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igns and symptoms

The 3 classic symptoms (less likely in younger children):

Fever
Headache
Meningeal signs
Symptoms in neonates:

Poor feeding
Lethargy
Irritability
Apnea
Listlessness
Apathy
Fever
Hypothermia
Seizures
Jaundice
Bulging fontanelle
Pallor
Shock
Hypotonia
Shrill cry
Hypoglycemia
Intractable metabolic acidosis
Symptoms in infants and children:

Nuchal rigidity
Opisthotonos
Bulging fontanelle
Convulsions
Photophobia
Headache
Alterations of the sensorium
Irritability
Lethargy
Anorexia
Nausea
Vomiting
Coma
Fever (generally present, although some severely ill children present with hypothermia)
See Clinical Presentation for more specific information on the signs and symptoms of pediatric bacterial
meningitis.

Diagnosis
Definitive diagnosis is based on the following:

Bacteria isolated from the CSF obtained via lumbar puncture


Meningeal inflammation demonstrated by increased pleocytosis, elevated protein level, and low
glucose level in the CSF
Bacterial meningitis score

Components of the bacterial meningitis score[1] are as follows:

Positive CSF Gram stain


CSF absolute neutrophil count 1000/L or higher
CSF protein level 80 mg/dL or higher
Peripheral blood absolute neutrophil count 10,000/L or higher
History of seizure before or at the time of presentation
See Workup for more specific information on testing and imaging modalities for pediatric bacterial
meningitis.

Management
IV antibiotics are required; if cause is unknown, agents can be based on childs age, as follows:

< 30 days, ampicillin and an aminoglycoside or a cephalosporin


30-60 days, ampicillin and a cephalosporin; because Streptococcus pneumoniae may occur in
this age range, consider vancomycin instead of ampicillin

In older children, a cephalosporin or ampicillin plus chloramphenicol with vancomycin (needs to


be added secondary to the possibility of S pneumoniae)
Guidelines and recommendations
Infectious Diseases Society of America:

Vancomycin plus either ceftriaxone or cefotaxime[2]


Duration of therapy:
o
Neisseria meningitidis - 7 days
o
Haemophilus influenzae - 7 days
o
Streptococcus pneumoniae - 10-14 days
o
S agalactiae (GBS) - 14-21 days
o
Aerobic gram-negative bacilli - 21 days or 2 weeks beyond the first sterile culture
(whichever is longer)
o
Listeria monocytogenes - 21 days or longer
American Academy of Pediatrics:

Duration of therapy should not be shorter than 5-7 days for meningococcus, 10 days for H
influenzae, and 14 days for S pneumoniae[3]
Prevention
Preventive therapy has been shown to reduce mortality and morbidity and consists of the following:

Chemoprophylaxis: Rifampin, ceftriaxone, ciprofloxacin; ciprofloxacin and ceftriaxone are more


effective against resistant strains of Neisseria meningitidis up to 4 weeks after treatment

Haemophilus influenzae type b (Hib): Rifampin chemoprophylaxis for contacts of index cases of
invasive Hib disease; MenHibrix provides immunization against Hib and meningococcal serogroups C
and Y

Neisseria meningitidis: Quadrivalent (ie, A, C, Y, W-135) meningococcal conjugate vaccine


recommended for high-risk groups
See Treatment and Medication for more specific information on pharmacologic and other therapies for
pediatric bacterial meningitis.

Image library

Acute bacterial meningitis. This axial nonenhanced CT scan shows mild


ventriculomegaly and sulcal effacement.

Background
Pediatric bacterial meningitis is a life-threatening illness that results from bacterial infection of the
meninges. Because bacterial meningitis in the neonatal period has its own unique epidemiologic and
etiologic features, it will be discussed separately in this article as necessary.
Beyond the neonatal period, the 3 most common organisms that cause acute bacterial meningitis
are Streptococcus pneumoniae, Neisseria meningitidis, andHaemophilus influenzae type b (Hib). Since
the routine use of Hib, conjugate pneumococcal, and conjugate meningococcal vaccines in the United
States, the incidence of meningitis has dramatically decreased.
Although S pneumoniae is now the leading cause of community-acquired bacterial meningitis in the
United States (1.1 cases per 100,000 population overall), the rate of pneumococcal meningitis is 59%
lower than it was before the introduction of the conjugate pneumococcal vaccine in 2000. The incidence
of disease caused by S pneumoniae is highest in children aged 1-23 months and in adults older than 60
years.
Predisposing factors include respiratory infection, otitis media, mastoiditis, head trauma,
hemoglobinopathy, human immunodeficiency virus (HIV) infection, and other immune deficiency states.
Meningitis is a life-threatening illness and leaves some survivors with significant sequelae. Therefore,
meticulous attention must be paid to appropriate treatment and monitoring of these patients. Patients
require hospitalization for antibiotic therapy and appropriate support. Adequate fluid administration is
necessary to maintain perfusion, especially cerebral perfusion. Fluid restrictions (to prevent cerebral
edema) may be more harmful because patients may be under resuscitated. Antibiotics must be promptly
administered.
The emergence of penicillin-resistant S pneumoniae has resulted in new challenges in the treatment of
bacterial meningitis.

Pathophysiology
Bacteria reach the subarachnoid space via a hematogenous route and may directly reach the meninges
in patients with a parameningeal focus of infection.
Once pathogens enter the subarachnoid space, an intense host inflammatory response is triggered by
lipoteichoic acid and other bacterial cell wall products produced as a result of bacterial lysis. This
response is mediated by the stimulation of macrophage-equivalent brain cells that produce cytokines and
other inflammatory mediators. This resultant cytokine activation then initiates several processes that
ultimately cause damage in the subarachnoid space, culminating in neuronal injury and apoptosis.
Interleukin (IL)1, tumor necrosis factor alpha (TNF-a), and enhanced nitric oxide production play critical
roles in triggering inflammatory response and ensuing neurologic damage. Infection and inflammatory
response later affect penetrating cortical vessels, resulting in swelling and proliferation of the endothelial

cells of arterioles. A similar process can involve the veins, causing mural thrombi and obstruction of flow.
The result is an increase in intracellular sodium and intracellular water.
The development of brain edema further compromises cerebral circulation, and this effect can result in
increased intracranial pressure (ICP) and uncal herniation. Increased secretion of antidiuretic hormone
(ADH), resulting in the syndrome of inappropriate antidiuretic hormone secretion (SIADH), occurs in most
patients with meningitis and causes further retention of free water. These factors contribute to the
development of focal or generalized seizures.
Severe brain edema also causes midline structures to shift caudally and become entrapped in the
tentorial notch or foramen magnum. Caudal shifts produce herniation of the parahippocampal gyri,
cerebellum, or both. These intracranial changes appear clinically as an alteration of consciousness and
postural reflexes. Caudal displacement of the brainstem causes palsy of the third and sixth cranial nerves.
If untreated, these changes result in decortication or decerebration and can progress rapidly to respiratory
and cardiac arrest.

Neonatal meningitis
Bacteria from the maternal genital tract colonize the neonate after rupture of membranes, and specific
bacteria, such as group B streptococci (GBS), enteric gram-negative rods, and Listeria
monocytogenes, can reach the fetus transplacentally and cause infection. Furthermore, newborns can
also acquire bacterial pathogens from their surroundings, and several host factors facilitate a
predisposition to bacterial sepsis and meningitis.
Bacteria reach the meninges via the bloodstream and cause inflammation. After arriving in the central
nervous system (CNS), bacteria spread from the longitudinal and lateral sinuses to the meninges, the
choroid plexus, and the ventricles.
IL-1 and TNF-a also mediate local inflammatory reactions by inducing phospholipase A2 activity, initiating
the production of platelet-activating factor and the arachidonic acid pathway. This process results in
production of prostaglandins, thromboxanes, and leukotrienes. Activation of adhesion-promoting
receptors on endothelial cells by these cytokines attracts leukocytes, and the release of proteolytic
enzymes from the leukocytes results in altered blood-brain permeability, activation of the coagulation
cascade, brain edema, and tissue damage.
Inflammation of the meninges and ventricles produces a polymorphonuclear response, an increase in
cerebrospinal fluid (CSF) protein content, and utilization of glucose in CSF. Inflammatory changes and
tissue destruction in the form of empyema and abscesses are more pronounced in gram-negative
meningitis. Thick inflammatory exudate causes blockage of the aqueduct of Sylvius and other CSF
pathways, resulting in both obstructive and communicating hydrocephalus.

Etiology
Causes in different age groups
Neonates
Bacteria are often acquired from the maternal vaginal flora. Gram-negative enteric flora and GBS are the
dominant pathogens. In premature newborns who receive multiple antibiotics, those on hyperalimentation,
and those who undergo various surgical procedures, Staphylococcus epidermidis and Candida species
are uncommon but are reported in greater frequency in neonates. L monocytogenes is another wellknown but fairly uncommon causative pathogen.
Early-onset GBS meningitis occurs during the first 7 days of life as a consequence of maternal
colonization and the absence of protective antibody in the neonate; it is often associated with obstetric
complications. The disease is seen most often in premature or low-birth-weight babies. Pathogens are
acquired before or during the birth process.

Late-onset meningitis is defined as disease occurring after 7 days of life. Causes include perinatally
acquired and nosocomial pathogens. Streptococcus agalactiae(GBS) is classified into 5 distinct
serotypes: Ia, Ib, Ic, II, and III. Although these serotypes occur with almost equal frequency in the early
onset of disease, serotype III causes 90% of late-onset disease.
Use of respiratory equipment in the nursery increases the risk of infection caused by Serratia
marcescens,Pseudomonas aeruginosa, and Proteus species. Invasive devices predispose infants to the
infections caused by S epidermidis andPseudomonas, Citrobacter, and Bacteroides species.
Infection with Citrobacter diversus, Citrobacter koseri, Salmonella species, andProteus species, though
uncommon, carries a high mortality. These patients often develop brain abscesses, particularly those
with Citrobacter, in whom meningitis produces brain abscesses in 80-90% of cases.
Infants and children
In children older than 4 weeks, S pneumoniae and N meningitidis are the most common etiologic agents.
Hib has essentially disappeared in countries where the conjugate vaccine is routinely used.

Causative organisms
Streptococcus pneumoniae
S pneumoniae is a gram-positive, lancet-shaped diplococcus that is the leading cause of meningitis. Of
the 84 serotypes, numbers 1, 3, 6, 7, 14, 19, and 23 are the ones most often associated with bacteremia
and meningitis. Children of any age may be affected, but the incidence and severity are highest in very
young and elderly persons.
In patients with recurrent meningitis, predisposing factors are anatomic defects, asplenia, and primary
immune deficiency. Often, the history includes recent or remote head trauma. This organism also has a
predilection for causing meningitis in patients with sickle cell disease, other hemoglobinopathies, and
functional asplenia. Immunity is type-specific and long-lasting.
S pneumoniae colonizes the upper respiratory tract of healthy individuals; however, disease often is
caused by a recently acquired isolate. Transmission is person-to-person, usually via direct contact;
secondary cases are rare. The incubation period is 1-7 days, and infections are more common in winter,
when viral respiratory disease is prevalent. The disease often results in sensorineural hearing loss,
hydrocephalus, and other central nervous system (CNS) sequelae. Prolonged fever despite adequate
therapy is common with S pneumoniaemeningitis.
Effective antimicrobial therapy can eradicate the organism from nasopharyngeal secretions within 24
hours. However, pneumococci have developed resistance to a variety of antibiotics; this development is
seen worldwide. Rates of resistance to penicillin range from 10% to 60%. Multicenter surveillance of
pneumococci isolated from the cerebrospinal fluid (CSF) has found resistance rates of 20% to penicillin
and 7% to ceftriaxone.
Penicillin resistance in pneumococci is due to alterations in enzymes necessary for growth and repair of
the penicillin-binding proteins; thus, beta-lactamase inhibitors offer no advantage. Penicillin-resistant
pneumococci are often resistant to trimethoprim-sulfamethoxazole, tetracyclines, chloramphenicol, and
macrolides. However, selected third-generation cephalosporins (eg, cefotaxime and ceftriaxone) do
exhibit activity against most penicillin-resistant pneumococcal isolates.
At present, all pneumococcal isolates remain susceptible to vancomycin and various oxazolidinones.
Several of the fluoroquinolones (eg, levofloxacin), though contraindicated in children, have excellent
activity against most pneumococci and achieve adequate CNS penetration.
Tolerance, a trait distinct from resistance, is the term used to characterize bacteria that stop growing in
the presence of antibiotic yet do not lyse and die. Pneumococci that are tolerant of penicillin and
vancomycin have been described in literature, and a subsequent link to recrudescent meningitis was
described in 1 child. The overall incidence and clinical impact of such bacterial strains are unknown.

However, the possibility of tolerance should be kept in mind in cases of recurrent pneumococcal
meningitis.
Neisseria meningitidis
N meningitidis is a gram-negative, kidney beanshaped organism that is frequently found intracellularly.
Organisms are grouped serologically on the basis of capsular polysaccharide; A, B, C, D, X, Y, Z, 29E,
and W-135 are the pathogenic serotypes. In developed countries, serotypes B, C, Y, and W-135 account
for most childhood cases. Group A strains are most prevalent in developing countries and have resulted in
epidemics of meningococcal meningitis throughout the world, as well as outbreaks in military barracks.
The upper respiratory tract frequently is colonized with meningococci, and transmission is person-toperson via direct contact with infected droplets of respiratory secretions, often from asymptomatic
carriers. The incubation period is generally less than 4 days (range, 1-7 days).
Most cases occur in infants aged 6-12 months; a second, lower peak occurs among adolescents. A
petechial or purpuric rash frequently is seen. Mortality is significant in patients who have a rapidly
progressive fulminant form of the disease. Normocellular CSF also has been reported in patients with
meningococcal meningitis. Most deaths occur within 24 hours of hospital admission in patients who have
features associated with poor prognosis, such as the following:

Hypotension
Shock
Neutropenia
Extremes of age
Petechiae and purpura of less than 12 hours duration
Disseminated intravascular coagulation (DIC)
Acidosis
Presence of the organism in white blood cells (WBCs) on peripheral smear
Low erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level
Serogroup C disease
Higher rates of fatality and physical sequelae (eg, scarring and amputation) are reported in survivors of
serogroup C disease. Long-term sequelae are rare in patients who have an uneventful hospital course.
Haemophilus influenzaetype b (Hib)
Hib is a pleomorphic gram-negative rod whose shape varies from a coccobacillary form to a long curved
rod. Hib meningitis occurs primarily in children who have not been immunized with Hib vaccine; 80-90%
of cases occur in children aged 1 month to 3 years. By age 3 years, a significant number of
nonimmunized children acquire antibodies against the capsular polyribophosphate of Hib, which are
protective.
The mode of transmission is person-to-person via direct contact with infected droplets of respiratory
secretions. The incubation period generally is less than 10 days. Current mortality is less than 5%. Most
fatalities occur during the first few days of the illness.
Plasmid-mediated resistance to ampicillin due to the production of beta-lactamase enzymes by bacterium
is increasingly being reported: 30-35% of Hib isolates are now ampicillin-resistant. As many as 30% of
cases may have subtle long-term sequelae. Administration of dexamethasone early in treatment reduces
morbidity and sequelae.
Listeria monocytogenes
L monocytogenes causes meningitis in newborns, immunocompromised children, and pregnant women.
The disease also has been associated with the consumption of contaminated foods (eg, milk and
cheese). Most cases are caused by serotypes Ia, Ib, and IVb. Signs and symptoms in patients with

listerial meningitis tend to be subtle, and diagnosis often is delayed. In the laboratory, this pathogen can
be misidentified as a diphtheroid or a hemolytic streptococcus.
Other organisms
S epidermidis and other coagulase-negative staphylococci frequently cause meningitis and CSF shunt
infection in patients with hydrocephalus or those who have undergone neurosurgical procedures.
Immunocompromised children can develop meningitis caused by Pseudomonas, Serratia,Proteus, and
diphtheroids.

Risk factors
Risk factors for bacterial meningitis include the following:

Age
Low family income
Attendance at day care
Head trauma
Splenectomy
Chronic disease
Children with facial cellulitis, periorbital cellulitis, sinusitis, and septic arthritis have an increased
risk of meningitis.

Maternal infection and pyrexia at the time of delivery are associated withneonatal meningitis
Use of Hib and pneumococcal vaccines decreases the likelihood of infection from these agents.

Epidemiology
United States statistics
The advent of vaccine has changed the incidence of pediatric bacterial meningitis. Before the routine use
of the pneumococcal conjugate vaccine, the incidence of bacterial meningitis in the United States was
about 6000 cases per year; roughly half of these were in pediatric patients (18 years). N
meningitidis caused about 4 cases per 100,000 children (aged 1-23 months). The rate of S
pneumoniaemeningitis was 6.5 cases per 100,000 children (aged 1-23 months). Today, disease caused
by H influenzae, S pneumoniae, and N meningitidis is much less common.
The advent of universal Hib vaccination in developed countries has led to the elimination of more than
99% of invasive disease. Protection continues even when Hib is coadministered with other vaccines. Just
as important, the vaccine continues to confer immunity into later childhood.
A similar effect occurs with pneumococcal vaccine. Given at ages 2, 4, and 6 months, this vaccine has
reduced invasive disease by more than 90%. Age groups most affected are those younger than 2 years
and those aged 2-5 years. This was proven in a surveillance study in Louisville, Kentucky.[4] Nearly half of
cases of pneumococcal disease are caused by nonvaccine serotypes. [5, 6]
Vaccine for Neisseria, however, has not been efficacious in younger children. This is due to poor
immunogenic response. Current recommendations target immunization for children older than 2 years
and high-risk patients with asplenic and terminal complement deficiencies. In addition, young adults living
in close quarters, such as dormitories or military barracks, will benefit.
A study analyzing reported cases of bacterial meningitis among residents in 8 surveillance areas of the
Emerging Infections Programs Network during 1998-2007 found a 31% decrease in meningitis cases
during this period and an increase in median patient age from 30.3 years in 1998-1999 to 41.9 years in
2006-2007; the case fatality rate did not change significantly.[7] Overall, approximately 4100 cases of
bacterial meningitis occurred annually in the United States from 2003 to 2007, with approximately 500
deaths.[7]

The incidence of neonatal bacterial meningitis is 0.25-1 case per 1000 live births (0.15 case per 1000 fullterm births and 2.5 cases per 1000 premature births). Approximately 30% of newborns with clinical sepsis
have associated bacterial meningitis.
After the initiation of intrapartum antibiotics in 1996, the national incidence of early-onset GBS infection
decreased substantially, from approximately 1.8 cases per 1000 live births in 1990 to 0.32 case per 1000
live births in 2003.

International statistics
Worldwide, the use of H influenzae type B and pneumococcal vaccines is increasing at a rate faster than
that observed with the use of hepatitis B vaccines. [8]
In a survey by the Hib and Pneumococcal Working Group, the incidence of meningitis in 2000 varied in
different regions of the world. The overall incidence of pneumococcal meningitis was 17 cases per
100,000, with the highest incidence in Africa, at 38 cases per 100,000, and the lowest incidence in
Europe, at 6 cases per 100,000.[9] The overall death rate was 10 cases per 100,000. The death rate was
highest in Africa, at 28 cases per 100,000, and lowest in Europe and Western Pacific regions, at 3 cases
per 100,000.
A similar trend was identified for Hib meningitis.[10] The overall incidence of Hib meningitis in 2000 was 31
cases per 100,000. The African region had the highest rate, at 46 cases per 100,000, and Europe had the
lowest, at 13 cases per 100,000. The overall death rate was 13 cases per 100,000. The highest death
rate was in Africa, at 31 cases per 100,000, and the lowest was in Europe, at 4 cases per 100,000.

Age-, sex-, and race-related demographics


Pediatric bacterial meningitis is most common in children younger than 4 years, with a peak incidence in
those aged 3-8 months.
Male infants have a higher incidence of gram-negative neonatal meningitis. Female infants are more
susceptible to L monocytogenes infection. S agalactiae (GBS) affects both sexes equally.
Bacterial meningitis occurs more frequently in black, Native American, and Hispanic children; this is
thought to be related to socioeconomic rather than racial factors.

Prognosis
Mortality and morbidity depend on the infectious agent, the age of the child, the childs general health,
and the promptness of diagnosis and treatment. Despite improvements in antibiotic and supportive
therapy, death and complication rates remain significant.
Overall mortality for bacterial meningitis is 5-10% and varies according to the causative organism and the
patients age. In neonates, mortality is 15-20%, whereas in older children, it is 3-10%. Of the meningitides
caused by the most common pathogens, S pneumoniae meningitis has the highest mortality, at 26.3-30%;
Hib meningitis has the next highest, at 7.7-10.3%; and N meningitidis has the lowest, at 3.5-10.3%.
As many as 30% of children have neurologic sequelae. This rate varies by organism, with S
pneumoniae being associated with the highest rate of complications. One study indicated that the
complication rate from S pneumoniaemeningitis was essentially the same for penicillin-sensitive strains as
for penicillin-resistant strains; this study also showed that dexamethasone did not improve outcomes. [11]
Prolonged or difficult-to-control seizures, especially after hospital day 4, are predictors of a complicated
hospital course with serious sequelae. On the other hand, seizures that occur during the first 3 days of
illness usually have little prognostic significance.
Approximately 6% of affected infants and children show signs of DIC and endotoxic shock. These signs
are indicative of a poor prognosis.

Studies have documented the development of profound bilateral hearing loss, which may occur in as
many as 4% of all bacterial meningitis cases.[12]Sensorineural hearing loss is one of the most frequent
problems. Children at greatest risk for hearing loss include those with evidence of increased ICP, those
with abnormal findings on computed tomography (CT), males, those with low CSF glucose levels, those
with S pneumoniae infection , and those with nuchal rigidity.
Because many of the children affected are very young and lack mature cognitive and motor skills, some
of the sequelae may not be recognized for years. In a study that followed children who recovered from
meningitis for 5-10 years, 1 of every 4 school-aged meningitis survivors had either serious and disabling
sequelae or a functionally important behavior disorder or neuropsychiatric or auditory dysfunction that
impaired their performance in school.
For tuberculous meningitis, morbidity and mortality are related to the stage of the disease. The rate of
significant morbidity is 30% for stage I, 56% for stage II, and 94% for stage III.

Patient Education
Because of the high incidence of sequelae, parents should be cautioned from the beginning that even
with appropriate medical care, the child may have some complications. Respond promptly to parents
concerns with adequate documentation.
Careful neurologic examination and visual and hearing screening tests (brainstem evoked potentials)
should be obtained and reviewed with parents so that parents are aware of any deficits. Early detection of
deficits should result in initiating appropriate physical and occupational therapy and in acquiring other
devices or modalities required by the patient to achieve the maximum possible benefit

Approach Considerations
Bacterial meningitis is a medical emergency. A firm diagnosis is usually made when bacteria are isolated
from the cerebrospinal fluid (CSF) and evidence of meningeal inflammation is demonstrated by increased
pleocytosis, elevated protein level, and low glucose level in the CSF. Timely collection and processing of
CSF and isolation of an organism allows optimization of choice of antimicrobial agent and duration of
therapy. CSF chemistries and cytology vary, depending on the maturity and age of the newborn.
A lumbar puncture (LP) may be contraindicated in some of the following conditions: unstable patients with
hypotension or respiratory distress who may not be able to tolerate the procedure, brain abscess, brain
tumors or other cause of raised intracranial pressure, and occasionally infection at the lumbar puncture
site.
The Bacterial Meningitis Score, a clinical decision rule developed by Nigrovic et al, [14] has shown high
accuracy and usability and continues to be evaluated with respect to its effectiveness as an aid to identify
those children with CSF pleocytosis who are at low risk for bacterial meningitis. [1] The components of the
score include the following:

Positive CSF Gram stain


CSF absolute neutrophil count of 1000/L or higher
CSF protein level of 80 mg/dL or higher
Peripheral blood absolute neutrophil count of 10,000/L or higher
History of seizure before or at the time of presentation
Specific hematologic, radiographic (eg, computed tomography [CT] and magnetic resonance imaging
[MRI]), and other studies assist in diagnosis.

Blood and Urine Studies


Blood studies that may be indicated include the following:

Complete blood count (CBC) with differential


Blood cultures

Coagulation studies
Serum glucose
Electrolytes
Measurement of the serum glucose level close to the time of CSF collection is helpful for interpreting CSF
glucose levels and assessing the likelihood of meningitis.
Bacterial antigen studies can be performed on urine and serum and can be useful in cases of pretreated
meningitis; however, a negative bacterial antigen study result does not rule out meningitis. The group B
streptococcal (GBS) antigen test in urine is unreliable and should not be used to make a diagnosis of
sepsis or meningitis.
Some data suggest that procalcitonin may be a useful biomarker for distinguishing bacterial meningitis
from aseptic meningitis. Its use may enhance the sensitivity of the Bacterial Meningitis Score. [15, 16, 14] In a
retrospective analysis of admitted patients with meningitis, Dubos et al found procalcitonin at a level of 0.5
ng/mL to have a sensitivity of 99% and a specificity of 83% for differentiating bacterial from aseptic
meningitis.[15]

Lumbar Puncture and CSF Analysis


Definitive diagnosis is based on examination of CSF obtained via lumbar puncture. Opening and closing
pressures should be measured in the cooperative patient. Similarly, the color of the CSF (eg, turbid, clear,
or bloody) should be recorded. If the CSF is not crystal clear, administer treatment immediately without
waiting for the results of CSF tests.
In a traumatic lumbar puncture, where bleeding occurs and the CSF is contaminated with blood,
interpretation becomes especially difficult. In this situation, it is better to initiate treatment before the
results of the CSF culture are available. In very bloody lumbar punctures, a drop of the fluid on the sterile
dressing usually will produce a double ring if CSF is present. Generally, when in doubt, proceed with
treatment and attempt the lumbar puncture again later.
In particular, if the patient shows signs of pending herniation, consider treatment without performing a
lumbar puncture. The puncture can be performed later, when intracranial pressure (ICP) has been
controlled and the patient is clinically stable. CT or MRI is helpful in managing patients who require
control of ICP and herniation.

CSF studies
Perform total and differential cell counts, chemistries (ie, glucose and protein), Gram stains, and cultures
on all CSF specimens. In a setting of antibiotic pretreatment, rapid bacterial antigen testing may be
considered. Note that patients with both fulminant disease and poor immune response may not show
cytologic or chemical changes in CSF. In about 2-3% of bacterial meningitis cases, bacterial cultures may
be positive even when the Gram stain is negative and the cell counts and glucose and protein levels are
normal.
White blood cell (WBC) counts higher than 1000/L are usually caused by bacterial infections. Counts of
500-1000/L may be bacterial or viral and call for further evaluation. Lower counts are usually associated
with viral infections.
The total WBC count cannot definitely distinguish between bacterial and other causes. At one time, it was
generally believed that a predominance of polymorphonuclear leukocytes (PMNs) pointed to bacterial
meningitis, but this has been an unreliable indicator; bacterial meningitis may also present with a
lymphocytic predominance. Attempts to differentiate bacterial and aseptic meningitis on the basis of
percentage and absolute number of premature neutrophils (ie, bands) have not yielded diagnostic results.
[17]

The use of a corrected ratio of WBCs to red blood cells (RBCs)that is, 1:500or the percentage of
neutrophils to normalize the cell count was shown to have limited utility in predicting which patients
would have meningitis. The corrected CSF was shown to underestimate the true WBC count, causing

clinicians to underdiagnose borderline meningitis cases. Formulas to adjust the WBC count have not
increased the specificity or sensitivity of CSF analysis in traumatic lumbar punctures in neonates. [18]
The CSF protein concentration is usually elevated in bacterial meningitis (greater than 50 mg/dL), but it is
also elevated by a traumatic lumbar puncture. The CSF glucose concentration is usually reduced in
bacterial meningitis. A normal CSF glucose level should be higher than two thirds of the serum glucose
level; a CSF level lower than 50% of the serum level is suggestive of bacterial meningitis. In patients with
very early disease, however, CSF protein and glucose values may be within the reference range.
A Gram stain of cytocentrifuged CSF may reveal bacterial morphology. The CSF should be plated
immediately onto a chocolate and blood agar media. Smears of petechial lesions may reveal
microorganisms on Gram stain. Although Gram stain may aid in diagnosis, the diagnosis may be missed
in up to 30-40% of cases of culture-proven disease. The sensitivity of a positive Gram stain is 67%. [19]
Examination of a buffy coat smear also may reveal intracellular microorganisms. The results of a
retrospective cohort study found that WBC counts in the CSF of febrile infants without bacterial or
enteroviral infection are lower than was previously reported. [20]
Even when CSF results are otherwise normal, the fluid should still be sent for culture. Both N
meningitidis meningitis and S pneumoniae meningitis are known to give normal CSF results. In an
evidence-based article, Ray et al found that meningitis may still exist in 10% of children who have normal
CSF analysis.[21]Their recommendation is to treat any child with antibiotics if there is a risk of bacterial
meningitis.
Several tests based on the principle of agglutination are available for the detection of bacterial antigens in
body fluids. Bacterial antigen detection can be carried out in samples of CSF, blood, and urine. A negative
result, however, does not rule out bacterial infection. Antigen detection tests are most helpful in patients
with partially treated meningitis in whom bacteria may not grow from CSF but antigens persist in body
fluids. Antigen detection in urine is particularly helpful in such circumstances because urine can be
concentrated severalfold in the laboratory.
Several gram-negative bacteria and higher serotypes of S pneumoniae have capsular antigens that
cross-react with H influenzae type b polyribophosphate. Capsular antigens of group B meningococcus
cross-react with K1-containingEscherichia coli. Gram stains of CSF are more sensitive than these rapid
diagnostic tests for the detection of N meningitidis.

Partially treated meningitis


Many children receive antibiotics before definitive diagnosis is made. As a rule, a few doses of oral
antimicrobial agents, or even a single injection of an antibiotic, do not significantly alter CSF findings,
including bacterial cultures, especially in patients with H influenzae type b (Hib) disease. Oral antibiotics
have never convincingly been shown to render patients with bacterial meningitis CSF culturenegative.
CSF cultures may become sterile rapidly if the pathogen was a pneumococcus or meningococcus, though
cellular changes, an increase in protein, and low glucose levels persist. In such cases, CSF, blood, and
urine should be tested for bacterial antigens; however, the presence of a negative antigen result does not
entirely rule out a bacterial source.
In cases where antibiotic administration leads to CSF sterilization, polymerase chain reaction (PCR)
testing may have a role to play in identifying the pathogen. PCR testing is able to identify the pathogen
quickly and accurately and does not require a large number of organisms; however, it does require further
validation in this setting.
Nigrovic et al found that Gram stain results (WBC count and absolute neutrophil count) in CSF were not
affected by pretreatment with antibiotics; however, the rates of positive CSF culture and blood culture
were lower with antibiotic pretreatment.[22] After pretreatment with antibiotics for 12 hours or longer, the
patients had higher CSF glucose levels and lower CSF protein levels.

CT and MRI
CT and MRI may reveal ventriculomegaly and sulcal effacement (see the images below).

Acute bacterial meningitis. This axial nonenhanced CT scan shows mild

ventriculomegaly and sulcal effacement.

Acute bacterial meningitis. This axial T2-

weighted MRI shows only mild ventriculomegaly.


Acute bacterial meningitis. This
contrast-enhanced, axial T1-weighted MRI shows leptomeningeal enhancement (arrows).