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THE KURSK STATE MEDICAL UNIVERSITY DEPARTMENT OF SURGICAL DISEASES 1

OSTEOMYELITIS

Information for self-training of English-speaking students The chair of surgical diseases N 1 (Chair-head - prof. S.V.Ivanov)

BY ASS. PROFESSOR I.S. IVANOV

KURSK-2010

INTRODUCTION Osteomyelitis is a difficult-to-treat infection of bone and bone marrow. It is progressive and results in inflammatory destruction of the bone, bone necrosis, and new bone formation. Bacterial osteomyelitis causes substantial morbidity worldwide, despite continued progress toward understanding its pathophysiology and optimal management. The approach to osteomyelitis depends upon the route by which bacteria gained access to bone, bacterial virulence, local and systemic host immune factors, and patient age. While imaging studies and nonspecific blood tests may suggest the diagnosis, an invasive technique is generally required to identify the causative pathogens. Antibacterial regimen selection has been largely guided by knowledge of the relative activities and pharmacokinetics of individual drugs, supported by data from animal models. Definitive therapy often requires a combined medical and surgical approach. Newer microvascular and distraction osteogenesis techniques and the use of laser Doppler allow more complete surgical resection of infected material while maintaining function. Despite recent advances, aggressive medical and surgical therapy fails in many patients with osteomyelitis. More accurate diagnostic methods, better ways to assess and monitor the effectiveness of therapy, and novel approaches to eradicate sequestered bacteria are needed. History of the Procedure: Osteomyelitis has been well known since antiquity. Problem: Osteomyelitis results in inflammatory destruction of the bone, bone necrosis, and new bone formation. Three major categories of osteomyelitis exist, based upon pathogenic mechanisms of infection, as follows:

Osteomyelitis following hematogenous spread of infection Osteomyelitis secondary to a contiguous focus of infection Osteomyelitis associated with vascular insufficiency

Three different subtypes of osteomyelitis are known: acute osteomyelitis, subacute osteomyelitis, and chronic osteomyelitis. Frequency: The overall prevalence of acute osteomyelitis is 2 cases per 10,000 children. Neonatal prevalence is approximately 1 case per 1000 children. The annual incidence in patients with sickle cell anemia is approximately 0.36%. The prevalence of osteomyelitis after foot puncture may be as high as 16% (30-40% in patients with diabetes). Excluding the axial skeleton, lower extremity osteomyelitis accounts for 90% of osteomyelitis cases and is much more common than upper extremity osteomyelitis, which accounts for 10% of extremity cases.

The most common bones involved in osteomyelitis in descending order are as follows:

Tibia (50%) Femur (30%) Fibula (12%) Humerus (3%) Ulna (3%) Radius (2%)

The prevalence of chronic osteomyelitis is 2 cases per 10,000 people. Most studies support the idea that incidence is similar in developed countries. In developing countries, incidence is higher due to higher incidence of puncture wounds, contaminated injuries, and less wound care. Epidemiology of vertebral osteomyelitis It is primarily a disease of adults; most patients are older than 50 years. Generally, the incidence increases progressively with each successive decade of life. Men are affected approximately twice as often as women in most case series. The reason for this male predominance is not clearly understood. Reliable information regarding the overall incidence of vertebral osteomyelitis is difficult to obtain. However, most authorities believe that the overall incidence of vertebral osteomyelitis has steadily increased in recent years for 3 primary reasons: increasing rates of nosocomial bacteremia due to intravascular devices and other forms of instrumentation, increasing age of the population, and increasing injection drug use. Etiology: While normal bone is resistant to infection, a number of conditions can predispose one to development of osteomyelitis, including the following:

Large inoculation of an organism Trauma leading to bone damage or infarction Presence of a foreign body Illnesses compromising host defense

A single pathogenic organism is almost always recovered from the bone. The most common bone isolates are Staphylococcus species, the most common gram-negative organism is Pseudomonas aeruginosa, and the most common anaerobes are Peptostreptococcus species. However, in immunocompromised patients, other organisms, including fungi and mycobacteria, also must be considered. Commonly isolated organisms in osteomyelitis can be summarized as follows:

Hematogenous osteomyelitis (monomicrobial infection) o Infants (<1 y) Group B Streptococcus Staphylococcus aureus Escherichia coli o Children (aged 1-16 y) S aureus Streptococcus pyogenes

Haemophilus influenzae o Adults (>16 y) S aureus Coagulase-negative Staphylococcus species Gram-negative bacilli P aeruginosa Serratia marcescens E coli Contiguous focus osteomyelitis (polymicrobial infection) o S aureus o Coagulase-negative Staphylococcus species o S pyogenes o Enterococcus species o Gram-negative bacilli o Anaerobes Diabetic foot osteomyelitis (polymicrobial Infection) o S aureus o Streptococcus species o Enterococcus species o Proteus mirabilis o P aeruginosa o Anaerobes

Pathophysiology: The pathogenesis of osteomyelitis is multifactorial and poorly understood. Some important factors include the following:

Virulence determinants of the organisms Underlying disease and the immune status of the host Type and location of the bone

It is clear that bacterial cells adhere to nucleated cells, platelets, and a variety of components of the extracellular bone matrix collagen and noncollagenous proteins. Cellular and molecular pathogenesis Cellular and molecular techniques provide new methods for determining the relative importance of the many potential virulence factors by facilitating study of the interaction between the host immune response and potential bacterial virulence factors. As an example, S aureus, which is an important cause of both hematogenous and contiguous focus osteomyelitis, produces a large number of extracellular and cell-associated factors that may contribute to virulence, including the following:

Bacterial adherence: Bacteria adhere to bone by expressing receptors for the components of bone matrix including fibronectin, laminin, collagen, and bone sialoglycoprotein. Adherence appears to play a central role in the early stages of S aureusinduced osteomyelitis or arthritis. Expression of adhesins permits attachment of the pathogen to cartilage and synovial membrane. Strains positive for collagen

adhesin are also associated with the production of high levels of immunoglobulin G (IgG) and interleukin (IL)6. Bone infection has been speculated to be possibly prevented by an adhesin-derived vaccine. Proteolytic activity: Potential proteolytic activity present in normal joints is inhibited in the absence of infection. However, this protective effect may be lost with infection. In an in vitro model of adult chondrocytes inoculated with S aureus, for example, overall protein synthesis was reduced by 84%, with an increase in the release of collagenase and gelatinase. Resistance to host defense mechanisms: The ability of microorganisms to resist host defense mechanisms at both the cellular and matrix levels presents difficulties in the treatment of osteomyelitis. S aureus can survive intracellularly in cultured osteoblasts. Furthermore, the presence of arachidonic acid metabolites such as prostaglandin E2, which is a strong osteoclast agonist, decreases the bacterial inoculum needed to produce infection. Once the microorganisms adhere to bone, they express phenotypic changes that make them resistant to antimicrobial treatment. o S aureus organisms express a 42-kd protein, protein A, which is bound covalently to the outer peptidoglycan layer of their cell walls. Protein A binds to the Fc portion of IgG on polymorphonuclear leukocytes, interfering with opsonization and phagocytosis of S aureus. This interference has been demonstrated in vitro and in animal models of subcutaneous abscess and peritonitis. o S aureus also secretes 2 toxins: exotoxin and toxic shock syndrome toxin (TSST)1, which exert a profound effect on the immune system when administered parenterally. The toxins act as superantigens and suppress plasma cell differentiation. They also stimulate production of cytokines, such as IL-1, interferon-gamma, and tumor necrosis factor-alpha. Animals infected with strains of S aureus isogenic for TSST-1 developed frequent and severe arthritis. Staphylococcal enterotoxin and TSST-1 subvert the cellular and humoral immune system, which may determine whether a local infection is eliminated or develops into osteomyelitis or septic arthritis. Nitric oxide: The increased turnover of bone in osteomyelitis suggests that the balance between bone formation and resorption is altered, an effect that may be mediated by nitric oxide. Greatly increased levels of nitric oxide and bone resorption have been recorded in the septic skeleton. This response may be driven by the increased levels of cytokines, enterotoxin, and TSST-1, which may stimulate nitric oxide production by endothelial, macrophage, and mesenchymal cells such as osteoblasts. Thus, while low concentrations of nitric oxide are typically thought to inhibit osteoclastic bone resorption, this response may be lost when cytokine and nitric oxide levels increase greatly in skeletal inflammatory disease. Adjunctive local treatment of osteomyelitis with nitric oxide synthetase inhibitors could be beneficial.

Routes of infection As noted above, osteomyelitis develops via 3 major routes: hematogenous, contiguous focus spread, and vascular insufficiency.

Hematogenous osteomyelitis: Hematogenous osteomyelitis is predominantly encountered in children; 85% of patients with hematogenous osteomyelitis are younger than 17 years, accounting for 20% percent of the total cases of osteomyelitis. In one study of 659 cases of S aureus osteomyelitis occurring in Denmark from 1959-1988, the number of hematogenous osteomyelitis cases declined, especially in children, and cases of vertebral osteomyelitis, more common in adults, increased. In children, the bone infection usually affects the long bones, while in adults, the lesion is usually located in the thoracic or lumbar vertebrae. Contiguous focus osteomyelitis without generalized vascular insufficiency: Osteomyelitis secondary to contiguous foci of infection accounts for at least one half of all cases and has increased in incidence. The organisms may be directly inoculated into the bone at the time of trauma, spread by nosocomial contamination during perioperative or intraoperative procedures, or extend from an adjacent soft tissue infection. Contiguous focus osteomyelitis with generalized vascular insufficiency: The primary cause of vascular insufficiency in patients with osteomyelitis is diabetes mellitus. The small bones of the feet, talus, calcaneus and distal fibula, and tibia are commonly involved. The patients in this group are aged 35-70 years. The infection frequently is initiated by a portal of entry for organisms, such as infected nail beds, cellulitis, or atrophic skin ulceration.

Diminished arterial blood supply has traditionally been considered to be the major predisposing factor for contiguous focus osteomyelitis with generalized vascular insufficiency in patients with diabetic foot. However, neuropathy now appears to be an equally important factor. Identifiable neuropathy as a complication of diabetes mellitus is present in approximately 80% of patients with foot disease. Neuropathy can cause foot ulceration through 3 main mechanisms, as follows:

Decreased sensation leads to mechanical or thermal injuries in the unaware patient that can develop into skin ulcerations. Motor neuropathy affecting the intrinsic muscles of the foot predisposes affected persons to gait disturbances and foot deformities, such as hammertoe, clawtoe deformity, and Charcot foot. These anatomic alterations can lead to a maldistribution of weight and elevated focal pressure over the bony prominences. Subsequently, the increase in pressure where the foot contacts the ground or rubs against shoes can lead to skin ulceration. Autonomic neuropathy interferes with sweating; the resultant dry, cracked skin allows entry of microorganisms into the soft tissue.

A higher rate of nasal and skin colonization with S aureus, defects in host immunity, and impaired wound healing are all important factors in diabetic foot infection. Superficial fungal skin infections, which are common in patients with diabetes, also can facilitate bacterial entry through macerated or broken skin. Pathological differences based on age Basic differences exist in the pathology of osteomyelitis in infants, children, and adults.

In infants, small capillaries cross the epiphyseal growth plate and permit extension of infection into the epiphysis and joint space. This is a newly well-understood condition referred to as septic osteomyelitis in infants. The cortical bone of neonates and infants is thin and loose, consisting predominantly of woven bone, which permits escape of the pressure caused by infection but promotes rapid spread of the infection directly into the subperiosteal region. A large sequestrum is not produced because extensive infarction of the cortex does not occur; however, a large subperiosteal abscess can form. In children older than 1 year, infection presumably starts in the metaphyseal sinusoidal veins and is contained by the growth plate. The joint is spared unless the metaphysis is intracapsular. The infection spreads laterally where it breaks through the cortex and lifts the loose periosteum to form a subperiosteal abscess. In adults, the growth plate has resorbed, and the infection may again extend to the joint spaces, as in infants. In addition, the periosteum is firmly attached to the underlying bone; as a result, subperiosteal abscess formation and intense periosteal proliferation are observed less frequently. The infection can erode through the periosteum, forming a draining sinus tract. Clinical: The clinical presentation and location of osteomyelitis differ in infants, children, and adults. In infants, medullary infection may spread to the epiphysis and joint surfaces through capillaries that cross the growth plate. In contrast, in children older than 1 year, the growth plate is avascular and infection is confined to the metaphysis and diaphysis. The joint is spared unless the metaphysis is intracapsular. Thus, cortical perforation at the proximal radius, humerus, or femur enables the infection to migrate to the elbow, shoulder, or hip joint, respectively, regardless of the age of the patient. Hematogenous osteomyelitis In hematogenous osteomyelitis, local symptoms referable to bones are more frequently absent in neonates than in children. In adults, soft tissue findings may be more prominent than bony involvement. In infants, local findings that may lead the clinician to suspect osteomyelitis are usually absent in neonates. When they develop, local findings can include decreased motion of a limb and edema (pseudoparalysis) and joint effusion adjacent to the bone infection (present in 60-70% of cases). Systemic symptoms are frequently present in S aureus osteomyelitis but may be absent when other pathogens are involved. Children with hematogenous osteomyelitis, in contrast with neonates, typically have the following systemic symptoms:

Abrupt fever Irritability Lethargy Refusal to use the affected limb Local signs of inflammation present for 3 weeks or less

While this is the classic presentation, signs of systemic toxicity other than minimal temperature elevation are absent in 50% of children with osteomyelitis. In adults, acute clinical presentations of fever, chills, swelling, and erythema over the involved bones are usually seen in acute hematogenous osteomyelitis. Vertebral osteomyelitis is usually hematogenous in origin but may be secondary to trauma. A preceding history of urinary tract infection or injection drug use often is present. Other sources of infection include skin and soft tissue, respiratory tract, infected intravascular device site, endocarditis, dental infection, or unknown sources. The patient usually presents with vague symptoms and signs consisting of dull, constant back pain and spasm of the paravertebral muscles. Localized pain and tenderness of the involved bone segments is present in at least 90% of cases. The pain is usually insidious and slowly progresses over 3 weeks to 3 months. Contiguous focus osteomyelitis without vascular compromise Common predisposing factors for contiguous focus osteomyelitis include surgical reduction and internal fixation of a fracture, open fractures, and chronic soft tissue infections. This form of osteomyelitis is biphasic in its age distribution. The infection occurs in younger persons secondary to trauma and related surgery and in older adults from decubitus ulcers. The infection usually manifests within 1 month after inoculation of the organisms from trauma, surgery, or a soft tissue infection. Affected patients typically present with lowgrade fever, pain, and drainage. Loss of bone stability, bone necrosis, and soft tissue damage frequently occur, making this form of osteomyelitis difficult to treat. Contiguous focus osteomyelitis with vascular compromise Osteomyelitis in patients with vascular compromise, who are often diabetic, can be difficult to diagnose. Patients can present with an apparently localized process including an ingrown toenail, a perforating foot ulcer, cellulitis, or a deep space infection. Concurrent peripheral neuropathy often alters the patient's perception of pain. Fever and systemic toxicity are frequently absent. Physical examination commonly reveals diminished dorsal pedis and posterior tibia pulses, poor capillary refill, and decreased sensation. Chronic osteomyelitis No exact criteria exist for defining when acute osteomyelitis becomes chronic. Clinically, the first bone infection is considered acute, and relapse of bone infection is labeled chronic. However, this simplistic classification is clearly inadequate. The hallmark of chronic osteomyelitis is the presence of dead bone (the sequestrum). Involucrum (reactive bony encasement of the sequestrum), local bone loss, persistent drainage, and/or sinus tracts are other common features of chronic disease. The patient with chronic osteomyelitis commonly presents with chronic pain and sinus formation with purulent drainage. Fever is usually low grade or absent. The chronic

infection usually does not progress or does so slowly. If a sinus tract becomes obstructed, the patient can present with a localized abscess, soft tissue infection, or both. Prospects of halting the infection are reduced when the integrity of surrounding soft tissue is poor or the bone is unstable due to an infected nonunion or an adjacent septic joint. Squamous cell carcinoma at the site of tissue drainage and amyloidosis are rare complications of chronic osteomyelitis. Host factors Systemic host factors affecting immune surveillance, metabolism, and vascularity include the following:

Diabetes mellitus Renal, hepatic failure Malnutrition Chronic hypoxia Immunosuppression Immunodeficiency Malignancy Immune disease Extremes of age

Local host factors affecting immune surveillance, metabolism, and vascularity include the following:

Major vessel compromise Small and medium vessel disease Extensive scarring Arteritis Radiation fibrosis Chronic lymphedema Tobacco abuse (>2 packs per day) Neuropathy Venous stasis

INDICATIONS Successful management of osteomyelitis requires aggressive pursuit of the diagnosis and early antimicrobial and surgical therapy. If acute osteomyelitis is not treated optimally, the risk is high of developing chronic osteomyelitis, which is significantly less amenable to treatment. Staging and classification systems may be used in determining appropriate treatment for osteomyelitis. Surgical intervention is indicated in the following situations:

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The patient has not responded to specific antimicrobial therapy within 48 hours. Evidence exists of a persistent soft tissue abscess. Concomitant joint infection is suspected or diagnosed.

In adults with hematogenous osteomyelitis, a thorough intramedullary reaming and unroofing is usually performed with or without bone grafting. Soft tissues are reapproximated, and the limb is protected by external means (brace or cast) until the structural integrity of the bone is reestablished by normal remodeling RELEVANT ANATOMY AND CONTRAINDICATIONS Relevant Anatomy: In long bones such as the tibia and femur, the metaphysis is most frequently involved, probably due to the anatomy of this region. The organization of blood vessels feeding the metaphyseal region leads to a slowing of blood flow in this area, which presumably allows bacteria to settle and initiate an inflammatory response. The nutrient artery ends in the metaphyses as marrow capillaries that make sharp loops near the growth plate and enter a system of large venous sinusoids where the blood flow becomes slow and turbulent. These capillary loops are essentially the end-artery branches of the nutrient artery. The histology of the region may also contribute to the localization of infection. The metaphyseal capillaries lack phagocytic lining cells, and the sinusoidal veins contain functionally inactive phagocytic cells, both of which allow growth of microorganisms. In addition, any form of end-capillary obstruction could produce an area of avascular necrosis. Minor trauma probably predisposes the infant or child to infection by producing a small hematoma, vascular obstruction, and subsequent bone necrosis, which leaves the region susceptible to inoculation from a transient bacteremia. Acute infection initially produces a local cellulitis, which results in a breakdown of leukocytes, increased bone pressure, reduced pH, and decreased oxygen tension. The cumulative effects of these physiologic factors further compromise the medullary circulation and enhance the spread of infection. Infection may proceed laterally through the haversian and Volkmann canal system, perforate the bony cortex, and lift the periosteum from the surface of the bone. When this occurs in the presence of medullary extension, the periosteal and endosteal circulations are compromised, capillaries are lost, and large segments of cortical and cancellous (trabecular) bone die. In infants, medullary infection may spread to the epiphysis and joint surfaces through capillaries that cross the growth plate. In contrast, in children older than 1 year, the growth plate is avascular and infection is confined to the metaphysis and diaphysis. The joint is spared unless the metaphysis is intracapsular. Thus, cortical perforation at the proximal radius, humerus, or femur enables the infection to migrate to the elbow, shoulder, or hip joint, respectively, regardless of the age of the patient. Contraindications: Contraindications to debridement of infected bone are limited and include the following:

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In acute osteomyelitis in infants, the infection usually responds well to medical therapy alone. Surgery should be reserved for nonresponsive cases. Suspicion of malignancy or presence of secondary bone infection with malignancy should not be treated with debridement alone. Tumor workup and biopsy should be performed first. If infection cannot be eradicated or tumor is not resectable, amputation is indicated. Massive debridement is not recommended in the presence of sickle cell disease; usually a mixture of infection and avascular necrosis is present that may improve after good reperfusion. Massive debridement may produce very large defects that may not be easily amenable to reconstruction surgeries. The use of a tourniquet is not recommended by many authors due to the acute bacteremic phase after the tourniquet is released and toxemia. Local anesthesia is generally ineffective and should be avoided due to the change in the local Ph of the tissue that prevents the metabolism of the local anesthetics to the active ingredients.

The general condition of the patient should not be considered a contraindication to urgent surgery. Delaying surgery may lead to further deterioration. WORKUP Lab Studies:

Routine laboratory test findings are usually nonspecific. These include CBC count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), renal and hepatic profile, and bone profile.
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Complete blood count: Leukocytosis is common in acute osteomyelitis but not in chronic osteomyelitis. Erythrocyte sedimentation rate The ESR is usually elevated but may be in the reference range. In a patient with a high ESR initially, monitoring the ESR may be useful in detecting a relapse. In patients with a foot ulcer and diabetes mellitus, an ESR greater than 100 mm/h is highly specific but insensitive for a diagnosis of osteomyelitis. Although ESR is associated with low sensitivity and specificity, it is widely employed. In the patient without a prior history of osteomyelitis, the ESR is most helpful when infection is unlikely. For example, in patients with low-back pain but without historical clues to suggest vertebral osteomyelitis (eg, recent urinary tract infection), a normal ESR is a reassuring finding. Conversely, an elevated ESR suggests the need for further evaluation. C-reactive protein CRP, like ESR, is an acute-phase reactant. Although said to be more specific for infection than ESR, it is also relatively insensitive and nonspecific.

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The primary difference between these tests is that the CRP has a shorter half-life than the ESR. Measuring in vitro clumping of venous leukocytes (leukergy) may more closely correlate with severity of infection than the ESR.

Renal and hepatic profile: Whether leukergy, which reflects altered surface expression of leukocyte adhesion molecules, will be useful for managing osteomyelitis is not known. This test is not routinely available.

Efforts have been made to develop serologic assays to diagnose osteomyelitis caused by S aureus. Patients with osteomyelitis mount a vigorous antibody response, but the utility of detecting antibodies to cell wall components such as peptidoglycan or teichoic acid has been limited by the presence of such antibodies in uninfected, healthy persons. In a preliminary study, serum antibodies to S aureus exoproteins differentiated 3 cases of S aureus osteomyelitis from 4 cases caused by other organisms. Another limitation of serology is that it is unlikely to be developed for nonstaphylococcal disease. However, highly specific assays for staphylococcal osteomyelitis would be very useful. At present, serology cannot be recommended clinically, and such tests are available only for research purposes. Blood culture results are positive in 50% percent of cases of acute osteomyelitis. A positive blood culture result in a patient with radiological findings consistent with osteomyelitis obviates the need for biopsy to obtain the specific microbiologic diagnosis.

Imaging Studies:

Plain films: Plain radiographs are relatively inexpensive, may be used to make the diagnosis, help in interpreting and choosing other studies, and allow one to exclude other conditions (eg, gas in the soft tissues). In uncomplicated acute infection, the triad of soft tissue swelling, bone destruction, and periosteal reaction is fairly specific for osteomyelitis and is sufficient to warrant a course of therapy (empiric until the microbiologic diagnosis has been established).
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Plain films are generally insensitive for the diagnosis of acute osteomyelitis. This is in part due to the 2-3 weeks required for bone changes to be evident on plain films, although changes may be seen at this time on the other imaging modalities. Furthermore, in complicated situations, bone changes may not be distinguishable from those due to another process, such as a Charcot joint, fractures, or cancer. Thus, the diagnosis of acute osteomyelitis cannot be excluded if the plain film findings are negative. Further testing should be performed because early therapy is essential to reduce the formation of necrotic bone and the development of chronic osteomyelitis. The primary findings are different in chronic osteomyelitis, which is characterized by bone sclerosis, periosteal new bone formation, and sequestra. It is difficult to distinguish active from inactive infection.

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CT scan: This modality is used to evaluate an area in which focal findings are present on examination and plain films findings are negative. The CT scan (with and without contrast) is very accurate for detecting cortical destruction, intraosseous gas, periosteal reaction, and soft tissue extension. MRI: This study is an alternative to CT scan and is especially useful in evaluating a patient for osteomyelitis in the vertebrae and in the infected foot. In vertebral osteomyelitis, findings on T1-weighted images include decreased signal intensity in the disk and adjacent vertebral bodies and loss of endplate definition. Findings on T2-weighted images include increased signal intensity in the disk and adjacent vertebral bodies. With gadolinium, there is enhancement of the disk, adjacent vertebral bodies, and involved paraspinal and epidural soft tissue.
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MRI provides useful anatomic detail in planning for surgical debridement, since it may show abscesses that need drainage, and can reduce the risk of operating on bland cellulitis. MRI can also be used to delineate soft tissue/epidural involvement and spinal cord impingement that cannot be seen on nuclear medicine images. When evaluating the foot for osteomyelitis, MRI is as specific or more specific and more sensitive than technetium bone scan. In one series in which bone biopsy was used as the criterion standard, the sensitivity was 72% for MRI, 68% for bone scan, and 45% for indium white blood cell scan. MRI cannot be used in patients with certain metal implants. In addition, falsepositive results can occur with bone infarct or fracture or in healed osteomyelitis. Differentiating cancer from osteomyelitis may be difficult with MRI. MRI for diabetic foot ulcers The diagnosis of osteomyelitis in diabetic foot ulcers is often missed because of 2 major factors: most cases occur in ulcers not exposing bone and most have no evidence of inflammation on physical examination. In comparison, osteomyelitis was present in all patients in whom bone was exposed in one series. MRI is the imaging procedure of choice for osteomyelitis in diabetic foot ulcers, being more accurate than the other modalities (95% vs 5070% for plain films, bone scan, and indium scan in one series). Two clinical factors also may be useful in these patients, probing the ulcer and ulcer size).

Ultrasonography: Ultrasound findings consistent with osteomyelitis include fluid collection adjacent to the bone without intervening soft tissue, elevation of the periosteum by more than 2 mm, and thickening of the periosteum. Ultrasound may also improve the yield from fine-needle biopsies.

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Scintigraphy: Multiple different nuclear medicine imaging procedures are available to evaluate for osteomyelitis, including bone scan, indium-labeled leukocyte scan, and bone marrow scan.
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Three-phase bone scan The 3-phase bone scan uses technetium Tc 99m bound to phosphorus as the tracer, which accumulates in areas of increased osteoblast activity (reactive new bone formation and increased blood flow). The images obtained are immediate (flow), 15 minute (blood pooling), and 4 hour (bone imaging). The scan findings are different in cellulitis and osteomyelitis. Cellulitis results in increased activity in the first 2 phases and normal or diffusely increased activity in the third phase. In comparison, osteomyelitis results in intense uptake in all 3 phases. The 3-phase technetium bone scan is the test of choice in evaluating for acute osteomyelitis if the plain film findings are normal. In this situation, it has an estimated sensitivity and specificity of almost 95% and findings generally are positive in 2-3 days of infection. However, any process that results in increased bone turnover appears as a hot spot that is indistinguishable from osteomyelitis. These false-positive findings can occur with posttraumatic injury, following surgery, diabetic feet, septic arthritis, noninfectious inflammatory bone disease, cancer, healed osteomyelitis, and Paget disease. Indium-labeled leukocyte scan: Indium-labeled leukocyte scanning uses white blood cells labeled with radioactive indium as the tracer. It accumulates at sites of inflammation or infection and in the bone marrow. It is not specific for bone. Since it accumulates in marrow, it is less sensitive for imaging those areas with red marrow (eg, the axial skeleton). The indium scan can also be used for the diagnosis of osteomyelitis at sites of fracture nonunion. Two prospective studies found a sensitivity and specificity of 91% and 97%, respectively, in this setting. Indium scans have better sensitivity and specificity than bone scans in diabetic feet, but the specificity is poor, especially in the hindfoot. Bone marrow scan: The bone marrow scan uses technetium Tc 99mlabeled sulfur colloid as the tracer. It is taken up by the reticuloendothelial system, including the bone marrow, spleen, and liver. It allows one to image the marrow instead of the bone. Its main use is in conjunction with the indiumtagged white blood cell scan to evaluate for suspected osteomyelitis in the axial skeleton, where the presence of marrow decreases the accuracy of the indium scan. Gallium citrate scanning: Gallium citrate scanning uses radioactive gallium citrate as the tracer. It acts as an analog of calcium and iron and attaches to transferrin to accumulate at sites of inflammation. Gallium imaging is the most sensitive and specific radionuclide scanning technique for vertebral

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osteomyelitis. A typical positive test result reveals intense uptake in 2 adjacent vertebrae with loss of the intervening disk space. In one study of 41 patients with suspected vertebral osteomyelitis, increased gallium uptake was detected in all of the 39 patients with biopsy-proven osteomyelitis.
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Dual tracer scans: Dual tracer examinations combine an inflammation imaging tracer (indium or gallium) with an "anatomic" tracer (either technetium bone scan or technetium sulfur colloid marrow scan), with images being collected either sequentially or simultaneously. Sequential studies combine the sensitivity of the bone scan (if findings are negative, no further imaging is done) with the specificity of the indium scan. Simultaneous studies combine the sensitivity and specificity of the indium scan and the bone scan to provide the anatomic detail needed to localize the infection to bone or soft tissue. Other: Radiolabeled antigranulocyte antibodies are being investigated in an attempt to find a more accurate tracer for localizing infection.

Other Tests:

Extended field of view ultrasound in musculoskeletal disorders: With the advent of high-resolution linear array transducers (7.5 MHz and 10 MHz), interest in musculoskeletal ultrasonography has continued to develop. Ultrasonography has been applied in the evaluation of infectious processes such as osteomyelitis, cellulitis, and subcutaneous abscesses. Extended field of view ultrasonography combines the convenience of a real-time scanner with the spatial advantages of a static B-mode scanner. Detailed examination of surfaces of cortical bone and cartilage has application in the evaluation of rheumatologic diseases for periarticular erosions, trauma for radiographically occult fractures, congenital hip dysplasia, and early osteomyelitis.

Diagnostic Procedures:

Bone biopsy: The criterion standard for the diagnosis of osteomyelitis is open bone biopsy with histopathologic examination and cultures. Histopathologic features indicating osteomyelitis include necrotic bone with extensive resorption adjacent to an inflammatory exudate. Needle biopsy is commonly used to obtain bone for histopathologic analysis. However, the incidence of sampling error is not negligible, with the sensitivity and specificity of this technique being 87% and 93%, respectively. Sensitivity of needle biopsy is particularly low in the postoperative or post-trauma patient.
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If the clinical suspicion is strong and blood culture results and the needle biopsy findings are negative, the needle biopsy should be repeated or an open biopsy should be performed. In patients with compromised vasculature, a bone sample can be obtained at debridement for the histopathologic diagnosis of osteomyelitis.

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Accurate cultures can be obtained only if the bone biopsy is performed through uninvolved tissue. In addition, cultures of the sinus tract are useful if S aureus and possibly Salmonella species are cultured. The presence of other common organisms does not predict those that will be found on bone biopsy.

Probing a diabetic foot ulcer

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In a recent report, the detection of bone when a diabetic foot ulcer was probed with a sterile probe was highly accurate in ruling in osteomyelitis. Seventyfive patients with 76 ulcers were studied, with the criterion standard for the diagnosis of osteomyelitis being histopathologic examination of bone resected at debridement. Contiguous osteomyelitis was present in 50 of the 76 ulcers. Of these, bone was palpable by probe in 33. The sensitivity and specificity were 66% and 85%, respectively, giving a positive predictive value of 89% and a negative predictive value of 56% in this population. These patients had a very high rate of osteomyelitis (61%); thus, the high positive predictive value is not likely to be applicable to ulcers with a lower risk of complicating osteomyelitis. The size of a diabetic foot ulcer also may be helpful. In one series, osteomyelitis was present in 94% of ulcers greater than 2 cm2 in area. Thus, in a diabetic patient with a foot ulcer, either probing of bone or ulcer area above 2 cm2 is associated with about a 90% probability of having underlying osteomyelitis. Further noninvasive testing is unlikely to improve the accuracy of diagnosis.

Histologic Findings: Acute osteomyelitis presents as a suppurative infection with acute inflammatory cells, accompanied by edema, vascular congestion, and small vessel thrombosis. In early acute disease, the vascular supply to the bone is compromised by infection extending into the surrounding soft tissue. When both the medullary and periosteal blood supplies are compromised, large areas of dead bone (sequestra) may be formed. Within this necrotic and ischemic tissue, the bacteria can be difficult to eradicate even after an intense host response, antibiotic therapy, or both. Pathologic features of chronic osteomyelitis include necrotic bone, the formation of new bone, and polymorphonuclear leukocyte exudation joined by large numbers of lymphocytes, histiocytes, and occasional plasma cells. Host defense and mesenchymal cells, mainly the polymorphonuclear leukocytes, macrophages, and the osteoclasts, release proteolytic enzymes that break down organic elements in the dead bone. Because of lost blood supply, dead bone appears whiter than living bone. Cancellous bone is absorbed rapidly and may be completely sequestrated or destroyed in 2-3 weeks, but necrotic cortex may require 2 weeks to 6 months for separation. After complete separation, the dead bone is slowly eroded by granulation tissue and absorbed.

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New bone formation is another characteristic feature of osteomyelitis. New bone forms from the surviving fragments of periosteum, endosteum, and the cortex in the region of the infection and is produced by a vascular reaction to the infection. New bone may be formed along the intact periosteal and endosteal surfaces and may arise when the periosteum forms an encasing sheath of live bone (involucrum) surrounding the dead bone. Involucrum is irregular and is often perforated by openings through which pus may track into the surrounding soft tissues and eventually to the skin surfaces through a sinus tract. The involucrum can gradually increase in density and thickness to form part or all of a new shaft. New bone increases in amount and density for weeks or months according to the size of the bone and the extent and duration of infection. Endosteal new bone may proliferate and obstruct the medullary canal. After host defense, removal or surgical removal of the sequestrum, the body, especially in children, may fill the remaining cavity with new bone. However, in adults, the cavity may persist or the space may be filled with fibrous tissue. The surviving bone in the osteomyelitis field usually becomes osteoporotic during the active period of infection. Osteoporosis is the result of the inflammatory reaction and disuse atrophy. After the infection subsides, bone density increases partially from reuse. It may be difficult to distinguish between the old living bone and the newly formed bone as time passes. All traces of osteomyelitis can disappear in children and, to a lesser extent, in adults. Staging: Waldvogel classification In 1970, Waldvogel described the first long bone osteomyelitis staging system. He described 3 categories of osteomyelitis, as follows: hematogenous, contiguous focus, and osteomyelitis associated with vascular insufficiency.

Hematogenous osteomyelitis is predominantly encountered in the pediatric population; 85% of patients are younger than 17 years. This form of osteomyelitis is more common in males at any age. The bone infection usually affects the long bones in children, while in adults, the lesion is usually located in the thoracic or lumbar vertebrae. Osteomyelitis secondary to a contiguous focus of infection can derive from a direct infection of bone, from a source outside the body (eg, soft tissue trauma, open fracture, surgery), or from the spread of infection from an adjacent focus (eg, soft tissue infection, dental abscess, decubitus ulcer). Contiguous focus osteomyelitis has a biphasic age distribution: the infection occurs in younger individuals secondary to trauma and related surgery and in older adults secondary to decubitus ulcers and infected total joint arthroplasties. Osteomyelitis associated with vascular insufficiency is usually seen in individuals with diabetes mellitus. Of the 31 patients in Waldvogel's study with this form of osteomyelitis, 25 had diabetes, 5 had severe atherosclerosis not related to diabetes,

18

and one had vasculitis secondary to rheumatoid arthritis. All of the infections affected the toes, metatarsals, tarsals, or hindfoot. Most patients in this group were aged 40-70 years. Waldvogel's remains the primary osteomyelitis classification system. However, it is an etiologic classification system that does not readily lend itself to guiding surgical or antibiotic therapy. As a result, other classification systems have been developed to emphasize different clinical aspects of osteomyelitis.

Kelly classification The Kelly classification system divides osteomyelitis in adults into 4 categories, as follows:

Hematogenous osteomyelitis Osteomyelitis in a united fracture (fracture with union) Osteomyelitis in a nonunion (fracture with nonunion) Postoperative osteomyelitis without fracture

This classification system emphasizes the etiology of the infection and its relationship to fracture healing. Weiland classification Weiland defined chronic osteomyelitis as a wound with exposed bone, positive bone culture results, and drainage for more than 6 months. A similar wound with drainage for less than 6 months was not considered to be a site of chronic osteomyelitis. The infection was further divided on the basis of soft tissue and the location of bone involved, as follows:

Type I osteomyelitis is defined as open exposed bone without evidence of osseous infection but with evidence of soft tissue infection. Type II osteomyelitis consists of circumferential, cortical, and endosteal infection. Radiographs demonstrate a diffuse inflammatory response, increased bone density, and spindle-shaped sclerotic thickening of the cortex. Other radiographic findings included areas of bony resorption and often a sequestrum with a surrounding involucrum. Type III osteomyelitis consists of cortical and endosteal infection associated with a segmental bone defect.

Ger classification The Ger classification system addresses the physiology of the wound as it relates to osteomyelitis. The categories include simple sinus, chronic superficial ulcer, multiple sinuses, and multiple skin-lined sinuses. If the wound is not appropriately treated, the bone infection cannot be arrested. Early coverage of open tibial fractures with soft tissue

19

prevents the nonunion.

later

development

of osteomyelitis,

ulceration,

and,

perhaps,

May classification The May classification system focuses on the status of the tibia after soft tissue and skeletal debridement (May, 1989). This system is useful in determining the length of rehabilitation that will be needed, under ideal conditions, before the patient will be able to ambulate without upper extremity aids.

Type I osteomyelitis is defined as an intact tibia and fibula capable of withstanding functional loads (rehabilitation time, 6-12 wk). Type II osteomyelitis consists of an intact tibia with bone graft only needed for structural support (rehabilitation time, 3-6 mo). Type III osteomyelitis demonstrates a tibial defect of 6 cm or less with an intact fibula (rehabilitation time, 6-12 mo). Type IV consists of a tibial defect greater than 6 cm and an intact fibula (rehabilitation time, 12-18 mo). Type V osteomyelitis consists of a tibial defect greater than 6 cm long with no usable intact fibula (rehabilitation time, 18 mo or more).

May's classification system with the estimated time for rehabilitation assists the decisionmaking process in patients with post-traumatic tibial osteomyelitis. However, many factors, including age, metabolic status, the mobility of the patient's foot and ankle, neurovascular integrity, and the patient's motivation, can greatly affect the time necessary for rehabilitation. Gordon classification The Gordon system classifies infected tibial nonunions and segmental defects based on the osseous defects (Gordon, 1988):

Type A includes tibial defects and nonunions without significant segmental loss. Type B includes tibial defects greater than 3 cm with an intact fibula. Type C includes tibial defects of greater than 3 cm in patients without an intact fibula.

The Gordon classification system correlates with the prognosis for successful free muscle transportation (ie, the microvascular movement of a muscle flap). Once the wound and infection have been successfully treated with staged microvascular muscle transplantation, the nature of the underlying osseous problem will dictate the clinical results.

Cierny-Mader classification

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The Cierny-Mader system is a good model for the diagnosis and treatment of long bone osteomyelitis, since it permits stratification of infection and the development of comprehensive treatment guidelines for each stage. The Cierny-Mader classification is based upon the anatomy of the bone infection and the physiology of the host. The stages are dynamic and may be altered by therapy outcome or change in host status. The classification is determined by the condition of the disease process itself, regardless of its etiology, region, or chronicity. The anatomic types of osteomyelitis are medullary, superficial, localized, and diffuse.

Stage 1, or medullary osteomyelitis, denotes infection confined to the intramedullary surfaces of the bone. Hematogenous osteomyelitis and infected intramedullary rods are examples of this anatomic type. Stage 2, or superficial osteomyelitis, is a true contiguous focus infection of bone; it occurs when an exposed infected necrotic surface of bone lies at the base of a soft tissue wound. Stage 3, or localized osteomyelitis, is usually characterized by a full-thickness cortical sequestration that can be removed surgically without compromising bony stability. Stage 4 or diffuse osteomyelitis is a through-and-through process that usually requires an intercalary resection of the bone to arrest the disease process. Diffuse osteomyelitis includes those infections with a loss of bony stability either before or after debridement surgery.

The patient is classified as an A, B, or C host.

An A host is a patient with normal physiologic, metabolic, and immunologic capabilities. A B host has systemic compromise, local compromise, or both. The C host is a patient in whom the morbidity of treatment is worse than that of the disease itself.

The terms acute osteomyelitis and chronic osteomyelitis are not used in this staging system, since areas of macronecrosis must be removed regardless of the duration of an uncontrolled infection. This classification system aids in the understanding, diagnosis, and treatment of bone infections in children and adults. It is used mainly to stratify the infection in research protocols but is also being built into many new research protocols. TREATMENT Medical therapy: A single pathogenic organism is almost always recovered from the bone. The most common bone isolates are staphylococci, the most common gram-negative organism is P aeruginosa, and the most common anaerobe is Peptostreptococcus species. However, in immunocompromised patients, other organisms must also be considered, including fungi and mycobacteria.

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Hematogenous osteomyelitis in children can usually be treated with antibiotic therapy alone. However, it is vital to identify a pathogen in order to select the optimal antibiotic therapy. Mismanagement with inappropriate antibiotic(s) encourages disease extension, necrosis, and sequestra formation. A bone biopsy for culture is necessary unless the patient has positive blood cultures along with radiographic findings consistent with osteomyelitis. After cultures are obtained, empiric antibiotics should be selected to cover the most probable pathogens. Once the etiologic organism is identified, the antibiotic regimen should be modified, if needed, based upon susceptibility patterns. The patient should be treated for 4-6 weeks with appropriate antimicrobial therapy, dating from the initiation of therapy or following the last major debridement surgery. If the initial medical management fails and the patient is clinically compromised by a recurrent infection, medullary and/or soft tissue debridement is necessary in conjunction with another 4- to 6-week course of antibiotics. Oral antibiotics can be used in pediatric hematogenous osteomyelitis. However, the child should receive 7-14 days of IV antibiotics or continue to receive IV antibiotics until systemic improvement occurs prior to changing to an oral regimen. The latest reports suggest the use of IV antibiotics for 3-4 days; this usually is enough for the systemic manifestations to improve. In order to undergo oral therapy, the patient must be compliant and have close outpatient follow-up care. Absorption and activity of the orally administered antibiotic should be monitored using serum cidal levels. High doses of the quinolone class of antibiotics can cause articular cartilage damage in young animals, generating some concern about the long-term use of these agents in infants and children. Thus, under most circumstances, children with osteomyelitis should not be treated with a quinolone. Table 1. Antibiotic Therapy in Osteomyelitis Organism S aureus First-Choice Antibiotics Alternative Antibiotics (methicillin

Nafcillin or cloxacillin Cefazolin 100-200 mg/kg/d q6h sensitive)

S aureus (methicillin resistant) Coagulase-negative organisms Group A streptococci Enterococci or B

Vancomycin 1 g q12h

Trimethoprimsulfamethoxazole or minocycline rifampin

plus

Vancomycin 1 g q12h or Cefazolin, clindamycin nafcillin 2 g q6h (if sensitive) Clindamycin 900 mg q8h Benzylpenicillin, cefazolin

Ampicillin 50-100 mg/kg/d q6h Vancomycin + gentamicin 5 mg/kg/d q8h

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E P mirabilis

coli,

Ampicillin 2 g q6h

Cefazolin, levofloxacin

gentamicin,

Surgical therapy: Surgical management of contiguous focus osteomyelitis can be very challenging. The principles of treating any infection are equally applicable to the treatment of infection in bone. These include adequate drainage, extensive debridement of all necrotic tissue, obliteration of dead spaces, stabilization, adequate soft tissue coverage, and restoration of an effective blood supply. The number and nature of the required surgical procedures increases with the severity of the infection, which can be divided into 4 categories, as follows:

Category 1 - Removal of necrotic tissue by extensive debridement Category 2 - Dead space obliteration with flaps, antibiotic beads, and bone grafts Category 3 - Provision of soft tissue coverage of the bone Category 4 - Stabilization of bone by external or open reduction and internal fixation

Category 1 Debridement surgery is the foundation of osteomyelitis treatment. It is the most commonly performed procedure and may need to be repeated multiple times. The goal of debridement is to reach healthy, viable tissue, but even when all necrotic tissue has been adequately debrided, the remaining bed of tissue must be considered contaminated with the responsible organism. Debridement should be direct, atraumatic and executed with reconstruction in mind. All dead or ischemic hard and soft tissue is excised unless a noncurative procedure has been chosen. Surgical excision of bone is carried down to uniform haversian or cancellous bleeding, known as the paprika sign. Category 2 Adequate debridement may leave a large bony defect (dead space). Appropriate management of dead space created by debridement surgery is mandatory in order to arrest the disease and to maintain the integrity of the skeletal part. The goal of dead space management is to replace dead bone and scar tissue with durable vascularized tissue. Local tissue flaps or free flaps may be used to fill dead space. An alternative technique is to place cancellous bone grafts beneath local or transferred tissues where structural augmentation is necessary. Careful preoperative planning is critical for conservation of the patient's limited cancellous bone reserves. Open cancellous grafts without soft tissue coverage are useful when a free tissue transfer is not a treatment option and local tissue flaps are inadequate. Complete primary or delayed primary wound closure should be performed whenever possible. Suction irrigation systems are not recommended because of the high incidence of associated nosocomial infections and the unreliability of the apparatus. Healing by secondary intent is also discouraged since the scar tissue that fills the defect may later become avascular. Antibiotic-impregnated acrylic beads can be used to sterilize and temporarily maintain dead space. The beads are usually removed within 2-4 weeks and

23

replaced with a cancellous bone graft. The most commonly used antibiotics in beads are vancomycin, tobramycin, and gentamicin. Local delivery of antibiotics (amikacin, clindamycin) into dead space can also be achieved with an implantable pump. Category 3 Adequate coverage of the bone by soft tissue is necessary to arrest osteomyelitis. Most soft tissue defects are closed primarily, but small soft tissue defects may be covered with a split thickness skin graft. In the presence of a large soft tissue defect or an inadequate soft tissue envelope, local muscle flaps and free vascularized muscle flaps may be placed in a 1- or 2stage procedure. Local and free muscle flaps, when combined with antibiotics and surgical debridement of all nonviable osseous and soft tissue for chronic osteomyelitis, have a success rate ranging from 65-100%. Local muscle flaps and free vascularized muscle transfers improve the local environment by supplying blood vessels (which are critical for host defense) antibiotic delivery, and osseous and soft tissue healing. Category 4 If movement is present at the site of infection, measures must be taken to achieve permanent stability of the skeletal unit. Stability can be achieved with plates, screws, rods, and/or an external fixator. One type of external fixation allows bone reconstruction of segmental defects and difficult infected nonunions. The Ilizarov external fixation method uses the theory of distraction histogenesis, in which bone is fractured in the metaphyseal region and slowly lengthened. The growth of new bone in the metaphyseal region pushes a segment of healthy bone into the defect left by surgery. The Ilizarov technique is used for difficult cases of osteomyelitis when stabilization and bone lengthening are necessary. It also can be used to compress nonunions and correct malunions and in a small group of patients for reconstruction of difficult deformities that result from osteomyelitis. However, this technique is labor intensive and requires an extended period of treatment, averaging 9 months in the device. The Ilizarov pins usually become infected, and the device is painful. Infected pseudoarthrosis with segmental osseous defects can be treated by debridement and microvascular bone transfers. Vascularized bone transfer is also useful for the treatment of infected segmental osseous defects of long bones that are more than 3 cm in length. Vascularized bone transfers can be placed after 1 month without clinical evidence of infection. Loss of bone stability, bone necrosis, and soft tissue damage frequently occur in contiguous focus osteomyelitis. Surgical debridement of infected bone and soft tissue provides specimens for culture and hastens eradication of the infection. Other steps in the surgical management of contiguous focus osteomyelitis should be tailored to the specific anatomy of the bone infection. When osteomyelitis is characterized by a full thickness cortical sequestration, patients usually can be treated with removal of the dead infected bone (bone saucerization). Bone grafting may be necessary to augment structural support. These patients may require external fixation for structural support while the bone graft

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incorporates. Complex reconstruction of both bone and soft tissue is frequently necessary. In some cases, osteomyelitis progresses to an infection involving the entire diameter of the bone. These patients often require an intercalary resection of the bone in order to arrest the disease process. Since this advanced stage of osteomyelitis involves an entire through-andthrough section of bone, a loss of bony stability occurs either before or after debridement surgery. As a result, treatment often must be directed toward establishing structural stability and obliterating debridement gaps by means of cancellous bone grafts or the Ilizarov technique. Vascularized bone grafting is the other possible treatment modality. Preoperative details: In addition to routine preoperative preparations, supportive therapy is needed; infants and children must be well hydrated and fever must be controlled before the patient undergoes general anesthesia. Patients who are medically compromised should be stabilized and supported. Diabetes should be controlled as much as possible, but this should not delay drainage because the presence of infection makes the blood sugar level refractory and difficult to control. Most of the systemic manifestations of osteomyelitis improve dramatically after drainage and debridement. Intraoperative details: Position the patient in the most accessible position to drain the infected areas. Prepare all containers and swabs, and prepare the requests before scrubbing. Prepare containers for tissue cultures. Prepare for Gram stain, aerobic culture and sensitivity, anaerobic culture and sensitivity, and fungal culture and sensitivity. (Acid-fast bacillus [AFB] stain and culture and sensitivity are recommended.) Incision should be generous for ease of access to the infected bone. Decompression may release intramedullary or subperiosteal pus. All necrotic soft tissue, bone, and devitalized tissue must be removed. Infected loculations must be broken, and thorough washing with as much as 2-4 L of isotonic sodium chloride solution is essential. Complete debridement of all the devitalized bone and soft tissue, regardless of the size of the wound created, is essential for cure. Immobilization of the bone by cast or external fixations is a must. Revascularization procedures are the best means of fighting recurrent infection; those involving local pedicle muscle flaps and myocutaneous flaps are now the ones most frequently used to fill the space created by surgery. Local muscle flaps are limited by the availability of adjacent muscle but are very useful because the vascular supply is kept intact. Myocutaneous flaps have the advantage of providing vascular supply to both the muscle and the overlying skin. Increasingly, microsurgically transplanted muscle flaps (ie, free-flaps) are being used in areas such as the distal tibia where no appropriate muscle exists. Complex orthopedic techniques are necessary to repair very large bone defects that would otherwise be considered untreatable except by amputation. In the Ilizarov technique, the resection of diseased tissue and bone creates a gap partially filled by a well-vascularized bone segment. Transfer of the bone graft leads to progressive local generation of new bone.

25

Postoperative details: Dramatic improvement is the usual course after debridement, but patients require attention to prevent complications related to their original medical conditions, such as diabetes and heart failure. IV fluids, IV antibiotics, and suitable analgesics are required for the first few days after surgery. ICU admission for respiratory support and blood gases and renal function monitoring should be considered for patients who have septicemia. The wound should be dressed daily, and early sitting and mobilization (affected limb must be immobilized) should be encouraged. If no improvement occurs within 48 hours, a second look debridement and dressing under general anesthesia is indicated. Follow-up care: The patient must be compliant with care and have close outpatient follow-up. The first visit is usually a week after discharge and consists of a general examination for evaluation of improvement. Local examination and documentation of pain, wound condition, tenderness, swelling, and discharges from wounds should be made in all visits. Repeat CBC count, CRP, ESR, and plain radiographs to evaluate the progression and behavior of the infection. The cast should be removed when infection is eradicated, which is usually determined by good reduction in the level of CRP, ESR, or both. The shoulder, elbow, and wrist should not be immobilized more than 3, 4, and 5 weeks, respectively. Physiotherapy is an essential part of follow-up care; isometric exercises should be started early, and once the cast is removed, active and passive range of motion exercises are suggested. COMPLICATIONS Recurrence of osteomyelitis has been reported in 3-40% of patients. Chronic osteomyelitis is very serious and more difficult to treat than acute osteomyelitis. In some cases, osteomyelitis progresses to an infection involving the entire diameter of the bone. These patients often require an intercalary resection of the bone in order to arrest the disease process. Since this advanced stage of osteomyelitis involves an entire through-andthrough section of bone, a loss of bony stability occurs either before or after debridement surgery. As a result, treatment often must be directed toward establishing structural stability and obliterating debridement gaps with cancellous bone grafts or the Ilizarov technique. Vascularized bone grafting is the other possible treatment modality. The most serious complication of vertebral osteomyelitis is neurologic impairment secondary to either abscess formation or bony collapse. Most patients have gradual alleviation of pain after therapy is begun. In most patients, the pain disappears after a bony fusion occurs. However, back pain occasionally persists. Major bone loss hinders limb length and results in permanent disability.

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The patient with extensive osteomyelitis and poor tissue oxygen perfusion usually requires some type of ablative surgery. Digital and ray resections (toe and corresponding metatarsal), transmetatarsal amputations, midfoot disarticulations, and Syme amputations (amputation of the foot with retention of the heel pad) permit the patient to ambulate without a prosthesis. The amputation level is determined by the vascularity of the tissues proximal to the site of infection and the requirements of a thorough debridement. The patient should be given 4 weeks of antibiotics when infected bone is surgically transected. Two weeks of antibiotics are prescribed when the infected bone is completely excised, but some residual soft tissue infection remains. However, when the amputation is performed proximal to the bone and soft tissue infection, the patient is only prescribed a 1- to 3-day antibiotic regimen. OUTCOME AND PROGNOSIS Acute osteomyelitis With new diagnostic methods and better treatment, those with ready access to health care can be anticipated to have only rare sequelae of hematogenous osteomyelitis. Infection control strategies and prophylactic antibiotics will further decrease the rate of postoperative infection. However, the increase in reconstructive orthopedic procedures with prosthetic materials will increase the overall number of infections, and whether any preventive measures can reduce the rate of infection to below 0.5% is doubtful. Osteopenia and osteoporosis After the infection subsides and use of the part is increased, bone density returns to baseline, and bone may undergo extensive transformation to meet the lines of the stress and strain. In time, distinguishing the old living bone from the newly formed bone may be difficult. Chronic osteomyelitis Chronic osteomyelitis entails a major financial burden and has a substantial impact on quality of life. Collaboration between patient and physician is essential in the treatment of this disease. A clear understanding of the risks, costs, and chances of success of treatment options should form the basis of an open dialogue between the physician and the patient with chronic osteomyelitis. Vertebral osteomyelitis Treatment results for patients vary. The outcome appears to be equivalent for patients who ambulate with stabilization from a cast, a corset, or a brace and those treated with bedrest alone. Recurrence of osteomyelitis has been reported in 3-40% of patients. However, the rate of chronic cases of vertebral osteomyelitis (patients demonstrating symptoms after 2 y) has been reduced and now ranges from 0-6%. The mortality rate from this disease in the antibiotic era has been less than 5%. Residual neurologic deficits among survivors should be less than 7%. Generally, the best way to reduce the morbidity and mortality associated

27

with vertebral osteomyelitis is to limit the amount of time between the onset of symptoms and the initiation of appropriate therapy. FUTURE AND CONTROVERSIES Hyperbaric oxygen therapy In situations in which osteomyelitis is associated with decreased systemic blood flow (eg, in diabetes, vasculitis) or segmental blood flow (eg, in trauma), hyperbaric oxygen therapy may be used as adjunctive therapy. Reduced oxygen tensions in infected bone have been shown to interfere with normal polymorphonuclear leukocyte activity. Hyperbaric oxygen therapy has been shown to increase the oxygen tensions within infected bone, thereby augmenting polymorphonuclear leukocyte and macrophage activity. Wound healing is a dynamic process that requires an adequate oxygen tension to proceed. In the ischemic or infected wound, hyperbaric oxygen therapy provides oxygen to promote collagen production, angiogenesis, and ultimately wound healing. Referral for hyperbaric oxygen is made whenever refractory osteomyelitis occurs or a soft tissue infection develops that is not amenable to a local or microvascular flap. Microvascular surgery Recent experience with the microvascular transfer of fibular grafts and composite osteocutaneous iliac flaps into infected areas of bone has shown that massive autogenous bone grafting with an intact vascular pedicle decreases the time needed for bone union and shortens the period of immobilization. Reconstruction of large bony and soft tissue defects has been facilitated by microvascular and distraction osteogenesis (Ilizarov) techniques. A large piece of bone, soft tissue, or both can be introduced immediately or gradually into a previously infected wound while maintaining its protective blood supply. This allows more radical bone excision, increasing the chance of cure. Local antibiotic delivery Systems for local delivery of antibiotics into tissues have been used to overcome limited penetration of systemic agents into poorly vascularized bone, to avoid toxicity, and to minimize the need for long-term parenteral antibiotics. Such systems include closed suction-irrigation, plaster pellets, fibrin, collagen, and porous calcium hydroxyapatite. The greatest experience has been with antibiotic-loaded polymethyl methacrylate (PMMA) bone cement. Antibiotic-loaded cement is used for prosthetic joint fixation to maintain and sterilize dead space with antibiotic-impregnated beads during surgery for chronic osteomyelitis and to maintain extremity length during 2-stage revision arthroplasty for infection. Aminoglycosides, penicillins, cephalosporins, and clindamycin elute most effectively, whereas vancomycin elutes much less well. Even for drugs that elute most effectively, only a fraction of antibiotic is released. Approximately 10% of gentamicin added to PMMA may be recovered from the urine 2 months following hip arthroplasty. However, extremely

28

high local concentrations are achieved as measured in surgical drains. To avoid systemic toxicity in adults, it is suggested that no more than 17.5 g of aminoglycoside be added to PMMA beads.