Local Antibiotic Delivery System Research Articles

Eradication of Staphylococcus aureus in Implant-Associated Osteomyelitis by an Injectable in situ-Forming Depot Antibiotics Delivery System.

Bone infections from Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics. CarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology. CarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement, and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9/12, and full eradication in 5/12 pigs. Sustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care.

Assessment of antibiotic release and antibacterial efficacy from pendant glutathione hydrogels using ex vivo porcine skin

Acute bacterial skin and skin structure infections (ABSSSIs) confer a substantial burden on the healthcare system. Local antibiotic delivery systems can provide controlled drug release directly to the site of infection to maximize efficacy and minimize systemic toxicity. The purpose of this study was to examine the antibacterial activity of antibiotic-loaded glutathione-conjugated poly(ethylene glycol) hydrogels (GSH-PEG) against ABSSSIs utilizing an ex vivo porcine dermal explant model. Vancomycin- or meropenem-loaded GSH-PEG hydrogels at 3 different dose levels were loaded over 1 h. Drug release was monitored in vitro under submerged conditions, by the Franz cell diffusion method, and ex vivo utilizing a porcine dermis model. Antibacterial activity was assessed ex vivo on porcine dermis explants inoculated with Staphylococcus aureus or Pseudomonas aeruginosa isolates treated with vancomycin- or meropenem-loaded GSH-PEG hydrogels, respectively. Histological assessment of the explants was conducted to evaluate tissue integrity and viability in the context of the experimental conditions. A dose-dependent release was observed from vancomycin and meropenem hydrogels, with in vitro Franz cell diffusion data closely representing ex vivo vancomycin release, but not high dose meropenem release. High dose vancomycin-loaded hydrogels resulted in a >3 log10 clearance against all S. aureus isolates at 48 h. High dose meropenem-loaded hydrogels achieved 6.5, 4, and 2 log10 reductions in CFU/ml against susceptible, intermediate, and resistant P. aeruginosa isolates, respectively. Our findings demonstrate the potential application of GSH-PEG hydrogels for flexible, local antibiotic delivery against bacterial skin infections.

Bovine Serum Albumin - Hydroxyapatite Nanoflowers as Potential Local Drug Delivery System of Ciprofloxacin.

Hybrid nanoflowers are structures consisting of organic (enzymes, proteins, nucleic acids) and inorganic components (mostly metal phosphates) with a flower-like hierarchical structure. Novel hybrid nanoflowers based on bovine serum albumin (BSA) and hydroxyapatite (HA) were obtained and characterized. Study on BSA-HA nanoflowers as potential drug delivery system is reported for the first time. Embedding ciprofloxacin in the structure of hybrid nanoflowers was confirmed by ATR-FTIR and thermogravimetric analysis. The inorganic phase of the nanoflowers was determined by X-ray diffraction. UV‒Vis spectroscopy was used to evaluate the release profiles of ciprofloxacin from nanoflowers in buffer solutions at pH 7.4 and 5. The agar disk diffusion method was used to study the antibacterial activity of the synthesized nanoflowers against Staphylococcus aureus and Pseudomonas aeruginosa. Bovine serum albumin - hydroxyapatite nanoflowers were obtained with diameters of ca. 1-2 µm. The kinetics of ciprofloxacin release from nanoflowers were described by the Korsmeyer-Peppas model. The antibacterial activity of the synthesized nanoflowers was demonstrated against S. aureus and P. aeruginosa, two main pathogens found in osteomyelitis. The formulated nanoflowers may act as an efficient local antibiotic delivery system. Due to the use of nonhazardous, biodegradable components and benign synthesis, hybrid nanoflowers are very promising drug delivery systems that could be applied in the treatment of skeletal system infections.

Chitosan Sponges Are Associated With Higher Rates of Wound Complications Compared to Calcium Sulfate Beads.

Background In this study, we aimed to determine if there is a difference in the rates of wound dehiscence, delayed union, nonunion, and unanticipated surgery after the use of bioabsorbable local antibiotic-delivery systems (LADS), specifically comparing antibiotic-impregnated calcium sulfate pellets (Osteoset-T, Wright Medical Technology Inc., Arlington, TN, USA, hereafter referred to as beads) and chitosan sponge (Sentrex BioSponge, Bionova Medical, Germantown, TN, USA, hereafter referred to as sponges) in the management of acute and chronic extremity wounds. Methodology We conducted a retrospective comparative cohort study in the setting of a level 1 trauma center. All patients who received either beads or sponges as an adjunct to surgical debridement from January 2010 to December 2017 were included, and 136 patients met the inclusion criteria. The intervention studied was extremity wounds that were treated with bioabsorbable LADS, either beads or sponges. The main outcome measurement was wound dehiscence and the need for unanticipated surgery. Results Of the 136 patients in the study cohort, 78% (106/136) were treated with beads, and 22% (30/136) were treated with sponges. Of the 136 patients, 50 (37%) experienced wound dehiscence, and 49 patients required unanticipated surgery. Overall, 62% (31/50) of patients with wound dehiscence and 67.4% (33/49) of patients requiring unanticipated surgery were seen in the bead cohort (p = 0.0001 and 0.025, respectively). However, in multivariable analyses, we found that the odds of having wound dehiscence and undergoing unanticipated surgery were, respectively, 4.9 (p = 0.001) and 2.8 (p = 0.021) times more likely to occur in the sponge than in the bead group. Conclusions Sentrex sponges appear to be associated with higher rates of wound dehiscence and the need for unanticipated surgery compared to Osteoset beads.

Local Antibiotic Delivery Ceramic Bone Substitutes for the Treatment of Infected Bone Cavities and Bone Regeneration: A Systematic Review on What We Have Learned from Animal Models.

the focus of this study is to evaluate if the combination of an antibiotic with a ceramic biomaterial is effective in treating osteomyelitis in an infected animal model and to define which model and protocol are best suited for in vivo experiments of local bone infection treatment. a systematic review was carried out based on PRISMA statement guidelines. A PubMed search was conducted to find original papers on animal models of bone infections using local antibiotic delivery systems with the characteristics of bone substitutes. Articles without a control group, differing from the experimental group only by the addition of antibiotics to the bone substitute, were excluded. a total of 1185 records were retrieved, and after a three-step selection, 34 papers were included. Six manuscripts studied the effect of antibiotic-loaded biomaterials on bone infection prevention. Five articles studied infection in the presence of foreign bodies. In all but one, the combination of an antibiotic with bioceramic bone substitutes tended to prevent or cure bone infection while promoting biomaterial osteointegration. this systematic review shows that the combination of antibiotics with bioceramic bone substitutes may be appropriate to treat bone infection when applied locally. The variability of the animal models, time to develop an infection, antibiotic used, way of carrying and releasing antibiotics, type of ceramic material, and endpoints limits the conclusions on the ideal therapy, enhancing the need for consistent models and guidelines to develop an adequate combination of material and antimicrobial agent leading to an effective human application.

Use of Antibiotic-impregnated Polymethylmethacrylate (PMMA) Plates for Prevention of Periprosthetic Infection in Breast Reconstruction.

A retrospective review of patients who underwent immediate breast reconstruction with prepectoral TEs over the span of 5 years performed by two surgeons was completed, revealing a total of 447 patients. Data pertaining to patient demographics, operative details, and postoperative outcomes were recorded. Fifty patients underwent TE reconstruction with the addition of a PMMA plate (Stryker, Kalamazoo, Michigan) impregnated with tobramycin and vancomycin. Antibiotic plates were removed at the time of TE-to-implant exchange. Patient-matching analysis was performed using the 397 patients without PMMA plates to generate a 50-patient nonintervention cohort for statistical analysis. The intervention cohort (n = 50) and 1:1 patient-matched nonintervention cohort (n = 50) demonstrated no statistically significant differences in patient demographics or operative characteristics other than PMMA plate placement. The rate of operative periprosthetic infection was 4% in the intervention group and 14% in the nonintervention group (P = 0.047). The rate of TE explantation was also reduced in the intervention group (6% versus 18%; P = 0.036). Follow-up averaged 9.1 and 8.9 months for the intervention and nonintervention groups, respectively (P = 0.255). Local antibiotic delivery using antibiotic-impregnated PMMA plates can be safely and effectively used for infection prevention with TE-based breast reconstruction.

Local Antibiotics in the Treatment of Diabetic Foot Infections: A Narrative Review.

Along with the increasing global burden of diabetes, diabetic foot infections (DFI) and diabetic foot osteomyelitis (DFO) remain major challenges for patients and society. Despite progress in the development of prominent international guidelines, the optimal medical treatment for DFI and DFO remains unclear as to whether local antibiotics, that is, topical agents and local delivery systems, should be used alone or concomitant to conventional systemic antibiotics. To better inform clinicians in this evolving field, we performed a narrative review and summarized key relevant observational studies and clinical trials of non-prophylactic local antibiotics for the treatment of DFI and DFO, both alone and in combination with systemic antibiotics. We searched PubMed for studies published between January 2000 and October 2022, identified 388 potentially eligible records, and included 19 studies. Our findings highlight that evidence for adding local antibiotic delivery systems to standard DFO treatment remains limited. Furthermore, we found that so far, local antibiotic interventions have mainly targeted forefoot DFO, although there is marked variation in the design of the included studies. Suggestive evidence emerging from observational studies underscores that the addition of local agents to conventional systemic antibiotics might help to shorten the clinical healing time and overall recovery rates in infected diabetic foot ulcers, although the effectiveness of local antibiotics as a standalone approach remains overlooked. In conclusion, despite the heterogeneous body of evidence, the possibility that the addition of local antibiotics to conventional systemic treatment may improve outcomes in DFI and DFO cannot be ruled out. Antibiotic stewardship principles call for further research to elucidate the potential benefits of local antibiotics alone and in combination with conventional systemic antibiotics for the treatment of DFI and DFO.

The Antibiotic Cement Bead Rouleaux: A Technical Trick to Maximize the Surface Area to Volume Ratio of Cement Beads to Improve the Elution of Antibiotics.

The use of antibiotic-impregnated cement as a local antibiotic delivery system is well-established as an adjunctive treatment for chronic osteomyelitis. Because the elution of antibiotics is a surface area phenomenon, the geometry of the cement is an important consideration. The antibiotic cement bead rouleaux technique is a simple and efficient method of bead fabrication that requires only 10 minutes of preparation time and readily available operating room supplies. The discoid structure of the beads provides 3 times the surface-area-to-volume ratio of a spherical bead, which facilitates antibiotic elution. Given the speed and ease of fabrication, along with optimized geometry, the antibiotic cement bead rouleaux is a useful addition to the surgeon's repertoire.

Improvement of a commercial calcium phosphate bone cement by means of drug delivery and increased injectability

Calcium phosphate cements (CPCs) have been increasingly used as synthetic bone substitutes for repair and regeneration of bone defects given their biocompatibility, resemblance to bone and malleability. Moreover, their use as local antibiotic delivery systems is of main interest against bone infections, avoiding the adverse effects of high dosages of conventional therapy. The main goals of this work were to improve the properties of a commercial CPC (Neocement®), turning it injectable, and to provide it with a new functionality as a drug delivery system able to ensure a sustained release of an antibiotic commonly used in orthopaedics (gentamicin sulphate, GS). For this, the influence of the liquid phase amount (%LP) and type of polymer contained in the formulation (chitosan, Chi, or hydroxypropyl methylcellulose, HPMC) on the basic properties of the material was evaluated. It was found that the formulation containing 42%LP + HPMC+1.87% wt GS was the best one. It showed suitable setting and mechanical properties, and injectability around 87% (much superior to the original Neocement®, with 31%). It ensured a sustained release of GS for at least 14 days, at antibacterial levels. The antibiotic released is highly effective against S. epidermidis, but also presents some antibacterial activity against S. aureus. The CPC revealed to be non-cytotoxic. Moreover, it demonstrated good flowability and connectivity with human cadaveric trabecular bone.

Cellular and sub-chronic toxicity of hydroxyapatite porous beads loaded with antibiotic in rabbits, indented for chronic osteomyelitis

Bioceramics have emerged as a hopeful remedy for site-specific drug delivery in orthopaedic complications, especially in chronic osteomyelitis. The bioresorbable nature of bioceramic materials shaped them into a versatile class of local antibiotic delivery systems in the treatment of chronic osteomyelitis. Hydroxyapatite (HA) based bioceramics with natural bone mimicking chemical composition are of particular interest due to their excellent biocompatibility, better osteoconductive and osteointegrative properties. Although HA has been widely recognized as an efficient tool for local delivery of antibiotics, information regarding its subchronic systemic toxicity have not been explored yet. Moreover, a detailed investigation of in vivo subchronic systemic toxicity of HA is critical for understanding its biocompatibility and futuristic clinical applications of these materials as novel therapeutic system in its long haul. Evaluation of biocompatibility and sub-chronic systemic toxicity are significant determinants in ensuring biomedical device’s long-term functionality and success. Sub-chronic systemic toxicity allows assessing the potential adverse effects caused by leachable and nanosized wear particles from the device materials under permissible human exposure to the distant organs that are not in direct contact with the devices. In this context, the present study evaluates the sub-chronic systemic toxicity of in-house developed Hydroxyapatite porous beads (HAPB), gentamicin-loaded HAPB (HAPB + G) and vancomycin- loaded HAPB (HAPB + V) through 4 and 26-week muscle implantation in New Zealand white rabbits, as per ISO 10993–6 and ISO 10993–11. Analysis of cellular responses of HAPB towards Human Osteosarcoma (HOS) cell line through MTT assay, direct contact cytotoxicity, live/dead assay based on Imaging Flow Cytometry (IFC) showed its non-cytotoxic behaviour. Histopathological analysis of muscle tissue, organs like heart, lungs, liver, kidney, spleen, adrenals, intestine, testes, ovaries, and uterus did not reveal any abnormal biological responses. Our study concludes that the HAPB, gentamicin-loaded HAPB (HAPB + G) and vancomycin-loaded HAPB (HAPB + V) are biocompatible and did not induce sub-chronic systemic toxicity and hence satisfies the criteria for regulatory approval of HAs as a plausible candidate for clinical applications.

Overcoming the rising incidence and evolving mechanisms of antibiotic resistance by novel drug delivery approaches - An overview.

Antimicrobial resistance is a normal evolutionary process for microorganisms. Antibiotics exerted accelerated selective pressure that hasten bacterial resistance through mutation, and acquisition external genes. These genes often carry multiple antibiotic resistant determinants allowing the recipient microbe an instant "super-bug" status. The extent of Antimicrobial Resistance (AMR) has reached a level of global crisis, existing antimicrobials are no long effective in treating infections caused by AMR pathogens. The great majority of clinically available antimicrobial agents are administered through oral and intra-venous routes. Overcoming antibacterial resistance by novel drug delivery approach offered new hopes, particularly in the treatment of AMR pathogens in sites less assessible through systemic circulation such as the lung and skin. In the current review, we will revisit the mechanism and incidence of important AMR pathogens. Finally, we will discuss novel drug delivery approaches including novel local antibiotic delivery systems, hybrid antibiotics, and nanoparticle-based antibiotic delivery systems.

Wound Leakage With the Use of Calcium Sulphate Beads in Prosthetic Joint Surgeries: A Systematic Review.

Since its first use as a bone void filler at the end of the 19th century, calcium sulphate products have been adapted in different ways to aid orthopaedic surgeons. Calcium sulphate local antibiotic delivery systems offer a promising solution in the delivery of high antibiotic concentrations locally for an extended period of time. Over the years, multiple centres have reported side effects such as wound drainage, heterotrophic ossification and hypercalcaemia. This study was carried out to assess the risk of wound drainage in prosthetic joints after implantation of antibiotic-impregnated calcium sulphate beads. Two reviewers searched the literature in three online databases using the Cochrane methodology for systematic reviews. The search of databases yielded 182 articles. The studies without reported post-operative complications, mainly drainage outcomes, were excluded. After screening, seven articles were deemed suitable and selected. Out of the 1,112 cases identified, 43 joints developed wound drainage after calcium sulphate bead placement. This complication was resolved in all these cases by either conservative or operative approaches. The factors implicated in the development of wound drainage include the volume of the product used, procedural placement and host factors. The result of this systematic review shows that calcium sulphate products can be used for treatment and prophylaxis in prosthetic joints with a risk of post-procedural wound drainage. This risk, however, is lesser with the use of synthetic calcium sulphate products as compared with conventional calcium sulphate products.

Local Antibiotic Delivery Systems in Diabetic Foot Osteomyelitis: A Brief Review.

Diabetic foot osteomyelitis (DFO) is a severe, difficult to treat infection. Local antibiotic delivery has been studied as a potential therapeutic adjunct following surgery for DFO. This review aims to summarize the evidence on local antibiotic delivery systems in DFO. PubMed database was searched up to March 2020. Overall, 16 studies were identified and included: 3 randomized controlled trials (RCTs), 3 retrospective studies (RSs), and 10 case series. In the RCTs, gentamicin-impregnated collagen sponges significantly improved clinical healing rates and slightly improved duration of hospitalization. In the RSs, antibiotic-impregnated calcium sulfate beads non-significantly improved all healing parameters, but did not reduce post-operative amputation rates or time of healing. The majority of case series used calcium sulfate beads, achieving adequate rates of healing and eradication of infection. In conclusion, evidence for add-on local antibiotic delivery in DFO is still limited; more data are needed to assess this therapeutic measure.

Coated nails: is their use supported by the literature?

Antibiotic-coated intramedullary nails have been popularized in recent decades for treating long-bone infections. They are especially useful in treating diaphyseal infections requiring stability, such as those involving fractures and nonunions. The nails are made by injecting antibiotic-impregnated polymethylmethacrylate or "cement" around a metal core using a silicone tube as a mold. There are a variety of techniques that can be used to customize the nail to the affected site. Antibiotic cement has long been demonstrated as an effective local antibiotic delivery system. It is able to elute high concentrations of antibiotics while having little systemic toxicity. Several case series have reported good outcomes using this technique, defined by bone union and infection control. Further research is needed to determine the amount of weight that can safely be transferred through the nail and to optimize antibiotic elution.

Antimicrobial loading of nanotubular titanium surfaces favoring surface coverage by mammalian cells over bacterial colonization

Titanium is frequently used for dental implants, percutaneous pins and screws or orthopedic joint prostheses. Implant surfaces can become peri-operatively contaminated by surgically introduced bacteria during implantation causing lack of surface coverage by mammalian cells and subsequent implant failure. Especially implants that have to function in a bacteria-laden environment such as dental implants or percutaneous pins, cannot be surgically implanted while being kept sterile. Accordingly, contaminating bacteria adhering to implant surfaces hamper successful surface coverage by mammalian cells required for long-term functioning. Here, nanotubular titanium surfaces were prepared and loaded with Ag nanoparticles or gentamicin with the aim of killing contaminating bacteria in order to favor surface coverage by mammalian cells. In mono-cultures, unloaded nanotubules did not cause bacterial killing, but loading of Ag nanoparticles or gentamicin reduced the number of adhering Staphylococcus aureus or Pseudomonas aeruginosa CFUs. A gentamicin-resistant Staphylococcus epidermidis was only killed upon loading with Ag nanoparticles. However, unlike low-level gentamicin loading, loading with Ag nanoparticles also caused tissue-cell death. In bi-cultures, low-level gentamicin-loading of nanotubular titanium surfaces effectively eradicated contaminating bacteria favoring surface coverage by mammalian cells. Thus, care must be taken in loading nanotubular titanium surfaces with Ag nanoparticles, while low-level gentamicin-loaded nanotubular titanium surfaces can be used as a local antibiotic delivery system to negate failure of titanium implants due to peri-operatively introduced, contaminating bacteria without hampering surface coverage by mammalian cells.

Management of infected nonunions of the femur and tibia with compression-distraction osteogenesis coupled with modern methods at a tertiary military establishment: a prospective case series

Background: Infected nonunions pose a daunting challenge to any orthopaedic surgeon. The essence of treatment is a radical debridement for eradication of infection coupled with various approaches to address the bone gap. Bone transport and acute docking along with a corticotomy and distraction osteogenesis have stood the test of time. Our purpose was to evaluate the treatment outcome of the modified Ilizarov technique in infected nonunions of the femur and tibia. Methods: Twenty-six patients with infected femoral and tibial nonunions underwent aggressive debridement and either bifocal compression-distraction osteogenesis or bone transport using an Ilizarov frame. Adjuvant methods such as local antibiotic delivery systems, bone marrow aspirate concentrate (BMAC) injections, pulsatile recombinant parathyroid hormone (PTH) injections, and negative pressure wound therapy (NPWT) were deployed, as deemed necessary, in specific situations. Results: The mean follow-up period was 24.2 mo. The mean time to union was 267.7 days. Union was achieved in 25 cases with complete eradication of infection. Bone results as per the Association for Study of Application of Methods of Ilizarov (ASAMI) scoring system were excellent in 19 patients, good in four, fair in two, and poor in one. The average duration for external fixation was 8.9 mo. Complications occurred in 30.8% of patients. Conclusions: The Ilizarov method, by itself or in combination with modern methods, gives satisfactory bone and functional results. Complication rates depend upon the surgeon’s adherence to the cardinal principles of Ilizarov. Level of Evidence: Level IV.

Heparin-mediated antibiotic delivery from an electrochemically-aligned collagen sheet.

Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue. To develop and evaluate a novel, biologic antimicrobial coating for medical implants. Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per a protocol developed by our group. Sheets were incubated in antibiotic solution (gentamicin or moxifloxacin) overnight, and in vitro activity was assessed with five-day diffusion assays against Pseudomonas aeruginosa. Antibiotic release over time from gentamicin-infused sheets was determined using in vitro elution and high performance liquid chromatography (HPLC). Collagen-heparin-antibiotic sheets demonstrated larger growth inhibition zones against P. aeruginosa compared to collagen-antibiotic alone sheets. This activity persisted for five days and was not impacted by rinsing sheets prior to evaluation. Rinsed collagen-antibiotic sheets did not produce any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was gradual and remained above the minimal inhibitory concentration for gentamicin-sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic load within 24 hours. Overall, heparin-associated sheets demonstrated larger inhibition zones against P. aeruginosa and prolonged elution profile via HPLC. We developed a novel, local antibiotic delivery system that could be used to coat medical implants/hardware in the future and reduce post-operative infections.

Local Antibiotic Delivery Systems in the Surgical Treatment of Diabetic Foot Osteomyelitis: Again, No Benefit?

This retrospective study aimed to compare the outcomes and healing parameters of 3 groups of surgical treatment combined with and without local antibiotic administration in diabetic foot osteomyelitis (DFO). Overall, 25 patients with DFO who met the criteria were included in the study. Surgical debridement was used with systemic antibiotic administration alone (group A; n = 8) or combined with local application of antibiotic-loaded polymethylmethacrylate beads (group B; n = 9) or antibiotic-loaded hydroxyapatite and calcium sulfate beads (group C; n = 8). In total, 87.5% patients in group A, 100% in group B, and 87.5% in group C healed (P = .543). Median time to healing was 17 weeks in group A, 18 weeks in group B, and 19 weeks in group C (P = .094). One patient (12.5%) in group A was amputated. DFO recurrence rate was 12.5% in group A and 12.5% in group C (P = .543). Median hospitalization was 9 days in group A, 8 days in group B, and 9 days in group C (P = .081). In conclusion, adjunctive local antibiotic therapy was not shown to improve outcomes in surgically treated DFO.

Development of local vancomycin delivery system from fibrin gel to prevent Staphylococcus aureus biofilms graft infection

Prosthetic vascular graft infection is one of the most severe vascular surgery complications. Fibrin gel (FG) has many useful characteristics as biocompatibility, biodegradation, adhesion, and haemostasis to develop the local antibiotic delivery system. In this study, human plasma was collected from peripheral blood that was used to create fibrin gel by supplement ion Ca2+. Antibiotic-containing fibrin gel was then evaluated in some characteristics such as surface structure, biodegradation, antibiotic delivery, cytotoxicity, and bacterial biofilm prevention in vitro and in vivo. The results showed that fibrin gel was excellent material for the extended delivery of antibiotics. Most importantly, antibiotic-containing fibrin gel was not toxic for human fibroblast cells in vitro and inhibited bacterial biofilm growth in vitro and in vivo. This research is the first step in developing an antibiotic delivery system for effective graft infection treatments.

Teicoplanin-loaded chitosan-PEO nanofibers for local antibiotic delivery and wound healing

Antibiotic-loaded nano-delivery systems offer an advanced approach to overcome several limitations associated with antibiotic therapy. Antibiotic-loaded nanofibers can be applied topically for skin and wound healing, post operation implants for the prevention of abdominal adhesion, and prophylaxis and treatment of infections in orthopedic surgery. Here, the authors report the development of local antibiotic delivery system using chitosan- polyethylene oxide (PEO) nanofibers for delivery of teicoplanin. Successful electrospinning of chitosan-PEO solution containing 2 and 4 w/v% teicoplanin resulted in uniform and bead-less nanofibers. Nanofibers were able to release teicoplanin up to 12 days. Antibacterial test in agar diffusion and time-kill study on Staphylococcus aureus also demonstrate that loading teicoplanin in chitosan-PEO nanofibers not only kept the antibacterial activity of antibiotic but also, enhanced it up to 1.5 to 2 fold. Teicoplanin loaded nanofibers did not show any cytotoxicity to human fibroblast. Moreover, in vivo study on rat full thickness wound model confirmed safety and efficacy of applying teicoplanin loaded nanofibers and significant improve in wound closure was observed especially with nanofibers containing 4% teicoplanin. The sustained release profile, enhanced drug activity, cytocompatibility, and significant wound healing activity affirm the potential applications of teicoplanin-loaded nanofibers in wound healing and local antibiotic delivery.