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Tobramycin exposure from active calcium sulfate bone graft substitute.

ABSTRACT: Bone graft substitute such as calcium sulfate are frequently used as carrier material for local antimicrobial therapy in orthopedic surgery. This study aimed to assess the systemic absorption and disposition of tobramycin in patients treated with a tobramycin-laden bone graft substitute (Osteoset® T).Nine blood samples were taken from 12 patients over 10 days after Osteoset® T surgical implantation. Tobramycin concentration was measured by fluorescence polarization. Population pharmacokinetic analysis was performed using NONMEM to assess the average value and variability (CV) of pharmacokinetic parameters. Bioavailability (F) was assessed by equating clearance (CL) with creatinine clearance (Cockcroft CLCr). Based on the final model, simulations with various doses and renal function levels were performed. (ClinicalTrials.gov number, NCT01938417).The patients were 52 +/- 20 years old, their mean body weight was 73 +/- 17 kg and their mean CLCr was 119 +/- 55 mL/min. Either 10 g or 20 g Osteoset® T with 4% tobramycin sulfate was implanted in various sites. Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing important variability. With CL equated to CLCr, mean absorption rate constant (ka) was 0.06 h-1, F was 63% or 32% (CV 74%) for 10 and 20 g Osteoset® T respectively, and volume of distribution (V) was 16.6 L (CV 89%). Simulations predicted sustained high, potentially toxic concentrations with 10 g, 30 g and 50 g Osteoset® T for CLCr values below 10, 20 and 30 mL/min, respectively.Osteoset® T does not raise toxicity concerns in subjects without significant renal failure. The risk/benefit ratio might turn unfavorable in case of severe renal failure, even after standard dose implantation.

SUBMITTER: Livio F

PROVIDER: S-EPMC3944781 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Tobramycin exposure from active calcium sulfate bone graft substitute.

Livio Françoise F Wahl Peter P Csajka Chantal C Gautier Emanuel E Buclin Thierry T

BMC pharmacology & toxicology 20140304

<h4>Background</h4>Bone graft substitute such as calcium sulfate are frequently used as carrier material for local antimicrobial therapy in orthopedic surgery. This study aimed to assess the systemic absorption and disposition of tobramycin in patients treated with a tobramycin-laden bone graft substitute (Osteoset® T).<h4>Methods</h4>Nine blood samples were taken from 12 patients over 10 days after Osteoset® T surgical implantation. Tobramycin concentration was measured by fluorescence polariza ...[more]

PMID: 24593819

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Project description:Background:The treatment of fracture- or non-union-related infections has persistently been a major challenge for both patients and treating surgeons. With rising aging of patients and increasing comorbidities, combined with the heterogeneity of germs and any number of multi-resistance against standard antibiotics, a successful treatment is increasingly difficult. One potential solution could be a custom-made individualized antibacterial coating of standard implants with a biphasic degradable biocarrier (Cerament G/V, supplied by Bonesupport AB, Lund, Sweden) that releases high doses of antibiotics around the bone-implant-interface. Here, we describe our technique of coating intramedullary nails, plates and press-fit shoulder endoprostheses which may prevent bacterial adhesion and biofilm formation. So far, there is very limited experience in individual coating of implants in hip or knee endoprostheses to prevent reoccurrence of surgical-site infection. Currently, no reports are available for coating of stems of shoulder prosthesis and nails or plates for fracture fixation. Methods:Here, we show our first experiences with a new individualized surgical technique of coating these implants with a resorbable antibiotic-loaded hydroxyapatite/calcium sulphate biocomposite to prevent biofilm formation and thereby recurrence of bone or joint infection. We describe three cases for coating of plates and nails for fracture fixation and coating of stems of a shoulder prosthesis. Results:No adverse events of the resorbable bone graft substitute were observed. In all of the cases, no recurrence of the infection was observed and osseointegration was achieved. After implant coating of the shoulder prosthesis, no radiological signs of loosening were detected. Conclusion:We present a new surgical approach of a surface coating of plates, intramedullary nails or prostheses. The osteoconductive- and anti-inflammatory effect of the gentamicin- or vancomycin-loaded hydroxyapatite/calcium sulphate bone graft substitutes shows promising results.

Project description:BackgroundManagement of large infected bone defects is a major clinical and socioeconomic problem. The induced membrane technique has been widely used as a solution. However, it has apparent disadvantages such as limited autologous bone graft supply and lack of continuous infection control. Meanwhile, calcium sulfate/calcium phosphate composites have efficacious osteogenesis and antibiotic delivery capacity. For the first time, we analyzed the efficiency of calcium sulfate/calcium phosphate composites as a bone graft expander in the induced membrane technique to treat large infected bone defects.MethodsWe retrospectively analyzed the clinical data of 12 patients with large infected bone defects of 6.1-17.2 cm treated with the induced membrane technique from November 2016 to July 2019. In the second reconstruction stage, the bone defect was filled with a mixture of the autogenous iliac bone and vancomycin-impregnated calcium sulfate/calcium phosphate composites at a ratio of 3:1. We assessed the bony union by Samantha X-ray score and recorded infection recurrence and complications. Paley scale and SF-36 score were used to evaluate the function of adjacent joint and quality of life pre and postoperatively. Pearson's correlation coefficients were calculated for union time and other clinical scores.ResultsThe mean follow-up was 69 weeks (ranging from 30 to 142) after the second stage of the operation. The mean Samantha X-ray score was 5.1 [3-6], preoperative and postoperative SF-36 scores showed that there were statistical differences in all the nine aspects, and the excellent rate of adjacent joint function was 75% (Paley). All cases were radiologically healed, and none of the 12 patients had infection recurrence or failure of fixation at the last follow-up. Two cases had delayed wound healing and were cured after dress changing. There was a significant correlation between union time and Samantha X-ray score (r =‒0.887; P=0.000), while there was no correlation between filling dose, size of the defect, and other outcomes.ConclusionsThis study provided evidence supporting calcium sulfate/calcium phosphate composites as an effective and safe bone graft expander in the induced membrane technique to treat large infected bone defect. This technique may help decrease the use of autologous bone graft and enhance the anti-infection effect of the induced membrane technique.

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Tobramycin exposure from active calcium sulfate bone graft substitute.

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Tobramycin exposure from active calcium sulfate bone graft substitute.

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