BackgroundIntracranial 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.

PathophysiologyBrain abscess is caused by intracranial inflammation with subsequent abscess formation. In at least 15% of cases, the source of the infection is unknown (cryptogenic). Infection may enter the intracranial compartment directly or indirectly via 3 routes.

Contiguous suppurative focus (45-50% of cases)

Direct extension may occur through necrotic areas of osteomyelitis in the posterior wall of the frontal sinus, as well as through the sphenoid and ethmoid sinuses.[3]This direct route of intracranial extension is more commonly associated with subacute and chronic otitic infection and mastoiditis than with sinusitis.[4] Frontal or ethmoid sinus infections generally spread to the frontal lobes. Odontogenic infections can spread to the intracranial space via direct extension or a hematogenous route. These 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.[5] 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.[6]

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.[7]

These infections are 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,[8] esophageal dilatation, injection drug use,[9] and HIV infection.

EpidemiologyFrequency

United States

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.[10] 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%. 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.[11]

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

History

In about two thirds of patients, 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.

Physical

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.

Cerebellar abscess - Nystagmus, ataxia, vomiting, and dysmetria

Brainstem abscess - Facial weakness, headache, fever, vomiting, dysphagia, and hemiparesis

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.

Causes

The etiology depends on the patient's age, site of primary infection, and the patient's immune status.[12, 13]

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.[12, 13, 14, 15]

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[16]

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, and Proteus species)

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)

Actinobacillus actinomycetemcomitans

Actinomyces

Nocardia asteroides

Mycobacterium species

Fungi (eg, Aspergillus, Candida, Cryptococcus, Mucorales, Coccidioides, Histoplasma capsulatum, Blastomyces dermatitidis, Bipolaris, Exophiala dermatitidis, Curvularia pallescense, Ochronosis gallopava, Ramichloridium mackenziei)

Protozoa (eg, Toxoplasma gondii, Entamoeba histolytica, Trypanosoma cruzi, Schistosoma, Paragonimus)

Helminths (eg, Taenia solium)

T gondii

Pseudallescheria boydii

The following organisms are associated with certain predisposing conditions:[17]

Sinus and dental infections - Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (eg, Prevotella, Porphyromonas, Bacteroides, Fusobacterium), microaerophilic streptococci (mainly Streptococcus milleri), Haemophillus, S aureus, Enterobacteriaceae)[14]

Ear infections (including mastoiditis) - Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli, Haemophillus, Pseudomonas, and Enterobacteriaceae

Pulmonary infections - Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (eg, Prevotella, Porphyromonas, Bacteroides), Fusobacterium, Actinomyces, Nocardia[9]

Endocarditis - Alpha hemolytic streptococci, S aureus

Congenital heart disease - Aerobic and microaerophilic streptococci, S aureus

Liver abscess or diabetes mellitus (reported in Southeast Asia) -Klebsiella pneumoniae[18]

Penetrating trauma -S aureus, aerobic streptococci, Enterobacteriaceae, Clostridium

Neurosurgical procedures-S aureus, Pseudomonas, Enterobacter,Propionibacterium acnes[19]

Neonates - Citrobacter[20]

Urinary tract-Pseudomonas, Enterobacteriaceae, Enterobacter

Transplantation - Aspergillus, Candida, Cryptococcus, Mucorales, Nocardia,T gondii[8]

Immunocompromised - Aerobic gram-negative bacilli, T gondii, Nocardia asteroids, Listeria monocytogenes, Aspergillus, Cryptococcus, Coccidioides immitis, Candida, Mucorales[21, 22, 23]

HIV infection -T gondii, Mycobacterium, Cryptococcus, Nocardia, L monocytogenes[10]

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.[24]

Differential Diagnoses1. Bacterial meningitis2. Brain cancer (primary or metastatic)3. Cryptococcosis4. Cysticercosis5. Epidural Abscess6. Focal encephalitis7. Mycotic aneurysm8. Septic cerebral emboli causing infarction9. Septic dural sinus thrombosis

Laboratory StudiesRoutine tests

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 [25]

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.[26]

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.[27]

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 (forNocardia), and special fungal stains (eg, methenamine silver, mucicarmine)

Serology anti-anticysticercal antibodies for the diagnosis of neurocysticercosis

Histopathological examination of the brain tissue

Imaging StudiesCT scanning has made other tests, such as angiography, ventriculography, pneumoencephalography, and radionuclide brain scanning, almost obsolete. 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.[28]

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.

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.

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.[29]

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).[30]

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.[31] 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%.

Other TestsECG occasionally reveals a focus of high voltage with slow activity. It is nonspecific and rarely of value in confirming the diagnosis. This is the least accurate procedure in the diagnostic evaluation.

ProceduresBiopsy 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.

StagingThe early stage of the infection (first 7-14 d) 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.[32]

Medical CareBefore the abscess has become encapsulated and localized, antimicrobial therapy, accompanied by measures to control increasing intracranial pressure, is essential. [33] 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.[34]

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.[35]

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.

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.[35]

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.

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.[36]

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 bacteriaPseudomonas aeruginosa infection.

Patients with HIV infection may require therapy for toxoplasmosis.

Specific antibiotics [37]

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 that are 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 in instances in which vancomycin is ineffective or can not be used.[16]

With the exception of the Bacteroides fragilis group and some strains of Prevotellaspecies, 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 Mucoralesinfections; 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 CareSurgical drainage 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.[34] 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.[38]

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.

ConsultationsThe 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 SummaryThe 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

(forNocardia 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, cefepime or ceftazidime, and metronidazole

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 cephalosporinVancomycin may be required where MRSA is suspected.

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.

AntibioticsClass Summary

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.

View full drug informationAmpicillin (Marcillin, Omnipen) 

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

View full drug informationCefotaxime (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.

View full drug informationCeftriaxone (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.

View full drug informationCeftazidime (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.

View full drug informationChloramphenicol (Chloromycetin) 

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

View full drug informationImipenem 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.

View full drug informationMeropenem (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.

View full drug informationMetronidazole (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.

View full drug informationVancomycin (Vancocin) 

Potent antibiotic directed against gram-positive organisms and active againstEnterococcus 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.

View full drug informationCefepime (Maxipime) 

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

CorticosteroidsClass Summary

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

View full drug informationDexamethasone (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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