Guideline for Management of Brain Abscess and Subdural Empyema

• Summary
  Click here to print a Quick Reference Guide
• Background
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Directed Antimicrobial Treatment (when microbiology results are known)
• Duration of Treatment
• Switch to oral agent(s)

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Brain abscess is a focal, intracerebral infection which usually begins as an area of cerebritis and develops into a collection of pus surrounded by a well-vascularised capsule. A brain abscess is initiated when micro-organisms are introduced into the brain tissue following trauma, contiguous pericranial infection, meningitis or haematogenous dissemination from a distant infective focus. Early studies reported that 40% of brain abscesses are associated with otitis media, but this number has been decreasing. (Sennaroglu & Sozeri, 2000). Brain abscess secondary to otogenic source are usually localized to the temporal lobe or cerebellum. Paranasal sinusitis continues to be an important predisposing condition with frontal lobe as the predominant abscess site, although the temporal lobe or sella turcica is the usual site when brain abscess complicates sphenoid sinusitis.

Haematogenous dissemination to the brain from a distant focus of infection usually results in multiple and multiloculated abscesses with a higher mortality rate. Brain abscess is rare after bacterial endocarditis (less than 5% of cases in most series) despite the presence of continuous bacteraemia. (Tunkel & Kaye,1993; Tunkel & Pradhan, 2002). However, about 20-30% of cases are classified as cryptic brain abscess, for which no obvious focus can be identified. ( Mathisen and Johnson, 1997)

Advances in modern neurosurgical techniques, newer antimicrobials and powerful imaging technologies have facilitated the diagnosis and management of intracranial pyogenic suppurations over past 20 years; however, it still remains a potentially fatal central nervous system infection. In one study of factors influencing the outcome in 39 cases of bacterial brain abscess, the prognosis was primarily determined by the rapidity of progression of the disease before hospitalization and the patient’s mental status on admission.( Seydoux & Francioli, 1992) Early recognition of predisposing conditions is important for improving the overall outcome. The relative frequency of mixed bacterial infections, limitations of anaerobic culture techniques, increase in immunosuppressed patients, decreased incidence of otogenic brain abscess and an increased incidence of post-traumatic or post-operative brain abscess have changed the epidemiology and clinical spectrum of brain abscess in recent years.

Predisposing conditions and microbiology of brain abscess

Clinical presentation

The clinical features in patients with an intracranial abscess evolve with time and depend upon the host pathogen interactions and location of the brain abscess.

Headache is the most common presenting symptom and is seen in almost all patients who are able to give a history. However, the headache is usually without particularly distinguishing features, accounting for frequent delays in diagnosis. Less than 50% of patients present with classical triad of fever, headache and neurological deficit. Absence of fever should not be used to exclude the diagnosis of brain abscess. (Chun et al, 1986). The presence of focal neurological findings (e.g., hemiparesis, hemisensory deficits, aphasia, and ataxia) depends on the location of the abscess, and these findings are seen in approximately one-third to one-half of cases. In addition, the clinical presentation in an immunocompromised patient may be masked by the diminished inflammatory response. Constitutional symptoms and signs (pyrexia, rigors, dehydration, and neck stiffness) and clinical features due to an infected source elsewhere in the body are surprisingly uncommon at the time of presentation.

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Unfortunately, there are no laboratory data that are pathognomic of brain abscess. WCC may be normal. CRP is usually elevated in up to 60% of patients, sometimes may be normal.

Recommendation: Blood cultures should be obtained when a diagnosis of brain abscess is suspected.
[Evidence Level B]
Hematogenous spread may be the source, and a positive blood culture result may help guide therapy once an organism and sensitivities are identified.

Recommendation: Lumbar puncture (LP) should be deferred in any case for which brain abscess is suspected because of the potential for CNS herniation and low likelihood of positive cultures.
[Evidence Level B]

The presence of any focal neurological finding or papilledema is an absolute indication for CT imaging prior to LP. CT scanning, preferably with contrast administration, provides a rapid means of detecting the size, the number, and the location of abscesses, and it has become the mainstay of diagnosis and follow-up care. MRI scanning demonstrates soft-tissue resolution and imaging details superior to CT scan (early recognition of cerebritis). An abscess appears as a ring-enhancing, space demanding process. The ring of enhancement is usually quite linear without the heterogeneous appearances characteristic of a malignant glioma. The most frequent abscess locations are frontal, temporal or cerebellar. They are usually sub-cortical, but small abscesses may abut the grey-white matter interface in the middle cerebral artery territory. A CT or MRI scan may also reveal an infected source such as a paranasal sinus or an ear infection.

Serial CT or MRI scans are crucial because abscesses may enlarge despite antibiotic treatment. If neurological deterioration occurs as a consequence of mass effect, surgical removal may become necessary.

Recommendation: Brain abscess pus (collected in a sterile universal container, NOT SWAB) should be sent to Microbiology for urgent microscopy, culture and sensitivity whenever possible.
[Evidence level B]
Careful culturing of abscess material obtained at the time of surgery provides the best opportunity to make a microbiological diagnosis.

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The treatment for brain abscess is a team approach, with collaboration between a Microbiologist, neuroradiologist, and neurosurgeon. No randomized controlled trials of therapies for brain abscess have been conducted because of the relative infrequency.

Antimicrobial therapy
Appropriate antimicrobial therapy for brain abscess depends on choosing antibiotics that are able to penetrate the abscess cavity and have activity against the suspected pathogens. Although there are considerable data on CSF antimicrobial levels in cases of bacterial meningitis, there is still limited information available on antimicrobial penetration into brain abscess cavities. The blood-CSF and the blood-brain barriers are histologically different and a high degree of CSF penetration does not guarantee penetration into the brain tissue. The third generation cephalosporins have good penetration into brain abscess cavities and excellent in-vitro activity against many of the pathogens isolated from brain abscesses. Concentrations of Penicillin G have been measured in brain abscess pus but it may get inactivated in pus, with the result that cultures may remain positive despite adequate penicillin concentrations. Vancomycin has also been shown to achieve excellent concentrations in abscess fluid after prolonged therapy. (Mandell, Douglas & Bennett’s Infectious Diseases, 7th edition)

Brain abscesses are frequently polymicrobial, the most common causative organisms in clinical series have been microaerophilic streptococci and anerobic bacteria. Additional organisms such as Staphylococcus aureus and Enterobacteriaceae (“coliforms”) are also seen depending on the underlying source.

Initial empirical therapy needs to be commenced as soon as the diagnosis is established and should be tailored to cover the most likely pathogens in individual cases depending upon the location of the abscess and predisposing focus (dental, paranasal sinuses, otogenic etc.). In most cases, attempts to biopsy the lesion to obtain a specimen for culture are essential, since the isolation of pathogenic bacteria allows for more selective antimicrobial therapy.

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Surgical management
Drainage or excision remains the treatment of choice for most brain abscesses (using ultrasound, frameless or frame based stereotaxy). Drainage allows control of intracranial pressure as well as microbiological diagnosis. Surgery also reduces the bulk of an abscess providing symptomatic relief and minimising the risks of abscess growth (intraventricular rupture, herniation, venous sinus thrombosis).

Abscesses require regular imaging follow-up and if on subsequent imaging the abscess appears to be re-accumulating, further drainage may be required. Very occasionally simple burr hole drainage is insufficient and in these cases (especially peripherally located abscesses) consideration should be given to excising the abscess. Abscesses may be associated with significant oedema and the use of Mannitol and/or steroids may be considered – although the use of the latter in the setting of infection is not ideal. Cerebral abscess formation is associated with a significant risk of epilepsy and while prophylactic administration with anticonvulsants in most forms of neurosurgery remains unproven, the rate of epilepsy associated with cerebral abscess formation is such that it is reasonable to consider giving prophylactic anticonvulsants. The installation of antibiotics into the abscess cavity is not recommended. One of the risks – both from treatment and spontaneously is the rupture of the abscess into the ventricular system. This is associated with an 80% mortality rate. If rupture does occur, the recommendation is for a craniotomy to be performed and the abscess excised and at the same time for the ventricular system to be “washed out” using normal saline. At the end of the procedure an EVD should be placed so that intrathecal antibiotics can be administered.

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*Dose may be increased to 3g in certain instances.
** Use ceftazidime as third generation cephalosporin if Pseudomonas infection suspected.
Contact Medical Microbiologist for advice if any risk factors for MRSA or resistant gram negative infections.

There have been a number of more recent case reports demonstrating successful non-operative treatment of brain abscess with antibiotics alone. This approach may be appropriate for clinically stable patients who are poor candidates for surgery or for patients with surgically inaccessible lesions. Small lesions (2 cm) located in the better-vascularized cortical areas are more likely to respond to antibiotics alone. Medical treatment alone should not be used when the diagnosis is in doubt or when pathological confirmations are not available.

Treatment of Primary Focus
To minimise the risk of recurrent or non-responsive intracranial infection any identifiable primary source requires aggressive treatment. This may include surgery for paranasal, middle ear or dental sepsis, physiotherapy and antibiotics for pulmonary infection and surveillance echocardiograms in patients with a cardiac source. The timing of such interventions does not need to coincide with intracranial surgery but should be undertaken in an expert, timely fashion.

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Targeted Antimicrobial Therapy

**Dose adjusted according to estimated Creatinine clearance; need to monitor Vancomycin trough levels.

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Recommended duration of therapy are:

• 3-4 weeks if abscess has been excised
• 4-6 weeks if abscess has been aspirated
• minimum of 4 weeks if abscess treated with antibiotics alone (demonstrate resolution of ring enhancing lesions on CT before stopping antibiotics)

[Evidence Level C]

The appropriate duration of antimicrobial therapy for brain abscess remains unclear. The recommendations based on past clinical practice favour a minimum of 4-6 weeks of therapy if the abscess has been excised or aspirated or 6-8 weeks, if the patient has been treated conservatively. More recently, shorter durations of antibiotic therapy have been proposed provided the aetiological organisms are susceptible and that adequate surgical drainage can be established based on correlation between clinical progress and CT findings.

CT scans are unreliable in measuring response to treatment since radiological changes lag behind both the reduction in size of the cavity and the clinical response. Provided the patient remains stable, repeating the scan at weekly intervals for 2 weeks and then at fortnightly intervals for a further 1-month enables re-accumulation of the abscess to be detected at a pre-clinical phase.

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Recommendation: Patients can be switched onto oral therapy when:

• CRP falls to normal levels if the patient is otherwise well.
•  Patient has no signs of fever.
• Appropriate oral agents are available.
• The patient can tolerate oral antibiotics.
  [Evidence Level C]

Please contact Microbiology to discuss oral antimicrobial options.

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