Osteomyelitis Treatment & Management


Background

Osteomyelitis is inflammation of the bone caused by an infecting organism. Although bone is normally resistant to bacterial colonization, events such as trauma, surgery, the presence of foreign bodies, or the placement of prostheses may disrupt bony integrity and lead to the onset of bone infection. Osteomyelitis can also result from hematogenous spread after bacteremia. When prosthetic joints are associated with infection, microorganisms typically grow in biofilm, which protects bacteria from antimicrobial treatment and the host immune response.

Early and specific treatment is important in osteomyelitis, and identification of the causative microorganisms is essential for antibiotic therapy. [1The major cause of bone infections is Staphylococcus aureus. Infections with an open fracture or associated with joint prostheses and trauma often must be treated with a combination of antimicrobial agents and surgery. When biofilm microorganisms are involved, as in joint prostheses, a combination of rifampin with other antibiotics might be necessary for treatment.

Anatomy

The bony skeleton is divided into two parts: the axial skeleton and the appendicular skeleton. The axial skeleton is the central core unit, consisting of the skull, vertebrae, ribs, and sternum; the appendicular skeleton comprises the bones of the extremities. The human skeleton consists of 213 bones, of which 126 are part of the appendicular skeleton, 74 are part of the axial skeleton, and six are part of the auditory ossicles.

Hematogenous osteomyelitis most commonly involves the vertebrae, but infection may also occur in the metaphysis of the long bones, pelvis, and clavicle. Vertebral osteomyelitis usually involves two adjacent vertebrae with the corresponding intervertebral disk. (See the image below.) The lumbar spine is most commonly affected, followed by the thoracic and cervical regions.

Osteomyelitis of T10 secondary to streptococcal diOsteomyelitis of T10 secondary to streptococcal disease. Photography by David Effron MD, FACEP.

Posttraumatic osteomyelitis begins outside the bony cortex and works its way in toward the medullary canal, typically found in the tibia. Contiguous-focus osteomyelitis often occurs in the bones of the feet in patients with diabetes mellitus and vascular compromise.

For more information about the relevant anatomy, see Skeletal System Anatomy in Adults and Osteology (Bone Anatomy).

Pathophysiology

Bone is normally resistant to infection. However, when microorganisms are introduced into bone hematogenously from surrounding structures or from direct inoculation related to surgery or trauma, osteomyelitis can occur. Bone infection may result from the treatment of trauma, which allows pathogens to enter bone and proliferate in the traumatized tissue. When bone infection persists for months, the resulting infection is referred to as chronic osteomyelitis and may be polymicrobial. Although all bones are subject to infection, the lower extremity is most commonly involved. [12]

Some important factors in the pathogenesis of osteomyelitis include the virulence of the infecting organism, underlying disease, immune status of the host, and the type, location, and vascularity of the bone. Bacteria may possess various factors that may contribute to the development of osteomyelitis. For example, factors promoted by S aureus may promote bacterial adherence, resistance to host defense mechanism, and proteolytic activity. [3]

Hematogenous osteomyelitis

In adults, the vertebrae are the most common site of hematogenous osteomyelitis, but infection may also occur in the long bones, pelvis, and clavicle. [4]

Primary hematogenous osteomyelitis is more common in infants and children, usually occurring in the long bone metaphysis. However, it may spread to the medullary canal or into the joint. When infection extends into soft tissue, sinus tracts may eventually form. Secondary hematogenous osteomyelitis is more common and occurs when a childhood infection is reactivated. In adults, the location is also usually metaphyseal. [4]

S aureus is the most common pathogenic organism recovered from bone, followed by Pseudomonas and Enterobacteriaceae. Less common organisms involved include anaerobe gram-negative bacilli. Intravenous drug users may acquire pseudomonal infections. Gastrointestinal or genitourinary infections may lead to osteomyelitis involving gram-negative organisms. Dental extraction has been associated with viridans streptococcal infections. In adults, infections often recur and usually present with minimal constitutional symptoms and pain. Acutely, patients may present with fever, chills, swelling, and erythema over the affected area. [25]

Contiguous-focus and posttraumatic osteomyelitis

The initiating factor in contiguous-focus osteomyelitis often consists of direct inoculation of bacteria via trauma, surgical reduction and internal fixation of fractures, prosthetic devices, spread from soft-tissue infection, spread from adjacent septic arthritis, or nosocomial contamination. Infection usually results approximately one month after inoculation.

Posttraumatic osteomyelitis more commonly affects adults and typically occurs in the tibia. The most commonly isolated organism is S aureus. At the same time, local soft-tissue vascularity may be compromised, leading to interference with healing. Compared with hematogenous infection, posttraumatic infection begins outside the bony cortex and works its way in toward the medullary canal. Low-grade fever, drainage, and pain may be present. Loss of bone stability, necrosis, and soft tissue damage may lead to a greater risk of recurrence. [45]

Septic arthritis may lead to osteomyelitis. Abnormalities at the joint margins or centrally, which may arise from overgrowth and hypertrophy of the synovial pannus and granulation tissue, may eventually extend into the underlying bone, leading to erosions and osteomyelitis. One study demonstrated that septic arthritis in elderly persons most commonly involves the knee and that, despite most of the patients having a history of surgery, 38% developed osteomyelitis. Septic arthritis is more common in neonates than in older children and is often associated with metaphyseal osteomyelitis. Although rare, gonococcal osteomyelitis may arise in a bone adjacent to a chronically infected joint. [67]

Many patients with vascular compromise, as in diabetes mellitus, are predisposed to osteomyelitis owing to an inadequate local tissue response. [4]

Infection is most often caused by minor trauma to the feet with multiple organisms isolated from bone, including Streptococcus species, Enterococcus species, coagulase-positive and -negative staphylococci, gram-negative bacilli, and anaerobic organisms. Foot ulcers allow bacteria to reach the bone. Patients may not experience any resulting pain, because of peripheral neuropathy, and may present with a perforating foot ulcer, cellulitis, or an ingrown toenail.

Physical examination may reveal decreased sensation, poor capillary refill, and decreased dorsalis pedis and posterior tibial pulses. Treatment is aimed at suppressing infection and improving vascularity. However, most patients develop recurrent or new bone infections. Resection or amputation of the affected tissue is sometimes necessary. Debridement, incision and drainage, and tendon lengthening are attempted first.

Vertebral osteomyelitis

The incidence of vertebral osteomyelitis generally increases progressively with age, with most affected patients being older than 50 years. Although devastating complications may result from a delay in diagnosis, vertebral osteomyelitis is rarely fatal since the development of antibiotics. However, the elderly have higher rates of bacteremia and infective endocarditis at the time of diagnosis, and they have a higher mortality than younger patients with osteomyelitis do. [8]

The infection usually originates hematogenously and generally involves two adjacent vertebrae with the corresponding intervertebral disk. The lumbar spine is most commonly affected, followed by the thoracic and cervical regions. [41 

Potential sources of infection include skin, soft tissue, respiratory tract, genitourinary tract, infected intravenous sites, and dental infections. S aureus is the most common isolated organism. However, Pseudomonas aeruginosa is more common in intravenous drug users.

Most patients with vertebral osteomyelitis present with localized pain and tenderness of the involved vertebrae with a slow progression over 3 weeks to 3 months. Fever may be present in approximately 50% of patients. Some 15% of patients may have motor and sensory deficits. Laboratory studies may reveal peripheral leukocytosis and an elevated erythrocyte sedimentation rate (ESR). Extension of the infection may lead to abscess formation. [4]

Osteomyelitis in children

Acute hematogenous osteomyelitis usually occurs after an episode of bacteremia in which the organisms inoculate the bone. The most common organisms isolated in these cases include S aureusStreptococcus pneumoniae, and Haemophilus influenza type b (less common since the use of vaccine for H influenza type b). The incidence of Kinsella kingae infection is increasing; such infection is a common cause of osteomyelitis in children younger than 4 years. [9]

Acute hematogenous S aureus osteomyelitis in children can lead to pathologic fractures. This can occur in about 5% of cases with a 72-day mean time from disease onset to fracture. [10]

In children with subacute focal osteomyelitis (see the image below), S aureus is the most commonly isolated organism.

Rarefaction and periosteal new-bone formation arouRarefaction and periosteal new-bone formation around the left upper fibula in a 12-year-old patient. This was caused by subacute osteomyelitis.

Gram-negative bacteria such as Pseudomonas species or Escherichia coli are common causes of infection after puncture wounds of the feet or open injuries to bone. Anaerobes can also cause bone infection after human or animal bites.

Osteomyelitis in the neonate results from hematogenous spread, especially in patients with indwelling central venous catheters. The common organisms in osteomyelitis of the neonate include those that frequently cause neonatal sepsis, namely group B Streptococcus species, and E coli. Infections in the neonate can involve multiple osseous sites, and approximately half of the cases also involve eventual development of septic arthritis in the adjacent joint.

Children with sickle cell disease are at an increased risk for bacterial infections, and osteomyelitis is the second most common infection in these patients. The most common organisms involved in osteomyelitis in children with sickle cell anemia include Salmonella species, S aureusSerratia species, and Proteus mirabilis.

Etiology

The major causes of osteomyelitis include the following:

  • Vascular insufficiency
  • Hematogenous seeding
  • Preceding trauma or surgery

Vascular insufficiency is most commonly seen in patients with diabetes, whereas hematogenous seeding primarily occurs in children and the elderly. The prevalence of posttraumatic and postoperative osteomyelitis is increasing, and this category may account for as many as 80% of bone infections. For example, open fractures have higher rates of osteomyelitis (3-50%) as compared with closed fractures (1-5%). [1112]

Epidemiology

Approximately 20% of adult cases of osteomyelitis are hematogenous, which is more common in males for unknown reasons. [4]

The incidence of spinal osteomyelitis was estimated to be 1 in 450,000 in 2001. In subsequent years, however, the overall incidence of vertebral osteomyelitis is believed to have increased as a consequence of intravenous drug use, increasing age of the population, and higher rates of nosocomial infection due to intravascular devices and other instrumentation. [1314The overall incidence of osteomyelitis is higher in developing countries.

Prognosis

Inadequate therapy may lead to relapsing infection and progression to chronic infection. Because of the relative avascularity of bone, chronic osteomyelitis is curable only with radical resection or amputation. These chronic infections may recur as acute exacerbations, which can be suppressed by debridement followed by parenteral and oral antimicrobial therapy. Rare complications of bone infection include pathologic fractures, secondary amyloidosis, and squamous cell carcinoma at the sinus tract cutaneous orifice.


History

Osteomyelitis is often diagnosed clinically with nonspecific symptoms such as fever, chills, fatigue, lethargy, or irritability. The classic signs of inflammation, including local pain, swelling, or redness, may also occur and usually disappear within 5-7 days. [1]

Chronic posttraumatic osteomyelitis requires a detailed history for diagnosis, including information regarding the initial injury and previous antibiotic and surgical treatment. Weightbearing and function of the involved extremity are typically disturbed. Local pain, swelling, erythema, and edema may also be reported. [2]

Physical Examination

On physical examination, scars or local disturbance of wound healing may be noted along with the cardinal signs of inflammation. [2Range of motion, deformity, and local signs of impaired vascularity are also sought in the involved extremity. If periosteal tissues are involved, point tenderness may be present. [5]

In children, the clinical presentation of osteomyelitis can be challenging for physicians because it can present with only nonspecific signs and symptoms and because the clinical findings are extremely variable. Children may present with decreased movement and pain in the affected limb and adjacent joint, as well as edema and erythema over the involved area. In addition, children may also present with fever, malaise, and irritability. Newborns with osteomyelitis may demonstrate decreased movement of a limb without any other signs or symptoms.

Complications

The most common complication in children with osteomyelitis is recurrence of bone infection. Although adverse outcomes are common with delays in treatment, chronic infection may still develop in 5-10% of patients treated appropriately. Common complications in children younger than 18 months include bone destruction, chronic osteomyelitis, and impaired bone growth, especially when the growth plate is affected. Although rare, extreme bone destruction or thinning of the cortex can lead to pathologic fractures.

When centrally placed intravenous catheters are used in cases that require prolonged antibiotic treatment intravenously, catheter-associated complications can occur. However, the use of peripherally inserted central venous catheters has decreased this complication.

In a study of 17,238 Taiwanese patients newly diagnosed with chronic osteomyelitis from 2000 to 2008 who were identified on the basis of Taiwanese National Health Insurance (NHI) inpatient claims, Tseng et al found chronic osteomyelitis to be associated with an increased risk of dementia, particularly among the younger patients studied.



Diagnostic Considerations

Crystal arthropathies (gout and pseudogout) presents in a similar manner to septic arthritis. The diagnosis can be made by polarized microscopic examination of monosodium urate crystals in gout or calcium pyrophosphate crystals in pseudogout. [16 

In children, Ewing sarcoma is a common form of bone malignancy. It presents with clinical symptoms of fever, pain, malaise, and swelling, which are very similar to those of osteomyelitis. Invasion of the tumor into the periarticular space is uncommon but, if present, can radiographically mimic septic arthritis. [17 

Septic arthritis generally presents with acute pain, swelling, warmth, and decreased range of motion in a single joint. Only 40-60% of patients will have a fever at presentation. Laboratory studies and synovial fluid analysis are helpful for diagnosis. [16]

In patients with sickle cell disease, it can be challenging to differentiate between a vaso-occlusive crisis and an infection such as osteomyelitis. An infectious etiology is less likely if more than one area of the body is affected. Osteomyelitis also tends to have clinical symptoms (eg, pain, swelling, and fever) developing over a longer time course than a vaso-occlusive crisis. [18]

Differential Diagnoses



Laboratory Studies

A complete blood count (CBC) is useful for evaluating leukocytosis and anemia. Leukocytosis is common in acute osteomyelitis before therapy. The leukocyte count rarely exceeds 15,000/µL acutely and is usually normal in chronic osteomyelitis. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are usually increased. [19220In metastatic and some metabolic bone disease, alkaline phosphatase, calcium, and phosphate are elevated, but they are within normal limits in osteomyelitis. [12]

Blood cultures are positive in only 50% of cases of osteomyelitis. [5They should be obtained before or at least 48 hours after antibiotic treatment. Although sinus tract cultures do not predict the presence of gram-negative organisms, they are helpful for confirming S aureus.

Imaging Studies

The American College of Radiology (ACR) has published imaging guidelines for the diagnosis of suspected osteomyelitis, septic arthritis, and soft-tissue infections in cases not involving the spine or the diabetic foot.  [21 (See Guidelines.)

Radiography

Conventional radiography is the initial imaging study at presentation of acute osteomyelitis. It is helpful to interpret current and old radiographs together. (See the image below.)

Osteomyelitis, chronic. Image in a 56-year-old manOsteomyelitis, chronic. Image in a 56-year-old man with diabetes shows chronic osteomyelitis of the calcaneum. Note air in the soft tissues.

Radiographic findings include periosteal thickening or elevation, as well as cortical thickening, sclerosis, and irregularity. Other changes include loss of trabecular architecture, osteolysis, and new bone formation. These changes may not be evident until 5-7 days in children and 10-14 days in adults. Plain films show lytic changes after at least 50%-75% of the bone matrix is destroyed. Therefore, negative radiographic studies do not exclude the diagnosis of acute osteomyelitis.

Healing fractures, cancers, and benign tumors may appear similarly on plain film. Subtle changes may indicate contiguous-focus or chronic osteomyelitis. [42522]

Computed tomography

Computed tomography (CT) is useful for guiding needle biopsies in closed infections and for preoperative planning to detect osseous abnormalities, foreign bodies, or necrotic bone and soft tissue. It may assist in the assessment of bony integrity, cortical disruption, and soft-tissue involvement. It may also reveal edema. Intraosseous fistula and cortical defects that lead to soft tissue sinus tracts are also demonstrated on CT.

Although CT may play a role in diagnosis of osteomyelitis, the scatter phenomenon may result in significant loss of image resolution when metal is near the area of inflammation. [425]

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is a very useful modality in detecting osteomyelitis and gauging the success of therapy because of high sensitivity and excellent spatial resolution. The extent and location of osteomyelitis is demonstrated along with pathologic changes of bone marrow and soft tissue. [4(See the image below.)

Osteomyelitis, chronic. T1- and T2-weighted sagittOsteomyelitis, chronic. T1- and T2-weighted sagittal MRIs show bone marrow edema in L1 and obliteration of the disk space between L1 and L2.

MRI shows a localized marrow abnormality in osteomyelitis. T1-weighted images typically show decreased signal intensity, whereas T2-weighted images produce increased signal intensity. [4Increased intensity on T2-weighted images may indicate sinus tracts, which extend from marrow and bone to skin through soft tissue. A decreased intensity on T1-weighted images with no change on T2-weighted images may indicate surgical or posttraumatic scarring of bone marrow.

Ultrasonography

The presence of fluid collection adjacent to the bone without intervening soft tissue usually suggests osteomyelitis. Other findings on ultrasonography include elevation and thickening of the periosteum. Ultrasonography may also be useful in cases with orthopedic hardware or in patients who are unable to undergo MRI. [23242522]

Nuclear medicine imaging

Three-phase bone scanning is helpful in evaluating acute osteomyelitic and doubtful diskitis. However, the specificity of this procedure is decreased in secondary osteomyelitis. The bone scan may reveal increased metabolic activity in osteomyelitis, but this finding is indistinguishable from posttraumatic injury or following surgery or cancer. [41(See the image below.)

Osteomyelitis, chronic. Three-phase technetium-99mOsteomyelitis, chronic. Three-phase technetium-99m diphosphonate bone scans (static component) show increased activity in the heel and in the first and second toes and in the fifth tarsometatarsal joint.

One approach makes use of white blood cells (WBCs) labeled with technetium-99m (99mTc) hexamethylpropylene amine oxime (99mTc-HMPAO) or indium-111 (111In) oxime. This method, when used in the combination of 111In-oxime WBC scanning with 99mTc-sulfur colloid bone marrow scanning, is helpful for evaluating infections of hip prostheses. Isotope accumulates in areas of increased blood flow and new bone formation in the 99mTc polyphosphate scan.

When the imaging is present on the labeled WBC scan but not on the 99mTc bone marrow scan, the test is positive for osteomyelitis. A negative test result may indicate an impaired blood supply to the affected area. When red marrow is present (ie, axial skeleton and spine), WBC scanning is less sensitive for imaging. [4122]

Gallium citrate attaches to transferrin, which then leaks into inflamed areas from the bloodstream. Increased uptake may occur in infection, cancer, and sterile inflammatory conditions. Performing a 99mTc scan along with the gallium-67 (67Ga) citrate scan may help distinguish bone and soft-tissue inflammation and show bone detail. [41However, the scan is most useful in cases of spondylodiskitis. [22]

In the assessment of inflammation of spinal lesions, 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) may provide high-resolution tomographic images and may represent an alternative to 67Ga citrate scanning. [118F-FDG PET scans have high sensitivity and specificity (97.5% and 86.3%, respectively) in detecting musculoskeletal infections. However, the specificity drops in cases of suspected knee prosthesis infections. [26]

Biopsy

Bone biopsy leads to a definitive diagnosis by isolation of pathogens directly from the bone lesion. [5 Bone biopsy should be performed through uninfected tissue and either before the initiation of antibiotics or more than 48 hours after discontinuance.

Open or percutaneous needle bone biopsy with histopathologic examination and culture is the routine for the diagnosis of osteomyelitis. This procedure may not be necessary if blood cultures are positive with consistent radiologic findings.

When clinical suspicion is high but blood cultures and needle biopsy have yielded negative results, a repeat needle biopsy or an open biopsy should be performed. A bone sample can be collected at the time of debridement for histopathologic diagnosis in patients with compromised vasculature. To obtain accurate cultures, bone biopsy must be performed through uninvolved tissue. Cultures of the sinus tract may be useful if S aureus and Salmonella species are isolated. [2728]

Histologic Findings

Acute osteomyelitis presents with acute inflammatory cells, edema, vascular congestion, and small-vessel thrombosis. In early disease, infection extends into the surrounding soft tissue, which compromises the vascular supply to the bone, as well as host response, surgery, and/or antibiotic therapy.

Large areas of dead bone may form if both medullary and periosteal blood supplies are compromised. Necrotic bone shows extensive resorption and inflammatory exudates on bone biopsy and appears whiter than living bone owing to the loss of blood supply. The development of granulation tissue occurs at the surface of dead bone, which is broken down by proteolytic enzymes, including polymorphonuclear leukocytes, macrophages, and osteoclasts. This occurs most rapidly at the junction of living and necrotic bone. A sequestrum is formed when dead cortical bone is gradually detached from living bone.

Chronic osteomyelitis presents with pathologic findings of necrotic bone, formation of new bone, and polymorphonuclear leukocyte exudation, which is joined by large numbers of lymphocytes, histiocytes, and occasional plasma cells.

The formation of new bone occurs over weeks or months as a vascular reaction to the infection. New bone arises from the surviving fragments of periosteum, endosteum, and cortex in the region of infection along the intact periosteal and endosteal surfaces. It may also occur when periosteum forms an involucrum, which is dead bone surrounded by a sheath of living bone. Involucrum may lead to sinus tracts due to perforations that allow pus to enter surrounding soft tissues and ultimately skin surface. A new shaft forms as the density and thickness of involucrum increases.

As a result of inflammatory reaction and atrophy disuse during the active period of osteomyelitis, surviving bone in the area of infection usually becomes osteoporotic. Bone density increases partially from reuse as the infection subsides and extensive transformation of bone may occur to conform to areas of new mechanical stresses. Over time, old living bone and newly formed bone may appear similar and might be indistinguishable, especially in children.

Staging

Two classification systems are commonly used for osteomyelitis.

In 1970, Waldvogel et al classified bone infections on the basis of pathogenesis and proposed the original osteomyelitis staging system. This system classifies bone infections as either hematogenous or osteomyelitis secondary to a contiguous focus of infection. Contiguous-focus osteomyelitis is further classified according to the presence or absence of vascular insufficiency. Both hematogenous and contiguous-focus osteomyelitis may then be classified as either acute or chronic. [29]

In 2003, Cierny-Mader et al developed their staging system, which at present is more commonly used. This system considers host immunocompetence in addition to anatomic osseous involvement and histologic features of osteomyelitis. [301 The first part of the system specifies four stages, as follows:

  • Stage 1 disease involves medullary bone and is usually caused by a single organism
  • Stage 2 disease involves the surfaces of bones and may occur with deep soft-tissue wounds or ulcers
  • Stage 3 disease is an advanced local infection of bone and soft tissue that often results from a polymicrobially infected intramedullary rod or open fracture; stage 3 osteomyelitis often responds well to limited surgical intervention that preserves bony stability
  • Stage 4 osteomyelitis represents extensive disease involving multiple bony and soft tissue layers; stage 4 disease is complex and requires a combination of medical and surgical therapies, and postoperative stabilization may be needed if the infected bone is an essential weightbearing bone

The second part of the Cierny-Mader classification system describes the physiologic status of the host, as follows:

  • Class A hosts have normal physiologic, metabolic, and immune functions
  • Class B hosts are systemically (Bs) or locally (Bl) immunocompromised; individuals with local and systemic immune deficiencies are labeled as ‘‘Bls’’
  • In Class C hosts, treatment poses a greater risk of harm than osteomyelitis itself; the state of the host is the strongest predictor of osteomyelitis treatment failure, and thus the physiologic class of the infected individual is often more important than the anatomic stage [5]

Other classification systems have been proposed for long-bone osteomyelitis. The Gordon classification classifies long-bone osteomyelitis on the basis of osseous defects, using infected tibial nonunions and segmental defects, as follows [31:

  • 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 Ger classification is used to address the physiology of the wound in osteomyelitis, which is categorized as follows [3233:

  • Simple sinus
  • Chronic superficial ulcer
  • Multiple sinuses
  • Multiple skin-lined sinuses

Bone infection persists if appropriate wound management is not undertaken. It is important to cover open tibial fractures with soft tissue early in the disease to prevent infection and ulceration.

The Weiland classification categorizes chronic osteomyelitis as a wound with exposed bone, positive bone culture results, and drainage for more than 6 months. [34This system also considers soft tissue and location of affected bone. It does not recognize chronic infection if wound drainage lasts less than 6 months. Weiland et al specified the following three types:

  • Type I osteomyelitis was defined as open exposed bone without evidence of osseous infection but with evidence of soft-tissue infection
  • Type II osteomyelitis showed circumferential, cortical, and endosteal infection, demonstrated on radiographs as 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 revealed cortical and endosteal infection associated with a segmental bone defect

The Kelly classification considers the following types of osteomyelitis in adults:

  • Hematogenous osteomyelitis
  • Osteomyelitis in a fracture with union
  • Osteomyelitis in a fracture with nonunion
  • Postoperative osteomyelitis without fracture

This system emphasizes the etiology of the infection along with its relation to fracture healing.



Approach Considerations

Surgery is indicated for osteomyelitis if the patient has not responded to specific antimicrobial treatment, if there is evidence of a persistent soft tissue abscess or subperiosteal collection, or if concomitant joint infection is suspected. Debridement of necrotic tissues, removal of foreign materials, and sometimes skin closure of chronic unhealed wounds are necessary in some cases.

Although vertebral osteomyelitis does not usually necessitate surgical treatment, indications include failure to respond to antimicrobial therapy, neural compression, spinal instability, or drainage of epidural or paravertebral abscesses.

The Infectious Diseases Society of America (IDSA) has published clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, including recommendations regarding antibiotic therapy and surgical intervention (see Guidelines). [36]

Medical Therapy

Antibiotic treatment should be based on the identification of pathogens from bone cultures at the time of bone biopsy or debridement. [14Bone cultures are obtained first, and suspected pathogens are then covered by initiation of a parenteral antimicrobial treatment. However, treatment may be modified once the organism is identified. Parenteral and oral antibiotics may be used alone or in combination depending on microorganism sensitivity results, patient compliance, and infectious disease consultation.

Prophylactic treatment with the bead pouch technique has been suggested in open fractures to reduce the risk of infection. Systemic antibiotics supplemented with antibiotic beads are preferred to systemic antibiotics alone.

Local antibiotic therapy with gentamicin-impregnated Septopal beads, though available in Europe, is controversial. [37 Factors involved in the debate include the length of implantation, the need for removal, and the choice of nonabsorbable versus bioabsorbable delivery vehicles. Prolonged implantation of antibiotic beads and spacers remains controversial owing to the risk of secondary infection and development of resistant organisms. Secondary infection stems from the beads, which may serve as a foreign body upon complete elution of antibiotic.

Traditionally, antibiotic treatment of osteomyelitis consists of a 4- to 6-week course. [4Animal studies and observations show that bone revascularization following debridement takes about 4 weeks. However, if all infected bone is removed, as in forefoot osteomyelitis, antibiotic therapy can be shortened to 10 days. [38]

Oral antibiotics that have been proved to be effective include clindamycin, rifampin, trimethoprim-sulfamethoxazole, and fluoroquinolones. Clindamycin is given orally after initial intravenous (IV) treatment for 1-2 weeks and has excellent bioavailability. It is active against most gram-positive bacteria, including staphylococci. Linezolid is active against methicillin-resistant staphylococci and vancomycin-resistant Enterococcus. It inhibits bacterial protein synthesis, has excellent bone penetration, and is administered intravenously or orally.

Oral quinolones are often used in adults for gram-negative organisms. Quinolones have excellent oral absorption and may be used as soon as patient is able to take them. Rifampin has an optimal intercellular concentration and a good sensitivity profile for methicillin-resistant staphylococci. It is used in combination with cell wall–active antibiotics to achieve synergistic killing and to avoid rapid emergence of resistant strains.

Empiric therapy is necessary when it is not possible to isolate organisms from the infection site. [1Hospital-acquired infections are usually derived from methicillin-resistant staphylococci. Infections contracted outside the hospital are often polymicrobial with the presence of gram-negative bacteria.

Infection may fail to improve owing to the ability of bacteria to resist antibiotics. Some bacteria, such as S epidermidis in prosthesis infections, adhere to a biofilm that protects the organism from phagocytosis and impedes delivery of the antibiotic. The use of rifampin in combination with other antibiotics has been found to be more effective than monotherapy for treating infection associated with surgical hardware. [139]

Suppressive antibiotic therapy should also be directed by bone culture and is given orally when surgery is contraindicated. [4Good bioavailability, low toxicity, and adequate bone penetration are important factors in treatment. If the infection recurs after 6 months of suppressive antibiotic treatment, a new lifelong regimen of suppressive therapy may be tried.

Extensive studies of suppressive therapy with administration of rifampin, ofloxacin, fusidic acid, and trimethoprim-sulfamethoxazole for 6-9 months have been performed in patients with infected orthopedic implants. Studies have shown that, after discontinuance of antibiotics, no recurrence of infection occurred in 67% of patients treated with trimethoprim-sulfamethoxazole, 55% of patients treated with rifampin and fusidic acid, and 50% of patients treated with rifampin and ofloxacin. [4]

Surgical Therapy

Preoperative planning

The Cierny-Mader classification system (see Workup) plays an important role in guiding treatment. As described above, stage 1 and 2 disease usually do not require surgical treatment, whereas stage 3 and 4 respond well to surgical treatment. In Cierny-Mader class C hosts, treatment may be more harmful than the osteomyelitis itself. [5]

Operative treatment consists of the following [4:

  • Adequate drainage
  • Extensive debridement of necrotic tissue
  • Management of dead space
  • Adequate soft-tissue coverage
  • Restoration of blood supply

When a fracture and stable hardware are involved, surgery is used to treat a residual infection after suppressing the infection until the fracture heals. Techniques involve second-stage hardware removal followed by treatment of an infected nonunion, often with an external fixator. External fixators, plates, screws, and rods may be used to restore skeletal stability at the infection site. [4Because hardware tends to become secondarily infected, external fixation is preferred to internal fixation.

Remission or cure is most likely with extensive debridement, obliteration of dead space, removal of any hardware, and appropriate antibiotic therapy.

Debridement of all nonviable or infected tissue is critical because retained necrotic or infected debris can result in osteomyelitis recurrence. Bone debridement is performed until punctuate bleeding is noted. [4The remaining tissue is still considered contaminated even after adequate debridement of necrotic tissue. Studies have shown that marginal resection may be sufficient in normal hosts. However, in compromised hosts, extensive resection seems to be much more important.

“Dead space” refers to the soft tissue and bony defect left behind after debridement. [4Appropriate management of this space is necessary to reduce the risk of persistent infection from poor vascularization of the area and to maintain the integrity of the skeletal part.

Dead space must be filled with durable vascularized tissue, sometimes from the fibula or ilium. Antibiotic-impregnated beads may be used for temporary sterilization of dead space. Vancomycin, tobramycin, and gentamicin are some of the common antibiotics used in these beads. Within 2-4 weeks, the beads may be replaced with cancellous bone graft.

Because two major aims of surgical treatment are resection of necrotic bone and thorough debridement of intraosseous and soft-tissue fistula, computed tomography (CT) is sometimes performed for the purpose of planning a surgical intervention and guiding surgery. Preoperatively, CT is helpful to characterize bone quality, demonstrate intraosseous fistula, and detect devitalized bone areas, or cortical defects that lead to soft-tissue sinus tracts. [2]

When osteomyelitis involves a fracture, it is also important to include a workup to be sure the fracture has healed. Antibiotic-impregnated beads may be used as an effective measure to maintain sterile dead space until a definitive surgical procedure can be performed.

In order to apply the Ilizarov method successfully and to prevent damage to vital nerves and blood vessels, preoperative planning is helpful with careful attention to "safe zones" during wire insertion. It is important to adjust the skin to prevent tension on the skin-wire interface. Correction of the deformity or lengthening is better achieved by appropriately constructing the Ilizarov frame. [40]

Ilizarov method

The Ilizarov method, developed by Ilizarov in 1951, promotes bone growth through distraction osteogenesis using a specialized device and systematic approach. This technique has facilitated limb lengthening, decreased the incidence of many complications, and decreased the level of surgical intervention necessary.

The Ilizarov method involves the use of a tissue-sparing cortical osteotomy-osteoclasis technique that preserves the osteogenic elements in the limb. To create a preliminary callus that can be lengthened, Ilizarov advocated a delay of several days before distraction is initiated. A high-frequency, small-step distraction rhythm permits regeneration of good-quality bone and less soft-tissue complications such as nerve and vessel injury. An advantage of using this procedure is that it minimizes the prevalence of nonunion and thus further bone grafting by producing good-quality bone formation.

The risk of repeat osteotomy and osteoclasis is also decreased owing to less-premature consolidation of the lengthened segment. [41However, Ilizarov techniques are often not tolerated well by patients, and other options, including amputation, may be preferred.

The Ilizarov external fixator is a popular device that is composed of wires, fixation bolts, rings, threaded rods, hinges, and plates, together allowing customized assemblies. Although this apparatus is stiff for bending and torsion, it is less stiff for axial loading. This feature is thought to help promote osteogenesis. [40]

The Ilizarov method is based on the concept of "tension stress," in which gradual distraction stimulates bone production and neogenesis. The Ilizarov device is attached to the distal or proximal portion of the affected bone. Bone regenerates as the screw and wire mechanism moves the healthy bone fragment at a maximal rate of approximately 0.25 mm four times per day for an overall rate of 1 mm per day.

Gentle distraction allows bone formation and decreases the need for supplemental bone grafting and internal fixation. The distraction force permits tissue fibers and cells to become oriented in the same direction as the distraction vector, which is thought to mimic the process of natural bone growth. [40]

Nonunions, malunions, or defects of any length can be treated and may also be corrected by using the Ilizarov method. At the same time, the Ilizarov technique is labor-intensive and may require at least 8 months of treatment. In addition, the fixator pins can be uncomfortable and often become infected. Amputation is an option if reconstruction is not suitable.

Wound closure

To arrest infection, it is necessary to provide adequate soft-tissue coverage. [4Over small soft-tissue defects, a split-thickness skin graft may be placed, whereas large soft-tissue defects may be covered with local muscle flaps and free vascularized muscle flaps. Rotation of a local muscle with its neurovascular supply must be possible anatomically for that procedure to be successful.

These flaps bring in a blood supply, which is important for host defense mechanisms, new bone regeneration, delivery of antibiotics, and healing. They also may be used in combination with antibiotics and surgical debridement of necrotic and infected tissues. The fibula and iliac crest are common donor sites for free flaps.

Adjunctive hyperbaric oxygen therapy

Adjunctive hyperbaric oxygen therapy can promote collagen production, angiogenesis, and healing in an ischemic or infected wound. [4]

Complications

The Ilizarov technique is usually well tolerated by the patient, with little associated pain. A few complications that have been reported include pin-tract infections and cellulitis, flexion contractures above and below the frame, limb edema, and bone fragment rotation with malunion. [42]

During the course of treatment with the Ilizarov technique, patients have a high emotional and physical burdens. However, these symptoms improve, and patients are similar to the general population postoperatively. Appropriate patient counseling regarding the psychological impact of this treatment is needed. [43]

The complication rate may be decreased by future efforts to improve the Ilizarov method. [41 Some goals include improving the technique to prevent pin-track infections and osteomyelitis, premature or delayed consolidation of bone, angular or axial deviation of the new bone, joint contracture or instability, neurovascular compromise, and psychological adjustment reactions.

Long-Term Monitoring

After a corticotomy is made for bone lengthening, a latency period is required before distraction. Once distraction has begun using the Ilizarov technique, new bone should be apparent within 3-4 weeks. After the appropriate length is obtained or the angular deformity corrected, the apparatus remains in place until completion of the consolidation phase. During the postoperative period, it is necessary to adjust or modify the assembly, and the apparatus is removed when the goal is achieved. [40]

Because the apparatus may be in place for an extended period, even as long as 1 year, special postoperative considerations are important. [40Pain management may be a challenge because of the duration of mild-to-moderate postoperative pain. For preventing flexion contractures of the surrounding joints, intensive physical therapy and splinting techniques are key elements. Successful treatment also requires psychological support and family counseling.

Problems to be particularly watchful for during the postoperative period include pin-track infections, premature or delayed consolidation, joint contractures, and pin breakage that may require replacement.

Imaging studies in the follow-up period are most useful in patients who have equivocal or worse clinical status at the end of therapy.


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