Antibiotic-impregnated Bone Graft Research Articles

Use of antibiotic-impregnated bone grafts in a rabbit osteomyelitis model.

Both osteomyelitis and prosthetic joint infection can be treated surgically with the use of antibiotic loaded bone grafts, as part of local antimicrobial therapy. The purpose of the study was to evaluate and to report on a novel, biodegradable, long-acting (4-6 weeks) antibiotic-impregnated bone graft (AIBG). A novel drug delivery system, containing vancomycin, was utilized in a rabbit osteomyelitis model in order to evaluate the antimicrobial efficacy of the antibiotic bone graft. Forty adult New Zealand rabbits were used. The animals were randomized into three Groups: healthy animals without osteomyelitis, where AIBG was used to fill a defect (Group I); osteomyelitis caused with a methicillin-resistant S.aureus strain (MRSA) treated with AIBG (Group II); osteomyelitis caused with MRSA and treated with bone grafts without local antibiotics (Group III). At six weeks post-operation, the animals were sacrificed and histological, laboratory and radiologic evaluations were performed. Of the 24 operated rabbits, osteomyelitis was confirmed in 18 animals. In groups with osteomyelitis, only minor radiological changes were observed on day 21 post-op. Radiographs taken on day 42 post-op showed radiological signs of chronic osteomyelitis in Group III, whereas in Group II, bone healing was observed. Bacterial cultures taken on day 42 post-op revealed the original MRSA strain in Group III, whereas no bacteria were detected in Group II. Histological examinations showed the presence of macrophage cells which slowly break down the DDS matrix. The presence of DDS did not inhibit re-ossification. The drug delivery system was effective against MRSA-induced osteomyelitis without negative effect on osteointegration. This biodegradable technology has the potential to be a powerful tool in fighting bone infections.

Use of Bioabsorbable Bone Graft in Osteomyelitis Associated with Ischial Pressure Sores

Sir: Traditional surgical principles in pressure sore management include soft-tissue débridement, removal of infected bone, and filling the dead space using local flaps. Antibiotic-impregnated methylmethacrylate beads have been used in chronic osteomyelitis to deliver antibiotics locally in high concentrations. However, once the antibiotics have leached out of the bead, the bead acts as a nidus for infection and requires removal.1 Bone graft substitutes impregnated with antibiotics have been used to replace bone defects in osteomyelitis of the long bones and spine with excellent results.2 However, their use has not been described in pressure sore–associated osteomyelitis. OsteoSet (Wright Medical Group, Inc., Arlington, Tenn.), a bioabsorbable calcium sulfate bone graft substitute, can be impregnated with antibiotics and used to fill the bony cavity.3 The concentration of antibiotics released from calcium sulfate preparations exceeds 100-fold the minimum inhibitory concentration in the first 24 hours and 10-fold the minimum inhibitory concentration for 3 to 4 days, with continued elution of the antibiotic beyond 10 days.4 New bone adheres to the reabsorbing OsteoSet and gradually fills in the defect. Obliteration of the bony dead space by bone graft substitutes reduces the need for extensive flap surgery. Our experience in three patients with ischial pressure sores and infected ischium was successful in curing osteomyelitis and closing wounds without extensive flap, and there was no occurrence of contralateral ischial pressure sores caused by traditional ischiectomy. After soft-tissue débridement, the outer cortex is opened with a dental burr to allow complete débridement of the infected cancellous bone. The remaining cortex is kept intact to provide housing for the bone graft substitute (Fig. 1). Multiple débridements may be required until the wound is clean. Then, OsteoSet antibiotic paste is molded into the bony cancellous defect within the cortical bone envelope, and layered closure of the wound is performed over a suction drain. Its placement should be deep; otherwise, subcutaneous bone formation will occur and can lead to ulceration. Culture-directed intravenous antibiotics are continued for 6 weeks.Fig. 1.: Ischial wound after soft-tissue and bony débridement shows preservation of ischial and pubic ramus bone cortex for placement of bone graft substitute antibiotic paste (above). Healed ischial area in a C7 quadriplegic patient after bone graft substitute and layered closure is seen at 42 months after surgery (below).Our first patient remained healed for 3 years after this procedure. A new area of osteomyelitis was then débrided and treated with OsteoSet. Healthy bone was noted in areas where OsteoSet had been placed initially. A second patient was recurrence free for over 3 years. Incidentally, he failed multiple conventional flap procedures for a contralateral ischial pressure sore that was treated at another institution. Our last patient underwent placement of OsteoSet with an inferior gluteal flap. Two recurrences at 3 and 5 years were managed with débridement, OsteoSet placement, and flap readvancement. The use of antibiotic-impregnated bone graft substitute is a simple and effective technique for pressure sore–associated osteomyelitis. Because recurrence rates can be as high as 69 percent after surgical management of pressure sores,5 it is common to exhaust most local flap options within a few years. Placement of a bone graft substitute obliterates the bony dead space and preserves local tissue to salvage future recurrences that are inevitable in this patient population. DISCLOSURE The authors have no financial interest to declare in relation to the content of this article. Matthias Solomon, M.B.B.S. Division of Plastic Surgery Mayo Clinic Rochester, Minn. Peyton Davis, M.B.Ch.B. Department of Emergency Medicine Oxford University Oxford, United Kingdom Nho V. Tran, M.D. Division of Plastic Surgery Mayo Clinic Rochester, Minn. Michael Rock, M.D. Department of Orthopedic Surgery Mayo Clinic Rochester, Minn.

Rationale for one stage exchange of infected hip replacement using uncemented implants and antibiotic impregnated bone graft

Infection of a total hip replacement (THR) is considered a devastating complication, necessitating its complete removal and thorough debridement of the site. It is undoubted that one stage exchange, if successful, would provide the best benefit both for the patient and the society. Still the fear of re-infection dominates the surgeons decisions and in the majority of cases directs them to multiple stage protocols. However, there is no scientifically based argument for that practice. Successful eradication of infection with two stage procedures is reported to average 80% to 98%. On the other hand a literature review of Jackson and Schmalzried (CORR 2000) summarizing the results of 1,299 infected hip replacements treated with direct exchange (almost exclusively using antibiotic loaded cement), reports of 1,077 (83%) having been successful. The comparable results suggest, that the major factor for a successful outcome with traditional approaches may be found in the quality of surgical debridement and dead space management. Failures in all protocols seem to be caused by small fragments of bacterial colonies remaining after debridement, whereas neither systemic antibiotics nor antibiotic loaded bone cement (PMMA) have been able to improve the situation significantly. Reasons for failure may be found in the limited sensitivity of traditional bacterial culturing and reduced antibiotic susceptibility of involved pathogens, especially considering biofilm formation. Whenever a new prosthesis is implanted into a previously infected site the surgeon must be aware of increased risk of failure, both in single or two stage revisions. Eventual removal therefore should be easy with low risk of additional damage to the bony substance. On the other hand it should also have potential of a good long term result in case of success. Cemented revisions generally show inferior long term results compared to uncemented techniques; the addition of antibiotics to cement reduces its biomechanical properties. Efficient cementing techniques will result in tight bonding with the underlying bone, making eventual removal time consuming and possibly associated with further damage to the osseous structures. All these issues are likely to make uncemented revisions more desirable. Allograft bone may be impregnated with high loads of antibiotics using special incubation techniques. The storage capacities and pharmacological kinetics of the resulting antibiotic bone compound (ABC) are more advantageous than the ones of antibiotic loaded cement. ABC provides local concentrations exceeding those of cement by more than a 100fold and efficient release is prolonged for several weeks. The same time they are likely to restore bone stock, which usually is compromised after removal of an infected endoprosthesis. ABC may be combined with uncemented implants for improved long term results and easy removal in case of a failure. Specifications of appropriate designs are outlined. Based on these considerations new protocols for one stage exchange of infected TJR have been established. Bone voids surrounding the implants may be filled with antibiotic impregnated bone graft; uncemented implants may be fixed in original bone. Recent studies indicate an overall success rate of more than 90% without any adverse side effects. Incorporation of allografts appears as after grafting with unimpregnated bone grafts. Antibiotic loaded bone graft seems to provide sufficient local antibiosis for protection against colonisation of uncemented implants, the eluted amounts of antibiotics are likely to eliminate biofilm remnants, dead space management is more complete and defects may be reconstructed efficiently. Uncemented implants provide improved long term results in case of success and facilitated re-revision in case of failure. One stage revision using ABC together with uncemented implants such should be at least comparably save as multiple stage procedures, taking advantage of the obvious benefits for patients and economy.

Extremity Trauma Research in the United States Army

Extremity wounds compose the burden of injury in the global war on terrorism, and there is a great need for research to improve the treatment of soldiers who incur these devastating injuries. The mission of the United States Army Institute of Surgical Research is to conduct combat casualty care research in several areas, including explosive injury mechanisms, field tourniquet use, external fixator pin coating, wound irrigation optimization, antibiotic-impregnated bone graft substitutes, segmental muscle defects, and outcomes research. Future research directions include development of bone and soft-tissue regenerative technologies, prevention and treatment of heterotopic ossification, and bacteriology of unique pathogens.

TOBRAMYCIN ELUTION FROM BONE SUBSTITUTE

Purpose: To determine the rate of antibiotic elution from tobramycin-impregnated ProOsteon (Interpore) and Collagraft (Zimmer). Methods: Five samples of Collagraft and ProOsteon were impregnated with a solution containing 1.2 g of tobramycin and 10 ml of sterile water. The samples were then allowed to dry overnight. These samples were stored at 37°C in separate test tubes containing phosphate buffered saline (PBS). The solution in each test tube was removed with a pipette at hours 3, 6, 9 and 12 and days 1, 2, 3, 5, 7, 9, 11 and 13. The PBS was then replaced. The pipetted solution was sent for laboratory quantification and also used in a bioassay to determine antibiotic level. To serve as a control, two additional samples of each bone graft that were not impregnated with antibiotic were placed in separate test tubes and subjected to the same protocol. Results: The antibiotic elution rate for both ProOsteon and Collagraft was high at 3 hours [5362 and 4875 μg/ml on day 3 (3.1 μg/ml) for the Collagraft and day 7 (3.7 μg/ml) for the ProOsteon]. Effective intravenous tobramycin level is considered to be 4–6 μg/ml. Conclusion: Bone graft substitute can be used as a delivery vehicle for tobramycin. In addition, antibiotic-impregnated synthetic bone graft may potentially fill a dead space or cavitary defect without the need for large autologous grafts and does not require later removal.

Management of small infected tibial defects with antibiotic-impregnated autogenic cancellous bone grafting.

Between January of 1991 and December of 1993, 36 patients who had tibia fractures complicated by small infected tibia defects were treated at the authors' service. The group included 30 men and 6 women whose average age was 36.5 years (range, 18-72 years). The average follow-up period was 3.7 years. By using the Cierney-Mader staging classification of chronic osteomyelitis, 26 of 36 patients (72%) were stage 4A and 10 of 36 patients (28%) were stage 4B. Ten patients required muscle transfer. All patients were treated with a two-stage protocol. In the first stage, antibiotic-impregnated polymethylmethacrylate bead chains were used to obliterate the debrided osseous defect. In the second stage, the beads were removed, and the defects were reconstructed with antibiotic-impregnated autogenic cancellous bone graft. The time between the first and second stage was 2 to 8 weeks for patients without muscle transfer and 8 to 12 weeks for the patients with muscle transfer. The bone defects ranged from 2 to 4 cm. Wound healing and bony union were achieved in all patients. Only two patients had recurrent infections. The infection arrest rate was 94.4%. Minor pin tract infection of the external skeletal fixation was seen in two patients. Two patients developed skin rashes secondary to antibiotic therapy. Radiographs at an average follow-up of 3.7 years showed good consolidation and hypertrophy of grafted bones in all patients. After 3 to 5 years of follow-up, our results suggest that the use of impregnating antibiotics have no adverse effects on autogenic cancellous bone graft incorporation and may help to eliminate infection. This treatment protocol provided rapid recovery from osteomyelitis. The use of antibiotic-impregnated autogenic bone graft seems to be an effective and safe method for the management of small infected tibial defects.

Antibiotic Impregnated Bone Graft

Antibiotic Impregnated Bone Graft