yanoikuyae Bacteremia, Japan.

We report a case of Sphingobium yanoikuyae bacteremia in an 89-year-old patient in Japan. No standard antimicrobial regimen has been established for S. yanoikuyae infections. However, ceftriaxone and ceftazidime treatments were effective in this case. Increased antimicrobial susceptibility data are needed to establish appropriate treatments for S. yanoikuyae.

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.

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.

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.

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.

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.