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1.
Proc Natl Acad Sci U S A ; 121(14): e2318391121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38527207

RESUMEN

The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.


Asunto(s)
Platino (Metal) , Infección de Heridas , Humanos , Platino (Metal)/farmacología , Cicatrización de Heridas , Vendajes , Antibacterianos/farmacología , Antibacterianos/química , Seda/química , Bacterias , Hidrogeles/farmacología
2.
Proc Natl Acad Sci U S A ; 119(51): e2212340119, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36520668

RESUMEN

A hallmark of microbial ecology is that interactions between members of a community shape community function. This includes microbial communities in human infections, such as chronic wounds, where interactions can result in more severe diseases. Staphylococcus aureus is the most common organism isolated from human chronic wound infections and has been shown to have both cooperative and competitive interactions with Pseudomonas aeruginosa. Still, despite considerable study, most interactions between these microbes have been characterized using in vitro well-mixed systems, which do not recapitulate the infection environment. Here, we characterized interactions between S. aureus and P. aeruginosa in chronic murine wounds, focusing on the role that both macro- and micro-scale spatial structures play in disease. We discovered that S. aureus and P. aeruginosa coexist at high cell densities in murine wounds. High-resolution imaging revealed that these microbes establish a patchy distribution, only occupying 5 to 25% of the wound volume. Using a quantitative framework, we identified a precise spatial structure at both the macro (mm)- and micro (µm)-scales, which was largely mediated by P. aeruginosa production of the antimicrobial 2-heptyl-4-hydroxyquinoline N-oxide, while the antimicrobial pyocyanin had no impact. Finally, we discovered that this precise spatial structure enhances S. aureus tolerance to aminoglycoside antibiotics but not vancomycin. Our results provide mechanistic insights into the biogeography of S. aureus and P. aeruginosa coinfected wounds and implicate spatial structure as a key determinant of antimicrobial tolerance in wound infections.


Asunto(s)
Coinfección , Staphylococcus aureus Resistente a Meticilina , Infecciones por Pseudomonas , Infecciones Estafilocócicas , Infección de Heridas , Humanos , Ratones , Animales , Staphylococcus aureus , Pseudomonas aeruginosa , Infección de Heridas/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/farmacología , Infecciones por Pseudomonas/tratamiento farmacológico , Biopelículas
3.
Nano Lett ; 24(26): 7868-7878, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38912706

RESUMEN

Wound infections, especially those caused by pathogenic bacteria, present a considerable public health concern due to associated complications and poor therapeutic outcomes. Herein, we developed antibacterial nanoparticles, namely, PGTP, by coordinating guanidine derivatives with a porphyrin-based sonosensitizer. The synthesized PGTP nanoparticles, characterized by their strong positive charge, effectively disrupted the bacterial biosynthesis process through charge interference, demonstrating efficacy against both Gram-negative and Gram-positive bacteria. Additionally, PGTP nanoparticles generated reactive oxygen species under ultrasound stimulation, resulting in the disruption of biofilm integrity and efficient elimination of pathogens. RNA-seq analysis unveiled the detailed mechanism of wound healing, revealing that PGTP nanoparticles, when coupled with ultrasound, impair bacterial metabolism by interfering with the synthesis and transcription of amino acids. This study presents a novel approach to combatting wound infections through ultrasound-driven charge-interfering therapy, facilitated by advanced antibacterial nanomaterials.


Asunto(s)
Antibacterianos , Biopelículas , Nanopartículas , Infección de Heridas , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Nanopartículas/química , Nanopartículas/uso terapéutico , Biopelículas/efectos de los fármacos , Animales , Ratones , Ondas Ultrasónicas , Especies Reactivas de Oxígeno/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Humanos , Porfirinas/química , Porfirinas/farmacología , Porfirinas/uso terapéutico , Terapia por Ultrasonido/métodos , Bacterias Grampositivas/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos
4.
Nano Lett ; 24(26): 8046-8054, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38912748

RESUMEN

Bacteria invasion is the main factor hindering the wound-healing process. However, current antibacterial therapies inevitably face complex challenges, such as the abuse of antibiotics or severe inflammation during treatment. Here, a drug-free bioclay enzyme (Bio-Clayzyme) consisting of Fe2+-tannic acid (TA) network-coated kaolinite nanoclay and glucose oxidase (GOx) was reported to destroy harmful bacteria via bimetal antibacterial therapy. At the wound site, Bio-Clayzyme was found to enhance the generation of toxic hydroxyl radicals for sterilization via cascade catalysis of GOx and Fe2+-mediated peroxidase mimetic activity. Specifically, the acidic characteristics of the infection microenvironment accelerated the release of Al3+ from kaolinite, which further led to bacterial membrane damage and amplified the antibacterial toxicity of Fe2+. Besides, Bio-Clayzyme also performed hemostasis and anti-inflammatory functions inherited from Kaol and TA. By the combination of hemostasis and anti-inflammatory and bimetal synergistic sterilization, Bio-Clayzyme achieves efficient healing of infected wounds, providing a revolutionary approach for infectious wound regeneration.


Asunto(s)
Antibacterianos , Glucosa Oxidasa , Cicatrización de Heridas , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Esterilización/métodos , Arcilla/química , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Hierro/química
5.
Emerg Infect Dis ; 30(5): 1055-1057, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38666739

RESUMEN

We report a clinical isolate of Burkholderia thailandensis 2022DZh obtained from a patient with an infected wound in southwest China. Genomic analysis indicates that this isolate clusters with B. thailandensis BPM, a human isolate from Chongqing, China. We recommend enhancing monitoring and surveillance for B. thailandensis infection in both humans and livestock.


Asunto(s)
Infecciones por Burkholderia , Burkholderia , Filogenia , Infección de Heridas , Humanos , Masculino , Burkholderia/genética , Burkholderia/aislamiento & purificación , Burkholderia/clasificación , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/diagnóstico , China/epidemiología , Genoma Bacteriano , Infección de Heridas/microbiología , Persona de Mediana Edad
6.
Antimicrob Agents Chemother ; 68(2): e0121623, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38214514

RESUMEN

The growing threat of antibiotic-resistant bacterial pathogens necessitates the development of alternative antimicrobial approaches. This is particularly true for chronic wound infections, which commonly harbor biofilm-dwelling bacteria. A novel electrochemical bandage (e-bandage) delivering low-levels of hypochlorous acid (HOCl) was evaluated against Pseudomonas aeruginosa murine wound biofilms. 5 mm skin wounds were created on the dorsum of mice and infected with 106 colony-forming units (CFU) of P. aeruginosa. Biofilms were formed over 2 days, after which e-bandages were placed on the wound beds and covered with Tegaderm. Mice were administered Tegaderm-only (control), non-polarized e-bandage (no HOCl production), or polarized e-bandage (using an HOCl-producing potentiostat), with or without systemic amikacin. Purulence and wound areas were measured before and after treatment. After 48 hours, wounds were harvested for bacterial quantification. Forty-eight hours of polarized e-bandage treatment resulted in mean biofilm reductions of 1.4 log10 CFUs/g (P = 0.0107) vs non-polarized controls and 2.2 log10 CFU/g (P = 0.004) vs Tegaderm-only controls. Amikacin improved CFU reduction in Tegaderm-only (P = 0.0045) and non-polarized control groups (P = 0.0312) but not in the polarized group (P = 0.3876). Compared to the Tegaderm-only group, there was less purulence in the polarized group (P = 0.009). Wound closure was neither impeded nor improved by either polarized or non-polarized e-bandage treatment. Concurrent amikacin did not impact wound closure or purulence. In conclusion, an HOCl-producing e-bandage reduced P. aeruginosa in wound biofilms with no impairment in wound healing, representing a promising antibiotic-free approach for addressing wound infection.


Asunto(s)
Infecciones por Pseudomonas , Infección de Heridas , Animales , Ratones , Pseudomonas aeruginosa , Ácido Hipocloroso , Amicacina , Infecciones por Pseudomonas/microbiología , Infección de Heridas/microbiología , Vendajes , Antibacterianos , Biopelículas
7.
Anal Chem ; 96(19): 7787-7796, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38702857

RESUMEN

Microorganism are ubiquitous and intimately connected with human health and disease management. The accurate and fast identification of pathogenic microorganisms is especially important for diagnosing infections. Herein, three tetraphenylethylene derivatives (S-TDs: TBN, TPN, and TPI) featuring different cationic groups, charge numbers, emission wavelengths, and hydrophobicities were successfully synthesized. Benefiting from distinct cell wall binding properties, S-TDs were collectively utilized to create a sensor array capable of imaging various microorganisms through their characteristic fluorescent signatures. Furthermore, the interaction mechanism between S-TDs and different microorganisms was explored by calculating the binding energy between S-TDs and cell membrane/wall constituents, including phospholipid bilayer and peptidoglycan. Using a combination of the fluorescence sensor array and a deep learning model of residual network (ResNet), readily differentiation of Gram-negative bacteria (G-), Gram-positive bacteria (G+), fungi, and their mixtures was achieved. Specifically, by extensive training of two ResNet models with large quantities of images data from 14 kinds of microorganism stained with S-TDs, identification of microorganism was achieved at high-level accuracy: over 92.8% for both Gram species and antibiotic-resistant species, with 90.35% accuracy for the detection of mixed microorganism in infected wound. This novel method provides a rapid and accurate method for microbial classification, potentially aiding in the diagnosis and treatment of infectious diseases.


Asunto(s)
Aprendizaje Profundo , Humanos , Estilbenos/química , Bacterias Grampositivas/aislamiento & purificación , Colorantes Fluorescentes/química , Bacterias Gramnegativas/aislamiento & purificación , Infección de Heridas/microbiología , Infección de Heridas/diagnóstico , Hongos/aislamiento & purificación
8.
BMC Biotechnol ; 24(1): 10, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38439037

RESUMEN

Polymicrobial communities lead to worsen the wound infections, due to mixed biofilms, increased antibiotic resistance, and altered virulence production. Promising approaches, including enzymes, may overcome the complicated condition of polymicrobial infections. Therefore, this study aimed to investigate Staphopain A-mediated virulence and resistance alteration in an animal model of Staphylococcus aureus and Pseudomonas aeruginosa co-infection. S. aureus and P. aeruginosa were co-cultured on the L-929 cell line and wound infection in an animal model. Then, recombinant staphopain A was purified and used to treat mono- and co-infections. Following the treatment, changes in virulence factors and resistance were investigated through phenotypic methods and RT-PCR. Staphopain A resulted in a notable reduction in the viability of S. aureus and P. aeruginosa. The biofilm formed in the wound infection in both animal model and cell culture was disrupted remarkably. Moreover, the biofilm-encoding genes, quorum sensing regulating genes, and virulence factors (hemolysin and pyocyanin) controlled by QS were down-regulated in both microorganisms. Furthermore, the resistance to vancomycin and doripenem decreased following treatment with staphopain A. According to this study, staphopain A might promote wound healing and cure co-infection. It seems to be a promising agent to combine with antibiotics to overcome hard-to-cure infections.


Asunto(s)
Coinfección , Infección de Heridas , Animales , Virulencia , Pseudomonas aeruginosa/genética , Staphylococcus aureus/genética , Coinfección/tratamiento farmacológico , Factores de Virulencia/genética , Modelos Animales , Farmacorresistencia Microbiana , Infección de Heridas/tratamiento farmacológico
9.
J Clin Microbiol ; 62(6): e0034224, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38785447

RESUMEN

A prior analysis suggested that wound swab culture (WSC) results were driving unnecessary antibiotic use in patients who were not already receiving treatment. As a quality-improvement initiative, our laboratory introduced an "exception-reporting" protocol on 1 March 2023, whereby typical wound pathogens susceptible to recommended empiric therapy (flucloxacillin/cefalexin) were not reported, and a comment was provided, stating no significant resistant organisms had been detected. Full results were available to clinicians on request. Cultures falling outside protocol criteria were reported in the standard fashion. This analysis sought to assess the effect of exception-reporting on post-report antibiotic initiation (PRAI). All community WSC results were matched to antibiotic dispensing records from October 2021 to December 2023. Sampling without treatment pre-report was termed "test and wait" (TaW). Following TaW, PRAI was identified if antibiotics were started within 5 days post-report. There were 1,819 and 764 WSCs received in the pre-change and post-change periods, respectively, where an initial TaW approach had been taken and an organism eligible for exception-reporting had been isolated. In the post-change period, 407 (53.3%) met the criteria and were exception-reported. PRAI occurred in 901 (49.5%) pre-change samples, compared to 102 (25.1%, P < 0.01) with exception-reporting. There was no detectable increase in hospitalization or repeat WSC collection in the 30 days following exception-reporting. Exception-reporting was associated with a markedly reduced proportion of patients being initiated on antibiotics following WSC where an organism had been isolated. The naming of organisms in reports appears to drive unnecessary antibiotic prescribing in many patients. These results require confirmation in other jurisdictions. IMPORTANCE: Wound swab culture is a high-volume test performed in clinical microbiology laboratories. In this analysis, we have shown that an alternative approach to reporting positive wound swab cultures has resulted in a large reduction in post-report antibiotic initiation, suggesting that the current standard method of reporting generates considerable unnecessary antibiotic use. If these findings are replicated elsewhere, wider adoption of this reporting would represent an opportunity for many clinical microbiology laboratories to have a significant impact on community antimicrobial stewardship.


Asunto(s)
Antibacterianos , Infección de Heridas , Humanos , Antibacterianos/uso terapéutico , Infección de Heridas/microbiología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/diagnóstico , Femenino , Masculino , Anciano , Persona de Mediana Edad , Adulto , Programas de Optimización del Uso de los Antimicrobianos , Manejo de Especímenes/métodos , Anciano de 80 o más Años
10.
Curr Opin Infect Dis ; 37(2): 95-104, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38085707

RESUMEN

PURPOSE OF REVIEW: This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS: Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY: We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.


Asunto(s)
Insuficiencia Cardíaca , Corazón Auxiliar , Infecciones Relacionadas con Prótesis , Enfermedades Cutáneas Infecciosas , Infecciones de los Tejidos Blandos , Infección de Heridas , Humanos , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/complicaciones , Corazón Auxiliar/efectos adversos , Calidad de Vida , Antibacterianos/uso terapéutico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Infección de Heridas/complicaciones , Infección de Heridas/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico
11.
PLoS Pathog ; 18(9): e1010766, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36067266

RESUMEN

Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E. coli and S. aureus polymicrobial interactions during wound infections. Here we show that E. coli kills Staphylococci, including S. aureus, both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the pks locus, which we identified in nearly 30% of human E. coli wound infection isolates. While it is not clear how colibactin is released from E. coli or how it penetrates target cells, we found that the colibactin intermediate N-myristoyl-D-Asn (NMDA) disrupts the S. aureus membrane. We also show that the BarA-UvrY two component system (TCS) senses the environment created during E. coli and S. aureus mixed species interaction, leading to upregulation of pks island genes. Further, we show that BarA-UvrY acts via the carbon storage global regulatory (Csr) system to control pks expression. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition.


Asunto(s)
Infecciones por Escherichia coli , Proteínas de Escherichia coli , Proteínas de la Membrana , Fosfotransferasas , Policétidos , Staphylococcus aureus , Factores de Transcripción , Animales , Antibacterianos/metabolismo , Carbono/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/metabolismo , Humanos , Proteínas de la Membrana/metabolismo , Ratones , Mutágenos/metabolismo , N-Metilaspartato/metabolismo , Péptidos , Fosfotransferasas/genética , Policétidos/metabolismo , Staphylococcus/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Factores de Transcripción/metabolismo , Infección de Heridas/microbiología
12.
BMC Microbiol ; 24(1): 166, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755533

RESUMEN

BACKGROUND: Bullet-related bacterial wound infection can be caused by high-velocity bullets and shrapnel injuries. In Ethiopia, significant injuries were reported that may cause severe wound infections, persistent systemic infections and may lead to amputation and mortality. The magnitude, antimicrobial susceptibility profiles, and factors associated with bacterial wound infections among patients with bullet-related injuries are not yet studied particularly at health facilities in Bahir Dar, Northwest Ethiopia. Therefore, this study was aimed to determine the prevalence, bacterial profiles, antimicrobial susceptibility profiles, and factors associated with bacterial infections among patients with bullet-related injuries at referral health facilities in Bahir Dar, Northwest Ethiopia. METHODS: A Hospital-based cross-sectional study was conducted among patients with bullet-related injuries at three referral health facilities in Bahir Dar from May 25 to July 27, 2022. A total of 384 patients with bullet-related injuries were included in the study. Sociodemographic and clinical data were collected using a structured questionnaire. Wound swabs were collected aseptically and cultured on Blood and MacConkey agar following bacteriological standards. Biochemical tests were performed to differentiate bacteria for positive cultivation and antimicrobial susceptibility profiles of the isolates were done on Muller Hinton agar using the Kirby-Bauer disk diffusion technique according to the 2021 Clinical Laboratory Standard Institute (CLSI) guideline. The data were entered using Epi-Info version 7.3 and analyzed using SPSS version 25. Descriptive data were presented using frequency, percentages, figures, and charts. Logistic regression was carried out to identify factors associated with bacterial wound infections. P-value < 0.05 was considered statistically significant. RESULTS: The prevalence of bullet-related bacterial wound infection among three referral hospitals in Bahir Dar city was 54.7%. The most commonly isolated Gram-negative organism was Klebsiella spps 49 (23.3%) while among Gram-positive organism, Staphylococcus aureus 58 (27.6%) and coagulase-negative staphylococci (CONS) 18 (8.6%). Contamination, hospitalization and smoking habit were significantly associated with the presence of bullet-related bacterial wound infections. Over 97% multidrug resistant (MDR) bacterial isolates were identified and of theses, E. coli, Proteus species, Citrobactor, and Staphylococcus aureus were highly drug resistant. CONCLUSION: Increased prevalence of bullet-related bacterial wound infection was noticed in this study. S. aureus followed by Klebsiella species were most commonly isolated bacteria. High frequency of resistance to Ampicillin, Oxacillin, Cefepime, Ceftriaxone, Ceftazidime, Vancomycin, and Norfloxacin was observed. Therefore, proper handling of bullet injuries, prompt investigation of bacterial infections, monitoring of drug sensitivity patterns and antibiotic usage are critical.


Asunto(s)
Antibacterianos , Pruebas de Sensibilidad Microbiana , Infección de Heridas , Humanos , Etiopía/epidemiología , Masculino , Estudios Transversales , Adulto , Femenino , Prevalencia , Infección de Heridas/microbiología , Infección de Heridas/epidemiología , Antibacterianos/farmacología , Adulto Joven , Heridas por Arma de Fuego/epidemiología , Heridas por Arma de Fuego/microbiología , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Persona de Mediana Edad , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Servicio de Urgencia en Hospital/estadística & datos numéricos , Adolescente
13.
Bioconjug Chem ; 35(6): 766-779, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38625106

RESUMEN

Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of -36.5 mV. This method demonstrates reduced side effects compared to conventional therapies, with almost 90% SSD and 72% VE release achieved in wound pH in a sustained manner. Cytotoxicity assessment shows 60% cell viability even at the highest concentration (175 µg/mL), while hemolysis test demonstrates RBC lysis below 5% at a concentration of 250 µg/mL. Vitamin E-SSD-loaded transethosomes (VSTEs) significantly enhance cellular migration and proliferation, achieving 95% closure within 24 h, underscoring their promising efficacy. The synergistic method effectively reduces bacterial burden, evidenced by an 80% reduction in Escherichia coli and Staphylococcus aureus within the wound microenvironment. This approach offers a promising strategy to address complications associated with skin injuries.


Asunto(s)
Portadores de Fármacos , Escherichia coli , Staphylococcus aureus , Vitamina E , Vitamina E/química , Portadores de Fármacos/química , Humanos , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Sulfadiazina de Plata/farmacología , Sulfadiazina de Plata/química , Sulfadiazina de Plata/uso terapéutico , Sulfadiazina de Plata/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Animales , Sistemas de Liberación de Medicamentos , Supervivencia Celular/efectos de los fármacos
14.
J Vasc Surg ; 79(2): 323-329.e2, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37802403

RESUMEN

OBJECTIVE: Groin wound complications are common following vascular surgery and can lead to significant patient morbidity. Sartorius muscle flap coverage may help to prevent vascular graft infection in the setting of wound dehiscence or infection. However, risk factors and consequences of wound complications following sartorius flap reconstruction remain incompletely investigated. METHODS: We retrospectively queried all patients who underwent sartorius flap reconstruction at a tertiary academic medical center. Data collected included patient demographics, medical comorbidities, surgical indication, index vascular procedure, and postoperative outcomes. The primary outcome was wound complication following sartorius flap procedure, which was defined as groin wound infection, dehiscence, or lymphocutaneous fistula. RESULTS: From 2012 to 2022, a total of 113 patients underwent sartorius flap reconstruction. Of these, 66 (58.4%) were performed after the development of a prior groin complication, and 47 (41.6%) were prophylactic. A total of 88 patients (77.9%) had a prosthetic bypass graft adjacent to the flap. Twenty-nine patients (25.7%) suffered a wound complication following sartorius flap reconstruction, including 14 (12.4%) with wound dehiscence, 13 (11.5%) with wound infection, and two (1.8%) with lymphocutaneous fistula. Patients with wound complications had a higher body mass index (28.8 vs 26.4 kg/m2; P =.03) and more frequently active smokers (86.2% vs 66.7%; P = .04). Additionally, patients with wound complications had a higher unplanned 30-day hospital readmission rates (72.4% vs 15.5%; P < .001), reintervention rates (75.9% vs 8.3%; P < .001), and re-do flap reconstruction rates (13.8% vs 2.4%; P = .02). On multivariable analysis, higher body mass index was independently associated with post-flap wound complications (adjusted odds ratio [aOR], 1.01; 95% confidence interval [CI], 1.001-1.03; P = .037). Consequently, wound complications were associated with both surgical reintervention (aOR, 35.4; 95% CI, 9.9-126.3; P < .001) and unplanned hospital readmission (aOR, 17.8; 95% CI, 5.9-54.1; P < .001). CONCLUSIONS: Sartorius flap reconstruction is an effective adjunct in facilitating wound healing of groin wounds. However, wound complications are common following sartorius flap reconstruction and may be associated with reintervention and unplanned hospital readmission. These data support the judicious and thoughtful utilization of sartorius flap procedures among high-risk patients.


Asunto(s)
Fístula , Infección de Heridas , Humanos , Estudios Retrospectivos , Colgajos Quirúrgicos/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Factores de Riesgo , Ingle/cirugía , Fístula/complicaciones , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/etiología
15.
Exp Dermatol ; 33(7): e15102, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38973268

RESUMEN

This study is aimed to analyse the risk factors associated with chronic non-healing wound infections, establish a clinical prediction model, and validate its performance. Clinical data were retrospectively collected from 260 patients with chronic non-healing wounds treated in the plastic surgery ward of Shanxi Provincial People's Hospital between January 2022 and December 2023 who met the inclusion criteria. Risk factors were analysed, and a clinical prediction model was constructed using both single and multifactor logistic regression analyses to determine the factors associated with chronic non-healing wound infections. The model's discrimination and calibration were assessed via the concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve. Multivariate logistic regression analysis identified several independent risk factors for chronic non-healing wound infection: long-term smoking (odds ratio [OR]: 4.122, 95% CI: 3.412-5.312, p < 0.05), history of diabetes (OR: 3.213, 95% CI: 2.867-4.521, p < 0.05), elevated C-reactive protein (OR: 2.981, 95% CI: 2.312-3.579, p < 0.05), elevated procalcitonin (OR: 2.253, 95% CI: 1.893-3.412, p < 0.05) and reduced albumin (OR: 1.892, 95% CI: 1.322-3.112, p < 0.05). The clinical prediction model's C-index was 0.762, with the corrected C-index from internal validation using the bootstrap method being 0.747. The ROC curve indicated an area under the curve (AUC) of 0.762 (95% CI: 0.702-0.822). Both the AUC and C-indexes ranged between 0.7 and 0.9, suggesting moderate-to-good predictive accuracy. The calibration chart demonstrated a good fit between the model's calibration curve and the ideal curve. Long-term smoking, diabetes, elevated C-reactive protein, elevated procalcitonin and reduced albumin are confirmed as independent risk factors for bacterial infection in patients with chronic non-healing wounds. The clinical prediction model based on these factors shows robust performance and substantial predictive value.


Asunto(s)
Proteína C-Reactiva , Cicatrización de Heridas , Humanos , Factores de Riesgo , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Anciano , Fumar/efectos adversos , Enfermedad Crónica , Curva ROC , Modelos Logísticos , Infección de Heridas/epidemiología , Polipéptido alfa Relacionado con Calcitonina/sangre , Diabetes Mellitus/epidemiología , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo
16.
Biotechnol Bioeng ; 121(4): 1453-1464, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38234099

RESUMEN

An ideal antibacterial wound dressing with strong antibacterial behavior versus highly drug-resistant bacteria and great wound-healing capacity is still being developed. There is a clinical requirement to progress the current clinical cares that fail to fully restore the skin structure due to post-wound infections. Here, we aim to introduce a novel two-layer wound dressing using decellularized bovine skin (DBS) tissue and antibacterial nanofibers to design a bioactive scaffold with bio-mimicking the native extracellular matrix of both dermis and epidermis. For this purpose, polyvinyl alcohol (PVA)/chitosan (CS) solution was loaded with antibiotics (colistin and meropenem) and electrospun on the surface of the DBS scaffold to fabricate a two-layer antibacterial wound dressing (DBS-PVA/CS/Abs). In detail, the characterization of the fabricated scaffold was conducted using biomechanical, biological, and antibacterial assays. Based on the results, the fabricated scaffold revealed a homogenous three-dimensional microstructure with a connected pore network, a high porosity and swelling ratio, and favorable mechanical properties. In addition, according to the cell culture result, our fabricated two-layer scaffold surface had a good interaction with fibroblast cells and provided an excellent substrate for cell proliferation and attachment. The antibacterial assay revealed a strong antibacterial activity of DBS-PVA/CS/Abs against both standard strain and multidrug-resistant clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. Our bilayer antibacterial wound dressing is strongly suggested as an admirable wound dressing for the management of infectious skin injuries and now promises to advance with preclinical and clinical research.


Asunto(s)
Quitosano , Nanofibras , Infección de Heridas , Animales , Bovinos , Antibacterianos/farmacología , Antibacterianos/química , Piel , Cicatrización de Heridas , Quitosano/química , Alcohol Polivinílico/química , Infección de Heridas/tratamiento farmacológico , Nanofibras/química
17.
Biomacromolecules ; 25(6): 3671-3684, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38720431

RESUMEN

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.


Asunto(s)
Ácido Hialurónico , Estructuras Metalorgánicas , Porfirinas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Porfirinas/química , Porfirinas/farmacología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Piel/efectos de los fármacos , Humanos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Hierro/química , Fotoquimioterapia/métodos , Hialuronoglucosaminidasa
18.
Biomacromolecules ; 25(6): 3345-3359, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38700942

RESUMEN

The management of diabetic ulcers poses a significant challenge worldwide, and persistent hyperglycemia makes patients susceptible to bacterial infections. Unfortunately, the overuse of antibiotics may lead to drug resistance and prolonged infections, contributing to chronic inflammation and hindering the healing process. To address these issues, a photothermal therapy technique was incorporated in the preparation of wound dressings. This innovative solution involved the formulation of a self-healing and injectable hydrogel matrix based on the Schiff base structure formed between the oxidized Bletilla striata polysaccharide (BSP) and hydroxypropyltrimethylammonium chloride chitosan. Furthermore, the introduction of CuO nanoparticles encapsulated in polydopamine imparted excellent photothermal properties to the hydrogel, which promoted the release of berberine (BER) loaded on the nanoparticles and boosted the antibacterial performance. In addition to providing a reliable physical protection to the wound, the developed hydrogel, which integrated the herbal components of BSP and BER, effectively accelerated wound closure via microenvironment regulation, including alleviated inflammatory reaction, stimulated re-epithelialization, and reduced oxidative stress based on the promising results from cell and animal experiments. These impressive outcomes highlighted their clinical potential in safeguarding the wound against bacterial intrusion and managing diabetic ulcers.


Asunto(s)
Quitosano , Hidrogeles , Polisacáridos , Cicatrización de Heridas , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Polisacáridos/química , Polisacáridos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Terapia Fototérmica/métodos , Ratones , Humanos , Berberina/farmacología , Berberina/química , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Cobre/química , Cobre/farmacología , Masculino , Polímeros/química , Polímeros/farmacología , Indoles/química , Indoles/farmacología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Nanopartículas/química , Staphylococcus aureus/efectos de los fármacos , Nanopartículas del Metal/química
19.
J Surg Res ; 297: 56-62, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38432084

RESUMEN

INTRODUCTION: Neonates with intestinal perforation often require laparotomy and intestinal stoma creation, with the stoma placed in either the laparotomy incision or a separate site. We aimed to investigate if stoma location is associated with risk of postoperative wound complications. METHODS: A multi-institutional retrospective review was performed for neonates ≤3 mo who underwent emergent laparotomy and intestinal stoma creation for intestinal perforation between January 1, 2009 and April 1, 2021. Patients were stratified by stoma location (laparotomy incision versus separate site). Outcomes included wound infection/dehiscence, stoma irritation, retraction, stricture, and prolapse. Multivariable regression identified factors associated with postoperative wound complications, controlling for gestational age, age and weight at surgery, and diagnosis. RESULTS: Overall, 79 neonates of median gestational age 28.8 wk (interquartile range [IQR]: 26.0-34.2 wk), median age 5 d (IQR: 2-11 d) and median weight 1.4 kg (IQR: 0.9-2.42 kg) had perforated bowel from necrotizing enterocolitis (40.5%), focal intestinal perforation (31.6%), or other etiologies (27.8%). Stomas were placed in the laparotomy incision for 41 (51.9%) patients and separate sites in 38 (48.1%) patients. Wound infection/dehiscence occurred in 7 (17.1%) neonates with laparotomy stomas and 5 (13.2%) neonates with separate site stomas (P = 0.63). There were no significant differences in peristomal irritation, stoma retraction, or stoma stricture between the two groups. On multivariable regression, separate site stomas were associated with increased likelihood of prolapse (odds ratio 6.54; 95% confidence interval: 1.14-37.5). CONCLUSIONS: Stoma incorporation within the laparotomy incision is not associated with wound complications. Separate site stomas may be associated with prolapse. Patient factors should be considered when planning stoma location in neonates undergoing surgery for intestinal perforation.


Asunto(s)
Perforación Intestinal , Estomas Quirúrgicos , Herida Quirúrgica , Infección de Heridas , Humanos , Recién Nacido , Preescolar , Adulto , Perforación Intestinal/cirugía , Constricción Patológica , Complicaciones Posoperatorias , Estudios Retrospectivos , Prolapso
20.
Wound Repair Regen ; 32(4): 407-418, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38602090

RESUMEN

An argon-based low-temperature plasma jet (LTPJ) was used to treat chronically infected wounds in Staphylococcus aureus-laden mice. Based on physicochemical property analysis and in vitro antibacterial experiments, the effects of plasma parameters on the reactive nitrogen and oxygen species (RNOS) content and antibacterial capacity were determined, and the optimal treatment parameters were determined to be 4 standard litre per minute and 35 W. Additionally, the plasma-treated activation solution had a bactericidal effect. Although RNOS are related to the antimicrobial effect of plasma, excess RNOS may be detrimental to wound remodelling. In vivo studies demonstrated that medium-dose LTPJ promoted MMP-9 expression and inhibited bacterial growth during the early stages of healing. Moreover, LTPJ increased collagen deposition, reduced inflammation, and restored blood vessel density and TGF-ß levels to normal in the later stages of wound healing. Therefore, when treating chronically infected wounds with LTPJ, selecting the medium dose of plasma is more advantageous for wound recovery. Overall, our study demonstrated that low-temperature plasma jets may be a potential tool for the treatment of chronically infected wounds.


Asunto(s)
Gases em Plasma , Staphylococcus aureus , Cicatrización de Heridas , Infección de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratones , Gases em Plasma/farmacología , Infección de Heridas/microbiología , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Infecciones Estafilocócicas , Masculino , Especies de Nitrógeno Reactivo/metabolismo
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