Intramedullary nailing of fractured long bones was developed by Kütschner in the 1940s, and since that time, has become the standard in the management of a number of long bone fractures. The intramedullary nail (IMN) acts as an internal splint, that, by virtue of the positive biomechanical properties offered by load-sharing, enhances bending stiffness, 1 and affords axial, bending and rotational stability (when statically locked). The biomechanical advantages and success of IMN fixation in the management of lower extremity fractures has spurred investigators to expand the indications of the IMN. In particular, the use of a transcalcaneal tibial intramedullary device has been adapted to extended arthrodeses of the ankle and hindfoot (i.e., tibiotalocalcaneal arthrodesis). 2–7 The adaptation of IMN fixation for ankle/hindfoot fusion has been fueled by data from previous investigations documenting a 14% nonunion rate for posttraumatic extended ankle arthrodesis performed with internal fixation. 5 In higher-risk patients (Charcot arthropathy, patients with subnormal arterial inflow) requiring peritalar fusions, the clinical nonunion rate with screw fixation has been reported to be as high as 31%. 4 The concept of achieving a tibiotalocalcaneal arthrodesis via a retrograde intramedullary nail (TTCA-RIMN) has been met with much clinical success, 2–7 which is backed by experimental data demonstrating superior bending and torsional stiffness of the IMN than screw constructs. 8 These mechanical advantages of IMN fixation afford great stability and theoretical enhancement of the healing process, which translates into potentially early ambulation after arthrodesis with intramedullary fixation. However, all operative interventions carry a list of inherent potential complications. Published data regarding the rate of infection after TTCA-RIMN is scant. Most published series contain only a few high-risk compromised patients and report postoperative infection rates ranging from 3%–7%, but fail to clearly stratify postoperative infections among compromised and normal hosts. 3,7,9 To date, the most concise study that analyzed the results of TTCA-RIMN in compromised high-risk patients identified a 29% infection rate. 6 In normal hosts, “infection” after TTCA-RIMN has been addressed by local wound care and antibiotics. 6 However, in clinical series that have dealt with more serious infections in higher-risk patients, treatments that have been required to control infection range form local debridement with antibiotics 6 to nail removal with antibiotics, 2,6,7,10 and amputation. 6,9 A particularly troublesome complication after TTCA-RIMN is the development of a high-grade osteomyelitis in the presence of a nonunion (effective bone loss) and intramedullary sepsis in a compromised host (Cierny-Mader Stages 1-Bs & 4-Bs) (Table 1). In this difficult situation, amputation of the infected limb is often the only treatment offered to the patient. However, many patients desire to retain their limbs, and amputation may not always be necessary. This paper describes a technique that uses the same instrumentation for the insertion of the retrograde nail, achieves bone debridement, provides internal splinting of the extremity, and simultaneously delivers local antibiotics. This is achieved by an IMN constructed of polymethylmethacrylate (PMMA) impregnated with antibiotics [ABX-PMMA]. Through a series of staged irrigation and débridements with implantation of an antibiotic IMN, supplemented by culture-specific systemic antibiotics, high grade intramedullary infections can be eradicated, preserving limb function and salvaging the extended ankle fusion. This relatively simple management protocol is a modification of a technique that has been used successfully in the management of infected femoral and tibial nails, as well as diffuse intramedullary sepsis, without prior intramedullary fixation (Bibbo, Patel, Tyndall, et al., unpublished data, 2000). This technique has been successfully applied to the infected TTCA-RIMN in compromised patients with high-grade osteomyelitis (Bibbo, Anderson, Davis, unpublished data, 2000). Such high-risk patients may otherwise require limb amputation to achieve disease control. Although the anatomic region is slightly different, the principals of intramedullary debridement and the delivery of local antibiotics via a temporary intramedullary splint are the same.
The concept of local antibiotic delivery has evolved from the landmark work of Buchholz and Engelbrecht in 1970, who first described the addition of antibiotics to PMMA cement. 11 Since that time, animal models of osteomyelitis have provided experimental evidence of achieving cure rates approaching 100%12,13 by the implantation of antibiotic-loaded PMMA. Clinical experiences in treating osteomyelitis with antibiotic-loaded PMMA have produced excellent results, 14,15 proving the clinical utility of local antibiotic delivery via PMMA to treat osteomyelitis. The concept of local antibiotic deposition is particularly critical in poorly perfused limbs. The use of antibiotics in bone cement offers several advantages, including the ability to achieve high local levels of antiobiotic, 16 low systemic toxicity, 17–19 and minimal local tissue toxicity. 18,20 The high local antibiotic level achieved also allows for the minimization of systemic antibiotic usage in patients who are intolerant of prolonged systemic antibiotic administration. 15
The polymerization process of PMMA is highly exothermic, with the heat of reaction averaging 94° C, 21 but, temperatures have been recorded up to 124° C. 22 Thus, the first rule in utilizing antibiotic impregnated PMMA (ABX-PMMA) is that the selected antibiotic must be heat stable. Fortunately, both vancomycin and tobramycin (the antibiotics most commonly used in PMMA) are heat stable and provide excellent empiric coverage. Both are available in a powder form that is compatible with the chemistry of the PMMA components. Gentamicin may also be used in PMMA. However, powdered gentamicin is not commercially available in the United States, but is available as a pre-made bead product. A number of other antibiotics are heat stable and have been successfully used with PMMA (Table 2), but availability of a powder form is variable, thus the hospital pharmacy should be consulted preoperatively concerning specific antibiotic stocks. Nonetheless, the vast majority of infectious pathogens that are suitably treated by the use of ABX-PMMA nail are adequately covered by a combination of two or more of these antibiotics, and in fact, multiple antibiotics loaded into PMMA has been shown to enhance in-vitro elution of antibiotic from PMMA. 23 However, with the number of multidrug resistant organisms on the rise, such as vancomycin-resistant enterococcus (VRE) and vancomycin-resistant Staphylococcus (VISA & VRSA), antibiotic compatibility in PMMA becomes a serious concern. For example, the two newer FDA approved antibiotics used to combat VRE become problematic when used with PMMA. Linazolid (Zyvox), while ostensibly heat stable (product is sterilized at 100° C), is unavailable in a plain powder form. The heat stability of quinupristin/dalfopristin (Synercid) is unknown. It is known to be unstable in aqueous solution at room temperature, but it is available in a powder form.
The concentration of antibiotics in cement has been somewhat of an issue, mostly in the arthroplasty literature, where the mechanical strength of cement may be diminished by excess addition of antibiotic. However, diminution of the compressive strength of ABX-PMMA has been shown to be less of an issue than the long-term fatigue strength after the addition of antibiotics to PMMA. 24 I have found that for the purpose of the technique of an ABX-PMMA nail, diminution of PMMA strength has not been an issue,* and consistently good elution characteristics are achieved when mixing the basic formula is used: the maximum vancomycin added is 4g/40 g PMA powder (1 gm powder = 1 vial); clindamycin 6g/40 g PMMA powder; and tobramycin 9.8 g/40 g PMMA powder (1.2 gm = 1 vial powder). 25 The minimum antibiotic per 40 grams of powdered cement is one gram vancomycin plus 3.6 grams tobramycin, otherwise elution kinetics result in suboptimal local antibiotic concentrations. 26 Powdered antibiotics tend to favor PMMA strength better than lyophilized antibiotic, 24 thus powdered antibiotics are preferred. Aqueous antibiotic solutions significantly decrease bone cement strength, and, certain antibiotics, such as rifampicin, may result in incomplete PMMA polymerization. 27
The elution of antibiotic from PMMA offers the advantage of immediate release of the antibiotic, with sufficient antibiotic eluted via surface release to achieve bactericidal levels within 45 minutes to 20 hours after impanation. 28 A total of 2%–10% of the antibiotic contained within the cement is released in the first 24 hours, 29 resulting in the greatest rate of elution occurring over the initial 24 hours. 30 Tobramycin PMMA beads demonstrate antibiotic release sustaining levels well above the breakpoint (antibiotic concentration at the point of transition between bacterial killing and resistance to antibiotic) for 90 days, whereas vancomycin levels may fall below the breakpoint concentration by day 12 16 or sooner. 31 Gentamicin and amikacin a have been shown to achieve bactericidal levels for 30 days by eluting from PMMA. 30 The actual PMMA cement product has an impact on antibiotic elution. Palacos (Richards, Memphis, Tennessee) cement has been proven to possess superior antibiotic elution characteristics over other brands of PMMA cement. 32–34
In-vivo human studies analyzing drain fluid from wounds with antibiotic loaded PMMA cement demonstrate vancomycin levels reaching five times the breakpoint sensitivity concentration (antibiotic concentration at point of transition between bacterial killing and resistance to antibiotic) after 24 hours, then equaling the breakpoint at four days. 31 Therefore, when drains are required after insertion of vancomycin loaded PMMA, I recommend clamping the drains for 4 days to maximize the local milieu in favor of a high antibiotic concentration. Other antibiotics may display vastly different elution kinetics. Ciprofloxacin has been shown to achieve adequate release from PMMA to achieve the MIC of susceptible organisms for up to 42 days. 35 However, in many institutions, ciprofloxacin may not be available in a powder form.
Antibiotics can leach from PMMA for extended periods of time (up to 5 years), 34 but levels are generally are well below the breakpoint level, offering little long-term therapeutic benefit. Thus, after reaching a certain point in time, the PMMA has the potential to act as a foreign body or induce bacterial resistance unless a microbiologic cure was achieved or prolonged systemic antibiotics are supplementing the local concentrations. Thus, timely repeat irrigation and debridement with repeat cultures is mandatory.
Because elution of the antibiotic from the PMMA is the cornerstone to the success of the delivery system of the ABX-PMMA nail, any measures that may enhance or maximize antibiotic elution from the ABX-PMMA should be rigorously followed. Antibiotics are initially released from the PMMA from the surface layer, then from a network of imperfections in bone cement (bubbles, voids, cracks). 21,36 Efforts to decrease these networks will impair the release of antibiotics. 21 Thus, hand-mixing, (without vacuum assistance) which encourages the formation of micro cracks and voids and bubbles, should be performed. Preparing PMMA impregnated with antibiotics under negative atmospheric pressure (vacuum mixing) has been shown to reduce antibiotic release by 50%, 37 and should be avoided. Chilling the monomer before hand mixing can also increase PMMA porosity, 38 enhancing antibiotic elution. Using a combination of antibiotics has also shown to enhance the elution of the antibiotics from the PMMA. 23 When fabricating either rods or beads, maintaining rounded surfaces (which increases the surface area to volume ratio) also enhances antibiotic elution. 39
Simplistically, the indications for this technique is the patient with an infected TTCA-RIMN with intramedullary sepsis that has not, or will not, go on to solid arthrodesis (i.e., Cierny-Mader stage IV osteomyelitis). This is especially true in patients who are metabolically compromised. Patients who are unable to undergo large revision TTCA via alternate techniques (such as blade plate fixation or because of poor soft tissue conditions that preclude a lengthy lower extremity incision) further expand the indications of the ABX-PMMA IMN. Patients who are not compromised and have a solid fusion but only have a local osteomyelitis may be best treated by removal of the TTCA nail, local debridement, and administration of systemic antibiotics. However, in the situation of an infected TTCA-RIMN in a high-risk patient that would otherwise require an amputation, the desire of the patient to retain their limb should prompt the surgeon to explore the use an ABX-PMMA IMN. Such high-risk patients include the diabetic with marginal blood supply, smokers, patients with poor physiologic reserve, and patients who possess a poor soft tissue envelop in which healing difficulties preclude extensive incisions. The contraindications to this procedure include: 1) infections due to organisms that require chemotherapeutic agents that are not heat stable; 2) severe unreconstructable vascular compromise that is not amenable to any vascular intervention, such that even the limited incisions of this technique may result in irreversible ischemic conditions (i.e., the treatment by the technique is worse than an amputation); 3) the patient has overwhelming sepsis and necrosis, and can not tolerate multiple procedures (this is the patient that requires limb ablation to reverse the sepsis syndrome); and 4) patients who are unable to comply with the required schedule of staged débridements and operative cultures. Although this technique is suitable for many fragile patients, it requires clinical experience to determine where the threshold for treatment exists in severely compromised patient.
The first and most obvious step is to determine that the TTCA-RIMN is indeed infected. Often, the clinical presentation of an infected TTC-RIMN is increasing pain with ambulation, night pain, and swelling. Frequently, the grossly infected TTCA-RIMN presents as a plantar abscess at the nail insertion site (Fig. 1), as purulent drainage from a sinus near a screw insertion site, or as a previous open wound. Good quality tibia-fibula films are essential, and must include the foot and ankle. Spot radiographs of the ankle and hindfoot are often helpful as well. Radiographic changes include increasing lysis around the nail, gross motion with fracture of locking screws, and even apparent nail migration (Fig. 2). Failure to achieve fusion in non-high-risk patients or nonsmokers is always suspect for occult infection.
Laboratory data in the work-up of an infected TTCA-RIMN acts as a diagnostic assistant and also serves as a baseline value to monitor the progress of treatment. In those patients presenting only with clinical complaints of increasing pain, laboratory evaluation may prove to be very helpful. A complete blood count with differential (CBCD), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are the first-line laboratories to obtain. These laboratories provide good indirect evidence of infection, and serve as a baseline when following the patient's response to treatment. When examining laboratory data, the clinician must be cognizant of factors that may cause spurious elevations in the ESR and CRP, such as renal insufficiency. Remember, although the CRP is an excellent surrogate laboratory indicator, is relatively more specific for infection than the ESR, and reflects changes in inflammatory processes over time faster than the ESR, it is not infallible. An indium-111 labeled white blood cell (I111 WBC) scan can be very helpful in the work-up of sub-clinical infection and is relatively specific when compared with other nuclear imaging studies and MRI, which tends to over-read infection based on bone edema patterns. I tend to reserve MRI for infectious processes in which I suspect a deep abscess that is not discernible on physical examination. Radionuclide labeled RBC studies may be an acceptable substitute.
Changes in host vascularity and cardiovascular status may occur between the index operation and the presentation of an infected TTC-RIMN. The following host parameters must always be re-evaluated: 1) current status of the vascular supply to the limb. The liberal use of noninvasive arterial studies should be used, including ankle-brachial indices and transcutaneous oxygen measurements. The patient must have the ability to heal any new or revisited incision; 2) the overall cardiovascular risk and the patient's physiological reserve. Is the host of sufficient reserve to successfully complete the treatment program and achieve a microbiologic cure? Cardiovascular risk stratification is essential in the elderly and in all patients with diabetes regardless of age or sex. Nutritional parameters should also be reviewed and taken into consideration before embarking on this technique (Table 3).
Preoperatively, the surgeon must have available the equipment to facilitate the operation (Table 4). The patient is placed in the supine position, with an ipsilateral hip bump, achieving a position where the anterior surface of the patella is facing the ceiling. The patient's foot is toward the end of the table. A thigh tourniquet in placed. Inflation of the tourniquet is not mandatory, and is avoided in patients who have subnormal arterial inflow, or in those who have undergone a past vascular bypass where prolonged reductions of flow velocities may be detrimental. General or regional (epidural/spinal) anesthesia is used. Indwelling regional catheters are an excellent method for postoperative pain control and reduce inhaled anesthetic exposure. Combined femoral and sciatic blocks are also an alternative for intraoperative and postoperative pain control. The limb is gently exsanguinated if a tourniquet is used. Perioperative antibiotics are held until intraoperative cultures are obtained. Fluoroscopic imaging is used to localize locking screws, which are removed. The plantar nail insertion incision is carefully opened. Often, a pointing abscess is present at the nail insertion site (Fig. 1). After removing any end cap and locking screws, the nail is removed with the manufactures distraction system. However, the nail can often be removed with just pliers or a large Kocher clamp. The hollow core of the nail is inspected; often a large string of slime and debris fills the nail core. This is sent to pathology and microbiology (Fig. 3). The contents of the tibial canal is cultured and sent for immediate Gram's stain. In instances where there is little intramedullary material, I will send an additional tissue sample for intraoperative frozen section. If frozen section fails to provide evidence of acute or chronic infection, samples are sent for screening polymerase chain reaction to detect 16S bacterial ribosomal DNA. A drill is used to slightly enlarge the proximal screw locking sites, or to create new holes if proximal locking screws have been removed or were not initially placed. A suction tip is paced into the hole (Fig. 4). This creates vent holes for the efflux of reamed materials, in an effort to decrease the occurrence of septic emboli. 40 With a suction tip in the proximal vent hole, the tibial canal and hindfoot is progressively reamed until the reaming product yields fatty marrow or normal, bloody cancellous bone (Fig. 4). Reaming material may also be sent for culture. After adequate reaming, a pulse lavage irrigation system (with a long wand attachment) is used to irrigate the tibial canal and hindfoot (Fig. 5). If the limb is particularly purulent, or the patient is seropositive for HIV, hepatitis, or other communicable blood-borne pathogens, I place the limb in a clear X-ray cassette cover, seal the proximal end with a clamp, place the irrigation device in a slit hole, and cut an effluent slit in the bottom, allowing drainage into a large basin with suction. This “limb-in-a-baggie” trick provides excellent protection for the operating surgeon as well as the operating room staff. Typically, I use three bags of irrigation, each bag containing three liters of irrigant. Antibiotics may be used in the irrigation. If only one bag or irrigation contains antibiotics, I use that bag last. Post irrigation and debridement cultures are then taken as well.
On the back table, a sterile plastic sheet (such as a Mayo stand cover) or plastic tray is laid-out for the preparation of the ABX-PMMA nail. Steinman pins are selected to match the original nail length. Ilizarov wires may be substituted. Dry powdered PMMA is mixed with the selected antibiotics (Fig. 6, Table 2). The PMMA is prepared by hand, without a vacuum. The PMMA components may be chilled to enhance porosity. After mixing the PMMA/antibiotics, the mixture is allowed to briefly sit until it achieves a workable form. The ABX-PMMA is rolled out longitudinally on the plastic sheet, shaping the ABX-PMMA to match the nail length. The Steinman pins are placed into the PMMA, acting as rebars (Fig. 7). The ABX-PMMA is rolled out with the final diameter designed to be just a bit narrower than the original nail diameter, as this facilitates easy placement of the antibiotic nail. While shaping the nail, it is important that during the drying period, a rolling action is maintained to shape the PMMA nail; otherwise the PMMA will spread and dry in a flattened position, resulting in a PMMA nail with a shape that will be very difficult to insert. A burr may be used to trim any prominences that impede insertion. When the ABX-PMMA nail has set and is cool, it is inserted into the limb (Fig. 8). It is important that the ABX-PMMA nail does not sit too proud, as it is not locked into position. However, it is very helpful to have a slight prominence to assist with retrieval at subsequent operative settings. Beads may be created from any left over PMMA, strung on a large-gauge, nonabsorbable suture and packed into any soft tissue dead spaces (Fig. 9). Wounds are closed with nonabsorbable suture. A bulky sterile dressing is applied, followed by a combination posterior and stirrup splint.
The patient is maintained nonweight bearing. In reliable patients, toe-touch weight bearing is permitted. If drains were placed, they are clamped for 36–72 hours. It is imperative that the patient be available when operative culture results are finalized. If the organisms are sensitive to the antibiotic loaded into the PMMA nail, then a peripheral indwelling central catheter (PICC line) is placed, and appropriate systemic antibiotic are begun. If the infecting organism(s) are not sensitive to the antibiotics loaded into the ABX-PMMA nail, then the nail is exchanged for an appropriate culture-directed ABX-PMMA nail. The wounds are checked in 10–14 days, and dressings applied. A walker boot is fitted, or a short-leg nonweight bearing cast applied. Repeat ESR, CRP, and CBCD are followed biweekly. Follow-up surveillance must be structured and enforced, not only to monitor changes in the ESR/CRP, but also to detect the development of complications from systemic antibiotics, such as changes in renal function and significant neutropenia, 41 which may necessitate altering or discontinuing the systemic antibiotics.
Typically, I leave the ABX-PMMA nail in place for 2–6 weeks while the patient is on culture-directed systemic antibiotics. If for any reason the patients has had their systemic antibiotics discontinued (e.g., severe reaction such as neutropenia), then I will remove the ABX-PMMA nail at approximately 2 weeks, in accordance with antibiotic elution-breakpoint level data, 16 and insert a fresh ABX-PMMA nail after irrigation and debridement. At ABX-PMMA nail exchange, an identical procedure is performed: nail removal, pre-irrigation and debridement cultures, reaming, irrigation, post-irrigation and debridement cultures, and placement of new ABX-PMMA nail. At the time of nail exchange, the patient has typically received 2–6 weeks of systemic antibiotics. If at any subsequent ABX-PMMA nail exchange the post-irrigation and debridement cultures remain negative, then consideration can be made to placement of a metallic implant and an attempt at re-arthrodesis. In difficult infections (extensive bone loss, resistant organisms), I may elect to complete 6 weeks of systemic antibiotics and place an ABX-PMMA nail 2–3 times, each nail spaced approximately 2 weeks apart. When the 6-week course of systemic antibiotics is complete, I wait approximately 2 weeks and re-culture the operative site before attempting metallic nail placement. A particularly difficult problem may arise when a complication from systemic antibiotics therapy demands cessation of the systemic therapy. 41 In this situation, the ABX-PMMA nail plays the essential role in infection control, and should be exchanged at routine intervals of 2–3 weeks, with close attention paid to culture techniques and culture results. In select fragile high-risk patients with limited activity level, the final ABX-PMMA nail may be left in place. With adequate protective bracing, these patients may perform limited ambulation and retain their ABX-PMMA nail indefinitely.
When it has been determined that the infection is cleared (clinical response to treatment, culture, and laboratory data), the surgeon must choose the pathway for further treatment. An attempt to achieve a bony union may be attempted. The placement of a metal nail (preferably one with a compression feature) plus bone grafting, is one option. Other fusion techniques may also be used if the clinical situation warrants. If a stable, painless fibrous union is achieved after elimination of the infection, the patient may function well with the addition of bracing and shoe modifications. In cases where a TTC-RIMN fusion was originally performed for a Charcot deformity, a sterile, painless, stable (or braceable) fibrous union is a reasonable and realistic goal.
RISKS AND COMPLICATIONS
The most common complications related to the use of the ABX-PMMA nail arise from technique in the operating room. Often, ABX-PMMA nails are inserted and left too proud, producing plantar heel pain. If an ABX-PMMA nail is excessively canal-filling and inserted too far, retrieval may be difficult. In this instance, nail retrieval is facilitated by creation of a proximal portal that allows retrograde disimpaction of the PMMA nail. Overzealous reaming may thin the tibial cortex, resulting in fracture. Casting is often sufficient to manage such a fracture. The creation of septic emboli is a serious potential complication. The risk of septic emboli is reduced by the creation of vent holes with the placement of negative suction. This maneuver appears to be quite efficacious in preventing septic emboli, and to date, no patient that I have treated by this technique has suffered a clinically detectable septic embolus during this procedure. Cardiovascular complications from the use of PMMA cement is not an issue, because the PMMA nail is inserted after it has set and cooled.
Blood loss from intramedullary reaming is usually self-limited, but may be extensive if the patient is on anticoagulation. For those patients on warfarin, I will operate when the INR lowers to approximately 1.5 or less. If their anticoagulation is critical (i.e., implanted prosthetic heart valve), I will convert their anticoagulation to unfractionated heparin, maintaining an APTT of 2–2.5 greater than normal. The unfractionated heparin is held 2–3 hours before surgery, then re-started immediately postoperatively. Warfarin may be started again when there exists a reasonable time period between the index operation and subsequent operative settings that permits stabilization of the patients INR (i.e., 1–2 weeks).
Premature unauthorized weight bearing may result in fracture of the ABX nail, in which case casting is initiated, followed by strict nonweight bearing. Proper rolling of the ABX-PMMA nail during curing helps to prevent lamination of the PMMA, which may contribute to a weakened PMMA nail. Close attention to the form of the ABX-PMMA nail and the use of an adequate number of Steinman pins (2–3 pins) in the PMMA ensures a stronger construct.
The use of the antibiotic-impregnated intramedullary PMMA nail has been quite efficacious in the treatment of high-grade osteomyelitis after extended ankle arthrodesis with an intramedullary device. Recently, there has been the introduction of various calcium-based biomaterials, which have been shown to be biocompatible. When mixed with many antibiotics, they demonstrate favorable elution kinetics 42 and have been shown to be capable in the treatment of osteomyelitis. 43 Poly anhydrides and poly lactide-glycolide polymers have also been successfully used as antibiotic delivery vehicles. 44–46 These newer products are designed to dissolve over time with subsequent structural weakening. These newer biodelivery products may be useful at a final operative setting, in situations where further operative visits are not planned. However, at this time, the implantation of a large caliber intramedullary mass (such as a nail) composed of these products would ostensibly take a great deal of time to be absorbed. Although these products are routinely used in orthopaedic surgery in limited quantity with few adverse effects, the biologic effect from extensive volumetric use of these products (such as in an intramedullary nail) is unknown. The load-bearing properties of these products in an application to create an intramedullary nail may also be limited. Thus, their use in a technique as described is currently not recommended. However, future advances in biomaterial sciences may prove these newer mineral and polymer products to be the materials of choice for antibiotic delivery.
1. Bechtold JE, Kyle RF, Perren SM. Biomechanics of intramedullary nailing. In: Browner BD, ed. The Science and Practice of Intramedullary Nailing
, ed.2. Williams & Wilkins, Media, PA. 1996: pp 89–101
2. Moore TJ, Prince R, Pochatko D, et al. Retrograde intramedullary nailing for arthrodesis. Foot Ankle Int 1995; 16:433–436.
3. Chou LB, Mann RA, Yaszay B, et al. Tibiotalocalcaneal arthrodesis. Foot Ankle Int 2000; 21:804–808.
4. Papa J, Myerson M, Girard P. Salvage, with arthrodesis, in intractable diabetic neuropathic arthropathy of the foot and ankle. J Bone Joint Surg Am 1993; 75:1056–1066.
5. Papa JA, Myerson MS. Pantalar and tibiotalocalcaneal arthrodesis for post-traumatic osteoarthritis of the ankle and hindfoot. J Bone Joint Surg Am 1988; 70:1304–1307.
6. Pinzur MS, Kelikian A. Charcot ankle fusion with a retrograde locked intramedullary nail. Foot Ankle Int 1997; 18:699–704.
7. Moore TJ, Prince R, Pochatko D, et al. Retrograde intramedullary nailing for ankle arthrodesis. Foot Ankle Int 1995; 16:433–436.
8. Berend ME, Glisson RR, Nunley JA. A biomechanical comparison of intramedullary nail and crossed lag screw fixation for tibiotalocalcaneal arthrodesis. Foot Ankle Int 1997; 18:639–643.
9. Kile TA, Donnelly RE, Gehrke JC, et al. Tibiotalocalcaneal arthrodesis with an intramedullary device. Foot Ankle Int 1994; 15:669–673.
10. Russotti GM, Johnson KA, Cass JR. Tibiotalocalcaneal arthrodesis for arthritis and deformity of the hind part of the foot. J Bone Joint Surg Am 1988; 70:1304–1307.
11. Buchholz HW, Engelbrecht H. Ueber die depotwirkung eigigner antibiotika bei vermischung mit dem kunstharz Palacos. Chirurg 1970; 40:511–515.
12. Evans RP, Nelson CL. Gentamicin-impregnated polymethylmethacrylate beads compared with systemic antibiotic therapy in the treatment of chronic osteomyelitis. Clin Orthop 1993; 295:37–42.
13. Nijhof MW, Stallmann HP, Vogely HC, et al. Prevention of infection
with tobramycin-containing bone cement or systemic cefazolin in an animal model. J Biomed Mater Res 2000; 52:709–715.
14. Calhoun JH, Henry SL, Anger DM, et al. The treatment of infected nonunions with gentamicin-polymethylmethacrylate antibiotic beads. Clin Orthop 1993; 295:23–27.
15. Walenkamp GH, Kleijn LL, de Leeuw M. Osteomyelitis treated with gentamicin-PMMA beads: 100 patients followed for 1-12 years. Acta Orthop Scand 1998; 69:518–522.
16. Mader JT, Calhoun J, Cobos J. In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads. Antimicrob Agents Chemother 1997; 41:415–418.
17. Savati EA, Callaghan JJ, Brause BD, et al. Reimplantation in infection
. Elution of gentamicin from cement and beads. Clin Orthop 1986; 201:83–93.
18. Peterson BH, Steimel LA, Black HR. Immunological responsiveness of guinea pigs to antibiotics diffusing from bone cement. Antimicrob Agents Chemother 1982; 22:704–706.
19. Haydon RC, Blaha JD, Mancinelli C, et al. Audiometric thresholds in osteomyelitis patients treated with gentamicin-impregnated methylmethacrylate beads (Septopal). Clin Orthop 1993; 295:43–46.
20. Jensen JS, Sylvest A, Trap B, et al. Genotoxicity of acrylic bone cements. Pharmacol Toxicol 1991; 69:386–389.
21. Baker AS, Greenham LW. Release of gentamicin from acrylic bone cement. J Bone Joint Surg 1988; 70-A;1551–1557.
22. Wang JS, Franzen H, Toksvig-Larsen S, et al. Does vacuum mixing of bone cement affect heat generation? Analysis of four cement brands. J Appl Biomater 1995; 6: 105–108.
23. Penner MJ, Masri BA, Duncan CP. Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement. J Arthroplasty 1996; 11:939–944.
24. Klekamp J, Dawson JM, Haas DW, et al. The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint Arthroplasty. J Arthroplasty 1999; 14:339–346.
25. Adams K, Couch L, Cierny G, et al. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop 1992; 278:244–252.
26. Masri BA, Duncan CP, Beauchamp CP. Long-term elution of antibiotics from bone-cement: an in vivo study using the prosthesis of antibiotic-loaded acrylic cement (PROSTLAC) system. J Arthroplasty 1998; 13:331–338.
27. De palma L, Greco F, Ciapaglini C, et al. The mechanical properties of “cement-antibiotic” mixtures. Ital J Orthop Traumatol 1982; 8:461–467.
28. Welch A. Antibiotics in acrylic bone cement. In vitro studies. J Biomed Mater Res 1978; 12:679–700.
29. Picknell B, Mizen L, Sutherland R. Antibacterial activity of antibiotics in acrylic bone cement. JBJS-B 1977; 59:302–307.
30. Ethell MT, Benett RA, Brown MP, et al. In vitro elution of gentamicin, amikacin, and ceftiofur from polymethylmethacrylate and hydroxyapatite. Vet Surg 2000; 29:375–382.
31. Chofi M, Langlais F, Fourastier J, et al. Pharmacokinetics, uses, and limitations of vancomycin-loaded bone cement. Int Orthop 1998; 22:171–177.
32. Greene N, Holtom PD, Warren CA, et al. In vitro elution of tobramycin and vancomycin polymethylmethacrylate beads and spacers from Simplex and palaces. Am J Orthop 1998; 27:201–205.
33. Penner MJ, Duncan CP, Masri BA. The in vitro elution characteristics of antibiotic-loaded CMW and palaces-R bone cements. J Arthroplasty 1999; 14:20–214.
34. Wahlig H, Dingeldein. Antibiotics and bone cements. Experimental and clinical long-term observations. Acta Orthop Scand 1980; 51:49–56.
35. DiMaio FR, O'Halloran JJ, Quale JM. In vitro elution of ciprofloxacin from polymethylmethacrylate cement beads. J Orthop Res 1994; 12:79–82.
36. Torrado S, Frutos P, Frutos G. Gentamicin bone cements: characterization and release (in vitro and in vivo assays). Int J Pharm 2001; 217:57–69.
37. Kuechle DK, Landon GC, Musher DM, et al. Elution of vancomycin, daptomycin and amikacin from acrylic bone cement. Clin Orthop 1991; 264:302–308.
38. Jasty M, Davies JP, O'Connor DO, et al. Porosity of various preparations of acrylic bone cements. Clin Orthop 1990; 259:122–129.
39. Masri BA, Duncan CP, Beauchamp CP, et al. Effect of varying surface patterns on antibiotic elution from antibiotic-loaded bone cement. J Arthroplasty 1995; 10:453–459.
40. Martin R, Leighton RK, Petrie D, et al. Effect of proximal and distal venting during intramedullary nailing. Clin Orthop 1996; 332:80–89.
41. Bibbo C, Barbieri RA, Deitch EA, et al. Neutropenic enterocolitis in a trauma patient during antibiotic therapy for osteomyelitis. J Trauma 2000; 49:760–763.
42. Mousset B, Benoit MA, Delloye C, et al. Biodegradable implants for potential use in bone infection
. An in vitro study of antibiotic-loaded calcium sulphate. Int Orthop 1995; 19:157–161.
43. Cornell CN, Tyndall D, Waller S, et al. Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute. J Orthop Res 1993; 11:619–626.
44. Lin SS, Ueng SW, Liu SJ, et al. Development of a biodegradable antibiotic delivery system. Clin Orthop 1999; 362:240–250.
45. Calhoun JH, Mader JT. Treatment of osteomyelitis with a biodegradable antibiotic implant. Clin Orthop 1997; 341:206–214.
46. Laurecin CT, Gerhart T, Witschger P, et al. Biodegradable polyanhidrides fro antibiotic drug delivery: in osteomyelitis treatment in a rat model. J Orthop Res 1993; 11:256–262.
Keywords:© 2002 Lippincott Williams & Wilkins, Inc.
infection; tibiotalocalcaneal fusion; retrograde intramedullary nail; antibiotic nail