Impregnation of bone chips with antibiotics and storage of antibiotics at different temperatures: an in vitro study

Infection is one of the most devastating adverse events following joint replacement surgery. Deep infection rates in primary hip replacement surgery are around 0.5% to 2%. These infections result in a reduced quality of life1,2. The patient often needs several re-operations, and if surgical debridement is not sufficient a Girdlestone situation is created; the patient then has to function without prosthesis for three to six months, which markedly limits physical activity. Furthermore, the hospitalisation costs for an infected patient are about 3.7 times those for a similar, uninfected patient1.

Bone impaction grafting (BIG) for joint replacement surgery has been used with satisfactory results in clinical practice, for acetabular reconstructions since 1979 and for femoral reconstructions since 19873-10. With BIG, first the segmental bone defects in acetabulum and femur are restored with metal meshes. Next, these defects are filled with tightly impacted morselised cancellous bone chips in combination with a cemented prosthesis. Osteoclasts will resorb necrotic graft remnants and osteoblasts will form new woven bone. This remodelling of newly formed bone into its characteristic structure will lead to the biological repair of the defect following surgery 11.

Surgery with BIG is more complex and time-consuming than primary hip surgery which may contribute to a higher infection rate in hip revision surgery (percentages ranging from 2.0% to 2.5%12-14). BIG creates an avascular area where local circulation is disrupted. If infections arise, this may prevent antibiotics that are administered systemically to reach the infected bone15. In addition, the formation of a biofilm on the surface of the implant renders systemic antibiotics less effective16.

Bone cements containing antibiotics were developed to solve this problem. These cements may serve as a drug delivery system and prophylaxis against infections as they make it possible to achieve higher local drug concentrations. However, controversy exists on the efficacy of the antibiotic-containing cements17. Probably 90% of the antibiotics contained in the cement is never released18. Only when cracks are formed in the cement layer will a small, sub-inhibitory amount of antibiotics be released into the surrounding tissue. This release can continue for years, potentially inducing resistance18.

Several studies have shown that morselised allograft bone, which is used not only in BIG but also in other surgeries, can be made to act as a carrier for antibiotics, either by impregnating the bone grafts with various antibiotic solutions19,23, or by mixing them with antibiotic powders24,25. Although these studies showed, in vitro as well as in vivo, that bone impregnated with antibiotics can be used effectively as prophylaxis against infections, they did not establish the concentration of antibiotic present in the bone after impregnation and how much was released locally. Furthermore, no correlation of antibiotic concentration and zone of inhibition was reported of the antibiotics used in combination with bone chips. Finally, allograft bone is stored at a bone bank at -80

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