scholarly journals Review of calcium-sulphate-based ceramics and synthetic bone substitutes used for antibiotic delivery in PJI and osteomyelitis treatment

2021 ◽  
Vol 6 (5) ◽  
pp. 297-304
Author(s):  
Razvan Ene ◽  
Mihai Nica ◽  
Dragos Ene ◽  
Adrian Cursaru ◽  
Catalin Cirstoiu
Keyword(s):  
Bacterial Colonization ◽  
Trauma Surgery ◽  
Bone Substitutes ◽  
Calcium Sulphate ◽  
Preclinical Research ◽  
Treatment And Prevention ◽  
Application Techniques ◽  
Biofilm Development ◽  
Local Antibiotic ◽  
Antibiotic Delivery

Infection in orthopaedic and trauma surgery remains a destructive complication with particularly challenging diagnosis and treatment due to bacterial antibiotic resistance and biofilm formation. Along with surgical debridement and systemic antibiotics, an important type of adjuvant therapy is local antibiotic delivery, with the purpose of eliminating bacterial colonization and biofilm development. Calcium sulphate, as a synthetic absorbable biomaterial used for local antibiotic delivery, has experienced an increasing popularity during the last decade, with multiple promoted advantages such as predictable antibiotic elution kinetics, complete and quick biodegradation, good biocompatibility, and limited associated complications. A series of commercially available antibiotic-delivery systems based on calcium sulphate are under investigation and in clinical use, with different presentations, compositions, and application techniques. The current article presents the main available calcium-sulphate-based products and the existing data about the clinical and preclinical research results, stemming from their implementation as local antibiotic carriers for surgical site and implant-associated infections treatment and prevention. Cite this article: EFORT Open Rev 2021;6:297-304. DOI: 10.1302/2058-5241.6.200083

scholarly journals Local Delivery of Antibiotics in the Context of Chronic Diabetic Foot Infection with Bony Involvement: A Case Series of 102 Patients

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0044
Author(s):  
James Widnall ◽  
David Harvey ◽  
Paul Evans ◽  
Gillian Jackson ◽  
Simon Platt
Keyword(s):  
Dead Space ◽  
Salvage Surgery ◽  
Case Series ◽  
Calcium Sulphate ◽  
Surgical Debridement ◽  
P Value ◽  
Space Management ◽  
Bony Involvement ◽  
Local Antibiotic ◽  
Antibiotic Delivery

Category: Diabetes Introduction/Purpose: Diabetic foot infection (DFI) is a devastating condition which poses risk to both life and limb. Treatment principles revolve around surgical debridement, dead space management, delivery of both local and systemic antibiotics and soft tissue cover. Dead space management and local antibiotic delivery can be achieved simultaneously by using an antibiotic loaded bone substitute. We report our retrospective case series of patients treated with surgical management involving local antibiotic delivery via calcium sulphate bone substitute (Stimulan™; Biocomposites, Keele, UK). Methods: All patients between January 2015 and June 2018 with DFI and proven bony involvement presenting to our university teaching hospital were treated via our extensive MDT approach. A total of 102 patients were included. Surgical debridement was performed along with simultaneous insertion of 10 ml calcium sulphate with 1 g vancomycin and 240 mg gentamycin. Outcome was classified as resolved, requiring prolonged treatment from other medical (endocrinologist) or surgical (plastic surgery, limb reconstruction) services or salvage surgery in the form of proximal amputation. Results: 45.1% of patients had a partial amputation at the index surgery. 52% had bony debridement and just 2.9% had soft tissue debridement in conjunction with calcium sulphate insertion. The surgical wound was primarily closed in 56.8% of patients. 7 patients had delayed wound closure and 36.2% of patients healed via secondary intention. 74 patients (72.5%) had resolution of their DFI with bony involvement following surgical intervention. 21 (20.6%) patients needed further treatment from allied specialties. 7 (6.9%) patients required salvage surgery in the form of a below knee amputation. There was no correlation between either closure type (2 p-value 0.75) or index surgery type and outcome (2 p-value 0.64). Conclusion: DFI is a difficult clinical scenario to treat effectively. An MDT approach is undoubtedly key to a good outcome. We believe that the use of calcium sulphate can be a useful adjunct at the time of surgical debridement to aid in both dead space management and allow local antibiotic delivery.

scholarly journals Current Insights in the Application of Bone Grafts for Local Antibiotic Delivery in Bone Reconstruction Surgery

2019 ◽  
Vol 4 (5) ◽  
pp. 245-253 ◽  
Author(s):  
Arne Peeters ◽  
Guy Putzeys ◽  
Lieven Thorrez
Keyword(s):  
Bone Grafts ◽  
Elution Profile ◽  
Clinical Use ◽  
Postoperative Infections ◽  
Bone Implant ◽  
Reconstruction Surgery ◽  
Treatment And Prevention ◽  
And Storage ◽  
Local Antibiotic ◽  
Antibiotic Delivery

Abstract. Introduction: Bone implant related infection is still one of the biggest challenges in bone and joint surgery. Antibiotic impregnated bone grafts seem to be promising in both treatment and prevention of these infections. However, great variance in methodology predominates this field of research. This paper gives an overview of the published literature.Methods: The PRISMA-flowchart was used as protocol for article selection. Medline was searched and articles were selected in accordance with predetermined exclusion criteria.Results: Forty-eight articles were included in the synthesis. Topics including bone graft type, manipulations of the graft, elution profile, bacterial inhibition, osteotoxicity, incorporation, special impregnation methods, clinical use and storage were investigated.Therapeutically, high initial levels seem appropriate for biofilm eradication. A single stage procedure in the treatment of bone implant related infection seems feasible. Prophylactically, the literature indicates a reduction of postoperative infections when using antibiotic impregnated bone grafts.Conclusion: Bone grafts are a suitable carrier for local antibiotic application both therapeutically and prophylactically.

scholarly journals Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karen E. Beenken ◽  
Mara J. Campbell ◽  
Aura M. Ramirez ◽  
Karrar Alghazali ◽  
Christopher M. Walker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Defect ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Bovine Bone ◽  
Bone Filler ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

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

2021 ◽  
pp. 1-12
Author(s):  
Olivia T. Cheng ◽  
Andrew P. Stein ◽  
Eric Babajanian ◽  
Kathryn R. Hoppe ◽  
Shawn Li ◽  
...  
Keyword(s):  
High Performance ◽  
Inhibitory Concentration ◽  
Medical Implants ◽  
Implantable Medical Devices ◽  
Antibiotic Solution ◽  
Inhibition Zones ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

BACKGROUND: Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue. OBJECTIVE: To develop and evaluate a novel, biologic antimicrobial coating for medical implants. METHODS: Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per 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 overtime from gentamicin infused sheets was determined using in vitro elution and high performance liquid chromatography (HPLC). RESULTS: 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 show any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was slow and remained above the minimal inhibitory concentration for gentamicin sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic payload within 24 hours. Overall, heparin associated sheets demonstrated larger inhibition zones against P. aeruginosa and prolonged elution profile via HPLC. CONCLUSION: 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.

scholarly journals The Role of Exopolysaccharides in Oral Biofilms

2019 ◽  
Vol 98 (7) ◽  
pp. 739-745 ◽  
Author(s):  
C. Cugini ◽  
M. Shanmugam ◽  
N. Landge ◽  
N. Ramasubbu
Keyword(s):  
Biofilm Formation ◽  
Bacterial Colonization ◽  
Super Resolution ◽  
Extracellular Proteins ◽  
Extracellular Polysaccharides ◽  
Oral Biofilms ◽  
The Matrix ◽  
Oral Microbes ◽  
Biofilm Development

The oral cavity contains a rich consortium of exopolysaccharide-producing microbes. These extracellular polysaccharides comprise a major component of the oral biofilm. Together with extracellular proteins, DNA, and lipids, they form the biofilm matrix, which contributes to bacterial colonization, biofilm formation and maintenance, and pathogenesis. While a number of oral microbes have been studied in detail with regard to biofilm formation and pathogenesis, the exopolysaccharides have been well characterized for only select organisms, namely Streptococcus mutans and Aggregatibacter actinomycetemcomitans. Studies on the exopolysaccharides of other oral organisms, however, are in their infancy. In this review, we present the current research on exopolysaccharides of oral microbes regarding their biosynthesis, regulation, contributions to biofilm formation and stability of the matrix, and immune evasion. In addition, insight into the role of exopolysaccharides in biofilms is highlighted through the evaluation of emerging techniques such as pH probing of biofilm colonies, solid-state nuclear magnetic resonance for macromolecular interactions within biofilms, and super-resolution microscopy analysis of biofilm development. Finally, exopolysaccharide as a potential nutrient source for species within a biofilm is discussed.

A systematic review of local antibiotic devices used to improve wound healing following the surgical management of foot infections in diabetics

2018 ◽  
Vol 100-B (11) ◽  
pp. 1409-1415 ◽  
Author(s):  
B. A. Marson ◽  
S. R. Deshmukh ◽  
D. J. C. Grindlay ◽  
B. J. Ollivere ◽  
B. E. Scammell
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Surgical Management ◽  
Case Series ◽  
Diabetic Patients ◽  
Local Antibiotics ◽  
Wound Breakdown ◽  
Patients With Diabetes ◽  
Local Antibiotic ◽  
Antibiotic Delivery

Aims Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery. Materials and Methods Databases were searched to identify eligible studies and 13 were identified for inclusion. Results Overall, the quality of the studies was poor. A single trial suggested that wound healing is quicker when a gentamicin-impregnated collagen sponge was implanted at time of surgery, with no difference in length of stay or rate of amputation. Results from studies with high risk of bias indicated no change in wound healing when a gentamicin-impregnated sponge was implanted during transmetatarsal amputation, but a reduction in the incidence of wound breakdown (8% vs 25%, not statistically significant) was identified. A significant cost reduction was identified when using an antimicrobial gel to deliver antibiotics and anti-biofilm agents (quorum-sensing inhibitors) compared with routine dressings and systemic antibiotics. Analyses of case series identified 485 patients who were treated using local antibiotic delivery devices. The rates of wound healing, re-operation, and mortality were comparable to those that have been previously reported for the routine management of these infections. Conclusion There is a lack of good-quality evidence to support the use of local antibiotic delivery devices in the treatment of foot infections in patients with diabetes. Cite this article: Bone Joint J 2018;100-B:1409–15.

scholarly journals In Vitro Evaluation of Gentamicin or Vancomycin Containing Bone Graft Substitute in the Prevention of Orthopedic Implant-Related Infections

2020 ◽  
Vol 21 (23) ◽  
pp. 9250
Author(s):  
Alessandro Bidossi ◽  
Marta Bottagisio ◽  
Nicola Logoluso ◽  
Elena De Vecchi
Keyword(s):  
Antibiotic Resistance ◽  
Bone Graft ◽  
Calcium Sulfate ◽  
Prolonged Exposure ◽  
Bacterial Colonization ◽  
Bone Graft Substitute ◽  
Bacterial Strains ◽  
Bone Graft Substitutes ◽  
Biofilm Development

Antibiotic-loaded bone graft substitutes are attractive clinical options and have been used for years either for prophylaxis or therapy for periprosthetic and fracture-related infections. Calcium sulfate and hydroxyapatite can be combined in an injectable and moldable bone graft substitute that provides dead space management with local release of high concentrations of antibiotics in a one-stage approach. With the aim to test preventive strategies against bone infections, a commercial hydroxyapatite/calcium sulfate bone graft substitute containing either gentamicin or vancomycin was tested against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, harboring different resistance determinants. The prevention of bacterial colonization and biofilm development by selected microorganisms was investigated along with the capability of the eluted antibiotics to select for antibiotic resistance. The addition of antibiotics drastically affected the ability of the selected strains to adhere to the tested compound. Furthermore, both the antibiotics eluted by the bone graft substitutes were able to negatively impair the biofilm maturation of all the staphylococcal strains. As expected, P. aeruginosa was significantly affected only by the gentamicin containing bone graft substitutes. Finally, the prolonged exposure to antibiotic-containing sulfate/hydroxyapatite discs did not lead to any stable or transient adaptations in either of the tested bacterial strains. No signs of the development of antibiotic resistance were found, which confirms the safety of this strategy for the prevention of infection in orthopedic surgery.

scholarly journals Characterization and Antibiofilm Activity of Mannitol–Chitosan-Blended Paste for Local Antibiotic Delivery System

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 517 ◽  
Author(s):  
Leslie R. Pace ◽  
Zoe L. Harrison ◽  
Madison N. Brown ◽  
Warren O. Haggard ◽  
J. Amber Jennings
Keyword(s):  
Infection Prevention ◽  
Bacterial Biofilm ◽  
Antibiofilm Activity ◽  
Persister Cells ◽  
In Vivo Evaluation ◽  
Musculoskeletal Infection ◽  
Prevention And Treatment ◽  
Local Antibiotic ◽  
Antibiotic Delivery

Mannitol, a polyalcohol bacterial metabolite, has been shown to activate dormant persister cells within bacterial biofilm. This study sought to evaluate an injectable blend of mannitol, chitosan, and polyethylene glycol for delivery of antibiotics and mannitol for eradication of Staphylococcal biofilm. Mannitol blends were injectable and had decreased dissociation and degradation in the enzyme lysozyme compared to blends without mannitol. Vancomycin and amikacin eluted in a burst response, with active concentrations extended to seven days compared to five days for blends without mannitol. Mannitol eluted from the paste in a burst the first day and continued through Day 4. Eluates from the mannitol pastes with and without antibiotics decreased viability of established S. aureus biofilm by up to 95.5% compared to blends without mannitol, which only decreased biofilm when loaded with antibiotics. Cytocompatibility tests indicated no adverse effects on viability of fibroblasts. In vivo evaluation of inflammatory response revealed mannitol blends scored within the 2–4 range at Week 1 (2.6 ± 1.1) and at Week 4 (3.0 ± 0.8), indicative of moderate inflammation and comparable to non-mannitol pastes (p = 0.065). Clinically, this paste could be loaded with clinician-selected antibiotics and used as an adjunctive therapy for musculoskeletal infection prevention and treatment.

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