Authors: Martin Buttaro, MD, Fernando Comba*, MD and Francisco Piccaluga, MD
Title: Vancomycin-Supplemented Impacted Bone Allografts: Infection Control and Biological Reconstruction in a Previously Infected THA
Addresses: Hip Surgery Unit, Institute of Orthopaedics "Carlos E. Ottolenghi", Italian Hospital, Buenos Aires, Argentina, Potosí 4215 (1199ACK) - Buenos Aires, Argentina
Purpose: The aim of this study is to present the experimental, pharmacokinetical, clinical and histological experience with the use of vancomycin-supplemented impacted bone allografts for the reconstruction of bone defects in revision hip surgery.
Methods: Experimental Study: cortical bone defects were surgically filled with vancomycin-supplemented bone allografts in 9 pigs and bone allografts without antibiotics in other 9 control-cases (Fig 1). Incorporation of vancomycin-supplemented allografts was studied by means of high resolution radiographs, immunohistochemistry and histology performed by three independent pathologists. Inmunohistochemical analysis assessed the number (and %) of osteocytes, osteoblasts, osteoprogenitor cells and chondrocytes with TGFβ2 cytoplasm positivity in the repair bone callus area. The number (and %) of hypertrophic chondrocytes and osteoblasts with MMP-13 cytoplasm positivity in the repair bone callus was also considered.
- Pharmacokinetical Study: Samples of the wound drainage, serum and urine samples were collected at different time intervals in 20 patients reconstructed with cancellous impacted bone allografts supplemented with vancomycin. Elution and nephrotoxicity of the vancomycin released from the allografts were tested in each sample. Biological activity of vancomycin was studied using kinetic killing curves in three American Type Culture Collection (ATCC) organisms at 5 time points (1, 6, 12, 24 and 48 h). The organisms used were methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosas.
- Clinical Study: 29 patients (18 women and 11 men with a mean age of 59 years (32 to 78)) with 30 infected total hip arthroplasties presenting bone loss were treated with removal of components, parenteral antibiotic therapy, followed by a second-stage re-implantation using vancomycin-supplemented impacted allografts. Patients were clinically and radiographically evaluated at 15, 45 and 90 days and then yearly.
- Histological Study: Biopsies during reoperation due to periprosthetic fractures were performed at 14 and 20 months respectively, in two patients who had been reconstructed with vancomycin-supplemented impacted allografts.
Results: Experimental Study: High quality roentgenographs, histological examination considering vascular ingrowth as well as the presence of mature bone and immunological expression of metalloproteinase-13 (MMP-13) and transforming growth factor-beta 2 (TGFβ2) indicated that vancomycin does not significantly affect graft incorporation (Figs 2 and 3).
- Pharmacokinetical Study: Local active bactericidal levels of vancomycin reached 1400.5 ug/ml (average 5 point level=367.19 ug/ml) without nephrotoxicity. Vancomycin was present in urine until the 15th day (Fig 4).
- Clinical Study: At a minimum 2 year f-up (mean 32.4 months, range 24-60 months) infection control was obtained in 29 of 30 cases (reinfection rate: 3.3%; CI 95%=0.08%-17%) without evidence of progressive radiolucent lines, demarcation or graft resorption. Radiographic allograft incorporation was observed in 96% of the cases (Fig 5).
- Histological Study: Viable trabecular bone was observed in the middle area of the specimen. The internal area showed fragments of necrotic and viable bone, interpreted as incorporated bone graft. The small fragments of necrotic trabecular bone were gradually replaced by viable new bone, suggested that the necrotic bone was allograft (Fig 6).
Discussion: Experimentally, no significant differences in bone incorporation between both groups were observed regarding radiographic, histological and immunohistochemical tests.
In the pharmacokinetical phase, local antibiotic measured levels were as high as 300 times higher than the required to achieve bactericidal effect. These levels were also 35 times higher than the ones eluted from the cement at the 5 time intervals we studied, without nephrotoxicity and without impairing methacrylate mechanical properties.
Vancomycin-supplemented impacted bone allografts biologically restored acetabular and femoral bone stock achieving sound fixation with a low reinfection rate. Our initial results, confirmed by the histological findings of the two biopsed cases, justify the utilization of this method. Bone loss in the presence of an infected total hip arthroplasty may be successfully restored using vancomycin-supplemented impacted bone allografts.
This experimental, pharmacokinetical, clinical and histological findings encourage the continued use of antibiotic-supplemented bone allografts in reconstructive orthopaedic surgery.