Osteo

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Chronic Osteomyelitis Chronic Osteomyelitis
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Craig M. Rodner, M.D. Bruce D. Browner, M.D., F.A.C.S. Ed Pesanti, M.D., F.A.C.P.
In adults, bone infections are most commonly seen after direct skeletal trauma or after operative treatment of bone. These infections, usually referred to as post-traumatic, exogenous, or chronic osteomyelitis, are difcult to treat and usually have a protracted clinical course. Surgical de bridement constitutes the cornerstone of management with antibiotic therapy playing only an adjunctive role.
TERMINOLOGY
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz Before embarking on a review of chronic osteomyelitis, it may be wise to begin with a few basic denitions. The term osteomyelitis simply refers to an infection in bone. Such infections are most often caused by pyogenic bacteria (such as Staphylococcus aureus), although other microbes, including mycobacteria and fungi, are sometimes responsible. In hematogenous osteomyelitis, which most frequently affects children, blood-borne bacteria seed previously healthy bone. In post-traumatic or exogenous osteomyelitis, the infection is almost always associated with trauma, whether it be of the unplanned variety (i.e., a motor vehicle accident) or the planned (i.e., a surgical procedure). The term acute osteomyelitis is often used interchangeably with the term hematogenous osteomyelitis; in current usage, both terms reect a form of osteomyelitis in which osteonecrosis has not yet occurred. On the other end of the spectrum, the term chronic osteomyelitis is dened as a bone infection predicated on preexisting osteonecrosis. Note that the difference between acute and chronic osteomyelitis is not based on the duration of infection, as their names might suggest, but rather on the absence or presence of dead bone. It is precisely the presence of dead bone that makes chronic osteomyelitis a primarily surgical disease. Although theoretically chronic osteomyelitis can result from an untreated or inadequately treated hematogenous
infection, it is most frequently traumatic in origin. It is important to recognize that infection occurring in the setting of skeletal trauma, however acutely chronologically, is in fact a chronic osteomyelitis from the start. In the post-traumatic milieu, opportunistic bacteria can be thought of as taking advantage of bone that has been devitalized by injury (quite the opposite from acute osteomyelitis, wherein microbes seed previously healthy bone). Because of the high congruence between osteonecrosis and a history of trauma, the terms chronic and post-traumatic or exogenous osteomyelitis are frequently used interchangeably. This is reasonable as long as one understands the subtle differences among them.
EPIDEMIOLOGY
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz Bone infection in the adult population is much more likely to be exogenous in origin than hematogenous, in part because of the demographics of high-speed motor vehicle accidents and orthopaedic surgery but also because the predilection for bacterial seeding of bone ceases with closure of the epiphyses. For this reason, hematogenous osteomyelitis is vanishingly rare in people beyond their teens, occurring only in immunocompromised hosts.31 Post-traumatic osteomyelitis is one of the few infectious diseases that has become more prevalent in this century, probably because it is one of the few diseases fueled by technology. With the development of bigger and more powerful automobiles, motorcycles, guns, and land mines, the past hundred years have been witness to an everincreasing potential for devastating soft tissue and skeletal injury. Infection is so closely linked with such injuries for two reasons. First, they provide ubiquitous microbes with an opportunity for breaching host defenses by exposing bone to the contamination of an accident scene. Second, once the microbes have bypassed external defenses, the
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Copyright 2003 Elsevier Science (USA). All rights reserved.
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SECTION I General Principles
trauma setting offers an ideal environment for adherence and colonization, namely, devitalized hard and soft tissues. It is not surprising, therefore, that there is a signicant incidence of deep infection, of either soft tissue or bone, secondary to open fractures. A review by Gustilo54 showed the deep infection rate in the setting of open fractures to be anywhere from 2% to 50%. Naturally, not all open fractures carry the same risk of infection. On the basis of the extent of soft tissue injury, the severity of open fractures has traditionally been classied as type I, II, or III according to criteria put forth by Gustilo and Anderson.52 Not surprisingly, it has been found that the more severe the open fracture, the greater the likelihood of infection: approximately 2% for type I and II open fractures and 10% to 50% percent in type III open fractures.25, 52, 54, 114 Gustilo54 cited several reasons type III fractures have been shown to be more susceptible to infection, such as lack of bone coverage, massive contamination of the wound, compromised perfusion, and instability of the fracture. The tibia is the most frequent location of open fractures37 and, accordingly, is also the most frequently infected. One retrospective study of 948 high-energy open tibial fractures reported a 56% post-traumatic infection rate.130 Although not involved as often as the lower extremity, the upper extremity is also vulnerable to accidental trauma and subsequent infection.138 In addition to traumatic injury, chronic osteomyelitis can result from surgical implants or, less commonly, from untreated or poorly treated hematogenous infection. In any discussion of the epidemiology of chronic osteomyelitis, one should not overlook the role of host factors. Patients with vascular insufciency, from conditions such as diabetes and peripheral vascular disease, have long been known to be at higher risk for posttraumatic or postoperative osteomyelitis.149 Even subtle injuries in this population, such as a chronic pressure sore, may lead to the development of exposed bone, surrounding cellulitis, and eventual gangrene of the soft tissues.119 Diabetic ulcers progress quickly in the setting of comorbid peripheral vascular disease, neuropathy, and repetitive trauma.58, 87 Additional host factors, such as malnutrition and alcoholism, are also said to contribute to the development of post-traumatic osteomyelitis77 but have not been rigorously studied. Although there are no studies focusing specically on the correlation between cigarette smoking and the incidence of post-traumatic osteomyelitis, there is evidence supporting signicantly faster healing in nonsmokers with tibial infection compared with smokers.50 Furthermore, there is a vast literature on the detrimental effects of smoking, and nicotine in particular, on wound healing, the survival of muscle aps and skin grafts, and the rate of fracture union. Although it is known that a vascular insult predisposes one to the development of chronic osteomyelitis, this progression should not be viewed solely as an inverse correlation between blood ow and risk of infection. In any acute inammatory process, the balance between host and microbe is determined in large part by the efcacy of the immune response to the infectious challenge. Patients suffering from a disorder of polymorphonuclear leukocytes, for example, have been shown to be at an increased
risk for the development and progression of osteomyelitis. In one series of 42 children with chronic granulomatous disease, the authors identied 13 patients who had osteomyelitis.129 Other immunocompromised individuals, such as organ transplant recipients,69, 154 patients with end-stage renal disease, or those receiving chemotherapy,17 also seem to be at an increased risk. Although human immunodeciency virus infection has not been identied as an independent risk factor in developing osteomyelitis,88 skeletal infection in this population is clearly associated with a more severe clinical course that has been associated with elevated morbidity and mortality.144
PATHOGENESIS
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz Although acute osteomyelitis and chronic osteomyelitis both describe infections of bone, they are fundamentally distinguished by the presence of dead bone in the latter. Unlike acute osteomyelitis, which usually occurs in the metaphyseal areas of long bones secondary to hematogenous seeding, chronic osteomyelitis is usually localized to the area of traumatic injury, which can be epiphyseal, metaphyseal, or diaphyseal.
Hematogenous Osteomyelitis
In hematogenous infection, microorganisms inltrate the metaphyseal end-arteries of long bone and replicate, thereby instigating a vigorous inammatory response from the host. Because bone is a hard and rigid tissue, this inux of inammatory cells into its canals has the unintended effect of raising intraosseous pressure and occluding its own blood supply.153 Unless the infection and subsequent inammation are rapidly controlled by the early administration of antibiotics, an area of devitalized bone begins to form. This fragment of necrotic bone, which is usually cortical and surrounded by inammatory exudate and granulation tissue, is called a sequestrum. An involucrum sheath of reactive bone forms around the sequestrum, effectively sealing it off from the blood stream much like a walled-off abscess. With the development of dead bone, the infection can properly be referred to as a chronic osteomyelitis. Because it is possible to interrupt this progression with early antibiotics or drainage, acute hematogenous infection rarely evolves into chronic osteomyelitis.148
Chronic Osteomyelitis
The adult immune system normally renders bacterial colonization of bone difcult. In a normal host, there are only a few circumstances in which such infection might occur. These include a large inoculum size (>105 organisms per gram of tissue),78, 115 an environment of ischemic bone and surrounding soft tissue, or the presence of a foreign body.31, 96 Unfortunately for the individual with a contaminated open fracture, virtually all of these conditions are present. In the setting of skeletal trauma and
CHAPTER 19 Chronic Osteomyelitis
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subsequent ischemia, the same bone that is normally quite resistant to bacterial inltration becomes an ideal target for bacterial adherence and subsequent proliferation.97 The rst step in the pathogenesis of chronic osteomyelitis is entry of the pathogenic organism through the hosts external defenses. Normally a difcult task, breaching the skin and mucous membranes becomes facile in the setting of an open fracture. However, the presence of a foreign microbe at or near bone is not sufcient to produce infection. Indeed, although most open fractures are contaminated by bacteria, only a fraction of these actually progress to osteomyelitis.139 For osteomyelitis to develop, the microbe must not only penetrate the hosts external defenses but actually become adherent to the underlying bone. Whereas the skeleton is normally resistant to bacterial adherence, traumatized tissue is susceptible to attack. This occurs, in part, because pathogenic bacteria have various receptors for host proteins that are laid open by injury to the bone. For example, S. aureus has been shown to have receptors for collagen, which is exposed by skeletal trauma, and bronectin, which covers injured tissue shortly after the initial insult.38, 49, 56, 139 Furthermore, external debris (in the case of open fractures) and even the necrotic bone fragments themselves can act as avascular foci for further bacterial adherence. Thus, as the osteonecrotic area expands, the disease is perpetuated by exposure of an increasing number of sites to which opportunistic bacteria can bind. In cases of chronic osteomyelitis secondary to internal xation, the hardware itself serves as another adherent surface.29, 34, 38, 49 After bacteria successfully adhere to bone, they are able to aggregate and replicate in the devitalized tissue. Effectively sealed off from the host immune system, as well as from antibiotics, the organisms at the avascular focus of infection proliferate undeterred in a medium of dead bone, clotted blood, and dead space. Eventually, the bacteria disperse to adjacent areas of bone and soft tissue and the infection expands. The rapid growth of bacteria can lead to abscess and sinus tract formation. As pus accumulates and abscesses form within the soft tissues adjacent to the necrotic tissue, the patient experiences cyclic episodes of pain followed by drainage. A chronic course ensues without aggressive surgical de bridement of all avascular tissue.
Bacteriology
Gustilo and Anderson52 reported that 70% of open fractures had positive wound cultures before the initiation of treatment. Of course, not every contaminated wound leads to frank bone infection. In some circumstances, the combination of host defenses and various treatment modalities is successful in preventing bacteria from reaching some critical threshold necessary for infection. However, as mentioned, there are a few factors that put one at increased risk for skeletal infection, such as a large inoculum size, an environment of ischemia and devitalized tissue, or the presence of a foreign body.31, 96 Under any of these circumstances, bacteria contaminating an open wound are much more likely to adhere successfully to bone and produce an osteomyelitis.
S. aureus is far and away the most common isolate in all types of bone infection and is implicated in 50% to 75% of cases of chronic osteomyelitis.22, 26 Although the coagulase-positive staphylococci (S. aureus) are often cultured from the wound at the time of initial inspection, superinfection with multiple other organisms, such as coagulase-negative staphylococci (Staphylococcus epidermidis) and aerobic gram-negatives (Escherichia coli and Pseudomonas species), also commonly occurs.52 One study suggested that S. epidermidis and various gram-negative bacilli are each involved in approximately one third of cases of chronic osteomyelitis.8 Other studies implicated gram-negative rods in 50% of cases.106 Although the exact distribution of microbes may vary from one study to another, a consistent nding has been the much higher incidence of polymicrobial infection in chronic osteomyelitis compared with hematogenous osteomyelitis.11 This distinction should be recalled when selecting antibiotic coverage for the patient with presumed post-traumatic infection. Staphylococci are so frequently cultured in open wounds because they are ubiquitous organisms. Both S. aureus and S. epidermidis are elements of normal skin ora, with S. aureus in greater numbers in the nares and anal mucosa and S. epidermidis more prevalent on the skin. Any traumatic event gives these bacteria a conduit to internal tissues. As mentioned, in the presence of wounded tissue, S. aureus has been shown to have an increased afnity for host proteins, a phenomenon ascribed to an interaction between its capsular polysaccharide and the exposed collagen and bronectin on traumatized bone.38, 49, 56, 139 Although S. aureus produces a variety of enzymes, such as coagulase, the role of these in vivo in blunting the impact of host defenses remains unclear. A surface factor that may be important in its pathogenicity is protein A, which has been shown to bind to immunoglobulin G and thereby inhibit host opsonization and phagocytosis. An additional reason S. aureus can lead to such persistent infection may be its ability to alter its structure altogether in surviving without a cell wall. This inactive L form allows S. aureus, and a variety of other bacteria, to live dormant for years, even in the presence of bactericidal levels of antibiotic.33, 42 Antimicrobial agents that exert their bactericidal activity by disrupting cell wall synthesis, as is the case with the beta-lactams (penicillins and cephalosporins), become ineffective when bacteria become cell wall decient or less metabolically active.147 Another way in which staphylococci, in particular S. epidermidis, elude antimicrobial action is by secreting biolm, a polysaccharide slime layer that dramatically increases bacterial adherence to virtually any substrate.14, 49, 83, 123, 152 First described by Zobell and Anderson in 1936,158 biolm is especially signicant in the pathogenesis of osteomyelitis because of its adherence to inert substrates, such as osteonecrotic bone, prosthetic devices, and acrylic cement. By establishing tight bonds with the glycoproteins of such substrates, biolm enables actively dividing staphylococci to form adherent, sessile communities. Like cell walldecient strains of S. aureus, these communities of dormant bacteria have demonstrated increased antimicrobial resistance.47, 91 In a similar fash-
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ion, biolm has been shown to protect S. epidermidis from the host immune response itself.43, 65 Like staphylococci, Pseudomonas aeruginosa is a ubiquitous organism, with soil and fresh water serving as its primary reservoirs. Puncture wounds of the foot involve P. aeruginosa in about 95% of cases,63 probably because of its prevalence in soil and moist, sweaty areas of skin. Pseudomonas species are implicated in many opportunistic infections, and thus its presence in the setting of chronic osteomyelitis is not unexpected. However, once P. aeruginosa has been introduced into host tissue, its pathogenic properties are less well dened than those of the staphylococci. Because this organism is one of the few obligately aerobic pathogenic bacteria (in contrast to S. aureus, a facultative anaerobe), its persistence in areas of hypoxic avascular bone is difcult to understand.
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CLASSIFICATION
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz There are a number of ways to classify a case of osteomyelitis. One way would be to label the osteomyelitis as either pediatric or adult, distinguishing the infection on the basis of its age of onset. Another possibility is describing it as either hematogenous or exogenousposttraumatic, distinguishing the infection on the basis of its pathogenesis. Finally, one could label it either acute or chronic, distinguishing the infection on the basis of whether it requires preexisting osteonecrosis. All of these classications are used more frequently than describing the osteomyelitis by its causative organism, which is of course the standard approach for classifying most other infectious diseases, such as labeling a pneumonia streptococcal or a meningitis meningococcal. The reason that the osteomyelitis literature has not used this nomenclature is probably that it is of little prognostic value. For example, it is of much greater therapeutic and prognostic consequence for the clinician to know whether osteonecrosis is present in a skeletal infection than whether S. aureus was one of the several microbes cultured. Whether the infection has been labeled as adult, post-traumatic, or chronic osteomyelitis, it is helpful to classify it further using the staging system developed by Cierny and colleagues in 1985.21 This system is currently the one most widely used for the classication of osteomyelitis.59 The Cierny-Mader staging system classies bone infection on the basis of two independent factors: (1) the anatomic area of bone involved and (2) the immunocompetence of the host. By combining one of the four anatomic types of osteomyelitis (I, medullary; II, supercial; III, localized; or IV, diffuse) with one of the three classes of host immunocompetence (A, B, or C), this system arrives at 12 clinical stages.21 Probably more important than memorizing each of these stages is understanding the different anatomic sites that can be involved in osteomyelitis (Fig. 191).21 As described by Cierny and colleagues, the primary lesion in medullary osteomyelitis (type I) is endosteal and conned to the intramedullary surfaces of bone (i.e., a hematogenous osteomyelitis or an infection of an intramedullary rod). Supercial osteomyelitis (type II) is a true
Localized
Diffuse
FIGURE 191. Anatomic types of osteomyelitis as they relate to the osseus compartment. (Redrawn from Cierny, G., III; Mader, J; Penninck, J. Contemp Orthop 10:5, 1985.)
contiguous focus infection in which the outermost layer of bone becomes infected from an adjacent source, such as a decubitus ulcer or a burn. Localized osteomyelitis (type III) produces full-thickness cortical cavitation within a segment of stable bone. It is frequently observed in the setting of fractures or when bone becomes infected from an adjacent implant. When the infected fracture does not heal and there is through-and-through disease of the hard and soft tissue, the condition is called diffuse osteomyelitis (type IV). Patients with post-traumatic osteomyelitis almost always have type III or type IV disease. The immunocompetence portion of the Cierny-Mader classication straties patients according to their ability to mount an immune response. A patient with a normal physiologic response is labeled an A host, a compromised patient a B host, and a patient who is so compromised that surgical intervention poses a greater risk than the infection itself is designated a C host. A further stratication is made in B hosts on the basis of whether the patient has a local (BL), systemic (BS), or combined (BS, L) deciency in wound healing. An example of a local decit in wound healing would be venous stasis at the site of injury, whereas systemic decits would include malnutrition, renal failure, diabetes, tobacco or alcohol use, or acquired immunodeciency syndrome. Other less frequently used classication systems have also been developed. One of the older classication systems was created by Kelly and co-workers66, 67 and stratied bone infections on the basis of their etiology: type I described an infection secondary to hematogenous spread, type II referred to an infection with fracture union, type III was an infected nonunion, and type IV meant that there was an exogenous infection without a fracture. A
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subsequent classication system for post-traumatic tibial osteomyelitis was based on the status of the tibia and bula after surgical de bridement.82 Although most of the classication systems developed for osteomyelitis address the extent of the skeletal infection, they do not give a detailed picture of the condition of the bone. Specically, they do not address issues such as limb length, limb alignment, involvement of adjacent joints, or the presence of bone gaps. Although these are all important, such descriptive features are not necessary in the initial evaluation of osteomyelitis and may only confuse the clinician as he or she tries to determine whether surgical intervention is needed. In order to make this determination, it is helpful to consult Cierny and Maders classication system. In their schema, dead space management does not play a large role in any infection deemed to be either a medullary (type I) or supercial (type II) osteomyelitis. However, if an infection is labeled a localized (type III) osteomyelitis, there is usually the need for simple measures to stabilize the bone and dead space management. Any infection classied as diffuse (type IV) osteomyelitis would require extensive skeletal stabilization and extensive dead space management. In this way, the Cierny-Mader classication for osteomyelitis remains the most useful of its kind.
rare. More commonly, recurrent drainage of small, trivialappearing sinus tracts is the only sign that infection may be present (Fig. 193). The extent of infection and the fact that these tracts communicate with bone are often underappreciated. In addition to determining the presence of infection, the involved limb in general should of course be assessed during the physical examination. This assessment includes a thorough evaluation of its neurovascular status, the condition of its soft tissues, its length, alignment, and the presence of any structural deformities. CULTURES Culturing drainage uid, if any is present, is easy to do in the ofce. Although potentially helpful in identifying causative bacteria and guiding antibiotic choice, these results must be interpreted with caution, because such specimens often yield opportunistic organisms that have simply colonized the nutrient-rich exudate. As a result, these cultures may provide no evidence of the organisms that are actually infecting the damaged bone.24 Because the results from cultures of sinus tracts and purulent discharge are dubious, the diagnosis of chronic osteomyelitis can be denitively made only by intraoperative biopsy.77 PLAIN FILM
DIAGNOSIS
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Initial Assessment
HISTORY Chronic osteomyelitis is a diagnosis that can potentially be achieved with a thorough history of the patient. It should be suspected in anyone presenting with bone pain who has a past history of trauma or orthopaedic surgery. Complaints include persistent pain, erythema, swelling, and drainage localized to an area of previous trauma, surgery, or wound infection. Walenkamp150 described a classic history as cyclical pain, increasing to severe deep tense pain with fever, that often subsides when pus breaks through in a stula. Although these cyclical episodes are almost pathognomonic for chronic osteomyelitis, they do not occur in everyone with the disease. Most of the time, symptoms are vague and generalized (e.g., My leg is red and hurts), making it difcult to differentiate between a cellulitis and a true infection of bone. EXAMINATION Classically, the cardinal signs of inammation are rubor (redness), dolor (tenderness), calor (heat), and tumor (swelling). If these signs are noted on physical examination, it is fair to conclude that an infection is present. However, as with the history, signs of an actual osteomyelitis are often difcult to distinguish from those of an overlying soft tissue infection. Ones suspicions of a bone infection may be conrmed by the presence of exposed necrotic bone, surgical hardware, or draining stulas (Fig. 192). However, such physical examination ndings are
Plain radiographs play an important role in the workup of chronic osteomyelitis, because they provide the clinician with a sense of the overall bony architecture, limb length and alignment and the presence of orthopaedic implants, as well as any fractures, malunions, or nonunions. Radiographic ndings of chronic osteomyelitis can be subtle and include osteopenia, thinning of the cortices, and loss of the trabecular architecture in cancellous bone.110 Once the bone becomes necrotic and separated from normal bone by an involucrum sheath, it becomes easier to identify on plain lm. When they are isolated in this way, sequestra appear radiodense relative to normal bone. It is essential to obtain views of the involved bone that include its adjacent joints so that their integrity may be adequately assessed. Furthermore, it is important to include oblique views so as to detect the presence of subtle malunions that may not be seen in the anteroposterior plane alone. Plain lms do not play as large a role in the initial workup of acute osteomyelitis, because they typically do not show changes in the bone characteristic of osteomyelitis until 10 to 14 days after the onset of infection. LABORATORY STUDIES White blood cell (WBC) counts, erythrocyte sedimentation rates (ESRs), and C-reactive protein (CRP) levels have traditionally been part of the workup of any patient with suspected musculoskeletal infection. In an immunocompetent individual, elevated levels of these laboratory values are fairly sensitive indicators of some sort of acute infection, particularly when the WBC count has a so-called left shift (i.e., an elevated ratio of polymorphonuclear leukocytes to other white cells). The ESR is a measurement
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FIGURE 192. The presence of (A) exposed bone or (B) exposed hardware can be an obvious sign that an underlying skeletal infection is present.
of the rate at which red blood cells sink toward the bottom of a test tube and separate from plasma. The ESR is elevated when the erythrocytes clump abnormally well because of an abundance of serum globulins, such as brinogen, which are usually produced in response to inammation. CRP is another acute phase reactant and a similar marker for systemic inammation. There is a paucity of studies showing a correlation between laboratory values and the presence of bone infection, although one group of investigators has shown
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FIGURE 193. The extent of skeletal infection is often underappreciated by physical examination.
CRP to be useful in the early detection of sequelae-prone acute osteomyelitis.116 Unfortunately, all of these values are rather nonspecic to skeletal infection and thus add little to the clinicians ability to distinguish a supercial inammatory process, such as a cellulitis, from a deeper osteomyelitic one. Furthermore, although theoretically helpful in screening for an acute infection, the WBC count, ESR, and CRP are frequently normal in the setting of chronic osteomyelitis and thus are neither sensitive nor specic for it.150 To understand why this may be so, it is helpful to reconsider the pathophysiology underlying acute and chronic osteomyelitis. Because acute osteomyelitis is a disease characterized by a vigorous inux of phagocytes and other inammatory cells into hematogenously seeded bone, it follows that a laboratory test that indicates systemic inammation should be a sensitive marker for infection. However, this should not necessarily be the case in chronic osteomyelitis, which is a disease characterized by devitalized tissues and a muted inammatory response. It makes sense, therefore, that WBC counts and acute phase reactants, such as ESR and CRP, are often normal in cases of chronic osteomyelitis. Although Cierny and Mader24 recommended following all their patients with monthly WBC counts and ESRs for 6 months, there is reason to believe from the vertebral osteomyelitis literature that these values do not always correlate well with response to treatment and may be of limited value.16 Nutritional parameters, such as albumin, prealbumin, and transferrin, are helpful to obtain in the workup of a patient with suspected chronic osteomyelitis so that malnutrition can be identied and reversed before taking the patient to the operating room. It has been shown that
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imaging (MRI), are frequently useful in determining whether skeletal infection is present and, if so, in helping to evaluate the extent of the disease. NUCLEAR MEDICINE STUDIES Traditionally, radionuclide scintigraphy has been the initial advanced imaging study ordered. The three-phase bone scan, as it is better known, is regarded as an excellent screening tool for chronic osteomyelitis, with a sensitivity exceeding 90%.81 Performed in three phases using Tc 99m methylene diphosphonate, the bone scan suggests soft tissue infection when the rst two phases (arterial and venous) are positive and the third phase (focal bone uptake) is negative. True skeletal infection should be considered when all three phases are positive, including the delayed (2- to 4-hour) images (Fig. 194).101 However, it is well known that a variety of noninfectious insults to bone, such as the repeated surgeries and hardware implants that are so common in this population of patients, also cause the third phase to be positive. As a result, the three-phase bone scan is a notoriously nonspecic test for chronic osteomyelitis (specicity as low as 10%).122 With a high sensitivity and a poor specicity, three-phase bone scintigraphy should be regarded as a screening tool for patients with suspected bone infection but may not be relied on for providing a denitive diagnosis. Another radiopharmaceutical that has been classically used in the diagnosis of osteomyelitis is gallium citrate. Gallium scintigraphy, in conjunction with the three-phase technetium scan, was the rst dual-tracer technique available for evaluating chronic osteomyelitis.74 As a calcium and iron analogue, gallium is thought to bind to transferrin as it leaks from the blood stream to areas of skeletal inammation. The primary role of gallium scintigraphy currently is in evaluating the patient with suspected vertebral osteomyelitis.101 Although gallium provides the best way to detect vertebral osteomyelitis radiographically, labeled leukocyte imaging is the nuclear imaging test of choice for osteomyelitis elsewhere in the body.101 The principle behind radiolabeled leukocyte imaging, which uses radionuclides such as indium and technetium, is that white blood cells localize around areas of inammation (Fig. 195). What makes this technique so useful in theory is that, unlike the situation in three-phase bone scintigraphy, labeled leukocytes should not accumulate around areas of increased bone mineral turnover unless an infection is present. Results have been variable over the years, with some
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FIGURE 194. With its increased localized activity of the tracer 3 to 4 hours after injection, this three-phase bone scan suggests infection of the patients distal left femur.
orthopaedic surgery patients who are malnourished have signicantly higher infection rates than those who have a normal nutritional status.64 Presumably, it would follow that patients who already have infection present would be more likely to respond to therapy if their nutrition were optimized beforehand.
Advanced Imaging Studies

History, physical examination, plain lms, and laboratory work usually establish the diagnosis of infection but do not always dene the extent to which the bone is involved and therefore the presence of a true osteomyelitis. Additional imaging modalities, such as a variety of nuclear medicine studies, computed tomography, and magnetic resonance
FIGURE 195. These leukocytelabeled images suggest multiple areas of bilateral pedal osteomyelitis.
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FIGURE 196. Sulfur colloid marrow scans can be used in conjunction with other studies to serve as a control of normal marrow activity. Congruence between the radionuclide uptake in the leukocyte-labeled image (WBC) and the sulfur colloid marrow scan (Marrow) suggests that there is not an infection present in this patients proximal tibia. Looking at the leukocyte-labeled image alone might lead one to the incorrect diagnosis.
studies reporting rather poor testing accuracies156 and others reporting outstanding ones, with sensitivities and specicities exceeding 90% for cases of nonvertebral chronic osteomyelitis.72, 85 On the whole, it can be said that most investigators have found leukocyte labeling to be just as sensitive as three-phase bone scintigraphy in detecting chronic osteomyelitis, but with a dramatically increased specicity. A fairly representative study was conducted by Blume and colleagues10 in 1997 that showed a nearly 60% increase in the specicity of leukocyte labeling (86%) over that of three-phase bone scintigraphy (29%) in the detection of pedal osteomyelitis. Specicity of leukocyte imaging can be increased further when performed in conjunction with a marrow scan. Marrow scans, such as those using sulfur colloid, improve diagnostic accuracy by delineating areas of normal bone marrow activity to compare with the areas of increased radionuclide uptake elsewhere. A congruence between the radionuclide uptake in a leukocytelabeled image and in a marrow scan suggests that there is not an actual infection present (Fig. 196). In contrast, an incongruence between the two is strongly suggestive of infection, with accuracies reported to be as high as 98%.100, 101 COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING Although nuclear medicine studies are frequently the rst radiologic tests used to supplement plain lm in the evaluation of bone infection, computed tomography and MRI can be useful as well. Computed tomographic scans are known to have excellent resolution of cortical bone and sequestra and may be helpful in the preoperative planning for difcult infections.126 In the 1990s, MRI began replacing computed tomography at most hospitals for evaluating the extent of osteomyelitis, because it provides the most detailed imaging of the hard and soft tissues (Fig. 197). MRI is highly benecial in surgical planning by providing information regarding the extent of soft tissue edema as well as the location of hidden sinus tracts and abscesses. Initial screening usually consists of T1- and T2-weighted images. On T1-weighted images, there is decreased signal intensity of the marrow in infected areas.
On T2-weighted images, infection is signaled by no change or an increased signal. This bright signal is due to the high water content of granulation tissue.133 Although there are false positives caused by tumors or healing fractures,143 the sensitivity and specicity of MRI in the diagnosis of osteomyelitis remain excellent, ranging from 92% to 100% and 89% to 100%, respectively.7, 133, 143 Because a negative MRI study effectively rules out the diagnosis of chronic osteomyelitis, it is recommended by some as the most appropriate step after a nondiagnostic radiograph in determining whether to treat.146 Although MRI has extremely high sensitivity and specicity for chronic osteomyelitis, it is frequently not possible to obtain this study because of the presence of metal at the site of infection, as is
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FIGURE 197. Magnetic resonance imaging (MRI) provides excellent detail of the hard and soft tissues. This MRI scan demonstrates extensive intramedullary involvement as well as surrounding soft tissue edema in a patient with post-traumatic osteomyelitis of the right femoral diaphysis.
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frequently the case in patients with a history of skeletal trauma.
MANAGEMENT
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Overview of Decision Making

The denitive treatment of chronic osteomyelitis includes the surgical elimination of all devitalized hard and soft tissues. Only by completely excising all avascular tissue is it possible to arrest this self-perpetuating infection. Filling in the dead space created by de bridement, providing adequate soft tissue coverage, stabilizing the fracture or nonunion (if present), and administering antibiotics are important adjuncts in management. The excision of necrotic tissue represents the key step in arresting infection in patients with chronic osteomyelitis. In certain cases in which the area of osteonecrosis is limited, only a modest excision may be required. In other instances, however, the extent of osteonecrosis may be so great that adequate de bridement necessitates a limb amputation. The rst question to be asked, then, when dealing with a patient with chronic osteomyelitis is precisely whether the limb can be salvaged. If limb salvage is deemed possible, the second question to ask is whether the patient can tolerate the procedure (or, as is so often the case, multiple procedures) required for complete de bridement. The answer to this question depends on the patients systemic and local capabilities for wound healing. For example, limb salvage procedures that may be feasible for a healthy teenager may be life-threatening for an elderly individual with cancer. These differences in host immunocompetence hearken back to the Cierny-Mader classication, which introduced the concept of C hosts as those in whom the risks of surgery outweigh the risks of infection.21 In such individuals, an alternative course of action to arresting the infection would be to retain the dead bone and suppress bacterial activity with long-term antimicrobial therapy. If limb salvage is deemed feasible and the patient is thought to be able tolerate the surgery, a third question to ask is whether the patient wishes to go down a path that frequently involves multiple surgical procedures and months, if not years, of physical and emotional hardship. Answering this question requires a thoughtful dialogue between doctor and patient as well as with the patients family. Finally, the patient and his or her family should understand that, despite embarking down the path of limb salvage surgery, the end result may still be an amputation. A study that reviewed 31 patients with long bone chronic osteomyelitis treated with combined de bridement, antibiotic bead placement, and bone grafting showed that 4 patients (13%) had received amputations at an average follow-up of 4 years.20 This gure is not insignicant and suggests that there is a select group of patients who would benet from early amputation. Because of the tremendous amount of resources allocated to ultimately failed limb salvage procedures, society at large may also benet from identifying this group.12
Although not specically directed at the population with chronic osteomyelitis, several classication systems have been described over the past few decades that attempt to sort out which post-traumatic injuries would most likely end in amputation. In 1976, Gustilo and Anderson52 demonstrated that type III open fractures had the worst prognosis for subsequent amputation. A decade later, they created a subclassication for type III fractures (IIIC, dened as those involving arterial injury requiring repair) that predicted even poorer outcomes.53 Amputation rates for type IIIC fractures have been reported to exceed 50%.55, 73 The Mangled Extremity Severity Index46 and Mangled Extremity Severity Score55 have also traditionally been used as guides for prognosis. Despite all of the classication systems that have been developed, the decision regarding amputation remains a highly subjective one based on the experience of the surgeon and the desires of the patient. Unless obvious criteria for amputation are met, this decision truly remains more of an art than a science.32
Amputation
As mentioned, at the beginning of every treatment algorithm for chronic osteomyelitis is the question of whether the limb is, in fact, salvageable. In circumstances in which patients have such extensive infection and osteonecrosis that segmental resection and limb reconstruction are not possible, amputation may be necessary to arrest the disease. Early amputation may give such an individual with extensive infection the best chance to be symptom-free and to return to his or her level of functioning as soon as possible. Once amputation is selected as a treatment modality, the level of amputation must be chosen. In the 1930s, most amputations for tibial osteomyelitis were done above the level of the knee to ensure that there was enough blood supply for adequate healing. With the experience of large numbers of below-knee amputees in World War II, this approach grew out of favor as it was learned that amputating across the femur put the patient at a disadvantage for future prosthetic use and ambulation.89 Although it has been shown that the energy expenditure required for ambulation is much greater in aboveknee than below-knee amputees,41 studies comparing energy expenditure for different levels of transtibial amputees indicate that there is no ideal level at which to perform a below-knee amputation (BKA). A reasonable empirical guideline that adjusts for differences in patients height is to select the level at which the calf muscle belly attens out into the aponeurosis. The most proximal level of a BKA that still allows proper knee function is just distal to the tibial tubercle where the extensor mechanism inserts. Using 15 cm below the knee joint line or 3 to 4 ngerbreadths distal to the tibial tubercle as landmarks has been shown to provide safe markers.5, 13 Although the surgical technique for performing amputations varies among surgeons, most would agree that the key to this operation is identifying and ligating all major neurovascular structures. Unlike amputations done for dry gangrene, amputations in the setting of infection (wet gangrene) are
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shrink wraps or Ace bandages become important in protecting the wound, promoting wound healing, and minimizing edema. These dressings are usually kept on for a few days unless signs or symptoms of infection develop. POSTOPERATIVE CARE During the rst couple of postoperative days, physical therapy should be initiated to aid in transfers and in-bed range-of-motion and strengthening exercises. Non weight-bearing ambulation with the aid of parallel bars, walkers, or crutches should begin soon thereafter. The patient is ready to be tted for a temporary prosthesis when the suture line is healed, usually 6 to 8 weeks postoperatively.5 Some prosthetists favor tting patients even before the suture line has healed, 10 to 14 days after surgery. Prostheses are of great practical value, because they require a considerably lower energy expenditure than ambulation with crutches.86 An important and often overlooked aspect of postoperative care is teaching the patient how to put on his or her prosthesis so that there is total contact between stump and prosthetic socket. Training can take 2 to 3 weeks for unilateral below-knee amputees. After the rst several postoperative weeks, physical and occupational therapists should focus their efforts on goals of increasing mobility and functional independence, especially as they relate to activities of daily living. The patient is usually tted for a permanent prosthesis at about 3 to 6 months, after the greatest amount of stump shrinkage has occurred. The preceding discussion has focused on BKAs simply because of the prevalence of post-traumatic osteomyelitis of the tibia. Of course, above-knee or through-knee amputations become necessary when the area of osteonecrosis and subsequent infection has expanded more proximally. The principles of these procedures, as well as amputations elsewhere in the body, are basically the same as those outlined for the BKA. Dissection should proceed compartment by compartment, with major neurovascular structures being identied and ligated. At approximately 6 to 8 weeks, the above-knee amputee who is a candidate for a prosthetic limb may be tted and begin gait training.5
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FIGURE 198. Below-knee amputations in the setting of osteomyelitis are usually left open and closed in a delayed fashion to minimize the chance of recurrent infection.
usually staged with initial open amputation followed by a delayed closure (Fig. 198). TECHNIQUE During a BKA, the surgeon should proceed systematically through each compartment of the lower leg, rst dissecting the soft tissues of the anterior compartment (anterior to the interosseus membrane) and isolating and clamping the anterior tibial vessels and deep peroneal nerve. Using a periosteal elevator, the periosteum of the tibia should be stripped distally from the level of transection. This process should continue posteriorly, carefully avoiding damage to the tibial vessels of the deep posterior compartment. The bula is then cleared of soft tissue a few centimeters proximal to the level of the tibial transection. Both the tibia and bula are transected, usually with an oscillating or Gigli saw. The posterior tibial and peroneal vessels, as well as the tibial nerve, are then isolated and clamped. The soleus muscle in the supercial posterior compartment is then dissected away from the medial and lateral heads of the gastrocnemius to the level of the tibial stump and transected just distal to the clamped neurovascular structures. The posterior ap, which consists of the remaining gastrocnemius muscle, receives its blood supply from sural arteries coursing off the popliteal artery. The muscles of the lateral compartment are excised and the supercial peroneal nerve is clamped. All vessels are ligated and all nerves are ligated in traction, transected distally, and allowed to withdraw from the stump. To avoid dislodgment of ligatures, pulsatile arteries should be suture-ligated. The end of the tibia, especially the anterior portion that lies subcutaneously, should be beveled and the sharp edges smoothed with a rasp. After the stump is closed, whether it be in primary or delayed fashion, immediate compressive dressings such as
Limb Salvage
In circumstances where there is a documented progressive destruction of bone, limb salvage is deemed feasible, and the patient is thought to be able to tolerate surgery, radical de bridement should be thought of as the most fundamental intervention. Even if the patient is asymptomatic, symptoms such as fever and pain are likely to return as long as the area of osteonecrosis remains. If the preceding criteria are met and the patient feels that the benets of limb salvage surgery (surgeries) outweigh its risks and hardships, treatment should be initiated along the following path21, 23, 24, 54, 134, 150: 1. 2. 3. 4. Thorough de bridement of necrotic tissue and bone Stabilization of bone Obtaining intraoperative tissue cultures Dead space management
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5. Soft tissue coverage 6. Limb reconstruction 7. Systemic antibiotic therapy We discuss each of these treatment principles in turn. DE uBRIDEMENT Make an incision or opening that will thoroughly uncover (saucerize) the infected area. . . . Remove as much foreign material and dead or dying tissue as possible . . . do not remove bony or soft parts that may contribute to repair. . . . Fill entire cavity. . . .99 Although this may look like the most recent guidelines for the treatment of chronic osteomyelitis, these excerpts were in fact taken from an article written by H. Winnett Orr in 1930. Although some of his recommendations on the management of bone infection are now outdated, his emphases on thorough de bridement and lling in of subsequent dead space are as relevant today as they were 70 years ago. Despite all the advances in medical technology over this time period, the quality of the surgical de bridement remains the most critical factor in successfully managing chronic osteomyelitis.134 Even with detailed imaging techniques such as MRI, it is often difcult to assess the extent of osteonecrosis and infection preoperatively. Before making an incision, Walenkamp150 supported the practice of injecting an obvious stula with methylene blue dye to localize the focus of infection. This, he said, should cause the patient to feel the same or similar pain as during the stowing of pus. Cierny and colleagues21 have not found the use of dyes to be helpful, however. Once the area of necrosis is localized, de bridement proceeds using a variety of instruments, such as curettes, rongeurs, and high-speed power burrs. Stated simply, the goal of surgery is the complete excision of all dead or ischemic hard and soft tissues (Fig. 199). If not removed, they would serve as a nidus for recurrent infection and cure would be impossible. If adequate de bridement is the key to treatment, the question arises: how does the surgeon know when all of the necrotic bone has been removed? Classically, punctate haversian bleeding, referred to as the paprika sign,21 has been used as a sign of healthy bone and helps establish the limits of de bridement. However, this sign may not always be relied on, such as during de bridements of dense cortical bone or operations in which a tourniquet is used. In such cases where there is less bleeding, the use of a laser Doppler probe may be helpful in establishing skeletal viability.131 However, in general, this practice can be rather cumbersome and is not currently regarded as the standard of care.134 In addition to surgical excision of all necrotic tissues, the infected areas should be copiously irrigated. Authors from Patzakis and colleagues106 to Gustilo and Anderson52 have recommended from 10 to 14 L of normal saline to wash out the contaminated material. The efcacy of de bridement has been shown to be optimized by highpressure pulsatile lavage using uid pressures of 50 to 70 pounds per square inch and 800 pulses per minute.9 Although adding various antibiotic solutions to the process
of irrigation has become common practice for many surgeons, such practices have not been supported by the literature. The work of Anglen and associates1, 2 has, in fact, shown soap solution to be the only mixture more effective than normal saline irrigation in reducing bacterial counts. Although a thorough de bridement is necessary for eliminating all pathogenic bacteria, it is frequently not sufcient. Because of antimicrobial resistance factors, such as bacterial secretion of biolm, persistent infection is unfortunately a fairly common occurrence. In a study of 53 patients who had positive cultures at the time of their initial de bridement for chronic osteomyelitis of the tibia, 26% still did at the time of their second de bridement.105 To arrest this disease, therefore, several trips to the operating room for repeated de bridements and a variety of reconstructive procedures are often necessary. In a study reviewing 189 patients with chronic osteomyelitis, Cierny and colleagues21 found that the average number of operations for a patient undergoing limb salvage was 3.8. In his approach to chronic osteomyelitis, Ciernys focus during the rst operation is on a thorough de bridement of all necrotic tissues, fracture stabilization, and the acquisition of tissue biopsies. He then takes patients back to the operating room approximately 5 to 7 days after this initial surgery for a repeated de bridement. Cierny uses this second look both to make sure that the wound is viable and to address the issue of dead space management (usually with the placement of antibiotic beads or a cancellous bone graft, or both). STABILIZATION OF BONE In 1974, Rittman and Perren113 conducted a study that showed that rigid stabilization of bone facilitated union in
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FIGURE 199. A thorough excision of all devitalized tissues constitutes the cornerstone of management in chronic osteomyelitis. Although adequate de bridement may sometimes require limb amputation, at other times, as shown here, the removal of a solitary mass of necrotic tissue and hardware is sufcient.
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the setting of chronic osteomyelitis. In this study, tibial osteotomies were performed on sheep and stabilized by plates of varying rigidities. Pathogenic bacteria were injected into the osteotomy site 1 week after surgery, which produced changes equivalent to those seen in chronic osteomyelitis. After 8 weeks of follow-up, it was shown that bone union of these infected sites was correlated with the degree of skeletal stabilization. One reason for this may be that skeletal stability promotes revascularization, thus enhancing perfusion at the fracture site.19 This enhanced perfusion may maximize the hosts immune response, which allows it to resist infection at the fracture site more effectively.19 The method by which fracture stability is obtained is not inconsequential. Although several studies support primary intramedullary nailing of open tibial fractures over external xation, citing superior postoperative outcomes,120, 121, 135 this technique is usually not recommended when the trauma is more than 12 hours old, when there is extensive soft tissue damage, or in the presence of osteomyelitis.109 In such cases, bacteria are more likely to gain access to the intramedullary canal and potentially infect the entire diaphysis. There are data to support the use of external xation in the presence of infection. After stabilizing experimental osteotomies with either an external xator or an intramedullary rod and then contaminating these sites with S. aureus, a group of investigators in 1995 found the sites stabilized with external xators to have fewer and less severe infections than those stabilized internally.28 Gustilo54 claimed that primary intramedullary nailing should be avoided altogether in all type III open fractures, arguing that they already have compromised periosteal and extraperiosteal circulations (i.e., from surrounding muscle) secondary to injury. In such cases, he recommended achieving skeletal stabilization through plating or external xation (Fig. 1910).54 INTRAOPERATIVE CULTURES The denitive diagnosis of post-traumatic osteomyelitis is made by isolating bacteria from the intraoperative biopsy specimen of the involved bone.77 Although the best specimens are generally thought to be tissue fragments directly from the center of infection,150 there is evidence to suggest that copious intraoperative cultures from a variety of sources may be benecial. Comparing the results of bacterial cultures from various sites in long bone chronic osteomyelitis, Patzakis and co-workers107 found the culture of bone biopsy specimens to be inadequate for identifying all organisms present. As a result, they recommended that intraoperative culture specimens be taken from the sinus tract, samples of purulent material, and samples of soft tissue, in addition, of course, to the involved bone. To avoid false-negative culture results, patients might be encouraged to stop taking antibiotics at least 1 week before surgery. Unfortunately, doing so may have the unintended effect of instigating a cellulitis in the soft tissues. If this occurs and becomes very uncomfortable for the patient, the clinician may wish to restart antibiotics. If the symptoms of the cellulitis are manageable, it is in the
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FIGURE 1910. External xators are frequently used to achieve fracture stabilization in the presence of infection or massive soft tissue injury.
patients best interest to remain without antibiotics before surgery. After deep cultures have been obtained in the operating room, broad-spectrum intravenous antibiotics are started if the causative organism is unknown. Coverage is narrowed when culture and sensitivity results return from the laboratory. DEAD SPACE MANAGEMENT When the bone and tissues deemed devitalized have been removed, the focus shifts toward managing the dead space that is left behind. Healing with secondary intention is discouraged, because the scar tissue that would ll the defect is avascular and may lead to persistent drainage.21 Antibiotic Beads Since the 1980s, many surgeons have favored lling this space, at least initially, with polymethyl methacrylate beads impregnated with antibiotic, usually an aminoglycoside (such as gentamicin) or vancomycin (Fig. 1911). Although polymethyl methacrylate is the most widely used drug delivery system, calcium hydroxyapatite implants that become incorporated into host bone have also been shown to be effective.157 Whatever the material, the antibiotic-laden beads are placed directly in the operative wound, which is then primarily closed. Unless the depot material is biodegradable, almost all antibiotic bead chains are intended for removal at a later date. Generally, they remain in the wound for approximately 4 weeks. Beads placed within the intramedullary canal, however, should be removed sooner (within 2 weeks) before the layer of granulation tissue has formed, which would make removal difcult.134 The beads should be oriented in layers from deepest to most supercial. Adequate concentrations of
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FIGURE 1911. Antibiotic beads serve a dual role as a local depot of antibiotic in the de bridement site as well as a temporary ller of dead space. Polymethylmethacrylate (PMMA) beads connected together in a chain are the most widely used drug delivery system.
from the iliac crests, greater trochanter, or proximal tibia. Grafting involves taking small strips of cancellous bone from these areas and packing them down over a fresh granulation bed in the de brided area. Papineau and colleagues104 pioneered this technique and recommended taking the grafts in strips 3 to 6 cm long by 3 mm thick by 4 mm wide and placing them in concentric and overlapping layers to ll in the defect completely.103 Cancellous grafts have the benet of being able to become rapidly revascularized and incorporated in the nal bone structure. Open cancellous grafting has produced some excellent outcomes, with clinical success rates ranging from 89% in 1979104 to 92% in 1984118 and 100% in 1995.36 SOFT TISSUE COVERAGE
antibiotic can be achieved only when it diffuses from the beads into the postoperative wound hematoma, which serves as a transport medium. Thus, open wound treatment or irrigation-suction drainage is incompatible with this mode of therapy.70 Several clinical trials have supported the efcacy of local antibiotic bead implantation.18, 70, 151 Even though the gentamicin concentration remains at sufcient levels for approximately 30 days after implantation, some skeptics may claim that beads are benecial only insofar as they are able to ll dead space. This argument is difcult to make in light of animal studies demonstrating the efcacy of antibiotic beads in eradicating osteomyelitis above and beyond placebo beads that have no antibiotic.92 Thus, it appears that bead chains are helpful not only by serving as a temporary ller of dead space before reconstruction but also as an effective depot for the local administration of antibiotic. Cancellous Bone Graft After antibiotic beads are placed, dressings are applied to the wound and changed frequently to promote the growth of a healthy layer of granulation tissue, a process that can take 2 to 4 weeks. After this time period, the wound is usually suitable for the second stage of dead space management, namely, reentry and bone reconstruction. Bone reconstruction is usually achieved with an autogenous cancellous bone graft. Bone chips are typically taken
The soft tissues covering the area of skeletal injury must be allowed to heal or the patient will be at a very high risk for persistent or recurrent infection. After the necrotic tissues are excised, the de brided (and possibly bone grafted) area can conceivably be covered in one of three ways: (1) simply by letting the tissues heal by secondary intention, (2) by split-thickness skin grafting, or (3) by muscle transfer (Fig. 1912). The last two techniques are favored in almost all cases of post-traumatic osteomyelitis and should be performed after a layer of granulation tissue has formed. Covering the de brided site with a well-vascularized tissue graft offers the healing bone a new blood supply and thus decreases the chance of deep infection.79, 155 Delayed coverage is associated with a higher chronic infection rate.60 Local muscle aps, which have the advantage of keeping vascular supply intact, are almost always used if an adjacent muscle is available. Although local muscle aps work well for the proximal two thirds of the tibia, the more distal one third requires the use of transplanted aps in order to provide a sufcient soft tissue envelope for healing. These so-called free aps were developed in the early 1980s and are usually from such donor muscles as rectus abdominis, latissimus dorsi, gracilis, and tensor fasciae latae.3 It is difcult to study the isolated effect that the use of muscle transfers has had on clinical outcome. After all, this technique is almost always used in combination with several other therapeutic modalities, such as bone grafting,
FIGURE 1912. The use of muscle transfers, with or without overlying skin grafts, guards against persistent or recurrent infection by lling the dead space created by surgical de bridement with well-vascularized tissue.
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antibiotics, and of course de bridement. Nonetheless, there is certainly a large amount of evidence that supports the use of muscle aps as part of the therapeutic regimen.3, 4, 39, 84 Fitzgerald and colleagues,39 using either local or free aps combined with thorough de bridement and antibiotics, reported a 93% success rate in treating a sample of 42 patients with chronic osteomyelitis. These results demonstrated a signicant improvement over previous treatment regimens that did not employ the use of muscle ap coverage. In another study, which retrospectively reviewed 34 patients with chronic osteomyelitis of the tibia, it was found that those who had received free muscle ap transfers as part of their surgical treatment were more likely to be drainage-free after more than 7 years of follow-up than patients who had received de bridement alone.84 Although the primary purpose of local or free muscle transfer is to revascularize the de brided area, it also serves a purpose akin to bone grafting by simply lling in the dead space created by surgery. This notion is supported by studies that have found the recurrence of infection in patients with lower leg osteomyelitis to be signicantly reduced when the muscle aps completely pack the cavity left by surgical de bridement.125, 141 LIMB RECONSTRUCTION Sometimes the segmental defects in bone left from de bridement or from the injury itself cannot be corrected with antibiotic beads, bone graft, and muscle aps alone. The technique used for the reconstruction of such defects (and the malunion and angulation deformities so common in the setting of infected open fractures) depends on the patient and the type of deformity that is present.102 Long-term cast therapy, for instance, is an option for the management of relatively minor nonunions. Other possibilities include open reduction and plate xation, intramedullary nailing, and electrical stimulation. Electrical stimulation is discussed in Complementary Therapies later in the chapter. One of the more recent developments in the management of more severe nonunions and infected nonunions has been the dynamic external xation technique described by Ilizarov. In the Ilizarov method,62 an area of noninfected bone is corticotomized and allowed to begin the healing process with a normal fracture callus. This area of callus is then distracted progressively over small increments using an external xator device. In this way, Ilizarov external xation gradually stimulates skeletal regeneration, which can be of obvious value in correcting the segmental, rotational, translational, and angular deformities frequently seen in patients with post-traumatic osteomyelitis. This method of so-called distraction osteogenesis, wherein bone is lengthened at one quarter of a millimeter every 6 hours, should be distinguished from compression osteogenesis, which can be described as pressing the bone ends together in a fracture or delayed union until they are stable enough to heal by themselves. In both distraction and compression techniques, bone transport may serve as an adjunct to facilitate osteogenesis across segmental defects. Although there are many drawbacks to the Ilizarov method, such as pain from the external xator, frequent
pin infections, and a long period of time spent in the device (almost 9 months on average),15, 30 it has produced excellent outcomes in several studies.30, 44, 102, 112, 142 What makes this mode of treatment even more valuable to patients is that it allows them to remain ambulatory throughout its duration.15, 45, 51, 62 Although the method of distraction osteogenesis has been shown time and again to aid in limb reconstruction, it should be remembered that it is not a cure-all. As emphasized earlier in the chapter, some extremities are so severely compromised by traumatic injury, infection, or the extent of surgical de bridement that amputation may be the inevitable outcome. These patients should be identied early and spared futile reconstructive attempts. However, even in patients who have salvageable limbs, Ilizarov limb relengthening is not a panacea. In part, its success depends on the preoperative planning of the orthopaedic surgeon, who must determine how to employ the principles of distraction osteogenesis during the course of reconstruction. Generally speaking, the surgeon may wish to proceed down one of two reconstructive paths: (1) acutely shortening the extremity via resection of a diseased or malunited segment of bone with compression at that site, followed by limb relengthening, or (2) holding the extremity out to length and using bone transport to ll in the gap. In patients who have only a short segment of diseased bone (i.e., on the order of 4 cm or less), the rst technique is probably the better option. However, if the length of the necrotic bone exceeds 4 cm, this technique becomes less favorable because of both the greater distance through which the limb must be shortened and the potential danger of kinking blood vessels when the excess soft tissue envelope is compressed together. In instances in which a large bone gap exists, it probably makes more sense to hold the limb out to length and transport bone into the defect. To elucidate the application of these two approaches, we describe how each was used in the care of patients seen in our bone infection clinic at the University of Connecticut Health Center. Illustrative Cases of Reconstructive Strategies
CASE 1
zzzzzzzz z z Acute Shortening and Relengthening z z z The reconstructive strategy of acute shortening and limb z z z relengthening consists of the following steps: (1) excising the z z z necrotic bone and avascular scar, (2) applying the Ilizarov z z z external xator, (3) acutely shortening the limb by compresz z z sion at the excision site, (4) making a corticotomy proximal or z z z distal to the excision site, (5) providing soft tissue coverage if z z necessary, and nally (6) relengthening through the cortiz z z cotomy site. z z z This technique, most effectively employed if the length of z z z the necrotic bone is less than or equal to 4 cm, is illustrated z z z by the case of Mr. J.S., a 27-year-old man who was referred to z z z our clinic with chronic osteomyelitis and nonunion of his z z z right tibia. Three years before, he had sustained a grade IIIB z z open fracture of his right tibial diaphysis in a motorcycle z z z accident. At the time of the accident, he was initially treated z z z with external xation, which was later converted to an z z z intramedullary nail. Unfortunately, because Mr. J.S. went on z z z
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to have a diaphyseal osteomyelitis, this nail had to be removed and a second external xator was applied (Fig. 1913). In addition to the massive comminution and displacement of the fracture, his right leg sustained signicant soft tissue damage secondary to the accident that required both a gastrocnemius muscle ap and a split-thickness skin graft to cover the exposed bone adequately (Fig. 1914). When the patient arrived at our clinic, he had no external xator in place and the skin grafts were healing quite well (Fig. 1915). He complained of pain with walking. On physical examination, the patients right leg was in obvious varus. There was no erythema, uctuance, or sinus tracts visible on the overlying skin. The gastrocnemius ap was pink, and he was neurovascularly intact with nearly full range of motion at the knee and ankle. Radiographic examination revealed a nonunion of the right tibia with approximately 25 degrees of varus and 30 degrees of dorsal angulation (Fig. 1916). A bone scan was negative for active infection. At this point, a lengthy conversation was held with the patient and limb salvage was decided on. Mr. J.S. was instructed to stop the oral antibiotics he had previously been prescribed (to optimize the yield of intraoperative cultures), and surgery was scheduled for a few weeks after this visit. In the operating room, it was rst important to determine how much tibial bone was involved in the disease process. To visualize the area in question, an incision was made lateral to the anterior muscle ap and dissection was continued down to the periosteum of the previous fracture site. Using a periosteal elevator to identify its cortices, the bone was found to be very sclerotic about 1.5 cm on either side of the nonunion. There was no evidence of frank pus. At this point, intraoperative biopsy specimens were obtained and sent for culture. Given the fact that the area of necrosis was limited,
z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z
the decision was made to pursue a course of acute shortening followed by limb relengthening. The next aspect of the surgery was thorough de bridement of the sclerotic bone at and around the nonunion site. Using an oscillating saw, a 4-cm portion of the tibia that included the nonunion site was resected. The diaphyseal bone both proximal and distal to the de bridement area was curetted to bleeding bone. The area was irrigated with several liters of soap and saline by pulsatile lavage. Drill holes were made both proximally and distally to allow adequate purchase of the reduction forceps that would compress the diaphyseal shaft. Before compression, a bular osteotomy was also done at this level, approximately at the junction of the middle and distal thirds of the bula. As the two ends of the tibia were compressed together, proper alignment was veried with anteroposterior and lateral uoroscopic imaging. After an adequate reduction was achieved, the focus of the operation turned toward application of the Ilizarov external xator frame. When the xator was pinned to the proximal and distal portions of the tibia, rotational alignment was veried under uoroscopy and the frame was secured. The excision site was then placed under forceful compression. The nal part of this operation was to make a more distal metaphyseal corticotomy to allow subsequent limb relengthening. Although proximal corticotomies are often employed in this technique, a distal site was chosen in this patient simply because skin graft lay adherent to the bone more proximally. If the corticotomy were performed through the skin graft site, there would not have been the pliability and elasticity in the remaining soft tissue envelope necessary for adequate closure. Thus, the corticotomy that would serve as the regenerate zone for future limb relengthening was made distal to the excision site.
FIGURE 1913. Sequential radiographs of Mr. J.S. showing, from left to right, his leg after he had his initial injury (with external xator in place); his leg after the external xator was replaced with an intramedullary nail; and, lastly, his leg after the nail became infected and was removed in favor of a second external xator.
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FIGURE 1914. The massive soft tissue loss Mr. J.S. suffered from his initial injury necessitated a gastrocnemius muscle ap and split-thickness skin graft over the open area.
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The immediate postoperative course for Mr. J.S. was unremarkable. He received early mobilization from physical therapy with weight bearing as tolerated on the right lower extremity. Before discharge from the hospital on postoperative day 3, the patient was instructed in how to lengthen the Ilizarov apparatus by approximately one quarter of a millimeter four times a day starting 1 week after the operation. Although he was maintained with intravenous antibiotics during his brief hospital stay, Mr. J.S. was discharged home with oral antibiotics (a rst-generation cephalosporin and
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rifampin) to which his intraoperative culture (S. aureus) would prove to be sensitive. Radiographs 2 weeks after his operation revealed excellent alignment and distraction at the distal corticotomy but unfortunately some distraction at the more proximal compression site. This area was compressed further in the ofce by tightening the Ilizarov rings closer together. Three weeks postoperatively, the patient was ambulating on crutches without difculty. Although the right leg was measured and found to be fully out to length approximately 4 months after the surgery, adequate fusion at the compression site remained problematic and the decision was made to augment the area with multiple half-pins and cancellous bone graft from the posterior iliac crest. After bone grafting, the patient did very well, and follow-up radiographs over the next several months
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FIGURE 1915. On our initial physical examination, Mr. J.S. demonstrated well-healed soft tissues of his leg.
FIGURE 1916. Initial radiographs of Mr. J.S. at our clinic revealed a nonunion of the right tibia with approximately 25 degrees of varus and 30 degrees of dorsal angulation.
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FIGURE 1917. Sequential radiographs of Mr. J.S.s leg over several months show, from left to right, increasing incorporation of the bone graft at the more proximal compression site as well as progressive lengthening, though in the more distal regenerate zone.
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z showed increasing incorporation of the bone graft at the z z compression site as well as progressive lengthening and bone z z z formation in the regenerate zone (Fig. 1917). z z z Because Ilizarov external xation allows early weight z z z bearing, Mr. J.S. remained active during the course of his z z z treatment and continued to enjoy many of his favorite z z z activities, including bow hunting (Fig. 1918). Seven months z z z after visiting our clinic, with radiographic evidence of z z excellent bone formation at both the proximal compression z z z site and the distal regenerate zone, Mr. J.S. was brought back z z z to the operating room to have the external xator removed. z z z He did extremely well in the months to follow, using only a z z z right leg orthosis for support. One year after the initial z z z operation, Mr. J.S. was found to have no leg length disparity z z z and to be enjoying an extremely active life. Radiographic z z examination showed excellent leg alignment, with further z z z callus formation at both the proximal and distal sites (Fig. z z z 1919). z z z zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz
CASE 2
z z z z z z z z z z z z z z z z z z z z z z z z
his left distal tibia in a motorcycle accident. His past medical history was signicant for insulin-dependent diabetes mellitus, intravenous drug abuse, and smoking two packs of cigarettes a day for over 20 years. Previous intraoperative cultures had been positive for methicillin-resistant S. aureus, for which Mr. J.L. had been treated with several months of intravenous vancomycin therapy. Surgically, he was initially treated with external xation, bone grafting, and free ap
zzzzzzzz z z Bone Transport z z z If the segment of necrotic bone and tissue to be resected is z z z large, employing a strategy of acute shortening and limb z z z relengthening may be difcult. Although it is certainly z z z possible, compressing together two diaphyseal ends over a z z z distance much greater than 4 cm risks buckling the remaining z z z soft tissue envelope and compromising its vascular supply. In z z such circumstances, a more favorable reconstructive strategy z z z z is not to shorten the limb at all but to hold it out to length and z z subsequently ll in segmental gaps with bone transport. This z z z technique consists of the following steps: (1) excising the z z z necrotic bone and avascular scar, (2) applying the Ilizarov z z z external xator, (3) holding the limb at length, (4) making a z z z corticotomy proximal or distal to the excision site, (5) z z providing soft tissue coverage if necessary, (6) lengthening z z z through the corticotomy site, and (7) transporting bone to the z z z excision site. z z z This strategy can be used to ll large gaps within bone, to z z z fuse diseased joints, or sometimes both, which happened to z z z be the case with Mr. J.L., a 39-year-old man who came to our z z z clinic 15 months after sustaining a grade IIIB open fracture of z z z
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FIGURE 1918. This picture of Mr. J.S. bow hunting with his Ilizarov external xator frame in place illustrates that patients are able to remain active during their treatment.
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FIGURE 1919. Sequential radiographs demonstrating, from left to right, progressive bone formation at both the proximal compression site and distal regenerate zone. The last lm was taken 1 year after Mr. J.S.s initial operation, approximately 5 months after his external xator was removed. It shows abundant callus formation at both the proximal and distal sites.
z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z
coverage. He had been doing fairly well until 1 year after his injury, when he suffered a fracture through his bone grafting site. At that point he had a repair of his nonunion, followed by repeated bone grafting. Since that time, from about 12 to 15 months after the initial trauma, he had been complaining of intermittent fevers and persistent drainage from his wounds. On initial physical examination, the patients left lower extremity was remarkable for a draining wound on both the medial and lateral aspects of his ankle. He had a free ap over the dorsum of his ankle that appeared to be healthy. He was
z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z
neurovascularly intact distally with fair range of motion at the ankle joint. Plain lms revealed a nonunion of his left distal tibia and bula with posterior and medial angulation of the distal fragment (Fig. 1920A). The presumptive diagnosis of an infected distal tibial metaphysis with articular involvement was made. At this point, a lengthy discussion was conducted with the patient and his family regarding therapeutic options. In particular, given the patients multiple co-morbidities and his treatment failure over a 15-month period with several previous surgeries and a prolonged vancomycin trial, amputation was given a great deal of consideration.
FIGURE 1920. A, Plain radiograph of Mr. J.L.s left leg at the time of his initial visit reveals a nonunion of his left distal tibia and bula with medial angulation of the distal fragment, in which there are ve screws. B, Plain lm 3 months postoperatively shows increasing distraction at the proximal corticotomy site. C, Radiograph 10 months after the initial surgery reveals a 9-cm distraction zone at the proximal corticotomy site, allowing the tibia nearly to reach the talus. D, At 14 months after the initial placement of the external xator, plain lm demonstrates bone fusion at the tibiotalar docking site and adequate bone growth in the regenerate zone.
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z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z z
Mr. J.L. understood that amputation would most likely return him to work sooner than if he embarked on a course of limb salvage surgery. Furthermore, he was made aware that proceeding down the path of attempted limb salvage would probably require an additional year in an external xator. The importance of ceasing all substance and tobacco use was emphasized. Finally, it was discussed that, despite everyones best efforts, embarking on a course of limb salvage might ultimately result in a below-knee amputation. In the end, Mr. J.L. was rm in his decision to try to save his leg. As a result, all antibiotics were stopped and surgery was scheduled. Because the amount of diseased bone appeared to be extensive (affecting the distal tibia and ankle joint), the planned approach was to resect all of the necrotic areas, hold the limb out to length, and use bone transport to achieve a fusion between the remaining tibia and the talus. Three weeks after his initial visit, Mr. J.L. was brought to the operating room and underwent a radical excision of approximately 7 cm of necrotic distal tibia. The area was irrigated copiously with pulsatile lavage. In addition, antibiotic beads were placed, an Ilizarov external xator applied, and a corticotomy performed proximal to the area of resection. Antibiotic beads were used in this case and not in that of Mr. J.S. because the site of disease here was being held out to length rather than being compressed. As a result, a vast potential space was created in which residual bacteria could proliferate. Before lling this dead space with antibiotic beads, intraoperative biopsy specimens were obtained and sent for culture. In the months that followed his surgery, Mr. J.L. did very well with oral antibiotics (trimethoprim-sulfamethoxazole and metronidazole) to which his intraoperative culture (methicillin-resistant S. aureus) was sensitive, remaining afebrile and without drainage. Radiographs showed increasing distraction at the proximal corticotomy site (see Fig. 1920B). The antibiotic beads were exchanged approximately 3 months after their placement and again at 5 months. Exchanging beads is important not only to maintain an adequate depot of local antibiotic but also to adjust to the decreasing size of the resection site. Ten months after the initial surgery, radiographs revealed a 9-cm distraction zone at the proximal corticotomy, allowing the tibia nearly to reach the talus (see Fig. 1920C). Proper alignment continued to be maintained. Because the limb was determined to be nearly out to length, Mr. J.L. was brought back to the operating room for the bone transport phase of the reconstruction. The antibiotic beads, having fullled their role as temporary llers of dead space, were removed to create room for the graft. The leading edges of the tibia and talus were rede brided to healthy, bleeding bone, and cancellous graft from the posterior iliac crest was transported to augment the fusion site. Although the patient did well immediately after the surgery, he returned 1 month postoperatively complaining of foul-smelling drainage from his medial and lateral ankle wounds. For this, the patient was soon brought back to the operating room for an incision and drainage. Cultures at that time revealed Xanthomonas and Enterococcus species sensitive to doxycycline. The patient did well with a regimen of doxycycline, trimethoprimsulfamethoxazole, and metronidazole and his wounds closed secondarily over the next several months. Approximately 14 months after the initial placement of the external xator, all of the drainage had cleared. Radiographically, the bone fusion at the tibiotalar docking site and the bone growth in the regenerate zone appeared sufciently strong (see Fig. 1920D). With the fusion site and regenerate zone no longer needing protection, the decision was made to bring the patient back to the operating room to have the
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FIGURE 1921. Radiographs of Mr. J.L.s leg at (A) 2 years and (B) 3 years after his initial operation conrm successful tibiotalar fusion and continued cortical re-formation of the regenerate zone.
external xator removed. This procedure went smoothly, and z z z 6 months later Mr. J.L. was symptom-free and ambulatory. z z z Radiographs at this time and 1 year later conrmed successful z z z tibiotalar fusion and continued cortical re-formation of the z z z regenerate zone (Fig. 1921). z z z zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz
SYSTEMIC ANTIBIOTIC THERAPY As mentioned from the outset, systemic antibiotic therapy is the most appropriate therapy for acute osteomyelitis, in which bone is still well vascularized. The treatment of vertebral osteomyelitis is also primarily with antibiotics,68 although there is a role for surgery in cases of severe vertebral destruction.80 In contrast, of course, the role for systemic antibiotics in the management of chronic osteomyelitis is mostly adjunctive, helping to keep the surrounding, viable tissues infection-free after de bridement. Much attention has been given in the past to the ability of various antibiotics to penetrate bone and to the role of high blood levels of antibiotics in promoting that penetration. In our view, this is problematic because the site of infection that is of fundamental concern is dead bone, usually surrounded by inammatory cells or frank pus. The focus of disease therefore is not only avascular but also surrounded by an acidic and hypoxic environment, precisely the conditions that render penicillins and cephalosporins unstable and
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aminoglycosides inactive.111, 136, 140, 145 Furthermore, in the necrotic bone, it is likely that the bacteria are not very metabolically active, rendering the action of any antibiotic much less potent.48, 90 It is clear that, in the setting of chronic osteomyelitis, systemic antibiotics should be thought of as adjuncts in the management of what is a primarily surgical illness. Antibiotic administration is helpful in this setting only insofar as it allows optimal healing of the operative site and decreases the risk of infection in surrounding and distant sites.137 After intraoperative tissue culture specimens are taken from the infected bone, the patient should be restarted with broad-spectrum intravenous antibiotics to cover the common offending agents, such as S. aureus and P. aeruginosa.52 When culture results are available, the antibiotic choice should be tailored to the patients specic organisms and their sensitivities. For S. aureus, a penicillinase-resistant penicillin or rst-generation cephalosporin is usually the best choice. If the S. aureus is oxacillin resistant, other agents may be effective, such as trimethoprim-sulfamethoxazole, clindamycin, doxycycline or minocycline, or a quinolone. It is our custom to supplement any agent used in treatment with 1 to 2 months of rifampin on the basis of animal studies95, 98, 128 as well as clinical data.93, 94 The approach is similar for other staphylococci and gram-negative organisms: choose an antibiotic on the basis of in vitro sensitivities and, with laboratory conrmation of rifampin sensitivity, supplement with rifampin. Although commonly used for therapy of tuberculosis and of difcult to treat staphylococcal infections, rifampin is truly a broad-spectrum antibiotic, inhibiting the majority of bacteria of any genus. Although a very active agent, it cannot be used as sole therapy because of a high spontaneous mutation rate in Staphylococcus, Mycobacterium, and presumably other species of bacteria. Patients treated with rifampin monotherapy for pyogenic infections can be expected to have active infections and rifampinresistant bacteria within 1 to 2 weeks. The appropriate duration of systemic antibiotic therapy is not currently known. Interestingly, some of the best results reported in the literature are from a group who used antibiotics only perioperatively, coupled with aggressive de bridement.35 Recalling the pathophysiology of chronic osteomyelitis, this approach seems to be entirely logical but one that requires incredible fortitude on the part of both patient and surgeon. Many of the patients in this study were taken to the operating room several times during the rst week. At the University of Connecticut Health Center, we generally have our patients continue antibiotics until the operative site has healed completely (approximately 3 to 4 months). As long as antibiotics are chosen that have been shown to be active against the infecting microbes in vitro, the route of antibiotic delivery (i.e., oral or intravenous) is probably inconsequential.132 Although intravenous therapy has long been the norm in the treatment of post-traumatic osteomyelitis, there is evidence to suggest that switching to an oral route of administration earlier in the postoperative course may yield a similar outcome. Swiontkowski and co-workers132 conducted a study in which they treated 93 patients with chronic osteomyelitis
with combined surgical de bridement, soft tissue coverage, and an antibiotic regimen of 5 to 7 days of intravenous therapy followed by oral antibiotics for 6 weeks. They compared the outcomes of these patients with those of a group of 22 patients treated previously with the same surgical management but 6 weeks of culture-specic intravenous antibiotics. Interestingly, there were no differences in the outcomes of the two groups. Certainly, if these data are reproduced, an increasing number of centers will adopt this treatment regimen given the inherent advantages of oral therapy: enhanced comfort of the patient, decreased chance of line infection, and improved costefciency. COMPLEMENTARY THERAPIES Several so-called complementary therapies have been used with some regularity in the treatment of chronic osteomyelitis and deserve mention in this chapter. Such therapies have as their goal either improvement of the host response to infection or promotion of healing of the bone. Hyperbaric oxygen has long been proposed as an adjunctive measure that would improve host defenses at the site of infection. The principle behind this treatment is that low oxygen tensions in infected bone inhibit the normal activity of immune mediators, such as macrophages and polymorphonuclear leukocytes. In in vitro studies, for example, S. aureus is not killed by polymorphonuclear leukocytes incubated in either severely hypoxic or anaerobic environments, with intermediate levels of hypoxia causing lesser reductions in killing efciency. Furthermore, as we have discussed, the activity of many antibiotics is greatest in aerobic environments. Hyperbaric oxygen therapy, which increases oxygen tension above 250 mm Hg, is theorized to augment the hosts immune system, create a hostile environment for anaerobes, allow the formation of peroxides that kill bacteria, and promote wound healing.75, 76 Although the use of hyperbaric oxygenation has shown some promise in several studies,57, 61, 75, 76 there has not yet been a single controlled study to our knowledge that demonstrates its utility in the treatment of chronic osteomyelitis. Other complementary modalities are used in an attempt to enhance skeletal healing after the infection has been controlled. One such modality is electrical stimulation. That electrical stimulation may have a role in inducing the healing of delayed unions and nonunions is based on ndings that fractures in bone have a negative charge and manipulating that potential can lead to alterations in fracture healing.6, 40 Three different types of electrical stimulation delivery are commonly described (direct current, inductive coupling, and capacitive coupling),108 and each of them has data that support its efcacy. One study from 1990 demonstrated healing in 12 of 20 patients with delayed tibial unions treated with inductive coupling compared with 1 of 20 who were in a randomized, blinded placebo group.127 A 1994 study reported equally impressive results in cases of long bone nonunions: 6 of 10 in the capacitive coupling group were healed versus 0 of 10 who received treatment with placebo.124 The indication for this mode of therapy is having a nonunion that is in acceptable alignment. Contraindications for electrical stimulation
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include an unacceptable malalignment, the presence of septic pseudarthrosis, and a gap of greater than half the diameter of the bone.27 Another means of stimulating bone healing is ultrasound. In a multicenter, prospective, randomized, doubleblind, placebo-controlled study, using low-intensity ultrasound was shown to decrease the amount of time to radiographic union in the treatment of displaced distal radius fractures.71 Although the reasons behind this nding are currently unclear, it is theorized that ultrasound waves act as a mechanical deforming force that acts as an impetus for accelerated bone formation.117 The role of ultrasound in treating chronic osteomyelitis is not well dened.
SUMMARY
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz Chronic osteomyelitis is most often due to trauma and generally has a protracted, indolent clinical course. It should be acknowledged as a concrete abscess and treated with a combined approach of surgical de bridement, skeletal stabilization, dead space management, soft tissue coverage, and antibiotic therapy. Although these principles are the cornerstone of management, it is important to recognize the formidable physical and psychologic challenges facing patients with chronic osteomyelitis and foster a multidisciplinary approach in their care. The entire staff of health care professionals, from physicians and nurses to physical therapists and social workers, must work together to communicate effectively and compassionately with the patient and his or her family to establish a dynamic, ongoing dialogue. In so doing, we may be able not only to treat disease but also to educate people about their condition, from the practical importance of dressing changes or quitting smoking to a more global understanding of its frequently unrelenting nature.
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SECTION I General Principles 66. Kelly, P.J.; William, W.J.; Coventry, M.B. Chronic osteomyelitis: Treatment with closed irrigation and suction. JAMA 213:1843, 1970. 67. Kelly, P.J. Infections of bones and joints in adult patients. Instr Course Lect 26:3, 1977. 68. Khan, I.A.; Vaccaro, A.R.; Zlotolow, D.A. Management of vertebral diskitis and osteomyelitis. Orthopedics 22:758, 1999. 69. Klein, M.B.; Chang, J. Management of hand and upper-extremity infections in heart transplant recipients. Plast Reconstr Surg 106:598, 2000. 70. Klemm, K. Antibiotic bead chains. Clin Orthop 295:63, 1993. 71. Kristiansen, T.K.; Ryaby, J.P.; McCabe, J.; et al. Accelerated healing of distal radial fractures with the use of specic low-intensity ultrasound. J Bone Joint Surg Am 79:961, 1997. 72. Krznaric, E.; DeRoo, M.; Verbruggen, A.; et al. Chronic osteomyelitis: Diagnosis with technetium-99m-D,L-hexamethylpropylene amine oxime labeled leukocytes. Eur J Nucl Med 23:792, 1996. 73. Lange, R.H. Limb reconstruction versus amputation decision making in massive lower extremity trauma. Clin Orthop 243:92, 1989. 74. Lisbona, R.; Rosenthall, L. Observations on the sequential use of 99mTc-phosphate complex and 67Ga imaging in osteomyelitis, cellulitis, and septic arthritis. Radiology 123:123, 1977. 75. Mader, J.T.; Adams, R.K.; Wallace, W.R.; et al. Hyperbaric oxygen as adjunctive therapy for osteomyelitis. Infect Dis Clin North Am 4:433, 1990. 76. Mader, J.T.; Brown, G.L.; Guckian, J.C.; et al. A mechanism for the amelioration by hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits. J Infect Dis 142:915, 1980. 77. Mader, J.T.; Cripps, M.W.; Calhoun, J.H. Adult posttraumatic osteomyelitis of the tibia. Clin Orthop 360:14, 1999. 78. Marshall, K.A.; Edgerton, M.T.; Rodeheaver, G.T.; et al. Quantitative microbiology: Its application to hand injuries. Am J Surg 131:730, 1976. 79. Mathes, S.J.; Alpert, B.S.; Chang, N. Use of the muscle ap in chronic osteomyelitis: Experimental and clinical correlation. Plast Reconstr Surg 69:815, 1982. 80. Matsui, H.; Hirano, N.; Sakaguchi, Y. Vertebral osteomyelitis: An analysis of 38 surgically treated cases. Eur Spine J 7:50, 1998. 81. Maurer, A.H.; Chen, D.C.P.; Camargo, E.E. Utility of three-phase scintigraphy in suspected osteomyelitis: Concise communication. J Nucl Med 22:941, 1981. 82. May, J.W.; Jupiter, J.B.; Weiland, A.J.; Byrd, H.S. Clinical classication of post-traumatic tibial osteomyelitis. J Bone Joint Surg Am 71:1422, 1989. 83. Mayberry-Carson, K.J.; Tober-Meyer, B.; Smith, J.K.; et al. Bacterial adherence and glycocalyx formation in osteomyelitis experimentally induced with Staphylococcus aureus. Infect Immun 43:825, 1984. 84. Maynor, M.L.; Moon, R.E.; Camporesi, E.M.; et al. Chronic osteomyelitis of the tibia: Treatment with hyperbaric oxygen and autogenous microsurgical muscle transplantation. J South Orthop Assoc 7:43, 1998. 85. McCarthy, K.; Velchik, M.G.; Alavi, A.; et al. Indium-111labeled white blood cells in the detection of osteomyelitis complicated by a pre-existing condition. J Nucl Med 29:1015, 1988. 86. Moshirfar, A.; Showers, D.; Logan, P.; Esterhai, J.L. Prosthetic options for below knee amputations and nonunion of the tibia. Clin Orthop 360:110, 1999. 87. Muha, J. Local wound care in diabetic foot complications. Aggressive risk management and ulcer treatment to avoid amputation. Postgrad Med 106:97, 1999. 88. Munoz-Fernandez, S.; Macia, M.A.; Pantoja, L.; et al. Osteoarticular infection in intravenous drug abusers: Inuence of HIV infection and differences with non drug abusers. Ann Rheum Dis 52:570, 1993. 89. Murdoch, G. Levels of amputation and limiting factors. Ann R Coll Surg Engl 40:204, 1967. 90. Musher, D.M.; Lamm, N.; Darouiche, R.O.; et al. The current spectrum of Staphylococcus aureus infection in a tertiary care hospital. Medicine (Baltimore) 73:186, 1994. 91. Naylor, P.T.; Myrvik, Q.N.; Gristina, A.B. Antibiotic resistance of biomaterial-adherent coagulase-negative and coagulase-positive staphylococci. Clin Orthop 26:126, 1990.
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