DISCITIS, VERTEBRAL OSTEOMYELITIS & EPIDURAL ABSCESS Learning Objectives Introduction Epidemiology/...

DISCITIS, VERTEBRAL

OSTEOMYELITIS & EPIDURAL ABSCESS

• Learning Objectives• Introduction• Epidemiology/ Risk f

actors• Pathophysiology• Causative organisms• Clinical Features• Blood tests• Imaging• Biopsy• Management• Antimicrobial therapy• Surgical options• Monitoring & Progno

sis• Key points• Summary• Questions

Discitis, Vertebral Osteomyelitis & Epidural Abscess

Tom Fletcher and Marcus de Matas

Tom Fletcher is a Specialist Registrar in Infectious Diseases and Tropical medicine at the Royal Liverpool University Hospital. He organises the regional bone and joint infection group and is also a physician in the Royal Army Medical Corps. His research interests are bone and joint infection and special pathogens.

Marcus de Matas is a Consultant Spinal Surgeon at the Royal Liverpool University Hospital with a specialist interest in the management of spinal infection.

Edited by Prof Tom Solomon and Dr Agam Jung

This session provides an overview of discitis, vertebral osteomyelitis and epidural abscess with particular reference to the epidemiology

and pathogenesis, aetiological organisms, clinical presentation, diagnostic approach and medical/surgical management.

http://www.braininfectionsuk.org/

http://www.liv.ac.uk/infection-and-global-health

http://www.rlbuht.nhs.uk/

http://www.liv.ac.uk/neuroidcourse

http://www.thewaltoncentre.nhs.uk/

http://www.lstmliverpool.ac.uk/

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Learning Objectives

By the end of this session you will be able to:

• Describe the epidemiology and pathogenesis of discitis, vertebral osteomyelitis and spinal abscess

• List the likely causative organisms

• Recognise the clinical presentation and describe the approach to diagnosis, including different imaging modalities

• List the medical management, particularly anti-microbial selection and duration of treatment

• Define the role of surgical intervention, overall prognosis and follow-up







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IntroductionThis session explores acute spinal infection focusing on discitis, vertebral osteomyelitis and epidural abscess. These have been recognised since the time of Hippocrates but despite advantages in microbiology, surgical techniques and public health, there is a still significant morbidity and mortality from these conditions.

Their incidence is increasing and they commonly occur in combination, sharing similar aetiologies and clinical presentations. As such vertebral osteomyelitis and discitis are commonly referred to collectively as spondylodiscitis. However, epidural abscess is distinct in that it often requires urgent surgical decompression or drainage. Both conditions require a keen index of suspicion, a focussed diagnostic approach and benefit from multi-disciplinary management.

This session first examines their pathogenesis and epidemiology, then discusses causative organisms, whose identification is crucial for subsequent management. It then highlights their clinical presentations and explains the required diagnostic approach. Finally, it will look at both medical and surgical management of these conditions.







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Epidemiology/ Risk Factors IThese conditions are primarily diseases of adults with the majority of patients being aged between 50-70, but there is also a peak of infection in early childhood. In adults there is also a male predominance that is not well explained.

It is difficult to obtain a true estimate of their collective incidence, but in western societies, ranges for spondylodiscitis are 0.4 to 2.4 per 100,000 each year. The most common levels involved are the lumbar spine (50% of cases) followed by the thoracic, then the cervical spine.

There is evidence that incidence is increasing, but this is influenced by the increased use of magnetic resonance imaging (MRI) as a more sensitive diagnostic modality. However, the increasing age of the population and numbers of patients undergoing spinal anaesthesia will have a recognised effect.

Infection following elective or emergency spinal surgery is well recognised as is the risk from spinal interventions such as epidural catheters or lumbar punctures. Epidural catheters are now being performed more frequently, particularly on patients with greater infection risks, suggesting that the previous risk figures of 1/2000 are an underestimate. It is important to realise that in the high-risk groups, the chance of developing an epidural abscess might be as high as 1 in 100–200.







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Epidemiology/ Risk Factors II







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Pathophysiology IPathogens can reach the bones and tissues of the spine by three routes:

• Haematogenous• Direct inoculation by invasive spinal procedures• Spread from adjacent soft tissue infection

Haematogenous spread is the most common and occurs commonly via arterial supply to the vertebral bodies, but may also occur through retrograde venous flow to the paravertebral plexus.

In adults the disc is avascular and it is hypothesised that infection occurs through organisms deposited within the vertebral body metaphysis, that results in bony ischaemia and infarction. The resulting bony destruction allows organism multiplication and direct spread into the adjacent disc space, epidural space and adjacent vertebral bodies.

LEFT: Arterial supply to spinal column.RIGHT: Venous drainage.

Courtesy and copyright of Primal Pictures







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Pathophysiology IIA high index of suspicion is essential for making a timely diagnosis as the natural history, except in children, is progression. Local spread to paraspinal tissues as well as into the canal can occur and neurological loss is always the most feared complication. This can occur through a variety of mechanisms, which are detailed in the table below:







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Likely causative organisms IA single organism is usually responsible, although polymicrobial infections do occur (up to 20% in some series).

Staphylococcus aureus: The most important organism is staphylococcus aureus, which is responsible for over 50% of infections. As theproportion of methicillin-resistant strains (MRSA)has increased, so has its importance and consideration. Picture is scanning electron micrograph of the Staphylococcus aureus.

Gram negative bacilli: Gram negative bacilli such as Escherichia coli are the next most common group (4-30%) often arising from genitourinary or gastro-intestinal infection.

Coagulase-negative staphylococci: Following invasive spinal procedures coagulase-negative staphylococci are more frequent (13-29%).

Anaerobic infection: Anaerobic infection and Group B and G hemolytic streptococci are more common in patients with diabetes mellitus. Streptococci are also frequently associated with a dental port of entry and endocarditis.

Pseudomonas aeuriginosa and candida spp: Although uncommon, these are frequently associated with intravascular access infections and injecting drug users.







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Likely causative organisms IIFungal Infection

The diagnosis of fungal spondylodiscitis is often delayed and is usually due to candida albicans, but may be due to other candida or aspergillus spp.

Fungal infection is strogly associated with specific risk factors:• Diabetes Mellitus• Immunosupression • Administration of broad spectrum antibiotics• Intensive care admission.

Mycobacterial infection

Granulomatous disease, the commonest being Mycobacterium tuberculosis should always be considered, particularly in patients who are immunosuppressed, homeless, alcoholics and in prisons.

It is more common in injecting drug users and immigrantsfrom sub-Saharan Africa, south-east Asia and the Indian sub-continent. Active or previous extra-spinal tuberculosis is diagnosed in 33-52% cases.

Brucella and salmonella spp are more prevalent in endemic areas and should be in considered if there is a history of travel to or habitation in these regions.







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Clinical Features IThe presentation and natural history will vary according to:• Age of patient• Immune status• Microbiology• Level involved/site affected

There is no diagnostic characteristic to the pain of spondylodiscitis but this is present in over 90% of cases:• Spinal pain usually begins insidiously and progressively worsens over several weeks and sometimes over several months.• The pain is often worse at night although, at least initially, it may be relieved by bed rest. One caveat is that pain may be absent in patients with paraplegia.• Fever is a less consistent finding but present in 60-70% of cases.

Patients who present with epidural abscess often have a more typical sequence of back pain, which is often focal and severe, then root pain, then neurological involvement causing motor weakness and sensory changes, and eventually paralysis.







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Clinical Features IIThe most reliable clinical sign is localised tenderness to gentle spinal percussion. This is frequently accompanied by reduced mobility and protective muscle spasm.

A detailed neurological examination must follow, recording any deficit and any bowel or bladder function disturbance. It is rare to present with spinal deformity or paralysis.

Approach to diagnosis

The diagnosis of acute spinal infection is difficult in some patients, and relatively easy and straight-forward in others. It is not uncommon for the pain to be erroneously attributed to distant or recent minor trauma or other causes, particularly in patients who have no risk factors.

Picture courtesy and copyright of Primal Pictures







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Tests and blood culturesInitial laboratory tests often show an inflammatory response and are one of the first clues of an infective process.

The leucocyte count may be normal or elevated, but in over 80% of cases the erythrocyte sedimentation rate (ESR) is raised. The acute phase reactant C-reactive protein (CRP) is often raised and both ESR and CRP can be used to assess response to treatment, with CRP having a more rapid fall.

Once the diagnosis is considered, imaging is then requested but the most important facet is the identification of the causative organism.

Blood cultures are positive in between 50-70% of patients and must be obtained in any patient where spinal infection is considered. They also often alleviate the need for further invasive sampling for microbiological identification.

Blood cultures are a key investigation in patients with suspected spinal infection







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Imaging IPlain radiographs are often normal when obtained in the early phases of infection and bone destruction may not be apparent for two to three weeks, or more, after the onset of symptoms.

Typical findings in spondylodiscitis consist of destructive changes of two contiguous vertebral bodies with collapse of the intervening disc space. On rare occasions when the infection is confined to a single vertebra, it may cause collapse that mimics an ordinary vertebral compression fracture.

Computed tomography (CT) shows typical or suggestive changes of spondylodiscitis before such changes are apparent on plain films.

CT scanning is also useful for detecting the presence of bony sequestra, adjacent soft tissue abscesses, and in finding and localising the optimal approach for a biopsy.

Subtle abnormalities detected by CT scanning such as end plate irregularities may not be specific for osteomyelitis and early destructive changes may also be missed. Plain CT also has a high false negative rate for epidural abscess.







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Imaging II

Plain film radiograph of spinal discitis/osteomyelitis.

Lateral view of the lumbar spine demonstrates L3-4 disc space narrowing (arrow) and end-plate irregularity.







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Imaging IIIWhile the radiographs may be normal initially, radioisotope bone scans will often be abnormal early on in the disease. Gallium scans, when used in conjunction with technetium scans, have an accuracy of about 94%.

However, gallium and technetium scans may be falsely negative in leucopenic patients and elderly patients that may suffer from relative ischaemia of the effected area. The use of Fluoro-deoxyglucose PET (FDG-PET) is an evolving modality in infection and may have a role in evaluating response to treatment.

LEFT: Technetium-99m diphosphonate bone scan shows increased activity in the upper lumbar spine in a patient with chronic osteomyelitis.RIGHT: FDG PET scan shows intense radiotracer accumulation in the lower lumbar spine.







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Imaging IVContrast enhanced magnetic resonance imaging (MRI) is the modality of choice for diagnosing spinal infection and exceeds any other modality currently available, both in sensitivity and specificity, as it is 95% accurate. In line with other modalities it can be negative in the first few weeks of infection, and repeat interval imaging may be required.

MRI demonstrates both anatomic change and local features of inflammation and can differentiate between pyogenic infection, neoplasia and tuberculosis. It also gives a clear image of paraspinal tissues, and canal involvement in particular.

The ability to examine the whole spine, and therefore locate other sites is also important. Its main limitation is that it cannot be used in patients with certain metal implants or foreign bodies. In this situation, radioisotope scanning and CT imaging is recommended.







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Imaging VFalse-negative MRI findings have been reported in patients especially in those with concurrent meningitis or with long linear abscesses lacking discrete margins. On the other hand, false positive results can occur with bone infarction or fracture.

Typical MRI findings in spondylodiscitis include:

• On T1 weighted images: Decreased signal intensity in the vertebral bodies and disc and loss of endplate definition.• On T2 weighted images: Increased disc and less often vertebral signal intensity.

Contrast sequences reveal gadolinium enhancement of the vertebral end-plate initially and then the vertebral body and disc as it progresses.

In addition, ring enhancement of paraspinal and epidural processes correlates with abscess formation.







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Imaging VI

T1 and T2-weighted images showing advanced L4/5 discitis and vertebral osteomyelitis. There is also associated epidural and paravertebral soft tissue abscesses.







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BiopsyIf blood cultures are negative, direct sampling, normally in the mode of CT guided biopsy, is the next stage. A biopsy should be undertaken by an experienced radiologist and multiple sites should be biopsied.

In comparison to open biopsy, percutaneous needle biopsy has gained popularity showing a good accuracy with a less invasive procedure. It is applicable to outpatients or day hospital patients, since general anaesthesia is rarely required.

Biopsy should sample both inferior and superior endplates and the disc. If there is disc space fluid present an aspirate should also be performed.

A pedicular or posterolateral approach is favoured and sometimes both, depending on how much the patient can tolerate with an understanding that they are often in significant discomfort with limited mobility.

Samples should be sent for microbiology and also histopathology.

Image: Diagram and CT showing biopsy approach. Courtesy and copyright primal images







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ManagementThe mainstay of the management of spondylodiscitis is appropriate antimicrobial therapy, which should lead to a good outcome in the majority of cases.

Bracing is used for upto three weeks to immobilise and reduces pain, maintains stability and prevents deformity.

Surgical intervention may, however, berequired and specialist spinal surgeonsshould be involved from the outset. In cases with associated epidural abscess, urgent surgical review and close supervision is mandatory.







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Antimicrobial Therapy IThe antimicrobial regime selected is dependent on the microbiology isolated from blood culture and biopsy. Because therapy is prolonged and negative microbiology may require re-sampling, therapy is delayed until results are obtained

Antimicrobial selection is based upon 3 factors:

• The sensitivities of the organism isolated and primary source of infection, if identified.• Ability to penetrate bone and disc tissue• Side effects and route of administration

In rare circumstances empirical antibiotics may be given (after blood cultures) when the patient is overtly septic, critically ill, neutropenic or neurologically compromised.

When empirical therapy is indicated, it should be broad spectrum, but still try to focus on the likely causative organism. Good anti-staphylococcal activity (including MRSA) and gram negative cover is the mainstay of empirical treatment and in many units, regimens such as Teicoplanin and oral ciprofloxacin are used.







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Antimicrobial Therapy IIThe ability of different antimicrobials to penetrate into bone is well established, with a clear consensus on which antibiotics should be used, see the table below.

Their ability to penetrate the disc is less well understood with most evidence from animal models and in humans looking at antimicrobial concentrations in samples taken at elective surgery, following induction antibiotics.







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Antimicrobial Therapy IIISix weeks of intravenous antibiotics, followed by six weeks of oral antibiotics is the commonly used regimen. This is supported by some evidence that treatment combinations of less duration are associated with a higher recurrence rates (15% vs. 3.9%), but no randomised control trials have evaluated treatment duration.

However, there is considerable variety between and within centres and continuing debate about when to switch to oral therapy. The six weeks of intravenous therapy can often take place in the community utilising resources such as out-patient home antibiotic therapy (OPHAT).

As opposed to a fixed treatment duration, discontinuation of antimicrobials should be individually patient focused and depend on a number of factors such as normalisation of inflammatory markers and patient and radiological improvement.

Learning biteFungal discitis is often diagnosed late and treatment

delayed. Liposomal amphotericin B followed by fluconazole is used for candida infection. In cases of aspergillus spp

infection voriconazole is recommended.







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Surgical ManagementThe indications for surgical intervention in the management of spinal infection are:

• Preservation of neurological function and prevention of progression of neurological deterioration• Debridement and drainage of spinal abscess as necessary• Maintenance of spinal alignment and stability• Deformity correction for late onset symptomatic deformity

The methods for surgical intervention in spinal infection are:

1. Percutaneous/ open drainage of abscess/ collection.2. Surgical decompression of spinal canal: i.e Laminectomy for epidural

compression with or without fusion. Fusion may be instrumented or un-instrumented.

3. Column spinal reconstruction: involving vertebral body resection/debridement, anterior column column reconstruction and posterior fixation.







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Monitoring and PrognosisPatients should be followed up throughout treatment and for 1 year after its completion to detect relapses. This should include regular clinical and inflammatory marker monitoring, with interval plain radiographs. There should also be therapeutic drug monitoring when indicated.

When patients are clearly improving follow-up MRI/CT is unnecessary and images may actually worsen despite clinical improvement.

Mortality varies between 2-11%, with patients with epidural abscess having the worst prognosis.

Recurrence occurs in up to 16 of patients, particularly those who are immunosuppressed.

Factors associated with a worse prognosis include:• Diagnostic delay• Nosocomial acquisition• Neurological involvement, particularly motor weakness or paralysis.

Significant functional sequelae are observed in upto 50% of patients.







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Key points• Acute spinal infections in the form of spondylodiscitis and epidural abscess are increasing in incidence

• Diagnosis is often missed and a high index of suspicion is required

• Haematogenous spread is the most common route of infection

• Staphylococcus aureus and gram-negative bacilli are the most common causative organisms. They are often isolated from blood cultures but CT guided biopsy may be required

• Back pain and fever are commonly present. Spinal tenderness on light percussion is the most reliable sign

• Contrast enhanced MRI is the most sensitive and specific imaging modality

• Prolonged appropriate antimicrobial therapy is the mainstay of treatment, but epidural abscess often requires surgical decompression

• Follow-up is required to detect relapses and there is a significant mortality and functional morbidity associated with these conditions







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SummaryHaving completed this session you will now be able to:

• Describe the epidemiology and pathogenesis of discitis, vertebral osteomyelitis and spinal abscess

• List the likely causative organisms

• Recognise the clinical presentation and describe the approach to diagnosis, including different imaging modalities

• List the medical management, particularly anti-microbial selection and duration of treatment

• Define the role of surgical intervention, overall prognosis and follow-up

Further reading

1. Darouiche RO. Spinal Epidural Abscess. N Engl J Med 2006; 355:2012-2020.

2. Cottle L & Riordan T. Infectious spondylodiscitis. Journal of Infection 2008; 56, 401-412.







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Question 1Select the single best answer from the options given. Click on the answer to see if it is correct and read an explanation.

Which of the following statements about acute spinal infection is NOT correct?

A. Diabetes mellitus is a recognised risk factor

B. Incidence is increasing

C. Direct inoculation is the most common route of infection

D. It has a bimodal age distribution







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