Indian J Pediatr

DOI 10.1007/s12098-017-2477-z

REVIEW ARTICLE

Bacterial Infections of the Central Nervous System

Renu Suthar 1 & Naveen Sankhyan 1

Received: 27 March 2017 / Accepted: 5 September 2017

# Dr. K C Chaudhuri Foundation 2018

Abstract Bacterial infections of the central nervous system
(CNS) continue to be an important cause of morbidity and
mortality in children. The spectrum of bacterial infection of
CNS includes; focal or multifocal infections like brain ab-
scesses or subdural empyema; or more generalized or diffuse
infections like pyogenic meningitis or ventriculitis. Focal and
generalized infections may co-exist in an individual patient.
Prompt and adequate antibiotic therapy and occasionally neu-
rosurgical interventions are the cornerstone of effective man-
agement. The recent emergence of several multidrug-resistant
bacteria poses a threat to the effective management of bacterial
CNS infections. Several adjunctive anti-inflammatory and
neuroprotective therapies are being tried, however; none has
made a remarkable impact on the outcome. Consequently,
bacterial CNS infections in children still remain a challenge
to manage. In this review, authors discuss the current updates
on the diagnostic and therapeutic aspects of bacterial infec-
tions of the CNS in children (post-neonatal age group).
Keywords Neuroinfections . Pyomeningitis . Intracranial
suppuration . Pyogenic brain abscess . Bacterial meningitides
* Naveen Sankhyan
drnsankhyan@yahoo.co.in
1
Pediatric Neurology and Neurodevelopment Unit, Department of
Pediatrics, Advanced Pediatric Centre, Post Graduate Institute of
Medical Education and Research, Chandigarh 160012, India
PART A: Generalized Infection
Acute Bacterial Meningitis
Introduction
The commonest bacterial infection of the central nervous sys-
tem (CNS) in children is bacterial meningitis. Bacterial men-
ingitis is the inflammation of the meninges affecting the pia,
arachnoid, and subarachnoid space in response to bacteria and
bacterial products [1]. According to the global burden of dis-
ease report 2010, bacterial meningitis led to 400,000 deaths,
and it is among the top 10 leading causes of deaths due to
communicable diseases [2].
Epidemiology
The incidence of bacterial meningitis is approximately 3 cases
per 100,000 persons in the developed countries, but the dis-
ease is at least 10-times more common in the developing
countries [3]. The incidence, morbidity and mortality rates
of bacterial meningitis vary and depend on several factors,
such as age, geographical region, causative organism and im-
munization status [4]. The epidemiology of bacterial menin-
gitis has seen a recent change with the introduction of effective
conjugate vaccines [4]. A decline in vaccine serotypes as the
cause of meningitis is a clear indicator of vaccine efficacy [5,
6]. However, in the low-income countries; because of poor
vaccination coverage, the disease continues to affect a large
number of children.

Etiological Agents
Almost all microbial agents pathogenic to humans have the
potential to cause bacterial meningitis in children, but only a
small number of organisms account for most of the cases.
H. influenzae type b, S. pneumoniae, N. meningitidis, group
B Streptococcus, Escherichia coli and Listeria monocytogenes
are the most common organisms responsible for most cases of
acute bacterial meningitis in infants and children (Table 1) [7].
Predisposing Risk Factors for Bacterial Meningitis
Epidemiology of community acquired bacterial meningitis is
changing especially in the developed countries due of large
scale implementation of childhood vaccination programs.
However; due to lack of effective vaccination program against
H. influenzae and S. pneumoniae, children in the developing
countries are at high risk for serious invasive diseases by these
organisms. Several other environmental, host related factors
and co morbid conditions increase the risk for bacterial men-
ingitis (Table 2) [8].
Clinical Presentation of Bacterial Meningitis
The clinical manifestations of acute bacterial meningitis can
be very subtle, non-specific or even absent especially in the
neonates and infants. Infants and children present with fever,
neck rigidity, lethargy, irritability, headache, nausea, vomiting,
and photophobia (Table 3). In one study, the classical triad of
fever, neck stiffness and altered sensorium was seen in only
44% patients [9]. Signs like rash, neck stiffness and encepha-
lopathy are late features [10]. Nuchal rigidity is the classical
sign of meningitis, however, it can be absent in infants and in
the early stage of the illness. The presence of a diffuse ery-
thematous maculopapular rash may be an early manifestation
of meningococcemia or viral fever. Purpuric and petechial
rash over the legs and trunk is suggestive of
meningococcemia. Such rash can also be seen with scrub ty-
phus, staphylococcal bacterial endocarditis or Echo virus in-
fection [7]. Sepsis and septic shock may be seen in about 20–
40% of patient with meningitis [11]. Waterhouse-
Table 1 Most common etiological agents of bacterial meningitis according to the age group
Age group
<7 d
>7 d – <2 mo
2 mo – 23 mo
2 y to 5 y
Adolescents
Indian J Pediatr
Friderischsen syndrome is seen in children with fulminant
meningococcemia. It is characterized by acute onset febrile
illness, large petechial hemorrhagic rash, disseminated intra-
vascular coagulation, and cardiovascular collapse [11]. In
presence of shock, meningeal signs can be overlooked.
Seizures occur in 30–40% of children with meningitis, usually
within first 3 d of illness. Approximately 15% children devel-
op focal neurological deficits, including cranial nerve palsies,
hemiparesis, and ataxia. Syndrome of Inappropriate
Antidiuretic Hormone Secretion and diabetes insipidus are
other common complications [7].
The differential diagnosis of the triad of fever, headache,
and stiff neck includes viral meningoencephalitis tubercular
meningitis, cryptococcal meningitis other fungal meningitis,
chemical meningitis, meningitis associated with inflammatory
diseases, cerebral abscess, and subarachnoid hemorrhage. In
infants febrile seizures can present similar to bacterial menin-
gitis and a CSF examination is necessary to rule out serious
bacterial meningitis. Acute febrile encephalopathy in children
can occur due to several other non-infectious etiologies.
Metabolic encephalopathy, inborn errors of metabolism
(IEM), epilepsy, epileptic encephalopathy, Dravet syndrome,
sepsis, septic shock, and intra cranial hemorrhage can mimic
acute bacterial meningitis. In older children, autoimmune en-
cephalitis, FIRES (febrile infection related epilepsy syn-
drome), metabolic encephalopathy, IEM, acute disseminated
encephalomyelitis (ADEM) and acute hemorrhagic and ische-
mic stroke can mimic acute bacterial meningitis in children.
Diagnosis
The diagnosis of bacterial meningitis rests on CSF analysis
and culture (Table 4). Lumbar puncture is a safe procedure
unless contraindicated due to suspicion of focal brain swell-
ing, raised intracranial pressure, cardio-respiratory compro-
mise, and risk of bleeding or local infection. Do not delay
lumbar CSF examination in children with suspected bacterial
meningitis.
Elevated CSF pressure in the range of 20–50 cm of water in
common in bacterial meningitis. The appearance of CSF in
bacterial meningitis can be normal to cloudy or turbid. The
Common organisms
Group B Streptococci, E. coli, Listeria monocytogenes, Enterobactericae
Neonatal pathogens plus
S. pneumoniae, N. meningitidis, H. influenzae type b, Staphylococcus aureus
S. pneumoniae, N. meningitides, H. influenzae type b, Non typhoidal salmonella,
Enterobacteriae
S. pneumoniae, H. influenzae, N. meningitidis
S. pneumoniae, N. meningitidis
Indian J Pediatr

Table 2 Predisposing risk factors for acute bacterial meningitis

Organism Age group Predisposing risk factors

S. pneumoniae Young age Day care attendance, unvaccinated, sinusitis, otitis media, fracture of nasal
cribriform plate, cochlear transplant, dermal skin sinus, fistulous
communication with CNS, asplenia, diabetes, nephrotic syndrome,
HIV, complement factor deficiency, hematological malignancy,
humoral immune deficiency
H. influenzae Infants, young children, adults Unvaccinated, day care attendance, sinusitis, otitis media, HIV, splenectomy,
asplenia, diminished humoral immunity, and complement factor deficiency
N. meningitidis Infants, adolescents/young adults Crowding, unvaccinated, common complement pathways deficiency,
and elderly >65 complement inhibitor treatment, asplenia, splenectomy, HIV infection
Listeria monocytogenes Neonates, elderly >50 y Immunodeficiency state, HIV, diabetes, liver disease, malignancy
Staphylococci All age CSF shunts, neurosurgical procedure, lumbosacral dermal sinuses,
meningomyelocele
Gram negative organisms All ages Health care associated infections, lumbosacral dermal sinuses,
meningomyelocele, neurosurgical procedure, CSF shunts

CNS Central nervous system, HIV Human immunodeficiency virus

CSF appears turbid in the presence of >200 WBC, >400 RBC, >15 mg/dl in the ventricular CSF is abnormal. The CSF gram
bacteria or elevated proteins [12]. The CSF sample for cytol- stain examination allows for rapid and accurate identification of
ogy needs to be examined immediately as WBC’s in CSF the organism. The gram stain is positive in 70% of untreated
tends to disintegrate within 90 min. A CSF cell count of >10 cases of bacterial meningitis. Most smears are positive in cases
neutrophils is abnormal. In 90% cases of bacterial meningitis with >105 CFU/ml. CSF culture is the gold standard for the
CSF cell count is >100 WBC/μl in CSF and 60–70% cases diagnosis of bacterial meningitis and is positive in 80–90% of
have >1000 WBC/μL CSF. The CSF classically shows neu- patients with acute community-acquired bacterial meningitis
trophilic predominance. However, early in the course, lym- before the start of treatment. However, if the patient has re-
phocytic predominance may be seen in 10% of the patients ceived intravenous antibiotics; the CSF culture can be sterile.
[13]. CSF glucose of less than 40 mg/dl is seen in 60% pa- Blood cultures identify the causative organism in 50–80% of
tients with bacterial meningitis. patients [15]. Do not forget sending blood cultures before ini-
An accurate estimation of CSF glucose with serum glucose tiation of antibiotic therapy. The yield of blood cultures de-
is more informative, a ratio of < 0.5 is indicative of bacterial creases by 20% or more if the patient has been pretreated with
meningitis, and is seen in 70% patients with bacterial meningi- antibiotics [15].
tis [14]. CSF protein of >50 mg/dl in the lumbar CSF and Polymerase chain reaction (PCR) using special bacterial
primers to detect the nucleic acid of S. pneumoniae, N.
meningitidis, H. influenzae, E. coli, S. agalactie and Listeria
Table 3 Clinical features suggestive of acute bacterial meningitis in monocytogenes is commercially available. However, the clinical
neonates and children usefulness of PCR is limited as culture results are often available
Age Clinical symptoms Signs within 24 h. PCR is more useful in patients who have been
group treated with prior antibiotics and in whom the cultures are neg-
ative [11, 16].
Neonates Temperature instability, Bulging fontanelle, poor state
lethargy, listlessness, high to state variability, seizures
pitch cry, irritability, feed CSF in Partially Treated Pyogenic Meningitis Children,
refusal, poor suck,
who have been treated with parenteral antibiotics before diag-
vomiting, diarrhea,
respiratory distress nosis, tend to have negative CSF gram stain and cultures. CSF
Infants Fever, irritability, nausea, Bulging fontanelle, glucose tends to normalize by day 3 of intravenous antibiotics
vomiting, lethargy, shrill encephalopathy, neck and CSF protein concentration tends to stay elevated till day
cry, altered sensorium, stiffness, retrocollis,
10. CSF cell count tends to decrease with antibiotic therapy,
respiratory distress seizures, focal neurological
deficits however, in >50% patients, a persistently elevated count can
Children Fever, neck stiffness, Nuchal rigidity, be seen till 7–10 d of antibiotics [17].
headache, irritability, encephalopathy, purpuric
lethargy, altered sensorium, or petechial rash, seizures,
seizures, photophobia, rash focal neurological deficits Neuroimaging The diagnosis of bacterial meningitis is clini-
cal and confirmation is done with CSF analysis. Imaging adds
 Indian J Pediatr

Table 4 Typical CSF findings in bacterial meningitis and viral meningitis

CSF parameter Normal Bacterial meningitis Aseptic/Viral meningitis

CSF pressure <10 cm H2O >18 cm H2O Normal or mild elevation

Appearance Clear Cloudy Clear
CSF cells <5 cells, lymphocytes >1000/mm3, predominant neutrophils 10-1000/mm3, lymphocytosis
CSF protein <40 mg/dl >50 mg/dl Normal or mild elevation
CSF glucose >60 mg/dl <40 mg/dl >45 mg/dl
CSF to serum glucose ratio >0.6 <0.4 >0.6
Gram stain Negative Positive in 70-90% untreated patients Negative
CSF lactate Normal >3.8 mmol/L Normal

CSF Cerebrospinal fluid

very little to the diagnosis of uncomplicated meningitis. The
value of neuroimaging lies in excluding other pathological
processes and in the investigation of complications (Fig. 1).
MRI is superior to CT scan in the identification of complica-
tions in children with bacterial meningitis.
Other Diagnostic Markers Rapid diagnostic tests such as
latex agglutination test have very poor sensitivity in gram
stain and culture negative cases. Serum procalcitonin and
C-reactive protein have been used to differentiate between
viral and bacterial meningitis. Promising marker for differ-
entiating bacterial meningitis from viral meningitis include
serum and CSF procalcitonin [18]. Other potential markers
in the CSF include cortisol, heparin binding protein, IL6,
IL12, IL1b, IL10, TNF-alpha, complement component B
[8]. These markers are limited to research setting and have
not made an impact on clinical care of children with bacte-
rial meningitis.
Management
Do not delay antibiotics if you are clinically suspecting
meningitis. The initial management includes stabilization
of the child, taking care of airway, breathing, and circula-
tion. Immediately after obtaining samples for blood culture
appropriate empirical antibiotics should be started
(Table 5). A delay in the initiation of antibiotics is associ-
ated with increased mortality and a poor neurological out-
come. In one study, a delay of 6 h was associated with an
eight-fold rise in mortality [19]. However, the initial empir-
ical antibiotics can cause alteration in the CSF picture and
gram stain and cultures can be negative after antibiotics.
Empirical antibiotics should not be delayed while
waiting for a lumbar puncture or a CT. The choice of em-
pirical cover should be based on history, risk factors, im-
mune status, and local antibiotic resistant pattern. A third
generation cephalosporin is generally the empiric agent of
choice. The decision to add vancomycin depends on the
rate of resistance to third-generation cephalosporins. In
areas where the prevalence of cephalosporin-resistant
S. pneumoniae is low (< 1% resistance), a third-
generation cephalosporin (either cefotaxime or ceftriaxone)
usually suffices as empirical treatment. In young infants
and children with T-cell immunodeficiency ampicillin
should be given to cover for L. monocytogenes. Antibiotic
therapy should be with intravenous agents to achieve high
CSF concentrations. There is no role of oral antibiotics in
children with suspected meningitis. It is also essential to use
directed antibiotic therapy once the causative organism and
antibiotic susceptibilities are available [10].

Corticosteroids and Other Anti-inflammatory Agents

Fig. 1 T1W post-contrast Axial MRI of the brain in a child with acute
bacterial meningitis showing meningeal enhancement and multiple areas Among experimental animals corticosteroids reduced brain
of post contrast enhancement suggesting areas of cerebritis and edema, reduced intracranial pressure, and stabilized the
infarctions blood-brain barrier. The stabilization for blood-brain
Indian J Pediatr

Table 5 Suggested empirical

antibiotic therapy in children with Predisposing factor Organism Empirical antimicrobial therapy
bacterial meningitis
0–4 wk Enteric gram negative Ampicillin + gentamicin
bacilli, Ampicillin + cefotaxime
L. monocytogenes,
Streptococcus pneumoniae,
S. agalactie
1–3 mo E. coli, Ampicillin + gentamicin
L. monocytogenes, Ampicillin + cefotaxime
S. agalactie,
S. pneumoniae,
H. influenzae,
N. meningitidis
3 mo–18 y S pneumoniae, Ceftriaxone or cefotaxime
H. influenzae,
N meningitidis
Immunocompromised state (Vancomycin + ceftriaxone) + ampicillin
(in those with T cell defects)
Head trauma S. pneumoniae, H. Vancomycin + ceftriaxone
influenzae
Neurosurgery, CSF shunt, or head Gram negative bacilli, Ceftazidime/meropenum + cloxacillin or
trauma Staphylococcus aureus, vancomycin
Coagulase negative
Staphylococci

CSF Cerebrospinal fluid

barrier reduces the concentration of antibiotics in the CSF.
Reduced concentrations of antibiotics within the CSF jeop-
ardize antibacterial effectiveness. Hence, the role of corti-
costeroids as adjuvant treatment in acute bacterial menin-
gitis remains controversial. A Cochrane review regarding
the steroid therapy in bacterial meningitis found no benefit
in outcome in poorly resourced centers [20]. However, cor-
ticosteroids significantly reduced hearing loss and neuro-
logical sequelae, but did not reduce overall mortality in
high-income countries [21]. Dexamethasone (0.15 mg/kg
every 6 h) is recommended for children (over 6 wk of
age) with H. influenzae meningitis and is suggested to be
started before or along with the first dose of antibiotic [22].
In meningitis due to other organisms, its role is less well
defined to allow for universal guidelines.
children is variable; and depends on the nature and sever-
ity of the complications as well as the response to
treatment.
Complications
The course of bacterial meningitis can be complicated by a
number of intracranial and occasionally extracranial compli-
cations (Table 6, and Figs. 1, 2, 3, 4). Raised intracranial
pressure (ICP), cerebral edema, electrolyte imbalance, sepsis,
Table 6 Immediate and long-term complications of bacterial
meningitis
Immediate complications Long-term complications

Cerebral edema Deafness

Duration of Antibiotics For non-complicated cases of bac-
Raised intracranial pressure Neuronal damage
terial meningitis duration of antibiotics depend upon the
Hyponatremia Focal sensorimotor deficits
nature of the pathological organism. For S. pneumoniae it
SIADH Intellectual disability
is 10–14 d, for H. influenza 7–10 d, for N. meningitidis 5–
Sepsis, septic shock Cortical blindness
7 d and for group B streptococci and gram-negative bacilli
Disseminated intravascular coagulation Epilepsy
14–21 d [10]. When an organism is not identified and the
Seizures Learning disability
course is uncomplicated a 10–14 d therapy should suffice.
Hydrocephalus Behavioral problems
However, in children with a gram positive organism and
Extraaxial fluid collection
resistant organisms repeat CSF may be required to docu-
Subdural
ment therapeutic response and neuroimaging to see for Subarachnoid
intracranial complications. The antibiotic duration in these

Fig. 2 T1 axial post contrast images of the brain of an infant showing
right ventriculomegaly and ependymal enhancement suggestive of
ventriculitis. Note the whole of left cerebral hemisphere is converted in
a cystic area, with peripheral contrast enhancement and thinning of the
cortical mental
septic shock and disseminated intravascular coagulation are
common complications in the acute stage of bacterial menin-
gitis. Seizures in the initial stage are secondary to the cortical
irritation; however in the later part of illness, suggest compli-
cations like infarcts, empyema and abscess. Persistent fever
despite adequate antibiotics suggests presence of suppurative
complication such as subdural empyema, brain abscess and
ventriculitis. Progressive increase in the head size of an infant,
or persistent signs of raised ICP suggest evolving hydroceph-
alus or ventriculitis. A repeat CSF may be warranted in chil-
dren with persistent fever spikes, gram negative organism and
staphylococcus meningitis.
Raised Intracranial Pressure (ICP) Almost all children with
bacterial meningitis tend to have raised intracranial pressure.
Clinical signs suggestive of raised ICP are progressively wors-
ening encephalopathy, dilated, poorly reactive pupils, abnor-
malities of ocular movements, irregular breathing, bradycar-
dia, and hypertension. Papilledema does not develop early in
the disease. Persistently elevated raised ICP may lead to her-
niation. Raised ICP should be managed aggressively with se-
dation and analgesia, head-end elevation and ventilation.
Mannitol or 3% saline infusion can be used to treat raised
ICP. Invasive ICP monitoring can be used in the children with
coma. Around 30–40% children have seizures during the
course of acute bacterial meningitis. Seizures should be man-
aged according to status epilepticus protocol.
A subdural collection can occur in patients with bacterial
meningitis and most common organism is the S. pneumoniae
[23]. Most extra-axial fluid collections resolve without inter-
vention. If fever and clinical signs persist, and fluid continues
Indian J Pediatr
to accumulate in subdural spaces, surgical drainage of the
fluid is indicated.
Chemoprophylaxis
Rifampin or ceftriaxone should be given to all close contact
with meningococcal meningitis. Chemoprophylaxis with ri-
fampin is recommended to all close contacts of
H. influenzae meningitis. For healthcare personnels, chemo-
prophylaxis is recommended only for those whose mouth or
nose is directly exposed to large particle droplets/secretions
from the respiratory tract of a probable or confirmed case of
meningococcal disease during acute illness until completed
24 h of systemic antibiotics.
PART B: Focal Suppurative Bacterial Infection
of the Nervous System
Brain Abscess
Brain abscess is an intraparenchymal suppurative collection of
pus in the brain. The incidence has been estimated at 0.3 to 1.3
per 100,000 people per year [24]. Typically, it begins with an
area of focal cerebritis evolving into a collection of pus
surrounded by a well-defined vascularized capsule. Bacterial
invasion of the brain and subsequent abscess formation can be
due to the direct spread of infection or through hematogenous
spread (Table 7) [25]. Bacterial invasion from contiguous foci
(otitis media, sinusitis, mastoiditis) can occur and most frequent
organisms are streptococcus species, staphylococcus or can be
polymicrobial (anaerobes and gram-negative organisms). The
Hematogenous spread of bacteria can occur from an underlying
cardiac, pulmonary disease, or a distant site of infection like
skin, subcutaneous tissue, paranasal sinuses, and teeth. These
lesions are often multiple, mulitloculated, poorly encapsulated
and located at gray matter and white matter junction. Abscesses
can also occur following a neurosurgical procedure or trauma. In
such a situation the common organisms are skin-colonizing bac-
teria such as Staphylococcus aureus and Staphylococcus
epidermidis. Most common organisms isolated from 491 brain
abscess pus cultures are streptococci (40%), staphylococcus
(12%) and enterobacteriace (25%) and bacterioids (21%) [26].
Pathogenesis
After gaining access to the brain parenchyma, in the first stage
of ‘early cerebritis’ (1–4 d), there is a central necrotic area with
surrounding white matter edema due to perivascular inflam-
matory response. Subsequently, the necrotic center reaches its
maximum size (late cerebritis, 4–10 d), and a capsule is
formed through the accumulation of fibroblasts and neovas-
cularization (early capsule formation, 11–14 d). The capsule
Indian J Pediatr
thickens with an abundance of reactive collagen, but inflam-
mation and edema extend beyond the capsule (late capsule
formation >14 d) [26].
Clinical Features
The clinical presentation of a brain abscess depends upon site,
number, size of the lesion and associated mass effect. The clas-
sic triad of brain abscess is fever, headache, and focal neuro-
logical deficits. Other common manifestations are headache,
nausea, vomiting, and encephalopathy. Seizures are a common
presenting feature in approximately 25–35% of children [27].
Focal neurological deficits depend on the site of lesion; frontal
lobe abscess can present with behavioral changes and
hemiparesis; posterior fossa lesions present with lower cranial
nerve palsies, ataxia, gait problems, and encephalopathy
Table 7 Predisposing conditions,
microbial isolates and most likely Predisposing condition
sites of bacterial abscess
Contiguous spread of bacteria
Paranasal sinusitis
Frontal sinus
Sphenoid sinus
Mastoid sinus
Otitis media and
mastoiditis
Middle ear
Open head trauma or
neurosurgery
Facial and scalp infections
Neonatal meningitis
Hematogeneous spread of bacteria
Cardiac disease
Congenital cyanotic heart
disease
Bacterial endocarditis
Lung abscess, empyema
and bronchiectasis
Dental infections
secondary to raised intracranial pressure. Symptoms and signs
in the newborn or infants can be very non specific and mislead-
ing. A very high index of suspicion is required for diagnosis.
Temperature instability, fever, irritability, lethargy, refusal to
feed, vomiting, bulging anterior fontanelle and encephalopathy
can be pointers towards diagnosis of brain abscess [28].
Diagnosis
Do not delay a neuroimaging in children with suspected brain
abscess. A contrast enhanced CT scan is a quick method for
detecting the site, size, and the number of abscesses. The
contrast CT scan will show a ring enhancing lesion with cen-
tral hypodensity and surrounding edema (Fig. 4). A contrast
MRI is more sensitive for the diagnosis of brain abscess. It
shows a T1 hypointense and T2 hyperintense center,
Organism Site of abscess
Streptococcus species
Peptostreptococci Frontal lobe
Bacteriods species Frontal lobe,
S. aureus cavernous sinus
Enterobacteriaceae Temporal lobe and
cerebellum
Streptococci Temporal lobe and
Peptostreptococci cerebellum
Bacteriods
Prevotella
Enterobacteriaceae
S. aureus Contiguous site
S. epidermidis
Streptococcus
Clostridium
Enterobacteriaceae
S. aureus Contiguous site
Streptococci
Proteus mirabilis
Enterobacter
Serratia
Streptococci Middle cerebral
Peptostreptococci artery territory
S. aureus
Streptococcus species
Fusobacterium, actinomyces, prevotella, bacterioids,
nocardia
Streptococcus species
Mixed infections with fusobacterium, actinomyces,
prevotella, bacterioids, nocardia
Streptococcus species

Fig. 3 Axial post contrast T1W MRI of the brain showing subdural
empyema in an infant with bacterial meningitis
surrounded by areas of T2 hyperintensity suggestive of edema
and post contrast images show a ring enhancement of the wall
of the lesion. The differential diagnoses are hematoma, fungal
abscess, tumor and infective granuloma.
Advanced MRI imaging such as diffusion-weighted imag-
ing (DWI) has a high sensitivity and specificity for the diag-
nosis of an abscess and helps in differentiation from a tumor.
The cellular pus in the center of the abscess produces a low
ADC value, and DWI shows diffusion restriction with central
bright signal [29].
Blood culture may be positive in 25% patients, particularly
in patients with a hematogenous spread of infection [28].
Lumbar puncture is not recommended because of the risk of
brain herniation. An underlying dental, paranasal sinus, ear, or
skin foci should be cultured, and surgically explored if re-
quired. Brain abscess tissue and material obtained through
diagnostic and therapeutic aspiration must be sent for gram
stain, bacterial, anerobic, fungal and tubercular cultures.
Treatment
Antibiotics should be started on clinical suspicion of brain
abscess and should be broad spectrum. The choice of initial
antibiotics should be based on the most likely cause of the
disease, on the risk factors, predisposing conditions, and the
pattern of antimicrobial susceptibility. The empirical antibi-
otics include cefotaxime or ceftriaxone and metronidazole
and vancomycin [29]. In immunocompromised individuals,
empirical cover should include antifungal agents.
Neurosurgical intervention is imperative for diagnostic aspi-
ration and therapeutic drainage. With modern stereotactic neu-
rosurgical techniques, any abscess >1 cm in size is amenable
for the aspiration. Stereotactic aspiration should be performed
for the purpose of diagnostic aspiration and decompression
Indian J Pediatr
Fig. 4 Axial CECT of the brain showing multiple brain abscesses in the
basi-frontal region with perilesional edema. The child had sinusitis
unless contraindicated. Total excision was recommended pre-
viously but now has a limited role. Any abscess >2.5 cm in
size, abscess abutting the ventricular wall should be subjected
to immediate aspiration.
Once the organism is identified in the cultures, the antibiotic
therapy can be modified to achieve the most effective therapy.
However, 27% brain abscesses are polymicrobial in nature and
a broad spectrum antibiotic is advised until cultures from brain
abscess itself are available or repeated blood cultures are sterile.
The duration of antimicrobial therapy is 6–8 wk. Cranial neu-
roimaging should be repeated immediately if there is neurolog-
ical deterioration, after 1–2 wk if there is no clinical improve-
ment and biweekly once recovery is evident until 3 mo.
Complications of brain abscess are raised ICP, herniation, hy-
drocephalus, rupture and ventriculitis (Fig. 4) [30].
Adjunctive glucocorticoids therapy helps in reducing the
cerebral edema. However, steroid therapy reduces the antibi-
otics passage in the CSF and their use is limited to cases with
marked raised ICP and brain herniation.
Subdural Empyema
Subdural empyema (SDE) is a collection of pus between the
dura mater and the arachnoid mater. In infants, subdural em-
pyema is a complication of purulent meningitis and in chil-
dren, subdural empyema is focal and secondary to direct ex-
tension from contiguous foci [31]. Cranial surgery, trauma
(depressed skull fractures), infected hematoma and subdural
effusion, middle ear and sinus infection and septic thrombo-
phlebitis, all predispose to subdural empyema. The common
causative organisms are anerobes, aerobic Streptococci,
Staphylococci, H. influenzae, S. pneumoniae, and other
gram-negative bacilli. The most common organisms in
Indian J Pediatr
intracranial SDE secondary to paranasal sinusitis are anerobic
and microaerophilic streptococci, in particular, those of the
S. milleri group (S. milleri and S. anginosus) [31].
The classical triad of SDE includes fever, sinusitis, and
neurological deficits. Headache, nausea, vomiting, seizures,
mental status changes and focal neurological signs are other
clinical features. If untreated, symptoms may progress to
drowsiness, stupor, and eventually, coma. Examination shows
meningismus, contralateral hemiplegia, and cranial nerve
palsies [32].
The diagnosis of SDE is based on neuroimaging and aspi-
ration of pus. On contrast enhanced CT scan, SDE appears as a
hypodense area over the hemisphere or along the falx. The
margins are better delineated with the infusion of contrast
material. The diagnostic procedure of choice for intracranial
SDE is MRI with gadolinium enhancement (Fig. 3).
Diffusion-weighted imaging has proved to be more sensitive
than conventional MRI in detecting the intra-axial involve-
ment [33].
Management
An early and accurate diagnosis, appropriate antibiotic thera-
py and timely surgical interventions are the keys to a more
favorable clinical outcome. Pus from the empyema should be
sent for aerobic and anerobic bacterial culture. MRI can accu-
rately localize the site of pus of collection which can be then
evacuated by a burr hole. A wide craniotomy with irrigation is
the procedure of choice because it improves the outcome in
SDE by allowing wide exposure, adequate exploration and
better evacuation of subdural purulent material [31].
Complications of SDE include seizures; cerebral infarction;
cavernous sinus thrombosis; septic thrombophlebitis; hydro-
cephalus; cerebral edema; cranial osteomyelitis, primarily in
adjacent cranial bones; and residual neurological deficits [32].
Intravenous antibiotics for a total period of 3 to 6 wk is re-
quired and monitoring can be done with ultrasound or repeat
CT or MRI head. In infants, subdural empyema is often sec-
ondary to meningitis, and antibiotic therapy is required for 6–
8 wk [33].
Conclusions
Bacterial infections of the nervous system are a medical
emergency, requiring early recognition and management.
All attempts should be made to identify the causative bac-
terial agent and tailor the therapy accordingly. The choice
of antibiotics should be guided by age, likely pathogen,
predisposing conditions, and local resistance patterns.
Despite antibiotic therapy, a bacterial neuroinfection can
result in severe neuronal damage and lasting sequelae in
children. Future identification of neuronal protection
strategies and novel therapeutic approaches may improve
outcomes. However, adequate primary prevention using
vaccines is the mainstay to reduce their burden.
Contributions RS: Reviewed the literature, wrote the manuscript; NS:
Reviewed the literature, and finalized the manuscript.
Compliance with Ethical Standards
Conflict of Interest None.
Source of Funding None.
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