Infection of bone represents a major challenge in orthopaedic surgery. Chronic cases are distinguished by necrosis of parts of the osseos structures. It is generally accepted, that sequestered bone comprises bacterial colonies that show inherent resistance to both host defence mechanisms and antimicrobial chemotherapy, leaving thorough removal of all necrotic tissue a prerequisite for cure. The resulting dead space needs to be filled – defects require reconstruction. Bone grafting is a well established procedure with well documented success, however, autologous bone is available only in limited amounts and recurrence rates are still high. Availability of allograft bone is unlimited but rarely used in florid osteomyelitis since surgeons fear grafts being at risk to become a focus of ongoing infection. Fresh frozen allogeneic bone contains bone marrow consisting of fat and necrotic cells. Fat is eliciting an inflammatory response that together with immunological reactions against cell membranes may create an environment promoting bacterial growth with the necroses as a growth medium. Removing bone marrow lowers the risk of infection. When using allograft bone in sites with high risks of infection it therefore should be free of all components of bone marrow.

Highly purified allograft bone, consisting of collagen and minerals as autologous bone, is unlikely to initiate or nourish a florid infection; however, the matrix surface may represent a substratum for adherence of bacteria with formation of biofilms. To avoid bacterial adhesion the matrix may be loaded with antibiotics. It has been shown that purified bone is capable of storing huge amounts of antibiotics for prolonged periods of time. This capacity offers the possibility to use allograft bone not only as a filler but the same as a carrier for antibiotic delivery.

In chronic osteomyelitis our most obstinate opponents are not the familiar planktonic pathogens but their phenotypically different sessile forms embedded in biofilms. Those require up to 1000 fold higher concentrations of antibiotics for elimination than their planktonic forms. Debridement removes the predominant amount of bioburden but some colonies disrupted from the biofilm during manipulation may find new habitats in niches of the site and cause recurrence after an indefinite period of time. Levels reached by systemic antibiosis or local therapy with commercially available antibiotic carriers mostly are not effective in eliminating biofilm remnants. Bone impregnated with high loads of vancomycin or tobramycin may provide for high local antibiotic concentations for several weeks (> 1000x MIC) that are likely to eliminate not only planktonic bacteria but also detached biofilm clusters. Allograft bone may be impregnated both in cancellous and cortical form, morsellized or structural. Indications for their use are all forms of chronic bone infection, including osteomyelitis, infected pseudarthroses, deeply infected diabetic feet and infected total joint replacement.

Osteomyelitic lesions and pseudarthroses of long bones may successfully be treated using antibiotic loaded allograft bone, providing dead space management, antibiotic delivery and reconstruction of deficient areas at the same time. As long as local antibiotic levels are higher than the dosage required for eliminating biofilm fragments no contamination of simultaneously implanted alloplastic material needs to be feared.

Infection of a total joint replacement (TJR) is considered a devastating complication, necessitating its complete removal and thorough debridement of the site. Usually at least two surgical interventions and antibiotic treatment within a period of several months are estimated being required for a favourable outcome. 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 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%, whereas there are no significant differences between revisions with or without antibiotic loaded cement, with short or long term antibiotic therapy, with or without the use of spacers and other differences. On the other hand a literature review of Jackson and Schmalzried (CORR 200) 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. For total knee replacement Jaemson et al. (Acta 2009) could show that the overall success rate in eradication of infection was 73–100% after one-stage revisions. It may be calculated, that adding a second one stage procedure for treating the failed cases the overall result with two operations may improve to > 95%, an outcome which is at least as good as the best results after two stage revisions, while requiring only one surgical intervention for the majority of cases.

Spacers have been proven to be useful for improving final functional results compared to temporary resection; however, concerning infection control no benefit could be shown. Dead space management is performed comparably effective by a new prosthesis as with a spacer. In addition a definitive prosthesis is providing increased stability, which a spacer does not. As long as protection against colonization is granted by high local antibiotic concentrations a prostheses is likely to provide better functional results than a spacer.

These results suggest, that the major factor for a successful outcome with traditional approaches may be found in the quality of the 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.

One stage exchange provides marked reduction of patients discomfort and costs but is performed only rarely due to a multitude of risks and disadvantages, related to the mandatory use of antibiotic loaded cement for fixation. Cemented revisions generally show inferior long term results compared to uncemented techniques; the addition of antibiotics to cement reduces its biomechanical properties. The release of antibiotics from cement is too short-lived and concentrations are too low for reliable eradication of eventually remaining pathogens, especially when they are embedded within biofilms. PMMA has been shown to be the ideal substrate for bacterial attachment and replication of sessile bacterial phenotypes. Aging cement releases antibiotics in subinhibitory amounts, leading to antibiotic resistance of adherent bacteria even years after implantation. 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 in such a case. On the other hand it should also have potential of a good long term result in case of success. Cemented systems seem to be less likely for that purpose since efficient cementing techniques will result in tight bonding with the underlying bone. Eventual removal such will be time consuming and possibly associated with further damage to the osseous structures.

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 100 fold 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 which in case of a failure markedly facilitates their removal. There is reduced risk of creating resistances since the stored antibiotics are eluted completely and elution is terminated after several weeks.

Based on this technology new protocols for one stage exchange of infected TJR have been established, both for hips and knees. Bone voids surrounding the implants are filled with antibiotic impregnated bone graft; uncemented implants are 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. The favourable results have initiated extension of the technique to simultaneous reconstruction of large septic defects using impregnated bulk allografts.

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. One stage revision such should be at least comparably save as multiple stage procedures, taking advantage of the obvious benefits for patients and economy.