Methicillin-resistant Staphylococcus Aureus Infection Research Articles

Photothermal-antibacterial bioactive noncrystalline nanosystem promotes infected wound tissue regeneration through thermo-ions activation

The efficient repair and tissue regeneration of chronic infected wounds is still a major challenge, among which the bacterial infection, inflammation and oxidative stress induced poor angiogenesis are the key obstacles. The nanosystem with single repair pathway could not meet the requirement of regenerating complicated wound tissue. Herein, we construct an photothermal multifunctional bioactive nanoglass (BGN) with the metal polyphenol coordination surface to treat methicillin-resistant Staphylococcus aureus（MRSA）infected wound. The BGN was coated with copper (Cu) coordinated polydopamine (PDA-Cu) to bioactive BGN@PDA-Cu nanoparticles, which release bioactive ions (Ca2+, SiO44- and Cu2+) and show the robust antibacterial/antioxidant/mild photothermal activities. BGN@PDA-Cu possesses the strong MRSA inhibition, reactive oxygen species scavenging, mild photothermal stimulation (41℃) and hemostatic ability. The antioxidant activity, thermal stimulation and sustainable bioactive ions release could significantly reverse the inflammatory phenotype of macrophage and enhance the angiogenesis through the activation of hypoxia-inducible factor HIF-1α and heat shock protein HSP90 pathways. The in vivo MRSA infected wound model demonstrated that BGN@PDA-Cu could significantly inhibit the MRSA infection and accelerate the wound repair which has 2 times improvement on healing rate compared with commercial bioglass dressing. This work demonstrates that bioactive ions release combined with mild thermal stimulation is a promising strategy to design multifunctional bioactive biomaterials for angiogenetic tissue regeneration.

Novel natural osthole-inspired amphiphiles as membrane targeting antibacterials against methicillin-resistant Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread pathogen causing clinical infections and is multi-resistant to many antibiotics, making it urgent need to develop novel antibacterials to combat MRSA. Herein, we designed and prepared a series of novel osthole amphiphiles 6a−6ad by mimicking the structures and function of antimicrobial peptides (AMPs). Antibacterial assays showed that osthole amphiphile 6aa strongly inhibited S. aureus and 10 clinical MRSA isolates with MIC values of 1–2 μg/mL, comparable to that of the commercial antibiotic vancomycin. Additionally, 6aa had the advantages of rapid bacteria killing without readily developing drug resistance, low toxicity, good membrane selectivity, and good plasma stability. Mechanistic studies indicated that 6aa possesses good membrane-targeting ability to bind to phosphatidylglycerol (PG) on the bacterial cell membranes, thereby disrupting the cell membranes and causing an increase in intracellular ROS as well as leakage of proteins and DNA, and accelerating bacterial death. Notably, in vivo activity results revealed that 6aa exhibits strong anti-MRSA efficacy than vancomycin as well as a substantial reduction in MRSA-induced proinflammatory cytokines, including TNF-α and IL-6. Given the impressive in vitro and in vivo anti-MRSA efficacy of 6aa, which makes it a potential candidate against MRSA infections.

Isolation and characterisation of a novel Silviavirus bacteriophage promising antimicrobial agent against methicillin-resistant Staphylococcus aureus infections

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) emphasises the urgent need for novel antimicrobial agents as alternatives to antibiotics. Bacteriophage therapy is one of the most promising antimicrobial strategies. Here, we isolated and comprehensively characterized a novel Staphylococcus phage, vB_SauM_VL10 (VL10), from urban sewage. The VL10 genome displays 141,746 bp of linear double-stranded DNA, containing 193 open reading frames and lacking tRNA, virulence, or antibiotic resistance genes. Phylogenetic analysis categorizes VL10 as a novel species within the Silviavirus genus, Twortvirinae subfamily. VL10 exhibits lytic behaviour characterized by efficient adsorption, a short latent period, and substantial burst size, with environmental stability. It demonstrates lytic activity against 79.06% of tested S. aureus strains, highlighting its species specificity. Additionally, VL10 effectively targets MRSA biofilms, reducing biomass and viable cells. In MRSA-infected G. mellonella larvae, VL10 enhances survival rates, supporting its potential for phage therapy applications. Moreover, the emergence of VL10-resistant S. aureus strains associated with fitness trade-offs, including reduced growth, biofilm formation, and virulence. Altogether, these findings emphasize VL10 as a promising candidate for developing therapeutic agents against MRSA infections, providing insights into phage biology and resistance dynamics.

PH-Responsive antibacterial metal-phenolic network coating on hernia meshes.

Polypropylene (PP) mesh is widely used in hernioplasty, but it is prone to contamination by pathogenic bacteria. Here, we present an infection microenvironment-responsive metal-phenolic network (MPN) coating, which is made up of Cu2+ and tannic acid (TA) (referred to as CT coating), and is fabricated on PP meshes by layer-by-layer (LbL) assembly. The CT coating provided a robust protection for the PP mesh from pathogenic bacterial infection in a pH-responsive manner due to the pH-responsive disassembly kinetics of MPN complexes. Moreover, the PP meshes with ten CT coating cycles (PP-CT(10)) exhibited excellent stability in a physiological environment, with the killing ratio against "superbug" methicillin-resistant Staphylococcus aureus (MRSA) at pH 5.5 exceeding 99% even after 28 days of PBS (pH 7.4) immersion. In addition, the PP-CT(10) exhibited excellent in vivo anti-infective ability in a rodent subcutaneous implant MRSA infection model, and the results of histological and immunohistochemical analyses demonstrated that the reduced bacterial number alleviated the inflammatory response at implant sites. This study revealed that MPN coating is a promising strategy, which could provide a self-defensive ability for various implants to combat post-surgical infections in a pH-responsive manner.

Antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated at tertiary care hospital in Riyadh, Saudi Arabia.

Staphylococcus aureus is an important human pathogen that has a major impact on public health. The objective of the present work was to determine the prevalence and the pattern of antibiotic susceptibility in S aureus (MRSA) isolates from the King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. The isolates were collected from different body sites of infection and the antibiotic susceptibility was confirmed on the Vitek 2 system. A total of 371 MRSA isolates from clinical samples were received over a 12-month period from January 2021 to December 2021. The results showed that infection was predominant among males (55.8%) and most of the isolates occurred in the older age groups, with a mean age of 43.7 years and an age span from <1 to 89 years old. The majority (34.5%) recovered from wound infection followed by (14.6%) from blood. We have observed peaks of MRSA infections during the autumn, especially in September and November. All MRSA isolates were resistant to Amoxicillin + clavulanic acid, Ampicillin, Imipenem, Oxacillin, Cloxacillin, and Penicillin while all isolates were sensitive to Daptomycin and Nitrofurantoin. Furthermore, Vancomycin was resistant in (0.3%) of MRSA isolates, and (2.9%) was resistant to Linezolid. The current study concluded that MRSA strains had developed resistance toward 24 tested antibiotics, including the previous effective drugs vancomycin and linezolid. Therefore, there is an urgent need for continuous review of infection control practices to prevent any further spread of resistant strains.

Distinguishing methicillin-resistant Staphylococcus aureus from methicillin-sensitive strains by combining Fe3O4 magnetic nanoparticle-based affinity mass spectrometry with a machine learning strategy

Pathogenic bacteria, including drug-resistant variants such as methicillin-resistant Staphylococcus aureus (MRSA), can cause severe infections in the human body. Early detection of MRSA is essential for clinical diagnosis and proper treatment, considering the distinct therapeutic strategies for methicillin-sensitive S. aureus (MSSA) and MRSA infections. However, the similarities between MRSA and MSSA properties present a challenge in promptly and accurately distinguishing between them. This work introduces an approach to differentiate MRSA from MSSA utilizing matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) in conjunction with a neural network-based classification model. Four distinct strains of S. aureus were utilized, comprising three MSSA strains and one MRSA strain. The classification accuracy of our model ranges from ~ 92 to ~ 97% for each strain. We used deep SHapley Additive exPlanations to reveal the unique feature peaks for each bacterial strain. Furthermore, Fe3O4 MNPs were used as affinity probes for sample enrichment to eliminate the overnight culture and reduce the time in sample preparation. The limit of detection of the MNP-based affinity approach toward S. aureus combined with our machine learning strategy was as low as ~ 8 × 103 CFU mL−1. The feasibility of using the current approach for the identification of S. aureus in juice samples was also demonstrated.Graphical

A natural inhibitor of diapophytoene desaturase attenuates methicillin-resistant Staphylococcus aureus (MRSA) pathogenicity and overcomes drug-resistance.

At present, the inhibition of staphyloxanthin biosynthesis has emerged as a prominent strategy in combating methicillin-resistant Staphylococcus aureus (MRSA) infection. Nonetheless, there remains a limited understanding regarding the bio-structural characteristics of staphyloxanthin biosynthetic enzymes, as well as the molecular mechanisms underlying the interaction between inhibitors and proteins. Furthermore, the functional scope of these inhibitors is relatively narrow. In this study, we address these limitations by harnessing the power of deep learning techniques to construct the 3D structure of diapophytoene desaturase (CrtN). We perform efficient virtual screening and unveil alnustone as a potent inhibitor of CrtN. Further investigations employing molecular modelling, site-directed mutagenesis and biolayer interferometry (BLI) confirmed that alnustone binds to the catalytic active site of CrtN. Transcriptomic analysis reveals that alnustone significantly down-regulates genes associated with staphyloxanthin, histidine and peptidoglycan biosynthesis. Under the effects of alnustone, MRSA strains exhibit enhanced sensitivity to various antibiotics and the host immune system, accompanied by increased cell membrane permeability. In a mouse model of systemic MRSA infection, the combination of alnustone and antibiotics exhibited a significant therapeutic effect, leading to reduced bacterial colony counts and attenuated pathological damage. Alnustone, as a natural inhibitor targeting CrtN, exhibits outstanding antibacterial properties that are single-targeted yet multifunctional. This finding provides a novel strategy and theoretical basis for the development of drugs targeting staphyloxanthin producing bacteria.

Phage-antibiotic combinations in various treatment modalities to manage MRSA infections.

Introduction: The emergence of antibiotic resistance is a significant challenge in the treatment of bacterial infections, particularly in patients in the intensive care unit (ICU). Phage-antibiotic combination therapy is now being utilized as a preferred therapeutic option for infections that are multi-drug resistant in nature. Methods: In this study, we examined the combined impact of the staph phage vB_Sau_S90 and four antibiotics on methicillin-resistant Staphylococcus aureus (MRSA). We conducted experiments on three different treatment sequences: a) administering phages before antibiotics, b) administering phages and antibiotics simultaneously, and c) administering antibiotics before phages. Results: When the media was supplemented with sub-inhibitory concentrations of 0.25μg/mL and 1μg/mL, the size of the plaque increased from 0.5 ± 0.1mm (in the control group with only the phage) to 4 ± 0.2mm, 1.6 ± 0.1mm, and 1.6 ± 0.4mm when fosfomycin, ciprofloxacin, and oxacillin were added, respectively. The checkerboard analysis revealed a synergistic effect between the phages and antibiotics investigated, as indicated by a FIC value of less than 0.5. The combination treatment of phages and antibiotics demonstrated universal efficacy across all treatments. Nevertheless, the optimal effectiveness was demonstrated when the antibiotics were delivered subsequent to the phages. Utilizing the Galleria mellonella model, in vivo experiments showed that the combination of phage-oxacillin effectively eliminated biofilm-infected larvae, resulting in a survival rate of up to 80% in the treated groups. Discussion: Our findings highlight the advantages of using a combination of phage and antibiotic over using phages alone in the treatment of MRSA infections.

Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients.

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18-64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.

Antimicrobial and antibiofilm effect of cannabinoids from Cannabis sativa against methicillin-resistant Staphylococcus aureus (MRSA) causing bovine mastitis.

Antimicrobial resistance (AMR) poses a serious threat to human, animal, and plant health on a global scale. Search and elimination techniques should be used to effectively counter the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections. With only a few novel drugs in clinical development, the quest for plant-based alternatives to prevent the spread of antibiotic resistance among bacteria has accelerated. Treatment of MRSA infections is challenging owing to rapidly emerging resistance mechanisms coupled with their protective biofilms. In the present research, we examined the antibacterial properties of ten plant-derived ethanolic leaf extracts. The most effective ethanolic leaf extract against MRSA in decreasing order of zone of inhibition, Cannabis sativa L. > Syzygium cumini > Murraya koenigii > Eucalyptus sp. > while Aloe barbadensis, Azadirachta indica, had very little impact. Mangifera indica, Curcuma longa, Tinospora cordifolia, and Carica papaya did not exhibit inhibitory effects against MRSA; hence, Cannabis was selected for further experimental study. The minimal inhibitory concentration (MIC) of Cannabis sativa L. extract was 0.25mgml-1 with 86% mortality. At a sub-MIC dosage of 0.125mgml-1, the biofilm formation was reduced by 71%. The two major cannabinoids detected were cannabidiol and delta-9-tetrahydrocannabinol (Δ9-THC), which were majorly attributed to substantial inhibitory action against MRSA. The time-kill kinetics demonstrated a bactericidal action at 4 MIC over an 8-20-h time window with a 90% reduction in growth rate. The results from SEM, and light microscopy Giemsa staining revealed a reduction in cells in the treated group with increased AKP activity, indicating bacterial cell membrane breakdown. These findings suggested cannabinoids may be a promising alternative to antibiotic therapy for bovine biofilm-associated MRSA.

Combination of curcuminoid and collagen marine peptides for healing diabetic wounds infected by methicillin-resistant Staphylococcus aureus

Background and Aim: The high prevalence of diabetes mellitus in Indonesia indirectly reflects the high risk of developing chronic wounds that are susceptible to infection. Methicillin-resistant Staphylococcus aureus (MRSA) is an infectious pathogen that is resistant to various antibiotics. Therefore, antibiotic therapy is ineffective enough to treat chronic hyperglycemic wounds caused by MRSA infection. Curcuminoids have anti-inflammatory and antibacterial effects by inhibiting the enzymatic pathways involved in the pathogenesis of inflammation. Collagen is a tissue regeneration inducer. The combination of these two ingredients is expected to be an alternative therapy for MRSA-infected hyperglycemic chronic wounds without the risk of antibiotic resistance. The aim of this study was to investigate the efficacy of hydrolacin-gel in wound healing and inhibiting the growth of MRSA bacteria, as well as to determine the optimal concentration of curcuminoids combined with collagen marine peptides (CMPs). Materials and Methods: Hydrolacin-gels were prepared by homogenizing curcuminoid nanoemulsions and CMPs. The evaluation of preparation includes stability tests and antibacterial activity tests. Wound diabetic mice were treated with various combinations of curcuminoid and CMPs. Wound healing was observed based on malondialdehyde levels as a marker of oxidative stress and histopathological changes in the skin wound. Results: Hydrolacin-gel was formulated by combining curcuminoid nanoemulsion (more water soluble) and CMPs, with the ratio of formula 1 (1:2, curcuminoid 43.3 mg and CMPs 5.58 mg), formula 2 (1:1, curcuminoid 86.8 mg and CMPs 3.72), and formula 3 (2:1, curcuminoid 130.2 mg and CMPs 1.87 mg) calculated based on the effective dose of curcuminoid 200 mg/kg body weight (BW) and CAMPs 0.9 g/kg BW. Hydrolacin-gel had a potential antibacterial activity against MRSA. Hydrolacin-gel induced wound tissue repair and reduced oxidative stress caused by inflammation in diabetic-infected MRSA. Hydrolacin-gel could be used for healing MRSA-infected diabetic wounds, especially formula 3 with the ratio of curcuminoid: CMPs = 2:1. Conclusion: Hydrolacin-gel combining curcuminoid nanoemulsion and CMPs effectively inhibited the inflammatory process and increased re-epithelialization in MRSA-infected diabetic wound healing. Hydrolacin-gel with curcuminoid (130.2 mg) and CMPs (1.87 mg) at a concentration ratio of 2:1 appeared to be the best formula against MRSA infection in diabetic wounds. Keywords: collagen marine peptides, curcuminoids, diabetic, methicillin-resistant Staphylococcus aureus, wound.

Comparison of broth microdilution and E-test for susceptibility of MRSA to vancomycin

Introduction: Healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) developed soon after the introduction of methicillin. These bacteria have shown resistance to multiple drugs and therefore vancomycin became the antibiotic of choice for treatment of MRSA infections. Vancomycin is a bactericidal antibiotic that acts by inhibiting bacterial cell wall synthesis. This study aimed to compare broth microdilution (BMD) and E-test in determining vancomycin minimum inhibitory concentration (MIC) against MRSA.Methods: A total of 30 clinical isolates of MRSA were acquired from Colombo South Teaching Hospital, Sri Lanka. These MRSA strains were identified by cefoxitin disk diffusion and the vancomycin MIC was determined through BMD and E-test. The Kruskal-Wallis test was applied to test if the samples originated from the same distribution with post hoc determination of the correlation between methods using the Mann-Whitney U test.Results: All 30 MRSA isolates were 100% vancomycin susceptible (≤2 μg/mL) irrespective of methodology, according to the Clinical and Laboratory Standards Institute (CLSI) established breakpoints. However, the E-test MIC values were 1 to 2 dilutions higher than those of BMD. A statistically significant difference between vancomycin MICs of BMD and E-test (p = &lt;0.00001) was calculated which indicated a difference in accuracy.Conclusion: Due to cost, convenience, and the ability to detect vancomycin intermediate Staphylococcus aureus (VISA), exploring the possibility of using E-test as an alternative to BMD is worthwhile.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2−) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (−4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

Injectable Phage-Loaded Microparticles Effectively Release Phages to Kill Methicillin-Resistant Staphylococcus aureus.

The increasing prevalence of bacterial multidrug antibiotic resistance has led to a serious threat to public health, emphasizing the urgent need for alternative antibacterial therapeutics. Lytic phages, a class of viruses that selectively infect and kill bacteria, offer promising potential as alternatives to antibiotics. However, injectable carriers with a desired release profile remain to be developed to deliver them to infection sites. To address this challenge, phage-loaded microparticles (Phage-MPs) have been developed to deliver phages to the infection site and release phages for an optimal therapeutic effect. The Phage-MPs are synthesized by allowing phages to be electrostatically attached onto the porous polyethylenimine-modified silk fibroin microparticles (SF-MPs). The high specific surface area of SF-MPs allows them to efficiently load phages, reaching about 1.25 × 1010 pfu per mg of microparticles. The Phage-MPs could release phages in a controlled manner to achieve potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Unlike the diffuse biodistribution of free phages post-intraperitoneal injection, Phage-MPs could continuously release phages to effectively boost the local phage concentration at the bacterial infection site after they are intraperitoneally injected into an abdominal MRSA-infected mouse model. In a mouse abdominal MRSA infection model, Phage-MPs significantly reduce the bacterial load in major organs, achieving an efficient therapeutic effect. Furthermore, Phage-MPs demonstrate outstanding biocompatibility both in vitro and in vivo. Overall, our research lays the foundation for a new generation of phage-based therapies to combat antibiotic-resistant bacterial infections.

Fractional order model of MRSA bacterial infection with real data fitting: Computational Analysis and Modeling

Bacterial infections in the health-care sector and social environments have been linked to the Methicillin-Resistant Staphylococcus aureus (MRSA) infection, a type of bacteria that has remained an international health risk since the 1960s. From mild colonization to a deadly invasive disease with an elevated mortality rate, the illness can present in many different forms. A fractional-order dynamic model of MRSA infection developed using real data for computational and modeling analysis on the north side of Cyprus is presented in this paper. Initially, we tested that the suggested model had a positively invariant region, bounded solutions, and uniqueness for the biological feasibility of the model. We study the equilibria of the model and assess the expression for the most significant threshold parameter, called the basic reproduction number (ℛ0). The reproductive number’s parameters are also subjected to sensitivity analysis through mathematical methods and simulations. Additionally, utilizing the power law kernel and the fixed-point approach, the existence, uniqueness, and generalized Ulam–Hyers–Rassias stability are presented. Chaos Control was used to regulate the linear responses approach to bring the system to stabilize according to its points of equilibrium, taking into account a fractional-order system with a managed design where solutions are bound in the feasible domain. Finally, numerical simulations demonstrating the effects of different parameters on MRSA infection are used to investigate the impact of the fractional operator on the generalized form of the power law kernel through a two-step Newton polynomial method. The impact of fractional orders is emphasized in the study so that the numerical solutions support the importance of these orders on MRSA infection. With the application of fractional order, the significance of cognizant antibiotic usage for MRSA infection is verified.

Effects of Phomopsidione on the Viability, Virulence, and Metabolites Profile of Methicillin-Resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) infections have become one of the most threatening multidrug-resistant pathogens. Thus, an ongoing search for anti-MRSA compounds remains an urgent need to effectively treating MRSA infections. Phomopsidione, a novel antibiotic isolated from Diaporthe fraxini, has previously demonstrated potent anti-candidal activity. The present study aimed to investigate the effects of phomopsidione on the viability, virulence, and metabolites profile of MRSA. MRSA was sensitive to phomopsidione in a concentration-dependent manner. Phomopsidione exhibited minimum inhibitory concentration and minimum bactericidal concentration of 62.5 and 500.00µg/mL against MRSA on broth microdilution assay. The compound showed significant reduction in virulence factors production including extracellular polymeric substances quantification, catalase, and lipase. An untargeted metabolomics analysis using liquid chromatography-high resolution mass spectrometry revealed a significant difference in the metabolites profile of MRSA with 13 putatively identified discriminant metabolites. The present study suggested the potential of phomopsidione as a promising anti-MRSA agent.

An unusual case of multiple skin abscesses caused by methicillin-resistant &lt;i&gt;Staphylococcus aureus &lt;/i&gt;in a 6-year-old boy

This report is a rare case of a 6-year-old child presenting with multiple skin abscesses resulting from a methicillin-resistant Staphylococcus aureus (MRSA) infection post blunt trauma to the pelvic region. Staphylococcus aureus poses challenges due to its antibiotic resistance. The child’s condition, marked by sepsis and extensive abscesses, prompted a multidisciplinary approach involving antibiotic therapy and surgical interventions. The MRSA strain exhibited resistance to various antibiotics, emphasizing the importance of individualized treatment as per the case. The case underlines the complexities of managing multi-site MRSA infections and emphasizes the significance of accurate diagnosis, appropriate antibiotic selection, and surgical intervention for successful outcomes.

The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

Antimicrobial activity of a natural compound and analogs against multi-drug-resistant Gram-positive pathogens.

The rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) isolates has precipitated a critical need for novel antibiotics. We have developed a one-pot synthesis method for naturally occurring compounds such as MC21-A (C58) and its chloro-analog, C59. Our findings demonstrate that these compounds kill MRSA isolates at lower or comparable concentrations to standard-of-care (SoC) antimicrobials. C59 eradicates MRSA cells in biofilms, which are notoriously difficult to treat with SoC antibiotics. Additionally, the lack of resistance development observed with C59 treatment is a significant advantage when compared to currently available antibiotics. Furthermore, these compounds are non-toxic to mammalian cell lines at effective concentrations. Our findings indicate the potential of these compounds to treat MRSA infections and underscore the importance of exploring natural products for novel antibiotics. Further investigation will be essential to fully realize the therapeutic potential of these next-generation antimicrobials to address the critical issue of antimicrobial resistance.

A systematic review and meta-analysis of antibiotic-loaded bone cement for prevention of deep surgical site infections following primary total joint replacement

BackgroundThe use of antibiotic-loaded bone cement (ALBC) as a mean for preventing deep surgical site infections (SSI) after total joint replacement is controversial. Therefore, we have conducted a meta-analysis to evaluate the prophylactic effect of ALBC for SSI prevention in patients undergoing arthroplasty. This study was conducted to revise treatment guidelines for MRSA infections in Japan. MethodsPubMed (Medline), Scopus, Embase, Web of Science and Cochrane library were searched for relevant articles comparing preventive effect of ALBC for patients undergoing primary total joint arthroplasty by August 2022. Primary outcome was the incidence of deep SSI. Subgroup analyses by type of surgery (total hip (THA) or knee (TKA) arthroplasty) and by causative pathogen (methicillin-resistant Staphylococcus aureus (MRSA)) were performed. ResultsOf the 3379 studies identified for screening, six studies involving 5745 patients were included. The use of ALBC significantly reduced the incidence of deep SSI in overall patients (risk ratio [RR] 0.60, 95% confidential interval [CI] 0.39–0.92), but the evidence level was very low. There was no significant preventive effect for ALBC compared with non-ALBC in both THA and TKA (THA, RR 0.52, 95% CI 0.23–1.16; TKA, RR 0.64, 95% CI 0.38–1.06), and for preventing MRSA-SSI (RR 0.27, 95% CI 0.03–2.41). ConclusionsAlthough the overall preventive effect of ALBC was significant, the evidence level was very low. Thus, the routine use of ALBC as a mean to prevent SSI in arthroplasty may not be suggested.