Combination Therapy With Vancomycin-loaded Calcium Sulfate And Vancomycin-loaded PMMA In The Treatment Of Chronic Traumatic Osteomyelitis

Background:Chronic traumatic osteomyelitis is usually definited as chronic infection of the bone,caused by open fracture,close fracture,firearm injuries,and contamination in the other orthopeadic surgery.It mainly includes chronic posttraumatic osteomyelitis and chronic postoperative osteomyelitis.Chronic posttraumatic and post-operative osteomyelitis is a refractory disease and a great challenge to the the traumatic orthopeatics,which usually requires treatment with antibiotics and debridement treatment.However,persistent infection or recurrence of infection may occur after the above treatments.In recent years,the antibiotic therapy and the surgical treatment had significant improvement,but the long-term recurrence rate of chronic osteomyelitis was still up to 20 %.Vancomycin-loaded calcium sulfate local delivery system and vancomycin-loaded polymethylmethacrylate(PMMA)local delivery system have been widely used in the treatment of chronic traumatic osteomyelitis,andgained a good therapeutic effect.However,with the extensive application of them,their own disadvantages have been revealed,and they also have their Inherent advantages.Currently,the vancomycin-loaded calcium sulfate local delivery system or vancomycin-loaded PMMA local delivery system was often separately applied in the treatment of chronic osteomyelitis,whether in basic research or clinical research.However,it was rarely reported that the safety and effectiveness of combination therapy with vancomycin-loaded calcium sulfate and vancomycin-loaded PMMA in the treatment of chronic post-traumatic and postoperative osteomyelitis.Objective:In this clinical study,we mainly evaluated the safety and effectiveness of combination therapy with vancomycin-loaded calcium sulfate and vancomycin-loaded PMMA in the treatment of chronic post-traumatic and postoperative osteomyelitis,comparing with vancomycin-loaded PMMA.And then,we also evaluated the effectiveness of the induced membrane technique in the treatment of bone defect caused by chronic traumatic osteomyelitis.Methods: Seventy-seven patients suffering from chronic posttraumatic or postoperative osteomyelitis of the lowerextremities were included in the retrospective study.The patients were assigned to the study group of the combination therapy with vancomycin-loaded calcium sulfate and vancomycinloaded PMMA or the control group of the vancomycin-loaded PMMA.Preoperatively,all patients of the two groups received combinations of two kinds of antibiotics for one week in order to achieve better control of infection,whether or not the result of the bacterial culture was informed.After that,all thepatients in the two groups underwent two stage surgical treatments.In the first-stage treatment,the surgical treatment of infectionwas performed under astandard protocol,with multipleconsecutive operative steps:removal of the internal fixation material,debridement of infected soft tissue andnecrotic bone tissue,resection of sclerotic bone within the infected site through high-speed burr,washing the wound with wound pulse irrigation system,obliteration of dead space with vancomycin-loaded PMMA spacer or combination PMMA spacer with vancomycin-loaded calcium sulfate pellets and vancomycin-loaded PMMA spacer,implantation of drainage tube,wound closure,re-fixation if necessary.Hematological parameters,eradication of infection,rate of infection recurrence and reoperation rate were evaluated during the follow-up after the first stage of surgical treatment.The second stage of treatment was performed on all the patients with eradication of infection six weeks to eight weeks after the first stage treatment.In the second stage of treatment,after incision and separation of soft tissue layer-by-layer with caution,the induced membrane was incised with great care to remove PMMA spacers,and then the reconstruction of the bony cavity was usually autogenous cancellous bone only,or combination with allogeneic cancellous bone or bone substitutes.After the bone grafting,the induced membrane was carefully sutured,the drainage tube was embedded into the wound,and the the incision was sutured layer-by-layer.Some of the patients with bone nonunion or with a high risk of fracture after surgery were treated with internal fixation or external fixation.The recurrent infection of bone graft recipient site,bone healing of bone graft recipient site and limb function were were evaluated during the follow-up after the second stage of surgical treatment.Results:In the retrospective study,the patients were followed up for an average of 26 months(range,12 months~46 months)after the first-stagesurgical operation.In the study group of combination therapy with vancomycin-loadedcalcium sulfate and vancomycin-loaded PMMA,all the patients revealed complete calcium sulfate resorption at an averageof 6 weeks(range,30 days~60days).In the study group,infection was primarily eradicated in 87.18 %(34 of 39)of patients and re-operation rate of 12.82 %(5 of 39)after the first-stage surgery.Five patients underwent further surgical operation in the study group.Three cases achieved infection eradication in the recurrent three cases,with asecondary infection eradication rate of 94.87 %(37 of 39).There was no persistent infection in the study group.In the control group of vancomycin-loaded PMMA,infection was eradicated in 68.42 %(26 of 38)of patients and re-operation rate was 31.58 %(12 of 38)after the first-stage surgery.Twelve patients in the control group underwent further surgical operation.Four cases achieved infection eradication in these cases who suffered from persistent or recurrent infection,with a secondary infection eradication rate of 78.95 %(30 of38).There was primarily higher infection eradication rate in the study group after the first-stage surgery(combination therapy group,87.18 % vs PMMA group,68.42 %;P?0.05).There was higher secondary infection eradication rate in the study group after repeat operation due to persistent infection or recurrent infection following by the first stage surgery(combination therapy group,94.87 % vs PMMA group,78.95 %;P ? 0.05).However,there was lower persistent infection or recurrent infection rate in the study group after repeat operation because of persistent infection or recurrent infection following by the first stage surgery(combination therapy group,5.13 % vs PMMA group,21.05 %;P ? 0.05).There was higher re-operation rate because of persistent infection or recurrent infection following by the first-stage surgery in the control group(PMMA group,31.58 % vs combination therapy group,12.82 %;P ?0.05).There was higher complications rate after the first-stage surgery in thecontrol group(PMMA group,28.95 % vs combination therapy group,10.26 %;P<0.05).The results of blood tests revealed that there was no hepatotoxicity and nephrotoxicity in the study group and the control group during the first-stage surgery.In the second stage treatment,a total of 48 patients with infection eradication in the two groups were underwent surgical reconstruction of bone graft.The plate internal fixation was performed on 30 cases after the reconstruction of bone graft,and the external fixation was performed on 10 cases after the reconstruction of bone graft.Eight patient did not need internal fixation or external fixation after the reconstruction of bone graft.The mean follow-up after the second stage treatment was 18 months(range,12 months ~ 24months).There was no recurrence of infection in bone graft recipient site.It averagely took 6 months for complete bone healing in bone graft recipient site by radiographic examination.At the end of the follow-up,it was allowed full or partial weight-bearing for the affected limb,the gait of the affected limbwas basically normal,and there was no pain in bone graft recipient site.Conclusion: Compared with vancomycin-loaded PMMA,the combination therapy with vancomycin-loaded calcium sulfate and vancomycin-loaded PMMApossibly achieved more effective control of infection in the treatment of chronic traumatic osteomyelitis through their synergistic effect.In the treatment of chronic traumatic osteomyelitis,this strategy combining vancomycin-loaded calcium sulfate with vancomycin-loaded PMMA can effectively improve the rate of infection eradication,reduce the rate of persistent infection or recurrent infection,reduce the rate of reoperation due to persistent infection or recurrent infection,and reduce the incidence of complications.The immediate structural stabilization and higher concentration of antibiotic at the local site of chronic traumatic osteomyelitis may beachieved through thecombination of biodegradable andnon-biodegradable devices in the treatment of chronictraumatic osteomyelitis.The induced membranestechnique is effective in the treatment of bone defect due to chronic traumatic osteomyelitis.