Antimicrobial Research Articles

Lichen and its Microbiome as an Untapped Source of Anti-biofilm Compounds.

Lichen substances have been firstly described in the 1870s and most of them have been evaluated for their activity on planktonic microorganisms (bacteria and fungi). More recently, microorganisms colonizing the lichen thallus have been isolated and identified giving access to a wild diversity of culturable microorganisms. The increasing research in lichens associated microbiome in recent years, has emphased a wide range of metabolites as a potential source of bioactive compounds. In parallel, humans are facing microbial resistance to conventional antimicrobial drugs. One of the reasons is the biofilm lifestyle of microorganisms. Indeed, the aggregation of microbial communities inside biofilms is now well-known and characterized and some possible ways to fight and destroy biofilms are identified (quorum sensing inhibitors,…). The present review aims to summarize the anti-biofilm potential of lichen metabolites and those from their associated microorganisms (bacteria and/or fungi). Are the metabolites isolated from lichens and their associated fungi displaying any anti-biofilm activity? This literature synthesis highlights the metabolites of interest as new anti-biofilm drugs and shows the lack of current biological research dealing with biofilm and lichen metabolites. Only two lichen metabolites, usnic acid and evernic acid, have been evaluated both as antifungal and antibacterial biofilm compounds.

Therapeutic drug monitoring for antimicrobial agents for people living with HIV (TAP)

Background Antimicrobial resistance (AMR) is a growing health concern, particularly in Africa, and is predicted to be the leading cause of death after cancer by 2050. Factors like overuse or inappropriate use of antibiotics, contribute to this crisis. People living with HIV (PLWH) are particularly vulnerable to AMR with potential drug-drug interactions between antiretroviral and antimicrobial agents against common organisms like Mycobacterium tuberculosis. There is limited data on the concentrations of commonly used antimicrobial agents in people living with HIV in resource-limited settings. Therapeutic Drug Monitoring (TDM) offers a promising approach to optimize antibiotic dosing and improve treatment outcomes for those with sub-optimal drug concentrations. TDM has been recommended for PLWH on anti-tuberculosis treatment due to sub-optimal drug concentrations found in a significant proportion of those with TB. Objectives The main objectives of this study are to determine the concentrations of selected antimicrobial agents in people living with HIV requiring antimicrobial therapy and to assess the utility of therapeutic drug monitoring in achieving therapeutic targets for PLWH receiving rifampicin and isoniazid for the treatment of tuberculosis Methods This prospective observational study will enroll adult PLWH receiving amoxicillin, azithromycin, ciprofloxacin, rifampicin, isoniazid, or ceftriaxone. Concentrations of these antibiotics will be measured locally using validated liquid chromatography mass spectrometry methods and high-performance liquid chromatography with ultraviolet detection. TDM with dose adjustment will be performed in a subset of participants on TB treatment. Pharmacokinetic parameters will be estimated using non-linear mixed effects models. Results This study was reviewed and approved by the research and ethics committee in February 2024. Enrolment is projected to begin by August 2024. Conclusions We anticipate that the findings from this research will characterize pharmacokinetic and pharmacodynamics relationships to predict treatment response for optimal antimicrobial therapeutic and anti-tuberculosis dosing among people living with HIV (PLWH). Clinical registration The study is registered with Pan African Clinical Trials Registry, registration number PACTR202409710100607, registration date 07 August 2024, pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31764

Vanadium complexes as potential metal-based antimicrobial drugs.

Radical increase of antibiotic resistance among microbes has become a serious problem for clinics all over the world that has led to the need for search of novel types of antimicrobial drugs. Each year, researchers synthesize a multitude of compounds in pursuit of identifying potential chemotherapeutic agents through diverse methodological evaluations. Among the vast array of biologically significant compounds, coordination compounds exhibit a broad range of activities within biological systems. Chelation, in particular, induces significant alterations in the biological properties of ligands and the metal component, contributing to their efficacy. Chelation increases the lipophilicity of metal complexes as a result of which they are easily absorbed by the microorganisms, thus leading to their easy passage across cell membrane. The research and development in the field of metallodrugs can be advantageous to overcome the problem encountered in antibiotic resistance. The multifaceted involvement of vanadium relative to other biometals within biological systems, coupled with its comparatively lower toxicity, underscores its utility in the advancement of novel metal-based therapeutic agents. This review aims to delineate the biological significance of V(V/IV/III) complexes as antimicrobial agents. The amassed data indicate a correlation between the potency of vanadium complexes as antimicrobial agents and the oxidation state of the metal, with III being the least toxic and V representing the most toxic oxidation state of vanadium.

Tailoring Synergistic Polylactic Acid–Based Nanocomposites for Sustainable Antimicrobial Fruit Packaging

ABSTRACTThe rising demand for sustainable and antimicrobial packaging materials has fuelled innovations in polymer‐based solutions, especially in the preservation of fresh fruit to reduce food waste and enhance food safety. This review delves into the advancement and refinement of nanocomposites based on polylactic acid (PLA) for sustainable antimicrobial fruit packaging, emphasising the synergistic effects of combining PLA with nanofillers and antimicrobial agents, such as metal and metal oxide nanoparticles, plant extracts and essential oils (EOs) and carbon nanomaterial. By elucidating the synergistic effects that emerge from these combinations, this review examines the ability to enhance mechanical and antibacterial properties of PLA, followed by a review of the recent changes in sustainable fruit packaging solutions that integrate technological features and environmental considerations. Ultimately, this review provides a comprehensive overview of the advancements in PLA‐based antimicrobial packaging, offering insights on the environmental benefits of integrating antimicrobial functionality into PLA‐based materials and the future of sustainable packaging for fruit preservation.

Current knowledge of vertebral osteomyelitis: a review.

As life expectancy increases worldwide, the elderly population in every country is growing in both the size and proportion. This review aims to provide a comprehensive overview of the microbiology, clinical presentation, diagnostic strategies, and therapeutic approaches to vertebral osteomyelitis, summarizing the latest evidence to guide effective treatment. A comprehensive literature search was conducted using the Medline and Embase databases to identify relevant studies on vertebral osteomyelitis. The search included the following keywords: "vertebral osteomyelitis," "spinal infection," "discitis," "spondylitis," " spondylodiscitis," and "spinal epidural abscess." Both retrospective and prospective studies, case series, and reviews were considered. This condition is commonly caused by bacteria such as Staphylococcus aureus or gram-negative bacilli, but can also be caused by other pathogens like fungi and parasites. The onset of vertebral osteomyelitis is insidious, with low specificity in clinical manifestations, often making early diagnosis difficult. Delayed or inadequate treatment may lead to sepsis, permanent neurological damage, or even death. Treatment strategies emphasize the importance of identifying the causative pathogen to guide effective antimicrobial therapy. Current consensus does not advocate for empirical antibiotic treatment unless patients exhibit signs of neurological impairment or severe sepsis. Severe cases involving neurological paralysis, spinal instability, or sepsis may require surgical intervention. Vertebral osteomyelitis requires prompt diagnosis and treatment for a good prognosis. Delayed diagnosis and treatment can lead to permanent neurological deficits or death. Identifying the causative organism is crucial for guiding appropriate antimicrobial therapy. In addition to conservative and surgical treatments, local drug delivery systems offer new approaches to managing spinal osteomyelitis.

Extended sequential intravenous and oral antimicrobial therapy improves cure rate in postoperative intracranial neurosurgical infections: a Spanish multicenter retrospective study

BackgroundPostoperative intracranial neurosurgical infections (PINI) complicate < 5% neurosurgeries. Scarce attention was dedicated to the extension and characteristics of its antimicrobial management considering their high morbidity, not negligible mortality, delayed hospital stay and increased healthcare costs.MethodsWe analyzed retrospectively (2014–2023) 162 PINI from eight Spanish third-level academic hospitals.ResultsElective clean craniotomies after tumor or vascular causes were the leading procedures. Epidural abscess (24.7%), scalp infections (19.8%), postsurgical meningitis (16.7%) and cranioplasty infections (16.7%) were the most frequent PINI. Gram negative bacteria (38.6%) and Staphylococcus spp (28.6%) were the predominant isolates. Overall 85.2% patients underwent pus drainage, mostly by craniotomy (40.3%). Interestingly 34% were already receiving antibiotics for extracranial infections before developing PINI while 16.8% did not receive pre-operative antibiotic prophylaxis. In total 77.2% patients started a combined intravenous (IV) antimicrobial therapy, of which 85.2% switched after 5 days to a second-line IV antibiotic regimen, in 41.3% cases combined, after pus culture results, for a median of 21 days. Overall 61.1% patients continued on oral antimicrobials after hospital discharge, 30.3% as a combined regimen, for a median of 42 days. Complete cure was obtained in 81.5% cases, while 11.1% relapsed, 7.4% failed to cure and 6.8% died after PINI complications. In the multivariate analysis oral antimicrobial therapy after hospital discharge (p = 0.001) was significantly associated with PINI cure with no effect on survival.ConclusionsWe conclude that an extended 6 weeks sequential IV and oral antimicrobial therapy in addition to neurosurgical correction increases PINI cure rate with no effect on survival.Clinical trial numberNot applicable.

Implementation of Mycoplasma genitalium Diagnostics with Macrolide-Resistance Detection Improves Patient Treatment Outcomes in Bulgaria.

Background/Objectives: The increasing prevalence of Mycoplasma genitalium infections with macrolide-resistance, causing high azithromycin failure rates, is a major concern internationally. In response to this challenge, diagnostics that simultaneously detect M. genitalium and genetic markers for macrolide-resistance enable the therapy to be individually tailored, i.e., to implement resistance-guided therapy (RGT). This study aimed to evaluate patient treatment outcomes of M. genitalium therapy, guided by a macrolide-resistance assay in Bulgaria. Methods: Consecutively referred M. genitalium infection cases (n = 17) were analyzed for macrolide-resistance mutations (MRMs) and specific antimicrobial treatment was recommended accordingly (MRMs-negative infections received azithromycin and MRMs-positive infections received moxifloxacin). The treatment outcome based on test-of-cure was recorded, and the treatment failure rates and time to achieve a microbiological cure were compared to treatment outcomes in patients treated before the implementation of RGT. Results: Among patients given RGT (n = 17), the overall treatment failure rate was 1/17 (5.9%). This was significantly lower than the rate (47.6%) observed in patients treated pre-RGT (p = 0.002). The time to achieve a microbiological cure was 29.4 days (CI 24.5-34.3), compared to 45.2 days (CI 36.5-53.7) pre-RGT (p = 0.001). Conclusions: The implementation of M. genitalium diagnostics with macrolide-resistance detection improved treatment outcomes in Bulgaria, with significantly lower treatment failure rates and reduced time to achieve a microbiological cure. In light of the limited treatment options and concerns about their decreasing efficacy in response to misuse and overuse, a diagnostic macrolide-resistance assay is critical to direct the appropriate first-line treatment, to maintain the efficacy of antimicrobial treatment (antibiotic stewardship) and to minimize the spread of antimicrobial resistance.

Exploring the enhanced bioactivity and reactivity of novel Fe(III) and Co(II) complexes incorporating sulfadiazine tetradentate ligand: Structural, DFT, molecular docking, and biological applications

This current work presented the synthesis, characterization and bio-evaluation of new Fe(III) (FePSD), and Co(II) (CoPSD) complexes based on N-[4-amino-5-cyano-6-(methylthio)pyridin-2-yl]-3-oxobutanamide in pyridine afford N-(4-amino-5-cyano-6-(methylthio) pyridin-2-yl)-3-oxo-2-([4-(pyrimidin-2-ylsulfamoyl) phenyl]hydrazono) butanamide (PSD). Interestingly, the FePSD and CoPSD complexes exhibit notable stability and solubility in organic solvents, with molar conductivity values of 79.35 Ω−1 cm2 mol−1 for FePSD and 8.89 Ω−1 cm2 mol−1 for CoPSD, indicating a 1:1 electrolytic nature for FePSD and non-electrolytic behavior for CoPSD. FTIR analysis confirmed metal–ligand interactions, as shifts in key bands were observed, while UV–Vis spectra and magnetic moment measurements supported octahedral geometries for both complexes. DFT calculations provided insights into the electronic structure, revealing that CoPSD has higher reactivity and electrophilicity, while FePSD showed moderate reactivity. Thermal and mass spectral analyses further characterized their stoichiometry and stability. The antibacterial and antifungal activities were evaluated against a range of Gram-positive and Gram-negative bacteria and fungal strains. The FePSD and CoPSD complexes demonstrated significantly enhanced antimicrobial efficacy compared to the parent ligand, as evidenced by larger inhibition zones, higher activity indices, and lower minimum inhibition concentrations (MIC). CoPSD exhibited superior antibacterial and antifungal activity compared to FePSD, nearing the effectiveness of standard antibiotics and antifungal drugs. Additionally, the anti-inflammatory potential of these compounds was assessed using the egg albumin denaturation method. Both FePSD and CoPSD showed remarkable inhibition of protein denaturation, surpassing the parent ligand and even outperforming the standard drug Ibuprofen at higher concentrations. The enhancement in biological activity is attributed to the metal chelation effect, which improves cell membrane permeability and reactive oxygen species (ROS) generation. Molecular docking studies further elucidated the binding interactions of PSD, FePSD, and CoPSD with target proteins, revealing stronger hydrophobic interactions and hydrogen bonding in the metal complexes, correlating with their superior biological activity. These findings highlight the potential of FePSD and CoPSD as promising antimicrobial and anti-inflammatory agents.

Towards effective antimicrobial agents: tailoring metal complexes derived acetyl acetone-4-imino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one and 2-aminothiazole schiff base

Towards effective antimicrobial agents: tailoring metal complexes derived acetyl acetone-4-imino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one and 2-aminothiazole schiff base

Green and chemical synthesis of iron oxide nanoparticles: Comparative study for antimicrobial activity and toxicity concerns

Infections caused by multidrug-resistant bacteria in healthcare settings highlight the critical need for robust infection control strategies and effective antimicrobial stewardship. This was further emphasized by the COVID-19 pandemic. This necessitates developing more effective antimicrobial agents. Iron oxide nanoparticles (IONPs) were reported to be biocompatible and possess a broad-spectrum antimicrobial activity with less susceptibilty of developing microbial resistance. Chemical synthesis is employed for industrial manufacture of IONPs. However, concerns about potential toxicity associated with chemical synthesis have led to a preference for green synthesis approaches, despite ongoing debates regarding their cytotoxicity. According to the authors' knowledge, the impact of synthesis methodology on the antimicrobial activity and cytotoxicity of IONPs has not been previously studied. Therefore, the current study is considered the first attempt to assess and compare the toxicity and antimicrobial effect of IONPs synthesized using different methodologies (green versus chemical synthesis) while correlating these effects to the physicochemical properties of IONPs. Additionally, this study addresses for the first time the disturbance of the microbial antioxidant defense system in multidrug-resistant bacteria after their exposure to IONPs. Both types of IONPs effectively eradicated SARS-CoV-2, and multidrug-resistant bacteria: S. aureus, and E. Coli, in addition, both disrupted the antioxidant bacterial defense mechanism, indicating that reactive oxygen species play a significant role in their antimicrobial activities. Chemically synthesized IONPs showed superior antimicrobial activity to those produced by green methods and in-vivo study demonstrated their greater compatibility with skin and eyes. Therefore, chemically synthesized IONPs might be used as a disinfectant in healthcare settings.

Luteolin Functionalized Zinc Oxide Nanoparticles for Cancer Therapy Based on Autophagy Activation and EMT Inhibition.

Natural bioactive compounds have become increasingly important antitumor and antimicrobial agents due to their high therapeutic potential and low systemic toxicity. However, they also have significant drawbacks like nontumor targeting and low bioavailability, which limit their wide therapeutic applications. There is an urgent need for a safe and compatible nanoparticle-mediated drug delivery system for the efficient transport of drug candidates into tumor tissues. In this paper, amine-modified zinc oxide nanoparticles are synthesized to load luteolin. The functionalized nanoparticles exhibit good synergistic effects in terms of antitumor and antibacterial activities. They show significant induction of oxidative stress and antitumor effects, while no significant inhibitory effect on normal cells is observed, suggesting that the nanocomposites have good targeting of cancer cells. Autophagy activation and EMT inhibition effects are studied to explain the good antitumor performances. The prepared nanocomposites are demonstrated to be attractive candidates for cancer therapy.

Nanocarrier-Mediated Dermal Drug Delivery System of Antimicrobial Agents for Targeting Skin and Soft Tissue Infections.

Antimicrobial resistance in disease-causing microbes is seen as a severe problem that affects the entire world, makes therapy less effective, and raises mortality rates. Dermal antimicrobial therapy becomes a desirable choice in the management of infectious disorders since the rising resistance to systemic antimicrobial treatment frequently necessitates the use of more toxic drugs. Nanoparticulate systems such as nanobactericides, which have built-in antibacterial activity, and nanocarriers, which function as drug delivery systems for conventional antimicrobials, are just two examples of the treatment methods made feasible by nanotechnology. Silver nanoparticles, zinc oxide nanoparticles, and titanium dioxide nanoparticles are examples of inorganic nanoparticles that are efficient on sensitive and multidrug-resistant bacterial strains both as nanobactericides and nanocarriers. To stop the growth of microorganisms that are resistant to standard antimicrobials, various antimicrobials for dermal application are widely used. This review covers the most prevalent microbes responsible for skin and soft tissue infections, techniques to deliver dermal antimicrobials, topical antimicrobial safety concerns, current issues, challenges, and potential future developments. A thorough and methodical search of databases, such as Google Scholar, PubMed, Science Direct, and others, using specified keyword combinations, such as "antimicrobials," "dermal," "nanocarriers," and numerous others, was used to gather relevant literature for this work.

Ferumoxytol nanozymes effectively target chronic biofilm infections in apical periodontitis.

Bacterial biofilms are pervasive and recalcitrant to current antimicrobials, causing numerous infections. Iron oxide-nanozymes, including an FDA-approved formulation (ferumoxytol, FMX), show potential against biofilm infections via catalytic activation of hydrogen peroxide (H2O2). However, clinical evidence on its efficacy and therapeutic mechanisms is lacking. Here, we investigate whether FMX-nanozymes can treat chronic biofilm infections and compare their bioactivity to gold-standard sodium hypochlorite (NaOCl), a potent but caustic disinfectant. Clinical performance was assessed in patients with apical periodontitis, an intractable endodontic infection affecting half of the global adult population. Data show robust antibiofilm activity by a single application of FMX with H2O2 achieving results comparable to NaOCl without adverse effects. FMX binds efficiently to bacterial pathogens Enterococcus faecalis and Fusobacterium nucleatum and remains catalytically active without being affected by dental tissues. This allows for effective eradication of endodontic biofilms via on-site free-radical generation without inducing cytotoxicity. Unexpectedly, FMX promotes growth of stem cells of apical papilla (SCAP), with transcriptomic analyses revealing upregulation of proliferation-associated pathways and downregulation of cell-cycle suppressor genes. Notably, FMX activates SCAP pluripotency and WNT/NOTCH signaling that induces its osteogenic capacity. Together, we show FMX nanozymes are clinically effective against severe chronic biofilm infection with pathogen targeting and unique stem cell-stimulatory properties, offering a regenerative approach to antimicrobial therapy.

Dimer-monomer transition defines a hyper-thermostable peptidoglycan hydrolase mined from bacterial proteome by lysin-derived antimicrobial peptide-primed screening.

Phage-derived peptidoglycan hydrolases (i.e. lysins) are considered promising alternatives to conventional antibiotics due to their direct peptidoglycan degradation activity and low risk of resistance development. The discovery of these enzymes is often hampered by the limited availability of phage genomes. Herein, we report a new strategy to mine active peptidoglycan hydrolases from bacterial proteomes by lysin-derived antimicrobial peptide-primed screening. As a proof-of-concept, five peptidoglycan hydrolases from the Acinetobacter baumannii proteome (PHAb7-PHAb11) were identified using PlyF307 lysin-derived peptide as a template. Among them, PHAb10 and PHAb11 showed potent bactericidal activity against multiple pathogens even after treatment at 100°C for 1 hr, while the other three were thermosensitive. We solved the crystal structures of PHAb8, PHAb10, and PHAb11 and unveiled that hyper-thermostable PHAb10 underwent a unique folding-refolding thermodynamic scheme mediated by a dimer-monomer transition, while thermosensitive PHAb8 formed a monomer. Two mouse models of bacterial infection further demonstrated the safety and efficacy of PHAb10. In conclusion, our antimicrobial peptide-primed strategy provides new clues for the discovery of promising antimicrobial drugs.

Microneedles Constructed by Swellable Hydrogels Loaded with Celastrol for Efficient Treatment of Skin Infections Induced by Drug-Resistant Bacterial Strains.

The urgent need for new antimicrobial drugs arises from the limited efficacy of traditional antibiotics against emerging drug-resistant strains. Celastrol (CSL) demonstrates an exceptional antibacterial property that remains unaffected by bacterial resistance, but its poor water solubility limits its wide applications. This study uses the hydrophobic inner cavity of mono-(6-diethylenetriamine-6-deoxy)-β-cyclodextrin (mβ-CD) (a derivative of cyclodextrin) to encapsulate CSL, constructing an inclusion complex (CSL@mβ-CD) to enhance the water solubility of CSL. The obtained inclusion complex is further incorporated into a swellable hydrogel microneedle (MN) to obtain CSL@mβ-CD/MN. The fabricated CSL@mβ-CD/MN can enable the sustained release of CSL, achieving effective bacterial eradication at infected sites. In vivo experiments demonstrate that CSL@mβ-CD/MN has a remarkable efficacy in the treatment of methicillin-resistant Staphylococcus aureus-induced subcutaneous abscesses and wound infections. Specifically, CSL@mβ-CD/MN can effectively penetrate the stratum corneum of the skin to realize rapid elimination of the bacteria in wounds. Moreover, CSL@mβ-CD/MN can efficiently scavenge reactive oxygen species, promote M2 polarization of macrophages, and relieve local inflammation at the wound sites. These results reveal that CSL@mβ-CD/MN holds great promise in the clinical treatment of acute skin infections induced by drug-resistant bacteria.

Synthesis and Characterization of Two Sparfloxacin Crystalline Salts: Enhancing Solubility and In Vitro Antibacterial Activity of Sparfloxacin

Background: To improve the solubility and permeability of Sparfloxacin (SPX) and enhance its antimicrobial activity in vitro, two unreported pharmaceutical crystalline salts were synthesized and characterized in this paper. One is a hydrated crystal of Sparfloxacin with Pimelic acid (PIA), another is a hydrated crystal of Sparfloxacin with Azelaic acid (AZA), namely, SPX-PIA-H2O (2C19H23F2N4O3·C7H10O4·2H2O) and SPX-AZA-H2O (4C19H23F2N4O3·2C9H14O4·5H2O). Methods: The structure and purity of two crystalline salts were analyzed using solid-state characterization methods such as single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and infrared spectroscopy. Additionally, the interaction characteristics between two crystal salt molecules were examined by constructing Hirshfeld surfaces and mapping specific real-space functions through Hirshfeld surface analysis. The solubility under physiological conditions, diffusivity across simulated biological membranes, and in vitro antibacterial activity against specific bacterial strains of two crystalline salts were evaluated using established assays, including minimum inhibitory concentration (MIC) tests. Results: Single-crystal X-ray diffraction and Hirshfeld surface analysis indicate that SPX forms stable crystal structures with PIA through charge-assisted hydrogen bonds N1-H1e···O10 (1.721 Å, 173.24°), N5-H5a···O11 (1.861 Å, 169.38°), and with AZA through charge-assisted hydrogen bonds N5-H5B···O8 (1.810 Å, 154.55°), N4-H4B···O6 (1.806 Å, 174.97°). The binding sites of two crystalline salts were at the nitrogen atoms on the piperazine ring of SPX. Compared with SPX, the equilibrium solubility of the two crystalline salts was improved by 1.17 and 0.33 times, respectively, and the permeability of the two crystalline salts was increased by 26.6% and 121.9%, respectively. In addition, SPX-AZA-H2O has much higher antibacterial activity on Pseudomonas aeruginosa and Bacillus subtilis than SPX. Conclusions: This research yielded the successful synthesis of two crystalline salts of Sparfloxacin (SPX), significantly improving its solubility and diffusivity, and bolstering its antibacterial efficacy against targeted bacterial species. These breakthroughs set the stage for innovative advancements in the realm of antimicrobial drug development.

Advancements and Challenges in the Management of Prosthetic Valve Endocarditis: A Review

Prosthetic valve endocarditis (PVE) is the medical term used to describe a focus of infection involving a valvular substitute within the heart. It is a significant concern in the field of cardiology, and the epidemiology of PVE has seen notable developments over the last five decades. The disease currently affects an older demographic and is becoming increasingly prevalent in patients with transcatheter-implanted valves. It is imperative that we urgently address the significant challenges posed by PVE. It is a disease that has a wide range of potential aetiologies, clinical presentations, and courses. In developed countries, Staphylococcus aureus is now the predominant causative organism, resulting in an aggressive form of disease that frequently afflicts vulnerable or elderly populations. However, it is clear that Enterococcus species present a significant challenge in the context of PVE following TAVR procedures, given their elevated prevalence. The 2023 Duke/International Society for Cardiovascular Infectious Diseases infective endocarditis diagnostic criteria now include significant developments in microbiological and image-based techniques for diagnostic purposes, specifically the incorporation of fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography. These developments unequivocally enhance the diagnostic sensitivity for PVE, while maintaining the specificity. They do so in accordance with the results of studies conducted specifically for the purpose of validation. The lack of rigorous scientific studies and a shortage of funding and resources for research have led to a significant gap in our understanding. Randomized controlled trials could provide invaluable insight and guidance for clinical practice, but they are missing, which represents a major gap. It is clear that there is an urgent need for more research. PVE is a life-threatening condition that must be handled by a multidisciplinary endocarditis team at a cardiac centre in order to improve outcomes. The emergence of innovative surgical techniques has empowered clinicians to steer more patients away from surgical procedures, despite the presence of clear indications for them. A select group of patients can now complete parenteral or oral antimicrobial treatment at home. Additionally, antibiotic prophylaxis is the best option for individuals with prosthetic valves who are going to have invasive dental procedures. These individuals should be given antibiotics beforehand.

Pharmacological Evaluation of Bakuchiol From Psoralea corylifolia L. as Potent Antimicrobial Agent Against Staphylococcus aureus.

The surge in multidrug resistance in Staphylococcus aureus is the pressing need to identify novel alternatives to combat antimicrobial resistance effectively. Bakuchiol is a bioactive prenylated phenolic meroterpene largely abundant in the seeds of Psoralea corylifolia. In this study, we present the biological assessment of bakuchiol derived from P. corylifolia as an antimicrobial agent. S. aureus, a significant opportunistic pathogen, attracts global concern for its biofilm formation and resilience against numerous antibiotics, escaping antibiotic pressure. The primary screening of bakuchiol as an antimicrobial agent against S. aureus delineated its potential as a strong bactericidal agent with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 2 and 8µg/mL, respectively. Importantly, bakuchiol also exhibited low toxicity against HepG2 cells, showing a favorable selectivity index (SI) of 14.4. Furthermore, bakuchiol demonstrated comparable activity (MIC=2µg/mL) against a laboratory-generated ciprofloxacin-resistant mutant of S. aureus. Bakuchiol could significantly inhibit the biofilm formation of S. aureus in a dose-dependent manner with minimum biofilm inhibitory concentration (MBIC)50 of 0.956µg/mL. Bakuchiol effectively inhibited DNA gyrase supercoiling activity at a concentration eight times the MIC, establishing DNA gyrase inhibition as the mechanism of action for bakuchiol. Our findings suggest bakuchiol as a potential therapeutic agent for S. aureus-mediated nosocomial infections.

Tannins and copper sulphate as antimicrobial agents to prevent contamination of Posidonia oceanica seedling culture for restoration purposes.

Seed-based restoration methods are increasingly recognized as a relevant tool contributing to halt and reverse the loss of seagrass meadows while providing genetic and evolutionary benefit for the conservation of these habitats. Ad-hoc protocols aimed at maximizing the survival of plantlets obtained from seeds in cultivation systems are therefore required. Previous trials of seedling culture of Posidonia oceanica, the dominant seagrass of the Mediterranean Sea, recorded up to 40% loss due to mould development. In this study we aim to (i) identify the putative causal agents of seed decay and (ii) test the efficacy of copper sulphate (0.2 and 2 ppm) and of tannin-based products derived from chestnut, tara and quebracho in reducing seed and seedling decay, while assessing possible phytotoxic effects on plant development. Halophytophthora lusitanica, H. thermoambigua and a putative new Halophytophtora species were identified as possible causal agents of seed loss. The antimicrobial agents (copper and tannins) reduced seed contamination by 20%, although copper sulphate at 2 ppm strongly inhibited the root growth. Among tannins, chestnut and tara reduced seeds germination by up to 75% and decreased shoot and root development, while quebracho showed a less severe phytotoxic effect. The use of copper sulphate at 0.2 ppm is therefore recommended to prevent P. oceanica seedling loss in culture facilities since it reduces seed contamination with no phytotoxic effects. Our results contribute to improving the seedling culture of one the key species of the Mediterranean Sea, increasing propagule availability for restoration purposes.

Ultra-high-throughput screening of antimicrobial combination therapies using a two-stage transparent machine learning model.

Here, we present M2D2, a two-stage machine learning (ML) pipeline that identifies promising antimicrobial drug combinations, which are crucial for combating drug resistance. M2D2 addresses key challenges in drug combination discovery by predicting drug synergies using computationally generated drug-protein interaction data, thereby circumventing the need for expensive omics data. The model improves the accuracy of drug target identification using high-throughput experimental and computational methods via feedback between ML stages. M2D2's transparent framework provides mechanistic insights into drug interactions and was benchmarked against chemogenomics, transcriptomics, and metabolomics datasets. We experimentally validated M2D2 using high-throughput screening of 946 combinations of Food and Drug Administration (FDA)- approved drugs and antibiotics against Escherichia coli . We discovered synergy between a cerebrovascular drug and a widely used penicillin antibiotic and validated predicted mechanisms of action using genome-wide CRISPR inhibition screens. M2D2 offers a transparent ML tool for rapidly designing combination therapies and guides repurposing efforts while providing mechanistic insights.