Approach

The first step in diagnosis of osteomyelitis is the compilation of a thorough patient history, because previous infections may appear dormant for months before recurring. Risk factors include history of penetrating injuries, intravenous drug misuse, diabetes, HIV infection, surgical contamination, or periodontitis.[1][26]​​​[31][37]​ ​A clinical assessment of the patient's wounds and sensation in the affected area is necessary. Supporting evidence of osteomyelitis comes from plain radiographs and cultures.​[4][13]​ Establishing an etiologic diagnosis and associated antimicrobial susceptibility nearly always requires obtaining bone for microbiologic evaluation (unless blood cultures are positive in the context of convincing radiographic findings).[9]

Presentation of osteomyelitis is multifactorial in nature; some signs may be present in clinical examination and diagnostic assessment, and others absent.

Osteomyelitis should be suspected in a patient presenting with:[1]

  • Fever

  • Bone pain

  • Reduced mobility

  • Local erythema, tenderness, warmth, swelling, and reduced range of movement.

In infants, pain may be expressed only as a failure to bear weight or reduced use of an extremity.[4] Children with presumed acute hematogenous osteomyelitis of the pelvic bones can present with nonlocalizing pain, limp, groin pain, or inability to bear weight.[4]

Native vertebral osteomyelitis should be suspected in a patient with:[13]

  • New or worsening back or neck pain and

    • Fever, or

    • Elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), or

    • Bloodstream infection or infective endocarditis

  • Fever and new neurologic symptoms with or without back pain

  • New localized neck or back pain, following a recent episode of Staphylococcus aureus bloodstream infection.

Back pain in native vertebral osteomyelitis is typically localized to the infected disk space area and is exacerbated by physical activity or percussion to the affected area.[13] Pain may radiate to the abdomen, hip, leg, scrotum, groin, or perineum.[44] Paravertebral muscle tenderness and spasm, and limitation of spine movement, are the predominant physical examination findings.[13]

In patients with diabetes, osteomyelitis should be considered if there is a local infection, a deep wound, or a chronic foot wound.[36] A patient with diabetes may not report pain due to neuropathy; hyperglycemia that is difficult to control may be the only presenting feature.[36][37]​ Any ulcer that probes to bone poses an increased risk of underlying osteomyelitis.[45][46]​ A hot, painful, or swollen foot in a patient with diabetes may be acute Charcot arthropathy. An interdisciplinary diabetic foot team should be consulted if there is diagnostic doubt. For more information, see Diabetic foot complications.

Chronic osteomyelitis is defined as a more protracted, often indolent disease process.[13] Chronic osteomyelitis should be suspected in a patient with:

  • More vague, nonspecific pain[4][5] or

  • Low-grade fever[5] or

  • Lethargy and malaise[5] or

  • Persistent drainage from a wound and/or sinus tract.[4][5]

[Figure caption and citation for the preceding image starts]: A 62-year-old man suffered an open tibial fracture, which became infected after internal fixation. He continued with intermittent discharge of pus from the front of his tibia for 21 years. Imaging confirmed the presence of chronic osteomyelitis with a central area of dead bone (sequestrum)Courtesy of the Oxford Bone Infection Unit; used with permission [Citation ends].com.bmj.content.model.Caption@30b2e00

Diagnosis should be made from clinical signs of infection, laboratory tests, imaging abnormalities, and, ideally, by positive bacterial culture from deep microbiologic samples obtained via radiologic guided biopsy or open surgery.[4]

Clinical evaluation

Clinical assessment is important in the evaluation of the integrity of the patient's musculoskeletal system.[47]

Signs:

  • Sinus or wound drainage[1]

  • Local inflammation, erythema, and swelling[1]

  • Acute or old healed sinuses[1][26]

  • Decreased range of motion above and below the infected segment[1]

  • Associated deformity of the limb, particularly following childhood osteomyelitis that may have resulted in premature fusion of the physeal plate, resulting in limb shortening or angular deformity[4]

  • Tenderness to percussion over the subcutaneous border of affected bones may be seen in chronic osteomyelitis

  • Cervical vertebral osteomyelitis may be suspected in patients with torticollis secondary to soft-tissue infection of the neck.[48][49] Lumbar vertebral osteomyelitis will present with low back pain and may be associated with recent urosepsis, possibly due to the anatomy of the Batson plexus.[50][51]

Symptoms:

  • Fever (typically low-grade)[1]

  • Nonspecific pain at the site of infection[4][5]

  • New or worsening back or neck pain in cases of vertebral osteomyelitis[13]

  • A motor deficit may indicate the presence of native vertebral osteomyelitis[13]

  • Decreased sensation in cases of diabetic foot and vertebral osteomyelitis​[13][37]

  • Malaise and fatigue.[4][5]

In patients with suspected native vertebral osteomyelitis, evaluation by an infectious disease specialist and a spine surgeon may be considered.[13]

Laboratory evaluation

There are no specific blood tests to confirm the diagnosis of bone infection. Diagnostic specificity must be obtained through clinical presentation, imaging, surgical findings, histology, and cultures.[9]

Complete blood count, and baseline ESR and CRP, are recommended in patients with suspected native vertebral osteomyelitis and in children with suspected acute hematogenous osteomyelitis.[1][4][12][13][37]​​​ In acute osteomyelitis, inflammatory markers such as the white blood cell count, ESR, and CRP levels are usually elevated, but these markers are often normal in chronic infection.[1][15]​​ The trend in blood inflammatory markers such as ESR and CRP may be useful in patients with suspected osteomyelitis, particularly for assessing improvement during treatment.​[4][13]

Inflammatory markers are nonspecific and may be elevated in other conditions such as inflammatory joint disease and gout. A persistently elevated ESR after treatment should trigger a further assessment.[52][53][54][55][56]​ CRP is also nonspecific as an inflammatory marker, but it may be more helpful than ESR because CRP normalizes more rapidly after successful treatment.

Inflammatory markers are often normal or only mildly elevated in patients with a diabetic foot problem.[36][37] Guidelines from the International Working Group on the Diabetic Foot (IWGDF) recommend using a combination of the probe-to-bone (PTB) test, ESR (or CRP and/or procalcitonin), and plain x-rays as the initial studies to diagnose osteomyelitis.[37]

Microbiology

Ideally, diagnosis should be confirmed by positive bacterial culture from deep microbiologic samples.[4][9]​​ Aspiration of deep fluid collections, guided percutaneous bone biopsies, and blood cultures may facilitate early diagnosis, therefore allowing treatment with antibiotics alone. These investigations are particularly useful in children, in patients with acute infection, and in people with diabetic foot infections.[37]

Obtaining an etiologic diagnosis is important for choosing the appropriate antimicrobial treatment.[9]​ However, if a patient has suspected sepsis, antibiotic therapy should not be delayed.[1]

If blood cultures are indicated, samples should be taken before initiating antibiotics, whenever possible.[1]​​[4][12]

Blood cultures should be considered:

  • In adults with suspected osteomyelitis who have a fever[1]

  • In all children with suspected ostemomyelitis.[12]

The Infectious Diseases Society of America (IDSA) recommends obtaining bacterial (aerobic and anaerobic) blood cultures (2 sets) and baseline ESR and CRP in all patients with suspected native vertebral osteomyelitis.[13] Serologic tests for Brucella species should be obtained in patients with suspected subacute native vertebral osteomyelitis residing in, or recently returning from, an area endemic for brucellosis.[13] Concomitant blood cultures for Brucella species are recommended but culture may be difficult and results slow to obtain, as the organism is intracellular and the number of circulating bacteria is usually low.[9][57]​​​​​​​​ The laboratory should be notified when Brucella species is considered a potential cause of osteomyelitis so that cultures are examined only in a biologic safety cabinet.[9]​ The IDSA further recommends that fungal blood cultures should be sought in patients with suspected native vertebral osteomyelitis who are at risk for fungal infection (epidemiologic risk or host risk factors).[13] In patients with suspected subacute native vertebral osteomyelitis who are at risk for Mycobacterium tuberculosis native vertebral osteomyelitis (i.e., those originating in, living in, or recently returning from tuberculosis-endemic regions, or with risk factors), a purified protein derivative (PPD) test (also known as an intradermal Mantoux test) or a serum interferon-gamma release assay should be obtained.[13]​ Commercial M tuberculosis nucleic acid amplification tests (NAAT) are not Food and Drug Administration (FDA)-cleared for nonrespiratory sites, so a laboratory-developed/validated test must be used if NAATs are requested.[9]

Surgery samples and timing of antibiotics

If surgery is indicated, the gold-standard diagnostic microbiologic test in chronic or device-related osteomyelitis requires taking multiple deep samples under aseptic conditions using separate instruments. To maximize the sensitivity of microbiologic sampling it is advisable to stop antibiotics for at least 2 weeks before surgical debridement. The false-negative rate from cultures in osteomyelitis rises from 23% to 55% if antibiotics are given within 2 weeks of sampling.[58] However, in children with presumed acute hematogenous osteomyelitis who appear ill or have rapidly progressive infection, the IDSA recommends that empiric antimicrobial therapy should be started immediately rather than withholding antibiotics until invasive diagnostic procedures are performed.[4] In children with presumed acute hematogenous osteomyelitis who are not clinically ill and for whom an aspirate or biopsy by invasive diagnostic procedure is being planned prior to initiating antibiotics, the IDSA recommends that antibiotics should be withheld for no more than 48-72 hours.[4]

Bone biopsy

Identification of the causative pathogen(s) is best accomplished through either open or percutaneous bone biopsy.[59] One specimen should be sent for Gram stain and culture (including aerobic, anaerobic, mycobacterial, and fungal cultures), and a second should be sent for histopathology. Bone biopsy is usually performed during the surgical debridement procedure.[1]​ Image-guided fine needle aspiration (FNA) is less disruptive to bone than biopsy and allows multiple samples to be taken. The IDSA recommends image-guided FNA of a disk space or vertebral endplate in patients with suspected native vertebral osteomyelitis (based on clinical, laboratory, and imaging studies) when a microbiologic diagnosis for a known associated organism (Staphylococcus aureus, S lugdunensis, and Brucella species) has not been established by blood cultures or serologic tests.[9][13] Specimens should be submitted for Gram stain and aerobic and anaerobic culture and, if adequate tissue can be obtained, histopathology.[9]​ If results are negative or inconclusive (e.g., Corynebacteriumspecies is isolated), a second imaging-guided aspiration biopsy, percutaneous endoscopic discectomy and drainage procedure, or open excisional biopsy, should be considered to collect additional specimens for repeat and additional testing.[9]​ In patients with neurologic compromise (with or without impending sepsis or hemodynamic instability), the IDSA recommends immediate surgical intervention and initiation of empiric antimicrobial therapy instead of withholding antimicrobial therapy prior to an image-guided diagnostic aspiration biopsy.[13] If adequate tissue can be safely obtained, specimens should be sent for pathologic examination to help confirm a diagnosis of native vertebral osteomyelitis and guide further diagnostic testing, especially in the setting of negative cultures.[13] In chronic osteomyelitis and implant-related infection, percutaneous biopsy is often negative. Multiple microbiology samples should be taken at the start of any debridement surgery to improve the sensitivity and specificity of the culture results.[60][61]​ Molecular diagnostics may be performed on bone biopsies but are not considered first-line diagnostic tests. Microorganism-specific nucleic acid amplification tests (NAATs) or a broader approach, such as 16S ribosomal RNA gene PCR/sequencing (for bacterial detection) may be considered.[9][62]

Culture duration and technique

Prolonged cultures for aerobic and anaerobic organisms are important in chronic or device-related bone infections. This is because some organisms, such as  Propionibacteria species and Mycobacteria species, are slow-growing. The diagnosis of tuberculous osteomyelitis is established by microscopy and culture of infected material. Tissue can be obtained by needle biopsy or aspiration for diagnosis in both solid and liquid media. Informing the laboratory of any unusual features allows special culture techniques to be employed. For example, immunocompromised patients should have culture for Nocardia species, mycobacteria, and fungi.[13] Although vertebral osteomyelitis due to nontuberculous mycobacteria is rare, immunocompromise (e.g., HIV infection; corticosteroid use) is a predisposing factor.[63]

Mycobacterial cultures at 77°F (25°C) may be needed if Mycobacterium marinum is suspected (an extremity infection related to tropical fish tank exposure).

Sonication has been used to increase microbiologic sensitivities by subjecting hard surfaces such as plates, screws, implants, or bone removed during surgery to ultrasonic energy while in a sterile saline solution. This liberates organisms from the biofilm and improves positive culture rates. It may be especially useful in low-grade implant infections where the bacterial load may be small.[64]

Culture of superficial swabs or fluid from sinuses has been shown to correlate poorly with the causative organism and should be avoided.[1][9]​​[65]

Histology

Histology can be utilized if the diagnosis is uncertain. Deep histologic sampling helps in the interpretation of microbiologic sampling results. Some infections, such as tuberculosis and actinomycosis, can be directly diagnosed by histology alone. Histopathologic features of osteomyelitis include the presence of necrotic bone adjacent to an inflammatory exudate.

In acute infection, direct microscopy with Gram staining of aspirated fluid gives a rapid indication of the type of organism present (e.g., gram-positive cocci), but continued treatment should be based on full culture results with antibiotic sensitivities.​[4][13]​​ The presence of a sinus tract is pathognomonic of chronic osteomyelitis.[1][4][5][66]​​​

Histology can also be used to confirm the diagnosis of culture-negative osteomyelitis by the demonstration of acute and chronic inflammatory cells, as well as dead bone, active bone resorption, and the presence of small sequestra. In suspected cases of fracture-related osteomyelitis, the presence of ≥5 + neutrophil polymorph counts per high-power field (x400 magnification) is a positive diagnostic test for infection.[67]​ In patients with mycetoma, a chronic soft tissue infection of the extremities which can extend into contiguous bone and connective tissue, sinus drainage may be examined grossly and microscopically for the presence of characteristic "sulfur granules".[9]

Imaging

X-ray

Plain radiographs should be performed to look for evidence of osteomyelitis or other relevant pathology such as fractures or bone tumors.[4][68] In acute osteomyelitis the initial radiograph may look relatively normal.[68] Subtle early radiographic findings of osteomyelitis include soft-tissue swelling and obscuration of the fat planes adjacent to the affected bone.[12][68] After 1-2 weeks, osteolysis, cortical loss, and periosteal reaction ensue.[68] Sequestra can sometimes be seen. In general, osteomyelitis must extend at least 1 cm and compromise 30% to 50% of bone mineral content to produce noticeable changes in plain radiographs.[69][70] Given that radiologic changes may not be reliably present, especially in the early stages of acute osteomyelitis, plain films are an inherently insensitive test.[71] Plain radiographs do, however, provide an appropriate baseline examination for comparison as the disease progresses.

In more established chronic infection, other signs are visible. Intramedullary scalloping, cavities, and cloacae may all be seen. A "fallen leaf" sign is noted when a piece of endosteal sequestrum has detached and fallen into the medullary canal. [Figure caption and citation for the preceding image starts]: Plain x-ray of the left femur showing a lytic lesion in the medullary canal along with a "fallen leaf" sign with intramedullary sequestrum noted in the cavityCourtesy of the Oxford Bone Infection Unit; used with permission [Citation ends].com.bmj.content.model.Caption@1d2ee85

Magnetic resonance imaging (MRI)

MRI is the most helpful imaging modality in osteomyelitis because it gives good cross-sectional information about the bone and provides excellent evaluation of the adjacent soft tissues including visualization of abscesses and fistulas.[12][68][72][73][74]​​ MRI is also sensitive at depicting marrow signal changes of acute osteomyelitis.[68] MRI allows early detection of osteomyelitis; it is highly sensitive for detecting osteomyelitis as soon as 3-5 days after the onset of infection.​[69][75]​​ MRI spine is recommended in patients with suspected native vertebral osteomyelitis.[13] However, for all other types of osteomyelitis do not routinely use MRI as initial imaging. It is advised if additional imaging is required after initial radiographs have been taken.[68][76]​​

High signal on the T2 images or fat suppression sequences may be seen, indicating infection in the medullary canal or surrounding soft tissues. Unfortunately, sequestra appear black on all MRI sequences, as does normal cortical bone. Therefore, MRI is not useful in detecting cortical sequestra.

Interpretation of MRI scans in osteomyelitis can be challenging, and input from a radiologist with a special interest in musculoskeletal imaging may be required. Although a sensitive test, MRI tends to overscore the extent of infection in the acute phase when bone edema is seen as high signal in the medullary canal.

MRI is useful for the evaluation of osteomyelitis or soft tissue infection in the setting of extra-articular surgical hardware.[68] Advances in metal artifact reduction techniques have improved orthopedic hardware imaging, particularly in the appendicular skeleton.[68][77] However, MRI must be used with caution in the post-operative or post-trauma period because bone marrow and soft tissue edema may persist, therefore mimicking infection.[68][78]

The use of intravenous contrast does not improve diagnosis of peripheral osteomyelitis; however, its use may improve the evaluation of soft tissue infections.[68] The American College of Radiology recommends MRI for suspected osteomyelitis of the foot in patients with diabetes, after plain x-rays have been performed.[35] For more information, see Diabetic foot complications.

Ultrasound

Although there is insufficient evidence to support the use of ultrasound for the initial evaluation of osteomyelitis, it may be a useful diagnostic tool when other modalities are not readily available.[68] Ultrasound is also useful for regions that are obscured by orthopedic instrumentation and therefore might not be easily visualized with MRI.[69] In acute osteomyelitis, ultrasound scans can be used to identify associated collections, subperiosteal abscesses, and adjacent joint effusions that might signify septic arthritis. Ultrasound can also be used to guide aspiration or biopsy for microbiologic diagnosis.[68]

Other imaging modalities

Local availability and the physician's preference and experience are primary factors in determining which other imaging modalities are selected.

Computed tomography (CT) has a very limited role in initial diagnosis for osteomyelitis.[70] CT is unable to demonstrate bone marrow edema; therefore, a normal CT does not exclude early osteomyelitis.[79] However, CT is superior to MRI for the detection of sequestra, cloacas, involucra, or intraosseous gas and can help in the guidance of needle biopsies and joint aspiration; it is also valuable in cases of vertebral osteomyelitis.​[69][80][81][82]​ CT has a key role in the detection of sequestra in chronic osteomyelitis, because necrotic bone can be masked by the surrounding osseous abnormalities on conventional radiography.[69] In chronic osteomyelitis, CT also demonstrates abnormal thickening of the affected cortical bone, with sclerotic changes, encroachment of the medullary cavity, and chronic draining sinus.[69]

Fluorodeoxyglucose positron emission tomography (FDG-PET) may be appropriate when initial radiographs are normal or show findings suggestive of osteomyelitis.​​​[68] FDG-PET is helpful when it is difficult to determine whether an abnormality seen in the bone on MRI represents active infection or structural derangement of the bone. Recent fracture or orthopedic implant may lower accuracy of FDG-PET as FDG-uptake can be seen in inflammation, including aseptic hardware loosening.[68]

Three-phase bone scans use a radionuclide tracer, typically technetium-99-m (Tc99m) bound to a phosphorus-containing compound, that accumulates in areas of bone turnover and increased osteoblast activity.[79]​ Although there is insufficient evidence to recommend a three-phase bone scan for the initial evaluation of osteomyelitis, this modality may be appropriate when initial radiographs are normal or show findings suggestive of osteomyelitis.[68] A three-phase bone scan can be used to rule out osteomyelitis and has high sensitivity if conventional radiographs are normal and when bone is not affected by other underlying conditions such as osteoarthritis, recent fracture, or recent hardware implantation.[68][83]​​​ However, a positive three-phase bone scan is nonspecific, and other underlying bone abnormalities such as neuroarthropathy, trauma, surgery, or tumor reduce specificity markedly.[68][84][85]​ For patients with suspected native vertebral osteomyelitis, when MRI is not feasible (e.g., with implantable cardiac devices, cochlear implants, claustrophobia, or unavailability), a combination spine gallium/Tc99m bone scan, or CT scan, or a positron emission tomography scan can be considered.[13]

Diabetic foot infection

In patients with diabetes and suspected osteomyelitis of the foot, the International Working Group on the Diabetic Foot (IWGDF) recommends that no further imaging of the foot is needed to establish the diagnosis if a plain x-ray and clinical and laboratory findings are compatible with osteomyelitis.[37][76]​ If the diagnosis of osteomyelitis remains in doubt, however, the IWGDF recommends that an advanced imaging study, such as MRI, 18F-FDG-PET/CT, or leukocyte scintigraphy (with or without CT) should be considered.[37] The American College of Radiology recommends MRI for suspected osteomyelitis of the foot in patients with diabetes, after plain x-rays have been performed.[35]​ For more information, see Diabetic foot complications.

Imaging: special considerations in children

For children suspected to have uncomplicated acute hematogenous osteomyelitis, imaging may not be required to establish or confirm the diagnosis. However, despite the low sensitivity of plain radiography for detecting acute hematogenous osteomyelitis on initial presentation, other important diagnoses may be ruled out by this investigation.[4] In children with discitis, lateral spine radiographs show late changes, especially decreased intervertebral space and/or erosion of the vertebral plate, at 2-3 weeks into the illness. In children with vertebral osteomyelitis, localized rarefication ("thinning") of a single vertebral body is seen initially; later, anterior bone destruction is observed.[12]​ In children, ultrasound can detect features of osteomyelitis several days earlier than conventional radiographs. Ultrasound may be more useful in identifying osteomyelitis in pediatric patients since the periosteum in the pediatric skeleton is more loosely adherent to the cortex than in the adult skeleton.[69][86] If a child does not respond to medical therapy within 24-48 hours, or signs and symptoms suggest a potential role for surgical debridement, MRI may be performed to better define the location and extent of infection or to evaluate for an alternative diagnosis such as a malignancy.[4] MRI can detect abnormalities in children within 3-5 days of onset.[12] MRI may be indicated when there is diagnostic doubt, in severe cases, or when a complication is suspected.[12] In children with suspected acute hematogenous osteomyelitis who have associated joint effusion or other concern for the spread of infection into an adjacent joint (or soft tissues), ultrasound evaluation may provide valuable diagnostic guidance for further management.[4]

Do not order MRI or CT in children until all appropriate clinical, laboratory and plain radiographic exams have been completed.[87]

Use of this content is subject to our disclaimer