Two stage management of long bone infection by using an antibiotic cement-coated locking plate: an outcome of 183 cases

Background The purpose of this study was to evaluate the clinical effect of antibiotic cement-coated locking plate as temporary internal fixation for the treatment of long bone infection in lower extremities . Methods Retrospective analysis the clinical data of 183 patients with lower extremities long bone infection admitted to our hospital from January 2013 to December 2017. All patients were treated with locking plate internal fixation after primary debridement. Antibiotic cement was used to fill the bone defect and wrap the plate. After infection control, bone grafting to reconstruct the bone defect. Results There were 81 cases of femur, 100 cases of tibia and 2 cases of fibula, after the first stage, 16(8.7%) patients had recurrence of infection after the first stage which have to debridement again. 4 tibial infecton patients had poor wound healing, 2 femoral patients had fixation failure, and 1 patient had femoral fracture due to fall down. After a mean time of 32.0 months (range 12 to 66) follow up, the recurrence rate of infection was 14.2% (26/183). Among them, eighteen patients underwent bone grafting after re-debridement, 6 patients received permanent placement of antibiotic bone cement after debridement, and 2 patients refused further treatment and chose amputation. Bone healing was achieved in 175(95.9%) patients in the last follow-up, and the average time of bone union was 5.4 months (range 4 to 12 months). Conclusions Temporary internal fixation with antibiotic cement coated locking plate has good clinical effect in the treatment of lower extremities long bone infection. It does not increase the difficulty of bone infection control. Pay attention to possible difficulty of skin coverage when applied in calves.

Background The purpose of this study was to evaluate the clinical effect of antibiotic cement-coated locking plate as temporary internal fixation for the treatment of long bone infection in lower extremities .
Methods Retrospective analysis the clinical data of 183 patients with lower extremities long bone infection admitted to our hospital from January 2013 to December 2017. All patients were treated with locking plate internal fixation after primary debridement. Antibiotic cement was used to fill the bone defect and wrap the plate. After infection control, bone grafting to reconstruct the bone defect.
Results There were 81 cases of femur, 100 cases of tibia and 2 cases of fibula, after the first stage, 16 Background Bone infection is a major problem in the field of orthopedics. Sufficient stabilization of bone defects after thorough debridement is conducive to infection control. External fixation was considered as the gold standard for the treatment of bone infections [1], which can not only provide stability, but also avoid the presence of foreign bodies in the infected wound and prevent the formation of biofilms which leading to the recurrence of infection [2]. However, external fixation have inherent limitations and many complications, such as pin track infection [3], poor stability, joint stiffness, and some patients can not tolerate the long-term impact of wearing external fixation. In order to make up for the above deficiencies and shortcomings, some scholars have explored the conditions of using internal fixation in bone infection sites. Liporace FA [4] and Conway JD[5] attempted to treat infected bone fractures with antibiotic-impregnated bone cement-coated locking plates, which was preliminarily reported, with small cases and short follow-up time. We report of long bone infection in lower extremities treated with locking plate internal fixation which coated with antibiotic cement, acquired good clinical efficacy for at least one years of follow up, so as to provide a reference for clinicians to apply this method.

Materials And Methods
The study was approved by the Ethics Committee of our hospital, and informed consent was obtained  Table.1 In the first stage, thoroughly debridement was performed, then internal fixation with locking plate and coated with antibiotic cement to stabilize the bone defect, filling the bone defect with antibiotic bone cement for the formation of induced membrane. In the second stage, bone graft to reconstruct the bone defect.
Determined the infection area according to X-rays, MRI and radionuclide examination. The sinus, sequestrum, inflammatory granulation tissue, ischemic sclerosis bone was thoroughly cleared. The medullary cavity was cleared by reaming drill until punctate hemorrhage appeared. The deep tissues were sampled at multiple sites for pathological examination and microbiological examination. A large amount of iodophor, hydrogen peroxide and saline were used to wash the operation area repeatedly during the operation. Bone tissue and soft tissue were continuously removed for 5mm and 2mm respectively. Locking compression plate was used to fix the femur and reconstruction locking plate was used to fix the tibia and fibula. The antibiotic cement (0.5g gentamicin per 40 g of PMMA mixed with 5 g vancomycin) was used to fill the defect area, wrap the plate and screw at the same time, and extend 1-2 cm to the proximal and distal ends to expand the volume of the induced membrane. Free flaps or local transfer flaps were used when it's hard to suture the section directly. Sensitive antibiotics were used after operation according to bacteria isolated, and third-generation cephalosporins were used in culture-negative patients. If the infection recurs, the first segment operation is done repeatly. Patients are encouraged to take the initiative to conduct joint exercise, full weight bearing of the affected limb is forbidden.
At least 6 weeks after primary debridement, the soft tissue condition was good (no swelling, fever, pain and sinus tract), Leukocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) returned to normal, and the imaging examination did not indicate infection, so the second stage operation was feasible. During the second stage surgery, the incision of the former was chosen and the induced membrane was cut longitudinally to protect the integrity of the induced membrane carefully. The bone cement and internal fixation were removed thoroughly, and the bone ends were decorticated. Autogenous cancellous bone was taken from iliac bone and allogenic bone was mixed for patients with large bone defect. Intramedullary nail, locking plate or intramedullary nail-assisted locking plate was selected for final fixation. The induced membrane was sutured carefully, and then the incision was sutured completely.
Follow-up were made every month after the first stage, and every three to six months after the second stage. The review included clinical symptoms and signs of affected limbs (such as swelling, fever, pain and sinus formation), laboratory examinations (Leukocyte count, ESR, CRP), and anteroposterior and lateral X-rays. The recurrence of infection, bone healing and complications were observed and recorded. When the Leukocyte count, ESR and CRP were normal and there was no clinical manifestation of local infection (such as swelling, fever, pain and sinus formation), no recurrence of infection was considered. The bone union time was obtained by X-ray, radiological union was defined as three-sided cortical bridging on two perpendicular X-rays of the defect zone[6].

Statistics
Data analysis was performed using SPSS 23.0 statistical software (SPSS Inc, USA). The measurement data is represented with ranges and the enumeration data is expressed by rate. Enumeration data were compared using Pearson or Continuity Correction chi-square test. and the test level α value is 0.05 on both sides.

Results
After the first stage, 16 (8.7%) cases had recurrence of infection, among them, 12 cases underwent two times debridement, 4 cases underwent three times debridement, and infection was controlled finally. Complications occurred in 7(3.8%) cases: delayed union of tibial incision in 4 cases; complications related to internal fixation in 3 cases: non-infectious femoral fracture in 1 case due to falls; and fixation failure in 2 cases of long segmental bone defect in the middle femur. There was significant difference in the recurrence rate between type A (4/103) and type B (12/68) patients after primary surgery (P < 0.05). There was no significant difference in recurrence rate among different

Discussion
Bone infection is a major problem in the field of orthopedics. Its essence is bacterial biofilms[7], which can resist host immunity and antibiotics [8,9]. Bacteria could easily adhere to the surface of metal surface and formation of biofilm which leads to infection recurrence [10,11]. Therefore, internal fixation is not recommended for bone infections. As widely accepted instrument, external fixator can span the infected area, avoid the exposure of metal foreign bodies, and prevent the formation of biofilms [12]. However, the high incidence of complications such as pin track infection limited its advantage [3]. When the infected site is close to the joint, trans-joint fixation leads to joint stiffness[13], which is not conducive to limb function recovery. The external fixator is bulky and difficult to wear, which affects patients' ordinary life [14]. Long-term wearing of the external fixator also has a negative impact on patients' mental health [15]. Mark [16] reported 11 cases of femur infection treated with plate internal fixation after complete debridement. Alemdar [17] reported that 15 cases of deep infection after lower limb fracture were treated with "non-contact" plate internal fixation on the basis of complete debridement, but no matter how thorough debridement, bacteria still existed [18], residual bacteria formed biofilm on the surface of the internal fixator, resulting in recurrence of infection.
Wrapping with antibiotic bone cement can prevent bacteria from adhering to the surface of the internal fixation, and the antibiotics released from antibiotic bone cement can kill the residual bacteria after debridement, preventing the internal fixation from becoming a new source of infection [19]. Our research applied internal fixations with locking plate which coated with antibiotic bone cement for the treatment of long bone infection. The infection control rate after the first debridement was 91.3%, breaking through the prohibition of internal fixation in the case of infection.
The premise is complete debridement of the bone and soft tissue, followed by good soft tissue coverage, therefore, thorough debridement is the core for bone infection treatment [20,21]. The ideal state of bone and soft tissue can be achieved by thorough debridement, so that the blood supply of tissue provide normal physiological function. The formation of biofilm is prevented by systemic antibiotics and local antibiotics [22][23][24][25]. At the same time, rigid stability is also an important factor for bone infection control [26,27]. Animal experiments confirmed that the infection rate in the unstable group was more than twice as high as that in the stable group [28]. The locking plate provides angular stability and axial stability [29], which provides excellent anchoring in osteoporotic bone, it can also help protect joint function by avoiding trans-articular fixation when bone infection occurs in the metaphysis. In addition, locking plate does not contact with bone cortex and helps to protect periosteal blood supply.
In this study, a total of 183 patients were treated with antibiotic cement coated locking plate. After the first debridement, 16 (8.7%) patients had recurrence of infection, which was manifested as wound nonunion, sinus, and local limb redness, swelling and pain. After postoperative review, the main cause of recurrence was incomplete debridement. After repeated debridement, the infection was controlled and bone reconstruction was carried out smoothly. This study found that the recurrence rate of type B (17.6%) after debridement was significantly higher than that of type A patients (3.9%) (P < 0.05). This finding is consistent with Simpson's prospective study. Simpson [30] found that patients defined as host B had a higher recurrence rate than patients defined as host A, and that host B patients were recommended for more extensive debridement. All 4 cases of local skin delayed union occurred in the lower leg, the condition of local soft tissue is bad due to infection and repeated surgery, resulted in greater tension of incision suture. Therefore, skin flaps are recommended to ensure tension-free suture of incision. Limb elevation and anti-swelling drugs were used after operation. Fracture or loosening of internal fixation is mainly related to weight bearing and accidental falls. Therefore, patients are recommended to walk with crutches without weight bearing or partial weight bearing after the first stage.

Consent for publication
Consent to publish was obtained for the patients or patient's legal guardian whose information appears in this publication.