eMedicine Specialties > Infectious Diseases > CNS Infections

Brain Abscess: Treatment & Medication

Author: Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Contributor Information and Disclosures

Updated: Jun 26, 2008

Treatment

Medical Care

Before the abscess has become encapsulated and localized, antimicrobial therapy, accompanied by measures to control increasing intracranial pressure, is essential.²¹ Once an abscess has formed, surgical excision or drainage combined with prolonged antibiotics (usually 4-8 wk) remains the treatment of choice. Some neurosurgeons advocate complete evacuation of the abscess, while others advocate repeated aspirations as indicated.²²

• The first step is to verify the presence, size, and number of abscesses using contrast CT scanning or MRI.
• Emergent surgery should be performed if a single abscess is present. Abscesses larger than 2.5 cm are excised or aspirated, while those smaller than 2.5 cm or which are at the cerebritis stage are aspirated for diagnostic purposes only.
• In cases of multiple abscesses or in abscesses in essential brain areas, repeated aspirations are preferred to complete excision. High-dose antibiotics for an extended period may be an alternative approach in this group of patients.
• An early effort at making a microbiologic diagnosis is important in planning appropriate antimicrobial therapy. The introduction of CT-guided needle aspiration may provide this important information. Frequent scanning, at least once per week, is essential in monitoring treatment response. Although surgical intervention remains an essential treatment, selected patients may respond to antibiotics alone.²³
• Corticosteroid use is controversial. Steroids can retard the encapsulation process, increase necrosis, reduce antibiotic penetration into the abscess, increase the risk of ventricular rupture, and alter the appearance on CT scans. Steroid therapy can also produce a rebound effect when discontinued. If used to reduce cerebral edema, therapy should be of short duration. The appropriate dosage, the proper timing, and any effect of steroid therapy on the course of the disease are unknown.
• Numerous factors should be considered when trying to decide the appropriate approach to therapy.
• Abscesses smaller than 2.5 cm generally respond to antimicrobial therapy, while abscesses larger than 2.5 cm have failed to respond to such treatment.
• Knowledge of the etiologic agent or agents by recovery from blood, CSF, abscess, or other normally sterile sites is essential because it allows for the most appropriate selection of antimicrobial agents.
• The duration of the symptoms before diagnosis is an important factor. Bacterial abscess in the brain is preceded by infarction and cerebritis. Antibiotic therapy during the early stage, when no evidence of an expanding mass lesion exists, may prevent the progress from cerebritis to abscess.
• Patients who have symptoms for less than a week have a more favorable response to medical therapy than patients with symptoms persisting longer than 1 week.
• Patients treated with medical therapy alone usually demonstrate clinical improvement before significant changes in the CT scan are observed.
• CT scanning and MRI should eventually show a decrease in the size of the lesion, a decrease in accompanying edema, and a lessening of the enhancement ring. Improvement on CT scans is generally observed within 1-4 weeks (average, 2.5 wk) and complete resolution in 1-11 months (average, 3.5 mo).
• The antimicrobial treatment of the brain abscess is generally long (6-8 wk) because of the prolonged time needed for brain tissue to repair and close abscess space. The initial course is through an intravenous route, often followed by additional 2-6 months of appropriate oral therapy. A shorter course (3-4 wk) may be adequate in patients who underwent surgical drainage.
• Because of the difficulty involved in the penetration of various antimicrobial agents through the blood-brain barrier, the choice of antibiotics is restricted, and maximal doses are often necessary.
• Initial empiric antimicrobial therapy should be based on the expected etiologic agents according to the likely predisposing conditions, the primary infection source, and the presumed pathogenesis of abscess formation. When abscess specimens are available, staining of the material can help guide selection of therapy. Whenever proper cultures are taken and organisms are isolated, the initial empiric therapy can be adjusted to specifically treat the isolated bacteria.²⁴
• Coverage for streptococci can be attained by a high dose of penicillin G or a third-generation cephalosporin (eg, cefotaxime, ceftriaxone). Metronidazole is included to cover penicillin-resistant anaerobes (ie, gram-negative bacilli).
• When S aureus is suspected (following neurosurgery or trauma), nafcillin or vancomycin (when methicillin resistance or penicillin allergy is present) is administered.
• Cefepime or ceftazidime is administered to treat Pseudomonas aeruginosa infection.
• Patients with HIV infection may require therapy for toxoplasmosis.
• Specific antibiotics²⁵   
• Penicillin penetrates well into the abscess cavity and is active against non–beta–lactamase-producing anaerobes and aerobic organisms.
• Chloramphenicol penetrates well into the intracranial space and is also active against Haemophilus species, S pneumoniae, and most obligate anaerobes. Its use has been curtailed dramatically in most US centers because of the availability of other equally efficacious and less toxic antimicrobial combinations (ie, cefotaxime plus metronidazole).
• Metronidazole penetrates well into the CNS and is not affected by concomitant corticosteroid therapy. However, it is only active against strict anaerobic bacteria, and its activity against anaerobic gram-positive cocci may be suboptimal.
• Third-generation cephalosporins (eg, cefotaxime, ceftriaxone) generally provide adequate therapy for aerobic gram-negative organisms. If pseudomonads are isolated or anticipated, the parenteral cephalosporin of choice is either ceftazidime or cefepime.
• Aminoglycosides do not penetrate well into the CNS and are relatively less active because of the anaerobic conditions and the acidic contents of the abscess.
• Beta-lactamase–resistant penicillins (eg, oxacillin, methicillin, nafcillin) provide good coverage against methicillin-sensitive S aureus. However, their penetration into the CNS is less than penicillin, and the addition of rifampin has been shown to be of benefit in staphylococcal meningitis.
• Vancomycin is most effective against methicillin-resistant S aureus and Staphylococcus epidermidis as well as aerobic and anaerobic streptococci and Clostridium species.
• With the exception of the Bacteroides fragilis group and some strains of Prevotella species, Porphyromonas species, and Fusobacterium species, most of the anaerobic pathogens isolated are sensitive to penicillin. Because these penicillin-resistant anaerobic organisms predominate in brain abscesses, empiric therapy should include agents effective against them that can also penetrate the blood-brain barrier. These include metronidazole, chloramphenicol, ticarcillin plus clavulanic acid, imipenem, and meropenem.
• Caution should be used in administering carbapenems and beta-lactamases in general, because high doses of these agents may be associated with seizure activity. Imipenem has been associated with an increased risk of seizures in patients with brain abscess. Although fluoroquinolones have good penetration into the CNS, data are limited regarding their use in treating brain abscesses.
• Therapy with penicillin should be added to metronidazole to cover aerobic and microaerophilic streptococci.
• The administration of beta-lactamase–resistant penicillin or vancomycin (if methicillin-resistant staphylococci are isolated) for the treatment of S aureus is generally recommended.
• Amphotericin B is administered for Candida, Cryptococcus, and Mucorales infections; voriconazole for Aspergillus and P boydii infections.
• T gondii infection is treated with pyrimethamine and sulfadiazine.
• Injection of antibiotics into the abscess cavity was advocated in the past in an effort to sterilize the area before operation. However, many antimicrobials penetrate brain abscess cavities fairly well, and instillation of antibiotics into the abscess after drainage is not needed.

Surgical Care

Surgical drainage provides the most optimal therapy. The procedures used are aspiration through a bur hole and complete excision after craniotomy.

Aspiration is the most common procedure and is often performed using a stereotactic procedure with the guidance of CT scanning or MRI.²² For optimal results, this is usually performed prior to the initiation of antibiotic therapy. Craniotomy is generally performed in patients with multiloculated abscesses and in those whose conditions fail to resolve.²⁶

Ventricular drainage combined with administration of intravenous and/or intrathecal antimicrobials is used to treat brain abscesses that rupture into the ventricles.

• If not recognized early, both subdural empyema and brain abscess can be fatal. Emergent surgery is needed if neurologic signs related to a mass lesion progress.
  • Antibiotics have improved the outlook.
  • Management of subdural empyema requires prompt surgical evacuation of the infected site and antimicrobial therapy.
  • Failure to perform surgical drainage can lead to a higher mortality rate.
• Although proper selection of antimicrobial therapy is most important in the management of intracranial infections, surgical drainage may be required. Optimal therapy of fungal brain abscess generally requires both medical and surgical approach.
  • A delay in surgical drainage and decompression can be associated with high morbidity and mortality.
  • Recent studies illustrate that brain abscess in the early phase of cerebritis may respond to antimicrobial therapy without surgical drainage.
  • Surgical drainage may be necessary in many patients to ensure adequate therapy and complete resolution of infection.
• Patients who do not meet the criteria for medical therapy alone require surgery. Currently, 2 surgical approaches are available: stereotactic-guided aspiration and excision. Needle aspiration is generally preferred to surgical excision because it results in fewer sequelae. Drainage may be delayed or avoided if the infection is at the cerebritis stage or the lesion is at a vital or inaccessible region.
  • The risk of repeating aspiration is that the procedure may cause bleeding.
  • Excision is clearly indicated in posterior fossa or multiloculated abscesses, those caused by unencapsulated lesions due to fungal or helminthic infection, those associated with traumatic brain injury (to remove foreign material), and those that reaccumulate following repeated aspirations. Excision is also indicated in patients with depressed sensorium, increased intracranial pressure, no clinical improvement within 7 days, and/or a progressively growing abscess.

Consultations

The management of a patient in whom a brain abscess is suspected or present involves cooperation among neurologists, neurosurgeons, and infectious disease specialists. Other specialists may be consulted as required by the patient's condition. The primary source of the infection may require the attention of specialists. This includes drainage of an infected sinus by an otolaryngologist or treatment of a dental infection (eg, periodontal abscess) by an oral surgeon or dentist.

Medication

The choice of combinations of empiric therapy must cover a broad spectrum of both aerobic and anaerobic bacterial pathogens. Predisposing factors include the following:

• Otitis, mastoiditis, and sinusitis - Combination of metronidazole plus a third-generation cephalosporin (in those with a predisposing condition)
• Dental infection - Penicillin plus metronidazole
• Pulmonary infections - Penicillin plus metronidazole and a sulfonamide (for Nocardia infections)
• Congenital heart disease - Third-generation cephalosporin with or without ampicillin
• Endocarditis - Vancomycin plus gentamicin
• Intravenous drug abuse - Nafcillin or vancomycin plus cefepime or ceftazidime
• Trauma - Vancomycin plus a third-generation cephalosporin
• Postsurgical - Vancomycin, cefepime or ceftazidime, and metronidazole
• Complications of meningitis in infants - Cefotaxime, ampicillin, and vancomycin
• No predisposing condition - Metronidazole, vancomycin or a third- or fourth-generation cephalosporin

Injection of antibiotics into the abscess cavity was advocated in the past in an effort to sterilize the area before operation. However, many antimicrobials penetrate brain abscess cavities fairly well, and instillation of antibiotics into the abscess after drainage is not needed.

The anti-inflammatory effects of corticosteroid therapy can decrease cerebral edema, reducing intracranial pressure. These benefits are offset somewhat by the fact that steroid use decreases antibiotic penetration into the abscess and may slow encapsulation of the abscess site.

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotic combinations are usually recommended for serious gram-negative bacillary infections. This approach ensures coverage for a broad range of organisms and polymicrobial infections. In addition, it prevents resistance from bacterial subpopulations and provides additive or synergistic effects. Once organisms and sensitivities are known, the use of antibiotic monotherapy is then recommended.

Ampicillin (Marcillin, Omnipen)

Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

Cefotaxime (Claforan)

Third-generation cephalosporin that has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. By binding to 1 or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth.

Ceftriaxone (Rocephin)

Third-generation cephalosporin that has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. By binding to 1 or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth.

Ceftazidime (Fortaz, Ceptaz, Tazidime)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.

Chloramphenicol (Chloromycetin)

Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.

Imipenem plus cilastatin (Primaxin)

For treatment of multiple organism infections in which other agents do not have wide spectrum coverage or are contraindicated due to potential for toxicity.

Meropenem (Merrem)

Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared to imipenem.

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for C difficile enterocolitis). May be absorbed into the cells, and the intermediate-metabolized compounds that bind DNA are then formed and inhibit synthesis, causing cell death.

Vancomycin (Vancocin)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci. To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use creatinine clearance to adjust dose in patients with renal impairment.

Cefepime (Maxipime)

Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Dexamethasone (Decadron, Dexasone)

Corticosteroid of choice for reducing intracranial pressure. Used in treatment of inflammatory diseases. May decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

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