Local Antibiotic Therapy in Osteomyelitis (original) (raw)
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Biodegradable vs non-biodegradable antibiotic delivery devices in the treatment of osteomyelitis
Expert Opinion on Drug Delivery, 2013
Introduction: Chronic osteomyelitis, or bone infection, is a major worldwide cause of morbidity and mortality, as it is exceptionally hard to treat due to patient and pathogen-associated factors. Successful treatment requires surgical debridement together with long-term, high antibiotic concentrations that are best achieved by local delivery devices, either made of degradable or non-degradable materials. Areas covered: Non-degradable delivery devices are frequently constituted by polymethylmethacrylate-based carriers. Drawbacks are the need to remove the carrier (as the carrier itself may provide a substratum for bacterial colonization), inefficient release kinetics and incompatibility with certain antibiotics. These drawbacks have led to the quest for degradable alternatives, but also devices made of biodegradable calcium sulphate, collagen sponges, calcium phosphate or polylactic acids have their specific disadvantages. Expert opinion: Antibiotic treatment of osteomyelitis with the current degradable and non-degradable delivery devices is effective in the majority of cases. Degradable carriers have an advantage over non-degradable carriers that they do not require surgical removal. Synthetic poly(trimethylene carbonate) may be preferred in the future over currently approved lactic/ glycolic acids, because it does not yield acidic degradation products. Moreover, degradable poly(trimethylene carbonate) yields a zero-order release kinetics that may not stimulate development of antibiotic-resistant bacterial strains due to the absence of long-term, low-concentration tail-release.
Acta Orthopaedica, 2009
Background and purpose Many investigations on biodegradable materials acting as an antibiotic carrier for local drug delivery are based on poly(lactide). However, the use of poly(lactide) implants in bone has been disputed because of poor bone regeneration at the site of implantation. Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polymer that does not produce acidic degradation products. We explored the suitability of PTMC as an antibiotic releasing polymer for the local treatment of osteomyelitis.
Local antibiotic diffusion in rabbit femurs from two new PMMA-based and nail-shaped composites, enriched with b-tricalcium phosphate (P-TCP) and BaSO 4 or only with BaSO 4 (P-BaSO 4), and soaked in a solution of gentamicin (G) and vancomycin (V) was studied. Nails were implanted into the intramedullary cavity of healthy and osteomyelitic femurs to study the resolution of infection and to quantify the antibiotic penetration into bone by microbiological, pharmacological, and histological tests. A significant progression of osteomyelitis was recorded 7 weeks after MRSA inoculation, whereas no bacteria were found in animals treated with antibiotic-loaded nails as confirmed by microbiology and histology (Smeltzer score). The release of both antibiotics from composites was high and prompt both in healthy and infected bone; the amount of V was higher than that of G in all bone samples. Antibiotics of both composites were still present in bone 3 weeks after nail implantation. The P-BaSO4 composite released a lower amount of antibiotics than did P-TCP. The G-V combination in vivo exerted a synergistic bactericidal effect, which was confirmed by microbiological, histo-logical, and clinical results (no infection). These new porous PMMA composites, soaked in G-V solution in the operating room, might be an effective and useful drug delivery system for osteomyelitis treatment. ß
Journal of Orthopaedic Research, 1993
Acute and chronic osteomyelitis can be difficult to treat by conventional means. Current methods of treatment involve the use of systemic antibiotics, the local implantation of non-degradable drug carriers, and surgical dkbridement. Each method has specific drawbacks. We report on the use of a new controlled release system utilizing gentamicin and bioerodible, biocompatible polymers (polyanhydrides) designed for drug delivery applications for the treatment of clinical osteomyelitis. We compared this system's ability to reduce bacterial levels in infected bone with that of conventional non-degradable delivery systems based on polymethylmethacrylate (PMMA) and gentamicin. Polyanhydride copolymers of bis-carboxyphenoxypropane and sebacic acid P loaded with gentamicin sulfate and PMMA/gentamicin matrices were implanted in the long bones of Sprague-Dawley rats infected with a strain of Staphylococcus aureus. After 3 weeks of implantation, the polymeric delivery devices were removed and quantitative cultures were used to determine bacterial levels in bone. The polyanhydride/gentamicin matrices demonstrated significant degradation over the 3 week implantation period. Levels of bacteria, measured in colony forming units, were significantly lower in bone implanted with the polyanhydride/gentamicin release system than in long bones of control animals without an implant (p < 0.01), of animals with a polyanhydride polymer implant alone (p < 0.01), and of animals with a PMMAigentamicin implant (p = 0.03). Bioerodible polyanhydrides show promise as a new treatment modality for infections in bone. Osteomyelitis, in both its acute and chronic forms, remains difficult to treat (29). In acute osteomyelitis, a rapidly progressing infection of bone takes place,
Journal of Biomedical Materials Research Part A, 2006
The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(d/l-lactide). Cylindrical composite pellets (1.0 ϫ 0.9 mm) were manufactured from bioabsorbable poly(d/l-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (Ͼ2 g/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 g/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, cip-rofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.
Local Delivery of Antibiotics in the Surgical Treatment of Bone Infections
Thorough surgical debridement and intelligent use of antibiotics are key factors in the treatment of implant-associated bone infections and osteomyelitis. The local use of antibiotics is intended to achieve high concentrations of the antimicrobial agents in the wound for eradication of the bacteria or at least to reduce the bacterial load combined with low systemic concentrations to eliminate systemic side effects. Moreover, it enables access to necrotic and devascularized infected bone fragments in the wound which cannot be reached by intravenous therapy. The intention of this article is to review different antibiotics and carrier systems to provide a practical guideline for the intraoperative use of these agents for the surgeon. Gentamicin, tobra-mycin, and vancomycin are the most frequently used antibiotics in septic orthopedic surgery. However, only rifampicin offers the combination of antibiofilm activity and intracellular activity against Staphylococcus aureus, however, its use in combination with poly-methylmethacrylate (PMMA) is compromised due to the interference with PMMA polymerization. In general, there are resorbable and nonresorbable carriers which offer different antibiotic loading options. PMMA is the most common nonresorbable carrier for which commercial products, such as beads or antibiotic-loaded spacer cements are available. Different antibiotic loadings for handmade PMMA delivery systems have been described in the literature including antifungal agents. Resorbable carrier systems lead to a material-tissue interaction with subsequent degradation of the material and do not require removal by an additional surgical procedure. Collagen-based, calcium sulfate-based, and calcium phosphate-based materials are typical biodegradable carriers that can be used for the local delivery of antibiotics.
European Cells and Materials, 2014
Open fractures are at risk of serious infection and, if infected, require several surgical interventions and courses of systemic antibiotics. We investigated a new injectable formulation that simultaneously hardens in vivo to form a porous scaffold for bone repair and delivers antibiotics at high concentrations to the local site of infection. Duration of antimicrobial activity against Staphylococcus aureus was determined using the serial plate transfer test. Ultimate compressive strength and porosity of the material was measured with and without antibiotics. The material was evaluated in vivo in an ovine medial femoral condyle defect model contaminated with S. aureus. Sheep were sacrificed at either 2 or 13 weeks and the defect and surrounding bone assessed using micro-computed tomography and histology. Antimicrobial activity in vitro persisted for 19-21 days. Sheep with antibiotic-free material and bacteria became infected, while those with antibiotic-containing material and bacteria did not. Similarly, new bone growth was seen in uninoculated animals with plain polymer, and in those with antibiotic polymer with bacteria, but not in sheep with plain polymer and bacteria. The antibiotic-impregnated scaffolds were effective in preventing S. aureus infections whilst supporting bone growth and repair. If translated into clinical practice, this approach might reduce the need for systemic antibiotics.
Antimicrobial biomaterials in the prevention and local treatment of infection in orthopedics
Chirurgia Narządów Ruchu i Ortopedia Polska, 2019
According to current views, infection around the orthopedic implant and in chronic osteomyelitis is associated with the development of a bacterial biofilm, which is a barrier to systemic administered antibiotics. This results in the inability to cure the infection with systemic antimicrobial therapy because the doses guaranteeing activity in the biofilm will be toxic to the patient. The antibiotic concentration effective against bacteria in the biofilm can be achieved by local administration. The main advantage of local antibiotic carriers is the local release of drugs in high concentrations that exceed those achievable after systemic administration, but without systemic toxicity. The vehicle should provide a high local concentration of antibiotic above the minimal inhibitory concentrations (MIC) for the most common pathogens an should be effective against sedentary forms of bacteria. It can not impair the regeneration of bone tissue and the biological integration of the implant with the bone. Carriers that are both a substitute for bone and have osteoconductive or osteoinductive properties protect the bone from re-infection and promote the reconstruction of cavernous defects. Local carriers of antibacterial drugs may be absorbable or non-absorbable and depending on physico-chemical properties include 6 classes of biomaterials. Local carriers of antibacterial substances are currently being and will probably remain the treatment of choice of infections of orthopedic implants and osteomyelitis.
Novel Local Bone Void Filling Antibiotic Carriers for the Treatment of Bone Infection
Orthopedic Research Online Journal, 2017
To combat acute and chronic osteomyelitis, particularly implant-associated osteomyelitis, local antibiotic delivery from a biodegradable carrier is favorable over systemic antibiotic treatment. Not only can this help to achieve high local concentration over a desired therapeutic window, but it can also fill the void space left after surgical debridement.This mini review will briefly consider the advantages and disadvantages of synthetic polymer-based materials, ceramics, and calcium-based materials such as calcium phosphate (CP), calcium sulphate (CS), and bioglass, which can be used as a local antibiotic carrier as well as a bone void filler.