Tibial fractures shaft fractures are the most common long bone fracture.1,2 Because of the lack of anterior soft tissue coverage, the tibia is the most common site for open fractures.3 Accordingly, studies have shown that the tibia is also the most frequent site of osteomyelitis.4 For example, in 1 retrospective review of 948 high-energy open tibial fractures, the authors demonstrated a 56% infection rate in which they found bone infection associated with the amount of bone loss, type of bacteria contamination, soft-tissue defects, compartment syndromes, and vascular injuries.5–7 The decreased soft tissue coverage and vascular supply of the tibial shaft make eradication of infection difficult. In this review we will outline our current strategy for management of these complex patients. Although the focus will be on treatment of infected tibial shaft fractures, these techniques could also be applied to other anatomic areas as well.
Central aims for treating infection after fracture fixation that was described in a recent review in Injury included fracture consolidation, eradication or suppression of infection until consolidation occurs, healing of the soft-tissue envelope, prevention of chronic osteomyelitis, and restoration of functionality.8 The 3 phases of infection treatment from a surgical perspective are: (1) debridement, (2) temporary stabilization during antibiotic treatment and infection eradication, and (3) secondary reconstruction.
The first intervention in the treatment of surgical site infection and osteomyelitis in the tibia after fracture fixation is a thorough debridement. Once the area of infection is encountered, debridement is started by excising grossly compromised soft tissue and bone. The goal of surgical treatment is the complete excision of necrotic and infected tissues. We recommend proceeding in a centripetal manner with debridement of skin followed by subcutaneous tissues, then muscle, periosteum and bone.
This can be accomplished with a wide variety of instruments including curettes, rongeurs, and high-speed burrs. In general, infected bone is debrided until the surgeon encounters punctate healthy bleeding bone. There are no scientific guidelines for how much bone to be removed, but in our opinion, similar to oncologic surgery, the surgeon should err on removing bone back to healthy tissue, particularly in the diaphyseal portions of the tibia. Incomplete excision of the infected material can serve as a nidus and pathway for recurrent infections.
Several serial debridements may be necessary to obtain a clean wound free from devitalized tissue. Serial debridements until cultures are negative (borrowing from treatment of acute open tibial fracture) may give the surgical team more confidence that local infection control has been achieved.9
Often times, substantial portions of the bony and soft tissue envelope of the tibia need to be removed to achieve source control of the infection (Figs 1, 2).
Local delivery of antibiotics using antibiotic laden bone cement beads or a spacer is an effective way of delivering local antibiotics directly to the wound bed.10–12 Borrowing from treatment of infected total joint arthroplasty, high doses of antibiotics are added to the cement to achieve high cement porosity and minimum inhibitory concentration (MIC) killing power based on the concentration gradient between the antibiotic beads or spacer and the host tissues.13
IMPLANT RETENTION AND REMOVAL
If deep infection occurs and the fracture is healed, we typically remove the implants from the tibia. Exceptions include implants that are remote to the infection site or otherwise thought to not be involved. When in doubt we tend to err toward removing the implants.
Infection in the setting of nonunited fracture presents a much more challenging and common problem. Infection is a known risk factor for nonunion and 50% of infections occur in the first 3 months so it is common for union to not have occurred when deep infection presents.14 If the implants are loose and there is gross mechanical instability at the fracture site, implant removal should typically be performed as it is no longer providing the adequate support necessary to achieve union. However, more often there is incomplete union or the implants are intact, but it is early enough that union would not yet be expected.
There is controversy regarding implant retention in this common scenario. In these situations, there is some support to attempt retention of hardware in the setting of a nonunited fracture with active acute infection. Success rates using this approach show a 71% union rate with debridement, hardware retention, and culture specific antibiotics for deep wound infections within 6 weeks of fracture internal fixation.15 Open fracture or presence of an intramedullary nail were risk factors that substantially increased the rate of failure with implant retention and treatment with systemic antibiotics.16 Implant retention is appealing as it is requires less extensive surgery and leaves the fracture with a mechanical construct that could at least theoretically heal.
The argument for implant removal is that once the biofilm is setup on the hardware then it will be very unlikely to clear the infection without eventual implant removal and the persistent infection may prevent union. The downside of implant removal is of course that the fracture is then mechanically unstable and further surgery will be needed to definitively repair the fracture. Temporary fixation with an external fixator or antibiotic nail or plate (see below) is often performed after hardware removal.
An intermediate position is implant “swapping” where the implants are removed, debridement performed, and then new implants are placed. The new implants can be placed during the same surgery where the old implants are removed or at a later debridement during the same hospital admission. This technique has anecdotally been particularly successful in upper extremity infections. If serial debridements are performed the plate can be changed out more than once. In all of these cases, if there is any doubt, we err on the side of implant removal.
TEMPORARY STABILIZATION DURING TREATMENT OF INFECTION
There are 3 options for temporary stabilization of the tibial shaft fracture during the interval between initial debridement and definitive fixation. Usually during this period antibiotic treatment is administered and any soft tissue envelope defects are addressed with local rotational or free tissue transfer.
Inherently stable fractures with relatively small bony defects and no soft tissue envelope defects can be treated with splint or cast stabilization during the interval before definitive fixation. However, this clinical scenario is uncommon in the treatment of infected tibial shaft fractures as mechanically unstable infected nonunions are more common. Most patients will require more robust temporary fixation during the treatment period.
At our center we have used antibiotic bone cement coated Ilizarov rods for the treatment of patients requiring temporary stabilization (Fig. 3).17 An advantage of this technique is the potential for local antibiotic delivery combined with some additional stability provided by the Ilizarov rod. This treatment also does not interfere with exterior soft tissue management procedures such as rotational or free tissue transfer. Usually after soft tissue coverage, patients wear a cast or fracture boot to supplement the stability of the antibiotic nail until later definitive fixation. We prefer this technique as opposed to cement coated antibiotic tibial nails as it reduces the possibility of delaminated cement being left behind in the intramedullary canal due to delamination from the nail.
For larger bone defects with less inherent stability, we tend to use temporary external fixation (Figs 1, 2) which provides not only more bony stability but also provides stability to the soft tissue envelope to encourage soft tissue recovery. One disadvantage of external fixation is that pin tract challenges are a constant concern and the fixator does present more obstruction to the surgeons performing the local or free tissue coverage of the wound.
ANTIBIOTIC BONE CEMENT BEADS
Antibiotic laden bone cement (polymethylmethacrylate) beads are powerful agents for local antibiotic delivery (Fig. 2). They allow high local temporary concentrations of antibiotics and can be fashioned by the surgeon with multiple heat stable antibiotics dependent on the biogram of the infecting organism These antibiotic beads are placed into the surgical debridement wound and the wound is closed or if unable to be closed sealed with a barrier dressing or wound VAC. The beads stay in the wound and are removed before definitive closure. Beads that are placed into the intramedullary canal are usually removed before they become incapsulated in scar which could make bead removal more difficult.18 These beads are often placed in chains to not only fill the dead space before a reconstructive procedure, but several clinical trials have supported the efficacy of beads for local and concentrated antibiotic administration.19–21 Because of the difficulty of late antibiotic bead removal, we typically use antibiotic laden bone cement beads only during the debridement phase of the treatment when the patient is going back to the operating room for serial debridements (Fig. 2). To fill dead space at the final debridement we usually place an antibiotic laden bone cement spacer which is easier to locate and remove at later surgeries and also adds some stability to the fracture site.
USE OF ANTIBIOTIC LADEN BONE CEMENT SPACERS
To help manage dead space present after bony debridement and to allow for local delivery of antibiotics, we typically use antibiotic laden bone cement spacers in the treatment of tibial osteomyelitis. These are solid block spacers which may had some intrinsic bony stability but also allow for local antibiotic delivery and a precursor for a Masquelet grafting technique (Fig. 1).22–26 We typically incorporate methylene blue dye into the cement to make the cement easier to visualize during the second-stage nonunion repair.
SOFT TISSUE RECONSTRUCTION
Often times adequate debridement of infected tibial fractures produces defects in the soft tissue envelope that are unable to be approximated for closure. Enlisting a soft tissue microvascular specialist is critical for the evaluation of these wounds. Although rotational muscle transfer is often adequate to obtain wound coverage, a surgeon skilled at both rotational and free tissue transfer is critical for success in managing tibial infection. Fear of soft tissue reconstruction should never prevent adequate debridement of the soft tissue envelope.
When advanced soft tissue reconstruction (rotational or free tissue transfer) is used, we typically will use either an antibiotic-coated rod or external fixator for temporary tibial stabilization. Ring fixators are powerful tools for bone defect management, but they do tend to occlude access to the soft tissues so we place them only after the soft tissue reconstructions have healed.
Along with thorough surgical debridement, systemic antibiotics also play a crucial role in the postoperative eradication of tibial SSI and osteomyelitis. The goal of systemic antibiotic therapy is to eliminate the remaining bacteria in the soft tissues surrounding the bone after debridement has occurred to prevent reinfection. The choice of antimicrobial agent, route of administration, and duration of treatment is often guided by an infectious disease specialist. The organisms must be susceptible, antimicrobial agent must be able to achieve a MIC to the soft tissues, and the patient must be able to tolerate the adverse effect profile of the drug. Empiric broad spectrum IV antibiotics are utilized initially when tibial SSI or osteomyelitis is suspected. Antibiotics typically do not penetrate well into abscesses or devitalized and necrotic bone. Oftentimes, high-dose intravenous antibiotics are needed to ensure MIC in these poorly perfused areas. Staphylococcus aureus, and its methicillin resistant (MRSA) strain, is one of the most common offending organisms in tibial SSI. In patients with a history of methicillin-resistant S. aureus infections or exposure, vancomycin is typically used. In the Torbert et al14 study done at the Shock Trauma Center, the authors found that MRSA can account for more than 50% of S. aureus and 32% of all organisms that cause surgical site infection after orthopedic trauma. In a follow-up study, Montalvo and colleagues quantified the bacteriology in deep SSI after fracture surgery in one institution from 2006 to 2015. Here, the authors identified 48% S. aureus, 40% gram negative rods, and 19% coagulase-negative staph species. Patients studied in the 2011 to 2015 cohort had a decreased incidence of S. aureus species compared with the 2006 to 2010 cohort.27 It should be noted that in around 10% of cases no pathogen is identified.14,27 In our institution, empiric antibiotic treatment usually consists of vancomycin and piperacillin/tazobactam (Zosyn) after the first operative debridement. Otherwise, empirical therapy before the operative debridement is withheld until deep cultures and samples are obtained. Targeted specific therapy is begun as soon as operative cultures and antibiotic susceptibility results are available. The broad-spectrum empiric antibiotics are narrowed to reduce the emergence of resistant organisms.
Given the high rate of recurrence of osteomyelitis, infectious disease specialists and surgeons adhere to a prolonged period of postoperative antibiotics. Traditionally, 4 to 6 weeks of parenteral antibiotics are common after surgical debridement followed by a period of oral antibiotics.28–30 Some studies advise a 12-week course of IV antibiotics if the tibial implants stay in place.31,32 When implants are retained, a biofilm-active antibiotic such as rifampicin for staphylococci species and quinolone for gram-negative bacteria are utilized.33,34 A few prospective studies showed the cure rate of 69% to 100% using a 6-month rifampicin/quinolone combination regimen, especially in early staph infections.35 If the bacteria are resistant to the biofilm-active agents, the surgeon shoulder consider removal of the implants.
Monitoring of inflammatory markers such as erythrocyte sedimentation rate, c-reactive protein, and white blood cell leukocyte as determined by the infectious disease specialist, wound checks and regular radiologic surveillance are often continued until clinical resolution of infection.
DEFINITIVE RECONSTRUCTION AFTER RESOLUTION OF INFECTION
After excision of all compromised devitalized hard and soft tissues, remaining bone defects in the tibia are common. Bone reconstruction is usually a second-stage procedure. At the discretion of the surgeon, one strategy for secondary reconstruction may be simply placement of a new tibial nail with bone grafting of any defects.17,36 We use this strategy typically for smaller bone defects. For larger bone defects, Masquelet reconstruction or bone transport are usually utilized.37–39
Masquelet-induced Membrane Technique for Infected Nonunions With Bone Defects
Bone grafting with a 2-stage approach with an antibiotic-laden spacer and later reconstruction is one option to manage large bone defects. Masquelet and Beque23 have described this technique of using an antibiotic cement spacer-induced membrane and delayed bone grafting (Fig. 4). Here, the polymethylmethacrylate antibiotic cement provides structural support and prevents fibrous tissue growth into the defect. An induced periosteal membrane is formed around the cement spacer, which adds osteogenicity, vascularity and mechanical stability for the subsequent graft material.22,24–26 Second-stage cancellous bone grafting is performed after 6 to 8 weeks. One study showed reduced reinfection rates when the bone graft is mixed with local antibiotics.40
This technique is advantageous due to the fact that the time it takes to fill the defect with solid bone does not depend on the size of the segmental defect.
This technique has been used with success and has been found to have low complication rates for both traumatic and infection-related bone defects.24–26 This technique can either be accomplished around a tibial nail or with ring fixator application.
The Ilizarov method of external fixation utilized a ring fixator that allows for correction of length, rotation, translation and angular deformities (Fig. 5). This type of stabilization allows the patient to remain ambulatory throughout the duration of treatment and has produced excellent clinical outcomes.41–43 Some of the main disadvantages of the ring external fixator include patient discomfort due to bulkiness, lengthy time in the device (average of 9 mo), and a high rate of pin tract infections. Other drawbacks of the Ilizarov external fixation system include ankle joint stiffness, and docking site nonunion or malunion.44 In addition significant clinical experience is needed to judge when to remove the ring fixator to reduce the risk of refracture due to incomplete healing at the time of removal.
Ring fixators are excellent tools for bone transport (Fig. 5). Bone transport involves placement of a ring fixator followed by a corticotomy in either the distal or proximal tibial metaphyseal bone. The intervening free diaphyseal segment is then transported through the tibial defect at a rate of around 1 mm/day until it “docks” with the native tibia at the other end of the defect. This is an extraordinarily powerful technique for managing tibial defects with excellent long-term results. However it does require quite some time for the patient to be in an external ring fixator. We usually tell patients that they will be in an external fixator frame for roughly 1 year after injury when treated with these techniques. It is possible that they may be able to be converted to internal fixation or have the frame removed earlier but this sets appropriate expectations.
Free vascularized bone transfers are another option for the management of isolated tibial bone defects. This approach is typically used with defects >5 to 6 cm. The success rate range from 76% to 97%, but secondary operations are often necessary.45 These transfers are limited in use due to the face that they are technically demanding and incur the risk of donor site morbidity, flap loss, postoperative deformity, stress fracture and the need for extended periods of immobilization.10
CONCLUSIONS AND FUTURE DIRECTIONS
Treatment of infected tibial fractures requires a multidisciplinary team or orthopedic surgeons, microvascular surgeons and infectious disease specialists to obtain a positive outcome. Aggressive operative debridement with a tendency to remove all retained implants in the tibia are mainstays of initial treatment. Antibiotic-coated rods and temporary external fixation can be used for temporary stabilization of tibial shaft fractures during the period of soft tissue reconstruction and infection eradication. After eradication of infection, options for reconstruction include tibial nailing with bone grafting, the Masquelet technique with a tibial nail or ring fixator, or bone transport using a ring fixator.
The authors thank Dori Kelly, MA for professional manuscript editing.
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