Antibiotic-loaded Polymethylmethacrylate Research Articles

Development of a Galleria mellonella Infection Model to Evaluate the Efficacy of Antibiotic-Loaded Polymethyl Methacrylate (PMMA) Bone Cement.

Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and antimicrobial efficacy of antimicrobial coatings and compounds. Here, we aim to utilize Galleria mellonella implant infection models to assess the antimicrobial activity of antibiotic-loaded bone cement (ALBC) implants. Therefore, we used commercially available bone cement loaded with either gentamicin alone (PALACOS R+G) or with a combination of gentamicin and vancomycin (COPAL G+V), compared to bone cement without antibiotics (PALACOS R). Firstly, the in vitro antimicrobial activity of ALBC was determined against Staphylococcus aureus. Next, the efficacy of ALBC implants was analyzed in both the G. mellonella hematogenous and early-stage biofilm implant infection model, by monitoring the survival of larvae over time. After 24 h, the number of bacteria on the implant surface and in the tissue was determined. Larvae receiving dual-loaded COPAL G+V implants showed higher survival rates compared to implants loaded with only gentamicin (PALACOS R+G) and the control implants without antibiotics (PALACOS R). In conclusion, G. mellonella larvae infection models with antibiotic-loaded bone cements are an excellent option to study (novel) antimicrobial approaches.

Tips and tricks for using cement augmentation of pedicle screws and vertebral body replacements—A literature review supported by two case reports

BackgroundThe prevalence of osteoporosis is escalating alongside an aging global population, increasing the demand for spinal surgeries, including those necessitating cement augmentation for enhanced construct stability. ObjectiveThis article delves into the nuanced application of cement augmentation techniques for pedicle screws and vertebral body replacements (VBR), aimed at optimizing surgical outcomes in osteoporotic spines. MethodDrawing from a comprehensive literature review according to important clinical and biomechanical studies and the authors’ clinical experiences, we elucidate strategies to mitigate complications and improve surgical efficacy. ResultsCement augmentation has shown promise in managing vertebral fractures and in securing pedicle screws within osteoporotic vertebrae, with the advent of polymethylmethacrylate (PMMA) bone cement marking a pivotal advancement in spinal surgery. We highlight intraoperative measures like the choice between pre-injecting cement and utilizing cannulated or fenestrated screws, emphasizing the importance of controlling cement viscosity to prevent leakage and embolism. Through two case reports, we demonstrate the practical application of endplate cementation following VBR. ConclusionWhile the use of cement augmentation poses certain risks, its judicious application—supported by evidence-based guidelines and surgical expertise—can substantially enhance the stability of spinal constructs in osteoporotic patients. This allows a reduction in instrumentation length by enhancing biomechanical stability concerning pullout, bending, and rotational forces. Furthermore, the incidence of endplate sintering following VBF can be significantly reduced. Future research, particularly on antibiotic-loaded PMMA, may further expand its utility and optimize its safety profile.

Pharmacokinetic Interpretation of Applying Local Drug Delivery System for the Treatment of Deep Surgical Site Infection in the Spine.

Surgical site infections (SSIs) after spinal surgery present significant challenges, including poor antibiotic penetration and biofilm formation on implants, leading to frequent treatment failures. Polymethylmethacrylate (PMMA) is widely used for localized drug delivery in bone infections, yet quantifying individual drug release kinetics is often impractical. This retrospective study analyzed 23 cases of deep SSIs (DSSIs) following spinal surgery treated with antibiotic-loaded PMMA. A mathematical model estimated personalized drug release kinetics from PMMA, considering disease types, pathogens, and various antibiotics. The study found that vancomycin (VAN), ceftriaxone (CRO), and ceftazidime (CAZ) reached peak concentrations of 15.43%, 15.42%, and 15.41%, respectively, within the first two days, which was followed by a lag phase (4.91-4.92%) on days 2-3. On days 5-7, concentrations stabilized, with CRO at 3.22% and CAZ/VAN between 3.63% and 3.65%, averaging 75.4 µg/cm2. Key factors influencing release kinetics include solubility, diffusivity, porosity, tortuosity, and bead diameter. Notably, a patient with a low glomerular filtration rate (ASA IV) was successfully treated with a shortened 9-day intravenous VAN regimen, avoiding systemic complications. This study affirms the effectiveness of local drug delivery systems (DDS) in treating DSSIs and underscores the value of mathematical modeling in determining drug release kinetics. Further research is essential to optimize release rates and durations and to mitigate risks of burst release and tissue toxicity.

Antibiotic-Loaded Ultrahigh Molecular Weight Polyethylenes.

The occurrence of periprosthetic joint infections (PJI) after total joint replacement constitutes a great burden for the patients and the healthcare system. Antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is often used in temporary spacers during antibiotic treatment. PMMA is not a load-bearing solution and needs to be replaced by a functional implant. Elution from the ultrahigh molecular weight polyethylene (UHMWPE) bearing surface for drug delivery can combine functionality with the release of clinically relevant doses of antibiotics. In this study, the feasibility of incorporating a range of antibiotics into UHMWPE is investigated. Drug stability is assessed by thermo-gravimetric analysis and nuclear magnetic resonance spectroscopy. Drug-loaded UHMWPEs are prepared by compression molding, using eight antibiotics at different loading. The predicted intra-articular concentrations of drugs eluted from UHMWPE are above minimum inhibitory concentration for at least 3 weeks against Staphylococci, which are the major causative bacteria for PJI. The antibacterial efficacy is confirmed for samples covering 2% of a representative knee implant in vitro over 72 h, showing that a small fraction of the implant surface loaded with antibiotics may be sufficient against Staphylococci.

Use of fibular graft in Masquelet technique in osteomyelitis of long bones-a novel modification in the technique

Background: Improper treatment of acute osteomyelitis mostly leads to chronic osteomyelitis. In the year 2000, Alain C. Masquelet described the Induced membrane technique for the first time. In this study, we aimed to determine the clinical efficiency of the Masquelet technique for bone loss due to osteomyelitis in the long bones. Methods: This study was conducted at our tertiary care centre Shri Vasantrao Naik medical college and hospital, Yavatmal between August 2016 and September 2020. Masquelet technique with some modification was performed in all cases. Results: In first stage, the defects were filled with antibiotic-loaded polymethyl methacrylate (PMMA) cement after radical debridement. In second stage after 6 to 8 weeks we used a combination of fibular strut graft with iliac cancellous graft. X-rays were taken before second stage and after 3 months, 6 months and 1 year to see for the union. The study included 10 patients, with 6 males and 4 females with mean age of 34 years (20 to 54). The mean duration of bone infection was 4 months (range: 3-5 months). All patients had an average follow-up period of 16 months (range, 12-24 months). Radiographic evidence of bone union was seen in 6 months (3 to 9 months) infection was not seen in any case. Conclusions: This modified Masquelet is an effective method for the treatment of chronic osteomyelitis of the long bones.

The Efficacy of Application of Oral Antibiotic Loaded Polymethyl Methacrylate Against Staphylococcus aureus

Chronic osteomyelitis is still common in the developing world and presents a continuing therapeutic challenge. Local antibiotic therapy is performed as the first stage treatment algorithm for 4 to 8 weeks. Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis and its treatment, it is important to find another effective and efficient treatment. Intravenous antibiotics and polymethylmethacrylate (PMMA) combination have shown effectiveness, but the potential of oral antibiotics and PMMA combination is still rare and is debatable. It aimed to compare efficacy among oral antibiotic-loaded PMMA in many concentrations (5%, 10%, 20%) and controls (0%) against Staphylococcus aureus. This experimental study was conducted in the Microbiology Department of Andalas University. The object was S. aureus. We used ten oral antibiotics and compared among its many concentrations (5%, 10%, 20%) and controls (0%). Data were analyzed by analysis of variance (ANOVA) test. The lowest counts of S. aureus were found in ciprofloxacin 20%, followed by tetracycline 10%, erythromycin 5%, rifampicin 10%, ofloxacin 20%, clindamycin 20%, amoxiclav 20%, cefixime 5%, cotrimoxazole 20%, and chloramphenicol 20% consecutively. All oral antibiotics loaded PMMA in each concentration might reduce the number of colonies up to 90%. A study in 2013 revealed that a combination of several antibiotics and PMMA was proven to be effective. The oral antibiotics loaded PMMA in various concentrations have a significant bactericidal effect on the growth of S. aureus and able to reduce the number of S. aureus.

Patient-specific articulating spacer for two-stage shoulder arthroplasty exchange.

Two-stage exchange with anantibiotic-loaded polymethylmethacrylate (PMMA) spacer is standard treatment for chronic periprosthetic joint infection of the shoulder. We present asafe and simple technique for patient-specific spacer implants. (Chronic) periprosthetic joint infection of the shoulder. Known allergy against components of PMMA bone cements. Inadequate compliance for two-stage exchange. Patient is unfit to undergo two-stage exchange. Hardware removal, histologic and microbiologic samples, and debridement. Preparation of targeted or calculated antibiotic-loaded PMMA. Tailoring of patient-specific spacer. Spacer implantation. Rehabilitation protocol. Antibiotic treatment. Reimplantation after successful eradication of infection.

Treatment of Fracture-Related Infections with Bone Abscess Formation after K-Wire Fixation of Pediatric Distal Radius Fractures in Adolescents—A Report of Two Clinical Cases

Closed reduction and K-wire fixation of displaced distal radius fractures in children and adolescents is an established and successful surgical procedure. Fracture-related infections after K-wire fixation are rare but can have significant consequences for the patient. There is a lack of literature on the treatment of K-wire-associated fracture-related infections in children and adolescents. Herein, we report two cases of fracture-related infection after initial closed reduction and Kirschner wire fixation in two adolescents. One 13-year-old boy and one 11-year-old girl were seen for fracture-related infections 4 and 8 weeks after closed reduction and percutaneous K-wire fixation of a distal radius, respectively. X-ray and magnetic resonance imaging (MRI) revealed a healed fracture with osteolytic changes in the metaphyseal radius with periosteal reaction and abscess formation of the surrounding soft tissue structures. A two-staged procedure was performed with adequate debridement of the bone and dead space management with an antibiotic-loaded polymethyl methacrylate (PMMA) spacer at stage 1. After infection control, the spacer was removed and the defect was filled with autologous bone in one case and with a calcium sulphate-hydroxyapatite biomaterial in the other case. In each of the two patients, the infection was controlled and a stable consolidation of the distal radius in good alignment was achieved. In one case, the epiphyseal plate was impaired by the infection and premature closure of the epiphyseal plate was noted resulting in a post-infection ulna plus variant. In conclusion, a fracture-related infection after Kirschner wire fixation of pediatric distal radius fractures is a rare complication but can occur. A two-stage procedure with infection control and subsequent bone defect reconstruction was successful in the presented two cases. Premature closure of the epiphyseal growth plate of the distal radius is a potential complication.

Antibiotic release from PMMA spacers and PMMA beads measured with ELISA: Assessment of in vitro samples and drain fluid samples of patients.

For prosthetic joint infections, antibiotic loaded poly methyl methacrylate (PMMA) spacer or beads can be used to release high concentrations of antibiotics locally at the infection site, while minimizing systemic toxicity.The aim of this study is to determine in vitro and in vivo pharmacokinetic release profile of antibiotics from PMMA spacers and PMMA beads.For the in vitro experiment, the PMMA spacers or beads were submerged in phosphate-buffered saline and gentamicin concentrations were determined from collected specimen at several times points, measured with enzyme-linked immunosorbent assays(ELISA).To assess the in vivo antibiotic release profile of different spacers, wound drainage fluid samples were collected after implantation of a spacer over a period of maximum 14 days.After 48 h, the burst gentamicin concentration elution was 9862 ± 1782 ng/ml (mean ± SD) from spacers versus 38,394 ± 7071 ng/ml (mean ± SD) for beads. Over 35 days, spacers had eluted a cumulative mean concentration of 13,812 ± 3548versus 55,048 ± 12,006 ng/ml for beads (p < 0.001). Clinical samples of patients with a Vancogenx® spacer showed higher gentamicin release than Refobacin™ spacers (p < 0.001).This is the first study that measured the release data of local antibiotics with ELISA. Compare to spacers, the exact release values of gentamicin from PMMA beads are more than 10 times higher and reached a maximum much later than spacers. This makes the use of PMMA beads more preferable to use for treatment of the infection itself.

Mechanical strength of antibiotic-loaded PMMA spacers in two-stage revision surgery

BackgroundAntibiotic-loaded polymethylmethacrylate (PMMA) bone cement spacers provide high local antibiotic concentrations and patient mobility during the interim period of two-stage revision for periprosthetic joint infection (PJI). This study compares mechanical characteristics of six dual antibiotic-loaded bone cement (dALBC) preparations made from three different PMMA bone cements. The study`s main objective was to determine the effect of time and antibiotic concentration on mechanical strength of dALBCs frequently used for spacer fabrication in the setting of two-stage revision for PJI.MethodsA total of 84 dual antibiotic-loaded bone cement specimens made of either Copal spacem, Copal G + V or Palacos R + G were fabricated. Each specimen contained 0.5 g of gentamicin and either 2 g (low concentration) or 4 g (high concentration) of vancomycin powder per 40 g bone cement. The bending strength was determined at two different timepoints, 24 h and six weeks after spacer fabrication, using the four-point bending test.ResultsPreparations made from Copal G + V showed the highest bending strength after incubation for 24 h with a mean of 57.6 ± 1.2 MPa (low concentration) and 50.4 ± 4.4 MPa (high concentration). After incubation for six weeks the bending strength had decreased in all six preparations and Palacos R + G showed the highest bending strength in the high concentration group (39.4 ± 1.6 MPa). All low concentration preparations showed superior mechanical strength compared to their high concentration (4 g of vancomycin) counterpart. This difference was statistically significant for Copal spacem and Copal G + V (both p < 0.001), but not for Palacos R + G (p = 0.09).ConclusionsThis study suggests that mechanical strength of antibiotic-loaded PMMA bone cement critically decreases even over the short time period of six weeks, which is the recommended interim period in the setting of two-stage revision. This potentially results in an increased risk for PMMA spacer fracture at the end of the interim period and especially in patients with prolonged interim periods. Finally, we conclude that intraoperative addition of 4 g of vancomycin powder per 40 g of gentamicin-premixed Palacos R + G (Group D) is mechanically the preparation of choice if a dual antibiotic-loaded bone cement spacer with high antibiotic concentrations and good stability is warranted. In any case the written and signed informed consent including the off-label use of custom-made antibiotic-loaded PMMA bone cement spacers must be obtained before surgery.

Bone regeneration after marginal bone resection in two-stage treatment of chronic long bone infection - a combined histopathological and clinical pilot study

IntroductionIn chronic bone infection, marginal bone resection avoids large and difficult to reconstruct bone defects. However, there is still a lack of knowledge on bone regeneration during chronic bone infection and bone healing capability after marginal bone resection. Therefore, the purpose of this study was to investigate the clinical and histopathological outcomes after marginal bone resection in chronic long bone infection. We hypothesized that there is a regenerative bone healing potential after marginal bone resection that results in an acceptable clinical outcome and improved pathohistological bone healing parameters during treatment. Materials and methodsNine patients were treated for chronic bone infections in a two-stage manner with marginal bone resection of the infected area and the placement of an antibiotic-loaded polymethyl methacrylate (PMMA) spacer at stage one followed by bone reconstruction at stage two combined with systemic antibiotic therapy. Comparable bone samples were harvested at the border region between vital and necrotic bone area during stage one and the identical location during stage two. Control bone samples were harvested from five healthy patients without bone infection. Clinical outcome in terms of infection eradication and bone consolidation were assessed. The phenotypic changes of osteocyte and morphological changes of lacunar-canalicular network were investigated by histological and immunohistochemical staining between the two observation periods. Furthermore, expression levels of major bone formation and resorption markers were investigated by immunohistochemical and tartrate-resistant acid phosphatase (TRAP) staining. ResultsThe clinical results with a follow-up of 12.9 months showed that eight of nine patients (88.9%) achieved bone consolidation after a planned two-stage procedure of marginal resection of necrotic bone and consecutive reconstruction. In four of the nine patients (44.4%), additional marginal debridements after stage two had to be performed. After marginal resection at stage one, the improved bone formation ability at stage two was demonstrated by significantly lower percentage of empty lacunae, significantly more mature osteocytes and higher BMP-2 positive cell density, whereas decreased resorption was indicated by significantly lower osteoclast density and RANKL/OPG ratio. In patients requiring additional debridement compared to patients without additional debridements, a significantly higher percentage of empty lacunae was found at stage one. ConclusionMarginal bone resection combined with local and systemic antibiotic therapy is a feasible treatment option to avoid large bone defects as bone from the marginal resection area seems to have good regenerative potential. Despite a high revision rate of 44.4%, this technique avoids large bone resection and revisions can be done by further marginal debridements.

PMMA-Cement-PLIF Is Safe and Effective as a Single-Stage Posterior Procedure in Treating Pyogenic Erosive Lumbar Spondylodiscitis-A Single-Center Retrospective Study of 73 Cases.

Background: Surgical treatment for erosive pyogenic spondylodiscitis of the lumbar spine is challenging as, following debridement of the intervertebral and bony abscess, a large and irregular defect is created. Sufficient defect reconstruction with conventional implants using a posterior approach is often impossible. Therefore, we developed the “Cement-PLIF”, a single-stage posterior lumbar procedure, combining posterior lumbar interbody fusion (PLIF) with defect-filling using antibiotic-loaded polymethylmethacrylate (PMMA). This study first describes and evaluates the procedure’s efficacy, safety, and infection eradication rate. Radiological implant stability, bone-regeneration, sagittal profile reconstruction, procedure-related complications, and pre-existing comorbidities were further analyzed. Methods: A retrospective cohort study analyzing 73 consecutive patients with a minimum of a one-year follow-up from 2000–2017. Patient-reported pain levels and improvement in infectious serological parameters evaluated the clinical outcome. Sagittal profile reconstruction, anterior bone-regeneration, and posterior fusion were analyzed in a.p. and lateral radiographs. A Kaplan–Meier analysis was used to determine the impact of pre-existing comorbidities on mortality. Pre-existing comorbidities were quantified using the Charlson-Comorbidity Index (CCI). Results: Mean follow-up was 3.3 (range: 1–16; ±3.2) years. There was no evidence of infection persistence in all patients at the one-year follow-up. One patient underwent revision surgery for early local infection recurrence (1.4%). Five (6.9%) patients required an early secondary intervention at the same level due to minor complications. Radiological follow-up revealed implant stability in 70/73 (95.9%) cases. Successful sagittal reconstruction was demonstrated in all patients (p < 0.001). There was a significant correlation between Kaplan–Meier survival and the number of pre-existing comorbidities (24-months-survival: CCI ≤ 3: 100%; CCI ≥ 3: 84.6%; p = 0.005). Conclusions: The Cement-PLIF procedure for pyogenic erosive spondylodiscitis is an effective and safe treatment as evaluated by infection elimination, clinical outcome, restoration, and maintenance of stability and sagittal alignment.

A Customized Knee Antibiotic-Loaded PMMA Spacer: A Preliminary Design Analysis.

A preliminary design of customized antibiotic-loaded poly-methyl-methacrylate (ALPMMA) spacer characterized by an appropriate footprint according to the specific patient’s anatomy and a reliable mechanical response to severe functional loads (i.e., level walking and 45° bent knee) is reported. The targeted virtual prototyping process takes origin from a novel patented 3D geometrical conceptualization characterized by added customization features and it is validated by a preliminary FEM-based analysis. Mechanical and thermomechanical properties of the antibiotic-doped orthopedic PMMA cement, which will be used for the future prototype manufacturing, were measured experimentally by testing samples taken during a real day-running orthopedic surgery and manufactured according to the surgeon protocol. FEM analysis results indicate that small area is subjected to intensive stresses, validating the proposed geometry from the mechanical point of view, under the two loading scenarios, moreover the value of safety margins results positive, and this is representative of the lower stress magnitude compared to the critical material limits. The experimental data confirm that the presence of antibiotic will last during the surgeon period moreover, the temperature dependent modulus of the bone cement is slightly affected by the body range temperature whereas it will drastically drop for higher temperature out the range of interest. A complete customization, according to a patient anatomy, and the corresponding real prototype spacer will be manufactured by 3D printing techniques, and it will be validated by destructive testing during the second stage of this activity before commercialization.

Influence of Porosity on Fracture Toughness and Fracture Behavior of Antibiotic-Loaded PMMA Bone Cement.

Aseptic loosening is the most common reason for the long-term revision of cemented arthroplasties with fracture of the cement being a postulated cause or contributing factor. In our previous studies we showed that adding an antibiotic to a polymethylmethacrylate (PMMA) bone cement led to detrimental effects on various mechanical properties of the cement such as bending strength, compressive strength and fracture toughness (KIC). This finding implied that the mechanical failure of antibiotic-loaded PMMA bone cement was influenced by its pore volume fraction. Up to now this aspect has not been studied. Hence the purposes of this study were to determine (1) the influence of antibiotic (telavancin) loading on the KIC of a widely used PMMA bone cement brand (Palacos®R) and (2) the influence of pore size and pore distribution on the fracture behavior of the KIC specimens. For (2) both experimental and numerical methods (extended finite element method [XFEM]) were used allowing a comparison between the two sets of results. We found that: (1) KIC decreased with increased porosity with the drop (relative to the value for the control cement) being significant when the telavancin loading was 4.8 wt/wt % (2 g of telavancin added to 40 g of control cement powder); (2) there was a critical pore size above which there was a significant decrease in KIC and is 1 mm; (3) crack propagation was strongly influenced by pore size and pore locations (pore-pore interactions); and, (4) there was good agreement between the experimental and XFEM results. The implications of these findings for the use of a telavancin-loaded PMMA bone cement in cemented total joint arthroplasties are commented upon.

Bioactive glass S53P4 to fill-up large cavitary bone defect after acute and chronic osteomyelitis treated with antibiotic-loaded cement beads: A prospective case series with a minimum 2-year follow-up

Introduction: Bioactive glass S53P4 (BAG-S53P4) has been used in the treatment of osteomyelitis with excellent results. The aim of this study was to evaluate the clinical and radiographic results of patients treated with use of antibiotic-loaded cement beads, followed by bone defects filling using bioglass. Methods: We treated a prospective series of patients presenting with acute or chronic osteomyelitis of a long bone of the upper or lower limb. The first-stage procedure involved debridement and filling of cavitary defects with antibiotic-loaded polymethylmethacrylate (PMMA) beads. When signs of infection subsided, the defects were filled with BAG-S53P4. The main outcomes assessed were the reinfection rate, need for reoperation, radiographic and functional evaluations (DASH and Lysholm scores). Results: Ten patients were included, aged between 4 and 66 years (mean 25.4 years). The source of infection was hematogenic in five cases and post-traumatic in the other five. Hematogenic infections required two debridements before filling with bioglass, whereas post-traumatic cases required only one. The time between the first debridement and the application of bioglass varied from 1 to 63 weeks (average of 17 weeks). All patients showed a favorable evolution after bioglass procedure, with no need for reoperation or relevant wound problems. The radiographic evaluation showed partial incorporation of the material and adequate bone formation, and functional scores were satisfactory in all cases. Conclusion: The treatment of osteomyelitis with surgical debridement and PMMA beads, followed by filling of bone defect with BAG-S53P4, was effective in all patients evaluated, with adequate infectious control and bone regeneration. No cases required reoperation after bioglass implantation. Patients with hematogenous osteomyelitis required a greater number of debridements before filling with bioglass.

Bioactive glass in the treatment of chronic osteomyelitis-a valid option?

Chronic osteomyelitis continues to represent a challenge both for patients and the treating physician, especially in the presence of multiple germs. We performed a literature review assessing the current role of the indications of bioactive glass. We included studies about patients with chronic osteomyelitis that were treated with S53P4. A literature review of Medline via PubMed was performed. After the exclusion of case reports, 7 studies were included in the narrative review. Recurrence of infection was defined as the main outcome parameter. Six of 7 studies were retrospective, or case studies with a relatively small sample size (total patient number N = 274). The overall recurrence rate was 10.6%. Studies that compared the outcome of the treatment with S53P4 versus antibiotic-loaded polymethyl methacrylate (PMMA) revealed no significant difference. The data reviewed indicate that in cases of multiple bacteria and resistance to antibiotic treatment, bioglass may be a valuable treatment alternative to other forms of spacers (e.g., PMMA). This statement is limited by the fact that the number of described cases is very low. Therefore, a definitive statement of its effectiveness cannot be made at this point.

Mechanical Safety Study and Antibiotic-loaded Polymethylmethacrylate Spacers Threshold, Manufactured Intraoperatively, in Orthopaedic Surgery

The study performed the biomechanical testing of polymethylmethacrylate (PMMA) specimens with unreinforced progressive antibiotic loading, compared to samples reinforced with Kirschner wires, by subjecting these specimens to mechanical compression forces. A difference was observed in the yield of the reinforced specimens with Kirschner wires, in which an antibiotic concentration that exceeded the usual amount was used. In this antibiotic combination of vancomycin powder and liquid gentamicin, the spacer seemed to have a superior structure compared to using only the antibiotic in liquid form. These results are superior to the usually loaded specimens (not exceeding the threshold of 4 g of antibiotic per 40 g of cement), the maximum force recorded being of 20.98 kN and the minimum of 11.54 kN. The reinforced specimens indicated higher values of force, registering differences that varied between 10 kN and approximately 19 kN, thus considering that through the reinforcement with Kirschner wires, the biomechanical qualities of the cement spacers considerably improved.

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.

Polyethylene-Based Knee Spacer for Infection Control: Design Concept and Pre-Clinical In Vitro Validations.

Antibiotic-loaded polymethyl methacrylate (PMMA) has been widely applied in the treatment of knee periprosthetic joint infections. However, problems with antibiotic-loaded PMMA-based spacers, such as structural fracture and implant dislocation, remain unresolved. A novel polyethylene-based spacer, designed with an ultra-congruent articulating surface and multiple fenestrations, was introduced in the current study. Validation tests for biomechanical safety, wear performance, and efficacy of antibiotic cement were reported. During cycle fatigue testing, no tibial spacer failures were observed, and less wear debris generation was reported compared to commercial PMMA-based spacers. The volumetric wear of the novel spacer was within the safety threshold for osteolysis-free volumetric wear. An effective infection control was demonstrated despite the application of lesser antibiotic cement in the 30-day antibiotic elution test. The tube dilution test confirmed adequate inhibitory capabilities against pathogens with the loaded antibiotic option utilized in the current study. The novel polyethylene-based knee spacer may offer sufficient biomechanical safety and serve as an adequate carrier of antibiotic-loaded cement for infection control. Further clinical trials shall be conducted for more comprehensive validation of the novel spacer for practical application.

The stability of carbapenems before and after admixture to PMMA-cement used for replacement surgery caused by Gram-negative bacteria

BackgroundProsthetic joint infection (PJI) is a serious complication of orthopedic implant surgery. Treatment often includes the use of an antibiotic-loaded Polymethyl methacrylate (PMMA) bone cement spacer. Several antibiotics are commonly used for the preparation of these spacers, but due to the increasing number of infections with resistant Gram-negative bacteria, there is a need for the use of carbapenem antibiotics such as meropenem and imipenem as drugs of last resort. Unfortunately, the reaction heat generated during the preparation of the bone cement can be a major problem for the stability of these antibiotics. In the present study, the stability of meropenem and imipenem was tested before and after the admixture to PMMA bone cements.MethodsHigh-performance liquid chromatography with ion-pairing reversed-phase separation and spectrophotometric detection was used for analysis. Stability tests with meropenem and imipenem were performed with antibiotics in solution and solid form at different temperatures (37 °C, 45 °C, 60 °C, 90 °C) and times (30 min, 60 min, 120 min). To test the stability of both antibiotics in PMMA after exposure to the reaction heat during polymerization, three different bone cements were used to generate specimens that contained defined amounts of antibiotics. Reaction heat was measured. The form bodies were mechanically crushed and aliquots were dissolved in ethyl acetate. Samples were prepared for HPLC DAD analysis.ResultsMeropenem and imipenem showed the highest degradation levels after heat stressed in solution, with maximum levels of 75% and 95%, respectively. In solid form, degradation levels decreased dramatically for meropenem (5%) and imipenem (13%). Stability tests of both carbapenems in bone cement showed that they remained largely stable during PMMA polymerization, with retrieved amounts of about 70% in Palacos® R and Copal® G+V, and between 80 and 90% in Copal® spacem.ConclusionsIn contrast to the results of meropenem and imipenem in solution, both antibiotics remain stable in solid form and mostly stable in the cement after PMMA polymerization. The low degradation levels of both antibiotics after exposure to temperatures > 100 °C allow the conclusion that they can potentially be used for an application in PMMA cements.