Introduction

Background
Although rare in developed countries, brain abscess is a serious, life-threatening emergency. Once having a dire outcome, morbidity and mortality have decreased because of advances in diagnostic modalities, antibiotic regimens, and earlier surgical interventions.1,2However, changes in epidemiology, including new disease pathogens and predisposing factors, have renewed concern about the diagnosis and treatment of this condition.

Pathophysiology
Brain abscess is a focal infection, which begins when organisms are inoculated into the brain parenchyma, usually from a site distant from the central nervous system !"#$. Abscess formation occurs through several stages. %nflammation during the &early cerebritis& stage evolves into a necrotic collection of pus, eventually surrounded by a well-vasculari'ed capsule after 2 wee(s.),* +he ) mechanisms of entry into the brain are as follows,2,-,. /irect e0tension, %nfections stemming from the sinuses, teeth, middle ear, or mastoid may gain access to the venous drainage of the brain via valveless emissary veins that drain these regions. Because of improved antibiotic therapy for ear infections, this mechanism is decreasing in incidence, accounting for only appro0imately 12-2-1 of cases.2,2 However, in developing countries, this is still a significant source accounting for at least -31 of cases.4 Hematogenous, #eeding of the brain occurs from distant infection sites and often results in multiple brain abscesses.5 +his remains an important cause of brain abscess. 6ollowing penetrating head in7ury or neurosurgery, 8reviously low in incidence, more brain abscesses are developing after head trauma and neurosurgical procedures. A case series found that )21 of brain abscesses were associated with head penetration.2,13

9p to )31 of abscesses are cryptogenic and have no clear source.2,4,5

Frequency
United States

Brain abscess is rare in the general population: however, immunocompromised patients have increasing incidence of brain abscess, often with fungal or proto'oan organisms. %n the 9nited #tates, 1-33-2-33 cases are reported per year.5

Mortality/Morbidity
+he mortality rate from brain abscess is currently appro0imately 131.1,2,4,11,12 However, if the abscess ruptures into the ventricular system, the mortality rate may be 431.2 ;orbidity in survivors is generally due to residual neurologic defects, increased incidence of sei'ures due to scar tissue foci, or neuropsychiatric changes.5

Race
"o compelling evidence e0ists for racial differences in the incidence of brain abscess.

Sex
Brain abscess occurs two to four times as often among men than women.2,*,2,4,1),1*

Age
+raditionally, brain abscesses were disproportionately diagnosed in the young. However, with changes in vaccination practices, treatment of pediatric infections, and the A%/# pandemic, current literature suggests a shift in pea( incidence toward the third to fifth decades of life.2,1*,1- +he minority of abscesses that do occur in children pea( in the age range of *-2 years.1.

linical
!istory
Headache is the most common presenting symptom of brain abscess -3-531 of cases$.2,2,1* 6ocal neurologic deficit -31$ may correlate with the local region of infection..,2 !lassic triad of headache, fever, and focal neurologic deficit is rarely seen <--231 of cases in case series$.2,4 #ei'ure *31$ and mental status changes -31$ are common.2,1* "ausea, vomiting, or stiff nec( may be reported with increased cerebral edema due to the mass lesion..,4 #udden worsening of a pree0isting headache accompanied with meningismus may be indicative of a catastrophic event=rupture of the abscess into the ventricular space..

Physical
6ever is typically low grade, but presence or absence of fever does not aid in diagnosis, as it is present in less than half of all cases..,1* Altered mental status ranges from subtle personality changes through drowsiness to fullblown coma.1* "uchal rigidity occurs in about 2-1 of cases.1* 6ocal neurologic findings are commonly present.,1* and can signal increasing cerebral edema around the abscess.* #ei'ures are typically generali'ed.1* 8apilledema indicates the disease process is well advanced and increased intracranial pressure is present.1* Bulging fontanelles, irritability, and enlarging head circumference may be noted in infants.-

auses
A wide variety of organisms can cause brain abscess, depending on the portal of entry, and up to one third may be polymicrobial.),.

/irect e0tension - #inus, odontogenic, and otogenic sources are common. o Streptococcus species aerobic and anaerobic$ are most fre>uently isolated. o Other organisms include Bacteroides, Enterobacteriaceae, Pseudomonas, Fusobacterium, Prevotella, Peptococcus, and Propionibacterium. Hematogenous spread - 8athogens depend on predisposing source. #ome common e0amples are listed below. o ?ndocarditis -Streptococcus viridans, Staphylococcus aureus o 8ulmonary infections -Streptococcus, Fusobacterium, Corynebacterium, and Peptococcus species o !ardiac defects with right-to-left shunt -Streptococcus species o %ntra-abdominal infections -Klebsiella species, E coli, other ?nterobacteriaceae, Streptococcusspecies, anaerobes o 9rinary tract infections - ?nterobacteriaceae, Pseudomonas species o @ound infection -S aureus 8enetrating head trauma, postoperative13 o S aureus is most commonly isolated. o ?nterobacteriaceae, other gram-negative bacilli, S epidermidis, Clostridium species, anaerobes, andPseudomonas species may also be found. o Propionibacterium acnes, an indolent gram-positive anaerobic organism, may cause delayed postoperative brain abscess, even 13 years after an intracranial procedure.12 Aarely, cases of brain abscess have been reported even after nonpenetrating traumatic intracranial hemorrhage.14 Opportunistic infection is an increasing cause of brain abscess, as there are more patients with organ transplant, H%B, and immunodeficiencies. !ommon organisms include Toxoplasma gondii and Nocardia, spergillus, and Candida species.*,-,. !ases of Nocardia are increasing even in immunocompetent patients and have high mortality.2,*,15 Other predisposing ris( factors include intravenous drug use, cardiac abnormalities ie, prosthetic valve, septal defect$, cyanotic congenital heart disease most common cause of multiple brain abscesses in children$, diabetes, chronic steroid use, alcoholism, and neoplasm.2,5,1* !ase reports of near drowning, foreign body aspiration, application of dental braces, tongue piercing, and upper endoscopic procedures such as esophageal dilatation and variceal ligation have also been associated with brain abscess.23,21,22,2),2*,2@hen there is no obvious source up to 2-1 of cases$, upper respiratory tract flora and anaerobes are often isolated.2 #everal sources have identified a patent foramen ovale by echocardiogram in these cases and propose this as a possible mechanism for seeding oral flora to the brain.2. #everal cases of community-ac>uired methicillin-resistant Staphylococcus aureus !A;A#A$ causing brain abscess have been reported recently, so this must be considered when initiating empiric therapy in patients presenting with neurologic symptoms who also have ris( factors for !A-;A#A.

"orkup
#aboratory Studies

Caboratory tests are rarely helpful in establishing a diagnosis of brain abscess.2,5 ?levated white blood cell @B!$ count or erythrocyte sedimentation rate ?#A$ is not reliably found..,)3 Blood culture results may only be positive in )31 of patients2,)1 but should always be obtained. Hematogenous spread may be the source as noted above, and a positive blood culture result may help guide therapy, especially if empiric antibiotics are started and abscess fluid culture yields no growth.2,. !ulture specimen from any other suspected focus of infection should also be collected, as this may also give clues for possible distant sources.1*

I$aging Studies
!+ imaging of the brain with and without contrast$ is the most readily available study for establishing diagnosis of brain abscess in the ?/. o ?arly in the course, abscess appears as a low-density, irregular 'one that does not enhance in the presence of intravenous contrast early cerebritis$. o !lassically, as the disease progresses, a distinctive &ring enhancement& appears on contrast-enhanced !+, as the abscess wall thic(ens. o Aarely, a well-organi'ed abscess wall fails to generate such ring enhancement. #uch false-negative results should not have an impact on ?/ care or disposition: they have more implications for inpatient care, where the timing of surgical intervention may be dictated by response to preliminary intravenous antibiotics and subse>uent organi'ation of the abscess wall.)2 !+ is generally sufficient to ma(e the preliminary diagnosis, which mandates neurosurgical consultation and admission to the hospital.2,),. However, ;A% is increasingly being used for further evaluation. o ;A% is more sensitive in detecting early cerebritis.2 o 8osterior fossa lesions may not be identified on !+ scan and may re>uire ;A% to ma(e the critical diagnosis.2,* o A ring-enhancing lesion on !+ scan may give rise to a differential diagnosis including abscess versus primary tumor or metastasis. Dadolinium-enhanced ;A% is helpful in characteri'ing these lesions. On diffusion-weighted imaging, pyogenic abscesses have a hyperintense signal, whereas nonpyogenic lesions will have a hypointense or mi0ed signal. Although not readily available in the emergency department, proton magnetic resonance spectroscopy may also be used to differentiate abscesses.)),)*,)-,).

#ee Brain, Abscess for images.

%ther &ests
9ltrasonography, As ultrasonography is becoming widely used in the emergency department, bedside ocular ultrasonography may be performed to assess for increased intracranial pressure.)2

Procedures

Cumbar puncture C8$ o C8 results are generally not helpful in the diagnosis of brain abscess. 8erforming this procedure in the emergency department is generally indicated only in cases highly suspicious for bacterial meningitis, with a careful balance between any potential change in management and the ris( of !"# herniation.*,1* o +he suspicion of brain abscess, presence of any focal neurologic finding, or of papilledema is an absolute indication for !+ imaging prior to C8.)4 %n cases where C8 had been performed, the findings were nonspecific and cultures were rarely positive.2,)5 Abscess aspiration, !ulture of the abscess fluid is the most important microbiological study to ensure appropriate targeted therapy. As a result, urgent or emergent neurosurgical consultation is necessary.

&reat$ent
Prehospital are

Aapid transport is the (ey component of prehospital care for suspected intracranial abscess.

'$ergency (epart$ent

are

+he initial evaluation is dictated by the severity of the patientEs condition. ?mergent intubation using a cerebroprotective rapid se>uence induction regimen is often necessary in patients with obtundation, inability to protect the airway, and suspected herniation. #table patients whose presentation suggests the diagnosis should undergo rapid neuroimaging after initial evaluation.2,),5 !lose monitoring of neurologic status is essential and having at least one nurse or advanced provider in attendance while the patient is undergoing imaging is probably advisable. Antibiotics should be administered as early as possible in the patientEs course in the ?/. +hese may be given prior to imaging in cases where the diagnosis is very strongly suspected.1* #ei'ures should be treated aggressively to decrease the ris( of sustained increases in intracranial pressure. 8rophylactic anticonvulsants are often used given the relatively high fre>uency of sei'ures in this population.)

onsultations
Once the diagnosis is clear, immediate neurosurgical consultation is mandatory.2,) %nfectious disease consultation may be necessary to optimi'e antibiotic therapy, especially in immunocompromised hosts.2,* "eurology consultation is helpful in guiding both immediate and long-term management. !onsultation with dentalForal-ma0illofacial surgeons or otolaryngologists may be helpful if the primary focus of infection is odontogenic or otorhinogenic, respectively, for cotreatment and eradication of the primary source.*3,*1

Medication

#election of appropriate antimicrobials with ade>uate !"# penetration and coverage of typical anaerobic and aerobic organisms is critical in controlling infection and preventing complications. %n the early phase of abscess formation, cerebritis, patients may respond to antibiotic therapy alone.-,5 However, in almost all cases, definitive treatment of brain abscess re>uires surgical drainage.2,) #ince sei'ures are a fre>uent complication of brain abscess, anticonvulsants for sei'ure prophyla0is are often recommended at the initial time of diagnosis and for a prolonged period of time, often greater than 1 year.),5

Antibiotics
%n the ?/, empirical regimens of antibiotic therapy are the first-line pharmacologic treatment of brain abscess based on presumed source,) /irect e0tension from sinuses, teeth, middle ear - 8enicillin D G metronida'ole G thirdgeneration cephalosporin Hematogenous spread or penetrating trauma - "afcillin G metronida'ole G thirdgeneration cephalosporin 8ostoperative - Bancomycin concern for ;A#A$ G cefta'idime or cefepime concern for Pseudomonas$ "o predisposing factor - ;etronida'ole G vancomycin G third-generation cephalosporin

%mipenem or meropenem can also be used for broad-spectrum coverage with e>ual or better cure rates compared to a standard regimen of cefota0ime and metronida'ole, but imipenem has been associated with sei'ures in patients with brain abscess.* Additional targeted therapy may also be initiated in suspected fungal or proto'oan infections, especially in immunocompromised patients.2,*2

e)triaxone *Rocephin+

+hird-generation cephalosporin with broad-spectrum, gram-negative activity: lower efficacy against gram-positive organisms: higher efficacy against resistant organisms. Bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins. ?0erts antimicrobial effect by interfering with synthesis of peptidoglycan, a ma7or structural component of bacterial cell wall. Bacteria eventually lyse due to the ongoing activity of cell wall autolytic en'ymes while cell wall assembly is arrested. Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gramnegative and gram-positive bacteria.
Adult
Dosing Interactions Contraindications Precautions

2 g %B >12-2*h, ma0 * gFd

Pediatric

133 mgF(gFd %B divided >12h

e)epi$e *Maxipi$e+

6ourth-generation cephalosporin. Dram-negative coverage comparable to cefta'idime but has better gram-positive coverage comparable to ceftria0one$. !overs Pseudomonas!
Adult
Dosing Interactions Contraindications Precautions

2 g %B >4-12h
Pediatric

"eonates, )3 mgF(g %B >12h H2 months, -3 mgF(g %B >4h ma0 2 gFdose$

I$ipene$ and cilastatin *Pri$axin+

6or treatment of multiple organism infections in which other agents do not have wide spectrum coverage or are contraindicated due to potential for to0icity.
Adult
Dosing Interactions Contraindications Precautions

-33-2-3 mg %B >.h: in healthy young adults with e0cellent renal function, doses of 1 g >.h may be necessary ma0 dose, * gFd$
Pediatric

%nfants H) months and children <12 years, 1--2- mgF(gFdose %B >.h 6ully susceptible organisms, "ot to e0ceed 2 gFd %nfections with moderately susceptible organisms, "ot to e0ceed * gFd H12 years, Administer as in adults

Meropene$ *Merre$ I,+

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


Adult

Dosing Interactions Contraindications Precautions

1-2 g %B >4h
Pediatric

<) months, "ot established H) months, *3 mgF(g %B >4h ma0 dose 2 gFdose$

Penicillin - *P)i.erpen+

;ay be used as first-line regimen for empiric treatment of brain abscess in ?/. 8rovides coverage for anaerobes and streptococci. 8enetrates well into abscess cavity.
Adult
Dosing Interactions Contraindications Precautions

. million 9 %B >.h
Pediatric

<1* (g )3 lb$, .33,333 9 %B >.h 1*-22 (g )3-.3 lb$, 533,333-1,233,333 9 %B >.h H22 (g H.3 lb$, Administer as in adults

Metronida.ole *Flagyl+

6irst line. %mida'ole ring-based antibiotic active against various anaerobic bacteria and proto'oa. Has proved especially effective in otogenic brain abscesses.
Adult
Dosing Interactions Contraindications Precautions

-33-2-3 mg %B >.h
Pediatric

)3 mgF(gFd %B

e)otaxi$e * la)oran+

6irst line. !overs streptococci, staphylococci, and "aemophilus and Enterobacter species. +his third-generation cephalosporin has broad gram-negative spectrum, lower efficacy against grampositive organisms, and higher efficacy against resistant organisms than earlier generation cephalosporins. Arrests bacteria cell wall synthesis and inhibits bacterial growth by binding to 1 or more penicillin-binding proteins.
Adult
Dosing Interactions Contraindications Precautions

2g %B >*-.h
Pediatric

"eonates, -3-233 mgF(gFd %B %nfants and children, 233 mgF(gFd %B divided into >.h->4h

/a)cillin *Unipen+

+reats infections caused by penicillinase-producing staphylococci. 9sed to initiate therapy when penicillin D-resistant staphylococcal infection suspected. /o not use for treatment of penicillin Dsusceptible staphylococci. 9se parenteral therapy initially in severe infections. Bery severe infections may re>uire very high doses. !hange to oral therapy as condition improves. Because of occasional occurrence of thrombophlebitis associated with parenteral route particularly in elderly persons$ administer parenterally only for short term 2*-*4 h$ and change to oral route if clinically possible.
Adult
Dosing Interactions Contraindications Precautions

2g %B >*h
Pediatric

"eonates, 1233-2333 g, <2 days, -3 mgF(gFd %B divided >12h H2333 g and <2 days or 1233-2333g and H2 days, 2- mgF(gFd %B divided >4h H2333 g, H2 days, 133-1*3 mgF(gFd %B divided >.h !hildren, 233 mgF(gFd in divided doses >*-.h

,anco$ycin *,ancocin+

Aeplaces nafcillin in both penicillin-allergic patients and those in whom ;A#A is suspected as etiologic agent. 8otent antibiotic directed against gram-positive organisms and active against enterococci. Also useful in treating septicemia and s(in structure infections. Ad7ust dose as

needed in patients with renal impairment. !hec( trough level after third dose )3 min prior to ne0t dose$ to avoid to0icity.
Adult
Dosing Interactions Contraindications Precautions

1 g %B >12h or loading dose of 1- mgF(g %B >4-12h /ose for pea(s 2--*3 mcgFmC, troughs --13 mcgFmC
Pediatric

.3 mgF(gFd %B in divided doses >.h

e)ta.idi$e *Forta.0

epta.+

Add to empiric regimens if pseudomonads are suspected. +hird-generation cephalosporin that has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms than many agents. Arrests bacteria cell wall synthesis and inhibits bacterial growth by binding to 1 or more penicillin-binding proteins.
Adult
Dosing Interactions Contraindications Precautions

. gFd %B
Pediatric

"ot established

orticosteroids
9se of steroids is controversial. +he anti-inflammatory effects of steroid therapy can decrease cerebral edema, reducing intracranial pressure %!8$. +hese benefits are offset somewhat by the fact that steroid use decreases antibiotic penetration into the abscess and may slow encapsulation of the abscess site. +herefore, many authors recommend steroids only in cases of massive cerebral edema with impending herniation.),1*

(exa$ethasone *(ecadron0 (exasone+

!orticosteroid of choice for reducing %!8. 9sed in treatment of inflammatory diseases. ;ay decrease inflammation by suppressing migration of polymorphonuclear leu(ocytes and reversing increased capillary permeability.
Dosing Interactions


Adult

Contraindications Precautions

Coading dose, 13-12 mg %B ;aintenance dose, * mg %B >.h

Pediatric

Coading dose, 1-2 mgF(gFdose %B once ;aintenance dose, 1-1.- mgF(gFd %B "ot to e0ceed 1. mgFd divided >*-.h for - d: taper dose for - d and discontinue

Follo12up
Further Inpatient

are

A combined medical and surgical approach is used for most brain abscesses to eradicate the invasive organism.12 /uration of antibiotic treatment is unclear and is dictated by clinical response. +raditionally .-4 wee(s of intravenous antibiotics has been used followed by oral antibiotics for another *-4 wee(s to prevent relapse.2,*,5,*) One series reported clinical resolution in some patients with only 2 wee(s of intravenous therapy,2 indicating that some patients may not need e0tended parenteral treatment. #urgery is the only way to precisely isolate the causative organism and tailor antibiotic therapy. One study concluded that antibiotic pretreatment for up to 13 days does not alter culture positivity of intracerebral specimen.1* However, other series show that up to *31 of abscess cultures may be negative,4 presumably due to early empiric antimicrobial therapy. At present, most neurosurgeons use nonoperative management ie, prolonged courses of parenteral antibiotics$ only in rare cases. %ndications may include patients with the following,2,),** o #ingle abscess smaller than 2 cm o ;ultiple abscesses o !ritical illness at a terminal stage o Abscess in an inaccessible location #urgical options include aspiration, incision and drainage, or e0cision depending on the location, si'e, number of sites, and other characteristics of the abscess as well as the patientEs clinical status.2,),*- +he specific choice of surgical techni>ue is less important than the basic principle of removing the pathogen.) ;any abscesses that were once inoperable can now be reached by stereotactic aspiration guided by precision mapping of the lesionEs location by !+ or ;A%.),*) #tereotactic aspiration is widely preferred to open craniotomy because it is minimally invasive, has low morbidityFmortality, and allows rapid drainage.2,.Aeports of magnetic resonance fluoroscopy to guide aspiration also e0ist.*. #ome interest e0ists in the possible role of hyperbaric o0ygen as an ad7unct therapy to the initial phase of treatment with intravenous antibiotics. Aeports in children*2 and in adults*4 suggest that such ad7unct therapy may reduce the length of inpatient stay by

decreasing the duration of antibiotics needed for clinical improvement: however, the number of cases studied to date is small.

Further %utpatient

are

%nterval !+ scans are recommended for inpatients and outpatients to follow up for complications and resolution of abscess,),* as there is a ris( of abscess reaccumulation or failure to resolve in some cases re>uiring reaspiration.2,12

&rans)er
Cac( of neurosurgical availability is an indication for transfer to a medical center that has such support.

o$plications
!omplications of brain abscess may include the following, 9ncal or tonsillar herniation due to increased intracranial pressure %!8$)3 Aupture of abscess into ventricles or subarachnoid space is a complication. +his is often lethal. High-ris( features for this complication include an abscess that is deep seated, multiloculated, andFor close to the ventricular wall.*5 Aecurrence of abscess2 Cong-term neurologic se>uelae in up to -31 of patients ie, hemiparesis, sei'ures$*,.,1*,)1

Prognosis
#urvival rates for brain abscess are e0cellent.12 !haracteristics associated with an e0cellent prognosis include the following, o Ioung age1* o Absence of severe neurologic defect on initial presentation1*,-3 o Absence of neurologic deterioration during initial wor(up1*,-3 o Absence of comorbid disease1*,-3 @orse prognosis of brain abscess is associated with the following, o #igns of herniation on initial presentation ;ortality rate e0ceeds -31.1* $ o Altered sensorium at time of presentation4 o ?0tent of brain lesion on radiology ie, increased si'e, critical location, more lesions, increasing edemaFmidline shift$-1 o #hort duration of symptom-onset before diagnosis* o /elay in surgical intervention*o Dram-negative infection-2 o "ocardial abscess ;ortality rate is ) times that of bacterial abscess and can reach fatality rates as high as -31 in immunocompromised patients.15 $

Patient 'ducation
6or e0cellent patient education resources, visit e;edicineEs %nfections !enter, Brain and "ervous #ystem !enter, and Brain and "ervous #ystem !enter. Also, see e;edicineEs patient education articles Brain %nfection,Antibiotics, and Brain %nfection.

Miscellaneous
Medicolegal Pit)alls
6ailure to obtain emergency neuroimaging in patients with headache and new neurologic defect 6ailure to accurately identify and distinguish brain abscess from other ring enhancing lesions and begin immediate treatment /ischarging a patient without e0plaining a new neurologic finding 6ailure to heed family concerns about unusual patient behavior when other symptoms suggestive of brain abscess are present.