RESUMEN
Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) was introduced to decrease wear debris and osteolysis. During cross-linking, free radicals are formed, making highly cross-linked polyethylene vulnerable to oxidative degradation. In order to reduce this process, anti-oxidant vitamin E can be incorporated in polyethylene. This review provides an overview of the effects of vitamin E incorporation on major complications in total joint arthroplasty: material failure due to oxidative degradation, wear debris and subsequent periprosthetic osteolysis, and prosthetic joint infections. Secondly, this review summarizes the first clinical results of total hip and knee arthroplasties with vitamin E incorporated highly cross-linked polyethylene. Based on in vitro studies, incorporation of vitamin E in polyethylene provides good oxidative protection and preserves low wear rates. Incorporation of vitamin E may have the beneficial effect of reduced inflammatory response to its wear particles. Some microorganisms showed reduced adherence to vitamin E-incorporated UHMWPE; however, clinical relevance is doubtful. Short-term clinical studies of total hip and knee arthroplasties with vitamin E-incorporated highly cross-linked UHMWPE reported good clinical results and wear rates similar to highly cross-linked UHMWPE without vitamin E.
Asunto(s)
Antioxidantes/farmacología , Artroplastia de Reemplazo/efectos adversos , Materiales Biocompatibles/farmacología , Prótesis Articulares/efectos adversos , Polietilenos/farmacología , Vitamina E/farmacología , Artroplastia de Reemplazo/instrumentación , Materiales Biocompatibles/efectos adversos , Humanos , Inmunidad/efectos de los fármacos , Infecciones/etiología , Ensayo de Materiales , Osteólisis/etiología , Estrés Oxidativo/efectos de los fármacos , Polietilenos/efectos adversos , Diseño de Prótesis , Falla de Prótesis/efectos de los fármacos , Falla de Prótesis/etiología , Infecciones Relacionadas con Prótesis/etiologíaRESUMEN
BACKGROUND.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using ß-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with ß-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of ß-lactams are confirmed and maybe also a potential benefit from adding rifampin.
Asunto(s)
Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/terapia , Infecciones Relacionadas con Prótesis/terapia , Infecciones Estreptocócicas/terapia , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Artritis Infecciosa/microbiología , Artritis Infecciosa/mortalidad , Biopelículas/efectos de los fármacos , Desbridamiento , Femenino , Humanos , Internacionalidad , Masculino , Pronóstico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Relacionadas con Prótesis/mortalidad , Estudios Retrospectivos , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Terapia Recuperativa , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus agalactiae/aislamiento & purificación , Insuficiencia del Tratamiento , beta-Lactamas/administración & dosificación , beta-Lactamas/uso terapéuticoRESUMEN
We present a rare case of an immunocompetent host who developed a Candida albicans-infected total hip prosthesis. The infection could not be eradicated with debridement and extensive antifungal therapy. Our patient first underwent a resection of the proximal femur and local treatment with gentamicin-loaded cement beads. In a second procedure, a handmade cement spacer impregnated with voriconazole, amphotericin B, and vancomycin was placed. After 3 months of additional systemic antibiotic therapy, the patient remained afebrile, and a tumor prosthesis was placed. Six years postoperatively, she is doing well, walking with a small limp and no signs of recurrent infection. This is the first report on elution of voriconazole and amphotericin B from bone cement delivered at clinically significant concentrations for at least 72 hours.
Asunto(s)
Antifúngicos/administración & dosificación , Artroplastia de Reemplazo de Cadera/efectos adversos , Candidiasis/terapia , Fracturas del Cuello Femoral/cirugía , Fémur/cirugía , Infecciones Relacionadas con Prótesis/terapia , Anciano , Antibacterianos/administración & dosificación , Cementos para Huesos , Trasplante Óseo , Candida albicans , Desbridamiento , Remoción de Dispositivos , Femenino , Prótesis de Cadera/efectos adversos , Prótesis de Cadera/microbiología , Humanos , Fracturas Periprotésicas/cirugía , Infecciones Relacionadas con Prótesis/microbiología , ReoperaciónRESUMEN
BACKGROUND: Around about 1970, a gentamicin-loaded poly (methylmethacrylate) (PMMA) bone cement brand (Refobacin Palacos R) was introduced to control infection in joint arthroplasties. In 2005, this brand was replaced by two gentamicin-loaded follow-up brands, Refobacin Bone Cement R and Palacos R + G. In addition, another gentamicin-loaded cement brand, SmartSet GHV, was introduced in Europe in 2003. In the present study, we investigated differences in gentamicin release and the antibacterial efficacy of the eluent between these four cement brands. METHODS: 200 µm-wide gaps were made in samples of each cement and filled with buffer in order to measure the gentamicin release. Release kinetics were related to bone cement powder particle characteristics and wettabilities of the cement surfaces. Gaps were also inoculated with bacteria isolated from infected prostheses for 24 h and their survival determined. Gentamicin release and bacterial survival were statistically analysed using the Student's t-test. RESULTS: All three Palacos variants showed equal burst releases but each of the successor Palacos cements showed significantly higher sustained releases. SmartSet GHV showed a significantly higher burst release, while its sustained release was comparable with original Palacos. A gentamicin-sensitive bacterium did not survive in the high gentamicin concentrations in the interfacial gaps, while a gentamicin-resistant strain did, regardless of the type of cement used. Survival was independent of the level of burst release by the bone cement. CONCLUSIONS: Although marketed as the original gentamicin-loaded Palacos cement, orthopaedic surgeons should be aware that the successor cements do not appear to have the same release characteristics as the original one. Overall, high gentamicin concentrations were reached inside our prosthesis-related interfacial gap model. These concentrations may be expected to effectively decontaminate the prosthesis-related interfacial gap directly after implantation, provided that these bacteria are sensitive for gentamicin.
Asunto(s)
Cementos para Huesos , Gentamicinas/farmacocinética , Metilmetacrilatos , Modelos Biológicos , Prótesis e Implantes , Animales , Polimetil Metacrilato/farmacocinética , Infecciones Relacionadas con Prótesis/prevención & control , Staphylococcus/crecimiento & desarrolloRESUMEN
BACKGROUND AND PURPOSE: Joint replacement with metal-on-metal (MOM) bearings have gained popularity in the last decades in young and active patients. However, the possible effects of MOM wear debris and its corrosion products are still the subject of debate. Alongside the potential disadvantages such as toxicity, the influences of metal particles and metal ions on infection risk are unclear. METHODS: We reviewed the available literature on the influence of degradation products of MOM bearings in total hip arthroplasties on infection risk. RESULTS: Wear products were found to influence the risk of infection by hampering the immune system, by inhibiting or accelerating bacterial growth, and by a possible antibiotic resistance and heavy metal co-selection mechanism. INTERPRETATION: Whether or not the combined effects of MOM wear products make MOM bearings less or more prone to infection requires investigation in the near future.
Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Metales/efectos adversos , Infecciones Relacionadas con Prótesis/etiología , Aleaciones/efectos adversos , Biopelículas/efectos de los fármacos , Biopelículas/efectos de la radiación , Farmacorresistencia Bacteriana/efectos de los fármacos , Prótesis de Cadera/efectos adversos , Humanos , Iones , Metales Pesados/efectos adversos , Tamaño de la Partícula , Diseño de Prótesis , Falla de Prótesis , Infecciones Relacionadas con Prótesis/inmunología , Infecciones Relacionadas con Prótesis/microbiología , Factores de RiesgoRESUMEN
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. METHODS: This study addressed 2 separate attributes of PTMC: (1) the release kinetics of gentamicin-loaded PTMC and (2) its behavior in inhibiting biofilm formation. Both of these characteristics were compared with those of commercially available gentamicin-loaded poly(methylmethacrylate) (PMMA) beads, which are commonly used in the local treatment of osteomyelitis. RESULTS: In a lipase solution that mimics the in vivo situation, PTMC discs with gentamicin incorporated were degraded by surface erosion and released 60% of the gentamicin within 14 days. This is similar to the gentamicin release from clinically used PMMA beads. Moreover, biofilm formation by Staphylococcus aureus was inhibited by approximately 80% over at least 14 days in the presence of gentamicin-loaded PTMC discs. This is similar to the effect of gentamicin-loaded PMMA beads. In the absence of the lipase, surface erosion of PTMC discs did not occur and gentamicin release and biofilm inhibition were limited. INTERPRETATION: Since gentamicin-loaded PTMC discs show antibiotic release characteristics and biofilm inhibition characteristics similar to those of gentamicin-loaded PMMA beads, PTMC appears to be a promising biodegradable carrier in the local treatment of osteomyelitis.
Asunto(s)
Antibacterianos/administración & dosificación , Dioxanos/administración & dosificación , Portadores de Fármacos , Gentamicinas/administración & dosificación , Osteomielitis/tratamiento farmacológico , Polímeros/administración & dosificación , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Implantes Absorbibles , Antibacterianos/farmacocinética , Biopelículas , Cementos para Huesos , Dioxanos/farmacocinética , Gentamicinas/farmacocinética , Humanos , Metilmetacrilato/administración & dosificación , Metilmetacrilato/farmacocinética , Polímeros/farmacocinéticaRESUMEN
BACKGROUND AND PURPOSE: Commercial gentamicin-loaded bone cement beads (Septopal) constitute an effective delivery system for local antibiotic therapy. These beads are not available in all parts of the world, and are too expensive for frequent use in others. Thus, orthopedic surgeons worldwide make antibiotic-loaded beads themselves. However, these beads are usually not as effective as the commercial beads because of inadequate release kinetics. Our purpose was to develop a simple, cheap, and effective formulation to prepare gentamicin-loaded beads with release properties and antibacterial efficacy similar to the commercially ones. METHODS: Acrylic beads were prepared with variable monomer content: 100% (500 microL/g polymer), 75%, and 50% to increase gentamicin release through creation of a less dense polymer matrix. Using the optimal monomer content, different gel-forming polymeric fillers were added to enhance the permeation of fluids into the beads. Polyvinylpyrrolidone (PVP) 17 was selected as a suitable filler; its concentration was varied and the antibiotic release and antibacterial efficacy of these beads were compared with the corresponding properties of the commercial ones. RESULTS: Gentamicin release rate and the extent of release from beads prepared with 50% monomer increased when the PVP17 content was increased. Beads with 15 w/w% PVP17 released 87% of their antibiotic content. This is substantially more than the gentamicin release from Septopal beads (59%). Acrylic beads with 15 w/w% PVP17 reduced bacterial growth by up to 93%, which is similar to the antibacterial properties of the commercial ones. INTERPRETATION: A simple, cheap, and effective formulation and preparation process has been described for hand-made gentamicin-releasing acrylic beads, with better release kinetics and with antibacterial efficacy similar to that of the commercial ones.
Asunto(s)
Cementos para Huesos , Portadores de Fármacos , Gentamicinas/administración & dosificación , Metilmetacrilatos/administración & dosificación , Biopelículas , Composición de Medicamentos/economía , Composición de Medicamentos/métodos , Implantes de Medicamentos , Gentamicinas/farmacocinética , Humanos , Ensayo de Materiales , Metilmetacrilatos/farmacocinética , Osteomielitis/tratamiento farmacológico , Osteomielitis/prevención & control , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/prevención & controlRESUMEN
Bone cements loaded with combinations of antibiotics are assumed more effective in preventing infection than bone cements with gentamicin as a single drug. Moreover, loading with an additional antibiotic may increase interconnectivity between antibiotic particles to enhance release. We hypothesize addition of clindamycin to a gentamicin-loaded cement yields higher antibiotic release and causes larger inhibition zones against clinical isolates grown on agar and stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Bacterial colony counting and confocal laser scanning microscopy of biofilms grown on the bone cements suggest antibiotic release reduced bacterial viability, most notably close to the cement surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin-resistant small colony variants on Palacos R-G and therefore Copal more effectively decreased biofilm formation than Palacos R-G.
Asunto(s)
Antibacterianos/farmacocinética , Biopelículas , Cementos para Huesos/farmacocinética , Clindamicina/farmacocinética , Gentamicinas/farmacocinética , Polimetil Metacrilato/farmacocinética , Difusión , Solubilidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
The increasing gentamicin resistance among bacteria in septic joint arthroplasty has stimulated interest in adding a second antibiotic into gentamicin-loaded bone cement. A first aim of this in vitro study is to investigate whether addition of fusidic acid or clindamycin to gentamicin-loaded bone cement has an additional antimicrobial effect against a collection of 38 clinical isolates, including 16 gentamicin-resistant strains. A modified Kirby-Bauer test, involving measurement of the inhibition zone around antibiotic-loaded bone cement discs on agar plates, was used to investigate whether adding a second antibiotic has an additional antimicrobial effect. Second, a selected number of strains was used to study their survival in an interfacial gap made in the different bone cements to mimic the gap between bone and cement as existing near a prosthesis. Gentamicin-loaded bone cement had an antimicrobial activity against 58% of the 38 bacterial strains included in this study, while 68% of the strains were affected by bone cement loaded with a combination of gentamicin and clindamycin. Bone cement loaded with the combination of gentamicin and fusidic acid had antimicrobial activity against 87% of the bacterial strains. In the prosthesis-related gap model, there was a clear trend toward less bacterial survival for gentamicin-loaded bone cement after adding clindamycin or fusidic acid. Addition of clindamycin or fusidic acid into gentamicin-loaded bone cement yields an additional antimicrobial effect. The combination gentamicin and fusidic acid was effective against a higher number of clinical isolates than the combination of gentamicin with clindamycin, including gentamicin-resistant strains.
Asunto(s)
Antibacterianos/farmacología , Cementos para Huesos , Clindamicina/farmacología , Ácido Fusídico/farmacología , Gentamicinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Combinación de Medicamentos , Sinergismo Farmacológico , Bacterias Gramnegativas/crecimiento & desarrollo , Técnicas In Vitro , Pruebas de Sensibilidad MicrobianaAsunto(s)
Biopelículas , Pie Diabético , Administración Oral , Anciano , Amputación Quirúrgica , Antibacterianos/administración & dosificación , Desbridamiento , Pie Diabético/tratamiento farmacológico , Pie Diabético/microbiología , Pie Diabético/cirugía , Humanos , Masculino , Persona de Mediana Edad , Dedos del Pie/cirugía , Cicatrización de HeridasRESUMEN
Standard antibiotic therapy in osteomyelitis patients is of limited value when methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), or small-colony variants (SCV) are present. Far better results are obtained by local drug delivery of antibiotic combinations including rifampicin, using a suitable carrier. We therefore investigated release kinetics of antibiotics from biodegradable poly(trimethylene carbonate) (PTMC) and in vitro biofilm inhibition of MRSA, MRSE, and S. aureus SCV strains in the course of 24, 72, and 168 h treatment by PTMC, either unloaded, gentamicin-loaded, loaded with rifampicin and fosfomycin, or rifampicin and vancomycin. PTMC appeared to be a suitable carrier for rifampicin alone or in combination with other antibiotics. Biofilm colony forming units and metabolic activity measurement (MTT assay) demonstrated significant (p < 0.05) inhibition for all strains when PTMC loaded with rifampicin and vancomycin was employed, especially after 168 h treatment. Confocal laser scanning microscopy images showed similar qualitative results. PTMC loaded with only gentamicin did not show any inhibition. This exemplifies that PTMC loaded with rifampicin and vancomycin holds promise for the treatment of recalcitrant osteomyelitis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1828-1837, 2016.
Asunto(s)
Antibacterianos/administración & dosificación , Biopelículas/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Rifampin/administración & dosificación , Vancomicina/administración & dosificación , Dioxanos , Portadores de Fármacos , Quimioterapia Combinada , Pruebas de Sensibilidad Microbiana , PolímerosRESUMEN
The formation of staphylococcal biofilms on experimental bone cements, loaded with 0.5 or 1.0 g of active gentamicin and an additional equivalent amount of gentamicin, clindamycin, or fusidic acid was investigated. The biofilms were formed in a modified Robbins device over a 3-day time span and the influence of the additional antibiotics was quantified by expressing the number of colony forming units relative to the corresponding bone cement containing only gentamicin. Combinations of gentamicin with either fusidic acid or clindamycin reduced growth of clinical isolates of both gentamicin-sensitive Staphylococcus aureus and gentamicin-resistant coagulase-negative staphylococci to approximately 28%. To determine whether adding a second antibiotic has influence on the gentamicin release, cement blocks were placed in phosphate buffer and aliquots were taken at designated sampling intervals. The influence of the additional antibiotics was quantified by expressing the percentage released of the total amount of antibiotic incorporated in the different bone cements. After 3 days, all bone cements had released similar percentages of gentamicin, whereas more clindamycin and fusidic acid were released after doubling their concentration in the bone cements. In conclusion, bone cements loaded with combinations of gentamicin and clindamycin or fusidic acid are more effective in preventing biofilm formation than bone cements with gentamicin as a single drug. In addition, the presence of clindamycin or fusidic acid in gentamicin-loaded bone cement has no influence on the total gentamicin release.
Asunto(s)
Biopelículas , Clindamicina , Ácido Fusídico , Gentamicinas , Polimetil Metacrilato , Biopelículas/efectos de los fármacos , Cementos para Huesos , Clindamicina/metabolismo , Ácido Fusídico/metabolismo , Gentamicinas/metabolismoRESUMEN
Antibiotic-loaded acrylic bone cement is widely used in total joint replacement to reduce infections. Walking results in cyclic loading, which has been suggested to stimulate antibiotic release. The goal of this study is to compare antibiotic release from cyclically loaded bone cement with the release from unloaded bone cement. Two models of the frontal aspect of a femoral stem were cemented with CMW 1 Radiopaque G, Palacos R-G and Palamed G. Both were immersed in water, and the gentamicin concentration in the water was monitored. One model was cyclically loaded at 5 Hz during immersion achieving physiological stresses in the bone cement mantle. After 10.8 x 10(6) cycles, initial release of gentamicin from Palamed G was increased significantly for loaded over unloaded, but not from CMW 1 Radiopaque G and Palacos R-G.
Asunto(s)
Artroplastia de Reemplazo de Cadera/métodos , Cementos para Huesos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Gentamicinas/administración & dosificación , Soporte de Peso , Artroplastia de Reemplazo de Cadera/efectos adversos , Prótesis de Cadera , Humanos , Control de Infecciones/métodos , Ensayo de MaterialesRESUMEN
We summarize different studies describing mechanisms through which bacteria in a biofilm mode of growth resist mechanical and chemical challenges. Acknowledging previous microscopic work describing voids and channels in biofilms that govern a biofilms response to such challenges, we advocate a more quantitative approach that builds on the relation between structure and composition of materials with their viscoelastic properties. Biofilms possess features of both viscoelastic solids and liquids, like skin or blood, and stress relaxation of biofilms has been found to be a corollary of their structure and composition, including the EPS matrix and bacterial interactions. Review of the literature on viscoelastic properties of biofilms in ancient and modern environments as well as of infectious biofilms reveals that the viscoelastic properties of a biofilm relate with antimicrobial penetration in a biofilm. In addition, also the removal of biofilm from surfaces appears governed by the viscoelasticity of a biofilm. Herewith, it is established that the viscoelasticity of biofilms, as a corollary of structure and composition, performs a role in their protection against mechanical and chemical challenges. Pathways are discussed to make biofilms more susceptible to antimicrobials by intervening with their viscoelasticity, as a quantifiable expression of their structure and composition.
Asunto(s)
Microbiología Ambiental , Antiinfecciosos/farmacología , Biopelículas/efectos de los fármacos , Viabilidad Microbiana , Viscosidad/efectos de los fármacosRESUMEN
In infected joint arthroplasty, high local levels of antibiotics are achieved through temporary implantation of non-biodegradable gentamicin-loaded polymethylmethacrylate beads. Despite their antibiotic release, these beads act as a biomaterial surface to which bacteria preferentially adhere, grow and potentially develop antibiotic resistance. In routine clinical practice, these beads are removed after 14 days, but for a variety of reasons, we were confronted with a patient in which these beads were left in situ for 5 years. Retrieval of gentamicin-loaded beads from this patient constituted an exceptional case to study the effects of long-term implantation on potentially colonizing microflora and gentamicin release. Gentamicin-release test revealed residual antibiotic release after being 5 years in situ and extensive microbiological sampling resulted in recovery of a gentamicin-resistant staphylococcal strain from the bead surface. This case emphasizes the importance of developing biodegradable antibiotic-loaded beads as an antibiotic delivery system.
Asunto(s)
Antibacterianos/administración & dosificación , Gentamicinas/administración & dosificación , Anciano , Materiales Biocompatibles , Implantes de Medicamentos/efectos adversos , Farmacorresistencia Bacteriana , Prótesis de Cadera/efectos adversos , Humanos , Masculino , Polimetil Metacrilato , Falla de Prótesis , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/microbiología , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación , Factores de TiempoRESUMEN
Gentamicin is added to polymethylmethacrylate bone cements in orthopedics as a measure against infection in total joint arthroplasties. Numerous studies have been published on gentamicin release from bone cements, but none have been able to estimate the local concentrations in the prosthesis-related interfacial gap, present after implantation. The aim of this study was to develop a method allowing determination of antibiotic release in such a gap. Two-hundred-micrometer-wide gaps with a volume of 6 microl and a surface area of 0.6 cm2 were created by inserting stainless-steel strips in gentamicin-loaded bone cement plugs prior to polymerization. After hardening, the gap surface was exposed to 6 microl or 10 ml of phosphate-buffered saline. Within 2 h, gentamicin concentrations in the gaps reached around 4000 microg/ml for 4 different CMW and Palamed cements and 2500 microg/ml for Palacos R. Concentrations measured in the larger volume were several hundred times lower than in the gaps. This simulated prosthesis-related interfacial gap model offers new insights in the clinical efficacy of antibiotic-loaded bone cements. It is demonstrated that concentrations up to 1000-fold the antibiotic resistance levels for most bacterial strains causing implant infection can be achieved in a realistic in vitro model.
Asunto(s)
Antibacterianos/metabolismo , Gentamicinas/metabolismo , Polimetil Metacrilato/metabolismo , Prótesis e ImplantesRESUMEN
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.
Asunto(s)
Implantes Absorbibles , Antibacterianos/administración & dosificación , Sistemas de Liberación de Medicamentos , Osteomielitis/tratamiento farmacológico , Animales , Dioxanos , Humanos , Ácido Láctico , Osteomielitis/microbiología , Poliésteres , Polímeros , Polimetil MetacrilatoRESUMEN
Cementless prostheses are increasingly popular in total hip arthroplasties. Therewith, common prophylactic measures to reduce the risk of postoperative infection like the use of antibiotic-loaded bone cements, will no longer be available. Alternative prophylactic measures may include the use of antibiotic-releasing coatings. Previously, we developed a gentamicin-releasing coating for cementless titanium hip prostheses and derived an appropriate dosing of this coating by adjusting the amount of gentamicin in the coating to match the antibacterial efficacy of clinically employed gentamicin-loaded bone cement. In this manuscript, we investigated two important issues regarding the prophylactic use of this 1 mg cm(-2) bioactive gentamicin-releasing coating in cementless total hip arthroplasty: (1) its ability to prevent bacterial growth in a geometrically relevant set-up and (2) its antibacterial spectrum. A geometrically relevant set-up was developed in which miniature titanium stems were surrounded by agar, contaminated with bioluminescent Staphylococcus aureus. Novel, bio-optical imaging was performed allowing noninvasive, longitudinal monitoring of staphylococcal growth around miniature stems with and without the gentamicin-releasing coating. Furthermore, the antibacterial efficacy of the gentamicin-releasing coating was determined against a wide variety of clinical isolates, including bioluminescent Staphylococcus aureus strains, using traditional zone of inhibition measurements. The gentamicin-releasing coating demonstrated a wide-spectrum of antibacterial efficacy and successfully prevented growth of bioluminescent staphylococci around a miniature stem mounted in bacterially contaminated agar for at least 60 h. This implies that the gentamicin-releasing coating has potential to contribute to the improvement of infection prophylaxis in cementless total hip arthroplasty.
Asunto(s)
Antibacterianos/farmacología , Cementos para Huesos/farmacología , Materiales Biocompatibles Revestidos/farmacología , Gentamicinas/farmacología , Prótesis de Cadera/microbiología , Mediciones Luminiscentes/métodos , Imagen Óptica/métodos , Pruebas de Sensibilidad Microbiana , Fotones , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Factores de Tiempo , Titanio/farmacologíaRESUMEN
Wear of metal-on-metal (cobalt-chromium, Co-Cr particles) and metal-on-polyethylene (ultra-high-molecular-weight polyethylene, UHMWPE particles) bearing surfaces in hip prostheses is a major problem in orthopedics. This study aimed to compare the influence of Co-Cr and UHMWPE particles on the persistence of infection. Bioluminescent Staphylococcus aureus Xen36 were injected in air pouches prepared in subcutaneous tissue of immuno-competent BALB/c mice (control), as a model for the joint space, in the absence or presence of Co-Cr or UHMWPE particles. Bioluminescence was monitored longitudinally up to 21 days, corrected for absorption and reflection by the particles and expressed relative to the bioluminescence found in the presence of staphylococci only. After termination, air pouch fluid and air pouch membrane were cultured and histologically analyzed. Bioluminescence was initially lower in mice exposed to UHMWPE particles with staphylococci than in mice injected with staphylococci only, possibly because UHMWPE particles initially stimulated a higher macrophage presence in murine air pouch membranes. For mice exposed to Co-Cr particles with staphylococci, bioluminescence was observed to be higher in two out of six animals compared to the presence of staphylococci alone. In the majority of mice, infection risk in the absence or presence of Co-Cr and UHMWPE particles appeared similar, assuming that the longevity of an elevated bioluminescence is indicative of a higher infection risk. However, the presence of Co-Cr particles yielded a higher bioluminescence in two out of six mice, possibly because the macrophage degradative function was hampered by the presence of Co-Cr particles.
Asunto(s)
Aleaciones de Cromo/efectos adversos , Prótesis Articulares/microbiología , Polietilenos , Infecciones Estafilocócicas , Animales , Mediciones Luminiscentes , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
PURPOSE: In the last decades, hip prostheses with a metal-on-metal (MOM) bearing have been implanted by orthopedic surgeons worldwide. However, concerns are now raised towards the metal particles and degradation products released by MOM-bearings into surrounding tissue, although effects of Co-Cr wear on infection are also unknown. Therefore, we here determine the viable volumes of staphylococcal biofilms formed on polystyrene in the absence and presence of Co-Cr particles and Co-Cr ions. METHODS: Three clinically derived and two commercially available staphylococcal strains were grown in the presence of 2 mg/mL Co-Cr particles or 1000/500 µg/L Co-Cr ions derived from Co-Cr salts or from particle supernatant, under static and dynamic growth conditions. A dynamic model simulates the conditions that apply for biofilm formation in the human body, as synovial fluid in mobile patients with hip prostheses is in constant motion with accompanying shear rates. Images of 24 h old biofilms were made with confocal laser scanning microscopy and analyzed with the mathematical computer program COMSTAT, yielding the biovolume of a biofilm. X-ray photoelectron spectroscopy was performed on the particles to study their elemental surface composition. RESULTS: Most isolates showed a tendency of reduced biofilm growth in the presence of Co-Cr particles compared to growth during exposure to metal ions, but this was only significant in one strain under the dynamic growth condition (Staphylococcus aureus 7388). Characterization of the outer surface of the particles revealed a Co-Cr oxide layer enriched by Mo relative to the bulk concentration. CONCLUSIONS: MOM bearings produce metal particles which were found to possess antibacterial characteristics under dynamic growth conditions. Further research is needed towards the clinical relevance of this finding.