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Staphylococcus aureus are frequently associated with biofilm formation on intravascular devices. Biofilms limit antimicrobial penetration and promote phenotypic resistance, challenging conventional treatment strategies. Vancomycin (VAN) and gentamicin (GEN) have been used clinically, but their combined antibiofilm activity remains underexplored. This study evaluates the efficacy of VAN and GEN, alone and in combination, against biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) on polyurethane. MICs were determined for VAN and GEN. Biofilm biomass and metabolic activity were quantified using crystal violet and MTT assays, respectively. Biofilm viability was assessed through fluorescence microscopy and a modified Calgary Biofilm Device. A continuous-flow peristaltic model was developed to test treatment under simulated catheter conditions. While monotherapy with VAN or GEN had modest effects, their combination significantly reduced biomass and metabolic activity. VAN 20 mg/L + GEN 8 mg/L and VAN 40 mg/L + GEN 8 mg/L achieved over 70% reduction in MRSA biofilm viability and complete eradication in MBEC assays. Dynamic model assays confirmed biofilm reduction with combination therapy. The combination of VAN/GEN exhibits synergistic antibiofilm activity against S. aureus, particularly MRSA. These findings support its potential application in catheter salvage strategies, including antibiotic lock therapy.

Pseudomonas aeruginosa is associated with several human infections, mainly related to healthcare services. In the hospital, it is associated with resistance to several antibiotics, which poses a great challenge to therapy. However, one of the biggest challenges in treating P. aeruginosa infections is that related to biofilms. The complex structure of the P. aeruginosa biofilm contributes an additional factor to the pathogenicity of this microorganism, leading to therapeutic failure, in addition to escape from the immune system, and generating chronic infections that are difficult to eradicate. In this review, we address several molecular aspects of the pathogenicity of P. aeruginosa biofilms.

Background: Central venous catheters (CVCs) are essential in intensive care units (ICUs) for monitoring and administering treatments; however, catheter-related bloodstream infections (CRBSIs) are significant complications, leading to severe outcomes and increased healthcare costs. The objective of this study was to evaluate the effectiveness of a simple and inexpensive impregnated dressing (intervention) compared to a non-impregnated dressing in reducing catheter-related infections among critically ill patients using vancomycin and chlorhexidine. Methods: This was a randomized, double-blind, controlled clinical trial in a university hospital in Brazil with 207 beds from June 2022 to October 2023. Patients over 18 years old admitted to the ICU and needing a CVC for a period exceeding 72 h were included. A CVC inserted outside the ICU and the need for two CVCs in the same patient simultaneously were exclusion criteria. One group received an impregnated dressing (intervention) compared to the other group, which received a standard dressing (comparator). The incidence of CRBSIs and the microbiological outcomes were evaluated. The primary endpoint was CRBSI. Results: The clinical trial included 516 patients randomized to receive either the new antimicrobial dressing or a control dressing. The dressing significantly reduced CVC colonization but not CRBSI rates. Conclusions: This new dressing provides enhanced antimicrobial protection but does not decrease CRBSI incidence. Future studies should further explore the cost-effectiveness and long-term benefits of this approach.

The increasing demand for orthopedic and neurosurgical implants has driven advancements in biomaterials, additive manufacturing, and antimicrobial strategies. With an increasingly aging population, and a high incidence of orthopedic trauma in developing countries, the need for effective, biocompatible, and infection-resistant implants is more critical than ever. This review explores the role of polymers in 3D printing for medical applications, focusing on their use in orthopedic and neurosurgical implants. Polylactic acid (PLA), polycaprolactone (PCL), and polyetheretherketone (PEEK) have gained attention due to their biocompatibility, mechanical properties, and potential for antimicrobial modifications. A major challenge in implantology is the risk of periprosthetic joint infections (PJI) and surgical site infections (SSI). Current strategies, such as antibiotic-loaded polymethylmethacrylate (PMMA) spacers and bioactive coatings, aim to reduce infection rates, but limitations remain. Additive manufacturing enables the creation of customized implants with tailored porosity for enhanced osseointegration while allowing for the incorporation of antimicrobial agents. Future perspectives include the integration of artificial intelligence for implant design, nanotechnology for smart coatings, and bioresorbable scaffolds for improved bone regeneration. Advancing these technologies will lead to more efficient, cost-effective, and patient-specific solutions, ultimately reducing infection rates and improving long-term clinical outcomes.

Staphylococcus aureus is a microorganism frequently associated with implant-related infections, owing to its ability to produce biofilms. These infections are difficult to treat because antimicrobials must cross the biofilm to effectively inhibit bacterial growth. Although some antibiotics can penetrate the biofilm and reduce the bacterial load, it is important to understand that the results of routine sensitivity tests are not always valid for interpreting the activity of different drugs. In this review, a broad discussion on the genes involved in biofilm formation, quorum sensing, and antimicrobial activity in monotherapy and combination therapy is presented that should benefit researchers engaged in optimizing the treatment of infections associated with S. aureus biofilms.

Reconstructive and regenerative medicine are critical disciplines dedicated to restoring tissues and organs affected by injury, disease, or congenital anomalies. These fields rely on biomaterials like synthetic polymers, metals, ceramics, and biological tissues to create substitutes that integrate seamlessly with the body. Personalized implants and prosthetics, designed using advanced imaging and computer-assisted techniques, ensure optimal functionality and fit. Regenerative medicine focuses on stimulating natural healing mechanisms through cellular therapies and biomaterial scaffolds, enhancing tissue regeneration. In bone repair, addressing defects requires advanced solutions such as bone grafts, essential in medical and dental practices worldwide. Bovine bone scaffolds offer advantages over autogenous grafts, reducing surgical risks and costs. Incorporating antimicrobial properties into bone substitutes, particularly with metals like zinc, copper, and silver, shows promise in preventing infections associated with graft procedures. Silver nanoparticles exhibit robust antimicrobial efficacy, while zinc nanoparticles aid in infection prevention and support bone healing; 3D printing technology facilitates the production of customized implants and scaffolds, revolutionizing treatment approaches across medical disciplines. In this review, we discuss the primary biomaterials and their association with antimicrobial agents.

Abstract This study aimed to analyze ESBL-producing Escherichia coli prevalence in urine samples collected between 2011–2019 in Curitiba, a large city in Brazil, and relating it to antibiotic consumption and sanitary conditions. This is a longitudinal study correlating prevalence of ESBL-producing E. coli isolates from urine samples with district-level antibiotic consumption and sociodemographic data during 2011–2019. E. coli isolates were tested for antibiotic susceptibility and ESBL by an automated method. Statistical analysis applied linear regressions, pooled ordinary least squares, and fixed effects models for districts or years. The Chow and Hausman tests indicated that the fixed effects model for individual districts fitted best. Chi-square test was used for qualitative variables (statistical significance was set when P < 0.05). Among the 886 535 urine sample cultures, 9.9% of isolates were ESBL-producing E. coli. Their prevalence increased from 4.7% in 2012 to 19.3% in 2019 (P < 0.0001; R2 = 0.922). This progressive increase correlated with age (P = 0.007; R2 = 0.8725) and male gender (P < 0.001) and increased antibiotic consumption (P = 0.0386; R2 = 0.47). The fixed effects model showed that district influences ESBL prevalence and that antibiotic consumption explains 20%–30% of this variation, with an increase of one defined daily dose accounting for an increase of 0.02084 percentage points of ESBL. The increasing prevalence of ESBL-producing E. coli can, to a considerable extent, be explained by increasing antibiotic consumption. Increased antibiotic consumption between 2011 and 2019 was associated with increased prevalence of ESBL-producing E. coli in urine samples.

Musculoskeletal allografts are used in reconstructive procedures, however, the risk of contamination with potential pathogens is possible, and safe transplantation requires multiple processing considerations. Hydrogen peroxide (H2O2) has commonly been used in bone washing because it can remove donor cells and eliminate antigens, pathogens, or cytotoxic agents from the matrix. The aim of this study was to evaluate the quantitative activity of H2O2 in a model of bone contamination with a high bacterial load to define the bioburden reduction. Twelve bone disc models were artificially contaminated with Staphylococcus aureus. The bones were treated with a washing process composed by antibiotics, 30% hydrogen peroxide, and 70% alcohol. Tryptic Soy Agar plates were directly inoculated with 100µL of each step of the washing process and colonies were counted in CFU/mL. Scanning electron microscopy was used for bone structural analysis before and after the washing process. After antibiotics, there was a drop of less than 1 log for cancellous bone and almost 1 log for cortical bone. However, after H2O2, there as a drop of 3 logs for cortical (p = 0.007), and 2 logs for cancellous bone (p = 0.063). The use of alcohol did not change the bioburden following H2O2 in cancellous and cortical bone. Despite the important drop of bacterial load, H2O2 was not enough to completely eradicate bacterial with this model of bioburden. H2O2 is useful in decontamination, but antibiotics have little activity, and alcohol is useless. The process is useful in decontamination up to 3 logs of bioburden.

Extracellular vesicles (EVs) are particles released from different cell types and represent key components of paracrine secretion. Accumulating evidence supports the beneficial effects of EVs for tissue regeneration. In this study, discarded human heart tissues were used to isolate human heart-derived extracellular vesicles (hH-EVs). We used nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) to physically characterize hH-EVs and mass spectrometry (MS) to profile the protein content in these particles. The MS analysis identified a total of 1248 proteins. Gene ontology (GO) enrichment analysis in hH-EVs revealed the proteins involved in processes, such as the regulation of cell death and response to wounding. The potential of hH-EVs to induce proliferation, adhesion, angiogenesis and wound healing was investigated in vitro. Our findings demonstrate that hH-EVs have the potential to induce proliferation and angiogenesis in endothelial cells, improve wound healing and reduce mesenchymal stem-cell adhesion. Last, we showed that hH-EVs were able to significantly promote mesenchymal stem-cell recellularization of decellularized porcine heart valve leaflets. Altogether our data confirmed that hH-EVs modulate cellular processes, shedding light on the potential of these particles for tissue regeneration and for scaffold recellularization.

Residual chemicals that are presented during tissue processing in human tissue banks can be a risk for the allograft recipient. Determine the residual concentrations of the antibiotics and detergent used in the process of human decellularized tissue-engineered heart valves stored in isotonic saline solution up to 18 months. A total of 24 human decellularized allografts were stored in sterile sodium chloride and analyzed immediately after the decellularization process (0 months) and after storage for 6, 12, and 18 months, which includes the use of sodium dodecyl sulfate (SDS) and antibiotics (cefoxitin, vancomycin hydrochloride, lincomycin hydrochloride, polymyxin B sulfate). These valves were used for suitability tests, the zone of inhibition evaluation, and direct contact cytotoxicity assay. The stock solution from 32 valves was used for LC–MS/MS analysis of antibiotics and SDS. Tissue samples from decellularized valves showed a zone of inhibition formation for S. aureus and B. subtilis, suggesting the presence of an inhibitory molecule in the tissue. Cytotoxicity tests were negative. Polymyxin B, vancomycin, and SDS were detected and quantified in human decellularized aortic and pulmonary allografts during all periods of the study. There were no traces of residual cefoxitin and lincomycin in the tissue stock solution. We found residual concentrations of the antibiotics and detergent used in the process of human decellularized tissue-engineered heart valves stored in isotonic saline solution up to 18 months.