Investigations
1st investigations to order
FBC
Test
Useful in acute osteomyelitis and early fracture-related infection, when it is usually raised; however white cell count has a low specificity for osteomyelitis.
Usually normal in chronic disease.
Result
may be raised
erythrocyte sedimentation rate (ESR)
Test
Usually raised but may be normal; non-specific, also raised in other inflammatory conditions and in malignancy. Can be used to monitor treatment; if persistently raised after treatment, should trigger further assessment.
Often normal in chronic disease.
Result
usually raised
CRP
Test
Usually raised. May be more helpful than ESR in monitoring response to treatment because it normalises more rapidly. Non-specific.
Often normal in chronic disease.
Result
usually raised
blood culture
Test
Aim to take blood for culture before starting antibiotics to guide ongoing care.[2][6]
The EANM/EBJIS/ESR/ESCMID consensus document for the diagnosis of peripheral bone infection in adults recommends considering taking blood cultures, especially if the patient has a fever.[2]
The European Society for Paediatric Infectious Diseases (ESPID) guideline on bone and joint infections recommends taking blood cultures in children.[6]
For a patient with suspected native vertebral osteomyelitis:[7]
Obtain two sets of bacterial (aerobic and anaerobic) blood cultures
Withhold antibiotics until microbiological samples (either blood or bone) have been obtained and their results have been reported, if the patient is haemodynamically stable and has no signs of sepsis.
Consider:
Obtaining serological tests for Brucella species in a patient with subacute native vertebral osteomyelitis residing in an area endemic for brucellosis[7]
Obtaining fungal blood cultures in a patient with suspected native vertebral osteomyelitis who is at risk for fungal infection (epidemiological risk or host risk factors).[7]
Result
may be positive, indicating the infecting organism and microbial sensitivities
plain x-rays of affected area
Test
Always request x-rays to look for evidence of peripheral osteomyelitis, as well as other pathologies such as fractures or bone tumours.[2]
Practical tip
Ensure that you ask for the x-ray to include the joint above and below the area of pain in order to exclude an alternative diagnosis such as a slipped capital femoral epiphysis causing pain and a limp. See our topic Slipped upper femoral epiphysis.
Result
acute disease:
may initially be normal
osteopenia appears 6-7 days after infection onset, and evidence of bone destruction, cortical breaches, and periosteal reaction follow quickly
involucra and sequestra can sometimes be seen, with further diffuse osteopenia developing later due to disuse of the affected limb
may show joint effusion in local joints
discitis:
lateral spine radiographs show late changes at 2–3 weeks into illness, especially decreased intervertebral space and/or erosion of the vertebral plate
vertebral osteomyelitis:
initially shows localised rarefication (‘thinning’) of a single vertebral body, and then later, anterior bone destruction
chronic disease:
intramedullary scalloping, cavities, and cloacae may be seen, with a ‘fallen leaf’ sign 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 [Citation ends].
Investigations to consider
bone samples and bone biopsy
Test
There is a lack of evidence and consensus on whether bone samples should always be obtained (irrespective of ease of access) prior to commencing antibiotics. If a patient has suspected sepsis, do not delay antibiotic therapy.[2][6][7]
In patients who are less sick, balance the invasiveness of the test with the need for an accurate aetiological diagnosis. Biopsies through sinus tracts are not recommended.[2]
The gold standard for accurate identification of infection and the causative microorganism is culture of infected bone, as obtaining an aetiological diagnosis is important for choosing the appropriate antimicrobial treatment.[2][6][7]
When indicated, obtain bone specimens from open bone biopsy, image-guided fine needle aspiration (FNA), or needle puncture. Bone biopsy is usually performed during the surgical debridement procedure.[2] FNA is less disruptive to bone than biopsy and allows multiple samples to be taken.[2] Be careful to prevent infection spreading to uninfected bone.[2]
Bone biopsies are generally conducted using CT guidance. MRI is rarely used for obtaining a bone biopsy, because of the electromagnetic radiation MRI-guided bone biopsy requires. In selected cases (e.g., in children) consider MRI-guided bone biopsy with a non-ferromagnetic stainless steel needle.
Collect at least three bone biopsy samples from a visibly inflamed area to reduce incorrect contamination reports.[2]
Divide collected samples for bacteriology and histology.[2]
Request aerobic and anaerobic cultures.[2]
For a patient with suspected native vertebral osteomyelitis (based on clinical, laboratory, and imaging studies), obtain an image-guided aspiration biopsy when a microbiological diagnosis for a known associated organism (Staphylococcus aureus, Staphylococcus lugdunensis, and Brucella species) has not been established by blood cultures or serological tests.[7]
Consider cultures for mycobacteria and fungi in patients living in or having visited endemic areas and with suggestive clinical features.[2]
In chronic or device-related bone infections, request prolonged cultures for aerobic and anaerobic organisms of 7 to 10 days to identify slow-growing organisms such as Propionibacteria species. Mycobacteria may take even longer.
Inform the laboratory of any unusual features so that appropriate culture techniques can be employed. For example, request:
Culture for Nocardia species, mycobacteria, and fungi if the patient is immunocompromised
Culture at 25°C (77°F) if you suspect Mycobacterium marinum (an extremity infection related to tropical fish tank exposure or aquatic environments).
Sonication has been used to increase microbiological 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 releases organisms from the biofilm and improves culture rates in low-grade implant infections where the bacterial load may be small.[46]
Result
may be positive, indicating the infecting organism and microbial sensitivities
may show other pathology such as tumour or granulomatous disease
polymerase chain reaction (PCR)
Test
May be helpful in identifying organisms when culture is negative, or when antibiotics have been given prior to taking microbiological samples.[6]
Nucleic acid amplification techniques such as PCR are highly specific and sensitive for rapidly identifying bacteria, fungi, parasites, and viruses from clinical samples, including those that are slow to grow or cannot be cultured.[31]
Results are available particularly quickly if multiplex real-time PCR is used.
PCR has been shown to be more sensitive than conventional culture when identifying some fastidious organisms (e.g., Kingella kingae in children <5 years).[6] However, samples need to be big enough to ensure sensitivity and the technique does not provide antibiotic susceptibility information.
PCR–hybridisation after sonication can improve diagnosis of infections related to implants.[31]
Consider PCR in a patient with native vertebral osteomyelitis to identify:[7]
Brucella species (if in endemic area)
Serum interferon-gamma release assay for Mycobacterium tuberculosis (if patient living in or returning from a TB-endemic region, or with risk factors)
Fungi.
Can identify Panton-Valentine leukocidin (PVL) gene.[56]
Result
may be positive
MALDI-TOF mass spectrometry
Test
Request 16s ribosomal protein profiles obtained by matrix-assisted laser desorption ionisation – time of flight (MALDI-TOF) mass spectrometry to identify bacteria and yeasts rapidly and effectively.[31]
Mass peaks achieved by the test strains are compared with those of known reference strains.[31]
Result
may match reference strains
swabs
Test
Do not send superficial skin swabs or aspirate from sinuses for microbiology sensitivity and culture because these have been shown to correlate poorly with the causative organism.[30]
Aspirate deep fluid collections and obtain deep wound swabs from patients with diabetes. 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 base continued treatment on full culture results with antibiotic sensitivities.
Practical tip
In chronic osteomyelitis:
Gram stain has a very low sensitivity and is of no practical use
In relation to implant-related infection, percutaneous biopsy is often negative.
To maximise the sensitivity of microbiological sampling, the patient should 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 with 2 weeks of sampling.[43]
Result
may indicate causative organism and microbial sensitivities
urine microscopy, culture, and sensitivities
Test
Consider urinalysis and mid-stream specimen of urine (MSU) in patients displaying symptoms of a urinary tract infection.
Result
may be positive
histology
Test
If taken, always send any bone samples for histology (as well as culture and sensitivity) because deep sampling helps in the interpretation of microbiological results and will identify a malignancy.
Some infections, such as tuberculosis and actinomycosis, can be diagnosed by histology alone, although it is useful to know that the culture was negative in these instances.
In acute infection, direct microscopy with Gram staining of aspirated fluid gives a rapid indication of the type of organism present, but continued treatment should be based on full culture results with antibiotic sensitivities.
In chronic osteomyelitis, Gram stain has a very low sensitivity and is of no practical use.
Histology can 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.[55]
Result
may identify infecting organisms or acute or chronic inflammatory cells, dead bone, active bone resorption, small sequestra, or malignancy
probe-to-bone test
Test
Palpation of the bone with a metal probe. This bedside procedure is based on the concept that if the probe can reach bone, so can infectious bacteria.[2][27] If a fistula is present, a probe-to-bone test in a diabetic foot is indicative of bone infection; however, there is no evidence to support this principle in peripheral bone infection.
Practical tip
A patient with diabetes may not report pain due to neuropathy; they may present only with hyperglycaemia that is difficult to control.
In a patient with diabetes, if you can palpate the bone with a probe, this is indicative of osteomyelitis; however, there is no evidence to support the utility of this in diagnosing peripheral bone infection in a patient without diabetes.[2] Be careful with a probe-to-bone test as it can cause harm.
Result
probe may reach bone, which can rule in osteomyelitis in a high-risk patient with diabetes[27]
bone MRI
Test
MRI is usually the most definitive and helpful imaging modality. May show signs of infection in the medullary canal or surrounding soft tissues. Not good at picking up cortical sequestra. Seek advice on interpretation from a radiologist with a special interest in musculoskeletal imaging.
Request a whole spine MRI for the patient with suspected native vertebral osteomyelitis.[7]
MRI can detect abnormalities in children within 3 to 5 days of onset.[6] It may be indicated when:
The child is very sick
There are doubts about the diagnosis
A complication is suspected.
Result
may show high signal on T2 images or fat suppression sequences
may show changes in children within 3-5 days of onset[6]
may show vertebral bone changes
ultrasound
Test
Helpful in acute osteomyelitis to look for signs of associated septic arthritis and infection. Use ultrasound to guide aspiration or biopsy for microbiological diagnosis.
Result
may show collections, subperiosteal abscesses, and adjacent joint infusions
CT scan
Test
Has a limited role in diagnosis, but useful for visualising extent of bone destruction; can identify abscesses and small sequestra more reliably than MRI.[51][52][53][54] It is sometimes helpful in aiding surgical planning.
Aspiration of subperiosteal or intraosseous spaces under fluoroscopy- or CT-guidance helps guide antibiotic treatment.
Local availability and experience are primary factors in determining CT or MRI preference.
Result
bone destruction, sequestra, abscess
radionuclide scan
Test
Fluorodeoxyglucose positron emission tomography and single-photon emission computed tomography scanning are good at demonstrating infection around implants (for when an abnormality is seen in the bone on MRI and it is difficult to determine whether it represents active infection or simply structural derangement of the bone).[57]
Result
increased uptake of radioactive injectate in infected sites
bone scintigraphy
echocardiogram
Test
Request to identify endocarditis.
Result
may identify valvular vegetations
chest x-ray
Test
Consider obtaining a chest x-ray if you suspect tuberculosis.[31] See our topic Extrapulmonary tuberculosis.
Result
may show primary or reactive tuberculosis
some signs of primary tuberculosis include patchy areas of consolidation, lobar consolidation, or a Ghon lesion; hilar and mediastinal (paratracheal) lymphadenopathy, particularly in children; pleural effusions, more frequently in adults
some signs of reactive tuberculosis include patchy consolidation or poorly defined linear and nodular opacities
Mantoux test
Test
Request a purified protein derivative (PPD) for Mycobacterium tuberculosis for a patient originating from or living in a TB-endemic region, or with risk factors.
Result
may be positive
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