Development Of Bacterial Resistance Research Articles

Costs are a major driver of antibacterial drug prescriptions in Germany: marketanalysis from 1985 to 2022.

In recent years, several threatening developments regarding antibacterial drugs, such as rising bacterial resistance and delivery bottlenecks, have occurred. Since antibacterial drugs are crucial for modern medicine, understanding events and influencing factors relevant for long-term developments is essential. Therefore, we analyzed the number of prescriptions and costs, defined daily dose (DDD) and DDD costs of antibacterial drugsin Germany, based on the Arzneiverordnungsreport (AVR, Drug description report) between 1985 and 2022. Based on prescription rates in 2022, we selected the TOP15 and TOP5. For a more in-depth analysis, we analyzed data from the wissenschaftliches Institut der AOK (WidO, scientific institute of the AOK). The number of prescriptions increased between 1985 and 2013, but since 2014, there has been a declining trend with a noticeable COVID-related dip. Over the years, a shift in drug classes occurred. Once very popular drugs like penicillins and tetracyclines are no longer as important. Conversely, aminopenicillins and cephalosporins have become more relevant. Particularly, the TOP5 drugs have seen an increasing proportion. DDD costs have decreased in most substance classes over time. There is a strong association between decreasing costs and rising prescriptions. Falling costs have a stronger immediate impact on prescriptions that rising costs. When costs are very low, drugs might be prescribed excessively. Supply bottlenecks can also result. The main prescribers are mainly in primary care. Their share of prescription has changed little over the years, but is decreasing regarding total consumption. In comparison to other European countries, Germany ranks in the lower third regarding prescriptions. In most countries, the COVID pandemic has led to a reduced prescription of antibacterial drugs. In conclusion, we provided a comprehensive overview of the antibacterial drug market in Germany over the past four decades and identified costs as a major driver of antibacterial drug prescriptions. Increased costs may reduce uncritical prescription of antibacterial drugs, development of bacterial resistance, supply shortages and occurrence of adverse effects.

Low Concentration of Wenyang Tonglin Decoction Promotes Conjugation and Transfer of Drug-Resistant Plasmids among Heterologous Strains.

To investigate the effect of low concentration of Wenyang Tonglin Decoction (WTD) on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism. Escherichia coli CP9 (R45) and Staphylococcus aureus RN450RF were cultured in medium containing WTD, and their minimum inhibitory concentration (MIC) values were obtained. Using promoter fusion technology, E. coli CP9 (R45) containing a promoter fusion was obtained. β-Galactosidase activity of TrfAp and TrbBp was tested, and the mRNA expression of regulatory factors (TrbA, KorA, and KorB) was detected by real-time fluorescent quantitative polymerase chain reaction. The MIC of E. coli CP9 (R45) was 400 g/L and that of S. aureus RN450RF was 200 g/L. When the drug concentration in the culture medium was 200 g/L, the highest number of conjugants was (3.47 ±0.20) × 107 CFU/mL At 90 h of conjugation, the maximum number of conjugants was (1.15 ±0.06) × 108 CFU/mL When the initial bacterial concentration was 108 CFU/mL, the maximum number of conjugants was (3.47 ± 0.20) × 107 CFU/mL. When the drug concentration was 200 g/L, the β-galactosidase activity of TrfAp and TrbBp significantly increased; the relative quantification of TrbA, KorA and KorB were significantly inhibited. Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors.

Efficacy of Chlorhexidine Impregnated Wipes for the Local Dysbiosis in Atopic Dogs: A Multicentric Prospective Study.

(1) Background: Dysbiosis is frequently observed in Canine Atopic Dermatitis (CAD). Antimicrobial treatment may be necessary to treat flare ups and the use of topical treatments is beneficial to prevent the development of bacterial resistance. Wipes are an easy way to apply antiseptic agents on the skin. The aim of this study was to evaluate the benefits of 3% chlorhexidine impregnated wipes (Pyoskin® wipes, MP Labo, France) on local areas of dysbiosis in dogs with CAD. (2) Methods: A total of 20 dogs suffering from CAD presented with localised areas of dysbiosis were included in this study. Affected areas were cleansed with the daily application of chlorhexidine wipes once a day for 14 days. Follow-up visits were scheduled after one and two weeks. Clinical signs (lesions and pruritus), dysbiosis scored by cytological counts (cocci and Malassezia) and investigator and owner global appreciation were evaluated. (3) Results: A statistically significant decrease in clinical scores and cytological counts were observed as soon as D7 and until D14. Both owner and investigator appreciation were considered high (4) Conclusions: The use of chlorhexidine impregnated wipes is a useful and easy way to manage localised dysbiosis in atopic dogs and allows limiting of systemic medication to prevent bacterial resistance.

Preparation and Effects of Manganese Oxide Nanoparticles Against Quinolone-Resistant Bacteria Isolated from Hospital Wastewater

Background: The widespread administration of quinolones may have led to an increase in bacterial resistance development. Objective: To synthesize and characterize manganese oxide nanoparticles (MnO2NPs) and evaluate their effects on the viability and biofilm formation of quinolone-resistant gram-positive and negative pathogenic bacteria. Methods: We prepared MnO2NPs using the photo-irradiation method and recorded their characteristics using XRD, TEM, and SEM. Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa were collected from the wastewater of Baghdad hospitals during the period from July 3rd to July 14th, 2023. We used the VITEK2 system to confirm and identify all of the isolates. We conducted biofilm formation and antibiotic susceptibility tests using nalidixic acid, ciprofloxacin, norfloxacin, aztreonam, levofloxacin, and ofloxacin, and also detected the qnrA and qnrB genes. Finally, we evaluated the effects of the prepared nanoparticles on the viability and biofilm formation of bacterial isolates. Results: MnO2NPs characterizations showed a diffraction peak at 2θ values with 21 nm average sizes; qnrA and qnrB genes were found in three and four isolates, respectively; and significant effects of MnO2NPs against viability and biofilm formation were recorded. Conclusions: The synthesized nanoparticles have antibacterial and anti-biofilm activities against a variety of bacteria possessing qnr genes. Even multi-resistant bacterial isolates have the potential to be strong antimicrobial agents against these pathogens.

Biomimetic protein structural transitions regulate activation and inhibition of the broad-spectrum bactericidal activity of cationic nanoparticles

The development of cationic polymers as alternative materials to antibiotics necessitates addressing the challenge of balancing their antimicrobial activity and toxicity. Here we propose a precise switching strategy inspired by biomimetic voltage-gated ion channels, enabling controlled activation and inhibition of cationic antimicrobial functions through protein conformational transitions in diverse physiological environments. Following thermodynamic studies on the specific recognition between mannose end groups on polycations and concanavalin A (ConA), we synthesized a type of ConA-polycation nanoparticle. The nanoparticle was inhibited under neutral conditions, with cationic moieties shielded by ConA's β-sheet. This shielding suppresses their antimicrobial activity, thereby ensuring satisfactory biocompatibility. In mildly acidic environments, however, the transition of a portion of ConA to an α-helix conformation exposed cations at the particle periphery, activating antibacterial functionality. Compared to inhibited nanoparticles, those in the activated state exhibited a 32–256 times reduction in the minimum bactericidal concentration against bacteria and fungi (2–16 µg/mL). In a murine acute pulmonary infection model, intravenous administration of inhibited nanoparticles effectively reduced bacterial counts by 4-log within 12 h. The biomimetic design, regulating cationic antimicrobial functionality through the alteration in protein secondary structure, significantly retards bacterial resistance development, holding great promise for intelligent antimicrobial materials. Statement of significanceCationic antimicrobial polymers exhibit advantages distinct from antibiotics due to their lower propensity for resistance development. However, the presence of cationic moieties also poses a threat to healthy cells and tissues, significantly constraining their potential for clinical applications. To address this challenge, we propose a biomimetic strategy that mimics voltage-gated ion channels to activate the antimicrobial functionality of cations selectively in bacterial environments through the conformational transitions of proteins between β–sheets and α–helices. In healthy tissues, the antimicrobial functionality is inhibited, ensuring satisfactory biocompatibility. Antimicrobial cationic materials capable of intelligent switching between an activated state and an inhibited state in response to environmental changes offer an effective strategy to prevent the development of resistance and mitigate potential side effects.

Unique aminothiazolyl coumarins as potential DNA and membrane disruptors towards Enterococcus faecalis

Aminothiazolyl coumarins as potentially new antimicrobial agents were designed and synthesized in an effort to overcome drug resistance. Biological activity assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungi including drug-resistant pathogens. Especially, aminothiazolyl 7-propyl coumarin 8b and 4-dichlorobenzyl derivative 11b exhibited bactericidal potential (MBC/MIC = 2) toward clinically drug-resistant Enterococcus faecalis with low cytotoxicity to human lung adenocarcinoma A549 cells, rapidly bactericidal effects and no obvious bacterial resistance development against E. faecalis. The preliminary antibacterial action mechanism studies suggested that compound 11b was able to disturb E. faecalis membrane effectively, and interact with bacterial DNA isolated from resistant E. faecalis through noncovalent bonds to cleave DNA, thus inhibiting the growth of E. faecalis strain. Further molecular modeling indicated that compounds 8b and 11b could bind with SER-1084 and ASP-1083 residues of gyrase-DNA complex through hydrogen bonds and hydrophobic interactions. Moreover, compound 11b showed low hemolysis and in vivo toxicity. These findings of aminothiazolyl coumarins as unique structural scaffolds might hold a large promise for the treatments of drug-resistant bacterial infection.

Exploiting the advantages of cationic copolymers and AgBr nanoparticles to optimize the antibacterial activity of chitosan

Recently, the chitosan (CS)-based composites have attracted increasing attention for controlling and preventing the spread of pathogenic microorganisms. Herein, an amphiphilic copolymer containing epoxy and quaternary ammonium groups (PBGDBr) was synthesized via three common acrylate monomers. The epoxy groups of this copolymer were then crosslinked with the amino groups of CS to synthesize a natural/synthetic (PBGDBr-C) composite to increase the water solubility of CS under alkaline conditions and enhance its antibacterial activity based on chemical contact-type modes. Moreover, silver bromide nanoparticles (AgBr NPs)-decorated PBGDBr-C (AgBr@PBGDBr-C) composite was prepared, which aimed to endow the final AgBr@PBGDBr-C composite with a photodynamic antibacterial mode relying on the formation of Ag/AgBr nanostructures catalyzed by visible light on AgBr NPs. The results showed that the final composite possessed satisfactory bactericidal effects at concentrations higher than 64 and 128 μg/mL against Escherichia coli and Staphylococcus aureus, respectively. Additionally, The L929 cells treated with the final composite retained high cell viability (>80 %) at a concentration of 128 μg/mL, indicating its low toxicity to L929 cells. Overall, our synthetic strategy exploits a multi-modal system that enables chemical-photodynamic synergies to treat infections caused by pathogenic bacteria while delaying the development of bacterial resistance.

Design, synthesis, and evaluation of N1,N3-dialkyldioxonaphthoimidazoliums as antibacterial agents against methicillin-resistant Staphylococcus aureus

Increasing antibiotic resistance of bacterial pathogens poses a serious threat to human health worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most deleterious bacterial pathogens owing to its multidrug resistance, necessitating the development of new antibacterial agents against it. We previously identified a novel dioxonaphthoimidazolium agent, c5, with moderate antibacterial activity against MRSA from an anticancer clinical candidate, YM155. In this study, we aimed to design and synthesize several novel cationic amphiphilic N1,N3-dialkyldioxonaphthoimidazolium bromides with enhanced lipophilicity of the two side chains in the imidazolium scaffold and improved antibacterial activities compared to those of c5 against gram-positive bacteria in vitro and in vivo. Our new antibacterial lead, N1,N3-n-octylbenzyldioxonaphthoimidazolium bromide (11), exhibited highly potent antibacterial activities against various gram-positive bacterial strains (MICs: 0.19–0.39 μg/mL), including MRSA, methicillin-sensitive S. aureus, and Bacillus subtilis. Moreover, antibacterial mechanism of 11 against MRSA based on the generation of reactive oxygen species (ROS) was evaluated. Although compound 11 exhibited cytotoxic effects in vitro and lacked a therapeutic index against the HEK293 and HDFa mammalian cell lines, it exhibited low toxicity in the Drosophila animal model. Remarkably, 11 exhibited better in vivo antibacterial efficacy than c5 and the clinically used antibiotic, vancomycin, in SA3-infected Drosophila model. Moreover, the development of bacterial resistance to 11 was not observed after 16 consecutive passages. Therefore, rational design of antibacterial cationic amphiphiles based on ROS-generating pharmacophores with optimized lipophilicity can facilitate the identification of potent antibacterial agents against drug-resistant infections.

Detection and Antibiotic Resistance Pattern of Multidrug Resistant Staphylococccus aureus from Wound Infection at Tertiary Hospital in Yenagoa, Nigeria

Multidrug resistant Staphylococcus aureus is increasingly prevalent worldwide, albeit with significant regional variations. The development of bacterial resistance to various antibacterial agents coupled with its virulence factors have significantly contributed to its pathogenicity. This investigation aimed to identify multidrug resistant S. aureus in wound infections. A total of 40 specimens from burn and cut wound specimens were examined utilizing culture, Gram staining, biochemical analysis, Kirby Bauer disc diffusion technique using ten multidisc antibiotics and plasmid profiling. Descriptive analysis was employed to determine the prevalence of S. aureus in specimens collected from individuals with open wounds, comprising 18 (45%) males and 22 (55%) females. Antibiogram profiles were used to determine the antibiotic resistance of the isolates. A total number of 19 (48%) S. aureus isolates were obtained in this study. Among patients with burn wounds, 12 (63.5%) exhibited the highest number of isolates, while those with cut wounds accounted for 7 (36.8%) representing the lowest count. The number of males with burn wounds was 7 (58.3%), higher than that of females 5 (41.7%). Females had a greater number of cut wounds with 5 (71.4%) compared to males with 2 (28.6%). The age group 16-25 years exhibited the highest number of isolates at 7 (37%), while the lowest was observed in the age group 66-75 years, with 1 (5%). Notably, these age intervals showed a statistically significant difference with P<0.05. The highest occurrence of isolate was recorded in males within the age group 16-25 years, totalling 5 (24%). In contrast, for females, the most prevalent isolate was found in the age 26-35 years, amounting to 3 (16%). The susceptibility profile of S. aureus revealed sensitivity to gentamycin 7 (36.8%) and levofloxacin 11 (57.9%), while resistance to norfloxacin, chloramphenicol, erythromycin, amoxil and ampiclox was 100%. Plasmid profiling identified multiple plasmid bands in the obtained multidrug resistant S. aureus, with a molecular weight of 9466kbp. The susceptibility pattern of the multidrug S. aureus both before and after plasmid curing indicated that previously resisted antibiotics became susceptible after curing except for amoxicillin-clavulanic acid and cefpodoxime. Cefotaxime, with a 25 mm zone of inhibition, was the most sensitive antibiotic after the plasmid curing. The discovery of plasmid in this study may prove valuable for the effective monitoring of antibiotic resistance patterns in bacteria from wound infections and clinical settings.

Synthesis of lithium and silver nanoparticles by green chemistry and its antimicrobial effect on Staphylococcus aureus and Klebsiella pneumoniae

Synthesis of lithium and silver nanoparticles by green chemistry and its antimicrobial effect on Staphylococcus aureus and Klebsiella pneumoniae. The synthesis of NPs (nanoparticles) using lithium and silver salts and its characterization by scanning electron microscopy (SEM) was carried out. The effect of silver (AgNPs) and Lithium (LiNPs) nanoparticles (NPs) on the proliferation of Staphylococcus aureus and Klebsiella pneumoniae, was evaluated. For all concentrations evaluated, inhibition of bacterial growth was observed with a MIC close to 0.8 mg/mL-AgNPs and 0.6 mg/mL-LiNPs against S. aureus and 1 mg/mL- AgNPs and 0.6 mg/mL- LiNPs against K. pneumonia. Given the actual development of bacterial resistance to antibiotics, we contributed with an alternative for the future treatment of bacterial infections in humans and animals by evaluation of activities of synthetic metallic nanoparticles.

Multidrug-resistant Stenotrophomonas maltophilia in residential aged care facilities: An emerging threat.

Stenotrophomonas maltophilia is a multidrug-resistant (MDR), Gram-negative bacterium intrinsically resistant to beta-lactams, including last-resort carbapenems. As an opportunistic pathogen, it can cause serious healthcare-related infections. This study assesses the prevalence, resistance profiles, and genetic diversity of S. maltophilia isolated from residential aged care facilities (RACFs). RACFs are known for their overuse and often inappropriate use of antibiotics, creating a strong selective environment that favors the development of bacterial resistance. The study was conducted on 73 S. maltophilia isolates recovered from wastewater and facility swab samples obtained from three RACFs and a retirement village. Phenotypic and genotypic assessments of the isolates revealed high carbapenem resistance, exemplifying their intrinsic beta-lactam resistance. Alarmingly, 49.3% (36/73) of the isolates were non-wild type for colistin, with minimum inhibitory concentration values of > 4 mg/L, and 11.0% (8/73) were resistant to trimethoprim-sulfamethoxazole. No resistance mechanisms were detected for either antimicrobial. Genotypic assessment of known lineages revealed isolates clustering with Sm17 and Sm18, lineages not previously reported in Australia, suggesting the potential ongoing spread of MDR S. maltophilia. Lastly, although only a few isolates were biocide tolerant (2.7%, 2/73), their ability to grow in high concentrations (64 mg/L) of triclosan is concerning, as it may be selecting for their survival and continued dissemination.

Unveiling Therapeutic Potential: Targeting Fusobacterium nucleatum's Lipopolysaccharide Biosynthesis for Endodontic Infections-An In Silico Screening Study.

Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.

Patients' Opinions on Antibiotics in the Treatment of Dental Infections: A Cross-Sectional Survey.

Background: The aim of this study was to evaluate patients' knowledge and perceptions of the use of systemic antibiotics in the treatment of endodontic infections and to determine the possible contribution of patients to the development of bacterial resistance. Methods: A total of 550 patients were asked to respond to a survey on the perception of systemic antibiotic use in the treatment of endodontic infections and antibiotic resistance during January 2022 and March 2023. A bivariate and multivariate analysis was performed to determine possible correlates in the population regarding antibiotic use in the endodontic world. Results: A total of 514 patients were included in the study, 65.9% of whom were women. While 34.6% of the population studied thought that it was always necessary to take antibiotics prior to endodontics, 49.4% considered that they were necessary after endodontics, regardless of the clinical symptoms. The prevalence of self-medication was 17.3%, and women self-medicate more than men, with significant differences (p < 0.05), although they have a greater knowledge of antibiotic resistance than men (p < 0.05). Forty-four percent of the population expected to take antibiotics when faced with dental pain, mainly women (p < 0.05). Conclusions: The general population is contributing to the serious problem of bacterial resistance. It is necessary to promote educational strategies focused on the correct use of antibiotics in the community. The worst results were found mainly in the population with a low level of education. The level of education was the variable that most influenced the knowledge and attitudes of the population, followed by the sex of the participants.

Space-confined nanozyme with cascade reaction based on PCN-224 for synergistic bacterial infection treatment and NIR fluorescence imaging of wound bacterial infections

The rapid development of bacterial infections has become a significant global health challenge. The overuse or prolonged use of antibiotics is considered a major contributor to the development of bacterial resistance. Therefore, there is an urgent need to develop a new therapeutic approach to combat infectious diseases caused by bacteria. In this study, we demonstrate the effectiveness of a novel strategy for synergistic antibacterial therapy and fluorescence imaging of wound bacterial infections through the nano-confined construction of LL-37-HA-Au-Pt@PCN-224 nanozymes. The nanozyme is composed of Au NPs and Pt NPs confined to PCN-224 through in situ reduction, with its outer layer modified with HA and LL-37. The nanozyme catalyzes the conversion of low-concentration H2O2 into O2 and •OH, with the generated O2 further catalyzed into 1O2 by PCN-224. In vivo imaging experiments demonstrate that LL-37-HA-Au-Pt@PCN-224 labeled with near-infrared fluorescent dye MPA can effectively realize fluorescence imaging of wound bacterial infections and real-time monitoring of the wound healing process. In vitro and in vivo antibacterial experiments reveal that LL-37-HA-Au-Pt@PCN-224 enhances the healing efficiency of bacteria-infected wounds due to its synergistic antibacterial effect. The multifunctional nanozyme offers various synergistic antibacterial therapies, including antimicrobial peptides, peroxide nanozymes, hydrogen peroxide nanozymes, and photodynamic therapy. Moreover, it provides real-time wound imaging and monitoring of the wound healing process, while maintaining high biocompatibility. Overall, this study presents a promising perspective on the potential use of nanozymes as antibacterial agents against wound bacterial infections in the future.

Nisin—A Promising Antimicrobial Compound from Lactic Acid Bacteria

Nisin is a classical bacteriocin consisting of thirty-four amino acid residues and undergoing a high degree of post-translational modification to form a unique pentacyclic structure. Nisin is mainly synthesised by lactic acid bacteria. Under natural conditions, it exhibits strong antibacterial activity against Gram-positive organisms and, when combined with chelating agents, is effective against Gram-negative organisms. An excellent safety profile, low cytotoxicity and slow development of resistance are additional benefits. Currently, the application of nisin is focused on food preservation. This is due to the fact that nisin is naturally present in a wide range of historical fermented foods and its safety is fully guaranteed. With the continuous development of bacterial drug resistance and the consequent demand for new anti-infective drugs, its biomedical applications are being actively explored. However, due to the problems of drug stability, safety, and in vivo activity, there is still a certain distance from clinical application. In this paper, the author summarized the structure, biosynthetic mechanism, applications, and possible research directions of nisin.

Differentiated approach to external acne therapy

Acne is a serious medical and social problem due to the widespread prevalence of the disease. Localized mainly on the face, acne leads to the development of disorders in the psycho-emotional sphere, significantly reducing the quality of life.&#x0D; The aim of the study was to study the effectiveness and safety of Epiduo/Effezel gel (adapalene 0.1% and benzoyl peroxide 2.5%) in patients with papulopustular acne.&#x0D; The Clinic of Skin and Sexually Transmitted Diseases of the Clinical Hospital No. 2 of Sechenov University has accumulated extensive experience in the treatment of acne. In the diagnostic and treatment department, patients with mild to moderate acne receive consultations and treatment almost every day. A dermatological examination is carried out visually with a simple count of eruptive elements: papules, pustules and nodes, on the basis of which the degree of severity is determined. Patients with severe forms of acne receive systemic retinoids with corrective therapy until a certain cumulative dose is reached, and then patients receive topical maintenance therapy intermittently for 12 months.&#x0D; Despite the development of effective methods for treating this dermatosis, patient adherence to treatment remains low. This is due, first of all, to the duration of therapy, not always the rapid achievement of the expected result, and to the development of psycho-emotional disorders in patients. In the latest edition of the Russian Society of Dermatovenerologists and Cosmetologists clinical guidelines for the treatment of mild to moderate acne with a high level of evidence A1, it is recommended to use benzoyl peroxide and a fixed combination of adapalene and benzene peroxide. When prescribing benzene peroxide (Baziron AS), we observed the best results in clearing the skin of rashes in the presence of a few papulopustular elements in the clinical picture due to the triple action of benzoyl peroxide ― antimicrobial, keratolytic and sebostatic. In our experience, it usually took 4 to 6 weeks to achieve clinical remission, and we did not note a single case of the development of bacterial resistance during treatment. For moderately widespread papulopustular acne rashes of moderate severity, as well as in cases of severe forms of the disease, when it is impossible to prescribe systemic isotretinoin or there is a tendency to scarring of the primary elements, we used a fixed combination of adapalene 0.1% and benzoyl peroxide 2.5% (Effezel) with anti-inflammatory, antimicrobial, keratolytic, sebostatic, comedolytic and anticomedogenic effects.&#x0D; In the arsenal of dermatologists and cosmetologists there are drugs for the external treatment of mild to moderate papulopustular acne with a high level of evidence. Thus, for papulopustular acne with a few inflammatory (papules and pustules) rashes, benzoyl peroxide gel may be recommended. For moderately widespread papulopustular acne with the presence of comedones (moderate severity), a fixed combination of adapalene and benzoyl peroxide can be recommended as the first line of therapy.

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.

Repurposing cinacalcet suppresses multidrug-resistant Staphylococcus aureus by disruption of cell membrane and inhibits biofilm by targeting IcaR.

MDR Staphylococcus aureus infections, along with the severity of biofilm-associated infections, continue to threaten human health to a great extent. It necessitates the urgent development of novel antimicrobial and antibiofilm agents. To reveal the mechanism and target of cinacalcet as an antibacterial and antimicrobial agent for S. aureus. Screening of non-antibiotic drugs for antibacterial and antibiofilm properties was conducted using a small-molecule drug library. In vivo efficacy was assessed through animal models, and the antibacterial mechanism was studied using quantitative proteomics, biochemical assays, LiP-SMap, BLI detection and gene knockout techniques. Cinacalcet, an FDA-approved drug, demonstrated antibacterial and antibiofilm activity against S. aureus, with less observed development of bacterial resistance. Importantly, cinacalcet significantly improved survival in a pneumonia model and bacterial clearance in a biofilm infection model. Moreover, the antibacterial mechanism of cinacalcet mainly involves the destruction of membrane-targeted structures, alteration of energy metabolism, and production of reactive oxygen species (ROS). Cinacalcet was found to target IcaR, inhibiting biofilm formation through the negative regulation of IcaADBC. The findings suggest that cinacalcet has potential for repurposing as a therapeutic agent for MDR S. aureus infections and associated biofilms, warranting further investigation.

Food chain milieus: Potential reservoirs and sources of metallo-beta-lactamase-producing antibiotic-resistant bacteria in Southeast Nigeria

Concerted efforts are needed to mitigate the development and transmission of bacterial resistance in the general environment. Metallo-beta-lactamase (MBL) is a carbapenemase that allows bacteria to resist the antimicrobial onslaught of carbapenems (e.g., imipenem [IPM]). We investigated the prevalence of MBL-producing Pseudomonas aeruginosa in poultry farms. Samples from poultry birds (n = 65) were studied for the isolation of antibiotic-resistant bacteria according to the Clinical and Laboratory Standards Institute criteria. The modified Hodge test was used to phenotypically detect MBL. Polymerase chain reaction (PCR) was used to confirm MBL production in the test isolates. To confirm the presence of plasmids in the isolates, a plasmid curing experiment was conducted. High levels of reduced susceptibility to cefotaxime (77.8%), IPM (69.4%), gentamicin (63.9%), amikacin (58.3%), fosfomycin (55.5%), ciprofloxacin (66.7%), tetracycline (75%), ertapenem (55.5%), sulfamethoxazole-trimethoprim (66.7%), and cefoxitin (52.8%) were recorded in the P. aeruginosa isolates. A total of 23 isolates of P. aeruginosa produced MBL. The presence of MBL genes in these P. aeruginosa isolates (n = 23) was confirmed by PCR, which detected blaIMP-1 (47.8%) and blaIMP-2 (26.1%). The isolates were multidrug resistant (50%) and carried plasmids, indicating horizontal transmission of resistance genes. Genes for bacterial resistance can be transmitted through mobile genetic elements. Therefore, sustainable interventions are needed to mitigate antibiotic use in poultry practices in Nigeria to curb the development of MBL-producing bacteria arising from selective (antibiotic) pressures in such an environment. These interventions can help to detect and stop infections caused by resistant bacteria before they become clinical cases in our hospitals.

Efficacy of outer membrane permeabilization in promoting aromatic isothiocyanates-mediated eradication of multidrug resistant Gram-negative bacteria and bacterial persisters.

Multidrug resistant (MDR) bacteria are recognized to be one of the most important problems in public health. The outer membrane permeability is a critical intrinsic mechanism of bacterial resistance. In addition, bacteria produce a small number of dormant persister cells causing multidrug tolerance that reduces antimicrobial efficacy. This study aimed to evaluate the inhibitory effects of the combination of aromatic isothiocyanates (ITCs) with membrane-active agents on bacterial persisters and MDR Gram-negative bacteria. Our study demonstrated that membrane-active agents, particularly ethylenediaminetetraacetic acid (EDTA) synergistically enhanced the inhibitory activity of aromatic benzyl ITC and phenethyl ITC against most Gram-negative bacteria strains with fractional inhibitory concentration index values ranging from 0.18 to 0.5 and 0.16 to 0.5, respectively, and contributed to an 8- to 64-fold minimal inhibitory concentration reduction compared with those of aromatic ITCs alone. The EDTA-aromatic ITCs combination effectively reduced the survival rates of tested bacteria and significantly eradicated bacterial persisters (p = 0.033 and 0.037, respectively). The growth kinetics analysis also supported the enhanced inhibitory effect of EDTA-aromatic ITCs combination against tested bacteria. Our results suggested an alternate treatment strategy against Gram-negative bacteria, promoting the entry of aromatic ITCs into bacterial cytoplasm to facilitate bacterial clearance and thus preventing the development of bacterial resistance.