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Principles in the Management of Infection With Hardware
The management of infections involving hardware is challenging and may potentially lead to complex reconstructive procedures or even devastating amputations. Bacteria can adhere to the metallic hardware or implant and form a biofilm that makes that bacteria resistant to the host immune response and antibiotics.
When there is hardware present in the context of an acute postoperative infection, surgeons face a dilemma. Should they remove the hardware and potentially compromise osseous stability, or leave hardware in place and risk harboring bacteria deep inside? An infection in the proximity of hardware long after osseous union may involve hardware removal without compromising stability. Studies have shown the infection incidence after clean orthopedic surgery to be as high as 6.5% and up to 16% in traumatic fractures.1–9
Successful infection management relies on early diagnosis, appropriate antibiotic therapy, and surgical intervention with a multidisciplinary team consisting of experienced specialists. Achieving osseous stability and optimizing functional outcomes should be the primary goals after eradication of the infection.
With these challenges in mind, we will review recently published consensus statements that provide diagnostic criteria for defining fracture-related infections (FRI) as well as treatment pathways for infection after fracture fixation. Due to the lack of quality studies involving FRI, the AO Foundation and the European Bone and Joint Infection Society created the Fracture-Related Infection Consensus Group and defined FRI, standardized diagnostic criteria, and provided treatment recommendations.10–13 We will review these guidelines in promoting proper diagnosis and management of infections in the setting of hardware postoperatively and then illustrate with a case study.
Understanding Risk Factors and Pathogenesis
Predisposing risk factors will increase the chance of developing infections related to hardware postoperatively. Extrinsic factors include external factors like an open injury, significant soft tissue injury, contamination, and delayed/compromised wound healing.14 Intrinsic factors include immunocompromise, age, diabetes, obesity, alcohol or tobacco abuse, steroid use, malnutrition, medications, previous radiation, and vascular insufficiency.14
Horton and colleagues noted that 35% of 451 patients failed initial surgery from FRI with initial polymicrobial cultures, removal of the implant, and Gustilo-Anderson type IIIB and IIIC injuries.14 Darouiche reported a 1–2% incidence of infection with an initially inserted internal fixation device for closed fractures and up to 30% for open fractures.15 Preoperative factors such as the delayed administration of preoperative prophylactic antibiotics, previous use of external fixation, prior multiple surgeries, and increased operative time can also lead to an increased risk of infection.16–18 Nonunion could be the result of infection preventing osseous healing.16,17
Mechanisms of infection typically occur from seeding or biofilm formation. When there is disruption of the soft tissue envelope, blood vessels, and periosteum that allows bacteria to evade the immune system, seeding can occur either with direct seeding of the implant-bone interface or by hematogenous seeding. Biofilm encloses microorganisms in a polymeric matrix of exopolysaccharide glycocalyx. Here, microbes are protected from antimicrobial agents and host immune responses. This resistance may be related to the reduced growth rate of biofilm microorganisms due to lowered access to metabolic substrates such as glucose or oxygen.19 Timely identification of infection will lead to less morbidity.
The timeframe after initial surgery to infection is also important concerning pathophysiological changes such as biofilm maturation and progression of a deeper infection. FRI are differentiated as early (<2 weeks), delayed (3–10 weeks), and late (>10 weeks) to help aid in treatment decisions.20 Baertl and colleagues studied 117 patients with FRI over a seven-year timeframe with early (n = 19), delayed (n = 60), and late (n = 38) infections and reported results of combination antibiotic therapy based on timeframe classification.21 The most common bacteria reported from these patients were methicillin-sensitive Staphylococcus aureus (39.7%), Staphylococcus epidermidis (17.2%), and gram-negative bacteria (16.4%). Twelve of the cases involved biofilm-active antibiotic resistant bacterial strains.
Trampuz and Zimmerli found earlier infections commonly presented with more severe symptoms like erythema, swelling, and pain and grow more virulent organisms such as Staphylococcus aureus and gram-negative bacilli.22 In contrast, they found delayed and late infections presented with more vague symptoms—such as pain, nonunion, and loosening of hardware—and lack systemic symptoms, and grew less virulent organisms such as coagulase-negative Staphylococcus. Such infections may occur following urinary, respiratory, or gastrointestinal infections.
FRI leads to significant morbidity with a possibly catastrophic socio-economic burden due to prolonged hospitalization, numerous surgeries, long-term antibiotics, and prolonged immobilization. Proper diagnosis of infected hardware, effective antimicrobial management, and appropriate surgical intervention will lead to optimizing patient outcomes.23
Why a Multidisciplinary Team Is Important for Infection Management
Utilize a comprehensive multidisciplinary team approach with a minimum of three disciplines: a surgeon with expertise in bone and soft tissue reconstruction, an infectious disease specialist, and a clinical pharmacist. Additional specialists that should be considered also include radiologists, pathologists, wound specialists, vascular surgeons, rehabilitation specialists, and any other medical specialists to optimize medical management is critical in achieving a successful outcome.11
Other key factors in the multidisciplinary team approach include soft tissue assessment (open wounds and edema), local neurovascular status (vascular insufficiency), baseline blood analysis, and initiation of patient optimization. Systemic targets for optimization include malnutrition, smoking, diabetes and cardiopulmonary status. The multidisciplinary team should regularly review surgical and antimicrobial treatments and adjust accordingly based on culture results and patient optimization. The coordination of treatment of complex revision cases requires a dedicated multidisciplinary team, preferably one with volume experience, to maximize successful outcomes and preserve a functional limb. Continued follow-up should extend to at least 12 months following completion of antibiotic therapy and surgical care.
Making an Early Diagnosis of Hardware Infection
One should suspect a hardware infection when a patient presents with a sinus tract, wound, or drainage over an area with previous hardware implantation. The first step in the workup of a patient with FRI is arriving at a well-established diagnosis.12 Govaert and coauthors recommend stopping antibiotics at least two weeks before obtaining a specimen if possible. Table 1 lists the diagnostic criteria that can be confirmatory or suggestive.10–12
Confirmatory criteria include:
- clinical signs such as fistula, sinus, wound breakdown with communication to bone or hardware;
- purulent drainage from wound or pus during surgery;
- phenotypically indistinguishable pathogens cultured from at least two separate deep specimens during surgery; and
- histopathological presence of microorganisms during surgery (>5 polymorphonucleocytes per high-power field).
Suggestive criteria include:
- clinical signs such as increasing pain without weight-bearing or new-onset, local redness and swelling; increased local temperature; and fever (≥38.3ºC, 101ºF);
- radiologic signs (bony lysis, implant loosening, sequestration, failure of bone healing, and presence of periosteal reaction);
- single deep pathogenic organism from deep tissue sampling;
- elevated serum inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell count (WBC);
- persisting, increasing, or new-onset wound drainage; and
- new-onset joint effusion.
Alternatively, McNally and colleagues outlined a practical guide for clinicians in determining the likelihood of periprosthetic joint infection utilizing a combination of clinical, synovial, microbiologcal, histological, and imaging findings.24
If there is a high clinical suspicion for hardware infection, then obtain baseline complete blood count, CRP, ESR, and imaging. Researchers recommend arthrocentesis in patients with an unexplained increase in CRP when dealing with joint implants.25
Plain films will not provide a definitive diagnosis of hardware infection, but may assist in identifying hardware loosening or fracturing. Computed tomography (CT) scans can visualize sequestration from hardware that is often difficult to visualize on plain radiographs. Cyteval and coworkers reviewed CT, magnetic resonance imaging (MRI), and positron emission tomography (PET) in assessing orthopedic implant infections.26 CT scans were 100% specific, but only 16% sensitive when periostitis was present for hardware infection. With sequestra present, CT scans became 100% specific and 87% sensitive for hardware infection.
MRI can be very specific for soft tissue pathology and it is very sensitive for the extent of bone and soft tissue involvement such as sequestra, cloacae, sinus tract, or subcortical abscesses. The sensitivity and specificity of MRI for the detection of FRI are reportedly 82–100% and 43–60% respectively. However, metallic implants cause MRI scattering that limit clear bone visualization. PET scans are being investigated in assessing hardware infections and show good promise with a sensitivity of 65–94% and a specificity of 76–100%. PET scans only require one scan instead of two, which is seen in white blood cell labeled scintigraphy. In addition to cost and access limitations, one cannot use PET scans within one month after surgery.
Surgical Intervention and Antimicrobial Therapy
Obtaining an early diagnosis of FRI requires obtaining a deep tissue specimen where debridement and either implant retention or exchange will be needed to identify infective organism(s) to direct antibiotic therapy. Table 2 summarizes the primary goals of surgical treatment of FRI, which include fracture consolidation, eradication of infection, healing of the soft tissue envelope, function restoration, and prevention of chronic infection.27 Successful surgical management may require a single or multiple stage process based on the patient’s response to therapy. The two main antimicrobial principles include infection eradication or suppression. The treatment timeframe for antibiotic therapy is not dictated by the depth of the infection or the anatomic location, but will be based on input from the multidisciplinary team members.
Factors that will influence decision-making for removal or exchanging of hardware include the time interval since surgery, stability of the hardware construct, sufficient debridement access (ie, intramedullary nail), infection severity, fracture localization, condition of the soft tissue envelope, and host physiology.
One should debride biofilm, non-viable soft tissues, non-bleeding bone, and non-essential foreign bodies (eg, broken or loose hardware, sutures) after deep tissue sampling.27 Hardware removal will be a judgment call by the surgeon in weighing the benefit of retention to provide osseous stability versus the risk of potentially harboring bacteria. Use separate instrumentation for each deep tissue specimen to lower the risk of cross-contamination.12 Bone debridement should be judicious only to bleeding bone with the assumption that bleeding bone has the ability to heal.28 Low-pressure irrigation of the affected area helps to decrease bacterial load and remove loose debris. After debridement, one can fill bone defects with bone cement with heat-labile antibiotics for direct delivery into the infected site.29 Absorbable bone void fillers with antibiotics are mostly off-label use, but have shown favorable results in prophylactic use in open fractures.30 Negative pressure wound therapy can assist with addressing soft tissue defects. Additional osseous stabilization with external fixation may be required in some cases.
In most cases, antimicrobial therapy can be delayed until after deep tissue sampling. In the presence of sepsis, immediate antibiosis prior to surgery should be prioritized. Start empiric intravenous (IV) antibiotics after tissue sampling. Broad spectrum coverage should include a glycopeptide and coverage against gram-negative bacilli. A curative approach with antibiotics is only effective with biofilm-active antibiotics (rifampin against most gram-positive bacteria and fluoroquinolones against most gram-negative bacteria).11 In addition, the same authors found short-term IV therapy had the same outcome in comparison to long-term IV therapy as long as physicians used appropriate antibiotic therapy. Targeted antimicrobial therapy should commence according to culture results as soon as possible. The common duration of antibiotic therapy is six to 12 weeks, but the multidisciplinary team should be consulted based on the patient’s response to therapy.
Berkes and coworkers retrospectively studied 121 patients with acute FRI who underwent irrigation and debridement and antibiotic therapy by retaining the original hardware.31 The fracture union rate was 71%, but out of this group 36% had hardware removed due to recurrent infection after union was achieved. Variables that were not significant, but trended towards failure included history of smoking, Pseudomonas infection, and involvement of the femur, tibia, ankle, or foot.
Researchers investigated risk factors in a total of 69 patients who achieved successful union with original hardware (47, 68%) in comparison to those who had to have hardware removal before union (22, 32%) with an average healing time of 130 days.32 Most failures occurred within 120 days from the time of the injury. Smoking showed a 3.7 times major risk of failure per month. The authors note the relative high rate of failure by retaining hardware and recommend all hardware be removed to lower the morbidity.
Delayed hardware infections of more than four weeks should either have hardware removed or implant exchanged in a single- or multiple-stage approach.33 Assess the construct integrity and osseous union. A single-stage approach is suggested for relatively healthy patients with adequate bone stock where the infected hardware is removed and replaced with antibiotic-loaded cement. Patients in one study had two to six weeks of IV antibiotics plus rifampin and then followed by three months of rifampin with ciprofloxacin or levofloxacin.25
A staged approach is common when hardware loosening occurs after initial hardware placement. The initial surgery should include hardware removal, debridement of soft tissue and bone, irrigation, and packing with antibiotic beads. After two to six weeks of IV antibiotics, improvement of inflammatory markers (ESR and CRP), and negative repeat tissue sampling, the second or definitive staged procedure demonstrated 90% success rate.34
Fracture stability is essential for fracture healing, but also for prevention and treatment of infection.35 Rittmann and Perren showed the positive influence that fracture stability has on infection.36 The stabilizing effect of implants outweighs the disadvantage of a foreign body effect. After osseous union, one can remove the hardware and thus remove biofilm and potentially prevent future infection. Alternatively, suppression antibiotic therapy can be an option if infection eradication is not possible.27,31
Primary surgical concepts include debridement, antimicrobial therapy, and either implant retention or implant removal in a single or multiple-staged manner. As discussed earlier, deep tissue microbiological sampling and soft tissue coverage are necessary. Implant removal or exchange depends on whether the fracture is unstable, reduction is not adequate, or host physiology is poor. In compromised cases or extensive infection, a nonsurgical approach or amputation with or without lifelong antibiotic suppression may be the only viable alternatives.27
Consult the multidisciplinary team regularly to review surgical treatment, monitor the response to antibiotic therapy, and adjust appropriately based on cultures to optimize patient outcome. After rehabilitation, patients should continue follow-up for a minimum of twelve months after cessation of surgical and antibiotic therapy.11
Case Study: MRSA Following Charcot Reconstruction
A 55-year-old patient with well-controlled diabetes presented with Charcot changes to the right foot resulting in deformity, swelling, and pain (Figure 1). Due to the risks of future complications and severity of deformity, the patient opted to undergo staged reconstructive surgery with tendo-Achilles lengthening, subtalar joint arthrodesis, and midfoot distraction with external fixation after a midfoot osteotomy (Figure 2). Surgeons removed the fixator and placed midfoot beaming screws two months after the index surgery. The patient was healing uneventfully through a period of non-weight-bearing immobilization and then transitioned into a removable boot with progressive osseous consolidation.
Sinus tracts formed at the medial first metatarsal midshaft level and the lateral calcaneus at eight months postoperatively. The medial sinus tract probed to the medial column screw and the lateral sinus tract probed into the calcaneus where an area of radiolucency was noted (Figure 3).
The patient did not demonstrate any systemic or local signs of infection, other than mild serous drainage, and was scheduled to have selective hardware removal (two screws near the posterior calcaneus and the medial column screw). Due to a lack of clinical signs of infection, the patient did not start on pre-op empiric antibiotics. At the time of hardware extraction, surgeons obtained multiple deep bone specimens from both affected areas. Surgeons also inserted absorbable bone cement with vancomycin into the screw holes and calcaneal void. Microbiology results identified methicillin-resistant Staphylococcus aureus from the deep bone cultures. Infectious disease specialists started IV vancomycin for six weeks and monitored inflammatory markers. Physicians consulted with the patient’s endocrinologist and internal medicine physician to optimize the patient’s diabetes and health. Inflammatory markers, ESR, and CRP were only mildly elevated without leukocytosis or bacteremia at the time of hardware removal and tissue sampling.
Prior to the completion of the IV antibiotic therapy, all inflammatory markers had normalized and the incisions healed with conventional wound care. The patient was then scheduled for reimplantation of a medial column screw for added stability (Figure 4). To avoid potential contamination from the same entry point, surgeons inserted the medial column screw from the posterior talus and into the first metatarsal. The team monitored the patient for 12 months after hardware exchange and completing IV antibiotics. The infectious disease specialist did not feel antibiotic suppression was warranted due to lack of extensive infection and normal bloodwork during this survey timeframe. After the 12-month survey, the patient was discharged by infectious disease. The patient has returned to ambulating in diabetic shoes without any complications to date and is seen annually for Charcot monitoring.
In Conclusion
Early clinical diagnosis and treatment with surgical debridement and antibiotic therapy are crucial for the successful management of FRI with a multidisciplinary team approach. When concerned with possible infected hardware, surgeons should utilize a combination of suggestive and confirmatory criteria for early diagnosis. After confirming FRI with deep tissue sampling and completing adequate debridement, antibiotic therapy should be based on culture and sensitivity results and should provide high tissue penetration and effectiveness against biofilm. The decision to retain or exchange hardware should be based on osseous stability. Multidisciplinary consultations should continue for at least one year after completion of surgical and antibiotic therapy. Adherence to this protocol should optimize functional outcomes in cases of FRI.
Dr. Husain is the Residency Director of the McLaren Oakland Hospital Podiatric Surgery and Medicine Residency Program in Pontiac, MI. He is a Fellow of the American College of Foot and Ankle Surgeons and a Fellow of the American Society of Podiatric Surgeons. Dr. Husain is also the President of the Michigan Podiatric Medical Association and Chairman of the Michigan Podiatric Residency Consortium.
Drs. Kipp and Behme are third-year podiatric residents at McLaren Oakland Hospital in Pontiac, MI.
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