RESUMEN
Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.
Asunto(s)
Antibacterianos , Gentamicinas , Osteomielitis , Infecciones Estafilocócicas , Staphylococcus aureus , Andamios del Tejido , Animales , Andamios del Tejido/química , Antibacterianos/farmacología , Antibacterianos/química , Infecciones Estafilocócicas/tratamiento farmacológico , Osteomielitis/tratamiento farmacológico , Conejos , Staphylococcus aureus/efectos de los fármacos , Gentamicinas/farmacología , Gentamicinas/administración & dosificación , Gentamicinas/química , Gentamicinas/uso terapéutico , Ratones , Vancomicina/farmacología , Vancomicina/química , Vancomicina/administración & dosificación , Durapatita/química , Cinética , Cicatrización de Heridas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Colágeno/química , FemeninoRESUMEN
Frequent occurrence of wound infection caused by multiple-resistant bacteria (MRB) has posed a serious challenge to the current healthcare system relying on antibiotics. The development of novel antimicrobial materials with high safety and efficacy to heal wound infection is of great importance in combating this crisis. Herein, we prepared a promising antibacterial hydrogel by cross-linking ferrous ions (Fe2+) with the deprotonated carboxyl anion in sodium alginate (Na-ALG) to cure wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, ferrous-modified Na-ALG (Fe-ALG) hydrogel demonstrated better properties compared to the traditional Na-ALG-based hydrogels, including injectability, self-healing, appropriate fluidity, high-water retention, potent MRSA-killing efficacy, and excellent biocompatibility. Importantly, the addition of Fe2+ enhances the antibacterial efficacy of the Na-ALG hydrogel, enabling it to effectively eliminate MRSA and accelerate the healing of antibiotic-resistant bacterial-infected wounds in a remarkably short period (10 days). This modification not only facilitates wound closure and fur generation, but also mitigates systemic inflammation, thereby effectively impeding the spread of MRSA to the lungs. Taken together, Fe-ALG hydrogel is a promising therapeutic material for treating wound infections by Staphylococcus aureus, especially by antibiotic-resistant strains like MRSA.
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Alginatos , Antibacterianos , Compuestos Ferrosos , Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Cicatrización de Heridas , Infección de Heridas , Alginatos/química , Alginatos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Infecciones Estafilocócicas/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones , Pruebas de Sensibilidad Microbiana , MasculinoRESUMEN
Orbital cellulitis is a common ophthalmologic consultation and has numerous risk factors; however, one that is seldomly encountered is chronic cocaine use. We describe a case of a 63-year-old man with a history of HIV and cocaine use who presented with OD pain, proptosis, and blurred vision. CT imaging revealed extensive erosions throughout the nasal septum, bilateral turbinates, ethmoid sinuses, and loss of the right medial orbital wall. The patient was treated empirically with broad-spectrum antibiotics, and a nasal biopsy and culture grew Staphylococcus aureus. After treatment with IV antibiotics, the patient's visual acuity returned to baseline with resolution of extraocular motility limitations. Although nasal erosions are a well-described sequela of cocaine use, full-thickness osseous defects of the orbital wall are rare and represent late-stage complications of cocaine-induced destructive midline lesions. Orbital cellulitis is a very rare complication in the setting of cocaine-induced destructive midline lesions. Clinicians should be aware of the link between cocaine use, rhino-orbital abnormalities, and orbital cellulitis.
Asunto(s)
Trastornos Relacionados con Cocaína , Celulitis Orbitaria , Tomografía Computarizada por Rayos X , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Cocaína/complicaciones , Celulitis Orbitaria/diagnóstico , Celulitis Orbitaria/inducido químicamente , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Bacterianas del Ojo/diagnóstico , Antibacterianos/efectos adversos , Staphylococcus aureus/aislamiento & purificación , Cocaína/efectos adversosRESUMEN
The rise of methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge in clinical settings due to its ability to evade conventional antibiotic treatments. This overview explores the potential of immunomodulatory strategies as alternative therapeutic approaches to combat MRSA infections. Traditional antibiotics are becoming less effective, necessitating innovative solutions that harness the body's immune system to enhance pathogen clearance. Recent advancements in immunotherapy, including the use of antimicrobial peptides, phage therapy, and mechanisms of immune cells, demonstrate promise in enhancing the body's ability to clear MRSA infections. However, the exact interactions between these therapies and immunomodulation are not fully understood, underscoring the need for further research. Hence, this review aims to provide a broad overview of the current understanding of non-traditional therapeutics and their impact on immune responses, which could lead to more effective MRSA treatment strategies. Additionally, combining immunomodulatory agents with existing antibiotics may improve outcomes, particularly for immunocompromised patients or those with chronic infections. As the landscape of antibiotic resistance evolves, the development of effective immunotherapeutic strategies could play a vital role in managing MRSA infections and reducing reliance on traditional antibiotics. Future research must focus on optimizing these approaches and validating their efficacy in diverse clinical populations to address the urgent need for effective MRSA management strategies.
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Inmunomodulación , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/terapia , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Inmunoterapia/métodos , Terapia de Fagos/métodos , Animales , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/uso terapéutico , Factores InmunológicosRESUMEN
Introduction. Staphylococcus aureus is a leading agent in community-acquired bacteraemia (CAB) and has been linked to elevated mortality rates and methicillin resistance in Costa Rica.Gap statement and aim. To update and enhance previous data obtained in this country, we analysed the clinical manifestations of 54 S. aureus CAB cases in a tertiary hospital and delineated the sequence types (STs), virulome, and resistome of the implicated isolates.Methodology. Clinical information was retrieved from patient files. Antibiotic susceptibility profiles were obtained with disc diffusion and automated phenotypic tests. Genomic data were exploited to type the isolates and for detection of resistance and virulence genes.Results. Primary infections predominantly manifested as bone and joint infections, followed by skin and soft tissue infections. Alarmingly, 70% of patients continued to exhibit positive haemocultures beyond 48 h of treatment modification, with nearly a quarter requiring mechanical ventilation or developing septic shock. The 30-day mortality rate reached an alarming 40%. More than 60% of the patients were found to have received suboptimal or inappropriate antibiotic treatment, and there was an alarming tendency towards the overuse of third-generation cephalosporins as empirical treatment. Laboratory tests indicated elevated creatinine levels, leukocytosis, and bandaemia within the first 24 h of hospitalization. However, most showed improvement after 48 h. The isolates were categorized into 13 STs, with a predominance of representatives from the clonal complexes CC72 (ST72), CC8 (ST8), CC5 (ST5, ST6), and CC1 (ST188). Twenty-four isolates tested positive for mecA, with ST72 strains accounting for 20. In addition, we detected genes conferring acquired resistance to aminoglycosides, MLSB antibiotics, trimethoprim/sulfamethoxazole, and mutations for fluoroquinolone resistance in the isolate collection. Genes associated with biofilm formation, capsule synthesis, and exotoxin production were prevalent, in contrast to the infrequent detection of enterotoxins or exfoliative toxin genes.Conclusions. Our findings broaden our understanding of S. aureus infections in a largely understudied region and can enhance patient management and treatment strategies.
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Antibacterianos , Bacteriemia , Infecciones Comunitarias Adquiridas , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus aureus , Centros de Atención Terciaria , Humanos , Costa Rica/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/mortalidad , Bacteriemia/microbiología , Bacteriemia/epidemiología , Bacteriemia/mortalidad , Bacteriemia/tratamiento farmacológico , Masculino , Staphylococcus aureus/genética , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Persona de Mediana Edad , Femenino , Anciano , Adulto , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Anciano de 80 o más Años , Adulto Joven , Adolescente , Factores de Virulencia/genética , NiñoRESUMEN
BACKGROUND: Staphylococcus aureus is an infectious bacterium that is frequently found in healthcare settings and the community. This study aimed to prepare rutin-loaded chitosan nanoparticles (Rut-CS NPs) and assess their antibacterial activity against pathogenic strains of S. aureus. RESULTS: The synthesized Rut-CS NPs exhibited an amorphous morphology with a size ranging from 160 to 240 nm and a zeta potential of 37.3 mV. Rut-CS NPs demonstrated significant antibacterial activity against S. aureus strains. Following exposure to Rut-CS NPs, the production of staphyloxanthin pigment decreased by 43.31-89.63%, leading to increased susceptibility of S. aureus to hydrogen peroxide. Additionally, visual inspection of cell morphology indicated changes in membrane integrity and permeability upon Rut-CS NPs exposure, leading to a substantial increase (107.07-191.08%) in cytoplasmic DNA leakage in the strains. Furthermore, ½ MIC of Rut-CS NPs effectively inhibited the biofilm formation (22.5-37.5%) and hemolytic activity (69-82.59%) in the S. aureus strains. CONCLUSIONS: Our study showcases that Rut-CS NPs can serve as a novel treatment agent to combat S. aureus infections by altering cell morphology and inhibiting virulence factors of S. aureus.
Asunto(s)
Antibacterianos , Biopelículas , Quitosano , Pruebas de Sensibilidad Microbiana , Nanopartículas , Rutina , Staphylococcus aureus , Xantófilas , Staphylococcus aureus/efectos de los fármacos , Quitosano/farmacología , Quitosano/química , Rutina/farmacología , Rutina/química , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Xantófilas/farmacología , Xantófilas/química , Hemólisis/efectos de los fármacos , Factores de Virulencia , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Humanos , Peróxido de Hidrógeno/farmacologíaRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that can cause severe bacterial pneumonia. Amygdalin is the main active pharmaceutical ingredient of bitter almond, which has broad-spectrum antibacterial, anti-inflammatory, anti-oxidation and immunomodulatory effects. It is also the main ingredient of Yinhua Pinggan granule, which is commonly used to moisten the lung and relieve cough. However, little is known about the effects of amygdalin on MRSA. In this study, we found that amygdalin exhibited good antimicrobial activity in vitro against MRSA. Amygdalin has a protective effect on MRSA infected cells, and the effect is better when combined with levofloxacin. It also can reduce the adhesion and invasion of MRSA to cells. Amygdalin has anti-inflammatory and antioxidant effects, which can significantly reduce the increase of inflammatory factors and the production of ROS caused by infection. The protective mechanism of amygdalin on cells may be related to inhibiting the expression of NLRP3, ASC and IL-1ß pyroptosis pathways. Taken together, our study suggests that amygdalin exerts antibacterial effects by affecting biofilm formation, the expression of virulence factors, and drug resistance genes. Amygdalin combined with levofloxacin has a protective effect on A549 cells infected with MRSA, and the mechanism may be related to the inhibition of inflammatory response, oxidative damage and pyroptosis.
Asunto(s)
Amigdalina , Antibacterianos , Inflamación , Staphylococcus aureus Resistente a Meticilina , Estrés Oxidativo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Amigdalina/farmacología , Humanos , Estrés Oxidativo/efectos de los fármacos , Células A549 , Antibacterianos/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/microbiología , Células Epiteliales/metabolismo , Pulmón/microbiología , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Biopelículas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Levofloxacino/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiologíaRESUMEN
INTRODUCTION: Tropical myositis - also known as pyomyositis - is a subacute, primary infection of skeletal muscle. Long considered a diagnosis exclusive to tropical climates, recently it has been reported increasingly in historically nontropical climates. We present a case of tropical myositis in Madison, Wisconsin, occurring in a febrile type 1 diabetic patient without travel or known exposure. CASE PRESENTATION: A 35-year-old male with a history of von Willebrand disease, type 1 diabetes, and financial insecurity resulting in insulin rationing presented with 2 weeks of generalized weakness. On exam, he had a multitude of large, erythematous "bumps" across his body, which had been increasing in size for more than 2 weeks. His blood glucose was 518, with leukocytosis and labs supportive of diabetic ketoacidosis. Computed tomography revealed extensive intramuscular and subcutaneous abscesses of the left chest, bilateral erector spinae, right gluteal muscles, bilateral thighs, left leg, and left upper and lower arm. Broad-spectrum antibiotics were initiated, as was treatment for diabetic ketoacidosis. Blood and urine cultures revealed oxacillin-susceptible Staphylococcus aureus. After clinical stabilization, he underwent initial incision and drainage of the abscesses. His condition would require 14 more operative incision and drainage procedures and wound closure attempts before he was discharged to a rehab facility after more than a month-long hospitalization. DISCUSSION: Severe tropical myositis is associated with high morbidity and high use of health care resources. The exponential rise in cases in the United States in recent years risks further stressing an already-burdened health care system. We explore potential causes of the increase in cases of tropical myositis in nontropical regions, including increasing rates of diabetes and poverty and climate change. Recent data suggest that the large majority of tropical myositis cases are caused by Panton-Valentine leukocidin toxin-producing Staphylococcus aureus strains. There is a theoretical mitigation of disease severity when patients receive early protein synthesis inhibitor antibiotic treatment, though these findings are limited to case reports and observational studies and lack controlled clinical trials. This case highlights the need for early identification, antibiotic administration, and surgical source control in suspected cases of tropical myositis.
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Diabetes Mellitus Tipo 1 , Piomiositis , Humanos , Masculino , Diabetes Mellitus Tipo 1/complicaciones , Adulto , Piomiositis/diagnóstico , Piomiositis/tratamiento farmacológico , Piomiositis/terapia , Diagnóstico Diferencial , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Wisconsin , Antibacterianos/uso terapéutico , Fiebre/etiología , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
In response to the escalating antibiotic resistance in multidrug-resistant pathogens, we propose an innovative phagemid-based capsid system to generate CRISPR-Cas13a-loaded antibacterial capsids (AB-capsids) for targeted therapy against multidrug-resistant Staphylococcus aureus. Our optimized phagemid system maximizes AB-capsid yield and purity, showing a positive correlation with phagemid copy number. Notably, an 8.65-fold increase in copy number results in a 2.54-fold rise in AB-capsid generation. Phagemids carrying terL-terS-rinA-rinB (prophage-encoded packaging site genes) consistently exhibit high packaging efficiency, and the generation of AB-capsids using lysogenized hosts with terL-terS deletion resulted in comparatively lower level of wild-type phage contamination, with minimal compromise on AB-capsid yield. These generated AB-capsids selectively eliminate S. aureus strains carrying the target gene while sparing non-target strains. In conclusion, our phagemid-based capsid system stands as a promising avenue for developing sequence-specific bactericidal agents, offering a streamlined approach to combat antibiotic-resistant pathogens within the constraints of efficient production and targeted efficacy.
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Antibacterianos , Sistemas CRISPR-Cas , Cápside , Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Cápside/metabolismo , Cápside/efectos de los fármacos , Antibacterianos/farmacología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
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.
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Antibacterianos , Biopelículas , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/fisiología , Animales , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/farmacología , Ratones , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Pruebas de Sensibilidad Microbiana , Modelos Animales de Enfermedad , Vancomicina/farmacología , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Cefazolina/farmacología , FemeninoRESUMEN
Antibacterial resistance requires an advanced strategy to increase the efficacy of current therapeutics in addition to the synthesis of new generations of antibiotics. In this study, copper oxide nanoparticles (CuO-NPs) were green synthesized using Moringa oleifera root extract. CuO-NPs fabricated into a form of aspartic acid-ciprofloxacin-polyethylene glycol coated copper oxide-nanotherapeutics (CIP-PEG-CuO) to improve the antibacterial activity of NPs and the efficacy of the drug with controlled cytotoxicity. These NPs were charachterized by Fourier transform infrared spectroscopy (FTIR), x-rays diffraction spectroscopy (XRD), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Antibacterial screening and bacterial chemotaxis investigations demonstrated that CIP-PEG-CuO NPs show enhanced antibacterial potential against Gram-positive and Gram-negative clinically isolated pathogenic bacterial strains as compared to CuO-NPs. In ex-vivo cytotoxicity CIP-PEG-CuO-nano-formulates revealed 88% viability of Baby Hamster Kidney 21 cell lines and 90% RBCs remained intact with nano-formulations during hemolysis assay. An in-vivo studies on animal models show that Staphylococcus aureus were eradicated by this newly developed formulate from the infected skin and showed wound-healing properties. By using specially designed nanoparticles that are engineered to precisely transport antimicrobial agents, these efficient nano-drug delivery systems can target localized infections, ensure targeted delivery, enhance efficacy through increased drug penetration through physical barriers, and reduce systemic side effects for more effective treatment.
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Antibacterianos , Ciprofloxacina , Cobre , Polietilenglicoles , Staphylococcus aureus , Cobre/química , Cobre/farmacología , Polietilenglicoles/química , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Animales , Ciprofloxacina/farmacología , Ciprofloxacina/química , Tecnología Química Verde , Pruebas de Sensibilidad Microbiana , Nanopartículas del Metal/química , Línea Celular , Infecciones Estafilocócicas/tratamiento farmacológico , Moringa oleifera/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Nanopartículas/química , CricetinaeRESUMEN
Staphylococcus aureus infections present a significant threat to the global healthcare system. The increasing resistance to existing antibiotics and their limited efficacy underscores the urgent need to identify new antibacterial agents with low toxicity to effectively combat various S. aureus infections. Hence, in this study, we have screened T-muurolol for possible interactions with several S. aureus-specific bacterial proteins to establish its potential as an alternative antibacterial agent. Based on its binding affinity and interactions with amino acids, T-muurolol was identified as a potential inhibitor of S. aureus lipase, dihydrofolate reductase, penicillin-binding protein 2a, D-Ala:D-Ala ligase, and ribosome protection proteins tetracycline resistance determinant (RPP TetM), which indicates its potentiality against S. aureus and its multi-drug-resistant strains. Also, T-muurolol exhibited good antioxidant and anti-inflammatory activity by showing strong binding interactions with flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, and cyclooxygenase-2. Consequently, molecular dynamics (MD) simulation and recalculating binding free energies elucidated its binding interaction stability with targeted proteins. Furthermore, quantum chemical structure analysis based on density functional theory (DFT) depicted a higher energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (EHOMO-LUMO) with a lower chemical potential index, and moderate electrophilicity suggests its chemical hardness and stability and less polarizability and reactivity. Additionally, pharmacological parameters based on ADMET, Lipinski's rules, and bioactivity score validated it as a promising drug candidate with high activity toward ion channel modulators, nuclear receptor ligands, and enzyme inhibitors. In conclusion, the current findings suggest T-muurolol as a promising alternative antibacterial agent that might be a potential phytochemical-based drug against S. aureus. This study also suggests further clinical research before human application.
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Antibacterianos , Descubrimiento de Drogas , Fitoquímicos , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/química , Descubrimiento de Drogas/métodos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Simulación por Computador , Humanos , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
Introduction: Despite years of efforts to develop new antibiotics for eradicating multidrug-resistant (MDR) and multi-virulent Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Staphylococcus aureus (VRSA) infections, treatment failures and poor prognoses in most cases have been common. Therefore, there is an urgent need for new therapeutic approaches targeting virulence arrays. Our aim is to discover new anti-virulence therapies targeting MRSA and VRSA virulence arrays. Methodology: We employed phenotypic, molecular docking, and genetic studies to screen for anti-virulence activities among selected promising compounds: Coumarin, Simvastatin, and Ibuprofen. Results: We found that nearly all detected MRSA and VRSA strains exhibited MDR and multi-virulent profiles. The molecular docking results aligned with the phenotypic and genetic assessments of virulence production. Biofilm and hemolysin productions were inhibited, and all virulence genes were downregulated upon treatment with sub-minimum inhibitory concentration (sub-MIC) of these promising compounds. Ibuprofen was the most active compound, exhibiting the highest inhibition and downregulation of virulence gene products. Moreover, in vivo and histopathological studies confirmed these results. Interestingly, we observed a significant decrease in wound area and improvements in re-epithelialization and tissue organization in the Ibuprofen and antimicrobial treated group compared with the group treated with antimicrobial alone. These findings support the idea that a combination of Ibuprofen and antimicrobial drugs may offer a promising new therapy for MRSA and VRSA infections. Conclusion: We hope that our findings can be implemented in clinical practice to assist physicians in making the most suitable treatment decisions.
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Antibacterianos , Biopelículas , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Infecciones Estafilocócicas , Staphylococcus aureus Resistente a Vancomicina , Factores de Virulencia , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Staphylococcus aureus Resistente a Meticilina/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Biopelículas/efectos de los fármacos , Factores de Virulencia/genética , Staphylococcus aureus Resistente a Vancomicina/efectos de los fármacos , Animales , Virulencia/efectos de los fármacos , Ibuprofeno/farmacología , Ibuprofeno/uso terapéutico , Humanos , Cumarinas/farmacología , Cumarinas/uso terapéutico , Ratones , Modelos Animales de Enfermedad , Proteínas Hemolisinas/antagonistas & inhibidores , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/genética , Farmacorresistencia Bacteriana MúltipleRESUMEN
Vancomycin has proven remarkably durable to resistance evolution by Staphylococcus aureus despite widespread treatment with vancomycin in the clinic. Only 16 cases of vancomycin-resistant S. aureus (VRSA) have been documented in the United States. It is thought that the failure of VRSA to spread is partly due to the fitness cost imposed by the vanA operon, which is the only known means of high-level resistance. Here, we show that the fitness cost of vanA-mediated resistance can be overcome through laboratory evolution of VRSA in the presence of vancomycin. Adaptation to vancomycin imposed a tradeoff such that fitness in the presence of vancomycin increased, while fitness in its absence decreased in evolved lineages. Comparing the genomes of vancomycin-exposed and vancomycin-unexposed lineages pinpointed the D-alanine:D-alanine ligase gene (ddl) as the target of loss-of-function mutations, which were associated with the observed fitness tradeoff. Vancomycin-exposed lineages exhibited vancomycin dependence and abnormal colony morphology in the absence of drug, which were associated with mutations in ddl. However, further evolution of vancomycin-exposed lineages in the absence of vancomycin enabled some evolved lineages to escape this fitness tradeoff. Many vancomycin-exposed lineages maintained resistance in the absence of vancomycin, unlike their ancestral VRSA strains. These results indicate that VRSA might be able to compensate for the fitness deficit associated with vanA-mediated resistance, which may pose a threat to the prolonged durability of vancomycin in the clinic. Our results also suggest vancomycin treatment should be immediately discontinued in patients after VRSA is identified to mitigate potential adaptations.
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Antibacterianos , Infecciones Estafilocócicas , Staphylococcus aureus Resistente a Vancomicina , Vancomicina , Vancomicina/farmacología , Antibacterianos/farmacología , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus Resistente a Vancomicina/genética , Resistencia a la Vancomicina/genética , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , MutaciónRESUMEN
Infections are a major complication of open fractures and fracture fixation. In this study, an innovative bioactive medical device was used to experimentally treat MRSE-induced osteomyelitis in rabbit tibia. This paper investigates the clinical significance of inflammatory biomarkers (NLR, PLR, MLR and PMR), SII and IL-6 and assesses their role in the development of osteomyelitis. The main objective is to identify the utility of hematological reports derived from neutrophils, leukocytes, monocytes and platelets in the evolution of implant-related osteomyelitis and the estimation of treatment efficiency. In particular, this study compares the response of these inflammatory markers to different treatments in the presence or absence of bioactive materials and/or topical antibiotics over time. The analysis of the threads showed that NLR, PLR and SII had high values in the acute phase of the disease, so that after chronicization, they decrease. The animals treated with vancomycin nano-functionalized peptide-enriched silk fibroin-coated implants showed lower levels of inflammatory biomarkers compared to the other groups (empty implants and peptide-enriched silk fibroin-coated implants). NLR, PLR and SII, complemented by IL-6 can be used as fairly accurate biomarkers for the diagnosis of osteomyelitis.
Asunto(s)
Biomarcadores , Modelos Animales de Enfermedad , Interleucina-6 , Osteomielitis , Infecciones Estafilocócicas , Animales , Conejos , Osteomielitis/microbiología , Osteomielitis/tratamiento farmacológico , Osteomielitis/inmunología , Interleucina-6/sangre , Interleucina-6/metabolismo , Biomarcadores/sangre , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis , Enfermedad Crónica , Antibacterianos/farmacología , Inflamación , Enfermedad Aguda , Vancomicina/farmacología , Relevancia ClínicaRESUMEN
BACKGROUND: Sternoclavicular joint arthritis is a rare condition that poses considerable diagnostic and therapeutic challenges, leading to severe complications and a high mortality rate. Although surgical interventions are often considered necessary for advanced cases, some reports have suggested that conservative management with antibiotic therapy can be effective in certain cases. However, to our knowledge, there are no reports of successful conservative treatment in cases exhibiting aggressive spread. This report highlights a case of advanced sternoclavicular joint arthritis with bone destruction and pulmonary infiltration, successfully treated conservatively with outpatient antibiotic therapy. CASE PRESENTATION: A 58-year-old Japanese male presented with a 1-month history of left-sided shoulder pain. Contrast-enhanced computed tomography showed abscess formation and clavicular bone destruction, with infiltrative shadows suggesting lung involvement. The diagnosis of sternoclavicular joint arthritis was made, and outpatient oral antibiotic therapy was initiated. The patient exhibited a marked reduction in inflammatory marker levels and symptoms, and antibiotic therapy was discontinued after 3 weeks, with no recurrence observed at a 4-month follow-up. CONCLUSIONS: This case highlights that conservative management with antibiotics can be effective for treating advanced sternoclavicular joint arthritis, emphasizing the need for individualized management and further research into non-surgical treatment options.
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Antibacterianos , Artritis Infecciosa , Tratamiento Conservador , Osteomielitis , Articulación Esternoclavicular , Humanos , Masculino , Articulación Esternoclavicular/diagnóstico por imagen , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Osteomielitis/tratamiento farmacológico , Osteomielitis/diagnóstico , Osteomielitis/terapia , Osteomielitis/diagnóstico por imagen , Artritis Infecciosa/terapia , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/diagnóstico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/complicacionesRESUMEN
Staphylococci are responsible for a wide range of infections in animals. The most common species infecting animals include Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus intermedius. Recent increases in antibiotic use and antibiotic resistance in animals highlight the need to understand the potential role of commercial livestock as a reservoir of staphylococci and antibiotic resistance genes. Nasal swabs were collected from 143 apparently healthy pigs and 21 pig farm workers, and 45 environmental swabs of feed and water troughs, from two commercial pig farms in the Western Cape, South Africa. Staphylococci were isolated, identified using mass-spectrometry, and antimicrobial susceptibility testing and Illumina whole genome sequencing were performed. One hundred and eighty-five (185) Staphylococcus spp. isolates were obtained, with Mammalicoccus sciuri (n = 57; 31%) being the most common, followed by S. hyicus (n = 40; 22%) and S. aureus (n = 29; 16%). S. epidermidis was predominantly identified in the farm workers (n = 18; 86%). Tetracycline resistance was observed across all species, with rates ranging from 67 to 100%. Majority of M. sciuri isolates (n = 40; 70%) were methicillin resistant, with 78% (n = 31) harbouring mecA. M. sciuri isolates had genes/elements which were associated with SCCmec_type_III (3A) and SCCmec_type_VIII(4A) and were mostly observed in ST61 strains. ST239 strains were associated with SCCmec_type_III(3A). High rates of tetracycline resistance were identified among staphylococci in the pig farms in Western Cape, South Africa. This highlights the need for policy makers to regulate the use of this antibiotic in pig farming.
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Antibacterianos , Granjas , Infecciones Estafilocócicas , Staphylococcus , Animales , Sudáfrica/epidemiología , Porcinos/microbiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus/efectos de los fármacos , Staphylococcus/genética , Staphylococcus/aislamiento & purificación , Antibacterianos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana/genética , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/epidemiologíaRESUMEN
BACKGROUND Septic arthritis of the shoulder is a rare and challenging condition to treat. Typically, arthroscopic debridement is the common approach. Specifically, septic arthritis of the shoulder caused by methicillin-resistant bacteria is extremely difficult to cure due to persistent infection and limited antibiotic options. However, recent studies have demonstrated that continuous local antibiotic perfusion (CLAP) can provide favorable results for bone and soft tissue infections. By administering the antibiotics required to suppress the biofilm, CLAP can effectively treat the infection while sparing the tissue. CASE REPORT A 46-year-old woman undergoing long-term hemodialysis treatment for congenital anomalies of the kidney and urinary tract experienced severe pain in the left shoulder joint during glucocorticoid treatment for amyloid arthritis of the right shoulder. Despite the absence of fever, significant swelling and fluid accumulation were observed in the left shoulder joint, leading to the performance of a puncture. A bacterial examination of the puncture fluid detected methicillin-resistant coagulase-negative Staphylococcus epidermidis (MRCNS). In this report, we present a case in which CLAP was administered for septic arthritis of the shoulder caused by methicillin-resistant bacteria. After irrigation debridement, the patient received intravenous antibiotics and CLAP. Following the initiation of treatment, the dosage of antibiotics was adjusted while performing therapeutic drug monitoring. An early improvement in the inflammatory response and sedation of the infection was observed, with no relapse after 2 years. CONCLUSIONS Septic arthritis can lead to serious functional impairment if left untreated. CLAP is a promising option for managing septic arthritis of the shoulder.
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Antibacterianos , Artritis Infecciosa , Articulación del Hombro , Infecciones Estafilocócicas , Humanos , Femenino , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/microbiología , Artritis Infecciosa/terapia , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Articulación del Hombro/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Desbridamiento , Estudios de Seguimiento , Staphylococcus epidermidis/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Resistencia a la MeticilinaRESUMEN
Staphylococcus aureus infection and colonization in patients may be transmitted to healthcare providers and the environment and subsequently cause healthcare-associated infections in other patients. Pathogenic S. aureus strains produce virulence factors, such as Panton-Valentine Leukocidin (PVL), that contribute to the severity of infections and aid in their spread. The emergence of antimicrobial resistance (AMR) is additional concern with respect to S. aureus infection. In this study, the virulence genes and antibiotic resistance profiles of S. aureus were characterized from patients' clinical isolates, healthcare workers' (HCWs') nasal colonization screenings, and the environment at a tertiary healthcare hospital in Addis Ababa, Ethiopia. A total of 365 samples were collected from September 2021 to September 2022: 73 patients' clinical specimens, 202 colonization screenings from HCWs, and 90 hospital environment's swabs. Fifty-one (25.2%) HCW and 10/90 (11.1%) environment S. aureus isolates were identified. Among the 134 isolates, 10 (7.5%) were methicillin-resistant S. aureus (MRSA). Three (4.1%), five (9.8%), and two (20.0%) of the MRSA isolates were identified from the patients, HCWs, and the environment, respectively. Overall, 118 (88.1%) were ampicillin and penicillin resistant; 70 (52.2%) were trimethoprim sulfamethoxazole resistant; and 28 (20.9%) were erythromycin resistant. S. aureus isolates from patients were more resistant to antibiotics than isolates from HCWs or the hospital environment (p<0.05). A total of 92/134 (68.6%) isolates possessed the lukfF-PV gene, which was identified in 62 (85.0%), 26 (51.0%), and 4 (40.0%) of the patient, HCWs, and the environment, respectively. The proportion of lukfF-PV gene containing S. aureus isolated from patient samples was statistically significant. Four (40.0%) of the MRSA isolates also had the lukfF-PV gene. The identification of highly AMR and virulence factors from patients, HCWs and the environment is concerning. Further studies are needed to identify potential transmission links and improve infection prevention and control.
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Antibacterianos , Personal de Salud , Infecciones Estafilocócicas , Staphylococcus aureus , Centros de Atención Terciaria , Humanos , Etiopía/epidemiología , Femenino , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto , Masculino , Staphylococcus aureus/genética , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Antibacterianos/farmacología , Persona de Mediana Edad , Pruebas de Sensibilidad Microbiana , Adolescente , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Adulto Joven , Factores de Virulencia/genética , Leucocidinas/genética , Niño , Exotoxinas/genética , Preescolar , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Farmacorresistencia Bacteriana/genética , Lactante , Anciano , Toxinas BacterianasRESUMEN
BACKGROUND: Wound healing pivots on a finely orchestrated inflammatory cascade, critical for tissue repair. Chronic wounds, compounded by persistent inflammation and susceptibility to infection, pose formidable clinical challenges. Nanofiber dressings offer promising avenues for wound care, yet their interaction with inflammation and infection remains elusive. We aim to delineate the inflammatory cascade preceding wound closure and assess Cu@Bbc nanofibers' therapeutic efficacy in mitigating inflammation and combating infection. Their unique attributes suggest promise in modulating inflammation, fostering tissue regeneration, and preventing microbial colonization. Investigating the intricate interplay between nanofiber scaffolds, inflammation, and infection may unveil mechanisms of enhanced wound healing. Our findings could stimulate the development of tailored dressings, urgently needed for effective wound management amidst immune dysregulation, infection, and inflammation. METHODS: In this investigation, we synthesized Cu@Bbc nanofibers, incorporating curcumin and berberine chloride, for wound healing applications. We evaluated their individual and combined antibacterial, anti-biofilm, and antioxidant activities, alongside binding affinity with pro-inflammatory cytokines through molecular docking. Morphological characterization was conducted via SEM, FTIR assessed functional groups, and wettability contact angle measured hydrophobic properties. The physical properties, including tensile strength, swelling behavior, and thermal stability, were evaluated using tensile testing, saline immersion method and thermogravimetric analysis. Biodegradability of the nanofibers was assessed through a soil burial test. Biocompatibility was determined via MTT assay, while wound healing efficacy was assessed with in vitro scratch assays. Controlled drug release and antibacterial activity against MRSA were examined, with in vivo assessment in a zebrafish model elucidating inflammatory responses and tissue remodeling. RESULTS: In this study, the synergistic action of curcumin and berberine chloride exhibited potent antibacterial efficacy against MRSA, with significant anti-mature biofilm disruption. Additionally, the combination demonstrated heightened antioxidant potential. Molecular docking studies revealed strong binding affinity with pro-inflammatory cytokines, suggesting a role in expediting the inflammatory response crucial for wound healing. Morphological analysis confirmed nanofiber quality, with drug presence verified via FTIR spectroscopy. Cu@Bbc demonstrated higher tensile strength, optimal swelling behavior, and robust thermal stability as evaluated through tensile testing and thermogravimetric analysis. Additionally, the Cu@Bbc nanofiber showed enhanced biodegradability, as confirmed by the soil burial test. Biocompatibility assessments showed favorable compatibility, while in vitro studies demonstrated potent antibacterial activity. In vivo zebrafish experiments revealed accelerated wound closure, re-epithelialization, and heightened immune response, indicative of enhanced wound healing. CONCLUSION: In summary, our investigation highlights the efficacy of Cu@Bbc nanofibers, laden with curcumin and berberine chloride, in displaying robust antibacterial and antioxidant attributes while also modulating immune responses and inflammatory cascades essential for wound healing. These results signify their potential as multifaceted wound dressings for clinical implementation.