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Osteomyelitis in adults: Medical Topics: First Consult

10/10/12 5:54 AM

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Osteomyelitis in adults
Contributors

Because not all answers are created equal

Key points
Osteomyelitis is an infection of the bone Many species of organisms have been implicated in the etiology of osteomyelitis, with Staphylococcus aureus being the most commonly isolated organism Patients with osteomyelitis typically present with localized pain and swelling accompanied by nonspecific symptoms, including chills, fever, and malaise Several diagnostic modalities are used to determine the presence of osteomyelitis, including laboratory tests, radiographic imaging, radionuclide studies, and cross-sectional imaging. The gold standard for diagnosing osteomyelitis is bone biopsy and culture Treatment of osteomyelitis involves both antimicrobial therapy, with administration of antibiotics for at least 4 to 6 weeks, and surgical intervention, which involves debridement, dead space management, and bone stabilization Complications of osteomyelitis include abscess formation, sepsis, bone deformity, limited range of movement, and motor and sensory deficits Approximately 20% to 30% of patients with osteomyelitis experience recurrence within 2 years, even with appropriate medical and surgical treatment

Background
Description
Osteomyelitis is an inflammation or infection of the bone and may include the marrow, cortex, and periosteum; surrounding soft tissues are often involved as well The condition may arise from trauma, bacteremia, surgery, or orthopedic implants that disrupt the integrity of the bone, as well as from overlying infections, such as those associated with diabetic foot ulcerations There are two major systems for classifying osteomyelitis. The Waldvogel classification system is based on the pathogenesis of the infection, whereas the Cierny-Mader staging and classification system categorizes the disease according to the extent of involvement and the patient's physiologic status, which is valuable in determining treatment and prognosis Waldvogel classification system Osteomyelitis is classified according to the mechanism of infection (hematogenous or contiguous) and the presence of vascular insufficiency: Hematogenous osteomyelitis Occurs when bone tissue is seeded by pathogenic organisms during the course of bacteremia Accounts for 20% of cases of osteomyelitis in adults The vertebrae are the most common site of hematogenous infection in adults, but the long bones, pelvis, and clavicle may also be affected Vertebral osteomyelitis is divided into the following two categories: Pyogenic infections, which are most commonly caused by S. aureus (40%-45% of all cases) Nonpyogenic (granulomatous) infections, which are most commonly caused by Mycobacterium tuberculosis Vertebral osteomyelitis occurs most commonly in men between 60 and 70 years of age and involves the lumbar spine Osteomyelitis secondary to a contiguous focus of infection Occurs after a traumatic bone injury or as a result of the spread of infection from a nearby source (eg, soft tissue infection) Common associated factors include a history of surgical reduction and internal fixation of fractures, prosthetic devices, open fractures, and chronic soft tissue infections; decubitus ulcer; burn; or regional soft tissue infection More common in older patients, who generally develop infections following cellulitis or arthroplasties; infection in younger patients usually occurs as a result of trauma or surgery Most often affects the tibia and femur Osteomyelitis associated with vascular insufficiency Caused by impaired blood supply to susceptible tissues Usually occurs in older patients and in patients with diabetes mellitus or severe atherosclerosis In patients with diabetes, the small bones of the feet are most often involved; neuropathy may also be present The risk of developing osteomyelitis is greater in patients with large (>2 cm in diameter) and deep (>3 mm) diabetic ulcers and if the bone is exposed Osteomyelitis may be classified as acute, subacute, or chronic, depending on the time to clinical presentation relative to the introduction of infection. Acute osteomyelitis is characterized as a suppurative infection presenting with edema, small vessel thrombosis, and vascular congestion within 2 weeks of onset Subacute osteomyelitis may be more indolent, presenting 1 to several months after infection Chronic osteomyelitis is the result of longstanding infection, which may take months or years to develop or which has been suppressed by the host ('remission') or partially treated so that it remains relatively dormant for long periods before becoming clinically apparent. Chronic osteomyelitis is characterized by the presence of necrotic bone (sequestrum); new bone formation; drainage or sinus tracts; and the presence of leukocytes, lymphocytes, and histiocytes. It can be recognized in patients with a history of osteomyelitis who experience a recurrence of pain, erythema, and swelling, along with a draining sinus Cierny-Mader staging and classification system Osteomyelitis is categorized according to the portion of bone affected; the physiologic status of the patient; and risk factors that affect immunity, metabolism, and vascularity. The first part of the system categorizes osteomyelitis according to anatomic type, as follows: Stage 1: medullary osteomyelitis Limited to the medullary cavity Often caused by a solitary organism Causes include hematogenous spread and infections from orthopedic devices (intramedullary rods) Stage 2: superficial osteomyelitis Involves the cortex Often caused by an adjacent soft tissue infection Exposed, infected outer necrotic surface of bone is observed at the base of a soft tissue wound Local ischemia is seen Stage 3: localized osteomyelitis May involve both the medulla and cortex, but the bone generally remains stable, as the infection does not involve its entire diameter Stage 4: diffuse osteomyelitis Extensive disease
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Osteomyelitis in adults: Medical Topics: First Consult

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May occur on both sides of a nonunion or a joint Involves the entire thickness of the bone, with loss of stability The second part of the system describes the patient's physiologic status, as deficiencies of leukocyte recruitment, phagocytosis, or vascular supplies may promote osteomyelitis and contribute to its chronicity. The physiologic class of the infected patient is often more important than the anatomic type because the state of the host is the strongest predictor of treatment failure. Class A: normal host Normal physiologic, metabolic, and immune functions Associated with a much better prognosis Class B: host factors limit normal immune response and healing Immunocompromised, either locally (Bl), systemically (Bs), or both (Bls) Local factors include problems of perfusion (peripheral vascular disease, vasculitis, venous stasis, lymphedema) Systemic factors include hypoxemia, illnesses associated with impaired immune function (chronic renal or hepatic insufficiency, malignancy, diabetes), or use of immunosuppressive medication (steroids) The goal of treatment is to remove the factors that lead to the development of osteomyelitis Class C: health of host does not allow full treatment Treatment poses a greater risk than the infection itself Surgery may not be possible because of the patient's debilitated or immunocompromised status Back to Top

Epidemiology
There are several recent trends in the epidemiology of osteomyelitis. Acute hematogenous osteomyelitis is decreasing in incidence, whereas the incidence of osteomyelitis due to direct inoculation or contiguous focus of infection is increasing. This is attributed to the increase in both trauma (due to motor vehicle accidents) and orthopedic surgical procedures Osteomyelitis secondary to open fractures occurs in 3% to 25% of cases, usually in young men in their twenties and thirties Foot ulcers occur in 2% of patients with diabetes every year, 15% of whom will develop osteomyelitis. Recurrent infection occurs in up to 36% of patients with diabetes Vertebral osteomyelitis is responsible for 2% to 4% of all cases of osteomyelitis, with an annual incidence of 5.3 cases per million persons. Men are more commonly affected than women, with a mean age at presentation of 61 years Back to Top

Causes and risk factors


Causes: The focus for hematogenous osteomyelitis may vary from a mild skin infection to bacterial endocarditis; it is also a complication among intravenous drug users Osteomyelitis secondary to a contiguous focus of infection may be caused by the direct inoculation of bacteria through trauma, from spread of adjacent soft tissue infection, or introduction of infection during preoperative or intraoperative procedures. Predisposing factors include surgical reduction and internal fixation of fractures, prosthetic devices, open fractures, and chronic soft tissue infections Osteomyelitis secondary to vascular insufficiency is often associated with diabetes mellitus. Infection often results from minor trauma to the feet, such as infected nail beds or skin ulceration. Inadequate tissue perfusion limits local tissue response to injury Multiple organisms are responsible for osteomyelitis in different populations. The causative organism is related to the age, clinical history, and immune status of the patient (see Table 1). S. aureus is the most common cause in all cases Table 1. Organisms Commonly Implicated in Osteomyelitis in Different Patient Populations

Category of Osteomyelitis Hematogenous osteomyelitis

Population Patients of all ages Neonates Infants and children Intravenous drug users Patients with sickle cell disease HIV-infected patients Patients with nosocomial infections

Vertebral osteomyelitis (hematogenous and contiguous focus)

Contiguous-focus osteomyelitis

Causative Organism(s) S. aureus Enterobacteriaceae, group B streptococci Haemophilus influenzae type B S. aureus, Pseudomonas aeruginosa, Candida species Streptococcus pneumoniae, Salmonella species Bartonella henselae S. aureus, Enterobacteriaceae, Candida species, Aspergillus (in immunocompromised patients) Adults (most commonly) S. aureus Patients with urinary tract infections Aerobic gram-negative bacilli, Enterococcus species Intravenous drug users S. aureus, P. aeruginosa Patients undergoing spinal surgery Coagulase-negative staphylococci, S. aureus, aerobic gram-negative bacilli Patients with infections of Candida species, staphylococci intravascular devices Patients living in endemic regions M. tuberculosis, Brucella species, regional fungi (coccidioidomycosis, blastomycosis, histoplasmosis), Coxiella burnetii (Q fever) Patients exposed to contaminated soil Clostridium species, Bacillus species, Stenotrophomonas maltophilia, Nocardia species, atypical mycobacteria, Aspergillus species, Rhizopus species, Mucor species Patients with orthopedic devices S. aureus, coagulase-negative staphylococci, Propionibacterium species Patients with decubitus ulcers Enterobacteriaceae, P. aeruginosa, enterococci,
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Osteomyelitis in adults: Medical Topics: First Consult

10/10/12 5:54 AM

Osteomyelitis associated with vascular insufficiency


HIV = human immunodeficiency virus Risk factors: Diabetes mellitus Immunocompromise Neuropathy Vascular insufficiency Intravenous drug use Open fractures Local trauma Orthopedic hardware (including prosthetic joints) Hemodialysis Sickle cell disease Dental infections Urinary tract infections Catheter-related bloodstream infection Back to Top

anaerobes, Candida species Patients with a history of cat bites Pasteurella multocida Patients with a history of human bites Eikenella corrodens, Moraxella species (including clenched-fist injury) Patients with puncture injuries on the P. aeruginosa foot Patients with periodontal infection Actinomyces species Patients with diabetes Polymicrobial: S. aureus, -hemolytic streptococci, Enterococcus faecalis, aerobic gram-negative bacilli

Associated disorders
Occurs more frequently in patients with diabetes mellitus, vascular insufficiency, or immunosuppression Recent history of surgical procedure or joint or bone trauma

Screening
Not applicable.

Primary prevention
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Summary approach
Patients with diabetes should have a complete examination of the lower extremities annually and inspection of the feet for wounds at interim routine follow-up visits. Measures to prevent diabetic foot ulcers should be emphasized. A high index of suspicion should be maintained for the contiguous spread of local diabetic foot infections to the bone, with continuous evaluation for signs and symptoms of the development of osteomyelitis Patients with open fractures who are able to receive antibiotics within 6 hours of injury and prompt surgical treatment have a reduced risk of developing osteomyelitis The use of prophylactic antibiotics prior to bone surgery has been shown to prevent wound infections Scrupulous care should be taken to avoid health careassociated osteomyelitis, with careful attention to intravascular and urinary catheters, surgical incisions, and other wounds Back to Top

Population at risk
Patients with diabetes mellitus Patients undergoing orthopedic surgery, including placement of prostheses and other clean surgery and management of open fractures Back to Top

Preventive measures [EBM]


In patients with diabetes mellitus: Measures to prevent diabetic foot include excellent foot hygiene, glycemic control, and use of protective footwear Patients should be instructed to examine their feet daily and to seek prompt medical care for new wounds or other injuries to the feet A complete evaluation of the lower extremities should be done annually, and the feet should be inspected for wounds at periodic follow-up visits in the interim Patients with Charcot joints or other abnormalities that result in friction with shoes may require specially adapted shoes In patients undergoing foot surgery or amputation, the use of protective footwear postoperatively is helpful in preventing subsequent ulceration and infection In patients with open fractures: Administration of antibiotics within 6 hours of injury and prompt surgical treatment are associated with a reduced risk of developing osteomyelitis A continued 24-hour regimen of penicillin or first-generation or second-generation cephalosporins is also beneficial In patients undergoing bone surgery: Administration of prophylactic antibiotics has proven to be successful in the prevention of infection following surgery, particularly in patients with noncompound hip

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fractures and those receiving total hip and knee prostheses In patients undergoing clean bone surgery, intravenous antibiotics are administered 30 minutes before skin incision and up to 24 hours following the procedure. A first-generation or second-generation cephalosporin is appropriate in many cases; vancomycin may be used in patients who are allergic to cephalosporin and in settings with a high prevalence of methicillin-resistant staphylococci In patients undergoing surgery for closed fractures, the use of penicillin, first-generation cephalosporins (eg, cefazolin), or second-generation cephalosporins (eg, cefamandole, cefuroxime) has led to a reduction in postsurgical infection Standard preoperative procedures, such as the use of antimicrobial shower, shaving, and topical disinfectants, should be followed. Observation of such procedures, together with the use of surgical rooms with laminar airflow and prophylactic antibiotic therapy, has led to a reduction in the postsurgical rate of infection to 0.5% to 2%, depending on the type of joint replacement Evidence An observational study of 2,847 patients receiving antibiotic prophylaxis for elective surgical procedures showed that surgical wound infections occurred in 0.6% of those who received antibiotics preoperatively, 1.4% of those who received antibiotics perioperatively (relative risk [RR], 2.4 compared to the preoperative group), 3.3% of those who received antibiotics postoperatively (RR, 5.8), and 3.8% of those who received early antibiotic treatment (RR, 6.7). Administration of antibiotics during the preoperative period was associated with the lowest risk of surgical wound infection.[1]Level of evidence: 1 Learn about evidence grading system

Diagnosis
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Summary approach
Osteomyelitis is diagnosed on the basis of data obtained from the history, physical examination, and laboratory tests. The diagnosis is confirmed by needle aspiration or bone biopsy, with subsequent demonstration of infectious microorganism by culture or histology Patients with osteomyelitis typically present with localized pain and swelling accompanied by nonspecific symptoms, including chills, fever, and malaise Laboratory tests and imaging techniques, including magnetic resonance imaging (MRI), computed tomography (CT) scan, positron emission tomography (PET) scan, and radionuclide studies, are important tools in establishing the diagnosis of osteomyelitis Back to Top

Clinical presentation
History Symptoms: Patients with osteomyelitis often present with nonspecific constitutional symptoms, including chills, fever, malaise, irritability, fatigue, and lethargy; localized pain, swelling, and redness may also be present Patients with diabetes and others with peripheral neuropathy may not experience pain Compared to younger patients, adults with osteomyelitis present less frequently with typical systemic symptoms Hematogenous osteomyelitis: Vague symptoms (nonspecific pain and low-grade fever, chills) Symptoms of vertebral osteomyelitis include axial skeletal pain; constant, dull back or neck pain that worsens upon straining; regional paraspinal muscle spasms; and limping Osteomyelitis secondary to a contiguous focus of infection: Localized bone pain Low-grade fever Osteomyelitis associated with vascular insufficiency: Systemic symptoms of infection, including fever, chills, and malaise, may be absent in patients with osteomyelitis associated with a diabetic foot Other historical factors: Presence of diabetes mellitus History of trauma, especially open fractures History of skin and soft tissue infections Previous surgical procedures, including placement of prosthetic devices Previous diagnosis of refractory infections (eg, methicillin-resistant S. aureus [MRSA], fungal infections) Presence of embedded foreign bodies (eg, gunshot wounds) Presence of other risk factors (eg, intravenous drug abuse, hemodialysis, vascular disease) Physical examination Neurologic function should be assessed in patients with vertebral osteomyelitis Examination of patients with diabetes should include inspection of the entire surface of both ankles and feet, assessment of neuropathy by monofilament testing, and examination of the vascular status of the lower extremities; osteomyelitis usually occurs at the base of chronic, nonhealing wounds in these patients Signs: Acute osteomyelitis: Tenderness, erythema, and calor over the affected area Limited range of motion Subacute and chronic osteomyelitis: Draining sinus tracts Sequestrum formation Deformity Instability Local signs of impaired vascularity, range of motion, and neurologic function Vertebral osteomyelitis There may be tenderness on palpation of the involved spinal segment, sustained paraspinal spasms, and limitation of motion

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Neurologic deficit or meningitis may be seen as a result of spread of the infection into the epidural space; paralysis is associated with epidural abscesses Osteomyelitis secondary to a contiguous focus of infection: Patients with an infected prosthesis may have pain and instability of the joint Probing a wound may show softened bone at the base Osteomyelitis secondary to vascular insufficiency: Patients with diabetes usually have purulent drainage from the wound, surrounding erythema, and exposed or palpable necrotic bone; there is sometimes a deceptive lack of inflammation because of poor perfusion Back to Top

Diagnostic testing
A leukocyte count and erythrocyte sedimentation rate (ESR) should be obtained, as leukocytosis (leukocyte count >10,000/mL) and ESR elevation occur early in the course of acute osteomyelitis. Leukocytosis may not be seen in patients with chronic infections C-reactive protein (CRP) is also a useful diagnostic tool but is not specific for osteomyelitis. CRP is synthesized by the liver whenever infection occurs. CRP levels increase within hours of infection; return to normal levels signifies improvement. Because of its short half-life, CRP can be used to gauge the response to treatment Blood cultures to identify the causative organism are critical to guide the selection of appropriate antibiotic therapy. In patients with hematogenous osteomyelitis, blood culture results may be positive at the time of diagnosis; in patients with health careassociated hematogenous infection, recent positive blood culture results also may provide a clue to the diagnosis Bone biopsy for histopathology and culture is the gold standard for the diagnosis of osteomyelitis and is often required to confirm the presence of osteomyelitis while excluding another inflammatory process and to identify the causative pathogen. A biopsy should be obtained before antibiotic therapy is initiated or, if not possible, at least 48 hours after treatment has been discontinued. Fine-needle aspiration bone biopsies have a sensitivity of 87% and a specificity of 93%. Specimens taken from draining sinus tracts or the wound surface often yield inaccurate results due to nonpathogenic microorganisms that often colonize the site. Isolates obtained from bone biopsy should be tested for both aerobic and anaerobic organisms, and cultures for mycobacterial and fungal infections also should be obtained The following imaging modalities have been used for the detection of osteomyelitis: Conventional radiography is the initial imaging study obtained in all patients in whom musculoskeletal infection is suspected In patients with negative or unequivocal radiographic findings, magnetic resonance imaging (MRI) has been used widely due to its excellent resolution, which shows inflammation and edema in bone tissue. Changes are evident much earlier than on plain radiographs, and MRI is more specific than bone scan Computed tomography (CT) scan is less sensitive than MRI but provides images of good resolution and may be helpful in patients who cannot undergo MRI; CT sinography and conventional tomography also may be done Radionuclide studies: Three-phase bone scan is readily available and very sensitive in unviolated bone, although uptake reflects increased metabolic activity and is not specific for infection Radiolabeled leukocyte scan may be helpful in patients with prosthetic joint infections Radiolabeled antibiotic scintigraphy can differentiate infection from a sterile inflammatory lesion Streptavidin/indium In 111 biotin complex scintigraphy has been shown to be very sensitive in identifying vertebral osteomyelitis within the first 2 weeks of infection Fludeoxyglucose F 18 (FDG)PET is a relatively new technique that has been shown to be accurate in establishing the diagnosis of osteomyelitis The combination of single-photon emission CT (SPECT) and CT can facilitate accurate diagnosis of osteomyelitis Transcutaneous oximetry and measurement of pulse pressure by Doppler ultrasonography are used to assess vascular compromise in patients with osteomyelitis secondary to vascular insufficiency
Leukocyte count

Description A venous blood sample is obtained, and the total leukocyte count and differential count are measured Normal ranges Total leukocyte count: 4,500 to 11,000/L Differential count (with percentage of the total count): Neutrophilssegmented: 1,800 to 7,800/L (56%) Neutrophilsbands: 0 to 700/L (3%) Lymphocytes: 1,000 to 4,800/L (34%) Monocytes: 0 to 800/L (4%) Eosinophils: 0 to 450/L (2.7%) Basophils: 0 to 200/L (0.3%) Comments The infective nature of osteomyelitis is responsible for elevations in markers of systemic infection, such as the leukocyte count Not specific for osteomyelitis; other infections, inflammatory conditions, and hematologic malignancies all can increase the leukocyte count Less specific and of less predictive value than CRP or ESR Should be used in conjunction with CRP and ESR to establish the diagnosis in patients in whom osteomyelitis is suspected May be normal in patients with chronic osteomyelitis or directly spread osteomyelitis Not widely used for monitoring or treatment of osteomyelitis
ESR

Description A venous blood sample is obtained, and the ESR (how rapidly erythrocytes settle in a tube of blood) is measured Normal range 0 to 20 mm/h Comments A useful screening method for differentiating mechanical from infective or inflammatory bone symptoms Can be used in conjunction with CRP for both diagnosis of osteomyelitis and monitoring of treatment

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Elevation suggests inflammation, with the increase in ESR approximately proportional to the degree of inflammation Not specific for osteomyelitis; other conditions, including cancers (particularly hematologic cancers, such as multiple myeloma), systemic infection (eg, sepsis in the respiratory or urinary tract, skin or soft tissue infection), and inflammatory conditions (eg, connective tissue disease, arteritis) may result in elevation of the ESR Less specific and has a lower predictive value than CRP Although an elevated ESR does not confirm the diagnosis of osteomyelitis, it can serve to alert the physician of the need for urgent orthopedic referral in patients in whom osteomyelitis is suspected May be falsely low in patients with conditions in which erythrocytes do not undergo rouleaux formation (eg, sickle cell anemia, hereditary spherocytosis)
CRP [EBM]

Description A venous blood sample is obtained, and the CRP level is measured Normal range 0.08 to 3.1 mg/L Comments A useful screening method in patients with bone symptoms Can be used in conjunction with CRP for both diagnosis of osteomyelitis and monitoring of treatment Elevation suggests inflammation, with the increase in CRP approximately proportional to the degree of inflammation Elevation in a patient with bony symptoms should raise the possibility of infection and prompt urgent referral to the hospital Not specific for osteomyelitis; other conditions, including cancers, systemic infection (eg, sepsis in the respiratory or urinary tract, skin or soft tissue infection), and inflammatory conditions (eg, connective tissue disease, arteritis) may result in elevation of the CRP level Although an elevated CRP level does not confirm the diagnosis of osteomyelitis, it can serve to alert the physician of the need for urgent orthopedic referral in patients in whom osteomyelitis is suspected In patients with hematogenous osteomyelitis, the CRP level increases and decreases significantly faster than the ESR, reflecting the effectiveness of therapy and predicting recovery more sensitively than the ESR or leukocyte count
Evidence

An observational study was conducted to determine the value of CRP in predicting healing versus infection or other complications in 52 patients undergoing soft tissue reconstructions following open fractures of the lower limbs, chronic infection, osteomyelitis, and nonunion. Of 41 patients whose CRP level peaked 4 or fewer days after surgery, 15% developed infection or required further surgery. Of 11 patients whose CRP level peaked more than 4 days postoperatively, 82% developed infection or required further surgery. Of 25 patients who achieved complete healing of a fracture, all had CRP levels <8 mg/L at the time of union; patients with nonunion all had CRP levels >8 mg/L. The investigators concluded that persistent elevation of CRP after the fourth postoperative day predicts complications in this setting.[2]Level of evidence: 2 Learn about evidence grading system
Blood cultures

Description Venous blood samples are obtained in specific bottles under scrupulous aseptic technique and set up for cultures Usually done in a laboratory but may involve the primary care physician, especially in rural settings Normal result No growth on culture Comments Results can effectively guide therapy A positive result is indicative of bacteremia, although contamination of the specimen is possible; positive results are also more likely if the patient has a fever when the sample is obtained. Microbiologic expertise is required in the interpretation of results Not specific for osteomyelitis; bacteremia occurs as a result of most other bacterial infections Recent or ongoing use of antibiotics may substantially reduce sensitivity
Bone biopsy [EBM]

Description Fine-needle aspiration or open biopsy with subsequent histopathologic and microbiologic examination of the bone Done by an orthopedic surgeon with the patient under local anesthesia Normal result Marrow cellularity appropriate to the patient's age Comments The gold standard for the diagnosis of osteomyelitis Should be done before antibiotic therapy is started or, if not possible, at least 48 hours after it has been discontinued Fine-needle aspiration has a sensitivity of 87% and a specificity of 93% Specimens taken from draining sinus tracts or the wound surface often yield inaccurate results due to nonpathogenic microorganisms that often colonize the site Invasive, with attendant risks (albeit low) of hemorrhage, infection, and wrong positioning of the needle, and unpleasant for the patient
Evidence

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A prospective study evaluated the sensitivity and specificity of fine-needle bone biopsy in 30 patients in whom osteomyelitis was suspected. The diagnosis of osteomyelitis was confirmed by conventional means in 15 patients. The sensitivity of fine-needle bone biopsy for diagnosing osteomyelitis was 87%, and the specificity was 93%.[3]Level of evidence: 2 Learn about evidence grading system
Conventional radiography

Description Plain radiographs of the affected area are obtained to screen for osteomyelitis Normal result No abnormality seen Comments Findings in patients with osteomyelitis include soft tissue swelling (earliest change seen); swelling of the muscles with obliteration of the soft tissues; and bone destruction and periosteal reaction, signifying that infection has been present for at least 1 to 2 weeks. Brodie abscesses, circumscribed lesions favoring the ends of long bones that may be formed during the subacute or chronic stages of osteomyelitis, also may be seen It takes 10 to 21 days after the onset of infection for the lesion to become visible, as bone density must be reduced by 30% to 50% to produce the radiographic change necessary for visualization Sensitivity is 43% to 75%, and specificity is 75% to 83%
MRI [EBM]

Description Magnetic and radio energy is used to create cross-sectional images or 'slices' of the body Normal result No abnormality detected Comments Useful in distinguishing between soft tissue infections and bone infections and in diagnosing early osteomyelitis; also aids in optimal surgical management by establishing the extent of disease and detecting abscesses and other anatomic features that may determine the surgical approach Widely used in the diagnosis of osteomyelitis associated with a diabetic foot In patients with acute osteomyelitis, the earliest finding is an alteration of the normal marrow signal density, which is present within 1 to 2 days of onset of infection (low signal intensity on T1-weighted images and high signal intensity on T2-weighted, short T1 inversion recovery, or fat-saturated sequences) In patients with subacute or chronic osteomyelitis, findings include Brodie abscess, which is a characteristic abscess surrounded by granulation tissue, an outer ring of fibrotic reaction, and a peripheral rim of endosteal reaction that creates a target appearance In patients with chronic osteomyelitis, low signal intensity on both T1-weighted and T2-weighted images reflects areas of devascularized fibrotic scarring. Bone sclerosis with cortical thickening from periosteal apposition can be observed, along with a focally reduced cavity of the bone marrow. Sinus tracts also can be seen. Normal and abnormal bone marrows are well delineated by a sharp interface Sensitivity is 82% to 100% (90%-100% in patients with diabetes), and specificity is 75% to 96% (80%-100% in patients with diabetes) Advantages include provision of excellent anatomic detail, lack of radiation exposure, and rapid completion Disadvantages include occasional inability to differentiate infectious inflammation from reactive inflammation, limitations in patients with prosthetic devices, high cost ($400-$3,500), and lack of availability in some areas
Evidence

A meta-analysis conducted to determine the diagnostic test performance of MRI for osteomyelitis of the foot identified 16 studies that met the inclusion criteria. The combined diagnostic odds ratio (OR) for MRI was 42.1, and the specificity at a 90% sensitivity cutoff was 82.5%. Diagnostic ORs for MRI compared with those for other diagnostic tests were as follows: 149.9 versus 3.6 for bone scan, 81.5 versus 3.3 for plain radiography, and 120.3 versus 3.4 for radiolabeled leukocyte scan.[4]Level of evidence: 2 Learn about evidence grading system
CT scan

Description Produces images with high spatial and contrast resolution of bone and tissue and excellent cortical bony detail Reliably identifies cortical destruction, periosteal proliferation, and soft tissue extension Normal result No abnormality detected Comments Findings in patients with acute osteomyelitis include increased density of the normal fatty medullary canal as it is replaced by infectious edema and the blurring of fat planes, eventual periosteal reaction, and loss of cortex Findings in patients with chronic osteomyelitis may include abnormal thickening of the affected cortical bone with sclerotic changes, encroachment of the medullary cavity, and sometimes a chronic draining sinus Sensitivity and specificity have not been fully established, although sensitivity is certainly lower than that of MRI Advantages are as follows: Assesses bone integrity and cortical destruction in patients in whom osteomyelitis is suspected Assists in preoperative planning by detecting necrotic debris, foreign bodies, etc.
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Detects sequestra, cloacae, involucra, and intraosseous gas (superior to MRI in this regard) Guides fine-needle biopsies Assists in optimizing surgical debridement by defining surgical boundaries Delineates abscess cavities Disadvantages include high cost, radiation exposure, and lack of availability
CT sinography

Uses contrast medium to opacify a sinus tract A small flexible catheter is inserted into a cutaneous opening, and a contrast medium is introduced, which charts the course and extent of the sinus tract and determines if there is communication with neighboring structures
Conventional tomography

Description Provides images of a series of sections or slices of the tissues at varying depths from the skin surface Normal result No abnormality detected Comments Helpful in evaluating abnormalities within high-contrast tissues, such as bone Able to detect sequestra (pieces of necrotic bone that are separated from living bone by granulation tissue) in patients with chronic osteomyelitis
Bone scan

Description Scintigraphy with triple-phase technetium Tc99m methylene diphosphonate Consists of the following three phases: Flow phase: immediately after injection, at a rate of 2 seconds per frame Blood-pool phase: 5 to 15 minutes after injection Delayed phase: 2 to 3 hours after injection A fourth phase may be taken after 24 hours if the results of the first three phases are ambiguous Normal result No bone lesions detected Comments Most useful radionuclide study for the diagnosis of osteomyelitis Positive results are seen within 24 to 48 hours of the onset of symptoms Classic findings in patients with osteomyelitis are focal hyperperfusion, focal hyperemia, and focal bone uptake A positive result on all three phases indicates a high sensitivity (69%-100%) for osteomyelitis but with a low specificity (38%-96%) Advantages include high sensitivity for osteomyelitis (can differentiate between cellulitis and osteomyelitis reliably when no complicating conditions are present), wide availability, relatively low cost, ease of performance, and rapid completion The main disadvantage is that abnormalities reflect the rate of new bone formation in general and not infection specifically. Thus, the specificity for osteomyelitis decreases when other conditions are present (eg, recent trauma, surgery, placement of orthopedic devices, or diabetes)
Radiolabeled leukocyte scan

Description The patient's leukocytes, which tend to accumulate in areas of acute infection, are isolated and labeled with indium In 111 before being administered back to the patient The majority of the labeled leukocytes are neutrophils; thus, the procedure is most practical for recognizing neutrophil-mediated inflammatory processes (bacterial infections) Comments Sensitivity is 88% to 89%, and specificity is 85%; the high specificity is the main advantage over technetium scans Cannot distinguish well between osteomyelitis and soft tissue infections Infrequently used when diagnostic urgency is present because the procedure is time intensive and requires 40 to 60 mL of whole blood
Radiolabeled antibiotic scintigraphy [EBM]

Description Ciprofloxacin labeled with technetium Tc 99m is administered, and uptake is observed Normal result High uptake of technetium Tc 99m by the kidneys, moderate uptake by the liver and spleen, and absence of uptake by the bone or bone marrow Comments Antibiotics tend to localize at the focus of infection, where they are taken up and metabolized by microorganisms Able to differentiate infection from a sterile inflammatory lesion One study showed a sensitivity of 97.2% and a specificity of 80%, with positive and negative predictive values of 94.6% and 88.9%, respectively
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Administration of antibiotics before bone biopsy may alter culture results


Evidence

A clinical trial in 45 patients with known or suspected bone infection who underwent 50 scans using scintigraphy with technetium Tc 99mradiolabeled ciprofloxacin (Infecton) found that the sensitivity and specificity of Infecton scintigraphy for detecting osteomyelitis were 97.2% and 80%, respectively, and the positive and negative predictive values were 94.6% and 88.9%, respectively.[5]Level of evidence: 2 Learn about evidence grading system
Streptavidin/indium In 111 biotin complex scintigraphy [EBM]

Description Streptavidin, a 65-kDA protein that builds up at sites of infection due to the locally increased vascularity and vascular permeability, is administered followed by administration of indium In 111 biotin, which has a high affinity to streptavidin and accumulates at the focus of infection Comments Has been shown to be very sensitive in the recognition of vertebral osteomyelitis within the first 2 weeks of infection; this is clinically significant because conventional radiography often yields negative results in the first 4 to 5 weeks after the onset of symptoms A potential disadvantage is the occurrence of immunogenic reactions that may develop in response to subsequent administration of the agent
Evidence

A clinical trial evaluated the diagnostic performance of streptavidin/indium In 111 biotin scintigraphy within 2 weeks of the onset of clinical symptoms in 55 consecutive patients in whom vertebral osteomyelitis was suspected. In addition to two-step streptavidin/indium In 111 biotin scintigraphy, patients underwent MRI and CT scan. Sensitivity and specificity were 94.12% and 95.24%, respectively, for streptavidin/indium In 111 biotin scintigraphy; 54.17% and 75%, respectively, for MRI; and 35.29% and 57.14%, respectively, for CT scan.[6]Level of evidence: 2 Learn about evidence grading system
FDG-PET [EBM]

Description FDG, a nonspecific indicator of increased intracellular glucose metabolism, builds up in sites of infection and inflammation Comments A relatively new modality used in the investigation of osteomyelitis Provides results within 30 to 60 minutes of administration, can distinguish between inflammatory cellular infiltrates and hematopoietic marrow, and can be used in patients with metallic implant artifacts Early bone healing also involves a short inflammatory phase, which could be mistaken for osteomyelitis Expensive ($3,000-$6,000) and not widely available Combination with CT provides the sensitivity of PET and the resolution of CT to establish a diagnosis and clearly define the extent of involvement, which is important for surgical planning
Evidence

A systematic review and meta-analysis conducted to determine the sensitivity and specificity of various imaging techniques in the diagnosis of chronic osteomyelitis identified 23 clinical studies. Techniques evaluated included radiography, MRI, CT scan, bone scintigraphy, leukocyte scintigraphy, gallium scintigraphy, combined bone and leukocyte scintigraphy, combined bone and gallium scintigraphy, and FDG-PET. Because there was only 1 study each on CT, gallium scintigraphy, and radiography, no meta-analysis was done on data evaluating those modalities. Results showed that FDG-PET is the most accurate for confirming or excluding the diagnosis of chronic osteomyelitis. Sensitivity and specificity were as follows: 96% and 91%, respectively, for FDG-PET; 82% and 25%, respectively, for bone scintigraphy; 61% and 77%, respectively, for leukocyte scintigraphy; 78% and 84%, respectively, for combined bone and leukocyte scintigraphy; and 84% and 60%, respectively, for MRI.[7]Level of evidence: 1 A prospective study compared the results of FDG-PET imaging with diagnosis established through surgical findings or long-term follow-up in 22 patients in whom chronic osteomyelitis was suspected. FDG-PET findings were consistent with the final diagnosis in 20 of 22 patients, resulting in a sensitivity of 100%, a specificity of 87.5%, and an accuracy of 90.9%.[8]Level of evidence: 2 Another prospective study evaluating the use of FDG-PET in the detection of chronic osteomyelitis found that FDG-PET identified 17 of 18 patients with osteomyelitis and 12 of 13 patients without osteomyelitis. Overall, sensitivity and specificity were 100% and 92%, respectively.[9]Level of evidence: 2 A retrospective study was conducted to evaluate the accuracy of combined FDG-PET/CT in trauma patients in whom chronic osteomyelitis was suspected. Of 33 PET/CT scans, 30 were accurate, including 17 that were positive and 13 that were negative; there were two false-positive results and one false-negative result. Sensitivity, specificity, and accuracy for FDG-PET/CT were 94%, 87%, and 91%, respectively, for the whole group; 88%, 100%, and 90%, respectively, for patients with lesions in the axial skeleton; and 100%, 85%, and 91%, respectively, for patients with lesions in the appendicular skeleton.[10]Level of evidence: 2 Learn about evidence grading system
SPECT/CT [EBM]

Description SPECT uses different radiopharmaceuticals, including technetium Tc99m methylene diphosphonate, gallium citrate Ga 67, and indium In 111 Supplementary anatomic information is provided by CT Comments Can facilitate correct diagnosis of osteomyelitis

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Evidence

The value of adding SPECT/CT to conventional three-phase nuclear bone scan was investigated in 31 patients in whom bone infection was suspected on the basis of clinical findings and abnormal scintigraphy findings. Osteomyelitis was confirmed or excluded by biopsy, surgery, or prolonged clinical follow-up. SPECT/CT findings were consistent with the ultimate diagnosis in 7 patient with documented osteomyelitis and in 19 patients without bone infection. There were two false-positive results and two false-negative results, and one scan was indeterminate (sensitivity, 78%; specificity, 86%). The investigators concluded that SPECT/CT is more frequently accurate than three-phase bone scan for the diagnosis of osteomyelitis.[11]Level of evidence: 2 Learn about evidence grading system Back to Top

Differential diagnosis
Septic arthritis

Septic arthritis is a rheumatologic emergency usually occurring as a result of occult bacteremia Patients present with fever, rigors, and joint pain The knee is most commonly affected Significant joint effusion is usually present, and aspiration will reveal purulent fluid May be complicated by osteomyelitis if not promptly diagnosed or when due to highly virulent organisms MRI can distinguish septic arthritis from osteomyelitis or may detect secondary infection of the contiguous bones
Soft tissue infection

Includes cellulitis, myositis, and abscesses Most commonly caused by S. aureus Often begins as superficial cellulitis Uncomplicated cases remain localized to subcutaneous tissues Infection may progress to include deeper tissues or may lead to the formation of a localized inflammatory abscess Technetium Tc 99m bone scan is used to differentiate cellulitis from osteomyelitis. Findings in patients with cellulitis are positive only in the first two phases of the triplephase bone scan, but normal uptake is seen in the third phase
Gaucher disease

Autosomal recessive deficiency of -glucocerebrosidase The hallmark of type 1 in adults is skeletal disease due to substrate buildup in the bones, which is manifested by bone pain and anemia Hepatomegaly and splenomegaly are seen, as well as bleeding and bruising Diagnosed on the basis of a low level of glucocerebrosidase in blood
Charcot arthropathy

Charcot arthropathy (also known as Charcot joint or neuropathic osteoarthropathy) presents with swelling, warmth, and edema of the affected area Skin ulceration is uncommon, whereas osteomyelitis is usually preceded by a skin ulcer Involves the midfoot, whereas osteomyelitis usually affects the forefoot MRI findings are useful in differentiating between the two disease entities
Bone tumors (primary and metastatic)

May be difficult to distinguish from osteomyelitis because clinical findings are often noncontributory, and radiologic features can be similar The penumbra sign (a higher signal intensity feature of the thin layer of granulation tissue that lines the abscess cavity on T1-weighted MRI) and a high CRP level support the diagnosis of osteomyelitis and may aid in the exclusion of a tumor Biopsy is the definitive diagnostic test

Treatment
Back to Top

Summary approach
The goals of treatment are as follows: Eradication of infection Relief of pain Preservation of articular function and normal bone growth Restoration or preservation of the neurologic status Preservation of the integrity of the affected limb Prevention of recurrence Restoration of anatomic contours (eg, cosmetic reconstruction for craniofacial osteomyelitis) Osteomyelitis, particularly chronic osteomyelitis, is characterized by a high rate of relapse, even when treated aggressively The best treatment approach is a combination of antimicrobial and surgical therapy. Treatment of osteomyelitis, in general, involves the following components: Debridement of necrotic tissue Treatment with antibiotics Management of dead space Coverage with soft tissues Surveillance and monitoring (ie, patient follow-up, imaging studies) In patients with chronic osteomyelitis, antibiotic therapy alone is inadequate. Radical debridement is required to eliminate necrotic bone and create a viable, vascularized environment. Inadequate debridement leads to high recurrence rates in patients with chronic osteomyelitis. Thus, surgery involves removal of sequestrum and resection of scarred and infected bone and tissue

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Drug therapy: Antimicrobial agents must be able to penetrate the areas of ongoing infection The selection of the appropriate antibiotic depends on the causative organism, the results of antibiotic susceptibility testing, and intrinsic host factors. Identification of the offending organism through blood or tissue culture is beneficial in guiding treatment In very ill patients or those in whom biopsy results are pending, empiric antibiotic therapy should be designed to treat the most likely etiologic organism based on the clinical circumstances, and the antibiotic regimen should then be tailored to the causative pathogen once the biopsy results are available In patients who are not severely ill (septic), empiric antibiotic therapy should not be initiated until a biopsy has been obtained for histology and culture. Initiation of antibiotic therapy before biopsy may suppress growth of the organism even several days or a week after treatment is stopped After the specimen is collected via debridement or bone biopsy, parenteral antimicrobial therapy is initiated based on the likely etiologic organisms and local antibiotic resistance patterns. Initial empiric antibiotic therapy should consist of parenteral penicillins (eg, aqueous penicillin G, nafcillin, ampicillin, and piperacillin-tazobactam), imipenem-cilastatin, vancomycin, or cephalosporins (eg, cefazolin, ceftriaxone, and cefepime) or an oral fluoroquinolone (eg, ciprofloxacin, levofloxacin); parenteral antibiotics were the standard of care in adults with osteomyelitis until the development of the fluoroquinolones made oral treatment feasible in some cases due to their high bioavailability and broad spectrum of activity. If multiple organisms are suspected, patients may require broad-spectrum antibiotics or combination therapy Some other oral antibiotics, such as linezolid, sulfamethoxazole-trimethoprim, and clindamycin, may be suitable for treating osteomyelitis due to sensitive organisms, but they are usually used only to complete therapy after a favorable response to intravenous therapy. In addition to the results of antibiotic susceptibility testing, other considerations in selecting an oral agent involve pharmacokinetic parameters, such as bioavailability and bone penetration Rifampin, which is well absorbed orally, is sometimes administered in conjunction with antistaphylococcal agents in the treatment of osteomyelitis due to S. aureus Once the diagnosis of osteomyelitis is confirmed and the etiologic organism identified, treatment with the appropriate antibiotic (see Table 2) should be initiated immediately to improve the long-term prognosis. Delaying treatment can lead to complications, such as prolonged fever, limited range of motion persistent pain, fractures, and amputations Local antibiotic delivery with the use of surgically placed antibiotic-impregnated implants has been used as an adjunctive therapy, but evidence on efficacy is limited Outpatient intravenous therapy with the use of a peripherally inserted central catheter, a Hickman catheter, or a Groshong catheter is another option. The use of long-term intravenous catheters in adults may decrease the length of hospitalization, allow for outpatient parenteral therapy, and reduce cost The optimal duration of antibiotic therapy has not been fully determined, as there is considerable variation in clinical presentation, but the general recommendation is 4 to 6 weeks. Some experts have achieved good results with treatment for 2 weeks after appropriate debridement in patients with uncomplicated infection (Cierny-Mader stage 2) who are otherwise healthy; other patients require extensive surgery, sometimes in stages, and prolonged antibiotic therapy until all of the necrotic material is removed, the bone is stabilized, and soft tissue coverage is achieved Treatment of osteomyelitis due to unusual organisms, such as mycobacteria and fungi, may require more prolonged therapy (eg, 6-9 months for tuberculosis of the bone, 12 months for coccidioidomycosis); guidelines specific to such pathogens should be consulted Some patients, particularly those with a prosthetic joint or other foreign material that cannot be removed, require long-term suppressive therapy to prevent symptomatic relapse Table 2. Antibiotic Therapy for Osteomyelitis-causing Microorganisms

Microorganism Methicillin-sensitive S. aureus

Antibiotic of Choice Nafcillin, 1.0 or 1.5 g intravenously every 4 to 6 hours, or Cefazolin, 2 g intravenously every 8 hours

Other Options Clindamycin, 600 mg intravenously every 6 hours, or Vancomycin, 1 g intravenously every 12 hours, or Ciprofloxacin, 750 mg orally every 12 hours, or Levofloxacin, 500 mg/d orally, plus rifampin, 600 mg/d orally Linezolid, 600 mg intravenously or orally every 12 hours, or Levofloxacin, 500 mg/d orally, plus rifampin, 600 mg/d orally Ceftriaxone, 1 to 2 g intravenously or intramuscularly every 24 hours, or Cefazolin, 1 to 2 g intravenously every 8 hours, or Clindamycin, 600 mg intravenously every 6 hours, or Erythromycin, 500 mg intravenously every 6 hours, or Vancomycin, 1 g intravenously every 12 hours

MRSA

Vancomycin, 1 g intravenously every 12 hours

Penicillin-sensitive streptococci (group A or B -hemolytic streptococci, S. pneumoniae)

Penicillin G, 12 to 20 million U/d intravenously as a continuous infusion or in 6 divided doses

Enterococci and other relatively penicillin-resistant streptococci (minimum inhibitory concentration >0.5 g/mL) Gram-negative enteric bacilli P. aeruginosa

Penicillin G, 20 million U/d Vancomycin, 1 g intravenously every 12 intravenously as a continuous infusion or hours, with or without gentamicin, 1 in 6 divided doses, with or without mg/kg intravenously every 8 hours, for gentamicin, 1 mg/kg intravenously every the first 1 to 2 weeks of treatment 8 hours, for the first 1 to 2 weeks of treatment Ciprofloxacin, 400 mg intravenously or Ceftriaxone, 1 to 2 g intravenously every 750 mg orally every 12 hours for 2 24 hours weeks Cefepime, 2 g intravenously every 12 Ciprofloxacin, 750 mg orally every hours 12 hours, or

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Note: Some experts recommend that aminoglycosides be used in conjunction with -lactams for at least some portion of the treatment course

Ceftazidime, 2 g intravenously every 8 hours, or Imipenem-cilastatin, 500 mg intravenously every 6 hours, or Piperacillin, 2 to 4 g intravenously every 4 hours, or Piperacillin-tazobactam, 3.375 g intravenously every 6 hours Ampicillin-sulbactam, 1.5 to 3 g intravenously every 6 hours or Metronidazole (for gram-negative anaerobes), 500 mg intravenously every 8 hours Imipenem, 500 mg intravenously every 6 hours

Anaerobes

Clindamycin, 600 mg intravenously or 300 to 450 mg orally every 6 hours

Mixed infections (aerobic and anaerobic organisms)


MRSA = methicillin-resistant S. aureus Non-drug therapy:

Ampicillin-sulbactam, 1.5 to 3 g intravenously every 6 hours

The principles of surgical intervention include bone debridement, reconstruction, and dead space management; bone stabilization; coverage with soft tissue; and restoration of vascularity Surgery depends on the extent, location, and duration of the infection and is indicated when antimicrobial therapy is not sufficient to resolve the infection, as is usually the case in patients with chronic infection, infected nonunion of fractures, or foreign bodies (including prostheses and fixation devices). Surgical treatment is always required in patients with abscesses, devascularized tissue, or sequestra Surgical debridement is not indicated if hematogenous osteomyelitis is diagnosed early. However, if antibiotic therapy alone is ineffective, debridement may be necessary, along with an additional 4- to 6-week course of antibiotic therapy In patients with osteomyelitis associated with an infected prosthesis (contiguous focus of infection), it is usually necessary to remove the prosthetic device. A combined antimicrobial and surgical approach is appropriate in patients with open fractures or in those with prosthetic joint infections In patients with osteomyelitis associated with vascular insufficiency, the goal of surgery is to revascularize the limb and preserve the maximum amount of foot function (foot salvage). Debridement coupled with antimicrobial therapy for at least 6 weeks is recommended in patients with good oxygen tension at the involved site Surgical placement of antibiotic-impregnated implants (eg, polymethyl methacrylate, calcium sulfate) helps to obliterate the dead space after debridement, as well as delivering high tissue levels of antibiotics, but evidence on efficacy is limited Hyperbaric oxygen therapy has been suggested as a complementary therapy, but data regarding its usefulness as an adjunctive treatment remain inconclusive Back to Top

Medications
Penicillins

Indication Treatment of bacterial osteomyelitis Dose information Aqueous penicillin G: 12 to 20 million U/d intravenously by continuous infusion or in six divided doses Nafcillin: 1 to 2 g intravenously every 4 hours Ampicillin-sulbactam: 1.5 to 3 g intravenously every 6 hours Piperacillin-tazobactam: 3.375 g intravenously every 6 hours Major contraindications Hypersensitivity to cephalosporins (piperacillin-tazobactam) Hypersensitivity to corn (penicillin G and nafcillin) Hypersensitivity to penicillins Comments Extensive experience in use for treatment of osteomyelitis Usually well tolerated
Imipenem-cilastatin

Indication

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Imipenem-cilastatin is used to treat bacterial osteomyelitis Dose information 500 mg intravenously every 6 hours Major contraindications Atrioventricular block Hypersensitivity to amide local anesthetic or carbapenems Shock Comments Extensive experience in use for treatment of osteomyelitis Usually well tolerated
Clindamycin

Indication Clindamycin is used to treat bacterial osteomyelitis Dose information 150 to 450 mg orally or 600 mg intravenously or intramuscularly every 6 hours (up to 2,700 mg/d) Major contraindications Hypersensitivity to clindamycin or lincomycin Pseudomembranous colitis Ulcerative colitis Comments Has exceptional bioavailability and bone penetration Has antibiotic effects against most gram-positive bacteria May be given orally after initial parenteral therapy for 2 weeks
Linezolid [EBM]

Indication Linezolid is used to treat bacterial osteomyelitis Dose information 600 mg intravenously or orally every 12 hours Major contraindications Monoamine oxidase inhibitor therapy Comments Effective against MRSA, methicillin-resistant coagulase-negative staphylococci, and vancomycin-resistant Enterococcus faecium Can be administered orally, with 100% bioavailability and good penetration into bones, joints, and soft tissue Resistance has developed in vancomycin-resistant E. faecium and MRSA strains in patients receiving prolonged therapy, as is sometimes required when an infected device cannot be removed
Evidence

The use of linezolid to treat gram-positive orthopedic infections was evaluated in 51 consecutive patients who were not candidates for treatment with vancomycin. Infections included chronic osteomyelitis or prosthetic joint infection in most cases, which were most often caused by S. aureus (n = 27) or coagulase-negative staphylococci (n = 19); 38 were determined to be methicillin resistant. Remission was achieved in 32 patients, obviating the need for long-term suppression. The duration of treatment ranged from 2 to 19 weeks; follow-up was from 3 to 50 months. Seventeen patients required long-term suppression, mostly because of prostheses or other hardware that could not be removed. One patient experienced clinical and microbiologic failure. Adverse events included thrombocytopenia (n = 5), anemia (n = 5), and reversible optic and irreversible peripheral neuropathy after 24 months.[12]Level of evidence: 2 Learn about evidence grading system
Fluoroquinolones [EBM]

Indication Treatment of bacterial osteomyelitis Dose information Ciprofloxacin: 500 to 750 mg orally or 400 mg intravenously every 12 hrs

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Levofloxacin: 500 to 750 mg orally every 24 hours Major contraindications Hypersensitivity to quinolones Comments Used in the treatment of osteomyelitis because of low toxicity and good bone penetration Oral fluoroquinolones have excellent bioavailability and are used as an alternative to extended parenteral therapy Generally limited activity against Streptococcus species, Enterococcus species, and many anaerobes Levofloxacin is effective against gram-positive, gram-negative, and some anaerobic organisms but is less effective against P. aeruginosa than ciprofloxacin. Because of its high serum and bone concentrations and its long serum half-life, levofloxacin is considered ideal for the treatment of osteomyelitis Fourth-generation quinolones (eg, moxifloxacin, gemifloxacin) have better activity against several gram-positive organisms, gram-negative organisms, and some anaerobes Use in the treatment of osteomyelitis caused by S. aureus and Staphylococcus epidermidis has produced varied results. Resistance to second- and third-generation quinolones is increasing Not recommended in patients with skeletal immaturity due to the risk of possible cartilage damage Use should be limited because of the risk of resistance
Evidence

A meta-analysis of seven randomized, controlled trials (RCTs) comparing fluoroquinolones versus -lactams for the treatment of osteomyelitis showed that fluoroquinolones are as effective as -lactams. There was no statistical difference between the two antibiotic classes in terms of treatment success (OR, 0.99), bacteriologic success (OR, 0.88), superinfections (OR, 1.75), relapses (OR, 1.23), or adverse events (OR, 0.47).[13]Level of evidence: 2 Learn about evidence grading system
Vancomycin

Indication Vancomycin is used to treat bacterial osteomyelitis Dose information 1,000 mg or 15 mg/kg intravenously every 12 hours Major contraindications Hypersensitivity to corn or vancomycin Comments Provides excellent coverage against S. aureus, making it useful against osteomyelitis due to MRSA Initial doses should be based on actual body weight, with subsequent doses adjusted for patient response, serum concentrations, and clinical judgment. Initial dosing intervals are typically every 12 hours to target serum concentrations four to five times greater than the bacterial minimum inhibitory concentration. Depending on the individual patient, dosing regimens may range from 15 mg/kg to 20 mg/kg actual body weight every 8 to 12 hours. Continuous infusion regimens are unlikely to substantially improve outcomes compared to intermittent dosing Guidelines produced by the American Society of Health System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists recommend monitoring trough serum concentrations to ensure optimal efficacy; in patients with osteomyelitis, serum trough concentrations should be maintained at 15 to 20 mg/L. Trough concentrations should be measured at a steady state before the next dose (usually after the fourth dose and before the fifth dose). Monitoring may be repeated until target concentrations are achieved, at which time the frequency may decrease. Patients receiving long-term therapy for osteomyelitis or other infections may require weekly measurement of trough concentrations
Cephalosporins

Indication Treatment of bacterial osteomyelitis Dose information Cefazolin: 1 to 2 g intravenously every 8 hours Ceftriaxone: 1 to 2 g intravenously or intramuscularly every 24 hours Cefepime: 2 g intravenously every 12 hours Major contraindications Hypersensitivity to cephalosporins Jaundice (ceftriaxone) Comments

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Extensive experience in use for treatment of osteomyelitis Usually well tolerated Ceftriaxone can be administered once daily, making outpatient intravenous therapy a convenient option
Rifampin

Indication Rifampin is used as an adjunctive treatment to facilitate elimination of intraleukocytic bacteria Dose information 600 mg orally once a day Major contraindications Hypersensitivity to rifamycin Liver disease Comments To prevent antibiotic resistance, rifampin should not be used alone Back to Top

Non-drug treatments
Surgical debridement

Description Removal of all infected and necrotic bone and soft tissue, along with adherent and surrounding scar tissue Atraumatic soft tissue handling and maintenance of blood supply are important requirements Comments Antibiotics do not adequately penetrate necrotic tissue, and, thus, if such material is not completely removed, it remains a nidus of infection and a cause of recurrence Tissues with scarring also must be removed, as they slow wound healing, produce tension, and act as a reservoir of infection Serial debridement is sometimes necessary to eliminate necrosis and, if necessary, establish a wound bed that will foster a graft or other therapeutic implant The significant dead space of bone and soft tissue resulting from debridement is poorly vascularized and, therefore, susceptible to progression of bone infection. This space must be addressed (eg, with antibiotic beads and bone grafting) in order to impede the progression of disease and preserve the integrity of the skeletal portion Several techniques can be used for reconstruction of bone defects, including healing by secondary intention, closed irrigation and suction systems, use of antibioticimpregnated implants, autologous bone grafting, and vascularized free fibula and iliac bone grafting
Surgical placement of antibiotic-impregnated implants

Serves a dual purpose of filling and stabilizing dead space and delivering antibiotic directly to the infected site Polymethyl methacrylate beads are used most commonly and have been shown to produce good clinical results, with a 92% success rate for staged wound management, when impregnated with clindamycin, vancomycin, or tobramycin Disadvantages of antibiotic-impregnated polymethyl methacrylate beads are their lack of absorbability, necessitating removal and replacement with a graft or other stabilizing mechanism, and the belief that local delivery of antibiotics is not sufficient (systemic therapy is usually given in addition) Other materials, such as calcium sulfate, which is bioabsorbable and does not require removal, have also been used for antibiotic delivery and wound stabilization, but data are limited
Hyperbaric oxygen therapy [EBM]

Wounds typically have a decreased oxygen supply that prevents optimal leukocyte function and wound healing. Exposure to high concentrations of oxygen under increased atmospheric pressure is believed to promote wound healing, despite the necessarily intermittent nature of the treatments Serious adverse events include seizures and pressure-related traumas, such as pneumothorax. Other adverse effects include earaches and barotraumatic otitis The quality of studies evaluating this modality is limited; additional studies are needed to determine its value
Evidence

A systematic literature review was conducted to determine whether hyperbaric oxygen therapy is an effective adjunctive treatment for hypoxic wounds. The category of chronic osteomyelitis was addressed as a specific subset. Five studies of moderate quality, none of which were RCTs and all of which differed significantly in their design, were identified for further analysis. In all studies, hyperbaric oxygen therapy was used in addition to standard therapy with antibiotics and surgical debridement. Four studies found remission rates of 85% associated with hyperbaric oxygen therapy and standard care, and the remaining study found that standard care alone resulted in a higher rate of remission than standard care combined with hyperbaric oxygen therapy. The reviewers concluded that RCTs must be conducted to determine whether hyperbaric oxygen therapy adds significantly to the efficacy of standard care.[14]Level of evidence: 2 Learn about evidence grading system Back to Top

Special circumstances
Comorbidities Coexisting disease: Diabetes mellitus (type 1 or type 2) or peripheral vascular disease tends to give rise to contiguously spread osteomyelitis of the foot. Different organisms are responsible for
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the infection in these circumstances (compared to hematogenously spread infection), so the treatment approach is different Any infection may worsen glycemic control, so blood glucose levels should be monitored carefully in patients with diabetes and osteomyelitis. It may be necessary to increase the insulin dose Coexisting medication: Certain antibiotics interact with various medications, particularly warfarin Patients taking warfarin should have their clotting profile monitored closely during treatment for osteomyelitis Special patient groups: Allergies to specific antibiotics should be carefully documented and should guide antibiotic therapy Patient satisfaction/lifestyle priorities Relief of pain and systemic toxemia are likely to be the patient's immediate priorities Maintenance of bony integrity and stability are long-term goals of treatment Back to Top

Consultation
Prompt diagnostic evaluation should take place as soon as osteomyelitis is suspected, and if the suspicion is strong, a hospital referral should be made while awaiting the results of laboratory investigations Patients with a history of musculoskeletal symptoms and systemic symptoms (eg, fever, malaise, anorexia) should be referred immediately for diagnostic evaluation Any CRP, ESR, or leukocyte count abnormalities or abnormal radiographic findings should prompt referral, although the results of these investigations may be normal, especially soon after the onset of symptoms Patients requiring bone biopsy or surgical debridement should be referred to an orthopedic surgeon and possibly an infectious disease specialist Patients with bony pain and loss of bone stability and patients with continuing pain and/or systemic symptoms (eg, fever, malaise, anorexia) following open fracture or orthopedic surgery should be referred to the hospital immediately Consultation with a rheumatologist should be obtained in patients with an underlying connective tissue disease requiring immunosuppressive therapy

Follow-up
Monitoring The follow-up of a patient with osteomyelitis depends largely on the type of disease All patients should be evaluated clinically with respect to ongoing symptoms (eg, pain) and clinical signs of persistent infection (fever, erythema, drainage) Serum CRP levels and ESR should be measured on a weekly basis during the course of treatment. CRP levels decrease faster than ESR in patients in whom treatment is successful. An ESR that returns to normal during the course of therapy is also a favorable prognostic sign. Persistent elevation of the CRP level, but not the ESR, at 4 to 6 weeks indicates persistent osteomyelitis Patients who undergo surgical intervention for vertebral osteomyelitis should be assessed for improvement of axial skeletal pain. ESR and CRP levels should be monitored to determine the response to treatment, and imaging studies can be done to determine if there is cessation of cortical destruction with subsequent osseous fusion Patients should be monitored for adverse reactions to antimicrobial agents with complete blood count and liver and kidney function tests; however, monitoring should be tailored to the particular antibiotic Prognosis Early initiation of antibiotic therapy, before extensive destruction of the bone occurs, produces the best results Even with appropriate medical and surgical treatment, 20% to 30% of patients with osteomyelitis experience recurrence within 2 years. Recurrent osteomyelitis is associated with high resistance to therapy and may result in bone deformities. Recurrence indicates that initial therapy may have only arrested the progression of the disease Osteomyelitis associated with vascular insufficiency: Remission rates of 25% to 88% have been reported in patients with diabetes who receive antibiotic therapy, either alone or in combination with surgical debridement Recurrent infections have been reported to occur in up to 36% of patients. Remission of infection is more likely to occur than eradication. Abscesses and necrotic regions that warrant drainage also occur in 20% of cases of recurrent infection Patients with diabetes develop foot ulcers at an annual incidence close to 2%. Of these patients, 15% will develop osteomyelitis, approximately 36% of whom will require lower-extremity amputation Before the advent of antibiotics, osteomyelitis was associated with a high mortality rate. Death from osteomyelitis is now rare, with a mortality rate of less than 5% for vertebral osteomyelitis Complications Treatment failure: The most common complication If treatment proves unsuccessful (eg, persistent radiographic abnormalities, persistently elevated serum markers), several possibilities should be considered, including the presence of an unrecognized pathogen and the need for (further) debridement.Consideration should be given to obtaining additional material for culture (at least several days after antibiotic therapy is stopped) and revising antibiotic therapy if indicated. If an effort was made to treat the infection despite the presence of a foreign body (eg, prosthesis or fixation device), removal should be reconsidered Antibiotic therapy is continued for an additional 4 to 6 weeks after further surgical treatment. In some cases (eg, multiple relapses, presence of a foreign body that cannot be removed), suppressive antibiotic therapy is given for a prolonged (often indefinite) period Abscess formation: May occur with acute or chronic infection Chronic osteomyelitis is characterized by the development of sinus tracts that allow drainage from infected bone through the overlying soft tissue to the skin. In some cases, partial healing occurs, resulting in blockage of the tract, deep abscess formation, and a symptomatic flare-up of pain, fever, and localized erythema and swelling Spontaneous drainage may occur, but surgical intervention may be required Squamous cell carcinoma of the sinus tract: Chronic discharge of purulent material leads to metaplasia of the epithelial lining of the sinus tract, with subsequent development of carcinoma

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Rareseen in 0.23% to 1.6% of patients Sepsis: In patients with osteomyelitis due to a vascular deficiency, antibiotics may not be enough to treat the infection; severe infections may be life or limb threatening Should be suspected in the presence of systemic signs and symptoms, such as fever, tachycardia, and hypotension Central nervous system disease: In patients with vertebral osteomyelitis, epidural and subdural abscesses may result from posterior extension of the infection; meningitis also may result. Paravertebral, retropharyngeal, mediastinal, subphrenic, or retroperitoneal abscesses may result from anterior or lateral extension Approximately 15% of patients may present with motor and sensory deficits Bone deformity: May occur as a result of recurrent osteomyelitis, which is associated with high resistance to therapy Soft tissue deformity: Surgical debridement often leaves a large bony defect termed 'dead space,' which must be managed appropriately to halt disease progression and maintain the integrity of the skeletal part. Dead bone and scar tissue must be replaced with durable vascularized tissue A free vascularized bone graft, usually obtained from the fibula or ilium, has been used to fill the dead space. Local tissue flaps or free flaps may also be used. As an alternative, cancellous bone grafts may be placed beneath local or transferred tissues where structural augmentation is needed Other complications include the following: Limited range of motion Persistent pain Fractures Amputations Avascular necrosis and growth disturbance due to physeal damage

Patient Education
Patients should be informed of the following: The variety of adverse reactions that may occur as a result of drug therapy, which vary according to the medication used The signs and symptoms of recurrence (bone pain, redness, warmth, swelling, fever, chills, and malaise), as approximately 20% to 30% of patients with osteomyelitis experience a recurrence within 2 years, even with medical and surgical treatment The possibility of complications that may result from osteomyelitis, including sepsis (signified by the presence of systemic signs and symptoms, such as fever, tachycardia, and hypotension), abscess formation, squamous cell carcinoma (rare), limited range of motion, persistent pain, fractures, and amputation Patients with diabetes should be advised to have an annual foot examination and should be given instructions on proper foot care to prevent the occurrence of ulcers, which may lead to osteomyelitis Back to Top

Online information for patients


American Academy of Orthopaedic Surgeons: Infections Cleveland Clinic: Osteomyelitis Mayo Clinic: Osteomyelitis

Resources
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Summary of evidence
Evidence Prevention An observational study of 2,847 patients receiving antibiotic prophylaxis for elective surgical procedures showed that surgical wound infections occurred in 0.6% of those who received antibiotics preoperatively, 1.4% of those who received antibiotics perioperatively (RR, 2.4 compared to the preoperative group), 3.3% of those who received antibiotics postoperatively (RR, 5.8), and 3.8% of those who received early antibiotic treatment (RR, 6.7). Administration of antibiotics during the preoperative period was associated with the lowest risk of surgical wound infection.[1]Level of evidence: 1 Diagnosis CRP: An observational study was conducted to determine the value of CRP in predicting healing versus infection or other complications in 52 patients undergoing soft tissue reconstructions following open fractures of the lower limbs, chronic infection, osteomyelitis, and nonunion. Of 41 patients whose CRP level peaked 4 or fewer days after surgery, 15% developed infection or required further surgery. Of 11 patients whose CRP level peaked more than 4 days postoperatively, 82% developed infection or required further surgery. Of 25 patients who achieved complete healing of a fracture, all had CRP levels <8 mg/L at the time of union; patients with nonunion all had CRP levels >8 mg/L. The investigators concluded that persistent elevation of CRP after the fourth postoperative day predicts complications in this setting.[2]Level of evidence: 2 Bone biopsy: A prospective study evaluated the sensitivity and specificity of fine-needle bone biopsy in 30 patients in whom osteomyelitis was suspected. The diagnosis of osteomyelitis was confirmed by conventional means in 15 patients. The sensitivity of fine-needle bone biopsy for diagnosing osteomyelitis was 87%, and the specificity was 93%.[3]Level of evidence: 2 MRI:

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A meta-analysis conducted to determine the diagnostic test performance of MRI for osteomyelitis of the foot identified 16 studies that met the inclusion criteria. The combined diagnostic OR for MRI was 42.1, and the specificity at a 90% sensitivity cutoff was 82.5%. Diagnostic ORs for MRI compared with those for other diagnostic tests were as follows: 149.9 versus 3.6 for bone scan, 81.5 versus 3.3 for plain radiography, and 120.3 versus 3.4 for radiolabeled leukocyte scan.[4]Level of evidence: 2 Radiolabeled antibiotic scintigraphy: A clinical trial in 45 patients with known or suspected bone infection who underwent 50 scans using scintigraphy with technetium Tc 99mradiolabeled ciprofloxacin (Infecton) found that the sensitivity and specificity of Infecton scintigraphy for detecting osteomyelitis were 97.2% and 80%, respectively, and the positive and negative predictive values were 94.6% and 88.9%, respectively.[5]Level of evidence: 2 Streptavidin/indium In 111 biotin complex scintigraphy: A clinical trial evaluated the diagnostic performance of streptavidin/indium In 111 biotin scintigraphy within 2 weeks of the onset of clinical symptoms in 55 consecutive patients in whom vertebral osteomyelitis was suspected. In addition to two-step streptavidin/indium In 111 biotin scintigraphy, patients underwent MRI and CT scan. Sensitivity and specificity were 94.12% and 95.24%, respectively, for streptavidin/indium In 111 biotin scintigraphy; 54.17% and 75%, respectively, for MRI; and 35.29% and 57.14%, respectively, for CT scan.[6]Level of evidence: 2 FDG-PET: A systematic review and meta-analysis conducted to determine the sensitivity and specificity of various imaging techniques in the diagnosis of chronic osteomyelitis identified 23 clinical studies. Techniques evaluated included radiography, MRI, CT scan, bone scintigraphy, leukocyte scintigraphy, gallium scintigraphy, combined bone and leukocyte scintigraphy, combined bone and gallium scintigraphy, and FDG-PET. Because there was only 1 study each on CT, gallium scintigraphy, and radiography, no meta-analysis was done on data evaluating those modalities. Results showed that FDG-PET is the most accurate for confirming or excluding the diagnosis of chronic osteomyelitis. Sensitivity and specificity were as follows: 96% and 91%, respectively, for FDG-PET; 82% and 25%, respectively, for bone scintigraphy; 61% and 77%, respectively, for leukocyte scintigraphy; 78% and 84%, respectively, for combined bone and leukocyte scintigraphy; and 84% and 60%, respectively, for MRI.[7]Level of evidence: 1 A prospective study compared the results of FDG-PET imaging with diagnosis established through surgical findings or long-term follow-up in 22 patients in whom chronic osteomyelitis was suspected. FDG-PET findings were consistent with the final diagnosis in 20 of 22 patients, resulting in a sensitivity of 100%, a specificity of 87.5%, and an accuracy of 90.9%.[8]Level of evidence: 2 Another prospective study evaluating the use of FDG-PET in the detection of chronic osteomyelitis found that FDG-PET identified 17 of 18 patients with osteomyelitis and 12 of 13 patients without osteomyelitis. Overall, sensitivity and specificity were 100% and 92%, respectively.[9]Level of evidence: 2 A retrospective study was conducted to evaluate the accuracy of combined FDG-PET/CT in trauma patients in whom chronic osteomyelitis was suspected. Of 33 PET/CT scans, 30 were accurate, including 17 that were positive and 13 that were negative; there were two false-positive results and one false-negative result. Sensitivity, specificity, and accuracy for FDG-PET/CT were 94%, 87%, and 91%, respectively, for the whole group; 88%, 100%, and 90%, respectively, for patients with lesions in the axial skeleton; and 100%, 85%, and 91%, respectively, for patients with lesions in the appendicular skeleton.[10]Level of evidence: 2 SPECT/CT: The value of adding SPECT/CT to conventional three-phase nuclear bone scan was investigated in 31 patients in whom bone infection was suspected on the basis of clinical findings and abnormal scintigraphy findings. Osteomyelitis was confirmed or excluded by biopsy, surgery, or prolonged clinical follow-up. SPECT/CT findings were consistent with the ultimate diagnosis in 7 patient with documented osteomyelitis and in 19 patients without bone infection. There were two false-positive results and two false-negative results, and one scan was indeterminate (sensitivity, 78%; specificity, 86%). The investigators concluded that SPECT/CT is more frequently accurate than three-phase bone scan for the diagnosis of osteomyelitis.[11]Level of evidence: 2 Treatment Linezolid: The use of linezolid to treat gram-positive orthopedic infections was evaluated in 51 consecutive patients who were not candidates for treatment with vancomycin. Infections included chronic osteomyelitis or prosthetic joint infection in most cases, which were most often caused by S. aureus (n = 27) or coagulase-negative staphylococci (n = 19); 38 were determined to be methicillin resistant. Remission was achieved in 32 patients, obviating the need for long-term suppression. The duration of treatment ranged from 2 to 19 weeks; follow-up was from 3 to 50 months. Seventeen patients required long-term suppression, mostly because of prostheses or other hardware that could not be removed. One patient experienced clinical and microbiologic failure. Adverse events included thrombocytopenia (n = 5), anemia (n = 5), and reversible optic and irreversible peripheral neuropathy after 24 months.[12]Level of evidence: 2 Fluoroquinolones: A meta-analysis of seven RCTs comparing fluoroquinolones versus -lactams for the treatment of osteomyelitis showed that fluoroquinolones are as effective as -lactams. There was no statistical difference between the two antibiotic classes in terms of treatment success (OR, 0.99), bacteriologic success (OR, 0.88), superinfections (OR, 1.75), relapses (OR, 1.23), or adverse events (OR, 0.47).[13]Level of evidence: 2 Hyperbaric oxygen therapy: A systematic literature review was conducted to determine whether hyperbaric oxygen therapy is an effective adjunctive treatment for hypoxic wounds. The category of chronic osteomyelitis was addressed as a specific subset. Five studies of moderate quality, none of which were RCTs and all of which differed significantly in their design, were identified for further analysis. In all studies, hyperbaric oxygen therapy was used in addition to standard therapy with antibiotics and surgical debridement. Four studies found remission rates of 85% associated with hyperbaric oxygen therapy and standard care, and the remaining study found that standard care alone resulted in a higher rate of remission than standard care combined with hyperbaric oxygen therapy. The reviewers concluded that RCTs must be conducted to determine whether hyperbaric oxygen therapy adds significantly to the efficacy of standard care.[14]Level of evidence: 2 Back to Top

References
Evidence references [1] Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992;326:281-6 CrossRef [2] Wright EH, Khan U. Serum complement-reactive protein (CRP) trends following local and free-tissue reconstructions for traumatic injuries or chronic wounds of the lower limb. J Plast Reconstr Aesthet Surg. 2010;63:1519-22 CrossRef

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[3] Howard CB, Einhorn M, Dagan R, Yagupski P, Porat S. Fine-needle bone biopsy to diagnose osteomyelitis. J Bone Joint Surg Br. 1994;76:311-4 [4] Kapoor A, Page S, Lavalley M, Gale DR, Felson DT. Magnetic resonance imaging for diagnosing foot osteomyelitis: a meta-analysis. Arch Intern Med. 2007;167:125-32 CrossRef [5] Malamitsi J, Giamarellou H, Kanellakopoulou K, et al. Infecton: a 99mTc-ciprofloxacin radiopharmaceutical for the detection of bone infection. Clin Microbiol Infect. 2003;9:101-9 [6] Lazzeri E, Pauwels EK, Erba PA, et al. Clinical feasibility of two-step streptavidin/111In-biotin scintigraphy in patients with suspected vertebral osteomyelitis. Eur J Nucl Med Mol Imaging. 2004;31:1505-11 CrossRef [7] Termaat MF, Raijmakers PG, Scholten HJ, Bakker FC, Patka P, Haarman HJ. The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-analysis. J Bone Joint Surg Am. 2005;87:2464-71 CrossRef [8] Zhuang H, Duarte PS, Pourdehand M, Shnier D, Alavi A. Exclusion of chronic osteomyelitis with F-18 fluorodeoxyglucose positron emission tomographic imaging. Clin Nucl Med. 2000;25:281-4 [9] Guhlmann A, Brecht-Krauss D, Suger G, et al. Chronic osteomyelitis: detection with FDG PET and correlation with histopathologic findings. Radiology. 1998;206:749-54 [10] Hartmann A, Eid K, Dora C, Trentz O, von Schulthess GK, Stumpe KD. Diagnostic value of 18F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis. Eur J Nucl Med Mol Imaging. 2007;34:704-14 CrossRef [11] Horger M, Eschmann SM, Pfannenberg C, et al. Added value of SPECT/CT in patients suspected of having bone infection: preliminary results. Arch Orthop Trauma Surg. 2007;127:211-21 CrossRef [12] Rao N, Hamilton CW. Efficacy and safety of linezolid for Gram-positive orthopedic infections: a prospective case series. Diagn Microbiol Infect Dis. 2007;59:173-9 CrossRef [13] Karamanis EM, Matthaiou DK, Moraitis LI, Falagas ME. Fluoroquinolones versus beta-lactam based regimens for the treatment of osteomyelitis: a meta-analysis of randomized controlled trials. Spine (Phila Pa 1976). 2008;33:E297-304 CrossRef [14] Goldman RJ. Hyperbaric oxygen therapy for wound healing and limb salvage: a systematic review. PM R. 2009;1:471-89 CrossRef Guidelines The American College of Radiology has produced the following: Schweitzer ME, Daffner RH, Weissman BN, et al. ACR Appropriateness Criteria: Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. Reston, VA: American College of Radiology; 2008 Further reading Carek PJ, Dickerson LM, Sack JL. Diagnosis and management of osteomyelitis. Am Fam Phys. 2001;63:2413-20 Pineda C, Vargas A, Vargas Rodriguez A. Imaging of osteomyelitis: current concepts. Infect Dis Clin North Am. 2006;20:789-825 Calhoun JD, Manring MM. Adult osteomyelitis. Infect Dis Clin North Am. 2005;19:765-86 Jaramillo-de la Torre JJ, Bohinski RJ, Kuntz C 4th. Vertebral osteomyelitis. Neurosurg Clin N Am. 2006;17:339-51, vii Santiago Restrepo C, Gimnez CR, McCarthy K. Imaging of osteomyelitis and musculoskeletal soft tissue infections: current concepts. Rheum Dis Clin North Am. 2003;29:89-109 Lew DP, Waldvogel FA. Osteomyelitis. Lancet. 2004;364:369-79 Lazzarini L, Mader JT, Calhoun JH. Osteomyelitis in long bones. J Bone Joint Surg Am. 2004;86:2305-18 Sia IG, Berbari EF. Infection and musculoskeletal conditions: osteomyelitis. Best Pract Res Clin Rheumatol. 2006;20:1065-81 Concia E, Prandini N, Massari L, et al. Osteomyelitis: clinical update for practical guidelines. Nucl Med Commun. 2006;27:645-60 Frykberg RG, Wittmayer B, Zgonis T. Surgical management of diabetic foot infections and osteomyelitis. Clin Podiatr Med Surg. 2007;24:469-82 Shank CF, Feibel JB. Osteomyelitis in the diabetic foot: diagnosis and management. Foot Ankle Clin North Am. 2006;11:775-89 Palestro CJ, Love C, Miller TT. Infection and musculoskeletal conditions: imaging of musculoskeletal infections. Best Pract Res Clin Rheumatol. 2006;20:1197-218 Tehranzadeh J, Wong E, Wang F, Sadighpour M. Imaging of osteomyelitis in the mature skeleton. Radiol Clin North Am. 2001;39:223-50 Keidar Z, Militianu D, Melamed E, Bar-Shalom R, Israel O. The diabetic foot: initial experience with 18F-FDG PET/CT. J Nucl Med. 2005;46:444-9 Fayad LM, Carrino JA, Fishman EK. Musculoskeletal infection: role of CT in the emergency department. Radiographics. 2007;27:1723-36 Shimose S, Sugita T, Kubo T, Matsuo T, Nobuto H, Ochi M. Differential diagnosis between osteomyelitis and bone tumors. Acta Radiol. 2008;49:928-33 Christian S, Kraas J, MD, Conway WF. Musculoskeletal infections. Semin Roentgenol. 2007;42:92-101 Mandracchia VJ, Sanders SM, Jaeger AJ, Nickles WA. Management of osteomyelitis. Clin Podiatr Med Surg. 2004;21:335-51 Gitelis S, Brebach GT. The treatment of chronic osteomyelitis with a biodegradeable antibiotic-impregnated implant. J Orthop Surg (Hong Kong). 2002;10:53-60 Rana B, Butcher I, Grigoris P, Murnaghan C, Seaton RA, Tobin CM. Linezolid penetration into osteo-articular tissues. J Antimicrob Chemother. 2002;50:747-50 Bernard L, Vaudaux P, Vuagnat A, et al. Effect of vancomycin therapy for osteomyelitis on colonization by methicillin-resistant Staphylococcus aureus: lack of emergence of glycopeptide resistance. Infect Control Hosp Epidemiol. 2003;24:650-4 Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66:82-98 Malloy KM, Davis GA. Summary of ASHP/IDSA/SIDP vancomycin monitoring recommendations: a focus on osteomyelitis. Orthopedics. 2009;32:499 Parsons B, Strauss E. Surgical management of chronic osteomyelitis. Am J Surg. 2004;188(Suppl 1A):57-66 Tetsworth K, Cierny G 3rd. Osteomyelitis debridement techniques. Clin Orthop Relat Res. 1999:87-96 McHenry MC, Easley KA, Locker GA. Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis. 2002;34:1342-50 Senneville E, Lombart A, Beltrand E, et al. Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study. Diabetes Care. 2008;31:637-42 Tice AD, Hoaglund PA, Shoultz DA. Outcomes of osteomyelitis among patients treated with outpatient parenteral antimicrobial therapy. Am J Med. 2003;114:723-8 Back to Top

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Codes
ICD-9 code 526.4 Inflammatory conditions 376.03 Orbital osteomyelitis 730.0 Acute osteomyelitis 730.1 Chronic osteomyelitis 730.18 Chronic osteomyelitis - other specified sites 730.19 Chronic osteomyelitis - multiple sites 730.2 Unspecified osteomyelitis 730.28 Unspecified osteomyelitis - other specified sites 730.29 Unspecified osteomyelitis - multiple sites 730.8 Other infections involving bone in disease classified elsewhere 730.9 Unspecified infection of bone 730.98 Unspecified infection of bone - other specified sites 730.99 Unspecified infection of bone - multiple sites Back to Top

FAQ
When should osteomyelitis be suspected? The diagnosis of osteomyelitis should be considered in patients with diabetes and unexplained musculoskeletal problems and in patients with recurring joint and soft tissue infections, especially in the setting of trauma or surgery What is the appropriate antibiotic for the treatment of osteomyelitis? The selection of antibiotic must be determined by the results of appropriate tissue sampling, often including a surgical biopsy of bone What are the indications for Doppler ultrasonography in patients with osteomyelitis? Doppler studies should be considered in patients with peripheral vascular disease to determine vascular adequacy [1] Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992;326:281-6 CrossRef [2] Wright EH, Khan U. Serum complement-reactive protein (CRP) trends following local and free-tissue reconstructions for traumatic injuries or chronic wounds of the lower limb. J Plast Reconstr Aesthet Surg. 2010;63:1519-22 CrossRef [3] Howard CB, Einhorn M, Dagan R, Yagupski P, Porat S. Fine-needle bone biopsy to diagnose osteomyelitis. J Bone Joint Surg Br. 1994;76:311-4 [4] Kapoor A, Page S, Lavalley M, Gale DR, Felson DT. Magnetic resonance imaging for diagnosing foot osteomyelitis: a meta-analysis. Arch Intern Med. 2007;167:125-32 CrossRef [5] Malamitsi J, Giamarellou H, Kanellakopoulou K, et al. Infecton: a 99mTc-ciprofloxacin radiopharmaceutical for the detection of bone infection. Clin Microbiol Infect. 2003;9:101-9 [6] Lazzeri E, Pauwels EK, Erba PA, et al. Clinical feasibility of two-step streptavidin/111In-biotin scintigraphy in patients with suspected vertebral osteomyelitis. Eur J Nucl Med Mol Imaging. 2004;31:1505-11 CrossRef [7] Termaat MF, Raijmakers PG, Scholten HJ, Bakker FC, Patka P, Haarman HJ. The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-analysis. J Bone Joint Surg Am. 2005;87:2464-71 CrossRef [8] Zhuang H, Duarte PS, Pourdehand M, Shnier D, Alavi A. Exclusion of chronic osteomyelitis with F-18 fluorodeoxyglucose positron emission tomographic imaging. Clin Nucl Med. 2000;25:281-4 [9] Guhlmann A, Brecht-Krauss D, Suger G, et al. Chronic osteomyelitis: detection with FDG PET and correlation with histopathologic findings. Radiology. 1998;206:749-54 [10] Hartmann A, Eid K, Dora C, Trentz O, von Schulthess GK, Stumpe KD. Diagnostic value of 18F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis. Eur J Nucl Med Mol Imaging. 2007;34:704-14 CrossRef [11] Horger M, Eschmann SM, Pfannenberg C, et al. Added value of SPECT/CT in patients suspected of having bone infection: preliminary results. Arch Orthop Trauma Surg. 2007;127:211-21 CrossRef [12] Rao N, Hamilton CW. Efficacy and safety of linezolid for Gram-positive orthopedic infections: a prospective case series. Diagn Microbiol Infect Dis. 2007;59:173-9 CrossRef [13] Karamanis EM, Matthaiou DK, Moraitis LI, Falagas ME. Fluoroquinolones versus beta-lactam based regimens for the treatment of osteomyelitis: a meta-analysis of randomized controlled trials. Spine (Phila Pa 1976). 2008;33:E297-304 CrossRef [14] Goldman RJ. Hyperbaric oxygen therapy for wound healing and limb salvage: a systematic review. PM R. 2009;1:471-89 CrossRef
Revised: 24 Feb 2011

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