Utility of an allograft tendon for scoliosis correction via the costo-transverse foreman.

Current convex tethering techniques for treatment of scoliosis have centered on anterior convex staples or polypropylene tethers. We hypothesized that an allograft tendon tether inserted via the costo-transverse foramen would correct an established spinal deformity. In the pilot study, six 8-week-old pigs underwent allograft tendon tethering via the costo-transverse foreman or sham to test the strength of the transplanted tendon to retard spine growth. After 4 months, spinal deformity in three planes was induced in all animals with allograft tendons. In the treatment study, the allograft tendon tether was used to treat established scoliosis in 11 8-week-old pigs (spinal deformity > 50°). Once the deformity was observed (4 months) animals were assigned to either no treatment group or allograft tendon tether group and progression assessed by monthly radiographs. At final follow-up, coronal Cobb angle and maximum vertebral axial rotation of the treatment group was significantly smaller than the non-treatment group, whereas sagittal kyphosis of the treatment group was significantly larger than the non-treatment group. In sum, a significant correction was achieved using a unilateral allograft tendon spinal tether, suggesting that an allograft tendon tethering approach may represent a novel fusion-less procedure to correct idiopathic scoliosis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:183-192, 2017.

Chitosan coating to enhance the therapeutic efficacy of calcium sulfate-based antibiotic therapy in the treatment of chronic osteomyelitis.

We demonstrate that coating calcium sulfate with deacetylated chitosan enhances the elution profile of daptomycin by prolonging the period during which high concentrations of antibiotic are released. Coatings reduced initial bolus release of daptomycin by a factor of 10 to approximately 1000 µg/ml, and levels remained above 100 µg/ml for up to 10 days. Chitosan-coated and uncoated calcium sulfate implants with and without 15% daptomycin were evaluated in an experimental model of staphylococcal osteomyelitis through bacteriology scores, radiology, histopathology, and Gram staining. Significant reduction in bacteriology scores was observed for implants containing daptomycin and coated with chitosan compared with all the other groups. We confirm that the use of chitosan-coated calcium sulfate beads for local antibiotic delivery can be correlated with an improved therapeutic outcome following surgical debridement in the treatment of chronic osteomyelitis.

Use of xylitol to enhance the therapeutic efficacy of polymethylmethacrylate-based antibiotic therapy in treatment of chronic osteomyelitis.

Using a rabbit model of postsurgical osteomyelitis, we demonstrate that incorporation of xylitol into polymethylmethacrylate (PMMA) bone cement enhances the elution of daptomycin under in vivo conditions. We also demonstrate that this can be correlated with an improved therapeutic outcome in the treatment of a chronic bone infection following surgical debridement.

Evaluation of dynamic [18F]-FDG-PET imaging for the detection of acute post-surgical bone infection.

Diagnosing bone infection in its acute early stage is of utmost clinical importance as the failure to do so results in a therapeutically recalcitrant chronic infection that can only be resolved with extensive surgical intervention, the end result often being a structurally unstable defect requiring reconstructive procedures. [(18)F]-FDG-PET has been extensively investigated for this purpose, but the results have been mixed in that, while highly sensitive, its specificity with respect to distinguishing between acute infection and sterile inflammatory processes, including normal recuperative post-surgical healing, is limited. This study investigated the possibility that alternative means of acquiring and analyzing FDG-PET data could be used to overcome this lack of specificity without an unacceptable loss of sensitivity. This was done in the context of an experimental rabbit model of post-surgical osteomyelitis with the objective of distinguishing between acute infection and sterile post-surgical inflammation. Imaging was done 7 and 14 days after surgery with continuous data acquisition for a 90-minute period after administration of tracer. Results were evaluated based on both single and dual time point data analysis. The results suggest that the diagnostic utility of FDG-PET is likely limited to well-defined clinical circumstances. We conclude that, in the complicated clinical context of acute post-surgical or post-traumatic infection, the diagnostic utility accuracy of FDG-PET is severely limited based on its focus on the increased glucose utilization that is generally characteristic of inflammatory processes.

Optimized elution of daptomycin from polymethylmethacrylate beads.

We demonstrate that xylitol can be added to polymethylmethacrylate (PMMA) bone cement to enhance the elution of daptomycin in terms of both the peak and sustained release of antibiotic. We also demonstrate that a PMMA-xylitol formulation optimized for daptomycin can be used to enhance the elution of both vancomycin and gentamicin.

Sucrose, xylitol, and erythritol increase PMMA permeability for depot antibiotics.

Release of antibiotics from antibiotic-loaded PMMA is dependent on its permeability. Loading PMMA with soluble particulate filler has been proposed to increase permeability and antibiotic release for beads and spacers. We therefore assessed particulate sucrose, xylitol, and erythritol as fillers to increase the permeability and elution kinetics of filler-loaded PMMA. Based on lower solubility, we hypothesized that erythritol would not enhance permeability and elution as much as xylitol and sucrose. We made filler-loaded PMMA beads with each of the three fillers combined with phenolphthalein, and soaked in 0.1% NaOH solution. Permeability was assessed qualitatively by relative depth of phenolphthalein color change caused by penetration of NaOH solution into subsequently split beads. Elution was quantitatively assessed by spectrophotometric light absorption measurements of the eluent. Fluid penetration reached the center of 7-mm beads by day 15, similar for all three materials. Elution of phenolphthalein was greater for xylitol than for the other two materials. Particulate sucrose, xylitol, and erythritol fillers increase PMMA permeability and elution kinetics but relative solubility did not determine the relative degree of enhancement of permeability and elution by these materials.

Xylitol and glycine fillers increase permeability of PMMA to enhance elution of daptomycin.

The elution of antibiotics from hand mixed antibiotic-laden polymethylmethacrylate (PMMA) must be increased to achieve clinical performance equivalent to commercially manufactured antibiotic beads (not available in the USA) in the management of musculoskeletal infections. Adding fillers such as glycine and dextran to polymethylmethacrylate increases the elution of antibiotics from antibiotic-laden PMMA. We propose xylitol, a naturally occurring sweetener with direct antibiofilm properties, as a filler material. To compare the efficacy of xylitol and glycine as fillers on the elution of antibiotics from PMMA, elution studies were performed on mixtures of Palacos polymethylmethacrylate and daptomycin (1 gm) with xylitol or glycine as the filler (28 g). Xylitol and glycine enhanced the daptomycin activity eluted from the polymethylmethacrylate. Xylitol was more effective than glycine, having a greater increase in daptomycin release at all data points; on day one xylitol increased the elution of daptomycin 2.67 times whereas glycine increased it 1.78 times also on day one. The eluant concentration of daptomycin remained higher longer for xylitol; 3.90 microg/mL for xylitol versus 2.25 microg/mL for glycine on day 9. Xylitol is inexpensive and readily available. It can be hand mixed with PMMA, and is more effective than glycine as a filler to enhance daptomycin release. Considering possible antibiofilm activity, xylitol may be a more advantageous choice.

Phenolphthalein used to assess permeability of antibiotic-laden polymethylmethacrylate: a pilot study.

Elution of antibiotics from polymethylmethacrylate laden with antibiotics is dependent on the permeability of the polymethylmethacrylate. Increasing polymethylmethacrylate permeability by adding fillers has been suggested to increase antibiotic elution but the resulting increase in permeability has not been assessed directly. A simple method to assess polymethylmethacrylate permeability is proposed. Phenolphthalein was added to the polymethylmethacrylate to indicate the level of penetration of fluid with pH of 10.3. Glycine in three different amounts (0.45 g, 7 g, and 28 g) or a combination of antibiotics (13.6 g) was added as a filler to increase the permeability. Beads of each mixture were made and soaked in fluid with a pH of 10.3. An immediate intense magenta coloration occurred on contact of the beads with the fluid. A zone of magenta was seen to penetrate into the depths of polymethylmethacrylate beads. That penetration increased with the amount of the filler and with time in the fluid bath. The type of filler material also affected the rate of fluid penetration. Permeability of various antibiotic polymethylmethacrylate mixtures can be determined qualitatively using this method. The observations may be useful to determine which mixtures warrant more expensive antibiotic elution studies.

Is aseptic loosening truly aseptic?

Surgeons who treat osteomyelitis or infected implants think that microorganisms can live on and around implanted biomaterials and necrotic bone without clinical manifestations of infection. Gristina and Costerton, in their seminal work, suggested that such bacteria persist within biofilms and that they are often overlooked when diagnosis is based on standard microbiologic culture techniques. Subsequent studies using specialized techniques including sonication to remove adherent bacteria and direct detection using various forms of microscopy have confirmed that bacteria are present in many culture-negative cases. This led to the suggestion that at least some cases of failed orthopaedic implants that were considered aseptic loosening based on the absence of clinical signs of infection and the failure to isolate bacteria may actually have an infectious etiology. In addition to biofilms, potentially important concepts that also may contribute to false-negative culture results include the failure to recognize small colony variants induced during growth in vivo and the presence of bacteria inside host cells including osteoblasts. Importantly, bacteria persisting as small colony variants within biofilms and/or inside osteoblasts also may be an explanation for the recurrent nature of musculoskeletal infection.

Early detection of bone infection and differentiation from post-surgical inflammation using 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography (FDG-PET) in an animal model.

Diagnosing bone infection in the context of post-surgical inflammation is problematic since many of the early signs of infection are similar to normal post-surgical changes. We used a rabbit osteomyelitis model to evaluate the use of 2-deoxy-2-[(18)F]-fluoro-d-glucose positron emission tomography (FDG-PET) as a means of detecting post-operative infection in the context of post-surgical inflammation. Comparisons were made between infected and non-infected rabbits in which infection with Staphylococcus aureus was initiated at the time of surgery. Weekly PET scans were obtained 30 and 60 min after the introduction of FDG and analyzed based on standardized uptake values (SUV) at the surgical site and visual assessment of the presence or absence of infection. Concurrent X-rays were taken immediately prior to scanning. At 4weeks post-operatively, animals were sacrificed for histologic and bacteriologic confirmation of infection. Uptake of FDG was evident in the bone of all rabbits on day 1 post-surgery, however, SUV comparisons from the surgical site could not be used to distinguish between the infected and uninfected groups until day 15. Visual analysis of FDG-PET scans revealed a significant difference (p<0.01) between the infected and uninfected groups as early as day 8. This was due in part to the ability to visualize regional lymph nodes by FDG-PET.

The effect of glycine filler on the elution rate of gentamicin from acrylic bone cement: a pilot study.

Elution of antibiotics from acrylic bone cement (polymethylmethacrylate [PMMA]) is dependent on the access of fluid to the depths of the cement that contains the antibiotic. Commercially prepared antibiotic beads that are porous have higher elution rates than hand-mixed, nonporous antibiotic PMMA mixtures. To increase the elution of gentamicin from hand-mixed PMMA, glycine was added as a filler to produce porosity. Elution of gentamicin from the antibiotic PMMA-glycine mixture increased with increasing amounts of glycine. With 3.6 g gentamicin powder and 14 g of crystalline glycine per batch of Palacos PMMA, the elution of gentamicin from the PMMA at 2 days was, similar to the previously documented elution of gentamicin from commercially prepared porous Septopal PMMA beads. With further investigation it may be possible to identify a specific filler and a volume of filler that can be hand mixed in antibiotic PMMA to produce the elution behavior that is needed for specific clinical requirements.

Surgical hand scrub practices in orthopaedic surgery.

The purpose of this study was to determine whether the practice of surgical hand scrubbing among orthopaedic surgeons, faculty, residents, and nurses met the institution's recommended 5-minute scrub policy and how often a 2-minute surgical hand scrub was used. Forty-eight subjects' hand scrub times were recorded discreetly for a total of 125 observations. All individuals scrubbed for a mean of 2.54 minutes and all scrubbed less than the 5-minute institutionally recommended policy. We found that 35.2% scrubbed less than 2 minutes and 64.8% scrubbed greater than 2 minutes. The subjects studied were polled to determine whether they knew the scrub policy, the minimum effective scrub time, and their perception of how long they scrub. Three of the 16 respondents correctly answered the question regarding the hospital's recommended policy regarding scrub time of 5 minutes. All stated they thought they scrubbed at least 2 minutes and all agreed that at least a 2-minute scrub should be done.

Detecting bacterial colonization of implanted orthopaedic devices by ultrasonication.

Glycocalyx-producing bacteria have been observed on orthopaedic devices that were removed for reasons other than infection. It has been suggested that the bacteria adhere to foreign surfaces within a biofilm and elude standard culture techniques. The authors adapted previously used ultrasonication protocols that disrupt the surface biofilm before culturing removed orthopaedic devices from patients without clinical evidence of infection. Patients having revision total joint arthroplasty of the hip or knee who lacked current or prior clinical evidence of infection were studied prospectively. During surgery, the femoral component and a corresponding control femoral implant were placed in separate sterile bags of saline. The implant and saline combination was placed in an ultrasonication bath for 30 minutes at 60 Hz. The saline solution was passed through a 0.45-microm pore filter, and the filter residue was cultured on sheep blood agar. None of the 21 implants yielded positive culture on routine microbiologic testing. However, using the ultrasonication protocol, a coagulase-negative Staphylococcus grew from one of the removed implants. Numerous total joint implant failures that are attributed to aseptic loosening may be a result of subclinical infection from bacteria within a biofilm. The current study supports the concept that biofilm-protected bacterial colonization of implants may occur without overt signs of infection and ultrasonication can be used to enhance identification of these bacteria.

The effect of sampling method on the elution of tobramycin from calcium sulfate.

Release rate is a critical property of all drug delivery vehicles, including antibiotic-laden bioerodibles. In vitro elution studies, used to evaluate release rates, use different sampling methods, including changing the entire amount of buffer and partial exchanges each day. Two groups of 10% calcium sulfate-tobramycin pellets were eluted in 20 mL of buffer for 30 days. Group I had 5 mL of buffer withdrawn and replaced daily whereas Group II had the entire 20 mL of buffer changed daily. The results show that the complete exchange method caused a significantly faster release of antibiotic than the partial exchange method. In the complete exchange group, greater than 50% of the tobramycin was released by 24 hours, whereas in the partial exchange group, 50% of the antibiotic was not released until Day 6. The two methods of sampling used to evaluate this bioerodible material provide data that allow the user to anticipate how the material will function in relatively inert and volatile environments. The method used to sample the elution of antibiotics from bioerodible materials affects the amount of antibiotic eluted. It therefore is important to know the method of sampling when making a decision to use a bioerodible material to deliver antibiotics locally.

The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets.

Calcium sulfate was used as a biodegradable delivery system for the administration of antibiotics in musculoskeletal infection. New Zealand white rabbits were infected with Staplylococcus aureus, debrided, and randomized to one of four treatment groups: calcium sulfate pellets with 10% tobramycin sulfate, placebo calcium sulfate pellets and IM tobramycin, placebo calcium sulfate pellets, or debridement. Serum and wound exudate tobramycin concentrations and serum calcium levels were measured. Radiographs, cultures, and histology were analyzed for efficacy and treatment. Rabbits treated with 10% tobramycin sulfate pellets showed a significantly higher eradication of infection (11/13) than rabbits treated with debridement only (5/12), placebo pellets and IM tobramycin (5/14). or placebo pellets (3/13). In the group receiving 10% tobramycin sulfate pellets, serum tobramycin concentrations peaked 3 h post-operatively at 5.87 microg/ml and were non-detectable after day 1. In the group receiving placebo pellets and IM tobramycin, serum concentrations peaked at 7.82 microg/ml 1 h post-operatively, fell to 6.12 microg/ml on day 2, and averaged 4.18 microg/ ml for the remainder of the treatment period. The wound exudate tobramycin concentrations in the animals treated with tobramycin sulfate pellets peaked at 11.9 mg/ml on day 1 and dropped to 2.5 microg/ml on day 7. There was no significant difference in the serum calcium levels in any of the treatment groups. Calcium sulfate containing tobramycin sulfate has potential utility as a biodegradable local antibiotic delivery system in the treatment of musculoskeletal infections.