Antimicrobial Research Articles

Unveiling the potent Antimicrobial Photodynamic Therapy in Gram-positive and Gram-negative bacteria – Water remediation with monocharged chlorins

Water pollution is a significant concern worldwide, and it includes contaminants such as antibiotic-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) offers a non-invasive and non-toxic alternative for the inactivation of these microorganisms. So, this study reports the synthesis, structural characterisation, photophysical properties, and aPDT efficacy of cationic free-base and zinc(II) chlorin (Chl) derivatives bearing N,N-dimethylpyrrolydinium groups (H2Chl 1a and ZnChl 1b). The aPDT assays were performed against two bacterial models: Staphylococcus aureus (Gram-(+)) and Escherichia coli (Gram-(–)). The H2Chl 1a and ZnChl 1b distinct’s solubility profile, coupled with their ability to generate singlet oxygen (1O2) under light exposure, (H2Chl 1a, ФΔ = 0.58 <TPP, ФΔ = 0.65 < ZnChl 1b, ФΔ = 0.83) opens up their potential application as photosensitizers (PS) in aPDT. The effectiveness of H2Chl 1a and ZnChl 1b at 1.0 and 5.0 μM in aPDT against S. aureus and E. coli at 500 W.m–2 (total exposure time: 60 –120 min) showed a viability reduction > 6.0 log10 CFU.mL–1. Additionally, KI was used as a coadjuvant to potentiate the photoinactivation of E. coli, reaching the method’s detection limit (> 4.0 log10 RLU). As most of the PS developed to inactivate Gram-negative bacteria are cationic with three or more charges, the fact that the H2Chl 1a and ZnChl 1b with only one cationic charge photoinactivate E. coli at low concentrations and with a reduced light dose, it is an importing discovery that deserves further exploration. These monocharged chlorin dyes have the potential for water remediation.

Extract from Psidium guineense Sw leaves: An alternative against resistant strains of Staphylococcus aureus

Psidium guineense SW., commonly known as sour guava, is used in traditional medicine to address diverse health issues, such as inflammation, infections, and gastrointestinal disorders. Although previous research has highlighted the antimicrobial properties of the root extract and the antioxidant potential of its fruits, information regarding the activities associated with the leaf extract is lacking. The aim of the study was to use the traditional knowledge of the biological properties of P. guineense and investigate its antimicrobial activity, mechanism of action, synergistic effects, and antivirulence activity against Staphylococcus aureus. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined for S. aureus, including antibiotic-resistant isolates. The synergy between the extract and antibiotics was evaluated. A growth curve was constructed for S. aureus treated with the extract. The anti-hemolytic activity was assessed by inhibiting hemolysis in human blood, and the inhibition of staphyloxanthin (STX) was examined. The extract effectively inhibited all strains with MIC and MBC values ranging from 256 to 512 µg/mL and 512 to 1024 µg/mL, respectively. Antimicrobial synergy experiments demonstrated the enhanced effectiveness of antibiotics, especially ciprofloxacin, when combined with the P. guineense extract, especially with ciprofloxacin, resulting in complete synergy against all S. aureus strains. In growth curve tests, the extract inhibited growth at MIC of 256 µg/mL within 8 h and significantly delayed it at MIC/2 (128 µg/mL) within 12 h. In antivirulence tests, the extract effectively reduced hemolysis and STX production by S. aureus at MIC and MIC/2, indicating its potential as an antimicrobial agent with antivirulence properties. The extract effectively inhibited S. aureus, including drug-resistant strains with low MIC and MBC values, exhibiting strong antimicrobial and synergistic properties with antibiotics. also In addition, the extract accelerated recovery by limiting bacterial growth and exhibiting antivirulence capabilities, reducing the severe symptoms of S. aureus infections.

Cholecalciferol Exhibits no Antibacterial Effect on Staphylococcus aureus and Escherichia coli: an in-vitro Study.

The pleiotropic effect of cholecalciferol (vitamin D3) has gained significant momentum and has been explored widely. The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli. An in-vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method. The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli. This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents.

Novel S-scheme WO3/ZnO-modified g-C3N4 heterojunction for optimizing norfloxacin photodegradation condition via DoE: Synthesis, characterization, and mechanism evaluation

Norfloxacin, an antimicrobial agent, has been recurrently observed in municipal wastewater facilities, posing a conjectured threat to human health and environmental integrity. Herein, novel ternary heterojunction of WO3/ZnO-modified g-C3N4 was fabricated utilizing the impregnation technique for the organic pollutant degradation, presenting a significant challenge. XRD, XPS, TEM, HR-TEM, SEM, EDS, BET, EIS, Mott-Schottky, ESR, PL, photocurrent, and DRS techniques were used to explore the structural, morphological, textural, and optical features of the produced materials. In this ternary system, ZnO served as an electron transfer conduit, facilitating the formation of a heterojunction interface between the semiconductor constituents. Establishment of the S-scheme within the charge transfer dynamics of the heterojunction markedly augmented charge separation, enhancing the efficacy of the photocatalytic activity. Under optimized conditions via the DoE software (i.e.; photocatalyst dosage: 0.54 g/L, NOR concentration: 25.87 mg/L, Irradiation time: 41.71 min and pH: 6.9), 97.19 % of NOR elimination was achieved by the optimized 20-WZC photocatalyst with a pseudo-first-order kinetic model (k = 0.05 min−1). ESR data, alongside quenching experiments, corroborated the pivotal involvement of O2−, OH, and h+ in the NOR degradation mechanism. The investigation of NOR's potential decontamination pathways was performed using HRLC-MS. TOC analysis revealed a significant mineralization of 82.45 %, indicating the conversion of NOR into H2O, CO2, and other degradable substances. The optimized photocatalyst also demonstrated notable efficiency in the degradation of Tetracycline: 98.15 %, Ciprofloxacin: 93.27 %, Methylene Blue: 98.89 %, and Enrofloxacin: 91.54 % pollutants. The photocatalytic activity of the 20-WZC catalyst remained consistently high, without significant reduction, over five successive cycles.

Comparison of the Efficacy of Cephalosporins and Non-cephalosporins in Preventing Surgical Site Infections in Colorectal Surgery Patients: An Updated Systematic Review and Meta-Analysis.

This study aims to compare the efficacy of cephalosporin and non-cephalosporin antibiotics in preventing surgical site infections (SSIs) in patients undergoing colorectal surgery, providing a scientific basis for the selection of perioperative antibiotics through systematic review and meta-analysis. Adhering to the PRISMA guidelines, this research employed an extensive literature search strategy across multiple databases to identify relevant studies, including randomized controlled trials (RCTs) and observational studies. Inclusion criteria were studies on adults undergoing colorectal surgery who received preoperative prophylaxis with either cephalosporin or non-cephalosporin antibiotics. Exclusion criteria included preoperative diagnosis of infectious diseases and preoperative use of antimicrobial agents. Meta-analysis was conducted using RevMan 5.3 software to assess the effectiveness of both antibiotic classes in preventing SSIs, including subgroup analyses. Eight studies met the inclusion criteria, comprising 872 patients. Meta-analysis revealed that the incidence of SSI in the cephalosporin group was lower than in the non-cephalosporin group (14.8% vs 25.1%), with statistical significance (OR = 1.94, 95% CI: 1.38-2.74, PP = =0.0001). However, no significant difference in SSI risk was observed between the groups within 30days (OR = =1.92, 95% CI: 1.08-3.42). Subgroup analysis indicated that higher-quality studies were associated with larger effect sizes. This study suggests that cephalosporin antibiotics may be superior to non-cephalosporins in preventing SSIs following colorectal surgery, especially in the short term. However, their long-term efficacy in SSI prevention may be similar. The selection of perioperative antibiotics should consider factors such as the antimicrobial spectrum, pharmacokinetic properties, and bacterial resistance.

Essential oils cause membrane disruption and autoaggregation of MDR Acinetobacter baumannii cells

Essential oils are promising antimicrobial agents against various bacteria. The aim of the study was to examine anti-Acinetobacter baumannii activity of nine essential oils and to elucidate essential oil mechanisms of action against this. In total, 8 out of 9 examined different essential oils exhibited activity against multidrug-resistant (MDR) A. baumannii isolates. The best anti-A. baumannii activity expressed Thymus serpyllum, Satureja hortensis and Oreganum majorana essential oil (MBC 1.29 to 2.58 µg mL−1), while essential oils of Menta x piperita, Hyssopus officinalis, Foeniculum vulgare and Artemisia dracunculus expressed the same effect in higher concentrations (1.80 to 3.80 µg mL−1). The effect of Juniperus sabina, Juniperus sibirica and S. hortensis essential oils against A. baumannii is for the first time reported here. The mechanisms of Myrtus communis, Eucalyptus camaldulensis, S. hortensis and T. serpyllum essential oils were further examined. The essential oil treatments led to concentration dependent leakage of biomolecules form the cells, causing an increase in the concentrations of lipids, carbohydrates, and proteins in the suspensions. Microstructural observations confirmed the essential oil effect on cell membranes and disruption the membrane integrity, with obvious leakage of intercellular substance, collapsed cells with perforations, debris presence and autoaggregated cells. The subinhibitory concentrations of oils did not obviously changed protein patterns determined by SDS-PAGE. These results indicate that the essential oils, particularly T. serpyllum, S. hortensis, M. communis and E. camaldulensis express its anti-A. baumannii activity via membrane disruption and increased membrane permeability, representing very promising alternative antibacterial agents against MDR wound isolates.

Zn(II) enhances the antimicrobial effect of chloroxine and structural analogues against drug-resistant ESKAPE pathogens in vitro

The emerging antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, pose a continuous threat to global health. In this study, we explored metalloantibiotics as promising therapeutics and innovative antimicrobial agents. The role of metal in the antimicrobial activity of chloroxine (5,7-dichloro-8-hydroxyquinoline), as a metalloantibiotic, was investigated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and UV–visible spectroscopy and PAR (4-(2-pyridylazo)-resorcinol) competition assays. Both chloroxine and its structural analogues exhibited increased antibacterial potency against Gram-positive bacteria compared to Gram-negative bacteria. The introduction of exogenous manganese or zinc ions significantly boosted chloroxine’s antibacterial efficacy against Gram-negative bacteria, including the notorious ESKAPE pathogens. However, the enhanced antibacterial activity induced by zinc ions could be negated in the presence of copper or ferrous iron ions, as well as changes in oxygen availability, highlighting the involvement of proton motive force, oxidative and antioxidative systems. Notably, chloroxine effectively inhibited the enzymatic activity of superoxide dismutase (SOD). In addition, chloroxine could reverse polymyxin and carbapenem resistance in E. coli in vitro. Therefore, these results suggested that chloroxine with zinc ions are promising therapeutics and antibiotics potentiator to combat multidrug-resistant ESKAPE pathogens

Extrapulmonary Mycobacterium abscessus Infections, France, 2012-20201.

Mycobacterium abscessus infection is challenging to treat. Extrapulmonary M. abscessus infections (EP-MAB) are less common than pulmonary M. abscessus infections. To evaluate treatment regimens, we retrospectively analyzed consecutive microbiologically confirmed EP-MAB cases diagnosed in France during 2012-2020. We studied 45 patients with EP-MAB, including 14 bone and joint infections, 10 skin and soft tissue infections, and 8 lymph node infections. Most (62%) patients had no reported immunodeficiency. In 27 patients, EP-MAB followed healthcare-associated (44%) or environmental (16%) injuries. Of the 45 isolates, 25 were subspecies abscessus, 10 bolletii, and 9 massiliense; 1 was unidentified. Cure was achieved for 36 (80%) patients who received a median antimicrobial regimen of 6 months; 22 (55%) also underwent surgery. Four patients died, and 5 were unavailable for follow-up. EP-MAB predominantly affects immunocompetent patients after an injury; outcomes are favorable. We propose a >6-month regimen of antimicrobial therapy with consideration for surgery and regular patient reassessment.

Molecular insights into antimicrobial resistant Staphylococcus aureus strains: A potential zoonosis of goat origin

Antimicrobial-resistant (AMR) Staphylococcus aureus (S. aureus) strains have attained global attention due to their life-threatening zoonotic nature. Being a member of ESKAPE group, S. aureus has an ability to escape the biocidal action of antimicrobial drugs. The current study investigated the prevalence and molecular characterization of methicillin-resistant S. aureus (MRSA), β-lactam-resistant S. aureus (BRSA), aminoglycoside-resistant S. aureus (ARSA), tetracycline-resistant S. aureus (TRSA), and fluoroquinolones-resistant S. aureus (FRSA) associated with goat subclinical mastitis (SCM). Furthermore, the antimicrobial resistance and susceptibility profile of various antibiotics and non-antibiotics (NSAIDs, nisin, N-acetylcysteine, vitamin-C) along with their possible role in modulating the antibiotic resistance of MDR isolates was also investigated. A total of 768 goat milk samples were subjected to California mastitis test for SCM followed by bacteriological and molecular characterization of S. aureus. Moreover, in-vitro susceptibility of resistant antibiotics, non-antibiotics, and their combination against MDR S. aureus were conducted through well diffusion and broth microdilution assays. The results depicted that 55.47% and 26.82% of milk samples were positive for SCM and S. aureus, respectively. The molecular assay confirmed 35.92% of isolates as MRSA, 45.63% as BRSA, 50.49% as ARSA, and 32.52% but no isolate was confirmed as FRSA on molecular basis. The multidrug resistance was observed in 62.13% and 47.09% isolates, respectively. Molecular characterized MDR S. aureus revealed high homology of study isolates with the isolates of neighboring countries like India, Korea, Iran, and China. Antimicrobial susceptibility trials on well diffusion assay showed higher efficacy of different non-antibiotics with resistant antibiotics as penicillin with ketoprofen and gentamicin with flunixin meglumine while oxytetracycline with N-acetylcystiene. The synergy testing by checkerboard assay revealed synergistic activity of penicillin with ketoprofen, gentamicin with flunixin meglumine, and oxytetracycline with N-acetylcysteine. The current study highlighted the emergence and spread of AMR S. aureus strains from goat SCM and provided insights into possible drug repurposing of various non-antibiotics to modulate the multidrug resistance of S. aureus which will be helpful in devising the therapeutic options and control measures for this pathogen.

Change starts at home: summary of the 2023 inaugural Small Animal Antimicrobial Stewardship Workshop for US Veterinary Schools.

Small animal antimicrobial stewardship (AS) is emerging as a priority area in the global battle against antimicrobial resistance. Veterinary practices have limited support for implementation of AS programs, and even within veterinary schools, efforts are largely siloed and often limited in scope. Increased collaboration is needed to support and unify AS and infection prevention and control efforts, and to identify priorities for continued research. To address this, a 2-day in-person small animal AS workshop was held in August 2023. Delegates representing 23 US veterinary schools and 4 corporations/government agencies gathered for a series of lightning talks and focused group discussions in 3 domains: implementation of clinical AS programs, research opportunities and needs, and education. The workshop's goal was to identify and propose solutions for AS challenges. Meeting discussion identified a lack of resources and training as the greatest barriers to hospital AS program advancement and suggested creating standards for AS programs and a road map to support program development. Assessing antimicrobial treatment effects and performing studies to establish necessary treatment durations were considered the highest research priorities. Integrated educational practices were recommended to support unified messaging of AS concepts between preclinical and clinical training. The development of strategies to implement these suggestions was delegated to working groups with a goal to continue meeting biennially as a large group. Sharing news of these efforts is considered integral to heightening awareness and promoting implementation of AS practices moving forward in academic, specialty, and primary care settings.

Evaluation of the antimicrobial and anticancer properties of Myrrh resin extract and its application in cacao beverages

Due to the potential health risks of synthetic food preservatives, there has been a noticeable increase in interest in finding natural food preservatives during the past few decades. The goal of this study was to investigate the use of a natural extract of Myrrh resin as an antimicrobial agent. The antioxidant properties of Myrrh resin extract (MRE) were analyzed using HPLC and GC–MS. The results showed that MRE contained potent antioxidant compounds, including 19 compounds, with the dominant compound being kaempferol, which had the highest value of 1896 µg/g. Quercetin was found to be the second most abundant compound, with a value of 520 µg/g.The efficacy of MRE as an antimicrobial agent against both Gram-positive and Gram-negative bacteria was tested, and its application in Cacao beverages was also studied. The results demonstrated that MRE was highly effective against all the tested bacteria both in vitro and in the total bacterial count of the produced cacao beverage. Additionally, the fungi in the cacao beverage were completely inhibited at all tested concentrations of MRE. The total soluble solids (TSS), pH value, and acidity of the produced untreated, treated cacao beverage with MRE and sodium benzoate were carried out, and all values mentioned were almost the same, with no differences noted. The sensory evaluation of Cacao beverage showed that the MRE had a minor impact on taste, odor, color, and texture of the produced cacao beverage in comparison with the control sample, which was very acceptable for judgments and recorded 95, 88, and 94 for the control and treated samples, respectively. Furthermore, the anti-cancer properties of MRE were evaluated, revealing significant cytotoxic effects against colon cancer (HCT) and liver cancer (HEPG2) cell lines. The IC50 values for HCT and HEPG2 cells were 55.69 µg/ml and 70.78 µg/ml, respectively, indicating the potential of MRE as an anti-cancer agent.

Pattern of Surgical Antibiotic Prophylaxis in a Tertiary Care Hospital of Bangladesh

Background: Surgical Site Infection (SSI) is a common form of hospital-acquired infection and major cause of postoperative illness accounting for approximately a quarter of all nosocomial infections. As a result, surgical antibiotic prophylaxis is now considered essential to conventional surgical procedure in order to reduce surgical site infections and improve postoperative recovery. The misuse and overuse of antibiotics has led to an increase in treatment costs and the emergence of antimicrobial resistance. The goal of the study is to identify the pattern of prophylactic antibiotic prescriptions for different surgical operations. Materials and methods: A retrospective observational study was conducted among 600 patients undergoing different surgeries in a tertiary care hospital of private setting in Dhaka, Bangladesh from July 2023 to December 2023. The demographic data, types of surgery, types of therapy, choice of antibiotic along with dosage formulations were collected. Results: Out of 600 patients, 245 (41%) were male and 355 (59%) were female. Highest bulk of patients were from Department of General Surgery (47.5%), followed by Department of Obstetrics &amp; Gynecology (24.16%) and Department of Otolaryngology (16.7%). Surgical prophylactic antibiotic was used in all 600 patients, and all antibiotics were given in intravenous route (100%). Almost 505 patients (84.2%) had received ceftriaxone as antimicrobial agent. Ceftriaxone with metronidazole or gentamicin and Cefuroxime with metronidazole or amikacin drugs combination were given to 75 (12.5%) and Cefuroxime, Amikacin, Metronidazole drugs combination were given to 20 patients (3.3%). 3rd generation cephalosporin, Ceftriaxone, was the most commonly prescribed antibiotic as monotherapy (94.3%), followed by 2nd generation cephalosporin, cefuroxime (4%). Conclusion: Ceftriaxone was the preferred antibiotic for surgical prophylaxis. Existence of an antimicrobial guideline along with antibiotic stewardship program in every hospital could be helpful for prescribers to play role in containment of antimicrobial resistance. EWMCJ Vol. 12, No. 1&amp;2, January-July 2024: 70-74

Antimicrobial Activity of Chitosan from Different Sources Against Non-Saccharomyces Wine Yeasts as a Tool for Producing Low-Sulphite Wine

Chitosan is used as an antimicrobial agent in different agri-food applications; in winemaking, the use of chitosan from Aspergillus niger is authorized, but other sources of chitin, and consequently of chitosan, are available, such as crustaceans and insects. This work investigates the antimicrobial efficiency of chitosan from crustaceans and insects (Hermetia illucens) against non-Saccharomyces yeasts in wine. For this aim, the first step was to evaluate the effect of crustacean chitosan, tested both alone and in combination with low sulphur dioxide (SO2) concentrations, on the cell viability of 20 non-Saccharomyces strains in the first step of fermentations inoculated with each strain. Furthermore, the strain resistance to crustacean- and insect-based chitosan was evaluated in agarized media, together with the addition of different antimicrobial concentrations. Finally, the efficiency of different antimicrobial treatments was evaluated during laboratory-scale fermentations inoculated with a selected S. cerevisiae strain. The tested strains exhibited medium/high resistance to the chitosan; in some cases, the behaviour varied in the function of species/strain, and only four strains exhibited different resistance levels, depending on the chitosan source. The addition of chitosan alone during fermentation inoculated with S. cerevisiae showed lower antimicrobial activity than SO2, but the combined use with SO2 showed a better effect than chitosan alone. The evaluation of the suitability of chitosan obtained from a sustainable source, such as insects, will allow us to give new information on the future applications of this natural compound for the production of wine with low sulphite content.

Non-surgical management of methicillin-sensitive Staphylococcus aureus bacteremia-related mediastinitis

Background: Acute mediastinitis is rarely caused by haematogenous spread of a remote infection. In this respect, since the only medical therapy is usually unsuccessful, treating acute mediastinitis with no source of infection detected is very challenging and management not standardized. In this case report, we describe non-surgical management experience of acute mediastinitis caused by methicillin-sensitive Staphylococcus aureus. Case presentation: In a 79-year-old man judged not eligible for cardiac surgery, we attempted the infection source control through vacuum-assisted closure therapy, together with antimicrobial therapy. We observed gradual clinical, laboratory and radiologic improvements: reduced swelling and normalization of the white blood cell count and C-reactive protein level were associated with reduction in size of a periaortic abscess. Conclusion: We managed a clinical condition with high mortality risk with chronic antimicrobial therapy alone, a strategy that is rarely considered. With this medical strategy we achieved an optimal response to a clinical picture that does not allow any other approach.

Transcatheter valve replacement as rescue treatment for heart failure in infective endocarditis. A multinational series.

Abstract Background Transcatheter valve replacement (TVR) could be a therapeutic alternative for refractory heart failure in patients with infective endocarditis (IE) unsuitable for open surgery. However, evidence of tis use in this scenario is limited to isolated case reports. Purpose We aimed to describe the clinical characteristics and outcome of IE patients in whom a TVR was performed during the active phase of infection in a multinational case series. Methods This retrospective study was conducted in 23 referral hospitals for IE and TVR procedure in 8 countries. All consecutive adult patients (≥18 y) with definite IE in whom a TVR was performed during antimicrobial treatment of within the 3 three months after its withdrawal were included. The inclusion period was between July 2011 and July 2023. Baseline, IE-related, TVR-related, outcome and follow-up (min. 3 months) variables were collected. Results Forty-five patients [median age 74 years (IQR 64 – 82), 35 males (78%), median Charlson comorbidity index 6 (4 – 7) points] were included in the study: 42 aortic TVR, 2 mitral TVR and 1 tricuspid TVR. In 20 patients (44%) TVR was performed on a native valve and in 25 on a prosthetic valve. The most frequent microorganisms causing IE were streptococci (n=16, 36%), staphylococci (n=13, 29%) and enterococci (n=5, 11%). Acute heart failure was present in 41 (91%). Of them, 23 (51%) developed acute pulmonary oedema or cardiogenic shock. The main reasons for excluding open surgery were: high surgical risk [n=39, 87%; median EuroSCORE 17 (9 – 28)] and technical impossibility (n=3, 7%). TVR was performed during antimicrobial treatment in 27 cases (60%) [median 25 (13 – 54) days after initiation] and within the first three months after its completion in 18 (40%) [median 25 (17 – 68) days after discontinuation]. Four patients (9%) died during admission. Over a median follow-up of 10 (6 -30) months, 7/41 patients (17%) died and there were 2/41 (5%) relapses, one of which required open valve replacement surgery 17 days after TVR procedure. Two other patients underwent open surgery due to paravalvular leaks (11 and 44 days after TVR). All cases of relapse and open surgery occurred when TVR was performed during antibiotic treatment. Conclusion TVR could be an option as rescue treatment for heart failure in selected IE patients unsuitable for open surgery. This represents a paradigm shift in the management of IE and may change the natural history of the disease in patients who would otherwise die.

Evaluation of anti-biofilm and anti-virulence effect of zinc sulfate on Staphylococcus aureus isolates

Staphylococcus aureus produces a plethora of virulence factors to invade and establish infections in the host system, and biofilms are more resistant to antibiotics than planktonic cells. In this study, we aimed to investigate the anti-virulence and anti-biofilm potentials of zinc sulfate against S. aureus isolates. The synergistic effect of zinc sulfate in combination with antibiotics on S. aureus was characterized using the checkerboard method. The influence of zinc sulfate on biofilm formation and virulence factors production by S. aureus was experimentally assessed. RT-qPCR was used to investigate the effect of zinc sulfate on the expression of biofilm-related genes. Zinc sulfate exhibited good antibacterial activity against S. aureus with a MIC of 128 µg/ml against all tested isolates. Also, the findings indicate a synergistic effect of a combination of zinc sulfate and antibiotics against the tested isolates. Zinc sulfate at 256 µg/ml concentration inhibited biofilm formation for all isolates. The expression of biofilm-related genes was significantly repressed in zinc sulfate-treated bacteria compared to untreated cells. Zinc sulfate could inhibit the hemolytic ability of S. aureus. Moreover, zinc sulfate-treated bacteria exhibited a significant decrease in coagulase and catalase activity relative to control untreated S. aureus. Our results support that zinc sulfate is a potential antimicrobial and anti-virulence agent against S. aureus infections.

Synthesis and antimicrobial activity of yttrium-doped cerium oxide nano-composite against wound pathogen

Abstract Nanocomposite materials have attracted considerable interest in several disciplines owing to their distinctive characteristics and possible uses. The primary objective of this study was to synthesize and characterize a nanocomposite material consisting of cerium that has been doped with yttrium. The shape, structure, and properties of the synthesized nanocomposite was characterized using various characterization techniques including ultraviolet spectrophotometry, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), zeta potential measurements, dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR).The antibacterial activity of the nanocomposite was assessed against a range of pathogenic bacteria including Gram-positive bacteria - Enterococcus faecalis, Staphylococcus aureus, and Gram-negative bacteria- Escherichia coli, Pseudomonas aeruginosa using standard microbiological techniques. The results indicate that the nanocomposite possesses strong antibacterial properties against a wide range of microorganisms, showcasing its potential as a highly effective antimicrobial agent for diverse applications in the biological, environmental, and industrial fields. Hemolysis is the process of red blood cell destruction, resulting in the release of hemoglobin into the surrounding fluid. In this study, 0.7:0.3M nanocomposite had showed effective biocompatibility with less than 5%. Furthermore, this particular composite remained identical in different time intervals, while other composites would normally fluctuate. Research has shown that meticulous material design and surface modification can reduce the harmful effects on red blood cells, hence improving the safety of nanocomposite for therapeutic purposes. In summary, this study offers valuable information on the creation, analysis, and assessment of nanocomposite materials with antimicrobial properties.

Combined Phase 1/2a Initial Clinical Safety Trials and Proof-of-Concept Assessment of a Novel Antimicrobial Peptide KSL-W Anti-Plaque Chewing Gum.

The effective control of dental plaque is crucial for oral health, given that pathogenic bacteria in plaque are the primary cause of dental caries. Current antimicrobial agents, although effective, disrupt the oral microbiome and lead to oral dysbiosis, hindering efforts to curb dental caries. Novel antimicrobial peptides offer a promising solution due to their selective bactericidal activity against cariogenic bacteria. This study explores the initial safety and efficacy of KSL-W formulated into chewing gum through a Phase 1 and 2a clinical trial. The combined trial, approved by the FDA, follows a double-blind, randomized, placebo-controlled design. Phase 1 assessed safety with single doses (2-100 mg), whereas Phase 2a explored both safety and proof of concept in reducing oral bacteria with multiple doses (4-75 mg). Besides adverse events (Phase 1), outcome measures included whole-mouth plaque and gingival index scores and bleeding on probing (Phase 2a). KSL-W demonstrated safety in both phases, with no severe adverse events. The proof-of-concept analysis revealed a decrease in plaque and gingival inflammation, particularly at doses ≥ 20 mg. The 30 mg dose appeared to yield optimal effects without any adverse reactions in subjects. Results from this study indicate that KSL-W is safe for use in humans and provides initial evidence of its potential efficacy in reducing plaque and gingival inflammation. Further research is essential to determine optimal usage and ultimate safety, and to assess its potential in diverse populations. The trial is registered with the FDA (Trial Registration Number: NCT01877421). The clinical trials were registered in the clinicaltrials.gov database under the title "Safety and Tolerability of Antiplaque Chewing Gum in a Gingivitis Population" and the identifier number is NCT01877421. The URL for accessing the study in clinicaltrials.gov is https://clinicaltrials.gov/study/NCT01877421?intr=Antiplaque%20chewing&rank=1.

Association of gut microbiota imbalance with risk of postoperative infections in patients with left ventricular assist device

Abstract Background Infections are the most common complications following left ventricular assist device (LVAD) implantation and associated with adverse events. Gut microbial imbalance may predispose to mucosal colonization with pathogens, resulting in a risk of subsequent serious infections. However, it remains unclear whether gut microbiota imbalance is associated with postoperative infections in patients with LVAD. Purpose The aim of this study was to investigate whether gut microbiota imbalance was associated with postoperative infections in patients with LVAD. Methods We prospectively examined 22 consecutive LVAD patients who were admitted to a university hospital for routine check-ups and had stool cultures taken between March 2022 and December 2023. All patients had no signs of infection. The patients were divided into two groups according to positive (normal bacterial flora and other bacteria including Streptococcus viridans, Klebsiella, or Extended-spectrum β-lactamase Escherichia coli; n = 7) and negative (normal bacterial flora only; n = 15) for stool culture. The primary outcome was serious infection requiring hospitalisation treated with intravenous antimicrobial agents. Results Patients were predominantly male (68%) and the median age was 49 (interquartile range [IQR] 29-58) years. There were no significant differences in age, sex, primary aetiology of heart failure, type of LVAD devices, time on LVAD support, the history of infection, or antibiotics use within six months between the groups. During a median follow-up period of 316 days (IQR 242-559), the primary outcome occurred in seven patients (32%), including four hospitalisation for driveline infections, two pneumoniae and bacterial bloodstream infections, and one lung abscess and bacterial bloodstream infection. Kaplan–Meier analysis showed that the adverse events more frequently occurred in LVAD patients with positive for stool culture (P = 0.010) (Figure). A multivariable Cox regression analysis showed that positive for stool culture was independently associated with an increased subsequent risk of the primary outcome (hazard ratio 6.99, 95% confidence interval 1.17-41.7, P = 0.033), even after adjustments for age, male, body mass index, diabetes, INTERMACS profile, mechanical circulatory support, serum creatinine, serum albumin, and white blood cell count, which are known to be strong determinants of worse clinical outcomes in patients with LVAD. Conclusions In patients with LVAD, gut microbial imbalance was associated with subsequent serious infections. These findings suggest that the screening of stool culture might be useful for early identification of high-risk patients for infectious complication after LVAD implantation.

Tryptamine‐Derived Schiff Bases: Potent Antimicrobial Agents and Evaluation of Cytotoxicity, ADME and DNA Binding Properties

Inspired by the fact that the introduction of indole pharmacophore in organic scaffolds could enable interesting pharmacological properties, the series of novel tryptamine‐derived Schiff bases was synthetized. Tryptamine was used as a source of indole pattern, as well as an example of biogenic amines which chemical transformations lead to the compounds with prominent biological activities. The obtained results for antimicrobial activity against a range of bacterial and fungal strains and cytotoxic activities have revealed that Schiff base TSB4 combining the tryptamine and p‐nitro aryl patterns in the structure showed better antifungal activity at low concentrations than standard drug Fluconazole, while compound TSB6 with molecular scaffold composed from tryptamine and quinoline moieties showed certain cytotoxic effect on HCT‐116 cell line with a strongly expressed selectivity about healthy fibroblast cells, MRC‐5. For these two selected compounds, additional ADME analysis and DNA interactions were performed. to obtain better insight into their pharmacokinetics and determination of binding mode for DNA molecules. As results suggested, strong binding of examined compounds to CT‐DNA was observed, while the ADME screening showed that selected compounds possess suitable physicochemical properties for oral bioavailability and druglikeness.