Infection remains as one of the major challenges of total joint surgery. One-stage irrigation, debridement and reimplantation or two-stage revision surgery with a temporary implantation of antibiotic eluting bone cement spacer followed by reimplantation are two methods often used to treat infected patients with mixed outcomes. Like bone cement, ultra-high molecular weight polyethylene (UHMWPE) can also be used as a carrier for antibiotics. Recently, we demonstrated that vancomycin and rifampin can be successfully delivered from UHMWPE implants at therapeutic levels to eradicate Staphylococcus aureus biofilm in a lupine animal model. There are regulatory challenges in translating these types of combination devices in to clinical use. One approach is to follow a stepwise strategy, with the first step of seeking clearance for a temporary UHMWPE spacer containing gentamicin sulfate. In this study, we explored the effect of gentamicin sulfate (GS) content in UHMWPE on GS elution rate and antimicrobial activity against methicillin-sensitive S. aureus(MSSA). We also assessed the effect of spacer fabrication on the activity of gentamicin sulfate. We prepared and consolidated UHMWPE/GS blends in varying concentrations. After consolidation, we fabricated test samples with surface area (350mm2) to volume (300mm3) ratio of 1.2 for elution in 1.5ml phosphate buffered saline at body temperature for up to six months and quantified eluted GS content using liquid chromatography – mass spectrometry (LCMS). We assessed the antibacterial activity of the obtained samples in vitro against various concentrations of MSSA (103–106 CFU/ml). Furthermore, we quantified the probability of bacterial colonization of UHMWPE impregnated with GS compared to GS containing bone cement. We assessed any detectable changes in activity of eluted GS caused by spacer fabrication by screening m/z peaks of GS isomers in mass spectra obtained from LC-MS. Gentamicin sulfate activity was not compromised by the elevated temperature and pressure used during spacer fabrication. Elution rate of GS increased with increasing GS content in the blends studied. At comparable elution rates, the GS-loaded UHMWPE was either equivalent or better in terms of antibacterial and anticolonization properties when compared with gentamicin containing bone cement. GS-impregnated UHMWPE is a promising material for temporary spacers

Introduction. Infection remains as one of the major challenges of total joint surgery. One-stage irrigation, debridement and reimplantation, or two-stage revision surgery with a temporary implantation of antibiotic eluting bone cement spacer followed by reimplantation are two methods often used to treat infected patients with mixed outcomes. Like bone cement, ultra-high molecular weight polyethylene (UHMWPE) can also be used as a carrier for antibiotics. Recently, we demonstrated that vancomycin and rifampin can be delivered from UHMWPE implants at therapeutic levels to eradicate Staphylococcus aureus biofilm in a lupine animal model. There are regulatory challenges in translating these types of combination devices to clinical use. Last year, at this meeting, we presented the preliminary pre-clinical testing for a temporary UHMWPE spacer containing gentamicin sulfate as a first step towards clinical use. Since then, we carried out a survey among the Knee Society membership about their preference for spacer use in two-stage revision surgery and found that 43% prefer to use a CoCr femoral component on an all-poly cemented tibial insert, 22% prefer bone cement spacers molded in the OR, 20% prefer static bone cement spacers, and 14% prefer pre-formed bone cement spacers. We modified our implant design based on the majority's preference for a total knee system, rather than bone cement spacers, in the temporary two-stage approach. In this study, we explored the effect of gentamicin sulfate (GS) elution from UHMWPE/GS tibial inserts on bacterial colonization on CoCr surfaces. Methods. We characterized the gentamicin sulfate (GS) particles with scanning electron microscopy (SEM). We molded UHMWPE/GS powder blends and characterized the morphology using SEM and Energy Dispersive X-Ray Spectroscopy (EDS). We submerged samples of molded UHMWPE/GS in buffered phosphate solution (PBS) at 37°C and quantified the extent of GS elution into PBS with a method described by Gubernator et al. using o-phthaladehyde (OPA) [1]. Under basic conditions, OPA reacts with primary amino groups to form fluorescent complexes. Since gentamicin is the only source of such amino acids in our elution samples, the number of fluorescent complexes formed is directly proportional to the amount of gentamicin in the sample. Using this method, we could quantify gentamicin elution by measuring sample fluorescence post OPA-reaction. We used a plate reader to excite the fluorescent complexes formed in the OPA reaction and measured the resulting emission at wavelengths of 340 nm and 455 nm, respectively. We also quantified the effect of the standard cleaning protocol (heated sonication in alkaline water and alcohol) used to clean UHMWPE implants on subsequent GS elution from UHMWPE/GS samples using the OPA method. We used agar diffusion tests to characterize antibacterial properties of UHMWPE/GS samples after cleaning. For these tests, we collected eluents collected from UHMWPE/GS and gentamicin-impregnated bone cement (BC/GS) following 1, 2, 3, and 4 weeks of elution, and tested against S. aureus (ATCC 12600). We used the “daughter cells” method developed by Bechert et al. to assess anticolonizing properties of UHMWPE/GS [2,3]. We also characterized the colonization of bacteria on CoCr surfaces in the presence of GS eluting from UHMWPE/GS test samples. For this we modified a Pin-on-Disc (PoD) wear tester: An UHMWPE/GS pin and UHMWPE pin (control) articulated against an implant-finish CoCr disc with Tryptic Soy Broth containing S. Aureus as the lubricant. After 18 hrs, we rinsed the articular surfaces of the pin and disc and stamped them onto Agar gel to transfer any adherent bacteria. We incubated the Agar plate overnight such that adherent bacteria proliferated and became visible. Results. SEM characterized the GS particles as hollow spheres (Fig 1a). These formed small groups of agglomerated domains at the virgin resin boundaries of UHMWPE after molding (Fig 1b). Sulfur signature from the EDS analysis identified the agglomerated domains as GS particles (Fig 2). Elution of GS started with an initial burst and was followed by steady elution up to 12 weeks (Fig 3). Cleaning reduced the initial burst GS elution; and the elution remained unchanged after 2 days (Fig 4). The agar diffusion test showed simmilar inhibition zones for the eluents collected from UHMWPE/GS and BC/GS, suggesting that these samples yield similar antibacterial activity against S. aureus (Fig 5). UHMWPE/GS demonstrated pronounced anticolonizing properties, effectively mitigating the proliferation of S. aureus “daughter” cells. Anticolonizing activity of Palacos R+G was not significantly different when compared with UHMWPE/GS. The PoD test showed little-to-no colonization of CoCr surfaces in the presence of UHMWPE/GS pins, indicative of excellent antibacterial properties of UHMWPE/GS against S. aureus. Conclusion. SEM and EDS has allowed us to visualize domains of gentamicin sulfate particles in UHMWPE. Our OPA method has greater precision than traditional agar-well diffusion methods of measuring gentamicin concentration and showed that gentamicin sulfate-loaded UHMWPE elutes at the same rate as Palacos R+G. Pin-on-disc experiments and the daughter cell method both confirmed that these two materials have similar anticolonization abilities. We also found that using the standard cleaning protocol for UHMWPE orthopedic implants decreased the burst of gentamicin eluting from UHMWPE, but after 2 days, it had no effect compared to uncleaned UHMWPE/GS. Finally, we found that UHMWPE/GS can reduce the colonization of bacteria on CoCr. UHMWPE/GS continues to be a promising material for treating PJI. 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Aims

The management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is challenging. The correct antibiotic management remains elusive due to differences in epidemiology and resistance between countries, and reports in the literature. Before the efficacy of surgical treatment is investigated, it is crucial to analyze the bacterial strains causing PJI, especially for patients in whom no organisms are grown.

The final results up to 15 years are reported of clinical trials of the management of tuberculosis of the spine in Korea and Hong Kong. In Korea, 350 patients with active spinal tuberculosis were randomised to ambulatory chemotherapy or bed rest in hospital (in Masan) or a plaster-of-Paris jacket for nine months (in Pusan). Patients in both centres were also randomised to either PAS plus isoniazid for 18 months or to the same drugs plus streptomycin for the first three months. In Hong Kong, all 150 patients were treated with the three-drug regime and randomised to either radical excision of the spinal lesion with bone graft or open debridement. On average, the disease was more extensive in Korea, but at 15 years (or 13 or 14 years in a proportion of the patients in Korea) the great majority of patients in both countries achieved a favourable status, no evidence of CNS involvement, no radiological evidence of disease, no sinus or clinically evident abscess, and no restriction of normal physical activity. Most patients had already achieved a favourable status much earlier. The earlier results of these trials are confirmed by the long-term follow-up with no late relapse or late-onset paraplegia. The results of chemotherapy on an outpatient basis were not improved by bed rest or a plaster jacket and the only advantage of the radical operation was less late deformity compared with debridement. A second series of studies has shown that short-course regimes based on isoniazid and rifampicin are as effective as the 18-month regimes: ambulatory chemotherapy with these regimes should now be the main management of uncomplicated spinal tuberculosis

Aims

The results of irrigation and debridement with component retention (IDCR) in the treatment of acutely infected total knee arthroplasties (TKAs) have been variable. The aim of this study was to assess the outcome after IDCR when combined with chronic antibiotic suppression. We also evaluated survivorship free from subsequent infection, removal of the components, and death, as well as the risk factors for failure.