Iontophoresis is a novel technique which may be used to facilitate the movement of antibiotics into the substance of bone using an electrical potential applied externally. We have examined the rate of early infection in allografts following application of this technique in clinical practice. A total of 31 patients undergoing revision arthroplasty or surgery for limb salvage received 34 iontophoresed sequential allografts, of which 26 survived for a minimum of two years. The mean serum antibiotic levels after operation were low (gentamicin 0.37 mg/l (0.2 to 0.5); flucloxacillin 1 mg/l (0 to 1) and the levels in the drains were high (gentamicin 40 mg/l (2.5 to 131); flucloxacillin 17 mg/l (1 to 43). There were no early deep infections. Two late infections were presumed to be haemotogenous; 28 of the 34 allografts were retained. In 12 patients with pre-existing proven infection further infection has not occurred at a mean follow-up of 51 months (24 to 82)

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (. sd. 15.7) to 124.6 (. sd. 46.2) in periosteal bone for gentamicin and 31.9 (. sd. 8.9) in endosteal and 2.9 (. sd. 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks. Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds

Introduction: Iontophoresis is a method to introduce antibiotic molecules into allograft bone using an electrical potential; the antibiotics may then be released at therapeutic levels for extended periods of time. This is the first report of iontophoresed allograft implantation into patients. Method: A method of loading tubular sections of cortical bone was used in theatre prior to implantation. Postoperative serum, drain and allograft antibiotic assays were performed. Patients were followed-up clinically and radiologically. All patients who received a bulk segmental allograft from June 1997 were entered into the trial. Results: Since June 1997, 35 patients have received 37 allografts. Indications for allograft insertion were limb salvage for tumour (18), and poor bone stock associated with infection (11), periprosthetic fracture (6), aseptic loosening (1) and recurrent dislocation of total hip replacement (1). Mean follow-up is 3.3 years, and no patients have been lost to follow-up. One patient received two allografts in different sites and one had an allograft exchange. There has been one superficial wound infection and one deep infection. The latter patient was revised to another iontophoresed allograft and has had no recurrence at 34 months. One allograft has been revised to a vascularised fibular graft and allograft exchange following fracture of metal fixation. There was one case of persistent non-union in a knee arthrodesis which was treated after 21 months by removal of the intramedullary fixation and use of an Illizarov frame. The allograft was not revised. All other allografts are in situ with no complications related to the allograft. Eleven patients had pre-existing proven infections. None of these patients have been re-infected to date. Therapeutic gentamicin and flucloxacillin levels were detected in drain fluid samples post-operatively. Conclusions: Iontophoresis is a safe and inexpensive technique that delivers high local dose of antibiotic, which may reduce infection in avascular allograft bone

Introduction and Aims: Iontophoresis is a method to introduce antibiotic molecules into allograft bone using an electrical potential. In-vitro testing has shown that these antibiotics should be released in their bioactive form at therapeutic levels for extended periods of time. This is the first report of iontophoresed allograft implantation into patients. Method: A method of loading tubular sections of cortical bone was used in theatre prior to implantation. The bone was held vertically in an antibiotic bath with a cylindrical outer electrode and a wire electrode down the centre of the bone. An electrical potential of approximately 90V was applied to drive the antibiotics into the bone. Post-operative serum, drain and allograft antibiotic assays were performed. All patients were followed-up clinically and radiologically. Patients who required a bulk segmental allograft from June 1997 to present were entered into the trial and received iontophoresed bone. Results: Since June 1997, 35 patients have received 37 iontophoresed allografts. Indications for allograft insertion were limb salvage for tumor (16), poor bone stock associated with infection (12), periprosthetic fracture (seven), aseptic loosening (one) and recurrent dislocation of total hip replacement (one). One patient had acute complications requiring amputation. No patients were lost to follow-up with a mean follow-up of 3.3 years. Two patients required an allograft exchange for fracture and infection. There were two late allograft infections at 10 and 18 months. One patient was revised to another iontophoresed allograft and has had no recurrence at two years. The other infection required above knee amputation. One allograft was revised with allograft exchange and vascularised fibular graft following fracture of metal fixation. There was one case of persistent non-union in a knee fusion, which was treated after 21 months by removal of the intermedullary fixation and allograft and use of an Ilizarov frame. All other allografts are in-situ with no complications related to the allograft. Twelve patients had pre-existing proven infections. None of these patients have been re-infected to date. Therapeutic gentamicin and flucloxacillin levels were detected in drain fluid samples post-operatively, averaging from 39.9 mg/L at two hours to 5.97mg/L at 48 hours for gentamicin and 16.83mg/L at two hours and 2.23 mg/L at 48 hours for flucloxacillin. This was significantly greater than the minimum inhibitory concentration (MIC) against Staphylococcus aureus for gentamicin (0.25mg/L) and flucloxacillin (0.30mg/L). At the same time, blood levels remained in a safe range. Conclusion: Iontophoresis is a safe and inexpensive method that can be executed in the operating theatre. Iontophoresed bone delivers a high local dose of antibiotic, which may prevent early biofilm formation initiated during allograft handling and exposure to theatre air. With no early infections and no re-infections, further assessment of this technique continues with guarded optimism

Objectives. The most concerning infection of allografts and operative procedures is methicillin resistant Staphylococcus aureus (MRSA) and no current iontophoresed antibiotics effectively combat this microbe. It was initially hypothesised that iontophoresis of vancomycin through bone would not be effective due to its large molecular size and lack of charge. The aim of this study was to determine whether this was a viable procedure and to find the optimum conditions for its use. . Methods. An iontophoresis cell was set up with varying concentrations of Vancomycin within the medulla of a section of sheep tibia, sealed from an external saline solution. The cell was run for varying times, Vancomycin concentrations and voltages, to gain information on optimisation of conditions for impregnating the graft. Each graft was then sectioned and dust ground from the exposed surface. The dust was serially washed to extract the Vancomycin and concentrations measured and plotted for all variables tested. Results. Vancomycin was successfully delivered and impregnated to the graft using the iontophoresis technique. The first order fit to the whole data set gave a significant result (p = 0.0233), with a significant concentration (p = 0.02774) component. The time component was the next most significant (p = 0.0597), but did not exceed the 95% confidence level. Conclusions. Iontophoresis is an effective method for delivering Vancomycin to allograft bone. The concentrations of the vancomycin solution affected the bone concentration, but results were highly variable. Further study should be done on the effectiveness of delivering different antibiotics using this method. Cite this article: Bone Joint Res 2014;3:101–7

Revision arthroplasty after infection can often be complicated by both extensive bone loss and a relatively high rate of re-infection. Using allograft to address the bone loss in such patients is controversial because of the perceived risk of bacterial infection from the use of avascular graft material. We describe 12 two-stage revisions for infection in which segmental allografts were loaded with antibiotics using iontophoresis, a technique using an electrical potential to drive ionised antibiotics into cortical bone. Iontophoresis produced high levels of antibiotic in the allograft, which eluted into the surrounding tissues. We postulate that this offers protection from infection in the high-risk peri-operative period. None of the 12 patients who had two-stage revision with iontophoresed allografts had further infection after a mean period of 47 months (14 to 78)

Introduction and Aims: This randomised, double-blind, placebo-controlled study evaluated the safety and effectiveness of dermal iontophoretic administration of Dexamethasone Sodium Phosphate 0.4% Injection, USP versus placebo in patients with medial and lateral elbow epicondylitis. Method: 199 patients with elbow epicondylitis received 40 mA-min of either active or placebo treatment on six occasions. Treatments were spaced one to three days apart and were completed within 15 days. Efficacy variables included patient and investigator global evaluation of improvement, patient and investigator pain evaluation, patient evaluation of symptoms, investigator disease severity assessment and investigator evaluation of tenderness. Baseline scores were compared with scores two days and one month after the sixth treatment. Results: Dexamethasone produced a 23 mm improvement in patient visual analog scale ratings compared with 14 mm for placebo (p=0.012) at two days and 24 mm compared with 19 mm (p=0.249) at one month. More dexamethasone patients than placebo patients had a score of moderate or better on the investigator global improvement score (52% vs 33%, p=0.013) at two days. This was not significant at one month (54% vs 49%, p=0.650). Investigator pain scores and tenderness scores favoured dexamethasone over placebo (p=0.019 and p< 0.001, respectively) at two days. Patients completing six treatments in ≤10 days appeared to show better efficacy than patients completing treatments over a longer period of time. Conclusion: Iontophoresis treatment was well tolerated by the majority of the patients and was effective in reducing symptoms of epicondylitis at short-term follow-up