Methicillin-resistant Staphylococcus Aureus Research Articles

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.

Chemoenzymatic Modification of Daptomycin: Aromatic Group Installation on Trp1.

Daptomycin is a cyclic lipodepsipeptide antibiotic used to treat infections caused by Gram-positive pathogens, including multi-drug resistant strains such as methicillin-resistant Staphylococcus au-reus (MRSA) and vancomycin-resistant enterococci (VRE). The emergence of daptomycin-resistant bacterial strains has renewed interest in generating daptomycin analogs. Previous studies have shown that replacing the tryptophan of daptomycin with aromatic groups can generate analogs with enhanced potency. Additionally, we have demonstrated that aromatic prenyltransferases can attach diverse groups to the tryptophan of daptomycin. Here, we report the use of the prenyltransferase CdpNPT to derivatize the tryptophan of daptomycin with a library of benzylic and heterocyclic pyrophosphates. An analytical-scale study revealed that CdpNPT can transfer various aromatic groups onto daptomycin. Subsequent scaled-up and purified reactions indicated that the enzyme can attach aromatic groups to N1, C2, C5 and C6 positions of Trp1 of daptomycin. In vitro antibacterial activity assays using six of these purified compounds identified aromatic substituted daptomycin analogs show potency against both daptomycin-susceptible and resistant strains of Gram-positive bacteria. These findings suggest that installing aromatic groups on the Trp1 of daptomycin can lead to the generation of potent daptomycin analogs.

Endophytic fungal diversity and bioactive potentials: investigating antimicrobial and antioxidant activities.

This study investigates the colonization of endophytic fungi in nettle leaf tissues and evaluates their antibacterial and antioxidant activities. Using an inverted optical microscope, extensive fungal colonization was observed in all leaf parts, with hyphae prevalent in epidermal cells, parenchyma cells, and vascular tissues. 144 endophytic fungal isolates were isolated from 800 leaf fragments, indicating an 18% retention rate. ANOVA analysis revealed significant differences (p < 0. 001) in colonization frequencies among 20 subjects, with subject 3 showing the highest frequency (40%) and subject 11 the lowest (2. 5%). Ethyl acetate extracts of the three most abundant endophytic fungi demonstrated notable antibacterial activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Inhibition zones ranged from 9. 5 to 15. 16 mm, with minimum inhibitory concentrations (MICs) between 0. 19 to 25 mg/mL. Alternaria sp. exhibited the highest antimicrobial activity against MRSA. Antioxidant activity was assessed using the DPPH radical scavenging test and FRAP method. All extracts showed substantial free radical scavenging properties, with IC50 values close to those of standards like BHT. Alternaria sp. had the highest antioxidant activity, followed by Epicocum sp. and Ulocladium sp. The FRAP method confirmed high reducing potential, with Alternaria sp. again exhibiting the highest activity. These findings highlight the potential of endophytic fungi in nettle leaves as sources of antimicrobial and antioxidant agents, with significant implications for pharmaceutical and biotechnological applications.

Exploring the potential of nanoparticles-based polydopamine for effective treatment of refractory keratitis: Mild photothermal loop therapy

Keratitis is the leading cause of blindness worldwide. In refractory cases, it can even lead to eyeball enucleation. The critical challenges of refractory keratitis are the drug-resistant bacteria and bacterial biofilms formation. Therefore, we established an innovative therapeutic approach for keratitis based on mild photothermal loop (MPL) therapy. First, we analyzed the bactericidal effect of methicillin-resistant Staphylococcus aureus (MRSA) under various loops and temperature durations to determine the optimal condition. Then, RAN-seq was applied to explore the underlying mechanisms. Additionally, we formulated a dual-purpose polyvinyl alcohol-polydopamine (PDA/PVA) hydrogel system and explored its effects on the reactive oxygen species (ROS) scavenging capability, antibacterial properties, and anti-inflammatory properties in vitro, as well as its effect in vivo. The results indicated substantial bactericidal properties after exposure in four loops, each lasting 10 min at 45 °C. RNA-seq revealed the altered genes related to virulence and biofilm formation. In addition to good photothermal performance, the PDA/PVA system could effectively eliminate MRSA, reduce ROS, inhibit biofilm formation, and decrease inflammatory factors expression. Moreover, the in vivo results demonstrated the potential of MPL for bacterial keratitis. This study serves as the first attempt to use MPL therapy for refractory keratitis, offering a new approach for clinical practice.

Unveiling the multitargeted potential of deprodone and control comparison with linezolid against hydrolase and transferase enzymes of methicillin-resistant Staphylococcus aureus

Staphylococcus aureus (S. aureus), commonly found on the skin and nose, causes minor skin conditions to life-threatening diseases, including boils or impetigo, pneumonia, and bloodstream infections. MRSA (Methicillin-Resistant S. aureus) is a strain resistant to many antibiotics and poses a significant challenge in clinical settings. Nowadays, the alternative drug Linezolid is used, and it is not clear when MRSA starts resistance to it, necessitating the need for more alternative drugs with the least chance of developing resistance. This study aims to identify a multitargeted drug candidate with better efficacy than Linezolid. We have taken three hydrolase and transferase proteins from S. aureus, performed the multitargeted docking studies with human-approved drugs, and compared them with the control drug Linezolid. The docking and MM\\GBSA scores ranging from −6.79 to −5.78 Kcal/mol and − 37.47 to 30.16 Kcal/mol, respectively, that revealed Deprodone (used for inflammatory skin disorders, bowel disease, and fatty acid metabolism disorders) can be a far better and multitargeted drug candidate than Linezolid. We extended our studies to include extensive pharmacokinetics and molecular interaction fingerprints for interaction pattern studies. Also, the DFT computations optimised the drug, and we extended our studies for MD Simulation in water for 100 ns, which showed the complexes among the identified drug with proteins are entirely stable with acceptable deviation, fluctuations and many intermolecular interactions that make them stable. We also performed the MM\\GBSA studies on MD simulation's all 1000 frames to understand the complex energy level. All the results reveal promising interactions between Deprodone and the targeted enzymes, suggesting its potential as a multitargeted therapeutic agent—however, experimental studies need to validate Deprodone against MRSA.

Clove mediated synthesis of Ag-ZnO doped fucoidan nanocomposites and their evaluation of antibacterial, antioxidant and cytotoxicity efficacy study

The Ag-ZnO/Fu nanocomposites were successfully synthesized in an environmentally friendly manner using an aqueous Clove buds extract from the Syzygium aromaticum plant. They were then examined for antibacterial activity against bacterium strains of Escherichia coli, Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Enterococcus faecalis. The UV–Visible spectrophotometry analysis confirmed the presence of zinc oxide (ZnO) nanoparticles at 334 nm, silver oxide (Ag) nanoparticles at 416 nm, and fucoidan at 589 nm in the synthesized nanocomposites. The FT-IR analysis confirmed the presence of five different functional linkages in the synthesized nanocomposites. The positions of diffraction peaks in pure Ag-ZnO/Fu nanocomposite patterns were identified using XRD analysis. The Ag-ZnO/Fu nanocomposites synthesized are more crystalline (77 %), and less amorphous (22.2 %). Silver, O, and Zn signals were detected in the SEM and EDX spectra of the Ag-ZnO/Fu nanocomposite. Different strains of Ag-ZnO/Fu nanocomposites showed stronger antibacterial properties. The DPPH technique was used to perform the antioxidant assay. Cytotoxicity testing was carried out on zebrafish embryos treated with several groups of Clove Ag ZnO/Fucoidan. The combination Ag-ZnO/Fucoidan (300 mg/mL) showed a marginally significant difference in survival (94 %).

Antibacterial Activity and Multi-Targeted Mechanism of Action of Suberanilic Acid Isolated from Pestalotiopsis trachycarpicola DCL44: An Endophytic Fungi from Ageratina adenophora.

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly threatening foodborne pathogen capable of causing severe organ and life-threatening diseases. Over the past years, various commercial antibiotics have been used to treat MRSA infections. However, these commercial antibiotics have not yielded efficient results and also cause other side effects; therefore, there is a need for the development of effective alternatives to replace these commercial antibiotics. Suberanilic acid, an amide alkaloid obtained from the endophytic fungus Pestalotiopsis trachycarpicola DCL44, has been identified as a significant antimicrobial agent. However, its antibiotic properties on multi-drug-resistant bacteria such as MRSA have not been fully explored. Therefore, to investigate the potential antimicrobial mechanism of suberanilic acid against MRSA, a quantitative proteomics approach using tandem mass tagging (TMT) was used. The results obtained in the study revealed that suberanilic acid targets multiple pathways in MRSA, including disruption of ribosome synthesis, inhibition of membrane translocation for nutrient uptake (ABC transporter system), and causing dysregulation of carbohydrate and amino acid energy metabolism. These results provide new insights into the mechanism of action of suberanilic acid against MRSA and offer technical support and a theoretical basis for the development of novel food antimicrobial agents derived from endophytic fungal origin.

Detection of Indicator Genes in Methicillin-Resistant Staphylococcus Aureus (MRSA) Isolated from Meat Samples

Aims: The presence of Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), on retail meat products is becoming more and more of a concern. The aim of the present study is to examine the recovered strains of methicillin-resistant Staphylococcus aureus (MRSA) from different retail beef in Najaf/ Iraq. Methodology and results: The phenotypically by conventional identification. Genotypical examination was made also by polymerase chain reaction (PCR) to detect the genes some diagnostic genes for the enterotoxins sea, seb, sed. More than 200 strains of Staphylococcus aureus, from different butchers meat shops. MRSA strains were characterized by streaking on different selective media and biochemically identified as Staphylococcus aureus MRSA. The results showed that the appearance of sea genes in 51% of the isolates. Seb gene was in 18.90% of the isolates while 5.40 % of the isolates displayed sed gene. Also, Resistance towards six different antimicrobial agents was assessed and revealed that the tested strains of Staphylococcus aureus showed different level of resistance for Streptomycin 100%, Cotrimoxazole 100% , Cephalothin 45.90%and Tetracycline 32.3%. Conclusion, significance and impact of study: the majority of molecular isolate types have been connected to human infections globally, demonstrating that these S. aureus strains in Iraq have a potential for serious pathogenicity. The presence of the genes (sea, sed, and seb) in the MERSA isolates from meat in this study is alarming and raising public health concerns.

Pediatric Clinical Outcomes of Nasal Methicillin-resistant Staphylococcus aureus Polymerase Chain Reaction Utilization.

Methicillin-resistant Staphylococcus aureus (MRSA) is a clinical challenge in selecting empiric antimicrobials for pediatric infections. We implemented nasal MRSA polymerase chain reaction (nMRSA PCR) screening as a diagnostic tool and evaluated its impact on empiric antibiotic use and clinical outcomes. A retrospective single-center study of patients hospitalized with infections who were empirically prescribed anti-MRSA antibiotics was conducted prior to and following the initiation of nMRSA PCR screening. Electronic medical records, pharmacy data and bacterial cultures results were reviewed. Predictive values of nMRSA PCR testing were calculated and the duration of anti-MRSA empiric therapy and clinical outcomes preimplementation and postimplementation were compared. During the preimplementation period, there were 382 distinct episodes (294 unique patients) that met the inclusion criteria and during post-nMRSA PCR implementation, 394 episodes (360 unique patients) were identified. The median time to discontinuation of anti-MRSA antibiotics and proportion of patients prescribed anti-MRSA antibiotics at discharge were significantly lower in postimplementation compared with preimplementation period; 48 versus 56 hours, P < 0.001 and 20.1% versus 40.3%, P < 0.001, respectively. The negative and positive predictive values of nMRSA PCR compared to clinical culture results were 95.6% and 51.2%, respectively. Predefined adverse outcomes were documented in 11 patients who had early anti-MRSA discontinuation with negative nMRSA PCR results but only 3 were restarted on anti-MRSA treatment and none grew MRSA in clinical cultures. Shortened anti-MRSA antibiotic duration, high negative predictive value and low adverse events provide promising evidence that nMRSA PCR is an effective, rapid antimicrobial stewardship tool for hospitalized children.

YjbH contributes to Staphylococcus aureus skin pathology and immune response through Agr-mediated α-toxin regulation

ABSTRACT Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant S. aureus (MRSA) strains being a major contributor in both community and hospital settings. S. aureus relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both in vitro and in vivo. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the ΔyjbIH mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the ΔyjbH mutant. This work continues to define the importance of YjbH in the pathogenesis of S. aureus infection as well as identify a new pathway important for Hla production.

Urinary tract infection among people living with human immunodeficiency virus attending selected hospitals in Addis Ababa and Adama, central Ethiopia.

Urinary tract infections (UTIs) and antibacterial resistance (ABR) are important public health problems, but they are not well-studied among people living with human immunodeficiency virus (PLHIV) globally, especially in low-income countries. Therefore, it is important to regularly measure the extent of UTIs and ABR in the most susceptible populations. This study aimed to investigate the prevalence of UTIs, associated factors, bacterial causal agents, and their antibiotic susceptibility profile among PLHIV in central Ethiopia. A hospital-based cross-sectional study was conducted to recruit 688 PLHIV by a simple random sampling method. Background information was gathered through interviews, while clinical information was gathered from recent information sheets of patient charts using organized, pretested, and validated study tools. Midstream urine was collected aseptically and transported to the Microbiology Laboratory of Aklilu Lemma Institute of Pathobiology within 4 h of collection, maintaining its cold chain. Standard conventional microbial culture methods and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry were used to identify the bacterial isolates at the species level. Kirby Bauer's disk diffusion method was used to determine the antibiotic susceptibility profile of the bacterial isolates based on the interpretation guidelines of the Clinical Laboratory Standard Institute. Logistic regression models were used to examine factors associated with the occurrence of UTIs among PLHIV attending selected hospitals in Addis Ababa, and Adama. Out of 688 PLHIVs involved in the current study, 144 (20.9%) were positive for UTIs, whereas the majority were asymptomatic for UTIs. In the multivariable logistic regression analysis, only HIV RNA ≥ 200 copies/ml [AOR = 12.24 (95% CI, 3.24, 46.20), p < 0.01] and being symptomatic for UTIs during the study period [AOR = 11.57 (95% CI, 5.83, 22.97), p < 0.01] were associated with the occurrence of UTIs. The dominant bacterial species isolated were Escherichia coli (E. coli; n = 65; 43%), followed by Enterococcus faecalis (E. faecalis; n = 16; 10.6%) and Klebsiella pneumoniae (K. pneumoniae; n = 11; 7.3%). Over half of the E. coli isolates were resistant to antibiotics such as gentamicin (GM; n = 44; 67.7%), amikacin (AN; n = 46; 70.8%), nalidixic acid (NA; n = 42; 64.6%), ciprofloxacin (CIP; n = 40; 61.5%), and azithromycin (AZM; n = 45; 69.2%). All of the K. pneumoniae isolates (n = 11; 100%), (n = 6; 54.5%), and (n = 7; 63.6%) were resistant to [amoxicillin as well as amoxicillin + clavulanic acid], ceftriaxone, and sulfamethoxazole + trimethoprim, respectively. All the Staphylococcus aureus (S. aureus) isolates were resistant to cefoxitin, which implies methicillin-resistant S. aureus (MRSA). The high prevalence of UTIs and antibiotic resistance revealed in the current study needs public health interventions such as educating the population about preventive measures and the importance of early treatment of UTIs. Our findings also highlight the need to provide UTI screening services for PLHIV, and healthcare providers should adopt antibiotic stewardship programs to promote and ensure their appropriate and judicious use.

The Effect of Immobilization Methods of P9-4 Antimicrobial Peptide Onto Gelatin Methacrylate on Multidrug-Resistant Bacteria: A Comparative Study.

Wound dressings play a crucial role in wound management by providing a protective barrier and creating an optimal environment for healing. Photocrosslinkable hydrogels, such as gelatin methacrylate (GelMA), have gained attention for their unique properties but often lack antimicrobial activity. To enhance their effectiveness, researchers are exploring methods to incorporate antimicrobial agents into photocrosslinkable hydrogel dressings. Immobilization of antimicrobial peptides (AMPs) onto hydrogel matrices may be achieved through physical or chemical methods. Although, chemical immobilization, using techniques like EDC/NHS chemistry, has shown promise in enhancing antimicrobial properties of hydrogels, the capacity for immobilization may be limited by the structure of hydrogel. Physical methods, such as immersing, offer alternatives but may have different efficacy and biocompatibility. The study aims to chemically immobilize GelMA with P9-4 AMP by photoinduced conjugation and EDC/NHS chemistry and compare its antimicrobial efficacy with a physical immobilization method. Chemical immobilization by EDC/NHS chemistry significantly enhances the antimicrobial effect of GelMA hydrogels against multi-drug resistant Psuedomonas aeruginosa (MDR P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) while maintaining favorable biocompatibility. Study highlights the potential of AMP-functionalized GelMA as advanced wound dressings for reducing infections caused by antibiotic-resistant bacteria and offers a promising approach for future research in wound management.

Evaluation of virulence determinants and cell surface properties associated with biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase (ESBL) Escherichia coli from livestock and poultry origin

Antibiotic resistance poses a persistent threat to modern medicine due to the emergence of novel antibiotic-resistant strains. Therefore, a timely understanding of antibiotic resistance and the virulence biology of pathogenic bacteria, particularly those of public health significance, is crucial for implementing effective mitigation strategies. This study aimed to investigate the virulence profiles of ten S. aureus isolates (NDa to NDj) and ten E. coli isolates (ND1 to ND10) originating from livestock and poultry, and to assess how various cell surface properties and biofilm formation abilities influence antibiotic resistance phenotypes. Antibiotic resistance profiling through phenotypic (AST) and genotypic methods (PCR) confirmed that NDa to NDe were methicillin-resistant S. aureus (MRSA) and ND1 to ND5 were extended-spectrum β-lactamase (ESBL) producing E. coli isolates. Virulence properties such as hemolytic activity, coagulase activity, and nuclease activity were found to be independent of the antibiotic resistance phenotype in S. aureus. In contrast, biofilm formation phenotype was observed to influence antibiotic resistance phenotypes, with MRSA and ESBL E. coli isolates demonstrating higher biofilm formation potency. Chemical and enzymatic analysis of S. aureus and E. coli biofilms revealed proteins and polysaccharides as major components, followed by nucleic acids. Furthermore, cell surface properties such as auto-aggregation and hydrophobicity were notably higher in isolates with strong to medium biofilm-forming capabilities (ESBL and MRSA isolates), corroborated by genomic confirmation of various genes associated with biofilm, adhesion, and colonization. In conclusion, this study highlights that surface hydrophobicity and biofilm formation ability of MRSA (NDa to NDe) and ESBL E. coli (ND1 to ND5) isolates may influence antibiotic resistance phenotypes.

Sonodynamic effect based on vancomycin-loaded microbubbles or meropenem-loaded microbubbles enhances elimination of different biofilms and bactericidal efficacy.

This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology. The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and E. coli biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and E. coli bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and E. coli were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups. Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics.

New Potent Sulfonamide-Based Inhibitors of S. aureus Biotin Protein Ligase.

The key regulatory metabolic enzyme, biotin protein ligase (BPL), is an attractive target for the development of novel antibiotics against multi-drug-resistant bacteria, such as Staphylococcus aureus. Here we report the synthesis and assay of a new series of inhibitors (6-9) against S. aureus BPL (SaBPL), where a component sulfonamide linker was used to mimic the acyl-phosphate group of the natural intermediate biotinyl-5'-AMP (1). A pivotal correlation between the acidity of the central NH of the sulfonamide linker of 6-9 and in vitro inhibitory activity against SaBPL was observed. Specifically, sulfonylcarbamate 8, with its highly acidic sulfonyl central NH, as evaluated by 1H NMR spectroscopy, showed exceptional potency (K i = 10.3 ± 3.8 nM). Furthermore, three inhibitors demonstrated minimum inhibitory concentrations of 16-32 μg/mL against clinical methicillin-resistant S. aureus (MRSA) strains.

Facile Surface Modification with Croconaine-Functionalized Polymer on Polypropylene for Antifouling and NIR-Light-Mediated Photothermal Sterilization.

Biomedical-device-associated infection (BAI) is undoubtedly a major concern and a serious challenge in modern medicine. Therefore, the development of biomedical materials that are capable of resisting or killing bacteria is of great importance. In this work, a croconaine-functionalized polymer with antifouling and near-infrared (NIR) photothermal bactericidal properties was prepared and facilely modified on polypropylene (PP) to combat medical device infections. Croconaine dye is elaborately modified as a "living" initiator, termed CR-4EBiB, for preparing amphiphilic block polymers by atom transfer radical polymerization (ATRP). In the formed polymer coating, the hydrophobic block can strongly adhere to the surface of the PP substrate, whereas the hydrophilic block is located on the outer layer by solvent-induced resistance to bacterial adhesion. Under the irradiation of an NIR laser (808 nm), the croconaine dye in the coating achieved maximum conversion of light to heat to effectively kill E. coli, S. aureus, and methicillin-resistant Staphylococcus aureus (MRSA). This work provides a facile and promising strategy for the development of implantable antibacterial biomedical materials.

Unraveling novel mutation patterns and morphological variations in two dalbavancin-resistant MRSA strains in Austria using whole genome sequencing and transmission electron microscopy

BackgroundThe increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains resistant to non-beta-lactam antimicrobials poses a significant challenge in treating severe MRSA bloodstream infections. This study explores resistance development and mechanisms in MRSA isolates, especially after the first dalbavancin-resistant MRSA strain in our hospital in 2016.MethodsThis study investigated 55 MRSA bloodstream isolates (02/2015–02/2021) from the University Hospital of the Medical University of Vienna, Austria. The MICs of dalbavancin, linezolid, and daptomycin were assessed. Two isolates (16–33 and 19–362) resistant to dalbavancin were analyzed via whole-genome sequencing, with morphology evaluated using transmission electron microscopy (TEM).ResultsS.aureus BSI strain 19–362 had two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene. Isolate 16–33 had a 534 bp deletion in the DHH domain of GdpP and a SNV in pbp2 (p.G146R). Both strains had mutations in the rpoB gene, but at different positions. TEM revealed significantly thicker cell walls in 16–33 (p < 0.05) compared to 19–362 and dalbavancin-susceptible strains. None of the MRSA isolates showed resistance to linezolid or daptomycin.ConclusionIn light of increasing vancomycin resistance reports, continuous surveillance is essential to comprehend the molecular mechanisms of resistance in alternative MRSA treatment options. In this work, two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene were newly identified as possible causes of dalbavancin resistance.

Real-World Clinical Characteristics and Outcomes with Daptomycin Use in Pediatric Patients: A Retrospective Case Series.

Daptomycin (DAP) is a cyclic lipopeptide that exhibits potent in vitro activity against many drug-resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Despite substantial reports evaluating the clinical outcomes of DAP within the adult population, real-world data are lacking in children. The primary goal of this evaluation was to describe the clinical characteristics and outcomes of DAP use in pediatric patients across a wide range of infections. This retrospective evaluation included patients < 18 years of age who were treated with DAP from January 2014 to May 2023. The primary objective was to evaluate the composite clinical success, which was defined as a 30-day survival, the lack of a 30-day microbiological recurrence, and the resolution of signs and symptoms of an acute infection without therapy modifications based on clinical failures. Secondary objectives included adverse effects potentially attributable to DAP and reasons for DAP utilization. Forty patients were included, which were predominately male (62.5%) and white (52.5%), with a median age of 8.7 [IQR, 4.4-16.0] years. DAP was used for a wide range of infections, including central line-associated bloodstream infections (CLABSIs; 32.5%), infective endocarditis (15.0%), surgical-site infections (12.5%), and osteomyelitis (12.5%). The most common pathogen isolated was MRSA (37.5%), and most patients were bacteremic (60.0%). The median DAP dose was 8 [IQR, 6-10] mg/kg, and the median duration of the DAP therapy was 11.5 [IQR, 4.8-18.8] days. Most patients achieved composite clinical success (75.0%). An adverse effect occurred in 5.0% of the patients. DAP was prescribed the most for its ease of use/ability to facilitate discharge (40.0%) and/or for issues with alternative therapies (37.5%). Most pediatric patients that received DAP demonstrated clinical success with a low incidence of adverse effects. Larger, real-world studies of DAP use are necessary to further assess clinical outcomes.

Green synthesis of reduced graphene oxide using Persea americana mill. extract: Characterization, oxygen reduction reaction and antibacterial application

Reduced graphene oxide (rGO) has garnered tremendous attention due to its salient properties that make it applicable in various electrochemical and environmental remediation fields. However, the commonly used chemical method to obtain rGO from graphene oxide (GO) involves toxic chemicals making both the process and product toxic and expensive. In the present work, the suitability of Avocado (Persea americana Mill) seed extract to reduce as-synthesized GO to rGO was investigated fully by optimising the reducing parameters such as the pH, temperature, amount of extract and reduction time. The formation of rGO from GO was confirmed with UV–Vis spectrophotometry (UV–Vis), Fourier Transform Infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and the thermogravimetric analysis (TGA). The optimal conditions for reducing GO with avocado seed extract are pH 8, 100 °C, and 12 h. The average thickness and width for the rGO was 5.55 nm and 11.39 nm accordingly. While GO exhibited a ζ of −29.9.3 mV, the reduced GO possessed a − 38.2 mV. Calculations from the Kotouckey-Levich's equation demonstrated that the obtained rGO can potentially be applied as an oxygen reduction reaction (ORR) catalyst for the generation of hydrogen peroxide since it follows a 2e− pathway mechanism where hydrogen peroxide is generated as an intermediate. Additionally, the avocado seed extract reduced GO demonstrated a slight growth inhibition of methicillin resistant S. aureus (MRSA).

Creation of a novel vancomycin dosing protocol in the electronic medical record and the use of analytics to show improved patient safety

AbstractVancomycin dosing guidelines recommend using first‐order analytic calculations or Bayesian software along with two drug concentrations at steady state to confirm an area under the serum concentration versus time curve (AUC24), which is safe and efficacious for the treatment of serious methicillin‐resistant Staphylococcus aureus (MRSA) infections. Evidence supporting optimal vancomycin dosing for empiric or nonserious MRSA infections is sparse. A systemwide vancomycin dosing protocol applying the latest guidelines and a novel dosing strategy to estimate AUC was created by a large, multicenter healthcare organization. A dosing calculator was embedded in the electronic medical record, and an analytics tool was created to monitor the incidence and predictors of vancomycin‐associated acute kidney injury (VA‐AKI). The incidence of VA‐AKI was tracked over time and between hospitals to identify opportunities to reduce variation. This article describes the implementation of the vancomycin protocol and the use of informatics to ensure patient safety.