Methicillin-resistant Staphylococcus Aureus Research Articles

Strategy against super-resistant bacteria: Curdlan-induced trained immunity combined with multi-epitope subunit vaccine

Methicillin-resistant Staphylococcus aureus (MRSA) is rapidly spreading worldwide, emerging as a leading cause of bacterial infections in healthcare and community settings. This poses serious risks to human health. The shortage of novel antibiotics and the absence of effective vaccines make MRSA particularly challenging to treat. Existing vaccine development strategies often fail to provide early protection against infections, highlighting the urgent need for solutions. Herein, we propose a novel strategy combining trained immunity with a multi-epitope subunit vaccine to combat MRSA infections. We comprehensively evaluated the trained immune phenotypes induced by β-glucan from barley and curdlan. Macrophages trained with curdlan exhibited a more balanced inflammatory response compared to β-glucan from barley, expressing higher levels of IL-1β, IFN-β, TGF-β, and CCL2 upon secondary stimulation. Furthermore, curdlan-induced trained immunity rapidly provided excellent protection against S. aureus infection in mice. RNA-sequencing analysis revealed that curdlan modulates the Wnt signaling pathway in macrophages, resolves inflammation, and promotes tissue repair. When combined with one or two doses of S. aureus multivalent epitope antigen against MRSA infection, curdlan-induced trained immunity enhanced early protection and promoted recovery. Our study demonstrates the feasibility of combining trained immunity with vaccine protection against MRSA, providing a strategy against multi-drug resistant bacteria.

Antimicrobial effect of lactoferrin and glycerol monolaurate on selected bacteria associated with newborn infections

Human breast milk contains a rich array of bioactive substances, such as immunoglobulins, lactoferrin antimicrobial peptides, and glycerol monolaurate, which play a crucial role in providing immune protection to infants. Infant formula manufacturers strive to match mother's milk's nutritional makeup, including immune-boosting ingredients. Lactoferrin and glycerol monolaurate (GML) are important antibacterial compounds in human milk. The study aimed to investigate the effect of bovine lactoferrin (bLf) and GML in preventing the growth of inoculated bacteria into infant formula. The study examined both individual and combined use of these components. The bacteria that were tested included: 1) Gram-negative bacteria: Cronobacter sakazakii strains 12868 and 29004, Pseudomonas aeruginosa, Salmonella enterica Typhimurium, and 2) Gram-positive bacteria: Methicillin-resistant Staphylococcus aureus (MRSA), and Listeria monocytogenes. The result of the agar diffusion assays showed that bLf, at a concentration of 16 mg/disc, exhibited strong inhibition (≥20 mm) of all the selected bacterial strains. On the other hand, GML at a concentration of 8 mg/disc showed strong inhibition of all strains; however, Gram-positive bacteria were more susceptible, so a concentration of 5 mg/disc was enough to achieve strong inhibition of these strains. The minimal bactericidal concentrations (MBC) analysis aimed to achieve a >3-log reduction in the growth of various bacterial strains. The results showed that S. enterica Typhimurium and L. monocytogenes were more susceptible to bLf than the other strains (MBC: 7 and 4.8 mg/ml, respectively, vs. 14.9–18.4 mg/ml for the other strains). In contrast, MRSA and L. monocytogenes were more susceptible to GML (MBC: 6 and 10 mg/ml, respectively, vs. 16–18 mg/ml for Gram-negative strains). The results of reconstituted powdered infant formulas (RPIF), with the addition of bLf, GML, or both at pathogen-specific MBC, showed significant log reductions in the growth of experimentally inoculated bacteria compared to the control at different time intervals. All bacterial strains exposed to bLf and GML exhibited >3-log reduction within 72 h, with Gram-positive strains showing >7-log reduction. GML and bLf combined had a stronger anti-bacterial activity than individual components, indicating the potential of combining GML and bLf as natural agents against specific pathogenic bacteria. Future studies are needed to understand the potential use of these compounds in different food matrices and clinical settings.

TRPA1 Influences Staphylococcus aureus Skin Infection in Mice and Associates with HIF-1a and MAPK Pathway Modulation.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major public health burden. Emerging antibiotic resistance has heightened the need for new treatment approaches for MRSA infection such as developing novel antimicrobial agents and enhancing the host's defense response. The thermo-ion channels Transient Receptor Potential (TRP-) A1 and V1 have been identified as modulators of S. aureus quorum sensing in cell culture models. However, their effects on in vivo infection control are unknown. In this study, we investigated the therapeutic effect of natural TRP ion channel inhibitors on MRSA skin infection in mice. While deletion of TRPV1 did not affect lesion size or inflammatory markers, TRPA1-/- mice demonstrated significantly reduced infection severity and abscess size. Treatment with natural inhibitors of TRPA1 with or without blockade of TRPV1 also reduced abscess size. Tissue transcriptomic data coupled with immunohistochemistry revealed that TRPA1 inhibition impacted heat shock protein expression (HSP), modulated the HIF-1a and MAPK pathways, and reduced IL4 expression. Additionally, metabolomics data showed an impact on purine and glycosaminoglycan pathways. Multi-omic integration of transcriptomic and metabolic data revealed that diacylglycerol metabolism was the likely bridge between metabolic and immunological impacts. Our findings suggest that TRPA1 antagonism could provide a promising and cost-effective therapeutic approach for reducing the severity of MRSA infection, and presents a novel underlying molecular mechanism.

Bactericidal behavior of silver nanoparticle decorated nano-sized magnetic hydroxyapatite.

Methicillin-resistant Staphylococcus aureus (MRSA) is the most common cause of acute bacterial arthritis. Due to the increase in antibiotic resistance in these bacteria, the discovery of new antibacterial agents has become one of the hot topics in the scientific community. Here, we prepared a nano-sized porous biocompatible magnetic hydroxyapatite through a solvothermal method. Then, we adopted a post-synthesis modification strategy to modify its surface for the stabilization of Ag NPs through a green reduction by the euphorbia plant extract. Moreover, the results show that the prepared composite perfectly prevents the aggregation of Ag NPs. This composite was used as a bactericidal and antibiofilm agent against MRSA bacteria in an in vitro environment, which showed excellent results. Also, the cell viability assay indicates that the prepared composite has low cytotoxicity, making it a perfect antibacterial agent for in vivo experiments.

Tunable Assembly of Photocatalytic Colloidal Coatings for Antibacterial Applications.

In this study, evaporation-induced size segregation and interparticle interactions are harnessed to tune the microstructure of photocatalytic colloidal coatings containing TiO2 nanoparticles and polymer particles. This enabled the fabrication of a library of five distinct microstructures: TiO2-on-top stratification, a thin top layer of polymer or TiO2, homogeneous films of raspberry particles, and a sandwich structure. The photocatalytic and antibacterial activities of the coatings were evaluated by testing the viability of Methicillin-resistant Staphylococcus aureus (MRSA) bacteria using the ISO-27447 protocol, showing a strong correlation with the microstructure. UVA irradiation for 4 h induces a reduction in MRSA viability in all coating systems, ranging from 0.6 to 1.1 log. Films with TiO2-enriched top surfaces exhibit better resistance to prolonged exposure to disinfection and bacterial testing. The remaining systems, nonetheless, present higher antibacterial activity because of a larger number of pores and coating defects that enhance light and water accessibility for the generation and transport of reactive oxygen species. This work establishes design rules for photocatalytic coatings based on the interplay between performance and film architecture, offering valuable insights for several applications, including antibacterial surfaces, self-cleaning/antifogging applications, and water purification.

Identification of Antimicrobial-Resistant Zoonotic Bacteria in Swine Production: Implications from the One Health Perspective.

Antimicrobial resistance poses a major threat to global health and food security and is primarily driven by antimicrobial use in human and veterinary medicine. Understanding its epidemiology at farm level is crucial for effective control measures. Despite the significant reduction in antibiotic use in conventional livestock production, the swine sector traditionally has a higher level of antibiotic use in veterinary medicine. Consequently, multidrug resistance (MDR) among microbial isolates of swine origin has been relatively frequent. The aim of this study was to assess the presence of multidrug-resistant (MDR) bacteria, enteric pathogens and resistance genes to the main antibiotics used in clinical practice, both within the environment and in animals across pig farms characterized by varying degrees of sanitary status. A total of 274 samples were collected. Of these, 34 samples were collected from the environment (wall swabs, slat swabs and slurry pit), and 240 samples were collected from animals (sows' and piglets' rectal faeces). All samples were analysed for MDR bacteria and enteric pathogens. The study revealed a high frequency of extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales and Campylobacter spp., with ESBL-producing Enterobacterales predominating in high health status farms (environment and animals) and Campylobacter spp. in both high health status and low health status environments. Additionally, a high percentage of methicillin-resistant Staphylococcus aureus (MRSA) was found, mainly in environmental samples from high health status farms, and Clostridioides difficile was distributed ubiquitously among farms and samples. Furthermore, though less frequently, vancomycin-resistant Enterococcus faecium (VRE) was isolated only in high health status farms, and Gram-negative bacilli resistant to carbapenems were isolated only in environmental samples of high health status and low health status farms. This study underscores the importance of surveillance for MDR bacteria in farm animals and their environment, including their waste. Such ecosystems serve as crucial reservoirs of bacteria, requiring national-level surveillance to promote responsible antibiotic use and pandemic control.

Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) harboring mupirocin and biocide resistance genes in a large health care system

We aimed to determine the prevalence of genes associated with high-level mupirocin and biocide resistance in methicillin-resistant Staphylococcus aureus (MRSA) isolates among hospitalized patients and to characterize their genomic and epidemiologic features. Study conducted on an integrated health system. Clinical cultures with MRSA from hospitalized patients collected between March 1, 2023, and January 20, 2024 underwent prospective whole-genome sequencing (WGS), including assessment for the presence of markers of resistance against mupirocin (mupA) and biocides (qac). Demographic and clinical characteristics were reviewed. We analyzed 463 MRSA isolates. The overall prevalence of mupA(+), qacA(+), and qacC(+) genes was 22.0%, 2.4%, and 19.0%, respectively. Most mupA(+) isolates belonged to ST8, but ST8732 (a novel variant of ST8) had the highest prevalence of mupA(+) isolates at 95%. Patients mupA(+) were older, and none of the isolates from pediatric patients harbored this gene. Through prospective WGS of MRSA isolates we detected a prevalence of genes conferring mupirocin resistance considerably higher than previously reported, particularly among MRSA ST8 variants. Our findings highlight the need for monitoring resistance to agents used for the prevention of Staphylococcus aureus infections, as these trends have implications for infection prevention programs and public health at large.

Analysis of genetic signatures of virulence and resistance in foodborne Staphylococcus aureus isolates from Algeria

Staphylococcus aureus, a frequent commensal of the human microbiota, also frequently associated with various infections. This study aimed to genetically characterize foodborne methicillin resistant S. aureus (MRSA) in Oran, Algeria. From a total of 474 food matrices, 30 MRSA strains were isolated and characterized using whole genome sequencing (WGS) and bioinformatics. The genomes were assessed for antimicrobial resistance and virulence genes, sequence and spa types and single nucleotide polymorphism (SNP) to establish their relationship. The prevalence of S. aureus was 34.38% with MRSA accounting for 18.40%. MRSA strains showed high resistance to penicillinG, ampicillin and tetracycline. However, inconsistencies were noted between phenotypic and genotypic resistance for methicillin, aminoglycosides, and phenicolates, with mecA gene identified in three isolates. The isolates revealed eight different sequence types (predominantly ST97 and ST45) and eleven spa types (mainly t230 and t8503), correlating with SNP clusters except for isolates belonging to ST7200.86.66% of isolates harboured at least one enterotoxin gene underscores their potential public health threat. This investigation highlights the genetic heterogeneity among S. aureus regarding virulence and antimicrobial resistance, shedding light into food safety in Algeria and the ease of using WGS approach to rapidly characterize bacterial pathogens in community environments.

PH-responsive mupirocin-loaded hybrid nanoparticles in hydrogel and film forming spray against resistant bacterial wound infections

The aim of this work was to fabricate smart Mupirocin loaded Lipid Polymeric Hybrid Nanoparticles (MUP-LPHNs) based hydrogel and Film forming spray (FFS) for targeted release of MUP in response to wound pH. The MUP-LPHNs were optimized through design expert v.12. The optimized MUP-LPHNs had a particle size of 270.7 ± 3.20 nm with zeta potential of 17.05 ± 1.20 mV and entrapment efficiency of 88.0 ± 0.35 %. MUP-LPHNs showed no major chemical interaction, spherical morphology and amorphous nature as confirmed by FTIR, SEM and XRD, respectively. MUP-LPHNs were loaded to MUP-LPHNs based hydrogel (MUP-LPHNs-HG) and MUP-LPHNs based film forming spray (MUP-LPHNs-FFS) with successful characterization. In vitro release data confirmed sustained and pH dependent release from both MUP-LPHNs-HG and MUP-LPHNs-FFS as higher release was observed at pH 7.4. MUP-LPHNs-HG and MUP-LPHNs-FFS showed high efficiency and long-term inhibition of Staphylococcus aureus (SA), Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) with 4–6 fold increase in the antibacterial activity compared to MUP solution. MUP-LPHNs-HG and MUP-LPHNs-FFS exhibited both in vitro and in vivo wound pH contingent, sustained drug release. Moreover, the prepared nanocarriers systems flaunted significant therapeutic efficacy against MRSA infected wound model by significant reduction in bacterial load and wound area, increased hydroxy proline level and antioxidant enzymes and reduced proinflammatory cytokines. Similarly, immunohistochemistry, histopathological and trichrome assessment showed significant reduction in level of inflammatory markers, accelerated and enhanced re-epithelization, improved connective tissue remodeling and effectively promote collagen deposition with effective wound regeneration, respectively. It can be concluded that LPHNs could be a potential carrier system for enhancing the therapeutic efficacy of MUP against resistant bacterial wound infections.

Development and Evaluation of Preparations Based on Ethanol Extract of Chrysopogon zizanioides, Asteracantha longifolia, Asparagus racemosus, Tinospora cordifolia

The emergence of antibiotic-resistant bacteria poses a critical challenge to global public health, necessitating the exploration of alternative therapeutic strategies. This study investigates the antimicrobial potential of bioactive compounds derived from four medicinal plants: Chrysopogon zizanioides, Asteracantha longifolia, Asparagus racemosus, and Tinospora cordifolia. These plants, traditionally used in various medicinal systems, contain compounds such as khusimol, stigmasterol, lupeol, shatavarin IV, asparagamine A, tinosporin, and cordifolioside A, which have shown promising antimicrobial properties against resistant pathogens. Two formulations were developed: Formulation 1, designed for oral administration, and Formulation 2, a topical cream, both targeting antibiotic-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli (MDR E. coli). The Minimum Inhibitory Concentration (MIC) of each extract and formulation was determined using a microdilution method. Results indicate that these plant-based formulations exhibit significant inhibitory effects on bacterial growth, with potential applications as complementary therapies to conventional antibiotics. This study highlights the potential of these medicinal plants as sources of novel antimicrobial agents, providing a sustainable approach to combating antibiotic resistance.

Methicillin resistant Staphylococcus aureus mazEF expression promotes infections by influencing cellular growth, antibiotic sensitivity, and formation of biofilms

Staphylococcus aureus infections are hard to treat due to the emergence of antibiotic resistant strains, as well as their ability to form biofilms. The MazEF toxin–antitoxin system is thought play a role in bacterial biofilm phenotype as well as antibiotic resistance. In S. aureus, the physiologic function of the mazEF gene in the disease transition from acute to chronic infection is not well understood. In methicillin resistant S. aureus (MRSA), loss of mazF expression results in loss of resistance to first generation cephalosporins. mazF::tn displayed sensitivity while the isogenic wild type (WT) remained resistant. mazF::tn displayed significantly increased growth of biofilms on metal implants over 48 h compared to WT and the complemented transposon mutant. mazF::tn biofilms displayed significantly decreased antibiotic tolerance to vancomycin and cefazolin in comparison to WT and complement biofilms. Mice given mazF::tn in a sepsis model displayed less abscess burden and increased survival (100%) when treated with cefazolin compared to WT bacteremia treated with cefazolin (20%). mazF::tn periprosthetic joint infections displayed increased biofilm burden at acute time points and decreased biofilm burden at chronic time points. Our data suggests MazEF in MRSA is responsible for controlling growth of biofilms, antibiotic tolerance, and influence chronic infections in vivo.

Genomic portraits of methicillin-resistant staphylococci (MRS) from food fish unveiled the genes associated with staphylococcal food poisoning (SFP), virulence and antimicrobial resistance

BackgroundCharacteristics of non-clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) especially from fishery environment are poorly understood. This research, in addition to comprehensive characterisation, sought to delineate the genetic relatedness between the MRSA strains originating from clinical as well as non-clinical settings. Out of 39 methicillin-resistant staphylococcal isolates from 197 fish samples, 6 (Three each of methicillin-resistant S. haemolyticus (MRSH) and MRSA) with distinct resistance profiles were selected for whole-genome sequencing. Using respective bioinformatics tools, MRSA genomes were comprehensively characterized for resistome, virulomes, molecular epidemiology and phylogenetic analysis. Simultaneously, MRSH genomes were specifically examined to characterize antimicrobial resistance genes (ARGs), owing to the fact that MRSH is often recognized as a reservoir for resistance determinants.ResultsThree MRSA clones identified in this study include ST672-IVd/t13599 (sequence type-SCCmec type/spa type), ST88-V/t2526, and ST672-IVa/t1309. Though, the isolates were phenotypically vancomycin-sensitive, five of the six genomes carried vancomycin resistance genes including the VanT (VanG cluster) or VanY (VanM cluster). Among the three MRSA, only one harbored the gene encoding Panton-Valentine Leukocidin (PVL) toxin, while staphylococcal enterotoxin (SEs) genes such as sea and seb, associated with staphylococcal food poisoning were identified in two other MRSA. Genomes of MRSH carried a composite of type V staphylococcal cassette chromosome mec (SCCmec) elements (5C2 & 5). This finding may be explained by the inversion and recombination events that may facilitate the integration of type V elements to the SCC elements of S. aureus with a methicillin-susceptible phenotype. Phylogenetically, MRSA from a non-clinical setting displayed a considerable relatedness to that from clinical settings.ConclusionThis study highlights the genetic diversity and resistance profiles of MRSA and MRSH, with non-clinical MRSA showing notable relatedness to clinical strains. Future research should explore resistance gene transfer mechanisms and environmental reservoirs to better manage MRSA spread.

Discovery of membrane-targeting amphiphilic honokiol derivatives containing an oxazolethione moiety to combat methicillin-resistant Staphylococcus aureus (MRSA) infections

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen causing infections in hospitals and the community, and there is an urgent need for the development of novel antibacterials to combat MRSA infections. Herein, a series of amphiphilic honokiol derivatives containing an oxazolethione moiety were prepared and evaluated for their in vitro antibacterial and hemolytic activities. The screened optimal derivative, I3, exhibited potent in vitro antibacterial activity against S. aureus and clinical MRSA isolates with MIC values of 2–4 μg/mL, which was superior to vancomycin in terms of its rapid bactericidal properties and was less susceptible to the development of resistance. The SARs analysis indicated that amphiphilic honokiol derivatives with fluorine substituents had better antibacterial activity than those with chlorine and bromine substituents. In vitro and in vivo toxicity studies revealed that I3 has relatively low toxicity. In a MRSA-infected mouse skin abscess model, I3 (5 mg/kg) effectively killed MRSA at the infected site and attenuated the inflammation effects, comparable to vancomycin. In a MRSA-infected mouse sepsis model, I3 (12 mg/kg) was found to significantly reduce the bacterial load in infected mice and increase survival of infected mice. Mechanistic studies indicated that I3 has membrane targeting properties and can interact with phosphatidylglycerol (PG) and cardiolipin (CL) of MRSA cell membranes, thereby disrupting MRSA cell membranes, further inducing the increase of reactive oxygen species (ROS), protein and DNA leakage to achieve rapid bactericidal effects. Finally, we hope that I3 is a potential candidate molecule for the development of antibiotics to conquer superbacteria-related infections.

Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia.

A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated antibiotic treatment during influenza infection causes a fungal dysbiosis that drive lung eosinophilia and impair MRSA clearance. Finally, we evaluated three cohorts of hospitalized patients and found eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs thereby increasing the risk of developing a secondary bacterial infection.

Natural agents derived Pickering emulsion enabled by silica nanoparticles with enhanced antibacterial activity against drug-resistant bacteria

The emergence of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) has become a global health challenge due to the overuse of antibiotics. Natural substances including enzymes and essential oils have shown great potential as alternative treatment options. However, the combinational use of these natural agents remains challenging due to the denaturation of enzymes upon direct contact with oil. In this study, we report the design of a Pickering emulsion containing two natural antibacterial agents, lysozyme and tea tree oil, stabilized by fractal silica nanoparticles. In this design, the enzyme activity is kept and the volatility problem of tea tree oil is mitigated. Due to synergistic bacterial cell wall digestion and membrane disruption functions, potent bactericidal efficacy in vitro against drug-resistant bacteria is achieved. The therapeutic potential is further demonstrated in a wound healing model with drug-resistant bacteria infection, better than a synthetic antibiotic, Ampicillin. This study opens new avenues for the development of natural product-based antimicrobial treatments with promising application potential.

Daptomycin Dosage Optimization in Renal Impairment Using Model-Informed Precision Dosing.

Daptomycin's efficacy and toxicity are closely related to its exposure, which can vary widely among individuals. The patient, a 59-year-old male with an estimated glomerular filtration rate (eGFR) of 12 mL/min/1.73 m² and a weight of 64 kg, was treated with 850 mg of daptomycin every other day for infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA). For patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m², the dosing recommendations are not explicitly defined in the endocarditis guidelines. Subsequently, the pharmacology department was contacted to adjust the dosage. A population pharmacokinetic model developed by Dvorchik et al. was used for Bayesian estimation of the patient's pharmacokinetic parameters. The 24-hour area under the curve (AUC24) of daptomycin was calculated at steady state using peak and trough plasma samples. The minimum inhibitory concentration (MIC) of the MRSA strain was 0.25 mg/L. An AUC24/MIC ratio below 666 is associated with higher mortality risk, while an AUC24 above 939 h·mg/L correlates with increased risk of muscular toxicity. Initial AUC24 estimation was 1091 h·mg/L. Following a dosage reduction to 700 mg every other day, the AUC24 increased to 1600 h·mg/L. Further reduction to 500 mg every other day brought the AUC24 down to 750 h mg/L, with two subsequent measurements showing consistent AUC24 values of 500 h·mg/L, which is within the target range. Daptomycin ended 6 weeks after the initial negative blood culture, with no adverse effects or recurrence of MRSA infection. This case underscores the need for therapeutic drug monitoring and a multidisciplinary approach to adjust daptomycin doses in patients with renal impairment.

3D printable gelatin/nisin biomaterial inks for antimicrobial tissue engineering applications.

Modern regenerative medicine approaches can rely on the fabrication of personalised medical devices and implants; however, many of these can fail due to infections, requiring antibiotics and revision surgeries. Given the rise in multidrug resistant bacteria, developing implants with antimicrobial activity without the use of traditional antibiotics is crucial for successful implant integration and improving patient outcomes. 3D printed gelatin-based implants have a broad range of applications in regenerative medicine due to their biocompatibility, ease of modification and degradability. In this paper, we report on the development of gelatin biomaterial inks loaded with the antimicrobial peptide, nisin, for extrusion-based 3D printing to produce scaffolds with controlled porosity, high shape fidelity, and structural stability. Rheological properties were comprehensively studied to develop inks that had shear thinning behaviour and viscoelastic properties to ensure optimal printability and extrudability, and enable precise deposition and structural integrity during 3D printing. The 3D printed scaffolds fabricated from the gelatin/nisin inks demonstrated excellent antimicrobial efficacy (complete kill) against Gram positive bacteria methicillin-resistant Staphylococcus aureus (MRSA). Overall, this ink's high printability and antimicrobial efficacy with the model antimicrobial peptide, nisin, offers the potential to develop customisable regenerative medicine implants that can effectively combat infection without contributing to the development of multidrug resistant bacteria.

Efficacy and Safety of Antibiotics in the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections: A Systematic Review and Network Meta-Analysis.

Vancomycin is a first-line drug for the treatment of MRSA infection. However, overuse of vancomycin can cause bacteria to become resistant, forming resistant strains and making infections more difficult to treat. This study aimed to evaluate the efficacy and safety of different antibiotics in the treatment of MRSA infections and to compare them, mainly with vancomycin, to find better vancomycin alternatives. All studies were obtained from the PubMed and Embase databases from inception to 13 April 2023. The three comprehensive indicators of clinical cure success rate, clinical microbiological success rate, and adverse reactions were evaluated, and the clinical cure success rates of three disease types, complex skin and skin structure infections (cSSSIs), complex skin and soft tissue infections (cSSTIs), and pneumonia, were analyzed in subgroups. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. A total of 38 trials with 6281 patients were included, and 13 drug treatments were evaluated. For MRSA infections, the results of network meta-analysis showed that the clinical success rates of linezolid, the combination of vancomycin and rifampin, and the combination of minocycline and rifampin were better than that of vancomycin (RR 1.71; 95%-CI 1.45-2.02), (RR 2.46; 95%-CI 1.10-5.49) (RR, 2.77; 95%-CI 1.06-7.21). The success rate of clinical microbiological treatment with vancomycin was inferior to that with telavancin (RR 0.74; 95%-CI 0.55-0.99). Linezolid had a higher rate of adverse reactions than teicoplanin (RR 5.35; 95%-CI 1.10-25.98). Subgroup analysis showed that vancomycin had a lower clinical success rate than linezolid in the treatment of MRSA-induced cSSSIs, cSSTIs, and pneumonia (RR 0.59; 95%-CI 0.44-0.80) (RR 0.55; 95%-CI 0.35-0.89) (RR 0.55; 95%-CI 0.32-0.93). This systematic review and NMA provide a new comparison framework for the clinical treatment of MRSA infection. The NMA suggests that linezolid may be the antibiotic of choice for the treatment of MRSA infections, with the ability to improve clinical and microbiological success rates despite its disadvantage in terms of adverse effects. At the same time, the combination of minocycline and rifampicin may be the most effective drug to treat MRSA-induced cSSSIs, tedizolid may be the best drug to treat MRSA-induced cSSTIs, and the combination of vancomycin and rifampicin may be the most effective treatment for MRSA-induced pneumonia. More high-quality studies are still needed in the future to further identify alternatives to vancomycin. PROSPERO registration number CRD42023416788.

Rapid de-escalation of anti-MRSA therapy guided by S. aureus nares screening for patients with pneumonia: protocol of a randomized controlled trial (SNAP study).

The current Infectious Disease Society of America and American Thoracic Society (IDSA/ATS) guidelines recommend linezolid or vancomycin as an empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospitalized patients with specific risk factors,. A nasal PCR-assay for MRSA, with its high negative predictive value, can guide a rapid antibiotic de-escalation avoiding unnecessary anti-MRSA treatment. The indiscriminate use of these drugs has contributed to the emergence of resistant S. aureus strains leading to adverse effects without any survival benefit, increasing hospital stays and associated costs. Aim of the study is the use of this diagnostic tool to reduce empirical anti-MRSA treatment duration in pneumonia, shortening antimicrobial therapy days while measuring in-hospital mortality, length of stay and adverse drug event incidence. It is a prospective, randomized single-center controlled trial planned to be conducted in the Azienda Consorziale Policlinico di Bari. The research project will have a duration of 12 months following the approval of the Ethical Committee of the University of Bari. The minimum sample size is 38 patients per group, for a total of 76 subjects, calculated assuming a standard deviation of 10, a power of 90%, a type I error of 5% and a 10% drop-out rate. We will enroll eligible patients ensuring their evidence-based management according to guidelines, we will perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative. For both arms, follow-up visits will be on day 2, 5, 7, 14, and 28 relatives to the enrollment visit (day 0). Data will be collected on the clinical course of pneumonia and laboratory tests. Our study will provide evidence on the duration (in days) of the antibiotic intake as a primary outcome of the study. Secondary outcome measures include in-hospital mortality, the length of stay and days of mechanical ventilation (in VAP), and the incidence of adverse events related to the administration of the therapy. https://classic.clinicaltrials.gov/ct2/show/NCT06238297, identifier NCT06238297.

Improving Antibiotic Use in Pediatric Preseptal Cellulitis Using a Clinical Practice Guideline.

The purpose of this study was to evaluate the impact of a clinical practice guideline (CPG) on antibiotic use and resource utilization for pediatric preseptal cellulitis. This retrospective quasiexperimental study included patients between the age of 2 months and 17 years admitted for preseptal cellulitis between January 2013 and December 2023. The preseptal cellulitis CPG was implemented in December 2020 using a multifaceted strategy that included buy-in from key stakeholders, education of frontline providers, the official CPG launch, and stakeholder check-ins. The primary outcome was the use of broad-spectrum antibiotics, including dual/triple therapy and methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics. The secondary outcome was resource utilization including blood testing and imaging. Outcomes were compared pre- and post-CPG implementation using the Fisher exact test and logistic regressions. Of 236 patients meeting inclusion criteria, 175 and 61 patients composed the pre- and post-CPG cohorts, respectively. Median age (interquartile range) was 4.0 (1.8-8.3) years and 46% of the population were female. Post-CPG implementation changes in empirical antibiotic use included decreases in broad-spectrum use from 100% to 66% (P < .001), dual/triple therapy from 47% to 16% (P < .001), and MRSA active agents from 86% to 26% (P < .001). There was a decrease in complete blood count and blood culture orders from 75% to 57% (P = .014) and 32% to 18% (P = .047), respectively. Use of broad-spectrum antibiotics, including dual/triple therapy and MRSA active antibiotics for the treatment of pediatric preseptal cellulitis, decreased after CPG implementation.