Prevalence of multi-drug resistant bacteria in intensive care units at Tripoli University Hospital, Tripoli, Libya.

Among hospitalized patients worldwide, infections caused by multidrug-resistant (MDR) bacteria are a major cause of morbidity and mortality. This study aimed to isolate MDR bacteria from five intensive care units (ICUs) at Tripoli University Hospital (TUH). A prospective cross-sectional study was conducted over a seven-month period (September 2022 to March 2023) across five ICUs at TUH. A total of 197 swabs were collected from Patients', healthcare workers' and ICUs equipment. Samples collected from patients were nasal swabs, oral cavity swabs, hand swabs, sputum specimens, skin swabs, umbilical venous catheter swabs, and around cannula. Swabs collected from health care workers were nasal swabs, whereas ICUs equipment's samples were from endotracheal tubes, oxygen masks, and neonatal incubators. Identification and antimicrobial susceptibility test was confirmed by using MicroScan auto SCAN 4 (Beckman Coulter). The most frequent strains were Gram negative bacilli 113 (57.4%) with the predominance of Acinetobacter baumannii 50/113 (44%) followed by Klebsiella pneumoniae 44/113 (40%) and Pseudomonas aeruginosa 6/113 (5.3%). The total Gram positive bacterial strains isolated were 84 (42.6%), coagulase negative Staphylococci 55 (66%) with MDRs (89%) were the most common isolates followed by Staphylococcus aureus 15 (17.8%). Different antibiotics were used against these isolates; Gram- negative isolates showed high resistance rates to ceftazidime, gentamicin, amikacin and ertapenem. A. baumannii were the most frequent MDROs (94%), and the highest resistance rates in Gram-positive strains were observed toward ampicillin, oxacillin, ampicillin/sulbactam and Cefoxitin, representing 90% of total MDR Gram-positive isolates. ESBL and MRS were identified in most of strains. The prevalence of antibiotic resistance was high for both Gram negative and Gram positive isolates. This prevalence requires strict infection prevention and control intervention, continuous monitoring, implementation of effective antibiotic stewardship, immediate, concerted and collaborative action to monitor its prevalence and spread in the hospital.

Monitoring of antimicrobial resistance in respiratory tract pathogens during the COVID-19 pandemic: A retrospective study.

To understand the distribution and antimicrobial resistance (AMR) of pathogens in respiratory samples in Changle District People's Hospital in Fujian Province in recent years, and provide empirical guidance for infection control and clinical treatment in the region. A retrospective analysis was conducted on 5137 isolates of pathogens from respiratory samples collected from 2019 to 2022. The AMR patterns were systematically analyzed. For research purposes, the data was accessed on October 12, 2023. A total of 3517 isolates were included in the study, including 811 (23.06%) gram-positive bacteria and 2706 (76.94%) gram-negative bacteria. The top 3 gram-positive bacteria were Staphylococcus aureus with 455 isolates (12.94%), Streptococcus pneumoniae with 99 isolates (2.81%), and Staphylococcus hemolytic with 99 isolates (2.81%). The top 3 gram-negative bacteria were Klebsiella pneumoniae with 815 isolates (23.17%), Pseudomonas aeruginosa with 589 isolates (16.75%), and Acinetobacter baumannii with 328 isolates (9.33%). The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and K pneumoniae fluctuated between 41.9% and 70.5%, and 18.6% and 20.9%, respectively. The resistance rates of E coli, K pneumoniae, P aeruginosa, and A baumannii to carbapenems were 2.36%, 8.9%, 18.5%, and 19.6%, respectively. The prevalence of methicillin-resistant S aureus (MRSA) was 48.55%, but it decreased to 38.4% by 2022. The resistance rate of Staphylococcus haemolyticus to methicillin was 100%, and 1 case of vancomycin-resistant strain was detected. K pneumoniae, P aeruginosa, A baumannii, and S aureus are the main pathogens in respiratory samples. Although the resistance rates of some multidrug-resistant strains have decreased, ESBL-producing Enterobacteriaceae, carbapenem-resistant bacteria have still increased. Therefore, it is necessary to strengthen the monitoring of pathogen resistance, promote rational use of antibiotics, and promptly report findings.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Exploring the dynamics of mixed-species biofilms involving Candida spp. and bacteria in cystic fibrosis.

Cystic fibrosis (CF) is an inherited disease that results from mutations in the gene responsible for the cystic fibrosis transmembrane conductance regulator (CFTR). The airways become clogged with thick, viscous mucus that traps microbes in respiratory tracts, facilitating colonization, inflammation and infection. CF is recognized as a biofilm-associated disease, it is commonly polymicrobial and can develop in biofilms. This review discusses Candida spp. and both Gram-positive and Gram-negative bacterial biofilms that affect the airways and cause pulmonary infections in the CF context, with a particular focus on mixed-species biofilms. In addition, the review explores the intricate interactions between fungal and bacterial species within these biofilms and elucidates the underlying molecular mechanisms that govern their dynamics. Moreover, the review addresses the multifaceted issue of antimicrobial resistance in the context of CF-associated biofilms. By synthesizing current knowledge and research findings, this review aims to provide insights into the pathogenesis of CF-related infections and identify potential therapeutic approaches to manage and combat these complex biofilm-mediated infections.

Design, synthesis, and bioactivity evaluation of clindamycin derivatives against multidrug-resistant bacterial strains.

Our research aims to reduce the bacterial resistance of clindamycin against Gram-positive bacteria and expand its range of bacterial susceptibility. First, we optimized the structure of clindamycin based on its structure-activity relationship. Second, we employed the fractional inhibitory concentration method to detect drugs suitable for combination with clindamycin derivatives. We then used a linker to connect the clindamycin derivatives with the identified combined therapy drugs. Finally, we tested antibacterial susceptibility testing and conducted in vitro bacterial inhibition activity assays to determine the compounds. with the highest efficacy. The results of our study show that we synthesized clindamycin propionate derivatives and clindamycin homo/heterodimer derivatives, which exhibited superior antibacterial activity compared to clindamycin and other antibiotics against both bacteria and fungi. In vitro bacteriostatic activity testing against four types of Gram-negative bacteria and one type of fungi revealed that all synthesized compounds had bacteriostatic effects at least 1000 times better than clindamycin and sulfonamides. The minimum inhibitory concentration (MIC) values for these compounds ranged from 0.25 to 0.0325 mM. Significantly, compound 5a demonstrated the most potent inhibitory activity against three distinct bacterial strains, displaying MIC values spanning from 0.0625 to 0.0325 mM. Furthermore, our calculations indicate that compound 5a is safe for cellular use. In conclusion, the synthesized compounds hold great promise in addressing bacterial antibiotic resistance.

Membrane-Active All-Hydrocarbon-Stapled α-Helical Amphiphilic Tat Peptides: Broad-Spectrum Antibacterial Activity and Low Incidence of Drug Resistance.

Multidrug resistance against conventional antibiotics has dramatically increased the difficulty of treatment and accelerated the need for novel antibacterial agents. The peptide Tat (47-57) is derived from the transactivating transcriptional activator of human immunodeficiency virus 1, which is well-known as a cell-penetrating peptide in mammalian cells. However, it is also reported that the Tat peptide (47-57) has antifungal activity. In this study, a series of membrane-active hydrocarbon-stapled α-helical amphiphilic peptides were synthesized and evaluated as antibacterial agents against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. The impact of hydrocarbon staple, the position of aromatic amino acid residue in the hydrophobic face, the various types of aromatic amino acids, and the hydrophobicity on bioactivity were also investigated and discussed in this study. Among those synthesized peptides, analogues P3 and P10 bearing a l-2-naphthylalanine (Φ) residue at the first position and a Tyr residue at the eighth position demonstrated the highest antimicrobial activity and negligible hemolytic toxicity. Notably, P3 and P10 showed obviously enhanced antimicrobial activity against multidrug-resistant bacteria, low drug resistance, high cell selectivity, extended half-life in plasma, and excellent performance against biofilm. The antibacterial mechanisms of P3 and P10 were also preliminarily investigated in this effort. In conclusion, P3 and P10 are promising antimicrobial alternatives for the treatment of the antimicrobial-resistance crisis.

Prediction of carbapenem-resistant gram-negative bacterial bloodstream infection in intensive care unit based on machine learning.

BACKGROUND: Predicting whether Carbapenem-Resistant Gram-Negative Bacterial (CRGNB) cause bloodstream infection when giving advice may guide the use of antibiotics because it takes 2-5 days conventionally to return the results from doctor's order. METHODS: It is a regional multi-center retrospective study in which patients with suspected bloodstream infections were divided into a positive and negative culture group. According to the positive results, patients were divided into the CRGNB group and other groups. We used the machine learning algorithm to predict whether the blood culture was positive and whether the pathogen was CRGNB once giving the order of blood culture. RESULTS: There were 952 patients with positive blood cultures, 418 patients in the CRGNB group, 534 in the non-CRGNB group, and 1422 with negative blood cultures. Mechanical ventilation, invasive catheterization, and carbapenem use history were the main high-risk factors for CRGNB bloodstream infection. The random forest model has the best prediction ability, with AUROC being 0.86, followed by the XGBoost prediction model in bloodstream infection prediction. In the CRGNB prediction model analysis, the SVM and random forest model have higher area under the receiver operating characteristic curves, which are 0.88 and 0.87, respectively. CONCLUSIONS: The machine learning algorithm can accurately predict the occurrence of ICU-acquired bloodstream infection and identify whether CRGNB causes it once giving the order of blood culture.

Changing patterns of bacterial profile and antimicrobial resistance in high-risk patients during the COVID-19 pandemic at a tertiary oncology hospital.

The widespread evolution of phenotypic resistance in clinical isolates over the years, coupled with the COVID-19 pandemic onset, has exacerbated the global challenge of antimicrobial resistance. This study aimed to explore changes in bacterial infection patterns and antimicrobial resistance during the COVID-19 pandemic. This study involved the periods before and during COVID-19: the pre-pandemic and pandemic eras. The surveillance results of bacterial isolates causing infections in cancer patients at an Egyptian tertiary oncology hospital were retrieved. The Vitek®2 or Phoenix systems were utilized for species identification and susceptibility testing. Statistical analyses were performed comparing microbiological trends before and during the pandemic. Out of 2856 bacterial isolates, Gram-negative bacteria (GNB) predominated (69.7%), and Gram-positive bacteria (GPB) comprised 30.3% of isolates. No significant change was found in GNB prevalence during the pandemic (P = 0.159). Elevated rates of Klebsiella and Pseudomonas species were demonstrated during the pandemic, as was a decrease in E. coli and Acinetobacter species (P < 0.001, 0.018, < 0.001, and 0.046, respectively) in hematological patients. In surgical patients, Enterobacteriaceae significantly increased (P = 0.012), while non-fermenters significantly decreased (P = 0.007). GPB species from either hematological or surgical wards exhibited no notable changes during the pandemic. GNB resistance increased in hematological patients to carbapenems, amikacin, and tigecycline and decreased in surgical patients to amikacin and cefoxitin (P < 0.001, 0.010, < 0.001, < 0.001, and 0.016, respectively). The study highlights notable shifts in the microbial landscape during the COVID-19 pandemic, particularly in the prevalence and resistance patterns of GNB in hematological and surgical wards.

Evaluation of an automated rapid phenotypic antimicrobial susceptibility testing (ASTar, Q-linea AB) applied directly on blood cultures bottles positive for Gram-negative pathogens.

We evaluated the performance of a new rapid phenotypic antimicrobial susceptibility test (ASTar; Q-linea AB) on Gram-negative bacilli, directly from positive blood cultures bottles. MIC values obtained by the routine reference method (Microscan, Beckman Coulter) were compared to the ones provided by the tested method (ASTar). ASTar demonstrated an overall essential agreement of 98% and a category agreement of 96.1%. The overall rate of major errors and very major errors was 2.5% and 3.3%, respectively. ASTar can represent a rapid, simple, and reliable method to speed up information about antimicrobial susceptibility of Gram-negative pathogens from positive blood culture bottles.

Combined effect of SAR-endolysin LysKpV475 with polymyxin B and Salmonella bacteriophage phSE-5.

Endolysins are bacteriophage (or phage)-encoded enzymes that catalyse the peptidoglycan breakdown in the bacterial cell wall. The exogenous action of recombinant phage endolysins against Gram-positive organisms has been extensively studied. However, the outer membrane acts as a physical barrier when considering the use of recombinant endolysins to combat Gram-negative bacteria. This study aimed to evaluate the antimicrobial activity of the SAR-endolysin LysKpV475 against Gram-negative bacteria as single or combined therapies, using an outer membrane permeabilizer (polymyxin B) and a phage, free or immobilized in a pullulan matrix. In the first step, the endolysin LysKpV475 in solution, alone and combined with polymyxin B, was tested in vitro and in vivo against ten Gram-negative bacteria, including highly virulent strains and multidrug-resistant isolates. In the second step, the lyophilized LysKpV475 endolysin was combined with the phage phSE-5 and investigated, free or immobilized in a pullulan matrix, against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The bacteriostatic action of purified LysKpV475 varied between 8.125 µg ml-1 against Pseudomonas aeruginosa ATCC 27853, 16.25 µg ml-1 against S. enterica Typhimurium ATCC 13311, and 32.50 µg ml-1 against Klebsiella pneumoniae ATCC BAA-2146 and Enterobacter cloacae P2224. LysKpV475 showed bactericidal activity only for P. aeruginosa ATCC 27853 (32.50 µg ml-1) and P. aeruginosa P2307 (65.00 µg ml-1) at the tested concentrations. The effect of the LysKpV475 combined with polymyxin B increased against K. pneumoniae ATCC BAA-2146 [fractional inhibitory concentration index (FICI) 0.34; a value lower than 1.0 indicates an additive/combined effect] and S. enterica Typhimurium ATCC 13311 (FICI 0.93). A synergistic effect against S. enterica Typhimurium was also observed when the lyophilized LysKpV475 at ⅔ MIC was combined with the phage phSE-5 (m.o.i. of 100). The lyophilized LysKpV475 immobilized in a pullulan matrix maintained a significant Salmonella reduction of 2 logs after 6 h of treatment. These results demonstrate the potential of SAR-endolysins, alone or in combination with other treatments, in the free form or immobilized in solid matrices, which paves the way for their application in different areas, such as in biocontrol at the food processing stage, biosanitation of food contact surfaces and biopreservation of processed food in active food packing.

Identification of Microorganism in Infected Wounds by Positively Charged Selective Sensor Array and Deep Learning Algorithm.

Microorganism are ubiquitous and intimately connected with human health and disease management. The accurate and fast identification of pathogenic microorganisms is especially important for diagnosing infections. Herein, three tetraphenylethylene derivatives (S-TDs: TBN, TPN, and TPI) featuring different cationic groups, charge numbers, emission wavelengths, and hydrophobicities were successfully synthesized. Benefiting from distinct cell wall binding properties, S-TDs were collectively utilized to create a sensor array capable of imaging various microorganisms through their characteristic fluorescent signatures. Furthermore, the interaction mechanism between S-TDs and different microorganisms was explored by calculating the binding energy between S-TDs and cell membrane/wall constituents, including phospholipid bilayer and peptidoglycan. Using a combination of the fluorescence sensor array and a deep learning model of residual network (ResNet), readily differentiation of Gram-negative bacteria (G-), Gram-positive bacteria (G+), fungi, and their mixtures was achieved. Specifically, by extensive training of two ResNet models with large quantities of images data from 14 kinds of microorganism stained with S-TDs, identification of microorganism was achieved at high-level accuracy: over 92.8% for both Gram species and antibiotic-resistant species, with 90.35% accuracy for the detection of mixed microorganism in infected wound. This novel method provides a rapid and accurate method for microbial classification, potentially aiding in the diagnosis and treatment of infectious diseases.

The Prediction of LptA and LptC Protein-Protein Interactions and Virtual Screening for Potential Inhibitors.

Antibiotic resistance in Gram-negative bacteria remains one of the most pressing challenges to global public health. Blocking the transportation of lipopolysaccharides (LPS), a crucial component of the outer membrane of Gram-negative bacteria, is considered a promising strategy for drug discovery. In the transportation process of LPS, two components of the LPS transport (Lpt) complex, LptA and LptC, are responsible for shuttling LPS across the periplasm to the outer membrane, highlighting their potential as targets for antibacterial drug development. In the current study, a protein-protein interaction (PPI) model of LptA and LptC was constructed, and a molecular screening strategy was employed to search a protein-protein interaction compound library. The screening results indicated that compound 18593 exhibits favorable binding free energy with LptA and LptC. In comparison with the molecular dynamics (MD) simulations on currently known inhibitors, compound 18593 shows more stable target binding ability at the same level. The current study suggests that compound 18593 may exhibit an inhibitory effect on the LPS transport process, making it a promising hit compound for further research.

Biomarker and proteome analysis of milk from dairy cows with clinical mastitis: Determining the effect of different bacterial pathogens on the response to infection.

Antimicrobial usage (AMU) could be reduced by differentiating the causative bacteria in cases of clinical mastitis (CM) as either Gram-positive or Gram-negative bacteria or identifying whether the case is culture-negative (no growth, NG) mastitis. Immunoassays for biomarker analysis and a Tandem Mass Tag (TMT) proteomic investigation were employed to identify differences between samples of milk from cows with CM caused by different bacteria. A total of 94 milk samples were collected from cows diagnosed with CM across seven farms in Scotland, categorized by severity as mild (score 1), moderate (score 2), or severe (score 3). Bovine haptoglobin (Hp), milk amyloid A (MAA), C-reactive protein (CRP), lactoferrin (LF), α-lactalbumin (LA) and cathelicidin (CATHL) were significantly higher in milk from cows with CM, regardless of culture results, than in milk from healthy cows (all P-values <0.001). Milk cathelicidin (CATHL) was evaluated using a novel ELISA technique that utilises an antibody to a peptide sequence of SSEANLYRLLELD (aa49-61) common to CATHL 1-7 isoforms. A classification tree was fitted on the six biomarkers to predict Gram-positive bacteria within mastitis severity scores 1 or 2, revealing that compared to the rest of the samples, Gram-positive samples were associated with CRP < 9.5 µg/ml and LF ≥ 325 µg/ml and MAA < 16 µg/ml. Sensitivity of the tree model was 64%, the specificity was 91%, and the overall misclassification rate was 18%. The area under the ROC curve for this tree model was 0.836 (95% bootstrap confidence interval: 0.742; 0.917). TMT proteomic analysis revealed little difference between the groups in protein abundance when the three groups (Gram-positive, Gram-negative and no growth) were compared, however when each group was compared against the entirety of the remaining samples, 28 differentially abundant protein were identified including ß-lactoglobulin and ribonuclease. Whilst further research is required to draw together and refine a suitable biomarker panel and diagnostic algorithm for differentiating Gram- positive/negative and NG CM, these results have highlighted a potential panel and diagnostic decision tree. Host-derived milk biomarkers offer significant potential to refine and reduce AMU and circumvent the many challenges associated with microbiological culture, both within the lab and on the farm, while providing the added benefit of reducing turnaround time from 14 to 16 h of microbiological culture to just 15 min with a lateral flow device (LFD).

In situ captured antibacterial action of membrane-incising peptide lamellae.

Developing unique mechanisms of action are essential to combat the growing issue of antimicrobial resistance. Supramolecular assemblies combining the improved biostability of non-natural compounds with the complex membrane-attacking mechanisms of natural peptides are promising alternatives to conventional antibiotics. However, for such compounds the direct visual insight on antibacterial action is still lacking. Here we employ a design strategy focusing on an inducible assembly mechanism and utilized electron microscopy (EM) to follow the formation of supramolecular structures of lysine-rich heterochiral ß3-peptides, termed lamellin-2K and lamellin-3K, triggered by bacterial cell surface lipopolysaccharides. Combined molecular dynamics simulations, EM and bacterial assays confirmed that the phosphate-induced conformational change on these lamellins led to the formation of striped lamellae capable of incising the cell envelope of Gram-negative bacteria thereby exerting antibacterial activity. Our findings also provide a mechanistic link for membrane-targeting agents depicting the antibiotic mechanism derived from the in-situ formation of active supramolecules.

Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria.

Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains of Escherichia coli. We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria. With the help of X-ray structures, this information was used to design inhibitors with activity on efflux-proficient, wild-type strains. Optimization of properties such as solubility, metabolic stability and serum protein binding resulted in compounds having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogens E. coli and Klebsiella pneumoniae. Other favorable properties of the series include a lack of pre-existing resistance in clinical isolates, and no loss of activity against strains expressing extended-spectrum-ß-lactamase, metallo-ß-lactamase, or carbapenemase-resistance genes. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance.

Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention - a comprehensive review.

Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.

Silver Organometallics that are Highly Potent Thioredoxin and Glutathione Reductase Inhibitors: Exploring the Correlations of Solution Chemistry with the Strong Antibacterial Effects.

The antibacterial activity of silver species is well-established; however, their mechanism of action has not been adequately explored. Furthermore, issues of low-molecular silver compounds with cytotoxicity, stability, and solubility hamper their progress to drug leads. We have investigated silver N-heterocyclic carbene (NHC) halido complexes [(NHC)AgX, X = Cl, Br, and I] as a promising new type of antibacterial silver organometallics. Spectroscopic studies and conductometry established a higher stability for the complexes with iodide ligands, and nephelometry indicated that the complexes could be administered in solutions with physiological chloride levels. The complexes showed a broad spectrum of strong activity against pathogenic Gram-negative bacteria. However, there was no significant activity against Gram-positive strains. Further studies clarified that tryptone and yeast extract, as components of the culture media, were responsible for this lack of activity. The reduction of biofilm formation and a strong inhibition of both glutathione and thioredoxin reductases with IC50 values in the nanomolar range were confirmed for selected compounds. In addition to their improved physicochemical properties, the compounds with iodide ligands did not display cytotoxic effects, unlike the other silver complexes. In summary, silver NHC complexes with iodide secondary ligands represent a useful scaffold for nontoxic silver organometallics with improved physicochemical properties and a distinct mechanism of action that is based on inhibition of thioredoxin and glutathione reductases.

Extending the Potency and Lifespan of Antibiotics: Inhibitors of Gram-Negative Bacterial Efflux Pumps.

Efflux is a natural process found in all prokaryotic and eukaryotic cells that removes a diverse range of substrates from inside to outside. Many antibiotics are substrates of bacterial efflux pumps, and modifications to the structure or overexpression of efflux pumps are an important resistance mechanism utilized by many multidrug-resistant bacteria. Therefore, chemical inhibition of bacterial efflux to revitalize existing antibiotics has been considered a promising approach for antimicrobial chemotherapy over two decades, and various strategies have been employed. In this review, we provide an overview of bacterial multidrug resistance (MDR) efflux pumps, of which the resistance nodulation division (RND) efflux pumps are considered the most clinically relevant in Gram-negative bacteria, and describe over 50 efflux inhibitors that target such systems. Although numerous efflux inhibitors have been identified to date, none have progressed into clinical use because of formulation, toxicity, and pharmacokinetic issues or a narrow spectrum of inhibition. For these reasons, the development of efflux inhibitors has been considered a difficult and complex area of research, and few active preclinical studies on efflux inhibitors are in progress. However, recently developed tools, including but not limited to computational tools including molecular docking models, offer hope that further research on efflux inhibitors can be a platform for research and development of new bacterial efflux inhibitors.

Film dressings from Thai mango seed kernel extracts versus nanocrystalline silver dressings in antibacterial properties.

Introduction: The extract from the Mango Seed Kernel (MSK) has been documented to exhibit antibacterial activity against Gram-positive and Gram-negative bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa. This suggests that biomaterials containing MSK extract could be a viable alternative to conventional wound treatments, such as nanocrystalline silver dressings. Despite this potential, there is a notable gap in the literature regarding comparing the antibacterial effectiveness of MSK film dressings with nanocrystalline silver dressings. This study aimed to develop film dressings containing MSK extract and evaluate their antibacterial properties compared to nanocrystalline silver dressings. Additionally, the study aimed to assess other vital physical properties of these dressings critical for effective wound care. Materials and methods: We prepared MSK film dressings from two cultivars of mango from Thailand, 'Chokanan' and 'Namdokmai'. The inhibition-zone method was employed to determine the antibacterial property. The morphology and chemical characterization of the prepared MSK film dressings were examined with scanning electron microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FTIR), respectively. The absorption of pseudo-wound exudate and water vapor transmission rate (WVTR) of film dressings were evaluated. Results: The results showed that 40% of MSKC film dressing had the highest inhibition zone (20.00 ± 0.00 mm against S. aureus and 17.00 ± 1.00 mm against P. aeruginosa) and 20%, 30%, and 40% of MSKC and MSKN film dressings had inhibition zones similar to nanocrystalline silver dressing for both S. aureus and P. aeruginosa (p > 0.05). In addition, all concentrations of the MSK film dressings had low absorption capacity, and Chokanan MSK (MSKC) film dressings had a higher WVTR than Namdokmai MSK (MSKN) film dressings. Conclusion: 20%, 30%, and 40% of MSK film dressing is nearly as effective as nanocrystalline silver dressing. Therefore, it has the potential to be an alternative antibacterial dressing and is suitable for wounds with low exudate levels.

Bioactive and biodegradable cotton fabrics produced via synergic effect of plant extracts and essential oils in chitosan coating system.

Functional antibacterial textile materials are in great demand in the medical sector. In this paper, we propose a facile, eco-friendly approach to the design of antibacterial biodegradable cotton fabrics. Cotton fiber fabrics were enhanced with a chitosan coating loaded with plant extracts and essential oils. We employed Fourier-transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS), UV-Vis spectrophotometry, optical microscopy, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) to characterize the color, structure, and thermal properties of the modified fabrics. The fabrics were found to effectively induce growth inhibition of Gram-positive and Gram-negative bacteria, especially when a synergic system of aloe vera extract and cinnamon essential oil was applied in the coating formulation. Additionally, we observed significant color and weight changes after 5, 10, and 20 days in soil biodegradability tests. Given the straightforward modification process and the use of non-toxic natural materials, these innovative bio-based and biodegradable cotton fabrics show great promise as protective antimicrobial textiles for healthcare applications.