|Year : 2016 | Volume
| Issue : 1 | Page : 17-22
Treatment of open fractures of the tibia with a locked intramedullary nail with a core release of antibiotics (SAFE DualCore Universal): Comparative study with a standard locked intramedullary nail
Department of Orthopedic Surgery, Reconstruction Unit, Hospital Garcia de Orta, Almada, Portugal
|Date of Submission||25-Nov-2015|
|Date of Acceptance||05-Apr-2016|
|Date of Web Publication||17-May-2016|
R. Margaridas, 48, Herdade da Aroeira, 2820 563 Charneca da Caparica
Source of Support: None, Conflict of Interest: None
Introduction: The SAFE Dualcore Universal Nail is an interlocking nail with an antibiotic cement core. We compared the clinical and radiological results with a standard interlocking nail for treating open fractures of the tibia.
Materials and Methods: Prospective, controlled cohort trial, including thirty patients with open fractures of the tibia. Patients were divided into two groups according to the treatment method: Group I (STD), consisting of 14 patients treated by delayed interlocking standard nailing, after an antibiotic treatment and bed rest. Group II (SAFE) had 16 patients treated with an interlocking intramedullary nail with a core of polymethyl methacrylate cement with antibiotics. Five of these were temporarily stabilized with an external fixator. We added vancomycin (2 g) and flucloxacillin (2 g) to the bone cement in the core of the nail. The two groups were similar on demographic data (age, gender), fracture, and extent of the wounds (P > 0.05). The mean follow-up was 2.4 years (5 months to 4 years) for the STD group and 2.1 years (4 months to 3 years) for the SAFE group.
Results: Fifteen of the 30 patients had positive cultures, including 13 cases growing Enterobacter, Enterococcus, Pseudomonas, and methicillin-susceptible Staphylococcus aureus (MSSA) groups. The infection rate was significantly more in STD at 43% (6/14 patients) compared to SAFE 6% (1/16 patients), (P = 0.02). Healing times was significantly more for STD group, at an average of 7.5 months (3-18 months) compared to 4.5 months (2-8.5 months) for the SAFE group (P = 0.02). The complication rate was 64% (9/14) in the STD group and 25% (4/16) for the SAFE, including the infection rate, a statistically significant difference (P = 0.03). The six infected STD nailing cases were salvaged with antibiotic coated cement nails, five of which healed. Infection recurred in the sixth case and was treated with the Ilizarov method.
Conclusion: SAFE nails had lesser infection, faster consolidation, and fewer complications compared with standard nails in treating open fractures of tibia. We can choose the type and dose of antibiotics eluted by the nail. The SAFE DualCore Universal nail is mechanical stable as well as biologically active. It allows fixation of intermediate bone segments, shortens hospital stay, healing time, and reduces the cost of treatment.
Level of Evidence: Level III.
Keywords: Bone infection, cement with antibiotic, intramedullary nailing, open fracture, osteomyelitis, tibia
|How to cite this article:|
Craveiro-Lopes N. Treatment of open fractures of the tibia with a locked intramedullary nail with a core release of antibiotics (SAFE DualCore Universal): Comparative study with a standard locked intramedullary nail. J Limb Lengthen Reconstr 2016;2:17-22
|How to cite this URL:|
Craveiro-Lopes N. Treatment of open fractures of the tibia with a locked intramedullary nail with a core release of antibiotics (SAFE DualCore Universal): Comparative study with a standard locked intramedullary nail. J Limb Lengthen Reconstr [serial online] 2016 [cited 2019 Jul 18];2:17-22. Available from: http://www.jlimblengthrecon.org/text.asp?2016/2/1/17/182571
| Introduction|| |
Bone infections challenge the orthopedic surgeon and are difficult for the patient. We estimate that infection complicates an average of 1% (range: 0.7-4.3%) of all orthopedic procedures. The incidence is increased in the presence of implants. ,, Bacteria adhere to implants and produce a biofilm which prevent the penetration of antibiotics and lead to infection. 
We reviewed 176 postoperative infections in 20,000 surgeries (0.9%) over 15 years in our department. Thirty-five percent of these were in long bones of lower limb.
Open fractures have a higher risk of infection after internal fixation: from 5% in Gustillo Type I to 50% in Gustillo Type III. ,, Converting external to internal fixation has a higher (40-70%) risk of infection when the external fixator is used for more than 2 weeks. 
Antibiotic-releasing implants have many advantages in the treatment of these disorders. They allow control of infection with the local release of high doses of antibiotics. They provide stability for immediate mobilization and prevent many complications of other methods of fixation.
These devices are available with different vehicles of antibiotics, including polymethyl methacrylate (PMMA), , polylactic acid,  and hydrogels.  The PMMA cement loaded with antibiotics is one of the oldest and most widely used methods for this purpose. ,
Ender nails  and interlocked nails covered with PMMA cement with antibiotics  have been used. However, such devices are mechanically weak and cannot allow immediate weight bearing. The procedure to prepare it on the table is time-consuming. Uneven size of the nail can cause it to jam in the canal. Decoupling of the thin layer of cement into the canal can occur while removing the nail. Fracture or bending of the small diameter nail is known.
Fuchs et al.  described a nail coated with a layer of reabsorbable polymer with gentamicin to prevent infection in open fractures. Though their device shows promise, its antibacterial spectrum is limited as is its short duration of elution.
To overcome infection problems in open fractures, we developed a new nail which we are using since 2009 [Figure 1].  DualCore refers to its double core of antibiotic-impregnated cement with a metal rod in its center. This combination gives more resistance to both acute bending and fatigue.
The metal core is inserted into the cement before polymerization. Central placement at the fracture ensures that proximal and distal locking holes are free.
Multiple locking holes release the antibiotics and also fix the comminuted fragments. We called it SAFE nail, an acronym for "self-releasing antibiotic fixation endomedular nail" [Figure 1].
Jigs help lock four screws proximally and distally and lock intermediate segments as well.
Mechanical testing showed that the SAFE nail had 220% more resistance than the Grosse nail and withstood more than 1.5 million cycles of load. This was equivalent to walking full weight bearing without union for 10 months. In vitro tests with 2 g of vancomycin showed antibiotic release at 14 times the minimum inhibitory concentration (MIC) for more than a year.
The aim of this study is to compare the clinical and radiographic results of SAFE nail with a standard interlocking nail for the treatment of open fractures of the tibia.
| Materials and Methods|| |
We designed a prospective controlled cohort study from 2009 to 2012 including thirty patients with open fractures of the tibia. Patients were divided into two groups according to the treatment method. Both groups were treated initially by debridement, suture, and intravenous 1 g of cefazolin and 80 mg of gentamicin for 1-2 weeks.
Group I (STD), comprising 14 patients were temporarily immobilized with a plaster cast or traction and then treated with a interlocking standard Grosse or T2 nails.
Group II (SAFE) comprising 16 patients were temporarily immobilized with cast 11 or an external fixator 5 and then were treated with a SAFE nail.
Soft tissue injuries in Gustillo Type III lesions were treated immediately or during the first week with musculocutaneous flaps, before nailing.
Conversion to nailing done after stabilization of soft tissue lesions posed less risk of deep infection. This took from 7 to 14 days in both groups: earlier in Gustillo Type I and II lesions and later in Gustillo Type III.
Both groups received prophylactic antibiotics for 48 hours and were discharged on the 3 rd day after partial weight bearing mobilization. Full weight bearing was permitted with crutches after three cortices showed healing on X-rays. The preparation of the SAFE nail is a 10 min procedure. A cement gun injects a mixture of cement and antibiotics inside the nail. A metal rod is inserted in the middle of the soft cement before polymerization, forming the "DualCore." 10 of the 16 cases treated with the SAFE nail had a combination of flucloxacillin and vancomycin where bacteriologic examination was negative. Gentamicin alone in 3, combination of meropenem and gentamicin, vancomycin, and meropenem alone in one each were used after culture.
The two groups were matched for age, gender, mechanism of injury and Gustilo classification. In STD group, the mean age was 40 years (22-77). In SAFE group, mean age was 47 years (18-74) (P = 0.31). In STD group, there were 9 male (64%) and 5 female (36%) and in SAFE group there were 14 (87%) male and 2 (13%) female patients (P = 0.18).
The most common mechanism of injury in all of the patients was motorcycle or car accident. A2 and B2 (AO) were the most common types of fractures in both groups.
Six fractures were Type I, seven Type II, and one was Type IIIA for STD group. Four were Type I, six Type II, and IIIA each in the SAFE group, (P = 0.14).
Ninety percent of the fractures occurred at the middle one-third of the tibia in both groups.
The mean follow-up was 2.4 years (5 months to 4 years) for the STD group and 2.1 years (4 months to 3 years) for the SAFE group (P = 0.19).
| Results|| |
In the STD group, six of the fourteen patients developed a postoperative infection with active fistulae [Figure 2]. Serratia, Enterobacter, Enterococcus + Proteus, MSSA, methicillin-resistant Staphylococcus aureus, and mixed flora were identified as causative. Five patients were operated later with a SAFE nail with appropriate antibiotics in five cases, four of which were cured. In one case, the infection recurred and was treated with the Ilizarov method.
|Figure 2: This was a 24-year-old man who was run over by a car with open fractures of both legs. He was operated with standard T2 interlocking nails and 1 month later, a fistulae appeared on the right leg and bacteriology revealed an Enterobacter cloacae infection (a and b). We removed the nail, cleaned the medullary canal with the RIA system, and introduced a second generation SAFE nail with meropenem and vancomycin, antibiotics guided by the sensibility tests (c). One month after surgery shows cure of the infection and patient doing full weight bearing (d)|
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Another case was treated with antibiotics continuously until the fracture healed. The nail was removed and infection healed in 8½ months. The antibiotics were guided by AST and included gentamicin in two cases, meropenem in one, and a combination of vancomycin with meropenem and with flucloxacillin in other two cases.
In the SAFE group, one MSSA and two mixed flora were detected in the patients where external fixation was used previous to the nailing. Pseudomonas aeruginosa, Enterococcus faecalis, and Enterobacter + Pseudomonas were grown in patients subjected to traction. All these patients have healed without visible infection.
One of these patients developed infection after SAFE nailing. The organism was Streptococcus viridans resistant to gentamicin, the preventive antibiotic introduced in the nail. This patient was operated again using a SAFE nail with flucloxacillin and cured uneventfully.
The infection rate after nailing was 43% (6/14 patients) for the standard group and 6% (1/16 cases) for the SAFE group, a statistically significant difference (P = 0.02).
The time to three cortical bridging was a mean of 7.5 months (3-18) for the STD group. For the SAFE group, the mean time to healing was 4.5 months (2-8.5), a statistically significant difference (P = 0.02).
The overall complication rate was 64% (9/14 cases) for the STD group and 25% (4/16 cases) for the SAFE group, a statistically significant difference (P = 0.03). In STD group, this included one transient common peroneal nerve palsy, one knee stiffness, and six cases of nail infection. These needed several surgical interventions, one of them leading to chronic fistulae.
In the SAFE group, we had a fracture of a first generation nail and a nail infection, both converted to a second generation SAFE DualCore nail, leading to consolidation and control of the infection.
| Discussion|| |
Intramedullary nailing after external fixation is in use since 1970's for open tibial fractures. , Reamed interlocking nailing in open tibial fractures has given disappointingly high rates of infection.  Unreamed nailing has been used for Gustilo Types I, II, and III open tibial fractures with controversial results. 
PMMA cement spacers or beads impregnated with antibiotics have been used since 1970 , in the treatment of bone infection. It is an effective method for prolonged local administration of high doses of antibiotics, while maintaining minimal or undetectable systemic levels. ,
The release of antibiotic contained in PMMA cement or other carriers in direct contact with the tissues follows a biphasic pattern with a high release phase for about 12 h, followed by a plateau release phase of variable length, some authors reporting levels above MIC for 6-8 months. ,,,,,,,,,
Our tests have also shown that the elution from a nail filled with PMMA impregnated with 1 g of vancomycin remained between seven and 12 times MICs. Higher doses of antibiotic release can be achieved with high amount of antibiotic in the cement.
Furthermore, the release of the antibiotic through the holes of the nail controls the level as a continuous and constant concentration, avoiding the initial peak of release observed when the cement is in full contact with the tissues, which could be associated with some described cases of toxicity. ,
Meta-analyses have shown that patients who received locally delivered antibiotics as prophylaxis, in addition to systemic antibiotics, had significantly lower infection rates than those receiving only systemic antibiotics.
For the most severe cases (GAIII B and C), the incidence of infections fell from over 31% with systemic antibiotics only to under 9% with the addition of local antibiotics. Given the severe consequences for patients and health care systems of such infections, these findings support an antibiotic prophylaxis regimen including locally delivered antibiotics. 
Antibiotic-coated interlocking nails are usually made with nails of 8-10 mm diameter. These may not have adequate resistance to fatigue and bending forces. The cement around such nails is prone to decoupling and jamming during insertion and extraction. 
The use of an interlocking nail covered with a thin polylactic acid film with gentamicin, releases the antibiotic with a biphasic pattern of short duration, most of it during the first 48 h and has a limited spectrum of coverage. 
The SAFE nail can be as thick as 12 mm since the cement is inside the nail. This avoids the problems of stability and cement debonding. Reinforcement with a metallic rod inside the cement provides a much higher resistance to bending and fatigue. 
We can also choose the antibiotic, more than one if necessary, and graduate the concentration to be released by the amount introduced in the cement. The added advantage is that the release can last as long as a year as shown in our in vitro tests. 
This study had six cases of Gustilo Gr III fractures in the SAFE group as compared to only one in the STD group. We did not have the confidence of using a large diameter nail in Gustillo Type III injuries due to an increased risk of infection, whereas the SAFE nail gave us that confidence.
Only one patient in 16 (6%), treated with the SAFE nail developed a deep infection due to an agent resistant to gentamicin, the antibiotic used at that time in the cement.
This infection healed after exchange of the SAFE nail for another with flucloxacillin, the antibiotic guided by antibiotic susceptibility testing (AST).
In our present study, the use of a standard interlocking nail lead to deep infection in 6 of the 14 patients (43%). Most of those infected nails were changed to a SAFE nail with appropriate antibiotics directed by AST.
Time to union was significantly shorter and the overall complication rate was significantly lower when a SAFE nail was used.
| Conclusion|| |
Despite the small sample size of this comparative study, the preliminary finding of advantages of the SAFE nail is very encouraging.
The procedure is simple and can be performed quickly. The nail is 2.2 times more resistant than the Grosse nail. It is possible to interlock intermediate fragments. There is a possibility to choose the right antibiotics and dose. With 2 g of antibiotics, the release is more than 14-fold the MIC throughout the time of implantation of the nail. Prevention of infection and the ability to ream and use a large diameter nail with increased stability lead to a faster consolidation. The clinical results are excellent, with a lower infection rate and with less hospital stay and treatment costs.
We have used a new generation of implant, one which is biologically active, with greater advantages compared with existing methods of treatment of open fractures. It is better than using standard interlocking nails or conversion of external to internal fixation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]