Intracranial abscesses are uncommon, serious, life-threatening infections. They include brain abscess and subdural or extradural empyema and are classified according to the anatomical location or the etiologic agent. The term brain abscess is used in this article to represent all types of intracranial abscesses.[1]
Intracranial abscesses can originate from infection of contiguous structures (eg, otitis media, dental infection, mastoiditis, sinusitis) secondary to hematogenous spread from a remote site (especially in patients with cyanotic congenital heart disease), after skull trauma or surgery, and, rarely, following meningitis. In at least 15% of cases, no source can be identified.[2]
In recent years, the complex array of etiologic agents that cause brain abscess has become better understood.
Brain abscess is caused by intracranial inflammation with subsequent abscess formation. The most frequent intracranial locations (in descending order of frequency) are frontal-temporal, frontal-parietal, parietal, cerebellar, and occipital lobes.[3] In at least 15% of cases, the source of the infection is unknown (cryptogenic).[4]
Infection may enter the intracranial compartment directly or indirectly via 3 routes.
Contiguous suppurative focus (45-50% of cases)
Direct extension usually causes a single brain abscess and may occur from necrotic areas of osteomyelitis in the posterior wall of the frontal sinus, the sphenoid and ethmoid sinuses, mandibular dental infections, as well as from subacute and chronic otitis media and mastoiditis.[5] This direct route of intracranial extension is more commonly associated with subacute and chronic otitic infection and mastoiditis than with sinusitis.[6]
Subacute and chronic otitis media and mastoiditis generally spread to the inferior temporal lobe and cerebellum. Frontal or ethmoid sinus spread to the frontal lobes. Odontogenic infections can spread to the intracranial space via direct extension or a hematogenous route. Mandibular odontogenic infections also generally spread to the frontal lobe.
The frequency of brain abscesses resulting from ear infections has declined in developed countries. However, abscesses complicating sinusitis has not decreased in frequency.[7, 8] Contiguous spread could extend to various sites in the central nervous system, causing cavernous sinus thrombosis; retrograde meningitis; and epidural, subdural, and brain abscess.
The valveless venous network that interconnects the intracranial venous system and the vasculature of the sinus mucosa provides an alternative route of intracranial bacterial entry. Thrombophlebitis originating in the mucosal veins progressively involves the emissary veins of the skull, the dural venous sinuses, the subdural veins, and, finally, the cerebral veins. By this mode, the subdural space may be selectively infected without contamination of the intermediary structure; a subdural empyema can exist without evidence of extradural infection or osteomyelitis.
Intracranial extension of the infection by the venous route is common in paranasal sinus disease, especially in acute exacerbation of chronic inflammation. Chronic otitis media and mastoiditis generally spread to the inferior temporal lobe and cerebellum, causing frontal or ethmoid sinus infection and dental infection of the frontal lobe.[9]
Trauma (10% of cases)
Trauma that causes an open skull fracture allows organisms to seed directly in the brain. Brain abscess can also occur as a complication of intracranial surgery, and foreign body, such as pencil tip, lawn dart, bullets, and shrapnel. Occasionally brain abscess can develop after trauma to the face.
Hematogenous spread from a distant focus (25% of cases)
These abscesses are more commonly multiple and multiloculated and are frequently found in the distribution of the middle cerebral artery. The most common effected lobes (in descending frequency) are the fontal, temporal, parietal, cerebellar, and occipital.[10]
Hematogenous spread is associated with cyanotic heart disease (mostly in children), pulmonary arteriovenous malformations, endocarditis, chronic lung infections (eg, abscess, empyema, bronchiectasis), skin infections, abdominal and pelvic infections, neutropenia, transplantation,[11] esophageal dilatation, injection drug use,[12] and HIV infection.
Before the emergence of the AIDS pandemic, brain abscesses were estimated to account for 1 per 10,000 hospital admissions, or 1500-2500 cases annually.[2] The prevalence of brain abscess in patients with AIDS is higher, so the overall rate has thus increased.[13] The frequency of fungal brain abscess has increased because of the frequent administration of broad-spectrum antimicrobials, immunosuppressive agents, and corticosteroids.
International
Brain abscesses are rare in developed countries but are a significant problem in developing countries. The predisposing factors vary in different parts of the world.
Mortality/Morbidity
With the introduction of antimicrobics and the increasing availability of imaging studies, such as CT scanning and MRI, the mortality rate has decreased to less than 5-15%. Stroke, older age, septicemia, pneumonia, meningitis, and hepatitis were associated with increased risk of in-hospital mortality. Ong et al[14] reported that the in-hospital mortality rate increases with age, from 4.22% among patients aged 0-14 years to 17.34% among individuals older than 60 years. Rupture of a brain abscess, however, is associated with a high mortality rate (up to 80%).
The frequency of neurological sequelae in persons who survive the infection varies from 20-79% and is predicated on how quickly the diagnosis is reached and antibiotics administered.[15]
Sex
Brain abscesses are more common in males than in females.
Age
Brain abscesses occur more frequently in the first 4 decades of life. Because the main predisposing cause of subdural empyema in young children is bacterial meningitis, a decrease in meningitis due to the Haemophilus influenzae vaccine has reduced the prevalence in young children.
In about two thirds of patients with brain abscess, symptoms are present for 2 weeks or less. The clinical course ranges from indolent to fulminant.
Most symptoms are a result of the size and location of the space-occupying lesion or lesions.
The triad of fever, headache (often severe and on the side of the abscess), and focal neurologic deficit occurs in less than half of patients. The frequency of common symptoms and signs is as follows:[1]
Headache - 70%
Mental status changes (may indicate cerebral edema) - 65%
Focal neurologic deficits - 65%
Fever - 50%
Seizures - 25-35%
Nausea and vomiting - 40%
Nuchal rigidity - 25%
Papilledema - 25%
A suddenly worsening headache, followed by emerging signs of meningismus, is often associated with rupture of the abscess.
The clinical manifestations of brain abscess are initially nonspecific, which can lead to delay in diagnosis. Brain abscess usually manifests as symptoms of a space-occupying lesion. The symptoms and signs include the following:
Low-grade or high-grade fever
Persistent headache (often localized)
Drowsiness
Confusion
Stupor
General or focal seizures
Nausea and vomiting
Focal motor or sensory impairments
Papilledema
Ataxia
Hemiparesis
Neck stiffness
Localized neurologic signs are eventually found in most patients. The signs and/or symptoms are a direct function of the intracranial location of the abscess, as follows:
Cerebellar abscess - Nystagmus, ataxia, vomiting, and dysmetria
Frontal abscess - Headache, inattention, drowsiness, mental status deterioration, motor speech disorder, hemiparesis with unilateral motor signs, and grand mal seizures
Temporal lobe abscess - Headache, ipsilateral aphasia (if in the dominant hemisphere), and visual defects
Occipital abscess- Neck rigidity
In the initial stages of the infection, an abscess can manifest as a nonspecific form of encephalitis accompanied by signs of increased intracranial pressure.
The headache associated with brain abscess can gradually develop or suddenly emerge and is often localized to the abscess' side. It is often severe and is not relieved by mild pain medications.
Papilledema may develop in older child and adults, and younger infants may exhibit bulging fontanels. This is a late expression of cerebral edema.
A ruptured brain abscess may produce purulent meningitis associated with signs of neurologic damage.
Vomiting commonly develops in association with increased intracranial pressure. Changes in mental status (lethargy progressing to coma) suggest severe cerebral edema.
Specific clinical symptoms are characteristic of some pathogens.
The microbial etiology of brain abscess depends on the patient's age, site of primary infection, and the patient's immune status.[16, 17]
Anaerobic and microaerophilic cocci and gram-negative and gram-positive anaerobic bacilli are the most important isolates. A significant number of brain abscesses are polymicrobic.[16, 17, 18, 19, 20]
Oral flora anaerobes generally originate from infected ears and sinuses and abdominal anaerobes (Bacteroides fragilis group) reach the intracranial cavity through bacteremia.
The predominant organisms include the following:
Staphylococcus aureus, including methicillin-resistant[21]
Aerobic, anaerobic, and microaerophilic streptococci, including alpha-hemolytic streptococci and Streptococcus anginosus (milleri) group (Streptococcus anginosus, Streptococcus constellatus, and Streptococcus intermedius)
Prevotella and Fusobacterium species and B fragilis
Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli, Enterobacter species, and Proteus species)[22]
Pseudomonas species
Other anaerobes (Veillonella, Eubacterium)
Less common causes include the following:
H influenzae
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus aphrophilus
Other Enterobacteriacae (Enterobacter species, Actinobacillus, actinomycetemcomitans, and Salmonella species)
Burkholderia pseudomallei (also known as Pseudomonas pseudomallei)[23]
HIV infection -T gondii, Mycobacterium, Cryptococcus, Nocardia, L monocytogenes[13]
Living, visiting, or immigrating from an endemic area: Taenia solium (causing cysticercosis), Schistosoma japonicum, Entamoeba histolytica, and Paragonimus species.
Al Masalma et al performed a 16S rDNA-based metagenomic analysis of cerebral abscesses and identified 80 distinct bacterial taxa, including 44 not previously described in brain abscess. Therefore, microbial flora of brain abscesses is far from being fully known and is differentially distributed depending on the abscess etiology. Further studies are warranted to determine the significance of the identification of the newly recovered bacteria associated within brain abscesses.[35]
Routine tests in patients with brain abscess include the following:
CBC count with differential and platelet count
Erythrocyte sedimentation rate (ESR; elevated in up to two thirds of patients)
Serum C-reactive protein (CRP) or Westergren sedimentation rate
Serological tests for some pathogens (eg, serum immunoglobulin G antibodies, CSF polymerase chain reaction [PCR] for Toxoplasma)
Blood cultures (at least 2; preferably before antibiotic usage)
Moderate leukocytosis is present, and the ESR and CRP level are generally elevated. Serum sodium levels may be low because of inappropriate antidiuretic hormone production. Platelet counts may be high or low.
Cerebrospinal fluid[36]
A lumbar puncture is rarely warranted and is contraindicated if increased intracranial pressure is present because of the potential for CNS herniation and death. The results are usually unrewarding, consisting of an elevated protein level, pleocytosis with variable neutrophil count, a normal glucose level, and sterile cultures. A lumbar puncture is mostly of value to rule out other disease processes, especially bacterial meningitis. CT imaging or MRI scanning prior to lumbar puncture is absolutely indicated upon the presence of any focal neurologic finding or papilledema.[37]
The white blood cell count is generally high. It reaches 100,000/µL or higher when the abscess ruptures into the ventricle. Many red blood cells are generally observed at that time, and the CSF lactic acid level is then elevated to more than 500 mg.[38]
Abscess aspirate (obtained via stereotactic CT or surgery)[2]
Culture aspirates of abscesses for aerobic, anaerobic, and acid-fast organisms and fungi
Gram stain, acid-fast stain (for Mycobacterium), modified acid-fast stain (for Nocardia), and special fungal stains (eg, methenamine silver, mucicarmine)
Serology anti-anticysticercal antibodies for the diagnosis of neurocysticercosis
Histopathological examination of the brain tissue
16S Ribosomal sequencing - Several studies using 16S ribosomal DNA polymerase chain reaction amplification increased the number of bacterial species recovered from brain abscesses as compared with standard culture.[35, 39]
CT scanning has made other tests, such as angiography, ventriculography, pneumoencephalography, and radionuclide brain scanning, almost obsolete in the workup of brain abscess. CT is not as sensitive as MRI but is easier to perform.
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. This method is used to confirm the diagnosis, to localize the lesion, and to monitor the progression after treatment. However, CT scan results can lag behind clinical findings.[40]
After the injection of a contrast material, CT scans characteristically show the brain abscess as a hypodense center with a peripheral uniform enhancement ring. Rarely, a well-organized abscess wall fails to generate such ring enhancement.
In the earlier cerebritis stages, CT scans show nodular enhancement with areas of low attenuation without enhancement. As the abscess forms, contrast enhancement is observed. After encapsulation, the contrast material cannot help differentiate the clear center and the CT scan is similar in appearance to those obtained during the early cerebritis stage.
See the image below.
View Image
CT scan of a brain abscess.
Many authorities consider MRI to be the first diagnostic method in the diagnosis of brain abscess. It allows for accurate diagnosis and excellent follow-up of the lesions because of its superior sensitivity and specificity. Compared with CT scanning, MRI offers a better ability to detect cerebritis, greater contrast between cerebral edema and the brain, and earlier detection of satellite lesions and the spread of inflammation into the ventricles and subarachnoid space.
See the image below.
View Image
MRI of a brain abscess.
Contrast enhancement with gadolinium diethylenetriaminepentaacetic acid (a paramagnetic agent) helps differentiate the abscess, the enhancement ring, and the cerebral edema around the abscess. T1-weighted images enhance the abscess capsule, and T2-weighted images can demonstrate the edema zone around the abscess.[41]
Diffusion-weighted (magnetic resonance) imaging (DWI) can be used to differentiate between ring-enhancing lesions caused by brain abscess (hypertensive on DWI) from a malignant lesion (hypotensive on DWI).[42]
Susceptibility-weighted phase imaging showed evidence of paramagnetic substances in agreement with the presence of free radicals from phagocytosis in a study of 14 patients with brain abscesses.[43] This technique may provide additional information that is valuable in the characterization of pyogenic brain abscesses.
Since the advent of CT scanning and MRI, the case-fatality rate has decreased by 90%.
ECG occasionally reveals a focus of high voltage with slow activity. It is nonspecific and rarely of value in confirming a diagnosis of brain abscess. This is the least accurate procedure in the diagnostic evaluation.
Biopsy of cerebral lesion: Hyphae and type of branching can assist in ion diagnosis of specific fungal infections. In patients with toxoplasmosis, special immunochemical tests can be used to detect the organism or its antigens. A brain-touch technique using immunofluorescence monoclonal antibodies against the organism can also provide rapid diagnosis.
The early stage of brain abscess (first 7-14 days) is called cerebritis and is associated with edema. Necrosis and liquefaction occur after 2-3 weeks, and the lesion becomes gradually surrounded by a fibrotic capsule.[44]
Before a brain abscess has become encapsulated and localized, antimicrobial therapy, accompanied by measures to control increasing intracranial pressure, is essential.[45] 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.[46]
The first step is to verify the presence, size, and number of abscesses using contrast CT scanning or MRI.[16]
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.[47]
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 because of contrast reduction. Steroid therapy can also produce a rebound effect when discontinued. Corticosteroids are used when a significant mass effect is visible on imaging and the patient’s mental status is depressed. When 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.[16]
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).
Antimicrobial treatment for a brain abscess is generally long (6-8 wk) because of the prolonged time needed for brain tissue to repair and close abscess space. The United Kingdom treatment guidelines advocate 4-6 weeks if the abscess has been drained or removed and 6-8 weeks if drainage occurred.[48] The antimicrobial course is through an intravenous route. There is no evidence that transition to oral therapy is appropriate. Furthermore, the concentrations of most oral antibiotics (except for metronidazole, rifampin, linezolid, and trimethoprim-sulfamethoxazole) in the abscess cavity would be inadequate to eradicate the pathogens.
The duration of therapy can be adjusted according to the patient’s condition, causative organism(s), number of abscesses and their size, and response to treatment. A shorter course (4-6 wk) may suffice for cerebritis and in patients who underwent surgical drainage.[47] A long course (>6 wk) is required for necrotic and/or encapsulated abscess with tissue necrosis, multiloculated abscess, abscesses in vital intracranial locations (ie, brain steam), and in immunocompromise.
The length of therapy is guided by continuous assessment of the clinical course and followup imaging studies. The antimicrobial therapy is continued until a clinical response occurs and CT or MRI findings show resolution. However, because the abscess site may show persistent enhancement for several months. This finding alone is not an indication to continue antimicrobial therapy or for 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.
Empiric treatment should cover oral streptococci (including milleri group), methicillin-susceptible staphylococci, anaerobes, and Enterobacteriaceae.[49] As brain abscesses are frequently polymicrobial, de-escalation based on microbiological results is safe only when aspiration samples have been processed optimally or when the primary diagnosis is endocarditis. Otherwise, many experts advocate for anaerobe coverage even with no documentation, given the suboptimal sensitivity of current techniques. A 6-week combination of third-generation cephalosporin and metronidazole cures most cases of community-acquired brain abscess in immunocompetent patients.
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 and their susceptibility is determined, the initial empiric therapy can be adjusted to specifically treat the isolated bacteria.[50]
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). This choice is appropriate for the treatment of an abscess of oral, otogenic, or sinus origin.
When S aureus is suspected (a hematogenic origin, or following neurosurgery or penetrating trauma), vancomycin (effective against methicillin resistance S aureus) is administered. Metronidazole may be added to cover anaerobic bacteria.
Cefepime or ceftazidime is administered to treat gram negative aerobic bacteria Pseudomonas aeruginosa infection.
Patients with HIV infection may require therapy for toxoplasmosis.
Specific antibiotics[16, 51]
Penicillin penetrates well into the abscess cavity and is active against non–beta–lactamase-producing anaerobes and aerobic organisms. However, the emergence of beta–lactamase-producing organisms limits it use.
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 anaerobes may be suboptimal.
Third-generation cephalosporins (eg, cefotaxime, ceftriaxone) generally provide adequate therapy for aerobic gram-negative organisms as well as microaerophilic and aerobic streptococci. If pseudomonads are isolated or anticipated, the parenteral cephalosporin of choice is a forth generation cephalosporin (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 (MSSA). 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. Because of the risk of methicillin-resistant S aureus (MRSA) infection they should only be administered to treat culture proved MSSA.
Vancomycin is most effective against MRSA and Staphylococcus epidermidis as well as aerobic and anaerobic streptococci and Clostridium species.
Antimicrobial alternatives to vancomycin include linezolid (600 mg IV or PO bid), trimethoprim-sulfamethoxazole (5 mg/kg q8-12h), and daptomycin (6 mg/kg IV qd). Limited data regarding their use in brain abscess are available. However, they may be considered when vancomycin is ineffective or cannot be used.[21]
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.
A study by Yu et al demonstrated that topical application of antibiotics into the brain abscess cavity helps to reduce the length of systemic antibiotic therapy, decreases the abscess recurrence rate, avoids the adverse effects of long-term high-dose antibiotics, shortens the hospitalization, and reduces treatment costs.[52]
Surgical drainage of the brain abscess provides the most optimal therapy. The procedures used are aspiration through a bur hole and complete excision after craniotomy. These procedures are also diagnostic and provide material that can guide antimicrobial therapy.
Needle aspiration is the preferred and the most commonly used procedure and is often performed using a stereotactic procedure with the guidance of ultrasound or CT scanning.[46] For optimal results, this is usually performed prior to the initiation of antibiotic therapy. It is repeated if the patient fails to respond to therapy. Aspiration is especially preferred if the speech, motor or sensory cortex area are involved or the patient is comatose. Craniotomy is generally performed in patients with multiloculated abscesses and in those whose conditions fail to resolve.[53]
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 even after initial aspiration or drainage in patients with depressed sensorium, increased intracranial pressure, no clinical improvement within 7 days, and/or a progressively growing abscess.
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.
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 or ampicillin-sulbactam plus a third-generation cephalosporin (in those with a predisposing condition)
Dental infection - Penicillin plus metronidazole or amoxicillin-sulbactam
Pulmonary infections - Penicillin plus metronidazole and a sulfonamide (for Nocardia infections)
Congenital heart disease - Third-generation cephalosporin with metronidazole or ampicillin-sulbactam
Endocarditis - Vancomycin plus gentamicin in prosthetic valve; ampicillin plus gentamicin or third-generation cephalosporin plus vancomycin in natural valve
Intravenous drug abuse - Nafcillin or vancomycin plus cefepime or ceftazidime
Penetrating trauma - Vancomycin plus a third-generation cephalosporin
Postsurgical - Vancomycin, plus cefepime or ceftazidime, or meropenem
Complications of meningitis in infants and children - third-generation cephalosporin, ampicillin, and vancomycin
Neonates- third-generation cephalosporin and ampicillin
No predisposing condition or the immunocompromised - Metronidazole, vancomycin, or a third-generation or fourth-generation cephalosporin
Vancomycin may be required where MRSA is suspected. Alternatives to vancomycin include linezolid, trimethoprim-sulfamethoxazole, and daptomycin.[54] If methicillin-sensitive S aureus is isolated, vancomycin can be substituted with nafcillin or oxacillin.
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.
Clinical Context:
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.
Clinical Context:
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.
Clinical Context:
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.
Clinical Context:
Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Clinical Context:
For treatment of multiple organism infections in which other agents do not have wide spectrum coverage or are contraindicated due to potential for toxicity.
Clinical Context:
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.
Clinical Context:
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.
Clinical Context:
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.
Clinical Context:
Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage.
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.
Clinical Context:
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.
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Most abscesses are managed with intravenous antibiotic therapy to enable the organization of the lesion and to reduce local extension of the infection. After that period, definitive treatment consists of aspiration, incision and drainage, or excision.
Currently, nonoperative approaches (ie, prolonged courses of parenteral antibiotics) are rarely used. An exception is an abscess at an inoperable site. Such cases are uncommon, as many abscesses that were once inoperable can now be reached by stereotactic aspiration guided by precision mapping of the lesion's location with CT or MRI. Magnetic resonance fluoroscopy is used to guide aspiration instead of stereotactic aspiration.
Permanent neurological damage may include hemiparesis, cranial nerve palsy, hydrocephalus, intellectual and behavioral disorders, ataxia, spasticity, visual defects, and optic atrophy. Recurrent seizures develop in about 10-30% of survivors.
Mortality has declined since the introduction of CT and MRI and the development of newer surgical techniques. Mortality rate is about 15%. The mortality is higher in immunocompromised, those who had a transplant, and those with brain stem or deep hemispheric abscesses.
A poorer prognosis is associated with a delayed diagnosis or a misdiagnosis, severe mental status changes at the time of diagnosis, rapid progression of the infection and neurological impairment, multiple and deep abscesses, ventricular rupture, the presence of coma or stupor at diagnosis, inadequate treatment, and specific organisms (ie, Aspergillus species, other fungi, Pseudomonas species).
For excellent patient education resources, visit eMedicineHealth's Infections Center and Brain and Nervous System Center. Also, see eMedicineHealth's patient education articles Brain Infection and Antibiotics.
Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Chief Editor
Pranatharthi Haran Chandrasekar, MBBS, MD, Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Jeffrey D Band, MD, FACP, FIDSA, Professor of Medicine, Oakland University William Beaumont School of Medicine; Health System Chair, Healthcare Epidemiology and International Medicine, Beaumont Health System; Former Chief of Infectious Diseases, Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine
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