Approach to prophylactic measures for central venous catheter‐related infections in hemodialysis: A critical review

Vascular access is the major risk factor for bacteremia, hospitalization, and mortality among hemodialysis (HD) patients. The type of vascular access most associated with bloodstream infection is central venous catheter (CVC). The incidence of catheter‐related bacteremia ranges between 0.6 and 6.5 episodes per 1000 catheter days and increases linearly with the duration of catheter use. Given the high prevalence of CVC use and its direct association with catheter‐related bacteremia, which adversely impacts morbidity and mortality rates and costs among HD patients, several prevention measures aimed at reducing the rates of CVC‐related infections have been proposed and implemented. As a result, a large number of clinical trials, systematic reviews, and meta‐analyses have been conducted in order to assess the effectiveness, clinical applicability, and long‐term adverse effects of such measures. In the following article, prophylactic measures against CVC‐related infections in HD patients and their possible advantages and limitations will be discussed, and the more recent literature on clinical experience with prophylactic antimicrobial lock therapy in HD CVCs will be reviewed.     

Recurrent Ochrobactrum anthropi and Shewanella putrefaciens bloodstream infection complicating hemodialysis

Bloodstream infections (BSIs) are common in hemodialysis, especially when the access is a catheter. These infections are more commonly gram-positive bacteria or gram-negative bacilli and on some occasions, fungi. Ochrobactrum anthropi and Shewanella putrefaciens are ubiquitous hydrophilic gram-negative bacilli. There have been three cases of O. anthropi BSI reported in hemodialysis patients (one from the United States and two from Vienna) and two cases of S. putrefaciens BSI in hemodialysis patients (one from the United States and the other from Japan). There have been few more cases reported of infections with these bacteria in peritoneal dialysis, especially outside the United States. We present a novel case of a patient with both recurrent O. anthropi and S. putrefaciens BSI complicating hemodialysis. There have been no reports in the literature of such a case. We also discuss the microbiology, clinical features, and the challenging aspects of treatment of such infections.     

Production,stabilisation and characterisation of silver nanoparticles coated with bioactive polymers pluronic F68, PVP and PVA

The increasing and alarming panorama of bacterial infections and associated morbidities that occur during medical and hospital procedures makes the development of technologies that aid in controlling such bacterial infections of utmost importance. Recent studies have shown that formulations with metal nanoparticles exhibit good antibacterial properties against a broad spectrum of microorganisms. Moreover, it was demonstrated that some biologically active polymeric materials, when applied in combination with chemical antimicrobial agents, enhance the therapeutic action of the latter. The research effort entertained herein aimed at the physico‐chemical characterisation of silver nanoparticles obtained by chemical reduction, stabilised by bioactive polymers polyvinyl alcohol and polyvinylpyrrolidone, and further co‐stabilised by pluronic F68. Scanning electron microscopy images of the nanoparticles produced, coated with different stabilisers, have shown that the chemical nature of the stabilisation effect promoted incorporation of pluronic in the nanoparticles and was closely related to an increase in the silver concentration in the nanoparticle samples obtained via energy‐dispersive X‐ray spectroscopy. The study described herein also shows that the nature of the stabiliser favours the interaction of pluronic F68 with samples containing silver nanoparticles.Inspec keywords: silver, nanoparticles, polymer films, coatings, nanocomposites, nanofabrication, microorganisms, biomedical materials, nanomedicine, antibacterial activity, reduction (chemical), scanning electron microscopy, X‐ray chemical analysisOther keywords: bioactive polymers pluronic F68 coated silver nanoparticles, PVP coated silver nanoparticles, PVA coated silver nanoparticles, bacterial infections, associated morbidities, medical procedures, hospital procedures, antibacterial properties, microorganisms, biologically active polymeric materials, chemical antimicrobial agents, therapeutic action, physicochemical characterisation, chemical reduction, bioactive polymers polyvinyl alcohol, polyvinylpyrrolidone, scanning electron microscopy, stabilisation effect, energy‐dispersive X‐ray spectroscopy, Ag     

In vitro antimicrobial and biological properties of laser assisted tricalcium phosphate coating

Implant related infections are of great concern in modern surgery. In order to improve the implant performance and to reduce implant related infections, titanium (Ti) surface was modified to simultaneously improve cell-material interactions and antimicrobial activity. Ti surface was first coated with tricalcium phosphate (TCP) using Laser Engineered Net Shaping (LENS?) to improve biocompatibility. Silver (Ag) was then electrodeposited from different concentrations of silver nitrate (AgNO₃) solutions to improve the antimicrobial activity. The Ag-TCP coatings were tested for cytotoxicy with human osteoblast cells. The antimicrobial activities of the Ag-TCP coatings were evaluated using Pseudomonas aeruginosa and Staphylococcus aureus bacteria. In vitro bacterial adhesion study indicated a significant reduction in bacterial colony on Ag-TCP coated surfaces when compared to TCP coated surface.     

Fabrication of silver nanocomposite films impregnated with curcumin for superior antibacterial applications

Silver nanocomposite films are found to be very effective material for anti-bacterial application. In the present work, sodium carboxylmethyl cellulose silver nanocomposite films (SCMC SNCF) were tried for antibacterial applications. To enhance their applicability novel film-silver nanoparticle-curcumin composites have been developed. SCMC SNCF are developed from sodium carboxylmethyl cellulose (SCMC), N,N ¹ -methylenebisacrylamide (MBA) and silver nitrate solution. These films were characterized by FTIR, UV–visible, XRD, TGA, DSC and TEM techniques. The formed silver nanoparticles have an average particle size of ~15 nm as observed by transmission electron microscopy (TEM). Curcumin loading into SCMC SNCF is achieved by diffusion mechanism. The UV–Visible analysis indicated that higher encapsulation of curcumin in the films with higher SCMC content. Further, it was observed that the presence of silver nanoparticles in the films enhanced the encapsulation of curcumin indicating an interaction between them. Moreover, the antibacterial activity showed that the SCMC films generated with silver nanoparticles have a synergistic effect in the antimicrobial activity against Escherichia coli (E. coli). In order improve the healing efficacy as antibacterial agents, curcumin loaded with SCMC SNCFs were developed which showed significant inhibition of E. coli growth than the silver nanoparticles and curcumin alone film. Therefore, the present study clearly provides novel antimicrobial films which are potentially useful in preventing/treating infections.     

Antimicrobial and anti-thrombogenic features combined in hydrophilic surface coatings for skin-penetrating catheters. Synergy of co-embedded silver particles and heparin

Percutaneous (skin-penetrating) catheters such as central venous catheters (CVCs), are used ubiquitously in the treatment of critically ill patients, although it is known that the risks for serious complications, particularly bloodstream infection and thromboembolism, are high. Materials science and engineering offer important new perspectives regarding further improvement of CVCs. A promising approach is the use of synthetic biocompatible hydrogel coatings with both silver particles and heparin embedded therein. Such formulations combine the well-known broad-spectrum antimicrobial features of silver with the anticoagulant activity of immobilized heparin. Previous work revealed that heparin augments antimicrobial activity of silver, while maintaining its anticoagulant function. This study set out to investigate the synergy of heparin and silver in more detail. Exit-challenge tests, experiments on bacterial killing and adherence, as well as in vitro challenge tests with three Staphylococcus aureus strains (one reference strain, and two clinical isolates) consistently showed the synergistic effect. In addition, the impact of changing the coating's hydrophilicity, and changing the silver concentration in the coatings, were examined. The experimental results, taken together and combined with data from the literature, point out that synergy of heparin and silver is best explained by binding of Ag(+) ions to heparin within the swollen coating, followed by release of heparin-Ag(+) complexes upon immersion of the coatings in an aqueous environment such as blood. Possible implications of this work regarding the development of improved/safer CVCs are briefly discussed.     

Effect of silver nanocoatings on catheters for haemodialysis in terms of cell viability, proliferation, morphology and antibacterial activity

The onset of infections associated to bacterial proliferation and biofilm formation on indwelling medical devices represents the major risk of morbidity and mortality among patients. In order to contain the risk of infections in clinical practice, there is a growing interest nowadays in silver-based products due to the strong antimicrobial efficacy of silver against a broad spectrum of microorganisms. In this work, temporary catheters for haemodialysis were coated with silver nano-particles through the in situ photo-reduction of a silver salt in alcoholic solution. A homogeneous distribution of silver particles firmly bonded to the substrate was obtained through the adopted technique. An optimisation study was required to define the amount of silver, in order to obtain good efficacy against Gram-positive and Gram-negative bacteria and no cytotoxic effect. At this purpose, three concentrations of silver, 0.1, 0.25 and 0.5 wt%, have been deposited and tested with respect to bacterial reduction percentage and cellular response. Particularly, bacterial enumeration on Escherichia coli and Staphylococcus aureus, and BrdU incorporation, TUNEL assay and Actin staining on a selected primary cell population were performed on catheters treated with the different silver solutions. The silver percentages tested demonstrated strong antibacterial properties together with a good cellular response, thus indicating that the developed product could be proposed in clinical practice and that the lower percentage tested can be preferred with evident advantages in terms of costs.     

The Binary Effect on Methicillin‐Resistant Staphylococcus aureus of Polymeric Nanovesicles Appended by Proline‐Rich Amino Acid Sequences and Inorganic Nanoparticles

Prevalent research underscores efforts to engineer highly sophisticated nanovesicles that are functionalized to combat antibiotic‐resistant bacterial infections, especially those caused by methicillin‐resistant Staphylococcus aureus (MRSA), and that aid with wound healing or immunomodulation. This is especially relevant for patients who are susceptible to Staphylococcus aureus infections postoperatively. Here, antibacterial formulations are incorporated into polymeric, biocompatible vesicles called polymersomes (PsNPs) that self‐assemble via hydrophobic interactions of admixed aqueous and organic substances. Nano‐PsNPs are synthesized using a high molecular weight amphiphilic block copolymer, and are conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver nanoparticles (AgNPs) inside their hydrophobic corona. In vitro testing on bacterial and human cell lines indicates that finely tuned treatment concentrations of AMP and AgNPs in PsNPs synergistically inhibits the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. A ratio of silver‐to‐AMP of about 1:5.8 corresponding to ≈11.6 µg mL^?1 of silver nanoparticles and 14.3 × 10^?6 m of the peptide, yields complete MRSA inhibition over a 23 h time frame. This bacteriostatic activity, coupled with nominal cytotoxicity toward native human dermal fibroblast cells, extends the potential for AMP/AgNP polymersome therapies to replace antibiotics in the clinical setting.     

Silver–clay nanohybrid structure for effective and diffusion-controlled antimicrobial activity

We describe here the synthesis and antimicrobial activity of silver–clay nanohybrid structure that was processed to exhibit a combination of accelerated and diffusion-controlled antimicrobial activity, with long term impact. The antimicrobial activity is assessed in terms of interaction with Escherichia coli, where the constituents of the nanohybrid structure play a synergistic role. Clay provides a physically stable surface for nucleation of silver nanoparticles. Additionally, the parallel- stacked layered structure of clay facilitates diffusion-controlled antimicrobial activity of in-situ precipitated silver. The antimicrobial activity is about four orders of magnitude greater than ex-situ precipitated bare silver particles. The study emphasizes the significance of controlling antimicrobial activity in nanostructured systems, which in the present case is enhanced and controlled antimicrobial activity with long term implication.     

Highly Stable and Dispersive Silver Nanoparticle–Graphene Composites by a Simple and Low‐Energy‐Consuming Approach and Their Antimicrobial Activity

A simple and low‐energy‐consuming approach to synthesize highly stable and dispersive silver nanoparticle–graphene (AgNP–GE) nanocomposites has been developed, in which the stability and dispersivity of the composites are varied greatly with the pH value and temperature of the reaction. The results demonstrate that the optimal reaction conditions are pH 11 at room temperature for 70 min. As‐synthesized composites display excellent antimicrobial activity, and can completely inhibit the growth of Escherichia coli cells at a concentration of 20 mg L^?1 (20 ppm). After treatment with 10 ppm AgNP–GE composites, the cells are killed completely within 3 h. The unique structure imparts such good antimicrobial properties to the composites. Firstly, the sheetlike AgNP–GE tends to be adsorbed and accumulated onto the surface of cells, which can change the permeability and enhance the antimicrobial activity. Secondly, Ag⁺ released from AgNPs can act on the cells effectively and fully, thereby resulting in cell death.     

Huge increase of therapeutic window at a bioactive silver/titania nanocomposite coating surface compared to solution

A silver containing coating used in the human body, e.g., on an implant should be both effectively antimicrobial and non-cytotoxic to human cells. It is generally believed that the biologic effect originates from silver ions released from the coating. Nanocomposites with well controlled Ag filling factor were prepared by co-sputtering, and the silver surface concentration and the silver release were determined by XPS and ICP-MS, respectively. Here we show that only a small therapeutic window exists for dissolved silver but the therapeutic window is largely increased at the surface. While the toxicity observed for mammalian cells in contact with the bioactive Ag/TiO₂ nanocomposite surface and for silver ions in solution is rather similar the antimicrobial activity is drastically enhanced at the surface. A model is proposed to explain the strong increase of the antimicrobial activity at the surface. The present results not only question well-established tests for antimicrobial activity but they are also important for the design of antimicrobial coatings, e.g., for biomedical devices.     

In situ generation of Ag nanoparticles on polyester fabrics by photoreduction using TiO2 nanoparticles

This study discusses the possibility of in situ generation of Ag nanoparticles on polyester fabric by photoreduction of Ag⁺ ions with deposited TiO₂ nanoparticles in the presence of amino acid alanine and methyl alcohol. The presence of TiO₂/Ag nanoparticles on the polyester fiber surface was confirmed by XRD, XPS, and SEM analyses. Such nanocomposite textile material provides excellent antimicrobial activity against Gram-negative bacterium E. coli, Gram-positive bacterium S. aureus, and fungus C. albicans. Maximum microbial reduction was preserved even after ten washing cycles. In spite of satisfactory laundering durability, the release of silver occurred during washing. The leaching of silver was also present when the fabrics were exposed to artificial sweat at pH 5.5 and pH 8.0 for 24 h. In addition to excellent antimicrobial properties, TiO₂/Ag nanoparticles imparted maximum UV protection to polyester fabrics.     

Evaluation of anti‐bacterial activity of silver nanoparticles synthesised by coprophilous fungus PM0651419

The study explored biological synthesis of metallic silver nanoparticles (AgNPs) from the less explored non‐pathogenic coprophilous fungus, sterile mycelium, PM0651419 and evaluates the antimicrobial efficacy of biosynthesised AgNPs when impregnated in wound fabrics and in combination with six antimicrobial agents. AgNPs alone proved to be potent antibacterial agents and in combination they enhanced the antibacterial activity and spectrum of antibacterials used in the study against a microbiologically diverse battery of Gram positive, Gram negative and multidrug‐resistant bacteria. AgNPs impregnated on the wound dressings established their antibacterial activity by significantly reducing the bacterial load of pathogenic bacteria like Staphylococcus aureus and Bacillus subtilis e stablishing potential as effective antimicrobial wound dressings for treatment of polymicrobial wound infections. This study presents the first report on the potential of biosynthesis of AgNPs from the under explored class of coprophilous fungi. Their promise to be used in wound dressings and as potent antibacterials alone and in combination is evaluatedInspec keywords: silver, nanoparticles, nanofabrication, nanomedicine, biomedical materials, microorganisms, antibacterial activity, wounds, fabricsOther keywords: antibacterial activity, coprophilous fungus PM0651419, biological synthesis, metallic silver nanoparticles, nonpathogenic coprophilous fungus, sterile mycelium, antimicrobial efficacy, biosynthesised AgNPs, wound fabrics, microbiologically diverse battery, Gram positive bacteria, Gram negative bacteria, multidrug‐resistant bacteria, wound dressings, bacterial load, pathogenic bacteria, Staphylococcus aureus, Bacillus subtilis, polymicrobial wound infections, Ag     

Broad-spectrum antimicrobial activity of bacterial cellulose silver nanocomposites with sustained release

Bacterial cellulose-based antifouling materials have been produced by incorporation of silver nanoparticles for broad-spectrum antimicrobial activity. Three variations of silver nitrate (AgNO₃) to reducing agent concentrations have been tried to vary the silver nanoparticle dimension. The formation of silver nanoparticles was also evidenced by the X-ray diffraction, and the crystallite size was found to decrease with increase in NaBH₄ concentration. AgBC composites having < 2% (W/W) of silver exhibited 99.9% antimicrobial activity which was sustained up to 72 h against spoiled food derived mixed microbial culture. On the other hand, only 90% activity was observed with colloidal AgNPs due to aggregate formation. Composites displayed superior antimicrobial activity than colloid with equivalent amount of silver. Food stuff was protected from microbial spoilage for 30 days when stored in AgBC nanocomposites, whereas spoilage was noticed within 15 days for food stuff stored in regular polythene bag. Therefore, the AgBC composite having < 2% silver can be used as a lining of regular food packaging material to extend shelf life till 30 days. Toxicity due to high amount of silver can be prevented with these composites and can be safely used in healthcare applications such as food packaging, wound dressing, hospital bed lining and surgical apparels.     

Ultrasmall Ag+-rich nanoclusters as highly efficient nanoreservoirs for bacterial killing

Metallic silver （Ag） and its ability to combat infection have been known since ancient history. In the wake of nanotechnology advancement, silver＇s efficacy to fight broad spectrum bacterial infections is further improved in the form of Ag nanoparticles （NPs）. Recent studies have ascribed the broad spectrum antimicrobial properties of Ag NPs to dissociation of Ag＊ ions from the NPs, which may not be entirely applicable when the size of Ag NPs decreases to the sub-2 nm range [denoted Ag nanoclusters （NCs）]. In this paper we report that ultrasmall glutathione （GSH）-protected Ag^＋-rich NCs （Ag^＋-R NCs for short, with a predominance of Ag＋ species in the NCs） have much higher antimicrobial activities towards both gram-negative and gram-positive bacteria than the reference NC, GSH-Ag^＋-R NCs. They have the same size and surface ligand, but with different oxidation states of the core silver. This interesting finding suggests that the undissociated Ag^＋-R NCs armed with abundant Ag^＋ ions on the surface are highly active in bacterial killing, which was not observed in the system of their larger counterpart, Ag NPs.     

A combined approach for the development of novel sutures with antibacterial and regenerative properties: the role of silver and silk sericin functionalization

Chronic wounds and related infections cause physical and psychological distress in patients, increased mortality, disability and high health care costs. The healing process can be delayed by several factors and in particular by the risk of infections, which can be further complicated by the increasing number of antibiotic-resistant microorganisms. New approaches in wounds management have been encouraged, aiming at preventing infections and improving wound healing. In this scenario, silver has emerged as an ideal antimicrobial agent due to its recognized efficacy against bacteria, viruses and fungi. Moreover, silk and in particular silk sericin from Bombyx mori has demonstrated excellent biological properties and can be considered a good candidate for skin tissue engineering. In this study absorbable PLGA sutures were functionalized with silk sericin and, then, they were treated with silver through an in situ photochemical deposition technology in order to develop an antibacterial and regenerative biomedical device. Morphological analysis was performed by Scanning Electron Microscopy and Energy Dispersive X-Ray Spectroscopy (SEM-EDX) in order to evaluate the presence and distribution of silver deposited on the sutures. The stability and durability of the sericin/silver coatings were tested and the results were related to both antibacterial properties and sample degradation. The biological analyses also aimed at studying the biocompatibility and wound healing properties of the device, evaluating the synergistic effect between sericin and silver.

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Hybrid fibers containing protein-templated nanomaterials and biologically active components as antibacterial materials

The persistent and emerging threat of bacterial infections now extends to many real world scenarios that drive a requirement for antimicrobial fabrics. Such functionalized textiles may find application in protective wear for medical and military personnel and provide functional wound dressings that reduce infection in situ. In this work, biomimetic enzyme entrapment and protein-directed nanomaterials synthesis is combined and applied to the antimicrobial functionalization of fabrics. A multi-faceted approach was adopted to address the fabrication of textiles with Ag nanoparticles, bactericidal proteins and mineral coatings that may contribute (singularly or in unison) to provide antimicrobial activity. Fibroin coordinated silver ions, for example, were chemically reduced to generate silver nanoparticles within the interior of silk fabric fibers. Silk textiles were further functionalized by the surface adsorption of the bactericidal enzyme lysozyme. The exposure of such lysozyme-conjugated fabrics to mineralizing solutions enabled the self-directed immobilization of the enzyme in a subsequent protective matrix of amorphous silica or titania. Silk-immobilized lysozyme was also utilized to adsorb nanocrystalline TiO₂ from solution onto the fabric surface; a subsequent layer of enzyme served to entrap the ceramic particles under a layer of biomimetically mineralized titania. The multiplicity of antimicrobial activities derived from this approach thereby combined; 1) the hydrolytic activity of lysozyme (demonstrated by radial diffusion assays), 2) the bactericidal properties of silver nanoparticles (demonstrated effective against Staphylococcus aureus, Escherichia coli, and silver resistant E. coli) and 3) the photocatalytic bactericidal response of TiO₂ under UV illumination.     

Anti-Infective catheters: A difficult search for effective slow delivery systems

Nosocomial infection are estimated to involve more than 2 million patients annually and in 1992 cost more than $4,5 billion in the USA (1). The surfaces of indwelling medical devices are an excellent platform for the formation of life-threatening infections. Although aseptic techniques can reduce the incidence of these infections, a significant risk remains. The coupling or incorporation of antimicrobial substances to or into catheter materials may be a suitable way to prevent the development of catheter associated infections as suggested by in vitro and in vivo studies. Various surface treatments are emerging as important. Early efforts that concentrated on adsorption of antibiotics to device surfaces achieved limited results as shown in several clinical studies. The promising approach features the incorporation of antimicrobial drugs into the polymer matrices that entrap but do not bind the drugs, allowing for extended release. Incorporation of antimicrobials in the bulk material that constitutes a device can be effective as shown in several in vitro and in vivo studies. In future, modification of both short-term and long term catheters by biofilm-active antimicrobials creating slow delivery systems may provide an effective method to protect patients from nosocomial infection.     

Extracellular biosynthesis,characterisation and in-vitro antibacterial potential of silver nanoparticles using Agaricus bisporus

Microbial silver nanoparticles have been known to have bactericidal effects but the antimicrobial mechanism has not been clearly revealed. The use of microorganisms in the synthesis of nanoparticles emerges as an ecofriendly and exciting approach. Here we report on the extracellular synthesis method for the preparation of silver nanoparticles in water using the extract of Agaricus bisporus, a naturally occurring edible mushroom, as reducing and protecting agents. The silver nanoparticles were characterised by ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-Ray diffraction (XRD) analysis. The synthesised silver nanoparticles showed antibacterial activity against the multi-drug resistant Gram positive and Gram negative bacterial pathogens.     

Antibacterial activated carbon fibre derived from phenolic resin fibre by use of co-graftpolymerization

Phenolic-resin fibre was co-graftpolymerized with methyl methacrylate and methacrylic acid. The weight of the fibre increased by 26% after grafting. The grafted fibre was soaked in silvernitrate solution to introduce silver ion on methacrylic acid in the graft by an ion-exchange reaction, followed by carbonization at 900 °C for 30 min under a nitrogen stream and activation at 900 °C under a steam stream. After activation for 40 min, the resulting fibre showed a silver content of 8.3 wt% a specific surface area of 1300 m²g^–1 and antimicrobial activity against Staphylococcus aureus and Escherichia coli. The average crystallite size of the silver in this fibre was 30 nm, which suggests co-graftpolymerization is a useful technique to disperse fine silver particles in the activated carbon fibre. After soaking in flowing tap water for 10 and 20 days, this activated carbon fibre lost about 50 wt% of silver but kept its antibacterial activity.