4 Abses Serebelum

Brain Abscess
92 Allan R. Tunkel
SHORT VIEW SUMMARY

Definition • Staphylococcus aureus accounts for 10% to ring-enhancing lesions and differentiating
• Brain abscess is a focal, intracerebral infection 20% of isolates, usually in patients with brain abscess from other cystic lesions of the
that begins as a localized area of cerebritis cranial trauma or infective endocarditis, and it brain, including tumors.
and develops into a collection of pus is often isolated in pure culture; cases caused • A major advance in the use of computed
surrounded by a well-vascularized capsule. by community-associated methicillin-resistant tomography (CT) in patients with suspected
S. aureus strains have been reported. brain abscess is the ability to perform
Epidemiology • The attention to proper culture techniques has stereotactic CT-guided aspiration to facilitate
• Before the advent of human immunodeficiency increased the isolation of anaerobes from microbiologic diagnosis and to guide
virus (HIV) infection, brain abscess accounted brain abscesses with Bacteroides and antimicrobial therapy; at the time of
for 1500 to 2500 cases treated in the United Prevotella spp., isolated in 20% to 40% of aspiration, specimens should be sent for
States each year; the incidence was estimated patients, often in mixed culture. Gram stain, routine aerobic and anaerobic
at 0.3 to 1.3 cases per 100,000 people per • Enteric gram-negative bacilli (e.g., Proteus cultures, and cultures for mycobacteria and
year. spp., Escherichia coli, Klebsiella spp., and fungi.
• In most pediatric and adult series, a male Pseudomonas spp.) are isolated in 23% to
predominance exists (a ratio of 2 : 1 to 3 : 1) Therapy
33% of patients, often in patients with otitic
with a median age of 30 to 40 years, although • When abscess material has been obtained for
foci of infection, with septicemia, who have
the age distribution varies depending on the microbiologic and histopathologic studies,
had neurosurgical procedures, or who are
predisposing condition leading to the empirical antimicrobial therapy should be
immunocompromised.
formation of brain abscess. initiated on the basis of the patient’s
• Nocardial brain abscess may occur as an
• The incidence of brain abscess is also affected predisposing conditions and the presumed
isolated central nervous system (CNS) lesion
by the general health of the population. In pathogenesis of abscess formation (see
or as part of a disseminated infection in
one study of 973 patients from one tertiary Table 92-3).
association with pulmonary or cutaneous
hospital in South Africa from 1983 to 2002, • In HIV-infected patients with CNS mass
disease.
the incidence declined during the study period lesions, the initial approach to management is
• The incidence of fungal brain abscess has
as a result of improvements in socioeconomic different because of the high likelihood of the
increased as a result of the prevalent
standards and availability of health care diagnosis of toxoplasmic encephalitis.
administration of immunosuppressive agents,
services. • Antimicrobial therapy with high-dose
broad-spectrum antimicrobial therapy, and
• The incidence of otogenic abscesses has intravenous agents has traditionally been
corticosteroids.
decreased, whereas the incidence of administered for 6 to 8 weeks in patients
post-traumatic and postoperative brain Diagnosis with bacterial brain abscesses.
abscesses has increased. • Magnetic resonance imaging (MRI) has been • Most patients with bacterial brain abscess
extensively evaluated in the diagnosis of brain require surgical management for optimal
Microbiology abscess and is the first imaging choice in the therapy.
• Streptococci (aerobic, anaerobic, and evaluation of a patient suspected to have this • The combination of surgical aspiration or
microaerophilic) are the bacteria most disorder. removal of all abscesses larger than 2.5 cm
commonly (70% of cases) cultured from • The combined use of proton MR spectroscopy, in diameter, a 6-week or longer course of
patients with bacterial brain abscess, and they diffusion-weighted imaging, and diffusion intravenous antimicrobial therapy, and
are frequently isolated in mixed infections tensor imaging has been shown to improve response on follow-up neuroimaging should
(30% to 60% of cases). the specificity of diagnosis of focal result in a cure rate of more than 90%.
Brain abscess is a focal, intracerebral infection that begins as a localized to 0.9 cases per 100,000 population.3a In most pediatric and adult series,
area of cerebritis and develops into a collection of pus surrounded by a male predominance exists (a ratio of 2 : 1 to 3 : 1) with a median age of
a well-vascularized capsule.1 Brain abscess was an almost uniformly 30 to 40 years, although the age distribution varies depending on the
fatal disease before the late 1800s, when surgical techniques (i.e., drain- predisposing condition leading to the formation of brain abscess. When
age) led to cure in selected patients.2 Further advances in the manage- the abscess is related to a focus in the paranasal sinuses, most patients
ment of brain abscess were made after the introduction of antimicrobial are 10 to 30 years of age; when the abscess is from an otitic focus,
therapy and stereotactic brain biopsy and aspiration techniques. In this patients are younger than 20 or older than 40 years.3,4 The incidence of
chapter, the common bacterial, fungal, and protozoal causes of brain brain abscess is also affected by the general health of the population. In
abscess are reviewed and the clinical presentation, diagnosis, and one study of 973 patients from one tertiary hospital in South Africa
approach to management are emphasized. from 1983 to 2002,5 the incidence declined during the study period as
a result of improvements in socioeconomic standards and availability
EPIDEMIOLOGY AND ETIOLOGY of health care services. In that series, the mean age was 24 years and
Brain abscess is one of the most serious complications of head and neck three fourths of patients were men; predisposing conditions were oto-
infections. Before the advent of human immunodeficiency virus (HIV) rhinogenic (38.6%), traumatic (32.8%), pulmonary (7%), cryptogenic
infection, brain abscess accounted for 1500 to 2500 cases treated in the (4.6%), postsurgical (3.2%), meningitis (2.8%), cardiac (2.7%), and
United States each year; the incidence was estimated at 0.3 to 1.3 cases other (8.6%). Overall, about 25% of cases of brain abscess occur in
per 100,000 people per year.3 More recent estimates are similar, with 0.4 children, most in the 4- to 7-year age group; and usually they originate
1164
Downloaded for Matdoan Rifkiah Aisyah (matdoan.rifkiah@ui.ac.id) at Universitas Indonesia from ClinicalKey.com by Elsevier on May 12, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
1164.e1
KEYWORDS
antimicrobial therapy; brain abscess; neuroimaging; neurosurgery;
nocardiosis; toxoplasmosis
Chapter 92 Brain Abscess
1165
from an otitic focus or in patients with cyanotic congenital heart disease. TABLE 92-1 Predisposing Conditions and
In a recent series of 27 children with bacterial brain abscess, however, Microbiology of Brain Abscess
sinusitis, meningitis, and traumatic brain injury were the most common
predisposing conditions.6 Brain abscess is extremely rare in patients PREDISPOSING CONDITION USUAL MICROBIAL ISOLATES

younger than 2 years. Brain abscess is a rare complication after cranial Otitis media or mastoiditis Streptococci (anaerobic or aerobic),
Bacteroides and Prevotella spp.,
operations, seen in 0.2% of 1587 operations in one report.7 The predispos- Enterobacteriaceae
ing conditions for brain abscess have changed in recent years; over the past
Sinusitis (frontoethmoid or Streptococci, Bacteroides spp.,
10 to 15 years, the incidence of otogenic abscesses decreased, whereas the sphenoid) Enterobacteriaceae, Staphylococcus
incidence of post-traumatic and postoperative brain abscesses increased.8 aureus, Haemophilus spp.
In more recent series of patients with brain abscess, there has been an Dental infection Mixed Fusobacterium, Prevotella,
increase in the number of cases seen in immunocompromised hosts. Actinomyces, and Bacteroides spp.,
Case-fatality rates in patients with brain abscess, even in the antibi- streptococci
otic era, ranged from 30% to 60% (similar to the rates in the preantibi- Penetrating trauma or S. aureus, streptococci,
otic era) until the period since the late 1970s, when the overall mortality postneurosurgical Enterobacteriaceae, Clostridium spp.
rate has ranged from 0% to 24%.3,4 This improvement has been attrib- Lung abscess, empyema, Fusobacterium, Actinomyces,
bronchiectasis Bacteroides, and Prevotella spp.,
uted to the availability of more effective antimicrobial regimens (e.g., streptococci, Nocardia spp.
the addition of metronidazole), new surgical techniques, and, most
Bacterial endocarditis S. aureus, streptococci
importantly, the availability of computed tomography (CT). Data from
Congenital heart disease Streptococci, Haemophilus spp.
the University of California in San Francisco showed a decrease in the
overall mortality rate from 44% during the 3 years before CT to 0% for Neutropenia Aerobic gram-negative bacilli,
Aspergillus spp., Mucorales, Candida
the 3 years after the introduction of CT in 1977.9 This lower mortality spp., Scedosporium spp.
rate was principally related to early diagnosis and an accurate method Transplantation Aspergillus spp., Candida spp.,
of postoperative follow-up with CT. In one review of outcome in Mucorales, Scedosporium spp.,
patients with brain abscess, specifically from an otitic focus, mortality Enterobacteriaceae, Nocardia spp.,
rates dropped systematically from 35% between 1953 and 1977 to 14% Toxoplasma gondii, Mycobacterium
tuberculosis
between 1978 and 1989 and 3% between 1990 and 2011.10 Similarly, in
a retrospective analysis of 620 cases of brain abscess from China over Human immunodeficiency virus T. gondii, Nocardia spp., Mycobacterium
infection spp., Listeria monocytogenes,
a 62-year period,232 mortality decreased from 22.8% in 1952 to 6.3% in Cryptococcus neoformans
2014, likely because of improvements in neurosurgical techniques,
cranial imaging, and antimicrobial regimens. However, in more general
series, mortality ranged from 8% to 25%.5,11,12-16,17
The incidence of neurologic sequelae in patients who survive a and Streptococcus intermedius), normally reside in the oral cavity,
brain abscess ranges from 20% to 70%. In one study of factors influenc- appendix, and female genital tract, and they have a proclivity for
ing the outcome in 39 cases of bacterial brain abscess, the prognosis abscess formation (see Chapter 205). Although streptococcal brain
was primarily determined by the rapidity of progression of the disease abscesses are seen most often in patients with oropharyngeal infections
before hospitalization and the patient’s mental status on admission.11 or infective endocarditis, they are also isolated after neurosurgical or
Poor prognostic factors have included poor Glasgow Coma Scale score other medical procedures.22 Group A streptococci are rare causes of
and the presence of underlying diseases (e.g., immunodeficiency, bacterial brain abscess.23 As whole-genome sequencing and targeted-
malignancy, hematologic disorders) and other comorbid conditions. In genome sequencing move into diagnostic microbiology laboratories, a
one study of 142 patients with brain abscess, Glasgow Coma Scale score larger range of microbial pathogens in brain abscesses is going to be
greater than 12 and no evidence of sepsis were associated with a more encountered, including more fastidious organisms.233 How that will
favorable outcome.15 In other series, outcome has been related to the impact therapy is yet to be determined.
approach to management. In one review of 80 surgically treated brain Staphylococcus aureus accounts for 10% to 20% of isolates, usually
abscesses in 59 patients,18 immunosuppression, hematogenous spread, in patients with cranial trauma or infective endocarditis, and it is often
and advanced age were predictors of poor outcome. In another series isolated in pure culture; cases caused by community-associated
of 973 brain abscess patients from South Africa,5 97% of whom under- methicillin-resistant S. aureus strains have been reported.24 The atten-
went surgical drainage, predictors of mortality included cerebral tion to proper culture techniques has increased the isolation of anaer-
infarction, ventriculitis, coma, hydrocephalus, dilated pupils, bilateral obes from brain abscesses with Bacteroides and Prevotella spp., isolated
abscesses, multiple abscesses, HIV coinfection, papilledema, and neu- in 20% to 40% of patients, often in mixed culture.3,25,26 Enteric gram-
rologic deterioration. In a 22-year retrospective study of 31 patients negative bacilli (e.g., Proteus spp., Escherichia coli, Klebsiella spp., and
who underwent nonoperative management of bacterial brain abscess, Pseudomonas spp.) are isolated in 23% to 33% of patients, often in
the overall mortality rate was 48%; the Glasgow Coma Scale score at patients with otitic foci of infection, with septicemia, who have had
presentation, septic shock, and neck stiffness were risk factors for poor neurosurgical procedures, or who are immunocompromised. At one
outcome.19 Early recognition of predisposing conditions is important center, Klebsiella was the most prevalent pathogen (usually associated
for improving the outcome in brain abscess. In patients with bacterial with hematogenous dissemination or postneurosurgical states),27,28 fol-
brain abscess complicated by intraventricular rupture, mortality rates lowed by Proteus and Enterobacter spp.29 In one review of 41 patients
are much higher, ranging from 27% to 85%.20 with otogenic brain abscess, Proteus was isolated in 41% of cases.30
When the microorganisms likely to be responsible for causing brain Multiple organisms are cultured in 14% to 28% of cases in patients with
abscesses are evaluated, the isolation frequency depends on the predis- positive culture results.3,12-15 The incidence of negative cultures has
posing condition (Table 92-1).3,13,21 Improved microbiologic culture ranged from 0% to 43% in selected series,* with the frequency often
techniques, particularly for anaerobes, have had a significant impact correlating with prior use of antimicrobial therapy.
on the awareness of microorganisms that are found in brain abscesses. Other bacterial pathogens may be isolated from brain abscesses in
The common bacteria, fungi, protozoa, and helminths that can produce selected patients or from immunocompromised patients. Although
brain abscess are reviewed next. Haemophilus influenzae, Streptococcus pneumoniae, and Listeria mono-
cytogenes are common etiologic agents of bacterial meningitis, they are
Bacterial Brain Abscess rarely isolated from patients with pyogenic brain abscesses (<1% of
Streptococci (aerobic, anaerobic, and microaerophilic) are the bacteria cases).33-36 However, these organisms may be seen in patients with
most commonly (70% of cases) cultured from patients with bacterial bacterial meningitis complicated by cerebritis resulting in abscess for-
brain abscess, and they are frequently isolated in mixed infections (30% mation during the clinical course.37 Brain abscess accounts for about
to 60% of cases).3,13 These bacteria, especially the Streptococcus angino-
sus (milleri) group (Streptococcus anginosus, Streptococcus constellatus, *References 3, 12-16, 25, 30, 31, 32.
1166
10% of central nervous system (CNS) infections caused by L. monocy- recipients of allogeneic bone marrow and stem cell transplants; and
togenes.35,38 Listeria brain abscess is usually seen in immunocompro- patients receiving long-term corticosteroid therapy.53,57,58
mised patients. In a review of 39 cases of Listeria brain abscess, 85% Mucormycosis (zygomycosis) is one of the most acute, fulminant
of the patients had significant underlying conditions (including leuke- fungal infections known. Many predisposing conditions to mucormy-
Part II Major Clinical Syndromes
mia, lymphoma, HIV infection, and various conditions requiring cor- cosis have been described, including diabetes mellitus (70% of cases)
ticosteroids or other immunosuppression), and disease was often usually in association with acidosis, acidemia from profound systemic
associated with concomitant meningitis (38% of cases) and bacteremia illnesses (e.g., sepsis, severe dehydration, severe diarrhea, chronic renal
(86% of cases).36 In contrast, although meningitis caused by other failure), hematologic neoplasms, renal transplantation, injection drug
facultative gram-negative organisms (e.g., Citrobacter koseri [diversus], use, and the use of deferoxamine.55,59,60 In the past 2 decades, mucor-
Proteus spp., Serratia marcescens, or Enterobacter spp.) is infrequent, it mycosis has emerged as an important invasive fungal infection in solid
is associated with concomitant brain abscess in more than 75% of organ and hematopoietic stem cell transplantation recipients61; among
cases1,39-41; children with bacteremia or meningitis caused by these hematopoietic stem cell transplant recipients with mucormycosis, 10% to
organisms should be evaluated for the possibility of brain abscess. 15% have CNS involvement, most frequently in the context of dissemina-
Salmonella spp. have rarely been reported to cause brain abscess, tion. Less than 5% of cases involve normal hosts. CNS disease may result
usually after bacteremia in the presence of some compromise of the from direct extension of the rhinocerebral form of mucormycosis, by
reticuloendothelial system.42 Cerebral abscesses may also be a compli- open-head trauma or by hematogenous dissemination. The order Muco-
cation of infection with Burkholderia pseudomallei.43 Actinomycosis of rales includes many species that have caused brain lesions (see Chapter
the CNS may manifest as brain abscess, usually secondary to hematog- 260), with Rhizopus arrhizus (oryzae) being one of the most common.
enous spread from a primary infection in the lung, abdomen, or pelvis, Infection with Scedosporium spp. (Scedosporium apiospermum and
although contiguous spread from foci of infection in the ears, paranasal Scedosporium prolificans) may cause CNS disease in normal and
sinuses, or cervicofacial regions may occur; actinomycotic brain immunocompromised hosts (e.g., patients with neutropenia or cellular
abscess should be considered in patients with head trauma, previous immunodeficiency).† S. apiospermum is the asexual form of Pseud-
surgery, and otorhinolaryngeal infections who present with a long allescheria boydii and may enter the CNS by direct trauma, by hema-
duration of neurologic symptoms and no fever.44 Nocardial brain togenous dissemination from a pulmonary route, by direct extension
abscess (usually caused by Nocardia asteroides) may occur as an iso- from infected sinuses, or perhaps by way of an intravenous catheter.
lated CNS lesion or as part of a disseminated infection in association One recent case was observed in a patient who underwent extracor-
with pulmonary or cutaneous disease.1 This organism is most often poreal membrane oxygenation.67 Brain abscess is the usual CNS mani-
isolated in patients with defects in cell-mediated immunity (in patients festation, although meningitis and ventriculitis have also been reported.
receiving corticosteroid therapy, in organ transplant recipients, in There is an association between near-drowning in polluted water and
patients infected with HIV, and in patients with neoplastic disease),45,46 subsequent illness, resulting from the pathogen’s presence in contami-
although 50% of patients with nocardiosis have no underlying condi- nated water and manure.
tions. In a series of organ transplant recipients with Nocardia brain Many of the etiologic agents of fungal meningitis may also cause
abscess,46 use of trimethoprim-sulfamethoxazole prophylaxis for Pneu- brain abscess (e.g., Cryptococcus neoformans, Coccidioides spp., Histo-
mocystis jirovecii (formerly P. carinii) was not shown to be protective plasma capsulatum, and Blastomyces dermatitidis); the epidemiologic
against Nocardia infection. Cases of nocardial brain abscess have also and etiologic characteristics of these organisms are described in other
been seen in pregnant patients.47 Mycobacterium tuberculosis and non- chapters of this book. Many of the melanized, or dematiaceous, fungi
tuberculous mycobacteria have been increasingly observed to cause have also been reported to cause brain abscess, including, in particular,
focal CNS lesions,1, 3,48 with cases reported in patients with HIV infec- Cladophialophora bantiana, Bipolaris hawaiiensis, Bipolaris spicifera,
tion and after solid-organ transplantation,49,50,51 although tuberculous Exophiala (Wangiella) dermatitidis, Ochroconis gallopava (Dactylaria
brain abscess can be seen in immunocompetent and immunocompro- constricta var. gallopava), Chaetomium strumarium, Curvularia
mised hosts.52 In a series of 715 cases of brain abscess in India from pallescens, Rhinocladiella mackenziei, Fonsecaea monophora, and Acro-
1999 to 2006, 60% of patients had infection with M. tuberculosis.8 phialophora fusispora.55,68-70 More than half of published cases were in
patients with no risk factors or immunodeficiency; no specific expo-
Fungal Brain Abscess sures were associated with onset of infection, although most cases seem
The incidence of fungal brain abscess has increased as a result of the to occur in rural areas.70
prevalent administration of immunosuppressive agents, broad-
spectrum antimicrobial therapy, and corticosteroids.53-55 The diagnosis Protozoal and Helminthic Brain Abscess
of fungal brain abscess is often unexpected, and many cases are not Several protozoa and helminths have been reported to produce brain
discovered until autopsy. In autopsy studies, Candida spp. have abscess,‡ including Trypanosoma cruzi, Entamoeba histolytica, Schisto-
emerged as the most prevalent etiologic agents; neuropathologic soma spp., and Paragonimus spp. In addition, free-living amebas (Nae-
lesions include microabscesses, macroabscesses, noncaseating granu- gleria spp., Acanthamoeba spp., and Balamuthia spp.) are preferentially
lomas, and diffuse glial nodules. Risk factors for invasive Candida neurotropic. Neurocysticercosis, caused by the larval form of Taenia
infection include the use of corticosteroids, broad-spectrum antimi- solium, is a major cause of brain lesions in the developing world.75,76
crobial therapy, and hyperalimentation. Disease is also seen in prema- The epidemiologic features and approach to diagnosis and manage-
ture infants; in patients with malignancy, neutropenia, chronic ment of these organisms are discussed in other chapters.
granulomatous disease, diabetes mellitus, or thermal injuries; and in Toxoplasma gondii is the most common protozoal cause of brain
patients with a central venous catheter in place.55,56 Several other patho- abscess.73,77 The incidence of human infection caused by T. gondii
genic fungi should be considered in the differential diagnosis of fungal depends on dietary habits (especially the amount of meat consumed
brain abscess, however, particularly in immunosuppressed patients. and whether eaten rare, raw, or well done), the number of stray cats
Cases of intracranial infection caused by Aspergillus spp. have been living in close proximity to humans, climatic conditions (moderate
reported worldwide, with most cases occurring in adults. Cerebral temperatures and high humidity favor oocyst survival in soil), and
aspergillosis is reported in 10% to 20% of all cases of invasive aspergil- the overall level of sanitation and hygiene. T. gondii infection of the
losis, and only rarely is the brain the only site of infection.57 The lungs CNS appears in various syndromes but is usually associated with the
are the usual site of primary infection, and intracranial seeding occurs development of intracerebral mass lesions or encephalitis in immuno-
during dissemination of the organism or by direct extension from an compromised hosts. In the past, most cases of CNS toxoplasmosis
area anatomically adjacent to the brain (e.g., the paranasal sinuses).55 occurred from reactivation of disease in patients with reticuloendothe-
Most cases of invasive aspergillosis are found in neutropenic patients lial malignancies (owing to either the malignancy itself or associated
who have an underlying hematologic malignancy. Other risk groups immunosuppressive or cytotoxic therapy), or in patients receiving
include patients with hepatic disease, Cushing’s syndrome, diabetes
mellitus, chronic granulomatous disease, or HIV infection; injection †
References 55, 62, 63, 64, 65, and 66.
drug abusers; postcraniotomy patients; organ transplant recipients; ‡
References 1, 3, 71, 72, 73, 74.
1167
immunosuppressive therapy after organ or bone marrow transplanta- malignant gliomas after craniotomy. These patients were treated with
tion or for treatment of collagen vascular disorders.73,77,78 Disease in Gliadel wafers,103 which are placed locally in the tumor bed and release
organ transplant recipients not only occurs secondary to reactivation carmustine after they undergo hydrolysis. The wafers may serve as a
but also may occur after the transfer of infected cysts in the allograft, nidus for subsequent infection.

most commonly in heart transplant recipients. The incidence of brain abscess formation after head trauma ranges
The number of cases of CNS toxoplasmosis has increased dramati- from 3% to 17% in military populations, where it is usually secondary
cally since 1981, specifically in patients with HIV infection.73,77,79-81 to retained bone fragments or contamination of initially “sterile”
Studies before the advent of antiretroviral therapy estimated that 5% missile sites with bacteria from skin, clothes, and the environment.104
to 47% of patients latently infected with T. gondii would develop CNS In a study of 160 war missile penetrating craniocerebral injuries in
disease.82 The use of trimethoprim-sulfamethoxazole prophylaxis of P. Croatia, in which 21 skull base injuries were treated surgically,105 the
jirovecii pneumonia and antiretroviral therapy has now substantially authors did not attempt to remove all retained metallic or bone frag-
decreased the incidence of Toxoplasma encephalitis.83,84 ments but only the accessible ones. Retained foreign bodies did not
seem to increase the infection rate except in cases with an in-driven
PATHOGENESIS AND cluster of bone fragments or cerebrospinal fluid (CSF) leak; three cases
PATHOPHYSIOLOGY of brain abscess were seen, for which repeat surgery was required.
Pathogenesis These findings were confirmed in another retrospective study from
Microorganisms can reach the brain by several different mechanisms Croatia in 88 patients with missile brain wounds in which only acces-
(see Table 92-1).§ The most common pathogenic mechanism of brain sible bone and metallic fragments were removed during intracranial
abscess formation is spread from a contiguous focus of infection, most débridement106; there were nine cases of brain abscess, and retained
often in the middle ear, mastoid cells, or paranasal sinuses. Brain fragments were not responsible for an increased rate of infection. In
abscess occurring secondary to otitis media is usually localized to the another study of 43 patients who survived low-velocity missile injuries
temporal lobe or the cerebellum; in one review of 41 cases of brain of the brain during military conflicts and who had retained intracranial
abscess from an otogenic source, 54% were in the temporal lobe, 44% fragments,107 suppurative sequelae were seen in 6 patients, and 2 of
were in the cerebellum, and 2% were in both locations.30 Early studies these progressed to brain abscess. Traumatic predisposing conditions
reported that 40% of brain abscesses were associated with otitis media, to brain abscess in the civilian population (incidence of 2.5% to 10.9%
but this number has been decreasing. Compared with earlier reports, after trauma) include compound depressed skull fractures, dog bites,
more recent series have shown a decrease in the number of cases sec- rooster pecking, horse bites, tongue piercing, and, especially in chil-
ondary to otitis media and an increase in cases after neurosurgery and dren, injury from lawn darts and pencil tips.108-111 Nosocomial brain
trauma.17 If antimicrobial therapy of otitis is neglected, however, there abscess has also been reported after halo pin insertion112 after electrode
is an increased risk for intracranial complications.30 Paranasal sinusitis insertion to localize seizure foci113 and after placement of deep brain
continues to be an important condition predisposing to brain abscess. stimulation hardware114 and intracranial pressure monitors.115
The frontal lobe is the predominant abscess site, although when brain Brain abscess is cryptogenic in 10% to 35% of patients.3,21 Patent
abscess complicates sphenoid sinusitis, the temporal lobe or sella foramen ovale has been suggested as a possible predisposing condition
turcica is usually involved. Dental infections are a less common cause in patients with cryptogenic brain abscess,116 although this report of
of brain abscess85,86; infections of molar teeth seem most often to be two patients did not establish patent foramen ovale as a definitive risk
the inciting factor. The frontal lobe is the usual site of the abscess after factor.
dental infection, but temporal lobe extension has also been reported.
A second mechanism of brain abscess formation is hematogenous Initiation of Infection
dissemination to the brain from a distant focus of infection. These Few studies have focused on the identification of the specific virulence
abscesses are usually multiple and multiloculated, and they have a factors of microorganisms that produce brain abscess. Contrary to
higher mortality rate than abscesses that arise secondary to contiguous common views, the brain may be more susceptible to infection than
foci of infection.3,4 The most common sources of initial infection in many other tissues. Compared with skin, the brain is significantly more
adults are chronic pyogenic lung diseases, especially lung abscess, susceptible to appropriate bacterial challenge; this was studied in a rat
bronchiectasis, empyema, and cystic fibrosis. Brain abscess may also model of experimental brain abscess. Injections of 104 colony-forming
occur hematogenously from wound and skin infections, osteomyelitis, units (CFUs) of S. aureus or 106 CFUs of E. coli failed to cause infection
pelvic infection, cholecystitis, and other intra-abdominal infections. in the skin, whereas brain tissue was susceptible to 102 CFUs of either
Another predisposing factor leading to hematogenously acquired brain organism, with resultant abscess formation.117
abscess is cyanotic congenital heart disease,87-89 which accounts for 5% The brain may also have different susceptibilities to infection by
to 15% of all brain abscess cases, with higher percentages in some different organisms. In a rat model of experimental brain abscess,
pediatric series. These are most commonly seen in patients with tetral- strains of E. coli were more virulent (i.e., leading to abscess formation
ogy of Fallot or transposition of the great vessels. Brain abscess is rare at lower inocula) than Pseudomonas aeruginosa, S. aureus, or Strepto-
after bacterial endocarditis (<5% of cases in most series),90,91,92 despite coccus pyogenes.118 E. coli strains possessing the K1 antigen were more
the presence of continuous bacteremia; one recent study found brain infective than K1-negative strains, indicating that certain encapsulated
abscess in 14 of 198 critically ill patients with infective endocarditis.93 strains may be more virulent in the production of brain abscess. The
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syn- role of the capsule among other bacterial species in the pathogenesis
drome) is a predisposing factor for brain abscess (occurring in about of brain abscess has not been evaluated. The inoculation of Bacteroides
1% of patients) and is almost always observed in patients with coexist- fragilis or microaerophilic organisms such as S. intermedius into rat
ing pulmonary arteriovenous malformations, perhaps by allowing brain failed to produce infection and abscess formation, although these
septic emboli to cross the pulmonary circulation without capillary organisms account for a high percentage of isolates from patients with
filtration or by bacterial seeding of an ischemic portion of the brain brain abscess (discussed earlier). This discrepancy may be explained
after paradoxical sterile emboli.94-97,98 The risk for developing brain because brain abscess is often a result of contiguous spread of chronic
abscesses in patients with hereditary hemorrhagic telangiectasia ranges otitic or sinus infections, and the synergistic infectivity of mixed popu-
from 5% to 9% and is 1000 times greater than in the general popula- lations of anaerobes plus a facultative organism may be necessary to
tion. Brain abscesses have also developed after esophageal dilation and establish the disease.119,120 In an experimental dog model of brain
after sclerosing therapy for esophageal varices.99-101 abscess formation, the inoculation of B. fragilis in mixed culture with
Trauma is a third pathogenic mechanism in the development of Staphylococcus epidermidis caused a virulent reaction,121 but each
brain abscess. Brain abscess occurs secondary to an open cranial frac- organism was not tested separately.
ture with dural breach or as a result of neurosurgery or a foreign body The role of other bacterial virulence factors in brain abscess for-
injury.102 Four cases of brain abscess were reported in patients with mation has not been evaluated. Despite extensive evidence impli-
cating bacterial lipopolysaccharide in the pathogenesis of bacterial
§
References 1, 3, 4, 12-17, 31, 33. meningitis (see Chapter 89), similar studies on the effect, if any, of
1168
lipopolysaccharide on brain abscess formation and evolution are abscess development was shown by the inability of heat-inactivated S.
unavailable. B. fragilis, a major pathogen producing brain abscess, has aureus to induce proinflammatory cytokine or chemokine expression
a lipopolysaccharide that is chemically distinct from the lipopolysac- in an experimental murine model127; α-toxin was identified as a key
charide of aerobic gram-negative bacilli, but the biologic function of virulence factor for survival of S. aureus in the brain and the subse-
B. fragilis lipopolysaccharide is poorly defined and is unknown in the quent development of brain abscess.
CNS.
An additional concern is the formation of brain abscesses in patients Host Defense Mechanisms
with bacterial meningitis. Brain abscess is a rare complication of bacte- The brain is usually protected from infection by an intact blood-brain
rial meningitis, with the exception of the high prevalence of abscess barrier. When brain infection is established, however, immune defenses
formation in neonates with Citrobacter koseri (diversus) meningitis.40,41 are inadequate to control the infection. Because local opsonization is
In this disease there is a propensity for contiguous inflammation in the deficient, encapsulated bacteria such as E. coli and B. fragilis may
cerebral white matter, which may reflect the effects of endotoxin on the escape efficient phagocytosis within the brain parenchyma. Several
small penetrating vessels in this area; this was examined in an infant studies have shown that phagocytosis of Bacteroides spp. requires heat-
rat model. Infection was initiated in rat pups with a high-grade bacte- labile serum factors (e.g., complement, lysozyme),128,129 and these
remia, followed by infiltration of the leptomeninges and the develop- factors are likely to be absent, or at very low concentrations, even in
ment of ventriculitis.122 Brain abscesses in these animals were found the presence of CNS inflammation early in disease. In addition, an
exclusively in the periventricular white matter, apparently from disrup- outer membrane component of Bacteroides spp. may be important in
tion of the ventricular ependymal lining and direct extension of the the inhibition of neutrophil chemotaxis, reducing the host response to
infection into the parenchyma. The virulence factors responsible for the brain abscess associated with this organism.130
propensity of this organism to cause brain abscess are undefined, The host inflammatory response after the initiation of infection has
although a minor outer membrane protein (32 kDa) may be a marker been evaluated by serial pathologic analysis in several animal models
for strains more likely to produce ventriculitis and brain abscess123; of brain abscess formation.121,124,125 During the early cerebritis stage,
strains that lack the 32-kDa outer membrane protein cause more bac- a border around the initial area of inoculation composed of acute
teremia, meningitis, and death. Other factors, such as fimbriation, inflammatory cells is observed, and this is accompanied by the rapid
biotype, and hemolysis, did not correlate with CNS invasion. development of a perivascular infiltration consisting of neutrophils,
plasma cells, and mononuclear cells. In an experimental rat model of
Natural History of Infection S. aureus brain abscess,131 production of the proinflammatory cytokines
Several animal models have been used to examine the pathophysio- interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α occurred
logic consequences and temporal course of brain abscesses after the 1 to 6 hours after S. aureus exposure. This was followed by enhanced
initiation of infection. A canine model was used to define the patho- concentrations of the CXC chemokine KC/CXCL1 24 hours after bacte-
logic stages of brain abscess formation after the inoculation of rial exposure, which correlated with the appearance of neutrophils in
α-hemolytic streptococci.124 On the basis of detailed histologic evalu- the abscess. Recently, the functional importance of major abscess-
ation, four stages of brain abscess evolution were defined: early cereb- associated T-cell subsets in modulating ongoing innate immune
ritis (days 1 to 3), late cerebritis (days 4 to 9), early capsule formation responses during infection was assessed. Results suggested that manip-
(days 10 to 13), and late capsule formation (day 14 and later after initial ulating Th1 and Th17 cells could expedite S. aureus clearance from the
inoculation). Although these stages are arbitrary, they are useful in CNS parenchyma and limit the extent of tissue damage132; Th1 and
classification and in comparing organisms with regard to their viru- Th17 cells facilitated bacterial clearance and neutrophil and macro-
lence in the production of brain abscess. The early cerebritis stage is phage infiltration/activation during the later stages of brain abscess
characterized by an acute inflammatory infiltrate with visible bacteria formation. In addition, the bacterial capsule was involved in modula-
on Gram stain and marked edema surrounding the lesion. The center tion of innate immunity and complement system activation in an
of the lesion becomes necrotic during the late cerebritis stage, and experimental mouse model in which a capsular strain of S. aureus
macrophages and fibroblasts begin to invade the periphery. With early proliferated faster and caused early expression of the chemokine
capsule formation, the necrotic center begins to decrease in size with CXCL2, resulting in more polymorphonuclear leukocyte infiltration
simultaneous development of a collagenous capsule that is less promi- into the abscess area133; this may benefit the host in terms of survival.
nent on the ventricular side of the lesion; cerebral edema also starts to To address the importance of neutrophils in the early containment
regress during this stage. In this canine model, the collagen capsule of S. aureus infection in the brain, mice transiently depleted of neutro-
was complete circumferentially by the end of the second week and then phils before implantation of bacteria-laden beads had higher CNS
increased in density and thickness. bacterial burdens than control animals.134 Macrophage inflammatory
Similar neuropathologic findings have been observed in a model of protein-2 (MIP-2) and KC/CXCL1, two neutrophil-attracting CXC
experimental anaerobic brain abscess,121 although capsule formation chemokines, were significantly elevated in the brain after S. aureus
could not be divided into early and late stages because of delayed exposure, indicating the importance of these CXCR2 ligands and also
encapsulation. A subsequent study revealed that S. aureus was more neutrophils in the acute host response to S. aureus in the brain. With
virulent than the α-hemolytic streptococci in brain abscess forma- progression to the late cerebritis stage, the acute inflammatory cells
tion125; the amount of necrosis, the total area of involvement after become mixed with macrophages and fibroblasts and reticulin forma-
staphylococcal challenge, the course of infection as it progressed tion surrounds the necrotic center. As the capsule begins to form,
toward resolution, the time for the abscess to reach a stable size, and increased numbers of fibroblasts and macrophages infiltrate the
the time to contain the necrotic region with a collagenous capsule all periphery, and mature collagen is deposited to form a capsule. With
were greater after inoculation of S. aureus. Capsule formation was less further encapsulation, the necrotic center continues to decrease in size
prominent on the ventricular than on the cortical surface in these while marked gliosis develops outside the capsule.
studies,121,124,125 perhaps because differences in vascularity between cor- The importance of this host inflammatory response in containment
tical gray and white matter allowed greater fibroblast proliferation on of the brain abscess has been examined in immunosuppressed animals.
the cortical side of the abscess; this may explain the tendency for brain Initial studies in the canine model of experimental brain abscess with
abscesses to rupture into the ventricular system, rather than into the S. aureus or Proteus mirabilis showed that the administration of dexa-
subarachnoid space. methasone slowed, but did not fully impair, capsule formation.135 In
An alternative hypothesis was supported in an experimental rat contrast, in another study, no evidence of encapsulation was found
model after inoculation of E. coli.126 It was suggested in this study that when dexamethasone was given to rabbits at the same time as inocula-
brain abscesses tended to rupture intraventricularly because the infection of either S. pyogenes or S. aureus.136 In an experimental rat model
tious process is directed along the major white matter tracts (areas of of E. coli brain abscess, dexamethasone administration led to a reduc-
low tissue resistance) rather than as a result of asymmetrical collagen tion in the macrophage and glial response, collagen deposition, and
deposition. The importance of virulence factor production in brain host survival, with an increased number of viable bacteria in the brain
1169
TABLE 92-2 Common Symptoms and Signs in The location of the brain abscess defines the clinical presenta-
Brain Abscess* tion.3,12-17,31,33 Patients with a frontal lobe abscess often present with
headache, drowsiness, inattention, deterioration of mental status,
SYMPTOM OR SIGN FREQUENCY (%) hemiparesis with unilateral motor signs, and a motor speech disorder.

Headache 49-97 The clinical presentation of cerebellar abscesses includes ataxia, nys-
Mental status changes 28-91 tagmus, vomiting, and dysmetria. Temporal lobe abscesses may cause
Focal neurologic deficits 20-66 ipsilateral headache and aphasia if the lesion is in the dominant hemi-
Fever 32-79 sphere; a visual field defect (e.g., an upper homonymous quadran-
Triad of headache, fever, and focal deficit <50 tanopia) may be the only presenting sign of a temporal lobe abscess.
Seizures 13-35 Abscesses of the brainstem usually manifest with facial weakness, fever,
Nausea and vomiting 27-85
headache, hemiparesis, dysphagia, and vomiting.141,142 The classic find-
ings of a well-defined brainstem syndrome are frequently lacking in
Nuchal rigidity 5-52
patients with brainstem abscesses because the abscess is likely to
Papilledema 9-51
extend longitudinally along fiber tracts, rather than expanding
*The clinical presentation varies depending on the size and location of the abscess. transversely.1
Data from references 1, 3, 5, 11, 21, 31, and 33. Certain pathogens may lead to the development of specific clinical
characteristics after CNS infection. In patients with nocardial brain
abscess, the presentation is generally nonspecific with fever, headache,
abscess.126 Co-administration of dexamethasone also impaired the and focal deficits determined by the site and size of the lesion.45,46,143
lymphocytic and fibroblastic response in a rat model of experimental The clinical suspicion of nocardial brain abscess may be increased by
S. aureus brain abscess137 but did not entirely halt the encapsulation or the presence of pulmonary, skin, or muscle lesions, which are present
reduce the associated cerebral edema. concurrently in many, but not all, cases. All patients with pulmonary
Another study used dogs that were immunosuppressed with aza- nocardiosis should undergo evaluation to exclude CNS disease. In
thioprine and prednisone 7 days before the intracerebral inoculation HIV-infected patients with tuberculous brain abscess, seizures, head-
of α-hemolytic streptococci.138 The immunosuppressed animals mani- ache, altered consciousness, and hemiparesis are prominent presenting
fested a decreased inflammatory response characterized by a reduction symptoms.51
in neutrophils and macrophages in the lesion, a decrease and delay in Patients with Aspergillus brain abscess most commonly manifest
collagen deposition, and persistence of viable organisms into the late signs of a stroke syndrome (secondary to ischemia or intracerebral
capsule stage. Neutrophils, plasma cells, lymphocytes, and macro- hemorrhage or both) referable to the involved area of brain.55 Head-
phages were markedly reduced in the areas surrounding the necrotic ache, encephalopathy, and seizures may also occur. Fever is an incon-
center of the abscess, and cerebritis was decreased outside the develop- sistent feature, and signs of meningeal irritation are rare. Patients who
ing capsule. Gliosis was markedly increased, however, in the area sur- are severely immunocompromised usually present with nonspecific
rounding the collagen capsule in these immunosuppressed dogs. findings (i.e., alteration in mental status or seizures or both) shortly
Although the decreased inflammatory response and edema formation before death, whereas patients who are less immunocompromised are
resulted in less mass effect initially, the eventual size and area of the more likely to have headache and focal neurologic deficits.57 Patients
abscess may have become larger as a result of the diminished host with Aspergillus brain abscess commonly have evidence of aspergillosis
response. involving other organ systems.
Rhinocerebral mucormycosis initially manifests as complaints refer-
CLINICAL PRESENTATION able to the eyes or sinuses, including headache (often unilateral), facial
The clinical course of brain abscess ranges from indolent to fulmi- pain, diplopia, lacrimation, and nasal stuffiness or epistaxis55,60; fever
nant.‖ Most clinical manifestations (Table 92-2) are not due to the is usual. As the infection spreads to contiguous structures, necrotic
systemic signs of infection but rather to the size and location of a lesions appear in the turbinates, nose, paranasal skin, or hard palate.
space-occupying lesion within the brain and the virulence of the Chemosis, proptosis, and external ophthalmoplegia may occur. Cranial
infecting microorganism. Headache is the most common presenting nerve abnormalities are common (including CN II through VII, IX, and
symptom and is observed in 70% to 75% of patients. The headache may X), and blindness may occur as a result of invasion of the cavernous
be moderate to severe and hemicranial or generalized, but it lacks sinus, ophthalmic artery, and orbit. Thrombosis is a striking feature of
particularly distinguishing features, accounting for frequent delays in this disease because the organism has a proclivity for blood vessel inva-
diagnosis. Sudden worsening of the headache, accompanied by a new sion. Focal neurologic deficits, such as hemiparesis, seizures, or monoc-
onset of meningismus, may signify rupture of the abscess into the ular blindness, suggest far-advanced disease. With further progression,
ventricular space139; this complication is often associated with a high invasion of the internal carotid artery in the cavernous sinus can occur,
mortality rate (85% in some series). accompanied by metastatic lesions in the frontoparietal cortex and
In a study of 33 consecutive patients with intraventricular rupture deepening coma. Among patients with nonrhinocerebral brain abscess
of brain abscess, severe headaches and signs of meningeal irritation caused by the Mucorales, fever, headache, or focal neurologic deficits
were prominent before rupture, with a rapidly deteriorating clinical were present in more than half the patients. In one review of 22 cases,59
condition developing within 10 days after the signs of meningeal irrita- 50% of the patients were injection drug users and the basal ganglia were
tion140; CT before rupture showed localized enhancement of the ven- the most commonly involved CNS site (83% of patients).
tricular wall adjacent to the abscess, most likely because capsule Brain abscess caused by S. apiospermum tends to occur in immu-
formation was more complete on the cortical side than on the ventricu- nocompromised patients or in patients 15 to 30 days after an episode
lar side of the abscess. In another study, intraventricular rupture was of near-drowning.63,64 Brain abscesses can be located in the cerebrum,
more likely if the abscess was deep seated, multiloculated, and in close cerebellum, or brainstem; clinical presentations include seizures,
proximity to the ventricular wall20; a reduction of 1 mm in the distance altered consciousness, headache, meningeal irritation, focal neurologic
between the ventricle and the abscess increased the rupture rate by deficits, abnormal behavior, and aphasia. The clinical manifestations of
10%. Less than 50% of patients with brain abscess present with the CNS disease caused by Cryptococcus, Histoplasma, Coccidioides,
classic triad of fever, headache, and focal neurologic deficit. In addi- Candida, and other fungal pathogens depend on the intracranial loca-
tion, the clinical presentation of brain abscess in an immunocompro- tion of the abscess. In one review, nearly one third of bone marrow
mised patient may be masked by the diminished inflammatory transplant recipients with brain abscess caused by Candida spp. had no
response.53,54 signs or symptoms54; these infections were commonly diagnosed at
postmortem examination.
The clinical manifestations of CNS toxoplasmosis in immunocom-
‖
References 1, 3, 11-17, 20, 21, 31, and 33. promised patients are variable, ranging from an insidious process
1170
evolving over several weeks to acute onset with a confusional state; the appearance is similar to that of the early cerebritis stage. CT is also useful
initial symptoms and signs may be focal or nonfocal or both.73,77 T. for following the course of brain abscess, although after aspiration,
gondii has a predilection to localize in the basal ganglia and brainstem, improvement in the CT appearance may not be seen for 5 weeks or longer.
producing extrapyramidal symptoms resembling those of Parkinson’s Magnetic resonance imaging (MRI) has been extensively evaluated
disease. Generally, patients who present with nonfocal abnormalities in the diagnosis of brain abscess and is the first imaging choice in the
develop signs of focal neurologic disease as the infection progresses, evaluation of a patient suspected to have this disorder. MRI is more
although some patients develop a diffuse, rapidly fatal encephalopathic sensitive than CT and offers significant advantages in the early detec-
process. Nonfocal evidence of neurologic dysfunction may predomi- tion of cerebritis, including greater contrast between cerebral edema
nate, including generalized weakness, headache, confusion, lethargy, and adjacent brain, more conspicuous spread of inflammation into the
alteration of mental status, personality changes, and coma. CNS toxo- ventricles and subarachnoid space, and earlier detection of satellite
plasmosis may also manifest differently depending on the risk group. lesions (Fig. 92-2).144 On T1-weighted images, the abscess capsule often
Infection in transplant recipients is often diffuse, disseminated disease. appears as a discrete rim that is isointense to mildly hyperintense.
Localizing neurologic signs tend to occur late in the course of infection Contrast enhancement with the paramagnetic agent gadolinium dieth-
in transplant recipients or not at all. In patients with underlying malig- ylenetriaminepentaacetic acid provides the added advantage of clearly
nancies (e.g., Hodgkin’s disease), the presentation of toxoplasmic differentiating the central abscess, the surrounding enhancing rim, and
encephalitis is evenly distributed between focal and nonfocal manifes- the cerebral edema surrounding the abscess.
tations of encephalitis. On T1-weighted images, enhancement of the abscess capsule
Patients with acquired immunodeficiency syndrome (AIDS) and occurs. On T2-weighted images, the zone of edema that surrounds the
toxoplasmic encephalitis often present subacutely with nonspecific abscess is one of marked high signal intensity; the capsule now appears
symptoms, such as neuropsychiatric complaints, headache, disorienta- as a well-defined hypointense rim at the margin of the abscess. Therapy
tion, confusion, and lethargy progressing over 2 to 8 weeks; associated with corticosteroids can decrease enhancement seen with CT and MRI.
fever and weight loss are also common.77,79,80,82 Patients develop clinical The combined use of fluid-attenuated inversion recovery (FLAIR)
evidence of focal CNS mass lesions with ataxia, aphasia, hemiparesis, imaging, proton MR spectroscopy, diffusion-weighted imaging, and
visual field loss, and vomiting or a more generalized encephalitis with diffusion tensor imaging has been shown to improve the specificity of
increasing confusion, dementia, and stupor; seizures are common and the diagnosis of focal ring-enhancing lesions and differentiate brain
may be the presenting clinical manifestation of CNS toxoplasmosis in abscess from other cystic lesions of the brain, including tumors.3,145,146
patients with AIDS. The distinction of abscess from rim-enhancing tumors is done by
demonstrating amino acids within the contents of the cysts, a finding
DIAGNOSIS that is essentially diagnostic of the presence of activated polymorpho-
CT has revolutionized the diagnosis of brain abscess. Before the advent nuclear leukocytes. Proton MR spectroscopy can differentiate necrotic/
of CT, delays in diagnosis contributed significantly to the high mor cystic tumors and cerebral abscesses; in combination with diffusion-
bidity and mortality in patients with brain abscess. CT has rendered weighted imaging, it can significantly increase the diagnostic accuracy
diagnostic tests such as angiography, ventriculography, pneumoen- of conventional MRI with a sensitivity of 72% to 96% and a specificity
cephalography, and radionuclide brain scanning virtually obsolete. The of 86% to 96%.146 Succinate and acetate peaks on proton MR spectros-
characteristic CT appearance of brain abscess is that of a hypodense copy, observed only in anaerobic infections due to glycolysis and sub-
center with a peripheral uniform ring enhancement after the injection sequent fermentation, can be used to further differentiate anaerobic
of contrast material; this is surrounded by a variable hypodense area from aerobic metabolism.146 Although the presence of amino acids in
of brain edema (Fig. 92-1).144 Other CT findings include nodular proton MR spectroscopy is a sensitive marker of pyogenic abscess, its
enhancement and areas of low attenuation without enhancement, the absence does not exclude a pyogenic etiology.147
latter of which is observed during the early cerebritis stage before CT and MRI are also quite sensitive in defining lesions in patients
abscess formation; as the abscess progresses, contrast enhancement is with fungal brain abscess; these modalities are not specific, although
observed. When the abscess becomes encapsulated in the later stages, some exceptions do exist. The finding of a cerebral infarct in a patient
contrast material no longer differentiates the lucent center and the CT with risk factors for invasive aspergillosis should suggest that
A B
FIGURE 92-1 CT of the head reveals a large rounded area of low attenuation in the right lentiform nucleus, with compression of the
horn of the right lateral ventricle, and a shift to the left with vasogenic edema. A, Unenhanced CT scan reveals increased signal within the
center of the area of low attenuation. B, After intravenous administration of a contrast agent there is ring enhancement of the abscess and evidence of
a smaller satellite lesion.
1171

A B C
FIGURE 92-2 MRI of the brain (same patient as shown in Fig. 92-1) reveals 2-cm, round, ring-enhancing lesion in right lentiform nucleus
with associated vasogenic edema and midline shift to the left. A, T1-weighted image reveals ill-defined area of low attenuation. B, T1-weighted
image after administration of gadolinium reveals ring enhancement of the abscess. C, T2-weighted image shows hypointensity of rim of abscess with
large area of high signal intensity consistent with cerebral edema.
diagnosis.55 The areas of infarction typically develop into either single States initiate a therapeutic trial of anti-Toxoplasma chemotherapy in
or multiple abscesses involving the cerebrum (usually frontal or tem- a patient with AIDS who is seropositive for T. gondii and has charac-
poral lobes) or cerebellum. In immunosuppressed patients with CNS teristic neuroradiographic abnormalities.150 This is generally a valid
aspergillosis, there is little or no contrast enhancement with MRI.58 In approach in patients with AIDS and presumed CNS toxoplasmosis (see
patients with rhinocerebral mucormycosis, CT and MRI may show Chapter 280).
characteristic changes, including sinus opacification, erosion of bone, CSF polymerase chain reaction (PCR) assay has also been used as
and obliteration of deep fascial planes. Frontal lobe involvement in a diagnostic test for toxoplasmic encephalitis; CSF PCR assay has a
mucormycosis may show little or no ring enhancement; the lack of specificity of 96% to 100% but a sensitivity of only about 50% in the
contrast enhancement is a poor prognostic sign because it indicates diagnosis of CNS toxoplasmosis.82 In contrast, in a study of 12 HIV-
failure of host defense mechanisms to isolate or encapsulate the offend- infected patients with suspected cerebral toxoplasmosis who neither
ing organism. Cavernous sinus involvement may be seen on MRI. met the diagnostic criteria from the Centers for Disease Control and
CT and MRI are extremely useful in the diagnosis of CNS toxo Prevention nor had positive mouse inoculation tests,151 11 of 12
plasmosis.77,79 The characteristic CT appearance (seen in 90% of patients with confirmed toxoplasmosis had positive PCR results in
patients) is that of rounded isodense or hypodense lesions with ring either blood or CSF, suggesting a high sensitivity, specificity, and clini-
enhancement after the administration of contrast material; homoge- cal utility of this test in the diagnosis of toxoplasmic encephalitis.
neous enhancement or no enhancement can also be seen. There are Further studies are needed to determine the utility of CSF PCR assay
multiple lesions in 70% to 80% of cases, often involving the corticome- in the diagnosis of toxoplasmic encephalitis.
dullary junction and the basal ganglia, although any part of the CNS A major advance in the use of CT in patients with suspected brain
may be involved. Marked edema and a mass effect are also frequently abscess is the ability to perform stereotactic CT-guided aspiration to
observed. A double-dose, delayed-contrast study may be a more sensi- facilitate microbiologic diagnosis and to guide antimicrobial therapy.
tive method for delineating the true extent of disease. CT usually Ultrasound-guided aspiration, via transdural insonation, has also been
underestimates the number of lesions documented pathologically at performed through a single bur hole and showed excellent abscess
autopsy. MRI has a greater sensitivity than CT and has detected lesions visualization in 10 patients in one study,152 although aspiration by CT
in patients with active toxoplasmic encephalitis whose CT scans were guidance is generally the preferred method. Aspiration during the
normal. MRI should be performed in patients with AIDS and neuro- cerebritis stage may be complicated by hemorrhage.
logic symptoms in whom CT shows no abnormality (or only cerebral At the time of aspiration, specimens should be sent for Gram stain,
atrophy). CT and MRI also may be useful in following the response to routine aerobic and anaerobic cultures, and cultures for mycobacteria
therapy because most patients show radiographic evidence of improve- and fungi. In patients with a likely bacterial brain abscess, 16S rRNA
ment within 10 to 14 days of initiation of anti-Toxoplasma therapy.81,148 gene sequencing and amplification may serve as an important adjunc-
In an immunosuppressed host with presumed toxoplasmic enceph- tive tool in patients with negative culture results but who have histo-
alitis, serologic testing aids in the diagnosis. In patients with AIDS, pathologic and Gram stain findings suggestive of a bacterial
toxoplasmic encephalitis occurs as a result of a recrudescence of a abscess153-156; this technique may provide a definitive etiologic diagno-
latent infection.79,80 In this situation, the presence of anti-Toxoplasma sis allowing for targeted antimicrobial therapy, although more studies
IgG antibody can almost uniformly be shown before the development are needed. In another study, use of multiple 16S ribosomal DNA
of the encephalitis. More than 97% of patients with AIDS and toxo- sequencing was found to dramatically increase the number of infec-
plasmic encephalitis have serum IgG antibody titers against T. gondii tious agents identified in cerebral abscesses.157 These data were con-
ranging from 1 : 8 to more than 1 : 102477; the predictive value of a posi- firmed in a subsequent study in which metagenomic analysis from 71
tive serologic result in patients with characteristic abnormalities on patients identified 71 taxa that had not been previously identified,
radiographic studies may be 80% in the United States.79,149 In contrast, including 37 that are yet uncultured158; the major source of these agents
in a retrospective review of 115 patients with AIDS and CNS toxoplas- was the sinuses and dental flora, and they were found in polymicrobial
mosis at San Francisco General Hospital between 1981 and 1990, 4 of specimens. However, it is not precisely clear as to the importance of
18 patients with pathologically confirmed disease had undetectable many of these pathogens in patients with brain abscess.159 In addition,
anti-Toxoplasma IgG antibody by an indirect immunofluorescence other special stains, such as acid-fast stains for mycobacteria, modified
assay.81 Despite these conflicting data, many physicians in the United acid-fast stains for Nocardia, and special stains (e.g., mucicarmine,
1172
methenamine silver) for fungi, should be used to aid in making an 4. Therapy with corticosteroids should be initiated in patients with
etiologic diagnosis. significant edema and an associated mass effect that is causing
Aspergillus spp. manifest as septate hyphae in tissue sections with increased intracranial pressure or a predisposition to transtentorial
acute-angle, dichotomous branching. Biopsy specimens of cerebral herniation. Phenytoin should be considered to prevent seizures
lesions in mucormycosis usually show irregular hyphae, right-angle during early stages of therapy.
branching, and a lack of septa. S. apiospermum, S. prolificans, and The empirical approach to antimicrobial therapy for bacterial brain
Fusarium hyphae cannot be distinguished reliably from Aspergillus spp. abscess should take into account the frequency of isolation of certain
Hyphae of melanized, or dematiaceous, fungi in the brain may be organisms.3 Because of the high rate of isolation of streptococci (par-
brownish on hematoxylin and eosin stain and tend to have swollen and ticularly the S. anginosus [milleri] group) from brain abscesses of
constricted areas in the hyphae, but they are not reliably distinguished various causes, high-dose intravenous penicillin G or another drug
from other molds. In patients with CNS toxoplasmosis,77 diagnosis (e.g., a third-generation cephalosporin, either cefotaxime or ceftriax-
may require specialized immunohistochemical techniques (peroxidase- one) active against this organism should be included in the initial
antiperoxidase) to detect the organisms or its antigens. Pseudocysts therapeutic regimen. Penicillin G is also active against most anaerobic
and tachyzoites, which are easily identifiable by histopathologic stains, species with the notable exception of B. fragilis, which may be isolated
may not be found in the center of the necrotic lesion and are best identified in a high percentage of cases of brain abscess; metronidazole should
at the periphery of the lesion or within normal brain tissue. A sensitive be included in the initial regimen when this organism is suspected.
test for rapid diagnosis is the immunofluorescence technique that uses Metronidazole has bactericidal activity against B. fragilis and Prevotella
monoclonal anti-Toxoplasma antibodies on brain touch preparations. melaninogenica and attains high concentrations in brain abscess pus, and
its entry into cerebral abscesses is not affected by concomitant corticoste-
INITIAL MANAGEMENT OF THE roid therapy.161 The combination of metronidazole plus a third-generation
PATIENT WITH BRAIN ABSCESS cephalosporin is a common regimen used in more recent series.17
The initial approach to the patient with a suspected brain abscess is a When S. aureus is considered a likely pathogen (e.g., after cranial
multidisciplinary one and should include evaluation by a neuroradi- trauma or after neurosurgery), vancomycin should be used, but therapy
ologist, a neurosurgeon, and an infectious diseases specialist utilizing should be changed to nafcillin if methicillin-sensitive organisms are
the following steps160: isolated.162 Because an increase in community-acquired methicillin-
1. MRI or contrast CT should be performed to verify the suspicion of resistant S. aureus has been observed in recent years, vancomycin
brain abscess. should be used empirically when S. aureus brain abscess is suspected
2. If single or multiple ring-enhancing lesions are found, the patient or proven,24,163 until in vitro susceptibility testing is performed. If P.
should undergo surgery. All lesions greater than 2.5 cm in diameter aeruginosa is a likely infecting pathogen, ceftazidime or cefepime is the
should be excised or stereotactically aspirated, and specimens agent of choice. In patients with a bacterial brain abscess of unclear
should be sent to the microbiology and pathology laboratories (dis- pathogenesis, empirical therapy with vancomycin, metronidazole, and
cussed earlier). For abscesses in the early cerebritis stage, or when a third- or fourth-generation cephalosporin (cefotaxime or ceftriax-
the abscesses are 2.5 cm in diameter or less, the largest lesion should one, or ceftazidime or cefepime if P. aeruginosa is suspected) is recom-
be aspirated for diagnosis and identification of the organism. mended pending culture results.
3. When abscess material has been obtained for microbiologic and In HIV-infected patients with CNS mass lesions, the initial approach
histopathologic studies, empirical antimicrobial therapy should be to management is different because of the high likelihood of the diag-
initiated on the basis of the patient’s predisposing conditions and nosis of toxoplasmic encephalitis.79,164 For patients with large lesions
the presumed pathogenesis of abscess formation (Table 92-3). If a showing a mass effect and threatening impending herniation, open
primary source of infection outside the CNS is recognized as poten- biopsy with decompression is the standard. In HIV-infected patients
tially having led to formation of the brain abscess, empirical anti- with multiple ring-enhancing lesions on contrast-enhanced CT or MRI
microbial therapy can be begun on the basis of microbiologic and positive anti-Toxoplasma IgG serologic tests, empirical therapy for
studies from the other source (e.g., positive blood cultures in a toxoplasmic encephalitis should be initiated (Table 92-4); clinical and
patient with infective endocarditis). radiographic improvement should be observed within 10 to 14 days in
95% of patients with toxoplasmic encephalitis.82,148
For patients with positive anti-Toxoplasma IgG serologic tests
and a single lesion identified by MRI, consideration should be
given to thallium 201 single-photon emission computed tomography
TABLE 92-3 Empirical Antimicrobial Therapy for (201Tl-SPECT) scanning. Although 201Tl-SPECT scans are not sensitive,
Bacterial Brain Abscess positive scans are highly specific for the diagnosis of primary CNS
lymphoma and would warrant stereotactic brain biopsy.165-167 A com-
PREDISPOSING CONDITION ANTIMICROBIAL REGIMEN
pilation of published studies revealed a mean sensitivity and specificity
Otitis media or mastoiditis Metronidazole + third-generation
cephalosporin*
of 92% and 89% for 201Tl-SPECT in distinguishing cerebral lymphoma
from toxoplasmic encephalitis in patients with AIDS.82 201Tl-SPECT
Sinusitis (frontoethmoid or Metronidazole + third-generation
sphenoid) cephalosporin*† was positive, however, in one patient with chronic lymphocytic leuke-
Dental infection Penicillin + metronidazole
mia and a Nocardia brain abscess.168 In addition, a more recent pro-
spective study of 14 HIV-infected patients (12 diagnosed by biopsy and
Penetrating trauma or Vancomycin + third- or fourth-
postneurosurgical generation cephalosporin*‡ 2 by clinical course and response to therapy) suggested limited accu-
Lung abscess, empyema, Penicillin + metronidazole +
racy of 201Tl-SPECT in differentiating lymphoma from non-neoplastic
bronchiectasis sulfonamide§ disease, in which a low uptake ratio did not exclude lymphoma and a
Bacterial endocarditis Vancomycin¶ high uptake ratio did not exclude an infectious cause.169 The accuracy
Congenital heart disease Third-generation cephalosporin*
of 201Tl-SPECT can be affected by the size of the lesion, grade of the
malignancy, presence of necrotic areas in the tumor, and location of
Unknown Vancomycin + metronidazole + third- or
fourth-generation cephalosporin*‡ the lesion. Similar results have been obtained with positron emission
tomography (PET) labeled with 18F-fluorodeoxyglucose combined
*Cefotaxime or ceftriaxone; the fourth-generation cephalosporin cefepime may
also be used.
with CT (18FDG-PET/CT).170,171 However, compared with its use in
†
Add vancomycin when infection caused by methicillin-resistant Staphylococcus patients with malignant neoplasms, fewer data are available on use of
aureus is suspected. PET/CT to image cerebral infections.172
In patients with mass lesions and negative anti-Toxoplasma IgG
‡
Use ceftazidime or cefepime as the cephalosporin if Pseudomonas aeruginosa is
suspected.
§
Trimethoprim-sulfamethoxazole; include if a Nocardia spp. is suspected.
serologic tests, the diagnosis of toxoplasmic encephalitis is possible,
¶
Additional agents should be added based upon other likely microbiologic but unlikely; scanning with 201Tl-SPECT or 18FDG-PET/CT may be
etiologies. helpful in this setting, although each test has limitations and should
1173
TABLE 92-4 Antimicrobial Therapy for Brain Abscess

ORGANISM STANDARD THERAPY ALTERNATIVE THERAPIES

Bacteria*
Actinomyces spp. Penicillin G Clindamycin
Bacteroides fragilis Metronidazole Clindamycin
Enterobacteriaceae Third-generation cephalosporin† Aztreonam, trimethoprim-sulfamethoxazole, fluoroquinolone, meropenem
Fusobacterium spp. Metronidazole Clindamycin, meropenem
Haemophilus spp. Third-generation cephalosporin† Aztreonam, trimethoprim-sulfamethoxazole
Listeria monocytogenes Ampicillin or penicillin G‡ Trimethoprim-sulfamethoxazole
Mycobacterium tuberculosis Isoniazid + rifampin + pyrazinamide + ethambutol
Nocardia spp. Trimethoprim-sulfamethoxazole or sulfadiazine Minocycline, imipenem, meropenem, third-generation cephalosporin,† amikacin
Prevotella melaninogenica Metronidazole Clindamycin, meropenem
Pseudomonas aeruginosa Ceftazidime or cefepime Aztreonam, fluoroquinolone, meropenem
Staphylococcus aureus
Methicillin-sensitive Nafcillin or oxacillin Vancomycin
Methicillin-resistant Vancomycin Trimethoprim-sulfamethoxazole
Streptococcus anginosus (milleri) Penicillin G Third-generation cephalosporin,† vancomycin
group, other streptococci
Fungi
Aspergillus spp. Voriconazole Amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid
complex, itraconazole,§ posaconazole§
Candida spp. Amphotericin B deoxycholate,¶ liposomal Fluconazole
amphotericin B,¶ amphotericin B lipid complex¶
Cryptococcus neoformans Amphotericin B deoxycholate,¶ liposomal Fluconazole
amphotericin B,¶ amphotericin B lipid complex¶
Mucorales Liposomal amphotericin B, amphotericin B lipid Posaconazole§
complex, amphotericin B deoxycholate
Scedosporium apiospermum Voriconazole Itraconazole,§ posaconazole§
Protozoa
Toxoplasma gondii Pyrimethamine + sulfadiazine Pyrimethamine + clindamycin; trimethoprim-sulfamethoxazole; pyrimethamine +
azithromycin, clarithromycin, atovaquone, or dapsone
*Depending on the pathogenesis of bacterial brain abscess (see text), these bacteria may be isolated as part of a mixed infection.
†
Cefotaxime or ceftriaxone.
‡
Addition of an aminoglycoside should be considered.
§
Consider for use in salvage therapy in nonresponding patients or in patients intolerant of amphotericin B–based therapies.
¶
Addition of flucytosine should be considered.
not be relied on in isolation because specific expertise is required for detected consistently only if the daily dosage in adults exceeded 24
interpretation, the tests are costly, and rigid diagnostic criteria have not million units; in some cases, penicillin G may be inactivated in pus,
yet been determined.82 Brain biopsy is optimal, although some experts with the result that bacteria can still be cultured despite adequate
have recommended an empirical trial of therapy for toxoplasmic penicillin concentrations. Limited data are available on the penetration
encephalitis in patients with multiple ring-enhancing lesions even if of the semisynthetic penicillins (e.g., nafcillin, oxacillin) into brain
the anti-Toxoplasma IgG serologic test is negative.164 Brain biopsy abscesses, although some studies suggest that concentrations of these
should be performed in patients who fail to respond. Patients with drugs in brain abscess fluid are variable.25
single lesions on MRI and negative serologic tests should undergo a Metronidazole has excellent in vitro activity against strict anaer-
stereotactic brain biopsy. A strategy for the management of suspected obes, making it an important agent for the treatment of patients with
Toxoplasma CNS lesions in HIV-infected patients can be found in brain abscess.161 Its excellent pharmacokinetic profile (i.e., good oral
Chapter 280. absorption and penetration into brain abscess cavities) has made
metronidazole a more attractive antianaerobic agent than chloram-
THERAPY phenicol for therapy of brain abscess. Metronidazole must always be
When the infecting pathogen is isolated, antimicrobial agents can be used in combination with an antimicrobial agent effective against
modified for optimal therapy. Recommendations for standard therapy, streptococci, however, because polymicrobial infections are common
with alternative agents, are provided in Table 92-4. Table 92-5 lists in patients with brain abscesses. Vancomycin has also been shown to
doses of these agents used for CNS infections. In this section the prin- have excellent concentrations in brain abscess fluid after prolonged
ciples of antimicrobial use and surgical therapy for bacterial and fungal therapy. In one study, simultaneous measurement of vancomycin con-
brain abscesses are reviewed. The therapeutic approach to toxoplasmic centrations in serum and brain abscess fluid was obtained 1 hour after
encephalitis is discussed in Chapter 280. a 500-mg dose162; vancomycin concentrations obtained before and
during operative removal of the brain abscess were 15 µg/mL and
Bacterial Brain Abscess 18 µg/mL, respectively, with a simultaneous serum vancomycin con-
Antimicrobial Therapy centration of 21 µg/mL.
There have been no randomized controlled trials that have evaluated The role of newer antimicrobial agents in the therapy for brain
the efficacy of different antimicrobial agents in the treatment of bacte- abscess is evolving. The third-generation cephalosporins are attractive
rial brain abscess. The antimicrobial agents used to treat bacterial brain agents for the therapy for brain abscess because of their good CNS
abscess should be able to penetrate into the abscess cavity and should penetration and excellent in vitro activity against many of the patho-
have in vitro activity against the pathogens isolated.1,3,4 The few studies gens isolated from bacterial brain abscesses. When cefotaxime was
that have addressed the penetration of antimicrobial agents into brain given in higher doses than usually recommended (3 g every 8 hours),
abscess fluid have included limited numbers of patients. Concentra- brain abscess concentrations of cefotaxime and its active metabolite,
tions of penicillin G have been measured in brain abscess pus but were desacetylcefotaxime, were greater than the minimal inhibitory
1174
TABLE 92-5 Recommended Dosages of associated with an increased risk for seizures, limiting its usefulness in
Antimicrobial Agents for Central Nervous System patients with CNS mass lesions. Meropenem, a carbapenem antimi-
Infections in Adultsa crobial agent similar to imipenem, was successful in one case of an
Enterobacter cloacae brain abscess,179 suggesting that this agent may be
ANTIMICROBIAL TOTAL DAILY DOSING useful in cases of brain abscess, especially when caused by resistant
AGENT DOSAGE INTERVAL (hr) pathogens. In an 11-year retrospective, nonrandomized study compar-
Amikacinb 15 mg/kg 8 ing intravenous cefotaxime and metronidazole to intravenous merope-
Amphotericin B deoxycholate 0.6-1.0 mg/kgc 24 nem or imipenem monotherapy, treatment with meropenem was
Amphotericin B lipid complex 5 mg/kg 24 associated with a significantly lower mortality rate and a lower seizure
Ampicillin 12 g 4 rate compared with imipenem.180 The fluoroquinolones have good
Atovaquoned 3000 mg 6 CNS penetration and have been used anecdotally in the treatment of
Azithromycin 1200-1500 mg 24 patients with brain abscess,181 although further data are needed to
Aztreonam 6-8 g 6-8 determine the efficacy of the fluoroquinolones for the treatment of
Cefepime 6 g 8
brain abscess.
Antimicrobial therapy with high-dose intravenous agents has tra-
Cefotaxime 8-12 g 4-6
ditionally been administered for 6 to 8 weeks in patients with bacterial
Ceftazidime 6 g 8
brain abscesses.1,3,21 This is often followed by oral antimicrobial therapy
Ceftriaxone 4 g 12 for 2 to 3 months if an appropriate agent or agents are available,
Chloramphenicol 4-6 g 6 although the efficacy and necessity of this approach have not been
Ciprofloxacin 800-1200 mg 8-12 established. Biweekly neuroimaging up to 3 months is also suggested
Clindamycin 2400-4800 mg 6 to monitor for abscess reexpansion or failure to resolve.21,160 The com-
Dapsoned 100 mg 24 bination of surgical aspiration or removal of all abscesses larger than
Ethambutold 15 mg/kg 24 2.5 cm in diameter, a 6-week or longer course of intravenous antimi-
Fluconazole 400-800 mg 24 crobial therapy, and improvement on follow-up neuroimaging should
Flucytosined,e 100 mg/kg 6
result in a cure rate of more than 90%.8 Patients should be followed
with neuroimaging until the abscess has completely resolved; if the
Gentamicinb 5 mg/kg 8
abscess enlarges after 2 weeks of antimicrobial therapy, or fails to
Isoniazidd 300 mg 24
resolve after 3 to 4 weeks, further surgical aspiration or excision should
Itraconazole 400-600 mg 12 be performed.
Linezolid 1200 mg 12 Shorter courses (3 to 4 weeks) of antimicrobial therapy may be
Liposomal amphotericin B 5-7.5 mg/kg 24 adequate for patients who have undergone surgical excision of the
Meropenem 6 g 8 abscess. Surgical therapy (i.e., excision or aspiration) is often required
Metronidazole 30 mg/kg 6 for the optimal management of brain abscess (discussed later), although
Nafcillin 12 g 4 certain subsets of patients may be treated with antimicrobial therapy
Oxacillin 12 g 4 alone.142,182-184 These are patients with medical conditions that increase
Penicillin 24 million U 4
the risk of surgery, multiple abscesses, abscesses in a deep or dominant
location, concomitant meningitis or ependymitis, early abscess reduc-
Posaconazoled 800 mg 6-12
tion with clinical improvement after antimicrobial therapy, and abscess
Pyrazinamided 15-30 mg/kg 24
size smaller than 3 cm. In one series, no abscess larger than 2.5 cm
Pyrimethamined 25-100 mgf 24 resolved without surgical therapy.182 The best candidates for medical
Rifampind 600 mg 24 therapy appear to be those with a small abscess (≤2.5 cm), in good
Sulfadiazined 4-6 g 6 clinical condition (Glasgow Coma Scale score >12), and a well-known
Tobramycind 5 mg/kg 8 etiology.185 However, surgery should be considered when the clinical
Trimethoprim-sulfamethoxazole 10-20 mg/kgg 6-12 condition is worsening or in those without clinical or radiologic
Vancomycinh 30-45 mg/kg 8-12 improvement within 1 to 2 weeks.
Voriconazolei 8 mg/kg 12 Patients treated with antimicrobial therapy alone may require pro-
a
longed (up to 12 weeks) courses of parenteral treatment and must
Patients with normal renal and hepatic function; unless indicated, IV mode of
administration used. receive careful clinical and radiographic follow-up. The Infection in
b
Need to monitor peak and trough serum concentrations. Neurosurgery Working Party of the British Society for Antimicrobial
c
Dosages up to 1.5 mg/kg/day may be used for aspergillosis or mucormycosis. Chemotherapy recommends intravenous therapy for 1 to 2 weeks for
d
e
Dosage for oral administration. bacterial brain abscess, after which time, and depending on the clinical
Maintain serum concentrations of 50-100 µg/mL.
f
Higher dosages used in acquired immunodeficiency syndrome patients with response, change to an appropriate oral regimen can be considered.186
toxoplasmic encephalitis; load with 100 to 200 mg. This approach has been used in several series,17,187,188 although it cannot
g
Dosage based on trimethoprim component; higher dose used for Nocardia be considered standard therapy in most patients with bacterial brain
brain abscess. abscess. The ability of MRI and diffusion-weighted imaging to track
h
Adjust dosage based on trough serum concentration; maintain at 15-20 µg/mL.
i
Load with 6 mg/kg IV every 12 hours for two doses; maintain serum trough resolution of the abscess has proved very useful in identifying patients
concentrations of 2-5 µg/mL. with bacterial brain abscess who may only need as little as 2 weeks of
postoperative intravenous antibiotics.234
When a brain abscess caused by Nocardia is suspected or proved,
the sulfonamides, with or without trimethoprim, are recommended
concentrations of most gram-positive and gram-negative organisms as first-line therapy,46,189,190 although treatment failures have been
against which cefotaxime is used systemically. When combined with reported.191 Alternative agents include minocycline, amikacin, imipe-
metronidazole and used in conjunction with surgical excision, high nem, third-generation cephalosporins, and linezolid, which are among
doses of cefotaxime also have been effective clinically in the treatment the most active agents against Nocardia in vitro.192-194 In vitro activity
of brain abscess.173 Ceftriaxone, ceftizoxime, and ceftazidime all have may not always correlate with clinical efficacy, however. Combination
been used in the treatment of brain abscess,174,175 although only a few therapies have been studied,195-199 and combination regimens contain-
patients have been studied. Ampicillin-sulbactam has also been shown ing third-generation cephalosporins or imipenem along with a sulfon-
to be therapeutically successful in patients with brain abscesses176; amide or amikacin should be considered for immunocompromised
intracavitary concentrations were variable, but adequate, in most cases. patients or patients in whom therapy fails.1,200 Linezolid was also shown
Imipenem has been used successfully to treat pyogenic and nocar- more recently to be efficacious in two patients with multiple Nocardia
dial brain abscesses,177,178 although the use of imipenem has been brain abscesses,201 although therapy was changed in one patient as a
1175
result of an adverse effect from linezolid. One patient was successfully through bur holes. In patients with intraventricular rupture of a puru-
treated with unexpectedly low doses of linezolid along with therapeutic lent brain abscess who have dilated ventricles and ventriculitis, ven-
drug monitoring for optimization of drug exposure.202 Brain abscess tricular drainage combined with the administration of appropriate
caused by Nocardia farcinica, a species highly resistant to various anti- intravenous or intrathecal antimicrobial agents, or both, is recom-

microbial agents, has been successfully treated with moxifloxacin, mended20,140; urgent craniotomy and abscess drainage with or without
either alone or in combination with another agent.203-205 The duration lavage of the ventricular system has also been suggested, although the
of antimicrobial therapy for nocardial brain abscess ranges from 3 to optimal approach has not been clarified.
12 months.46,206 Therapy in immunosuppressed patients should prob-
ably be continued for 1 year,143 with careful follow-up to monitor for Fungal Brain Abscess
relapse. The optimal therapy for fungal brain abscesses usually requires a com-
The therapy for tuberculous brain abscess is similar to that for bined medical and surgical approach; surgery involves either excision
tuberculosis in other locations; treatment is more complex, however, or drainage of the abscess. Therapy for fungal brain abscess in immu-
for patients with tuberculous brain abscess caused by multidrug- nocompromised patients carries a high mortality rate, however, despite
resistant and extremely drug-resistant strains. Because published surgery and antifungal therapy.217a Nevertheless, early recognition of
reports on tuberculous brain abscess consist mainly of case reports and this infection can lead to a successful outcome, especially if leuko-
case series, overall mortality rates are not well defined.51 cyte counts return to normal or if the dosages of immunosuppressive
agents can be reduced.1 The mainstay of medical therapy for candidal
Surgical Therapy brain abscess is an amphotericin B preparation plus 5-flucytosine.55
Most patients with bacterial brain abscess require surgical manage- The efficacy of fluconazole in the treatment of Candida brain abscess
ment for optimal therapy. The two procedures available are aspiration has not been evaluated, although one case report in a premature
of the abscess after bur hole placement and complete excision after infant with Candida albicans brain abscess showed a decrease in
craniotomy.21,32,33,207 No prospective trial comparing the two proce- abscess size after the addition of fluconazole to amphotericin B plus
dures has ever been performed, although in a series of 142 patients 5-flucytosine.218
with brain abscess, no significant differences in outcome were observed The antifungal therapy of choice for Aspergillus brain abscess was
in patients treated with excision, craniotomy with drainage, or stereo- previously amphotericin B deoxycholate (0.8 to 1.25 mg/kg/day); doses
tactic drainage.16 However, in one retrospective review of 47 studies up to 1.5 mg/kg/day have been used, depending on the clinical
from 1990 to 2008, patients who underwent aspiration had a mortality response.219 Liposomal amphotericin B (AmBisome), 5 mg/kg daily, is
of 6.6% compared with 12.7% in those who underwent surgical exci- the preferred formulation. However, voriconazole is now the drug of
sion.208 The choice of procedure must be individualized for each choice in patients with Aspergillus brain abscess.220 In one review of
patient. Aspiration may be performed by a stereotactic procedure using voriconazole in the treatment of invasive aspergillosis that included 19
CT or MRI guidance, which affords the surgeon rapid, accurate, and patients with cerebral disease, 3 (16%) patients had a partial response
safe access to virtually any intracranial point, including areas located to treatment,221 although the response rate in more recent studies is
in deep critical regions of the CNS (e.g., brainstem, cerebellum, or approximately 35%.58,220 Combination therapy (voriconazole, com-
diencephalic structures adjacent to the ventricles)175,209-213; aspiration bined with either caspofungin or liposomal amphotericin B) has also
can also be used for swift relief of increased intracranial pressure. In been advocated.222-224
one series of patients with brain abscess from an initially otitic focus, Mucormycosis also should be treated with amphotericin B deoxy-
immediate radical mastoidectomy was used, followed by evacuation of cholate or one of its lipid formulations, along with correction of
the abscess through the mastoidectomy cavity.30 Safety of this surgical underlying metabolic derangements and aggressive surgical débride-
approach is unclear. ment.55,60,225,226 Some data have suggested that the lipid formulations of
Complete excision by craniotomy is now infrequently performed amphotericin B resulted in higher recovery rates than did amphoteri-
because of the development of aspiration and closed drainage tech- cin B deoxycholate in patients with mucormycosis and hematologic
niques described previously, but it may be required in patients with diseases or solid-organ transplantation, leading to a recommendation
multiloculated abscesses (for whom aspiration techniques have failed), for use of a lipid formulation, usually liposomal amphotericin B, as
abscesses containing gas, or abscesses that fail to resolve. Post-traumatic first-line therapy.61 The role of surgery in the treatment of cerebral
abscesses containing foreign bodies or retained bone fragments usually mucormycosis cannot be overemphasized. Because of their propensity
require excision to prevent recurrence, as do abscesses resulting from for invading blood vessels, the Mucorales cause extensive tissue infarc-
fistulous communications and abscesses localized to one lobe but con- tion, impairing the delivery of antifungal agents to the site of infection.
tiguous to a primary focus.21 Excision of abscesses in the cerebellar area Surgery is often the only modality that may effectively eliminate the
has also been recommended, although in recent years, bur hole aspira- invading microorganisms. Amphotericin B has also been applied topi-
tion has emerged as a satisfactory method of drainage8; drainage is cally in the orbital cavities in patients with rhinocerebral mucormyco-
important because precipitous neurologic deterioration can occur in sis,226 although it is unclear if this is beneficial. Posaconazole may be
the relatively smaller volume of the posterior fossa in the presence of considered as follow-up therapy in patients who have already responded
disproportionate edema, especially in children.214 In one retrospective to amphotericin B–based therapies, provided that they are eating well
review, there was a lower mortality in the excision group.215 Patients enough to absorb the antifungal agent.227 Hyperbaric oxygen therapy
with cerebellar abscesses that demonstrate mass effect, effacement, or has been reported to be a useful adjunct in cerebral mucormyco-
displacement of the fourth ventricle, in the setting of overt or incipient sis,228,229 although no prospective, controlled trials have been done to
hydrocephalus, should also have CSF diversion with placement of an assess its efficacy adequately.
external ventricular drain5,8; the presence of a periventricular lucency For Scedosporium brain abscess, surgical drainage is the corner-
is an absolute indication for immediate ventricular drainage regardless stone of effective therapy.63 The organism shows in vitro resistance to
of the level of consciousness. amphotericin B. Based on clinical experience and the absence of good
Craniotomy with total excision is difficult in cases of nocardial alternative agents, voriconazole is now the antifungal agent of choice
brain abscess because these abscesses are usually multiloculated.143 In for treatment of S. apiospermum brain abscess. In one review of the use
one review of 11 patients with nocardial brain abscess,216 aspiration of voriconazole, which included 21 patients with CNS disease caused
alone (which was repeated as clinically indicated) was a safe, efficacious by Scedosporium, 43% had a therapeutic response.230 The combination
treatment for 9 patients. In another series of 3 patients with nocardial of voriconazole and terbinafine was successful in one patient with
brain abscess, cure was achieved only after neurosurgical enucle- chronic granulomatous disease and a brain abscess caused by S. prolifi-
ation,217 suggesting that an aggressive approach should be used. In cans, a species highly resistant to most antifungal agents.231
patients with tuberculous brain abscess, an early surgical procedure is Complete excision of brain abscess caused by melanized, or dema-
mandatory to establish the diagnosis and improve the efficacy of anti- tiaceous, fungi whenever feasible, is associated with better outcomes
tuberculous therapy52; procedures include stereotactic-guided aspira- than aspiration or partial excision.70 However, the outcome remains
tion, simple puncture, continuous drainage, and repeated aspiration poor, with an overall mortality of greater than 70%.
1176
Key References Central Nervous System. 3rd ed. Philadelphia: Lippincott
Williams & Wilkins; 2004:713-734.
148. Luft BJ, Hafner R, Korzun AH, et al. Toxoplasmic encepha-
litis in patients with the acquired immunodeficiency syn-
56. Walsh TJ, Hier DB, Caplan LP. Fungal infections of the drome. N Engl J Med. 1993;329:995-1000.
The complete reference list is available online at Expert Consult.
central nervous system: comparative analysis of risk factors 157. Al Masalma M, Armougom F, Scheld WM, et al. The
and clinical signs in 57 patients. Neurology. 1985;35: expansion of the microbiologic spectrum of brain abscess
1. Mathisen GE, Johnson JP. Brain abscess. Clin Infect Dis.
1654-1657. with use of multiple 16S ribosomal DNA sequencing. Clin
1997;25:763-781.
57. Denning DW. Invasive aspergillosis. Clin Infect Dis. 1998; Infect Dis. 2009;48:1169-1178.
3. Klein M, Pfister HW, Tunkel AR, et al. Brain abscess. In:
26:781-805. 158. Al Masalma M, Lonjon M, Richet H, et al. Metagenomic
Scheld WM, Whitley RJ, Marra CM, eds. Infections of the
61. Lanternier F, Sun HY, Ribaud P, et al. Mucormycosis in analysis of brain abscesses identifies specific bacterial asso-
Central Nervous System. 4th ed. Philadelphia: Lippincott
organ and stem cell transplant recipients. Clin Infect Dis. ciations. Clin Infect Dis. 2012;54:202-210.
2012;54:1629-1636. 159. DiGiulio DB, Relman DA. Majority rules? Tallying the
3a. Brouwer MC, Tunkel AR, McKhann GM, et al. Brain
64. Dworzack DL, Clark RB, Borkowski WJ, et al. Pseud- microbial census in an abscess by means of molecular
abscess. N Engl J Med. 2014;371:447-456.
allescheria boydii brain abscess: association with near- methods. Clin Infect Dis. 2009;48:1179-1181.
5. Nathoo N, Nadvi SS, Narotam PK, et al. Brain abscess:
drowning and efficacy of high-dose, prolonged miconazole 160. Mamelak AN, Mampalam TJ, Obana WG, et al. Improved
management and outcome analysis of a computed tomog-
therapy in patients with multiple abscesses. Medicine. management of multiple brain abscesses: a combined sur-
raphy era experience with 973 patients. World Neurosurg.
1989;68:218-224. gical and medical approach. Neurosurgery. 1995;36:76-86.
2011;75:716-726.
73. Walker M, Zunt JR. Parasitic central nervous system infec- 164. Quality Standards Subcommittee of the American Academy
8. Muzumdar D, Jhawar S, Goel A. Brain abscess: an over-
tions in immunocompromised hosts. Clin Infect Dis. of Neurology. Evaluation and management of intracranial
view. Int J Surg. 2011;9:136-144.
2005;40:1005-1015. mass lesions in AIDS. Neurology. 1998;50:21-26.
9. Rosenblum ML, Joff JT, Norman D, et al. Decreased mor-
74. Walker M, Kublin JG, Zunt JR. Parasitic central nervous 173. Sjolin J, Lilja A, Eriksson N, et al. Treatment of brain
tality from brain abscesses since advent of computerized
system infections in immunocompromised hosts: malaria, abscess with cefotaxime and metronidazole: prospective
tomography. J Neurosurg. 1978;49:658-668.
microsporidiosis, leishmaniasis, and African trypanoso- study on 15 consecutive patients. Clin Infect Dis. 1993;17:
11. Seydoux C, Francioli P. Bacterial brain abscess: factors
miasis. Clin Infect Dis. 2006;42:115-125. 857-863.
influencing mortality and sequelae. Clin Infect Dis. 1992;15:
77. Luft BJ, Sivadas R. Toxoplasmosis of the central nervous 180. Martin-Canal G, Saavedra A, Asensi JM, et al. Meropenem
394-401.
system. In: Scheld WM, Whitley RJ, Marra CM, eds. Infec- monotherapy is as effective as and safer than imipenem to
17. Carpenter J, Stapleton S, Holliman R. Retrospective analy-
tions of the Central Nervous System. 3rd ed. Philadelphia: treat brain abscess. Int J Antimicrob Agents. 2010;35:301-304.
sis of 49 cases of brain abscess and review of the literature.
Lippincott Williams & Wilkins; 2004:755-776. 185. Arlotti M, Grossi P, Pea F, et al. Consensus document on
Eur J Clin Microbiol Infect Dis. 2007;26:1-11.
79. Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. controversial issues for the treatment of infections of the
20. Lee TH, Chang WN, Thung-Ming S, et al. Clinical features
Clin Infect Dis. 1992;15:211-222. central nervous system: bacterial brain abscess. Int J Infect
and predictive factors of intraventricular rupture in
80. Renold C, Sugar A, Chave JP, et al. Toxoplasma encephalitis Dis. 2010;14S4:S79-S92.
patients who have bacterial brain abscess. J Neurol Neuro-
in patients with acquired immunodeficiency syndrome. 208. Ratnaike TE, Das S, Gregson BA, Mendelow AD. A review
surg Psychiatry. 2007;78:303-309.
Medicine. 1992;71:224-239. of brain abscess surgical treatment—78 years: aspiration
21. Lu CH, Chang WN, Lui CC. Strategies for the management
81. Porter SB, Sande MA. Toxoplasmosis of the central nervous versus excision. World Neurosurg. 2011;76:431-436.
of bacterial brain abscess. J Clin Neurosci. 2006;13:979-985.
system in the acquired immunodeficiency syndrome. 214. Woo PC, Wong HT, Poon WS. Brain abscess: an antedilu-
31. Yang SY. Brain abscess: a review of 400 cases. J Neurosurg.
N Engl J Med. 1992;327:1643-1648. vian affliction of the past? World Neurosurg. 2011;76:
1981;55:794-799.
91. Tunkel AR, Kaye D. Neurologic complications of infective 385-387.
32. Mampalam TJ, Rosenblum ML. Trends in the management
endocarditis. Neurol Clin. 1993;11:419-440. 217a. McCarthy M, Rosengart A, Scheutz AN, et al. Mold infec-
of bacterial brain abscesses: a review of 102 cases over 17
98. Mathis S, Dupuis-Girod S, Plauchu H, et al. Cerebral tions of the central nervous system. N Engl J Med. 2014;
years. Neurosurgery. 1988;23:451-458.
abscesses in hereditary haemorrhagic telangiectasia: a 371:150-160.
33. Chun CH, Johnson JD, Hofstetter M, et al. Brain abscess: a
clinical and microbiological evaluation. Clin Neurol Neuro- 219. Denning DW, Stevens DA. Antifungal and surgical treat-
study of 45 consecutive cases. Medicine. 1986;65:415-431.
surg. 2012;114:235-240. ment of invasive aspergillosis: review of 2,121 published
36. Eckburg PB, Montoya JG, Vosti KL. Brain abscess due to
102. Tunkel AR, Turtz AR. Posttraumatic infection of the cases. Rev Infect Dis. 1990;12:1147-1201.
Listeria monocytogenes: five cases and a review of the litera-
central nervous system. In: Evans RW, ed. Neurology and 220. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of
ture. Medicine (Baltimore). 2001;80:223-235.
Trauma. 2nd ed. Oxford: Oxford University Press; aspergillosis: clinical practice guidelines of the Infectious
38. Clauss HE, Lorber B. Central nervous system infection
2006:628-638. Diseases Society of America. Clin Infect Dis. 2008;46:
with Listeria monocytogenes. Curr Infect Dis Rep. 2008;10:
124. Britt RH, Enzmann DR, Yeager AS. Neuropathological and 327-360.
300-306.
computerized tomographic findings in experimental brain 221. Denning DW, Ribaud P, Milpied N, et al. Efficacy and safety
46. Peleg AY, Husain S, Qureshi ZA. Risk factors, clinical char-
abscess. J Neurosurg. 1981;55:590-603. of voriconazole in the treatment of acute invasive aspergil-
acteristics, and outcome of Nocardia infection in organ
142. Carpenter JL. Brain stem abscesses: cure with medical losis. Clin Infect Dis. 2002;34:563-571.
transplant recipients: a matched case-control study. Clin
therapy, case report, and review. Clin Infect Dis. 1994;18: 232. Zhang Z, Cai X, Kang X, et al. Retrospective analysis of 620
Infect Dis. 2007;44:1307-1314.
219-226. cases of brain abscess in Chinese patients in a single center
51. Nelson CA, Zunt JR. Tuberculosis of the central nervous
143. Mamelak AN, Obana WG, Flaherty JF, et al. Nocardial over a 62-year period. Acta Neurochir. 2016;158:733-739.
system in immunocompromised patients: HIV infection
brain abscess: treatment strategies and factors influencing 233. Mishra AK, Dufour H, Roche PH, et al. Molecular revolu-
and solid organ transplant recipients. Clin Infect Dis. 2011;
outcome. Neurosurgery. 1994;35:622-631. tion in the diagnosis of microbial brain abscesses. Eur J Clin
53:915-926.
144. Zimmerman RA, Wong AM, Girard N. Imaging of intra- Microbiol Infect Dis. 2014;33:2083-2093.
52. Cardenas G, Soto-Hernandez JL, Orozco RV, et al. Tubercu-
cranial infections. In: Scheld WM, Whitley RJ, Marra CM, 234. Xia C, Jiang X, Niu C. May short-course intravenous anti-
lous brain abscesses in immunocompetent patients: man-
eds. Infections of the Central Nervous System. 3rd ed. Phila- microbial administration be as a standard therapy for bac-
agement and outcome. Neurosurgery. 2010;67:1081-1087.
delphia: Lippincott Williams & Wilkins; 2004:31-55. terial brain abscess treated surgically? Neurol Res.
53. Salaki JS, Louria DB, Chmel H. Fungal and yeast infections
146. Villanueva-Meyer JE, Cha S. From shades of gray to micro- 2016;38:414-419.
of the central nervous system: a clinical review. Medicine.
biologic imaging: a historical review of brain abscess
1984;63:108-132.
imaging: RSNA Centennial Article. Radiographics. 2015;35:
55. Cortez KJ, Walsh TJ. Space-occupying fungal lesions. In:
1555-1562.
1176.e1
References 32. Mampalam TJ, Rosenblum ML. Trends in the management
of bacterial brain abscesses: a review of 102 cases over 17
63. Berenguer J, Diaz-Mediavilla J, Urra D, et al. Central
nervous system infection caused by Pseudallescheria boydii.
1. Mathisen GE, Johnson JP. Brain abscess. Clin Infect Dis.
years. Neurosurgery. 1988;23:451-458. Rev Infect Dis. 1989;11:890-896.
1997;25:763-781.
33. Chun CH, Johnson JD, Hofstetter M, et al. Brain abscess: 64. Dworzack DL, Clark RB, Borkowski WJ, et al. Pseud-
2. Canale DJ. William Macewen and the treatment of brain

a study of 45 consecutive cases. Medicine. 1986;65: allescheria boydii brain abscess: association with near-
abscesses: revisited after one hundred years. J Neurosurg.
415-431. drowning and efficacy of high-dose, prolonged miconazole
1996;84:133-142.
34. Grigoriadis E, Gold WL. Pyogenic brain abscess caused by therapy in patients with multiple abscesses. Medicine. 1989;
3. Klein M, Pfister HW, Tunkel AR, et al. Brain abscess. In:
Streptococcus pneumoniae: case report and review. Clin 68:218-224.
Infect Dis. 1997;25:1108-1112. 65. Kershaw P, Freeman R, Templeton D, et al. Pseudallescheria
Central Nervous System. 4th ed. Philadelphia: Lippincott
35. Lorber B. Listeriosis. Clin Infect Dis. 1997;24:1-11. boydii infection of the central nervous system. Arch Neurol.
36. Eckburg PB, Montoya JG, Vosti KL. Brain abscess due to 1990;47:468-472.
3a. Brouwer MC, Tunkel AR, McKhann GM, et al. Brain
Listeria monocytogenes: five cases and a review of the litera- 66. Lamaris G, Chamilos G, Lewis RE, et al. Scedosporium
abscess. N Engl J Med. 2014;371:447-456.
ture. Medicine (Baltimore). 2001;80:223-235. infection in a tertiary care cancer center: a review of 25
4. Heilpern KL, Lorber B. Focal intracranial infections. Infect
37. Jim KK, Brouwer MC, van der Ende A, et al. Cerebral cases from 1989-2006. Clin Infect Dis. 2006;43:1580-1584.
Dis Clin North Am. 1996;10:879-898.
abscesses in patients with bacterial meningitis. J Infect. 67. Al-Jehani H, Guiot MC, Torres C, et al. Scedosporium cere-
5. Nathoo N, Nadvi SS, Narotam PK, et al. Brain abscess:
2012;64:236-238. bral abscesses after extra-corporeal membrane oxygen-
management and outcome analysis of a computed tomog-
38. Clauss HE, Lorber B. Central nervous system infection ation. Can J Neurol Sci. 2010;37:671-676.
raphy era experience with 973 patients. World Neurosurg.
with Listeria monocytogenes. Curr Infect Dis Rep. 2008;10: 68. Cristini A, Garcia-Hermoso D, Celard M, et al. Cerebral
2011;75:716-726.
300-306. phaeohyphomycosis caused by Rhinocladiella mackenziei
6. Shachor-Meyouhas Y, Bar-Joseph G, Builburd JN, et al.
39. Renier D, Flandin C, Hirsch E, et al. Brain abscesses in in a woman native to Afghanistan. J Clin Microbiol. 2010;
Brain abscess in children—epidemiology, predisposing
neonates: a study of 30 cases. J Neurosurg. 1988;69: 48:3451-3454.
factors and management in the modern medicine era. Acta
877-882. 69. Rosow L, Jiang JX, Deuel T, et al. Cerebral phaeohyphomy-
Paediatr. 2010;99:1163-1167.
40. Kline MW. Citrobacter meningitis and brain abscess in cosis caused by Bipolaris spicifera after heart transplanta-
7. McClelland S 3rd, Hall WA. Postoperative central nervous
infancy: epidemiology, pathogenesis, and treatment. tion. Transplant Infect Dis. 2011;13:419-423.
system infection: incidence and associated factors in 2111
J Pediatr. 1988;113:430-434. 70. Revankar SG, Sutton DA. Melanized fungi in human
neurosurgical procedures. Clin Infect Dis. 2007;45:55-59.
41. Morgan MG, Stuart C, Leonard AT, et al. Citrobacter diver- disease. Clin Microbiol Rev. 2010;23:884-928.
8. Muzumdar D, Jhawar S, Goel A. Brain abscess: an over-
sus brain abscess: case reports and molecular epidemiol- 71. Bia FJ, Barry M. Parasitic infections of the central nervous
view. Int J Surg. 2011;9:136-144.
ogy. J Med Microbiol. 1992;36:273-278. system. Neurol Clin. 1986;4:171-206.
9. Rosenblum ML, Joff JT, Norman D, et al. Decreased mor-
42. Kuruvath S, Basu S, Elwitigala JP, et al. Salmonella enteriti- 72. Campbell S. Amebic brain abscess and meningoencephali-
tality from brain abscesses since advent of computerized
dis brain abscess in a sickle cell disease patient: case report tis. Semin Neurol. 1993;13:153-160.
tomography. J Neurosurg. 1978;49:658-668.
and review of the literature. Int J Infect Dis. 2008;12: 73. Walker M, Zunt JR. Parasitic central nervous system infec-
10. Szyfter W, Kruk-Zagajewska A, Borucki L, et al. Evolution
298-302. tions in immunocompromised hosts. Clin Infect Dis.
in management of otogenic brain abscess. Otol Neurotol.
43. Chadwick DR, Ang B, Sitoh YY, et al. Cerebral melioidosis 2005;40:1005-1015.
2012;33:393-395.
in Singapore: a review of five cases. Trans R Soc Trop Med 74. Walker M, Kublin JG, Zunt JR. Parasitic central nervous
11. Seydoux C, Francioli P. Bacterial brain abscess: factors
Hyg. 2002;96:72-76. system infections in immunocompromised hosts: malaria,
influencing mortality and sequelae. Clin Infect Dis. 1992;
44. Akhaddar A, Elouennass M, Baallal H, et al. Focal intra- microsporidiosis, leishmaniasis, and African trypanoso-
15:394-401.
cranial infections due to Actinomyces species in immuno- miasis. Clin Infect Dis. 2006;42:115-125.
12. Xiao F, Tseng MY, Teng LJ, et al. Brain abscess: clinical
competent patients: diagnostic and therapeutic challenges. 75. White AC Jr. Neurocysticercosis: a major cause of neuro-
experience and analysis of prognostic factors. Surg Neurol.
World Neurosurg. 2010;74:346-350. logical disease worldwide. Clin Infect Dis. 1997;24:101-115.
2005;63:442-450.
45. Lerner PI. Nocardiosis. Clin Infect Dis. 1996;22:891-905. 76. Marconi VC, Garcia HH, Katz JT. Neurocysticercosis. Curr
13. Prasad KN, Mishra AM, Gupta D, et al. Analysis of micro-
46. Peleg AY, Husain S, Qureshi ZA. Risk factors, clinical char- Infect Dis Rep. 2006;8:293-300.
bial etiology and mortality in patients with brain abscess.
acteristics, and outcome of Nocardia infection in organ 77. Luft BJ, Sivadas R. Toxoplasmosis of the central nervous
J Infect. 2006;53:221-227.
transplant recipients: a matched case-control study. Clin system. In: Scheld WM, Whitley RJ, Marra CM, eds. Infec-
14. Hakan T, Ceran N, Erdem I, et al. Bacterial brain abscesses:
Infect Dis. 2007;44:1307-1314. tions of the Central Nervous System. 3rd ed. Philadelphia:
an evaluation of 96 cases. J Infect. 2006;52:359-366.
47. Braun TI, Kerson LA, Eisenberg FP. Nocardial brain Lippincott Williams & Wilkins; 2004:755-776.
15. Tseng JH, Steng MY. Brain abscess in 142 patients: factors
abscesses in a pregnant woman. Rev Infect Dis. 1991;13: 78. Mele A, Paterson PJ, Prentice HG, et al. Toxoplasmosis in
influencing outcome and mortality. Surg Neurol. 2006;65:
630-632. bone marrow transplantation: a report of two cases and
557-562.
48. Kumar R, Pandey CK, Bose N, et al. Tuberculous brain systematic review of the literature. Bone Marrow Trans-
16. Tonon E, Scotton PG, Gallucci M, et al. Brain abscess:
abscess: clinical presentation, pathophysiology and treat- plant. 2002;29:691-698.
clinical aspects of 100 patients. Int J Infect Dis. 2006;10:
ment (in children). Childs Nerv Syst. 2002;18:118-123. 79. Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS.
103-109.
49. Farrar DJ, Flanigan TP, Gordon NM, et al. Tuberculous Clin Infect Dis. 1992;15:211-222.
17. Carpenter J, Stapleton S, Holliman R. Retrospective analy-
brain abscess in a patient with HIV infection: case report 80. Renold C, Sugar A, Chave JP, et al. Toxoplasma encephalitis
sis of 49 cases of brain abscess and review of the literature.
and review. Am J Med. 1997;102:297-301. in patients with acquired immunodeficiency syndrome.
Eur J Clin Microbiol Infect Dis. 2007;26:1-11.
50. Monno L, Carbonara S, Costa D, et al. Cerebral lesions in Medicine. 1992;71:224-239.
18. Landriel F, Ajler P, Hem S, et al. Supratentorial and
two patients with AIDS: the possible role of Mycobacterium 81. Porter SB, Sande MA. Toxoplasmosis of the central nervous
infratentorial brain abscesses: surgical treatment, compli-
kansasii. Clin Infect Dis. 1996;22:1130-1131. system in the acquired immunodeficiency syndrome.
cations and outcomes—a 10-year single-center study. Acta
51. Nelson CA, Zunt JR. Tuberculosis of the central nervous N Engl J Med. 1992;327:1643-1648.
Neurochir. 2012;154:903-911.
system in immunocompromised patients: HIV infection 82. Skiest DJ. Focal neurological disease in patients with
19. Hsiao SY, Chang WN, Lin WC, et al. The experiences of
and solid organ transplant recipients. Clin Infect Dis. 2011; acquired immunodeficiency syndrome. Clin Infect Dis.
non-operative treatment in patients with bacterial brain
53:915-926. 2002;34:103-115.
abscess. Clin Microbiol Infect. 2011;17:615-620.
52. Cardenas G, Soto-Hernandez JL, Orozco RV, et al. Tubercu- 83. Sacktor N, Lyles RH, Skolasky R, et al. HIV-associated
20. Lee TH, Chang WN, Thung-Ming S, et al. Clinical features
lous brain abscesses in immunocompetent patients: man- neurologic disease incidence changes: multicenter AIDS
and predictive factors of intraventricular rupture in
agement and outcome. Neurosurgery. 2010;67:1081-1087. Cohort Study, 1990-1998. Neurology. 2001;56:257-260.
patients who have bacterial brain abscess. J Neurol Neuro-
53. Salaki JS, Louria DB, Chmel H. Fungal and yeast infections 84. Abgrall S, Rabaud C, Costagliola D, et al. Incidence and
surg Psychiatry. 2007;78:303-309.
of the central nervous system: a clinical review. Medicine. risk factors for toxoplasmic encephalitis in human immu-
21. Lu CH, Chang WN, Lui CC. Strategies for the management
1984;63:108-132. nodeficiency virus-infected patients before and during the
of bacterial brain abscess. J Clin Neurosci. 2006;13:979-985.
54. Hagensee ME, Bauwens JE, Kjos B, et al. Brain abscess highly active antiretroviral therapy era. Clin Infect Dis.
22. Su TM, Lin YC, Lu CH, et al. Streptococcal brain abscess:
following marrow transplantation: experience at the Fred 2001;33:1747-1755.
analysis of clinical features in 20 patients. Surg Neurol.
Hutchinson Cancer Center, 1984-1992. Clin Infect Dis. 85. Corson MA, Postlethwaite KP, Seymour RA. Are dental
2001;56:189-194.
1994;19:402-408. infections a cause of brain abscess? Case report and review
23. Hayashi A, Takano T, Suzuki A, et al. Group A streptococ-
55. Cortez KJ, Walsh TJ. Space-occupying fungal lesions. In: of the literature. Oral Dis. 2001;7:61-65.
cal brain abscess: a case report and a review of the literature
Scheld WM, Whitley RJ, Marra CM, eds. Infections of the 86. Vargas J, Hernandez M, Silvestri C, et al. Brain abscess due
since 1988. Scand J Infect Dis. 2011;43:553-555.
Central Nervous System. 3rd ed. Philadelphia: Lippincott to Arcanobacterium haemolyticum after dental extraction.
24. Sifri CD, Park J, Helm G, et al. Fatal brain abscess due
Williams & Wilkins; 2004:713-734. Clin Infect Dis. 2006;42:1810-1811.
to community-associated methicillin-resistant Staphylo-
56. Walsh TJ, Hier DB, Caplan LP. Fungal infections of the 87. Yang SY. Brain abscess associated with congenital heart
coccus aureus strain USA300. Clin Infect Dis. 2007;45:
central nervous system: comparative analysis of risk factors disease. Surg Neurol. 1989;31:129-132.
e113-e117.
and clinical signs in 57 patients. Neurology. 1985;35: 88. Park SC, Neeches WH. The neurologic complications of
25. De Louvois J, Gortvai P, Hurley R. Bacteriology of abscesses
1654-1657. congenital heart disease. Neurol Clin. 1993;11:441-462.
of the central nervous system: a multicentre prospective
57. Denning DW. Invasive aspergillosis. Clin Infect Dis. 1998; 89. Takeshita M, Kagawa M, Yato S, et al. Current treatment of
study. BMJ. 1977;2:981-984.
26:781-805. brain abscess in patients with congenital cyanotic heart
26. De Louvois J. The bacteriology and chemotherapy of brain
58. Ruhnke M, Kofla G, Otto K, et al. CNS aspergillosis: rec- disease. Neurosurgery. 1997;41:1270-1279.
abscess. J Antimicrob Chemother. 1978;4:395-413.
ognition, diagnosis and management. CNS Drugs. 2007;21: 90. Pruitt AA, Rubin RHJ, Karchmer AW, et al. Neurologic
27. Liliang PC, Lin YC, Su TM, et al. Klebsiella brain abscess
659-676. complications of bacterial endocarditis. Medicine. 1978;57:
in adults. Infection. 2001;29:81-86.
59. Stave GM, Heimberger T, Kerkering TM. Zygomycosis of 329-343.
28. Lu CH, Chang WN, Lin YC, et al. Bacterial brain abscess:
the basal ganglia in intravenous drug users. Am J Med. 91. Tunkel AR, Kaye D. Neurologic complications of infective
microbiological features, epidemiological trends and thera-
1989;86:115-117. endocarditis. Neurol Clin. 1993;11:419-440.
peutic outcomes. QJM. 2002;95:501-509.
60. Sugar AM. Mucormycosis. Clin Infect Dis. 1992;14: 92. Tunkel AR, Pradhan SK. Central nervous system infections
29. Rau CS, Chang WN, Lin YC, et al. Brain abscess caused
S126-S129. in injection drug users. Infect Dis Clin North Am. 2002;
by aerobic gram-negative bacilli: clinical features and
61. Lanternier F, Sun HY, Ribaud P, et al. Mucormycosis in 16:589-605.
therapeutic outcomes. Clin Neurol Neurosurg. 2002;105:
organ and stem cell transplant recipients. Clin Infect Dis. 93. Sonneville R, Mirabel M, Hajage D, et al. Neurologic com-
60-65.
2012;54:1629-1636. plications and outcomes of infective endocarditis in criti-
30. Sennaroglu L, Sozeri B. Otogenic brain abscess: review of
62. Travis LB, Roberts GD, Wilson WR. Clinical significance cally ill patients: the ENDOcardite en REAnimation
41 cases. Otolaryngol Head Neck Surg. 2000;123:751-755.
of Pseudallescheria boydii: a review of ten years’ experience. prospective multicenter study. Crit Care Med. 2011;39:
31. Yang SY. Brain abscess: a review of 400 cases. J Neurosurg.
Mayo Clin Proc. 1985;60:531-537. 1474-1481.
1981;55:794-799.
1176.e2
94. Press OW, Ramsey PG. Central nervous system infections 124. Britt RH, Enzmann DR, Yeager AS. Neuropathological and 151. Joseph P, Calderon MM, Gilman RH, et al. Optimization
associated with hereditary hemorrhagic telangiectasia. Am computerized tomographic findings in experimental brain and evaluation of a PCR assay for detecting toxoplasmic
J Med. 1984;77:86-92. abscess. J Neurosurg. 1981;55:590-603. encephalitis in patients with AIDS. J Clin Microbiol. 2002;
95. Gelfand MS, Stephens DS, Howell EI, et al. Brain abscess: 125. Enzmann DR, Britt RR, Obana WG, et al. Experimental 40:4499-4503.
association with pulmonary arteriovenous fistula and Staphylococcus aureus brain abscess. AJNR Am J Neurora- 152. Strowitzki M, Schwerdtfeger K, Steudel WI. Ultrasound-
hereditary hemorrhagic telangiectasia—report of three diol. 1986;7:395-402. guided aspiration of brain abscess through a single burr
cases. Am J Med. 1988;85:718-720. 126. Neuwelt EA, Lawrence MS, Blank NK. Effect of gentamicin hole. Minim Invasive Neurosurg. 2001;44:135-140.
96. Dupuis-Girod S, Giraud S, Decullier E, et al. Hemorrhagic and dexamethasone on the natural history of the rat Esch- 153. Petti CA, Simmon KE, Bender J, et al. Culture-negative
hereditary telangiectasia (Rendu-Osler disease) and infec- erichia coli brain abscess model with histopathological cor- intracerebral abscesses in children and adolescents from
tious diseases: an underestimated association. Clin Infect relation. Neurosurgery. 1984;15:475-483. Streptococcus anginosus group infection: a case series. Clin
Dis. 2007;44:841-845. 127. Kielian T, Cheung A, Hickey WF. Diminished virulence Infect Dis. 2008;46:1578-1580.
97. Sell B, Evans J, Horn D. Brain abscess and hereditary hem- of an alpha-toxin mutant of Staphylococcus aureus in 154. Keller PM, Rampini SK, Bloemberg GV. Detection of a
orrhagic telangiectasia. South Med J. 2008;101:618-625. experimental brain abscess. Infect Immun. 2001;69: mixed infection in a culture-negative brain abscess by
98. Mathis S, Dupuis-Girod S, Plauchu H, et al. Cerebral 6902-6911. broad-spectrum bacterial 16S rRNA gene PCR. J Clin
abscesses in hereditary haemorrhagic telangiectasia: a 128. Casciato DA, Rosenblatt JE, Goldberg LS, et al. In vitro Microbiol. 2010;48:2250-2252.
clinical and microbiological evaluation. Clin Neurol Neuro- interaction of Bacteroides fragilis with polymorphonuclear 155. Valour F, Boisset S, Lebras L, et al. Clostridium sordellii
surg. 2012;114:235-240. leukocytes and serum factors. Infect Immun. 1975;11: brain abscess diagnosed by 16S rRNA gene sequencing.
99. Kuman P, Mehta SK, Deri BI, et al. Pyogenic meningitis 337-342. J Clin Microbiol. 2010;48:3443-3444.
and cerebral abscesses after endoscopic injection sclero- 129. Ingham HR, Sisson PR, Middleton RL, et al. Phagocytosis 156. Saito N, Hida A, Koide Y, et al. Culture-negative brain abscess
therapy. Am J Gastroenterol. 1991;86:1672-1674. and killing of bacteria in aerobic and anaerobic conditions. with Streptococcus intermedius infection with diagnosis estab-
100. Algood L, Boon P, DeVos M, et al. Brain abscess after Med Microbiol. 1981;14:391-399. lished by direct nucleotide sequence analysis of the 16S ribo-
esophageal dilatation for stenosis. Clin Neurol Neurosurg. 130. Adamu SA, Sperry JF. Polymorphonuclear neutrophil che- somal RNA gene. Intern Med. 2012;51:211-216.
1992;94:169-172. motaxis induced and inhibited by Bacteroides spp. Infect 157. Al Masalma M, Armougom F, Scheld WM, et al. The
101. Gaini S, Grand M, Michelsen J. Brain abscess after esopha- Immun. 1981;33:806-810. expansion of the microbiologic spectrum of brain abscess
geal dilatation: case report. Infection. 2008;36:71-73. 131. Kielian T, Hickey WF. Proinflammatory cytokine, chemo- with use of multiple 16S ribosomal DNA sequencing. Clin
102. Tunkel AR, Turtz AR. Posttraumatic infection of the kine, and cellular adhesion molecule expression during the Infect Dis. 2009;48:1169-1178.
central nervous system. In: Evans RW, ed. Neurology and acute phase of experimental brain abscess development. 158. Al Masalma M, Lonjon M, Richet H, et al. Metagenomic
Trauma. 2nd ed. Oxford: Oxford University Press; 2006: Am J Pathol. 2000;157:647-658. analysis of brain abscesses identifies specific bacterial asso-
628-638. 132. Holley MM, Kielian T. Th1 and Th17 cells regulate innate ciations. Clin Infect Dis. 2012;54:202-210.
103. McGovern PC, Lautenbach E, Brennan PJ, et al. Risk immune responses and bacterial clearance during central 159. DiGiulio DB, Relman DA. Majority rules? Tallying the
factors for postcraniotomy surgical site infection after nervous system infection. J Immunol. 2012;188:1360-1370. microbial census in an abscess by means of molecular
1,3-bis (2-chloroethyl)-1-nitrosourea (Gliadel) wafer 133. Esen N, Wagoner G, Philips N. Evaluation of capsular and methods. Clin Infect Dis. 2009;48:1179-1181.
placement. Clin Infect Dis. 2003;36:759-765. acapsular strains of S. aureus in an experimental brain 160. Mamelak AN, Mampalam TJ, Obana WG, et al. Improved
104. Rish BL, Careness WF, Dillon JD, et al. Analysis of brain abscess model. J Neuroimmunol. 2010;218:83-93. management of multiple brain abscesses: a combined sur-
abscess after penetrating craniocerebral injuries in 134. Kielian T, Barry B, Hickey WF. CXC chemokine receptor-2 gical and medical approach. Neurosurgery. 1995;36:76-86.
Vietnam. Neurosurgery. 1981;9:535-541. ligands are required for neutrophil-mediated host defense 161. Alderson D, Strong AJ, Ingham MR, et al. Fifteen year
105. Splavski B, Sisljagic V, Peric LJ, et al. Intracranial infection in experimental brain abscesses. J Immunol. 2001;166: review of the mortality of brain abscess. Neurosurgery.
as a common complication following war missile skull base 4634-4643. 1981;8:1-6.
injury. Injury. 2000;31:233-237. 135. Long WD, Meacham WF. Experimental method for produc- 162. Levy RM, Gutin PH, Baskin DS, et al. Vancomycin penetra-
106. Hecimovic I, Dmitrovic B, Kurbel S, et al. Intracranial ing brain abscess in dogs with evaluation of the effect of tion of a brain abscess: case report and review of the litera-
infection after missile brain wound: 15 war cases. Zentralbl dexamethasone and antibiotic therapy on the pathogenesis ture. Neurosurgery. 1986;18:633-636.
Neurochir. 2000;61:95-102. of intracerebral abscesses. Surg Forum. 1968;19:437-438. 163. Khan MA, Greig JR, Jayamohan J. Community-acquired
107. Bhatoe HS. Retained intracranial splinters: a follow up 136. Quartey GRC, Johnston JA, Rozdilsky B. Decadron in the methicillin-resistant Staphylococcus aureus brain abscess in
study in survivors of low intensity military conflicts. Neurol treatment of cerebral abscess: an experimental study. J Neu- an immunocompetent individual. Scand J Infect Dis. 2000;
India. 2001;49:29-32. rosurg. 1976;45:301-310. 32:423-424.
108. Foy P, Schair M. Cerebral abscesses in children after pencil 137. Yildizhan A, Pasaoglu A, Kandemir B. Effect of dexametha- 164. Quality Standards Subcommittee of the American
tip injuries. Lancet. 1980;2:662-663. sone on various stages of experimental brain abscess. Acta Academy of Neurology. Evaluation and management of
109. Tay JS, Garland JS. Serious head injuries from lawn darts. Neurochir. 1989;96:141-148. intracranial mass lesions in AIDS. Neurology. 1998;50:
Pediatrics. 1987;79:260-263. 138. Obana WG, Britt RH, Placone RC, et al. Experimental 21-26.
110. Martinello RA, Cooney EL. Cerebellar brain abscess asso- brain abscess development in the chronically immunosup- 165. Ruiz A, Ganz WI, Post MJD, et al. Use of thallium-201
ciated with tongue piercing. Clin Infect Dis. 2003;36: pressed host: computerized tomographic and neuropatho- brain SPECT to differentiate cerebral lymphoma from
e32-e34. logic correlations. J Neurosurg. 1986;65:382-391. Toxoplasma encephalitis in AIDS patients. AJNR Am J Neu-
111. Brouwer MC, Kasanmoentalib ES, Opstelten FWJ, et al. A 139. Zeidman SM, Geisler FH, Olivi A. Intraventricular rupture roradiol. 1994;15:1885-1894.
horse bite to remember. Lancet. 2010;376:1194. of a purulent brain abscess: case report. Neurosurgery. 166. Berry I, Gaillard JF, Guo Z, et al. Cerebral lesions in AIDS:
112. Saeed MU, Dacuycuy AC, Kennedy DJ. Halo pin insertion– 1995;36:189-193. what can be expected from scintigraphy? Cerebral tomo-
associated brain abscess. Spine. 2007;32:E271-E274. 140. Takeshita M, Kawamata T, Izawa M, et al. Prodromal signs graphic scintigraphy using thallium-201: a contribution to
113. Yee-Guardino S, Danziger-Isakov L, Knouse M, et al. and clinical factors influencing outcome in patients with the differential diagnosis of lymphomas and infectious
Nosocomially acquired Pseudomonas stutzeri brain abscess intraventricular rupture of purulent brain abscess. Neuro- lesions. J Neuroradiol. 1995;22:218-228.
in a child: case report and review. Infect Cont Hosp Epide- surgery. 2001;48:310-317. 167. O’Malley JP, Ziessman HA, Kumar PN, et al. Diagnosis of
miol. 2006;27:630-632. 141. Dake MD, McMurdo SK, Rosenblum ML, et al. Pyogenic intracranial lymphoma in patients with AIDS: value of 201Tl
114. Fily F, Haegelen C, Tattevin P, et al. Deep brain stimulation abscess of the medulla oblongata. Neurosurgery. 1986;18: single photon emission computed tomography. AJR Am J
hardware-related infections: a report of 12 cases and review 370-372. Roentgenol. 1994;163:417-421.
of the literature. Clin Infect Dis. 2011;52:1020-1023. 142. Carpenter JL. Brain stem abscesses: cure with medical 168. Garcia-Morales F, Chengazi VU, O’Mara RE. Nocardia
115. Morton R, Lucas TH 2nd, Ko A, et al. Intracerebral abscess therapy, case report, and review. Clin Infect Dis. 1994;18: brain abscess identification with Tl-201 SPECT. Clin Nucl
associated with the Camino intracranial pressure monitor: 219-226. Med. 2001;26:981-982.
case report and review of the literature. Neurosurgery. 143. Mamelak AN, Obana WG, Flaherty JF, et al. Nocardial 169. Licho R, Litofsky NS, Senitko M, et al. Inaccuracy of
2012;71:E193-E198. brain abscess: treatment strategies and factors influencing Tl-201 SPECT in distinguishing cerebral infections from
116. Kawamata T, Takeshita M, Ishizuka N, et al. Patent foramen outcome. Neurosurgery. 1994;35:622-631. lymphoma in patients with AIDS. Clin Nucl Med. 2002;27:
ovale as a possible risk factor for cryptogenic brain abscess: 144. Zimmerman RA, Wong AM, Girard N. Imaging of intra- 81-86.
report of two cases. Neurosurgery. 2001;49:204-207. cranial infections. In: Scheld WM, Whitley RJ, Marra CM, 170. Hoffman JM, Waskin HA, Schifter T, et al. FDG-PET in
117. Mendes M, Moore P, Wheeler CB, et al. Susceptibility of eds. Infections of the Central Nervous System. 3rd ed. Phila- differentiating lymphoma from nonmalignant central
brain and skin to bacterial challenge. J Neurosurg. 1980; delphia: Lippincott Williams & Wilkins; 2004:31-55. nervous system lesions in patients with AIDS. J Nucl Med.
52:772-775. 145. Kapsalaki EZ, Gotsis ED, Fountas KN, et al. The role of 1993;34:567-575.
118. Costello GT, Heppe R, Winn HR, et al. Susceptibility of proton magnetic resonance spectroscopy in the diagnosis 171. Pierce MA, Johnson MD, Maciunas RJ, et al. Evaluating
brain to aerobic, anaerobic, and fungal organisms. Infect and categorization of cerebral abscesses. Neurosurg Focus. contrast enhancing brain lesions in patients with AIDS by
Immun. 1983;41:535-539. 2008;24:E7. using positron emission tomography. Ann Intern Med.
119. Onderonk AB, Kasper DL, Cisneros RL, et al. The capsular 146. Villanueva-Meyer JE, Cha S. From shades of gray to micro- 1995;123:594-598.
polysaccharide of Bacteroides fragilis as a virulence factor: biologic imaging: a historical review of brain abscess 172. Haroon A, Zumla A, Bomanji J. Role of fluorine 18 fluoro-
comparison of the pathogenic potential of encapsulated imaging: RSNA Centennial Article. Radiographics. 2015; deoxyglucose positron emission tomography–computed
and unencapsulated strains. J Infect Dis. 1977;136:82-89. 35:1555-1562. tomography in focal and generalized infections and inflam-
120. Onderonk AB, Kasper DL, Mansheim BJ, et al. Experimen- 147. Pal D, Bhattacharyya A, Husain M, et al. In vivo proton MR matory disorders. Clin Infect Dis. 2012;54:1333-1341.
tal animal models for anaerobic infections. Rev Infect Dis. spectroscopy evaluation of pyogenic brain abscesses: a 173. Sjolin J, Lilja A, Eriksson N, et al. Treatment of brain
1979;1:291-301. report of 194 cases. AJNR. 2010;31:360-366. abscess with cefotaxime and metronidazole: prospective
121. Britt RH, Enzmann DR, Placone RC Jr, et al. Experimental 148. Luft BJ, Hafner R, Korzun AH, et al. Toxoplasmic encepha- study on 15 consecutive patients. Clin Infect Dis. 1993;17:
anaerobic brain abscess: computerized tomographic and litis in patients with the acquired immunodeficiency syn- 857-863.
neuropathological correlations. J Neurosurg. 1984;60: drome. N Engl J Med. 1993;329:995-1000. 174. Green HT, O’Donoghue MA, Shaw MD, Dowling C. Pen-
1148-1159. 149. Cohn JA, McMeeking A, Cohen W, et al. Evaluation of the etration of ceftazidime into intracranial abscesses. J Anti-
122. Kline MW, Kaplan SL, Hawkins EP, et al. Pathogenesis of policy of empiric treatment of suspected Toxoplasma microb Chemother. 1989;24:431-436.
brain abscess formation in an infant rat model of Citrobac- encephalitis in patients with the acquired immunodefi- 175. Skrap M, Melatini A, Vassallo A, et al. Stereotactic aspira-
ter diversus bacteremia and meningitis. J Infect Dis. 1988; ciency syndrome. Am J Med. 1989;86:521-527. tion and drainage of brain abscesses: experience with 9
157:106-112. 150. Cimino C, Lipton RB, Williams A, et al. The evaluation of cases. Minim Invasive Neurosurg. 1996;39:108-112.
123. Kline MW, Mason EO Jr, Kaplan SL. Characterization of patients with human immunodeficiency virus–related dis- 176. Adova M, Akalin HE, Korten V, et al. Treatment of intra-
Citrobacter diversus strains causing neonatal meningitis. orders and brain mass lesions. Arch Intern Med. 1991;151: cranial abscesses: experience with sulbactam/ampicillin.
J Infect Dis. 1988;157:101-105. 1381-1384. J Chemother. 1993;5:181-185.
1176.e3
177. Aseni V, Carton JA, Maradona JA, et al. Imipenem therapy 197. Garlando F, Bodmer T, Lee C, et al. Successful treatment of 217. Valarezo J, Cohen JE, Valarezo L, et al. Nocardial cerebral
of brain abscesses. Eur J Clin Microbiol Infect Dis. 1996;15: disseminated nocardiosis complicated by cerebral abscess abscess: report of three cases and review of the current
653-657. with ceftriaxone and amikacin: case report. Clin Infect Dis. neurosurgical management. Neurol Res. 2003;25:27-30.
178. Aseni V, Carton JA, Maradona JA, et al. Therapy of brain 1992;15:1039-1040. 217a. McCarthy M, Rosengart A, Scheutz AN, et al. Mold infec-

abscess with imipenem—a safe therapeutic choice? J Anti- 198. Jansen C, Frenay HM, Vandertop WP, et al. Intracerebral tions of the central nervous system. N Engl J Med. 2014;
microb Chemother. 1996;37:200-203. Nocardia asteroides abscess treated by neurosurgical aspira- 371:150-160.
179. Meis JFGM, Groot-Loonen J, Hoogkamp-Korstanje JAA. tion and combined therapy with sulfadiazine and cefotax- 218. Kamitsuka MD, Nugent NA, Conrad PD, et al. Candida
A brain abscess due to multiply-resistant Enterobacter ime. Clin Neurol Neurosurg. 1991;93:253-255. albicans brain abscesses in a premature infant treated with
cloacae successfully treated with meropenem. Clin Infect 199. Gombert ME, du Bouchet L, Aulicino TM, et al. Anti amphotericin B, flucytosine and fluconazole. Pediatr Infect
Dis. 1995;20:1567. microbial synergism in the therapy of experimental Dis J. 1995;14:329-331.
180. Martin-Canal G, Saavedra A, Asensi JM, et al. Meropenem cerebral nocardiosis. J Antimicrob Chemother. 1989;24: 219. Denning DW, Stevens DA. Antifungal and surgical treat-
monotherapy is as effective as and safer than imipenem to 39-43. ment of invasive aspergillosis: review of 2,121 published
treat brain abscess. Int J Antimicrob Agents. 2010;35:301-304. 200. Fleetwood IG, Embil JM, Ross IB. Nocardia asteroides cere- cases. Rev Infect Dis. 1990;12:1147-1201.
181. Wessalowksi R, Thomas L, Kivit J, et al. Multiple brain bral abscess in immunocompetent hosts: report of three 220. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of
abscesses caused by Salmonella enteritidis in a neonate: cases and review of surgical recommendations. Surg aspergillosis: clinical practice guidelines of the Infectious
successful treatment with ciprofloxacin. Pediatr Infect Dis Neurol. 2000;53:605-610. Diseases Society of America. Clin Infect Dis. 2008;46:
J. 1993;12:683-688. 201. Moylett EH, Pacheco SE, Brown-Elliott BA, et al. Clinical 327-360.
182. Rosenblum ML, Hoff JT, Norman D, et al. Nonoperative experience with linezolid for the treatment of Nocardia 221. Denning DW, Ribaud P, Milpied N, et al. Efficacy and safety
treatment of brain abscesses in selected high-risk patients. infection. Clin Infect Dis. 2003;36:313-318. of voriconazole in the treatment of acute invasive aspergil-
J Neurosurg. 1980;52:217-225. 202. Pea F, Cojutti P, Pagotto A, et al. Successful long-term treat- losis. Clin Infect Dis. 2002;34:563-571.
183. Boom WH, Tuazon CU. Successful treatment of multiple ment of cerebral nocardiosis with unexpectedly low doses 222. Gubler C, Wildi SM, Imhof A, et al. Disseminated invasive
brain abscesses with antibiotics alone. Rev Infect Dis. 1985; of linezolid in an immunocompromised patient receiving aspergillosis with cerebral involvement treated with caspo-
7:189-199. complex polytherapy. Antimicrob Agents Chemother. 2012; fungin and voriconazole. Infection. 2007;35:364-366.
184. Fulgham JR, Wijdicks EFM, Wright AJ. Cure of a solitary 56:3438-3440. 223. Ehrmann S, Bastides F, Gissot V, et al. Cerebral aspergil-
brainstem abscess with antibiotic therapy: case report. Neu- 203. Fihman V, Bercot B, Mateo J, et al. First successful treat- losis in the critically ill: two cases of successful medical
rology. 1996;46:1451-1454. ment of Nocardia farcinica brain abscess with moxifloxacin. treatment. Intensive Care Med. 2005;31:738-742.
185. Arlotti M, Grossi P, Pea F, et al. Consensus document on J Infect. 2006;52:e99-e102. 224. Damaj G, Ivanov V, Le Brigand B, et al. Rapid improvement
controversial issues for the treatment of infections of the 204. Fellows GA, Kalsi PS, Martin AJ. Nocardia farcinica brain of disseminated aspergillosis with caspofungin/voriconazole
central nervous system: bacterial brain abscess. Int J Infect abscess in a patient without immunocompromise. Br J Neu- combination in an adult leukemic patient. Ann Hematol.
Dis. 2010;14S4:S79-S92. rosurg. 2007;21:301. 2004;83:390-393.
186. Infection in Neurosurgery Working Party of the British 205. Kandasamy J, Iqbal HJ, Cooke RPD, et al. Primary 225. Ochi JW, Harris JP, Feldman JI, et al. Rhinocerebral mucor-
Society for Antimicrobial Chemotherapy. The rational use Nocardia farcinica brain abscess with secondary men- mycosis: results of aggressive surgical debridement and
of antibiotics in the treatment of brain abscess. Br J Neuro- ingitis and ventriculitis in an immunocompetent amphotericin B. Laryngoscope. 1988;98:1339-1342.
surg. 2000;14:525-530. patient, successfully treated with moxifloxacin. Acta 226. Talmi YP, Goldschmied-Reouven A, Bakon M, et al.
187. Skoutelis AT, Gogos CA, Maraziotis TE, et al. Management Neurochir (Wien). 2008;150:505-506. Rhinoorbital and rhino-orbital-cerebral mucormycosis.
of brain abscesses with sequential intravenous/oral antibiotic 206. Filice GA, Simpson GL. Management of Nocardia infections. Otolaryngol Head Neck Surg. 2002;127:22-31.
therapy. Eur J Clin Microbiol Infect Dis. 2000;19:332-335. In: Remington JS, Swartz MN, eds. Current Clinical Topics 227. van Burik AH, Hare RS, Solomon HF, et al. Posaconazole
188. Jansson AK, Enbland P, Sjolin J. Efficacy and safety of cefo- in Infectious Diseases. New York: McGraw-Hill; 1984:49- is effective as salvage therapy in zygomycosis: a retrospec-
taxime in combination with metronidazole for empirical 64. tive summary of 91 cases. Clin Infect Dis. 2006;42:e61-
treatment of brain abscess in clinical practice: a retrospec- 207. Stephanov S. Surgical treatment of brain abscess. Neurosur- e65.
tive study of 66 consecutive cases. Eur J Clin Microbiol gery. 1988;22:724-730. 228. Couch L, Theilen F, Mader JT. Rhinocerebral mucormyco-
Infect Dis. 2004;23:7-14. 208. Ratnaike TE, Das S, Gregson BA, Mendelow AD. A review sis with cerebral extension successfully treated with
189. Wallace RJ Jr, Septimus EJ, Williams TW Jr, et al. Use of of brain abscess surgical treatment—78 years: aspiration adjunctive hyperbaric oxygen therapy. Arch Otolaryngol
trimethoprim-sulfamethoxazole for treatment of infections versus excision. World Neurosurg. 2011;76:431-436. Head Neck Surg. 1988;114:791-794.
due to Nocardia. Rev Infect Dis. 1982;4:315-325. 209. Dyste GN, Hitchon PW, Menezes AH, et al. Stereotaxic 229. Ferguson BJ, Mitchell TG, Moon R, et al. Adjunctive hyper-
190. Smego RA Jr, Moeller MB, Gallis HA. Trimethoprim- surgery in the treatment of multiple brain abscesses. J Neu- baric oxygen for treatment of rhinocerebral mucormycosis.
sulfamethoxazole therapy for Nocardia infections. Arch rosurg. 1988;69:188-194. Rev Infect Dis. 1988;10:551-559.
Intern Med. 1983;143:711-718. 210. Itakura T, Yokote H, Ozaki F, et al. Stereotactic operation 230. Troke P, Aguirrebengoa K, Arteaga C, et al. Treatment
191. Overkamp D, Waldmann B, Lins T, et al. Successful treat- for brain abscess. Surg Neurol. 1987;28:196-200. of scedosporiosis with voriconazole: clinical experience
ment of brain abscess caused by Nocardia in an immuno- 211. Shahzadi S, Lozano AM, Bernstein M, et al. Stereotactic with 107 patients. Antimicrob Agents Chemother. 2008;52:
compromised patient after failure of co-trimoxazole. management of bacterial brain abscesses. Can J Neurol Sci. 1743-1750.
Infection. 1992;20:365-366. 1996;23:34-39. 231. Bhat SV, Paterson DL, Rinaldi MG, et al. Scedosporium
192. Wallace RJ Jr, Steele LC, Sumter G, et al. Antimicrobial 212. Laborde G, Klimek L, Harders A, et al. Frameless stereo- prolificans brain abscess in a patient with chronic granu
susceptibility patterns of Nocardia asteroides. Antimicrob tactic drainage of intracranial abscesses. Surg Neurol. 1993; lomatous disease: successful combination therapy with
Agents Chemother. 1988;32:1776-1779. 40:16-21. voriconazole and terbinafine. Scand J Infect Dis. 2007;39:
193. Berkey P, Moore D, Rolston K. In vitro susceptibilities of 213. Ghannane H, Laghmari M, Aniba K, et al. Diagnostic and 87-90.
Nocardia species to newer antimicrobial agents. Antimicrob management of pediatric brain stem abscess, a case-based 232. Zhang Z, Cai X, Kang X, et al. Retrospective analysis of 620
Agents Chemother. 1988;32:1078-1079. update. Childs Nerv Syst. 2011;27:1053-1062. cases of brain abscess in Chinese patients in a single center
194. Brown-Elliott BA, Warad SC, Crist CJ, et al. In vitro activi- 214. Woo PC, Wong HT, Poon WS. Brain abscess: an antedilu- over a 62-year period. Acta Neurochir. 2016;158:733-739.
ties of linezolid against multiple Nocardia species. Antimi- vian affliction of the past? World Neurosurg. 2011;76: 233. Mishra AK, Dufour H, Roche PH, et al. Molecular revolu-
crob Agents Chemother. 2001;45:1295-1297. 385-387. tion in the diagnosis of microbial brain abscesses. Eur J Clin
195. Krone A, Schaal KP, Brawanski A, et al. Nocardial cerebral 215. Madhugiri VS, Sastri BVS, Srikantha U, et al. Focal Microbiol Infect Dis. 2014;33:2083-2093.
abscess cured with imipenem/amikacin and enucleation. intradural brain infections in children: an analysis of 234. Xia C, Jiang X, Niu C. May short-course intravenous anti-
Neurosurg Rev. 1989;12:333-340. management and outcome. Pediatr Neurosurg. 2011;47: microbial administration be as a standard therapy for bac-
196. Kim J, Minamoto GY, Hoy CD, et al. Presumptive 113-124. terial brain abscess treated surgically? Neurol Res.
cerebral Nocardia asteroides infection in AIDS: treatment 216. Lee GYF, Daniel RT, Brophy BP, et al. Surgical treatment 2016;38:414-419.
with ceftriaxone and minocycline. Am J Med. 1991;90: of nocardial brain abscesses. Neurosurgery. 2002;51:
656-658. 668-672.

4 Abses Serebelum

Загружено:

Сведения о документе

Оригинальное название

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

4 Abses Serebelum

Загружено:

Авторское право:

Доступные форматы

Brain Abscess

92 Allan R. Tunkel

SHORT VIEW SUMMARY

Chapter 92 Brain Abscess

Chapter 92 Brain Abscess

Chapter 92 Brain Abscess

Chapter 92 Brain Abscess

Chapter 92 Brain Abscess

TABLE 92-4 Antimicrobial Therapy for Brain Abscess

Chapter 92 Brain Abscess

Chapter 92 Brain Abscess

Chapter 92 Brain Abscess

Chapter 92 Brain Abscess

Вам также может понравиться