Medication Summary
Medical therapy alone may be adequate in a select group of patients [100] ; however, for most, surgical aspiration and drainage is required for definitive treatment. [81, 41]
Initial empiric parenteral antimicrobial selection must take into account host status, mode of transmission, and antimicrobial CNS penetration. Immunocompromised hosts may warrant empiric coverage for fungal and parasitic infections. In general, antimicrobial selection should attempt to maximize bactericidal activity and be tolerable for weeks to months of therapy. [57, 81]
When hematogenous spread is suspected, antibiotic selection should also take into account site penetration at the source of infection. Although empiric treatment with antibiotics for several days prior to biopsy may reduce the yield, the true effect is not known.
Seizures may occur at the time of presentation or may complicate the patient’s course during disease progression and resolution; therefore, prophylaxis with anticonvulsants is a mainstay of treatment. Anticonvulsant therapy may be initiated in the emergency department and may continue until complete disease resolution, or longer. First-line agents include phenytoin, carbamazepine, valproate, and levetiracetam.
Glucocorticoids remain controversial, and many authors recommend they only be considered as a life-saving measure in an unstable patient for whom there is concern for imminent brain herniation.
Antibiotics
Class Summary
In an immunocompetent host with direct extension of infection from a contiguous site, infection is frequently polymicrobial and empiric therapy should be directed at covering anaerobes and aerobes, including Streptococcus species. In addition to Streptococcus, site-specific pathogens include the following:
- Otitis media and mastoiditis: Bacteroides, Enterobacteriaceae, Pseudomonas, Fusobacterium, Prevotella, Peptococcus, and Propionibacterium
- Sinusitis: Bacteroides, Enterobacteriaceae, S aureus, Haemophilus
- Odontogenic infection: Fusobacterium, Prevotella, Actinomyces, and Bacteroides
- Penetrating trauma or surgical: S aureus, Streptococcus, Enterobacteriaceae, and Clostridium
Treatment for these infections typically includes a third- or fourth-generation cephalosporin in combination with metronidazole. Penicillin G offers coverage for anaerobic and aerobic Streptococcus species and has excellent CNS penetration but must be used in combination with an agent that targets anaerobic gram-negative bacilli such as metronidazole. For penetrating head trauma or a postoperative patient, MRSA coverage is strongly advised.
When hematogenous infection is suspected, antimicrobial coverage must be directed towards site-specific pathogens, as follows:
- Endocarditis: S viridans, S aureus
- Pulmonary infections: Streptococcus, Fusobacterium, Corynebacterium, Peptococcus, Fusobacterium, Actinomyces, Bacteroides, Prevotella, and Nocardia
- Cardiac defects: Streptococcus and Haemophilus
- Intra-abdominal infections: Klebsiella, E coli, Enterobacteriaceae, and Streptococcus
- Urinary tract infections: Enterobacteriaceae and Pseudomonas
- Wound infection: S aureus
In many instances, antibiotics with beta-lactam–beta/lactamase inhibitor (eg, ampicillin-sulbactam, ticarcillin-clavulanate, or piperacillin-tazobactam) cross the blood-brain barrier and can be used effectively. However, overall evidence for appropriate therapy is lacking. A recent Cochrane review found that there are no randomized controlled trials addressing the effectiveness of antibiotic regimens for brain abscess in the setting of cyanotic congenital heart disease. [76]
Where MRSA is suspected, vancomycin is a frequent choice; however, some authors have argued that it has poor CNS penetration and favor linezolid. [63] MRSA infection should be suspected if the patient is postoperative following a neurosurgical procedure, in the case of penetrating head wounds, or from hematogenous spread of a known MRSA infection. MRSA infection can also be community acquired. [101, 102, 103]
For immunocompromised hosts, pathogens and treatment vary with host factors, as follows:
- HIV/AIDS infection: T gondii, Nocardia, Mycobacterium, L monocytogenes, or C neoformans
- Transplantation: Aspergillus, Candida, Mucorales, Enterobacteriaceae, Nocardia, or T gondii
- Neutropenia: Aerobic gram-negative bacilli, Aspergillus, Mucorales, or Candida
Aspergillus infection has been shown to respond to voriconazole, while amphotericin B remains a mainstay of treatment for most other fungal infections. [104, 49] First-line therapy for the protozoal infection T gondii is with pyrimethamine plus sulfadiazine. Effective first-line agents for Nocardia include sulfadiazine or trimethoprim-sulfamethoxazole. Finally, several mycotic, protozoal, and helminthic infections should be considered, in certain cases, where they are endemic to the region, as follows:
- Mycoses: H capsulatum, B dermatitidis, and C immitis
- Protozoal: T cruzi, E histolytica, Schistosoma, and Paragonimus
- Helminthic: Neurocysticercosis, caused by the larval form of T solium
In these instances, targeted therapy is required, and selection depends on the suspected organism.
When initial investigation does not reveal a likely cause of brain abscess, the recommended empiric coverage is a third- or fourth-generation cephalosporin, plus vancomycin, and metronidazole.
Ceftriaxone (Rocephin)
Ceftriaxone is a third-generation cephalosporins generally achieve effective levels in the CNS and is highly active against a broad spectrum of bacterial pathogens, including most gram-negative bacilli and aerobic streptococci. However, ceftriaxone has lower efficacy against gram-positive organisms and certain anaerobes and is therefore frequently used in combination with metronidazole. Its bactericidal effect is achieved via inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins. Ceftriaxone is stable in the presence of beta-lactamases and frequently has better efficacy against resistant organisms.
Cefepime (Maxipime)
Cefepime is a fourth-generation cephalosporin with excellent pseudomonal coverage. Gram-negative coverage is similar to ceftazidime, but it has better gram-positive coverage (comparable to ceftriaxone).
Imipenem and cilastatin (Primaxin)
This combination agent is a carbapenem with broad-spectrum activity. It is given with cilastatin, which prevents renal metabolism of imipenem. Imipenem is used for the treatment of multiorganism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential for toxicity. Caution should be used, given the association with seizure activity. It is considered to achieve somewhat poor concentrations in CSF.
Meropenem (Merrem IV)
Similar to imipenem, meropenem is a carbapenem with bactericidal broad-spectrum activity that inhibits cell-wall synthesis. It is effective against most gram-positive and gram-negative bacteria. It has slightly increased activity against gram-negatives and slightly decreased activity against staphylococci and streptococci, when compared with imipenem.
Penicillin G (Pfizerpen)
Given the high prevalence of streptococcal infection, high-dose intravenous penicillin G may be used as a first-line regimen for empiric treatment of brain abscess in the emergency department. It provides coverage for anaerobes and streptococci. It penetrates well into the CNS and, most often, the abscess cavity. However, emergence of beta-lactamase resistance limits its efficacy. It does not cover B fragilis and therefore must be used in conjunction with metronidazole.
Metronidazole (Flagyl)
Metronidazole is considered first-line therapy since it targets anaerobic bacteria as well as certain protozoal species and achieves high concentration in abscess fluid. It is frequently used in combination with a third- or fourth-generation cephalosporin or penicillin G therapy. It may be especially useful in otogenic brain abscesses.
Cefotaxime (Claforan)
Cefotaxime is a first-line agent. It covers streptococci, staphylococci, and Haemophilus and Enterobacter species. This third-generation cephalosporin has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms than earlier-generation cephalosporins. It arrests bacteria cell wall synthesis and inhibits bacterial growth by binding to 1 or more penicillin-binding proteins.
Nafcillin (Unipen)
High-dose parenteral use of nafcillin is indicated for initial treatment of staphylococcal infections that are not methicillin resistant. It is effective against penicillinase-producing staphylococci. It may be changed to oral therapy after initial intravenous treatment response. Adverse effects of parenteral administration include thrombophlebitis, and therefore recommended parenteral administration is for when short-term (24-48 h) intravenous therapy is warranted; then change to the oral route if clinically possible. Ampicillin or ampicillin/sulbactam are other potential selections.
Vancomycin (Vancocin)
Vancomycin is reserved for cases when MRSA is suspected or if the patient is penicillin-allergic. Vancomycin is effective against gram-positive organisms and has activity against enterococci. Vancomycin is bactericidal at high concentrations. It is also useful in treating septicemia and skin structure infections. The narrow therapeutic window requires frequent monitoring and dose adjustment. Adverse effects may include renal injury or red man syndrome. Random drug levels and/or trough levels are frequently monitored to avoid toxic effects.
Ceftazidime (Fortaz, Ceptaz)
Ceftazidime can be added to empiric regimens if pseudomonads are suspected. It is a third-generation cephalosporin that has a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms than many agents. It arrests bacteria cell wall synthesis and inhibits bacterial growth by binding to 1 or more penicillin-binding proteins.
Corticosteroids
Class Summary
The use of corticosteroids in brain abscess is controversial. Intravenous steroids are usually reserved for patients who have severely increased intracranial pressure, either from mass effect or substantial edema around the periphery of the abscess. Steroids are thought to reduce intracranial pressure by decreasing edema via their anti-inflammatory properties. However, steroid use may also decrease antibiotic penetration, as well as slow the encapsulation of the suppurative fluid, thus potentially offsetting the beneficial effects. Significant and potentially serious metabolic adverse effects can occur with high dosages.
Dexamethasone (Decadron, Dexasone)
Dexamethasone is the corticosteroid of choice for reducing intracranial pressure. It is used in the treatment of inflammatory diseases. It may decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
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Brain abscess.
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Sagittal (a) and axial (b) gadolinium-enhanced T1-weighted MRI images from a patient who presented with headache, word-finding difficulties, stuttering speech, and right hand/foot numbness. Note the peripheral enhancement of a lesion in the left insula with surrounding edema.
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CT (a) and T2 fluid-attenuated inversion recovery (FLAIR) MRI (b, c) images from the same patient as the first image. Images a and b were obtained at the time of initial diagnosis, and image c was obtained 5 months later following successful treatment.
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Diffusion-weighted (a), T2 fluid-attenuated inversion recovery (FLAIR) (b), and post-gadolinium enhanced T1-weighted (c) images from a patient who presented initially with vomiting, followed by fever and coma. Numerous abscesses are demonstrated with coalescence in the right occipital and basal ganglia with surrounding edema and midline shift.
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Axial (a) and coronal (b) CT images from the same patient as the third image. Multiple hypodensities with cerebral edema and mass effect are noted.
