Bacterial meningitis in children older than one month: Clinical features and diagnosis

Author Sheldon L Kaplan, MD

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Literature review current through: Apr 2014. | This topic last updated: Mar 05, 2014.
INTRODUCTION Meningitis is an inflammatory disease of the leptomeninges, the
tissues surrounding the brain and spinal cord. The meninges consist of three parts: the pia,
arachnoid, and dura mater. Meningitis reflects inflammation of the arachnoid mater and the
cerebrospinal fluid (CSF) in both the subarachnoid space and in the cerebral ventricles.
Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps
must be taken to establish the specific cause so that appropriate antimicrobial therapy can
be initiated. The mortality rate of untreated bacterial meningitis approaches 100 percent.
Even with optimal therapy, morbidity and mortality may occur. Neurologic sequelae are
common among survivors.
The clinical and laboratory features of bacterial meningitis in infants and children older
than one month will be reviewed here. The epidemiology, pathogenesis, treatment,
prognosis, and prevention of acute meningitis and the clinical features, diagnosis,
treatment, and prognosis of bacterial meningitis in neonates (<1 month of age) and adults
are discussed separately. (See "Pathogenesis and pathophysiology of bacterial meningitis"
and "Bacterial meningitis in children older than one month: Treatment and prognosis" and
"Bacterial meningitis in the neonate: Clinical features and diagnosis" and "Bacterial
meningitis in the neonate: Treatment and outcome" and "Epidemiology of bacterial
meningitis in adults" and "Clinical features and diagnosis of acute bacterial meningitis in
adults" and "Initial therapy and prognosis of bacterial meningitis in adults" and "Treatment
of bacterial meningitis caused by specific pathogens in adults".)
EPIDEMIOLOGY After the introduction of the Haemophilus influenzae type b (Hib)
and pneumococcal conjugate vaccines to the infant immunization schedule (in 1990 and
2000, respectively) the incidence of bacterial meningitis declined in all age groups except
children younger than two months [1]. The median age shifted from <5 years to 42 years
[1,2]. The peak incidence continues to occur in children younger than two months.
In population-based surveillance (2006 to 2007), the incidence of bacterial meningitis in
United States children varied with age [1]:
<2 months 80.69 per 100,000 population
2 through 23 months 6.91 per 100,000 population
2 through 10 years 0.56 per 100,000 population
11 through 17 years 0.43 per 100,000 population
Causative organisms The organisms responsible for acute bacterial meningitis depend in
part upon the route of acquisition and underlying host factors (table 1 and table 2).
The relative frequency of pathogens causing bacterial meningitis in children changed after
the introduction of the Hib and pneumococcal conjugate vaccines to the routine childhood
immunization schedule (figure 1) [3]. In a retrospective review of 231 cases of bacterial
meningitis in children (1 month through 18 years of age) who presented to 20 pediatric
emergency departments in the United States between 2001 and 2004, the most frequent
pathogens varied according to age, as follows:
1 month and <3 months Group B streptococcus (39 percent), gram-negative bacilli (32
percent), Streptococcus pneumoniae (14 percent), Neisseria meningitidis (12 percent)
3 months and <3 years S. pneumoniae (45 percent), N. meningitidis (34 percent), group
B streptococcus (11 percent), gram-negative bacilli (9 percent)
3 years and <10 years S. pneumoniae (47 percent), N. meningitidis (32 percent)
10 years and <19 years N. meningitidis (55 percent)
Similar findings were noted in 587 cases of bacterial meningitis in children (0 to 18 years)
identified through the Emerging Infections Program Network between 1998 and 2007 [1].
Before widespread vaccination for Hib in the United States, Hib was the major cause of
bacterial meningitis in children [4]. Although the incidence of pneumococcal meningitis in
children in the United States declined by 55 to 60 percent after widespread vaccination for
S. pneumoniae, S. pneumoniae remains the most frequent cause of bacterial meningitis in
children [1,3,5-7]. Even with prompt and appropriate therapy, pneumococcal meningitis is
an important cause of childhood morbidity and mortality [3]. (See "Pneumococcal
meningitis in children", section on 'Outcome'.)
Predisposing factors In addition to specific factors that may predispose certain hosts to
bacterial meningitis with a particular organism (table 2), the following factors also may
increase the risk of bacterial meningitis [8]:
Recent exposure to someone with meningococcal or Hib meningitis
Recent infection (especially respiratory or otic infection)
Recent travel to areas with endemic meningococcal disease, such as sub-Saharan Africa
Penetrating head trauma
Cerebrospinal fluid (CSF) otorrhea (including congenital defects, such as Mondini
dysplasia) or CSF rhinorrhea
Cochlear implant devices, particularly those with a positioner (see "Cochlear implant
infections", section on 'Risk of meningitis')
Anatomic defects (eg, dermal sinus (picture 1) or urinary tract anomaly) or recent
neurosurgical procedure (eg, ventricular shunt placement) may predispose to meningitis
with Staphylococcus aureus, coagulase-negative staphylococcus, and enteric gram-negative
organisms, such as Escherichia coli and Klebsiella species [9]. (See "Epidemiology and
clinical features of gram-negative bacillary meningitis".)
CLINICAL FEATURES
Course Acute bacterial meningitis has two patterns of presentation [10,11]. In the first,
meningitis develops progressively over one or several days and may be preceded by a
febrile illness. In the second, the course is acute and fulminant, with manifestations of
sepsis and meningitis developing rapidly over several hours [10]. The rapidly progressive
form is frequently associated with severe brain edema.
Presentation Most patients with bacterial meningitis present with fever and symptoms
and signs of meningeal inflammation (nausea, vomiting, irritability, anorexia, headache,
confusion, back pain, and nuchal rigidity) [12-14]. These findings are often preceded by
symptoms of upper respiratory infection [15]. However, the clinical manifestations of
bacterial meningitis are variable and nonspecific; no single sign is pathognomonic [10,13].
Previous receipt of oral antibiotics does not affect the clinical presentation of acute
bacterial meningitis.
The symptoms and signs depend, to some extent, upon the duration of illness, the host
response to infection, and the age of the patient [10]. The triad of fever, neck stiffness, and
mental status changes is present in only 44 percent of adults with bacterial meningitis [7],
and in even fewer children. In older children, clinical manifestations may include fever,
headache, photophobia, nausea, vomiting, confusion, lethargy, and/or irritability [10,14]. In
infants, manifestations may include fever, hypothermia, lethargy, respiratory distress,
jaundice, poor feeding, vomiting, diarrhea, seizures, restlessness, irritability, and/or bulging
fontanel [10,13,16].
Meningeal signs Although meningeal signs are present at the time of admission in the
majority of patients, they are not invariably present. In one review of 1064 cases of acute
bacterial meningitis in children older than one month, 16 (1.5 percent) had no meningeal
signs during their entire period of hospitalization [17]. Nuchal rigidity may not be elicited
in comatose patients or those with focal or diffuse neurologic deficits [14]. In addition,
nuchal rigidity may occur late in the course, particularly in young children.
Nuchal rigidity is manifest by the inability to place the chin on the chest, limitation of
passive neck flexion, and Kernig and Brudzinski signs.
Kernig sign Kernig sign is present if the patient, in the supine position with the hip and
knee flexed at 90, cannot extend the knee more than 135 and/or there is flexion of the
opposite knee (movie 1A).
Brudzinski sign Brudzinski sign is present if the patient, while in the supine position,
flexes the lower extremities during attempted passive flexion of the neck (movie 1B).
Signs of meningeal irritation are present in 60 to 80 percent of children with bacterial
meningitis at the time of presentation and in approximately 25 percent of children with
normal cerebrospinal fluid (CSF) findings [11,15,18]. Other causes of nuchal rigidity are
discussed below. (See 'Differential diagnosis' below.)
Neurologic findings
Altered consciousness In one review of 235 children with bacterial meningitis,
approximately 78 percent were irritable or lethargic, 7 percent were somnolent, and 15
percent semicomatose or comatose at the time of admission [14]. Among patients with
pneumococcal meningitis, 29 percent were semicomatose or comatose at the time of
admission.

The level of consciousness at the time of admission has prognostic significance [19];
patients who are obtunded, semicomatose, or comatose at the time of admission are
significantly more likely to have an adverse outcome than those who are lethargic or
somnolent [20]. (See "Bacterial meningitis in children older than one month: Treatment and
prognosis", section on 'Prognostic factors'.)
Increased ICP Increased intracranial pressure may be manifest by complaints of
headache in older children and bulging fontanel or diastasis of the cranial sutures in infants
[13,14]. Bulging fontanel is neither sensitive nor specific for bacterial meningitis. In one
review, bulging fontanel was present in 20 percent of infants with meningitis, but also in 13
percent of infants with normal CSF and viral infections other than meningitis [18]. (See
"Elevated intracranial pressure (ICP) in children".)

Other signs of increased intracranial pressure that may occur in bacterial meningitis include
palsies of the third, fourth, and sixth cranial nerves. (See "Third cranial nerve (oculomotor
nerve) palsy in children" and "Fourth cranial nerve (trochlear nerve) palsy in children" and
"Sixth cranial nerve (abducens nerve) palsy in children", section on 'Clinical
manifestations'.)

Papilledema, which takes several days to become apparent, is an uncommon finding in
acute bacterial meningitis. The finding of papilledema should prompt evaluation for venous
sinus occlusion, subdural empyema, or brain abscess [10]. (See 'Imaging' below.)
Seizures Seizures, typically generalized, occur before admission to the hospital or
within the first 48 hours of admission in 20 to 30 percent of patients with meningitis
[14,21]. Seizures later in the course are more often focal and may indicate cerebral injury
[10,21,22]. (See "Bacterial meningitis in children: Neurologic complications", section on
'Seizures'.)

A simple seizure is rarely the sole manifestation of bacterial meningitis [23]. In one series
of 410 consecutive cases of documented bacterial meningitis in children 2 months to 15
years of age, 27 percent had seizures at or before the time of presentation [23]. All of the
children with bacterial meningitis who presented with seizures had other signs or symptoms
of meningitis (altered consciousness, nuchal rigidity, petechial rash). Altered consciousness
and nuchal rigidity may be difficult to assess during the post-ictal period, particularly in
infants younger than one year.
Focal findings In one review of 235 children with bacterial meningitis, focal neurologic
findings (hemiparesis, quadriparesis, facial palsy, visual field defects) were present at the
time of admission in 16 percent of patients overall and in 34 percent of those with
pneumococcal meningitis [14]. The presence of focal neurologic signs at the time of
admission correlated with persistent abnormal neurologic examination one year after
discharge and with cognitive impairment.

Focal neurologic findings also may occur late in the course of meningitis [10]. (See
"Bacterial meningitis in children: Neurologic complications", section on 'Focal deficits'.)
Cutaneous findings Petechiae and purpura may occur with any of the bacterial
pathogens but are most commonly seen in N. meningitidis [10]. The lesions are usually
more pronounced on the extremities and can be preceded by an erythematous
maculopapular eruption. (See "Clinical manifestations of meningococcal infection", section
on 'Rash'.)
Complications Complications that may occur during therapy for bacterial meningitis
include seizures, increased ICP, cerebral edema, ischemia, infected subdural effusion, and
disseminated illness (septic arthritis, pericarditis, etc). Neurologic complications are
discussed separately. (See "Bacterial meningitis in children: Neurologic complications".)
Arthritis is most common with meningococcal disease but may occur with other infections
[14]. Early in the course of meningitis, arthritis may be related to direct invasion of the
joint, whereas arthritis that develops late in the course is considered an immune complex-
mediated event. (See "Clinical manifestations of meningococcal infection", section on
'Arthritis'.)
Pericardial effusions also may develop in patients with disseminated illness. They usually
resolve during the course of antibiotic therapy [14]. In some cases, pericardial effusions are
the cause of persistent fever, and pericardiocentesis or an open drainage procedure may be
required. (See "Clinical manifestations of meningococcal infection", section on 'Arthritis'
and "Clinical manifestations of meningococcal infection", section on 'Pericarditis'.)
EVALUATION
Overview Suspected bacterial meningitis is a medical emergency, and immediate
diagnostic steps must be taken to establish the specific cause (algorithm 1). Ideally, a
careful history, physical examination, blood tests, and lumbar puncture (LP) should be
performed before the initiation of therapy for meningitis.
However, in fulminant cases with hypotension and end-organ failure, rapid intervention is
particularly necessary; administration of antibiotics may precede complete history,
examination, and LP. In such cases, blood culture should be obtained before administration
of antibiotics, and LP performed as soon as is feasible. (See "Bacterial meningitis in
children older than one month: Treatment and prognosis", section on 'Immediate
management'.)
History Important aspects of the history in the child with suspected bacterial meningitis
include:
The course of illness. (See 'Course' above.)
The presence of symptoms consistent with meningeal inflammation. (See 'Meningeal
signs' above.)
The presence of seizures, an important prognostic finding. (See "Bacterial meningitis in
children older than one month: Treatment and prognosis", section on 'Prognosis'.)
The presence of predisposing factors In addition to predisposing conditions delineated
in the tables (table 1 and table 2), recent respiratory or ear infection, penetrating head
trauma or craniotomy, travel to an area with endemic meningococcal disease, exposure to
someone with bacterial meningitis, cochlear implantation device, or anatomic defects (eg,
dermal sinus or urinary tract anomaly). (See 'Predisposing factors' above.)
Immunization history (particularly the H. influenzae type b [Hib] conjugate vaccine,
pneumococcal conjugate or polysaccharide vaccine, and meningococcal conjugate or
polysaccharide vaccine); receipt of a full series of any of these vaccines does not alter the
need for cerebrospinal fluid (CSF) examination or initial empiric therapy, but depending
upon age, may affect the need for chemoprophylaxis or evaluation of the immune system.
(See "Prevention of Haemophilus influenzae infection", section on 'Antibiotic prophylaxis
of close contacts' and "Treatment and prevention of meningococcal infection" and "IgG
subclass deficiency".)
History of drug allergies, particularly anaphylactic reactions to antibiotics, which, if
present, may affect the choice of antimicrobial therapy. (See "Bacterial meningitis in
children older than one month: Treatment and prognosis", section on 'Chemoprophylaxis'.)
Recent use of antibiotics, which may affect the yield of blood and/or CSF culture. (See
'Interpretation of CSF in pretreated patients' below.)
Examination Important aspects of the examination of a child with suspected bacterial
meningitis include vital signs, general appearance, presence of meningeal signs, neurologic
examination, and cutaneous examination.
The vital signs provide clues to volume status, presence of shock, and the presence of
increased intracranial pressure. The constellation of systemic hypertension (calculator 1 and
calculator 2), bradycardia, and respiratory depression (Cushing triad) is a late sign of
increased intracranial pressure. (See "Elevated intracranial pressure (ICP) in children".)
Head circumference should be measured at the time of admission in children younger than
18 months of age [24]. (See "Bacterial meningitis in children older than one month:
Treatment and prognosis", section on 'Monitoring'.)
Elicitation of meningeal signs and important aspects of the neurologic and cutaneous
examinations are discussed above. (See 'Clinical features' above.)
Patients with acute bacterial meningitis may also have clinical manifestations of other
bacterial infections (eg, facial cellulitis, sinusitis, otitis media, arthritis, pneumonia).
LABORATORY EVALUATION
Blood tests Initial blood tests should include a complete blood count with differential
and platelet count and two aerobic blood cultures of appropriate volume. Serum electrolytes
and glucose, blood urea nitrogen, and creatinine concentrations are helpful in determining
the cerebrospinal fluid- (CSF) to-blood glucose ratio, and in planning fluid administration.
Evaluation of clotting function is especially indicated if petechiae or purpuric lesions are
noted. (See 'Glucose and protein' below and "Bacterial meningitis in children older than one
month: Treatment and prognosis", section on 'Pretreatment evaluation'.)
Blood cultures are positive in at least one-half of patients with bacterial meningitis [25]. In
one prospective study, blood was obtained for culture from every patient with bacterial
meningitis, 44 percent of whom had received antimicrobial therapy before evaluation [26].
Blood cultures were positive in 80 percent of children with H. influenzae type b (Hib)
meningitis, 52 percent of children with pneumococcal meningitis, and 33 percent of
children with meningococcal meningitis. Among children who were not pretreated with
antibiotics, blood cultures were positive in approximately 90 percent of children with Hib
and meningococcal meningitis and 80 percent of children with pneumococcal meningitis.
CSF examination Analysis of the CSF is critical to the diagnosis of meningitis and the
differentiation of bacterial from other etiologies (table 3). A lumbar puncture (LP) should
be performed on any child in whom, after careful history and physical examination, the
diagnosis of meningitis is suspected, unless specific contraindications to LP are present
[14]. The threshold for CSF examination should be lower in high-risk patients (table 2).
(See 'Predisposing factors' above.)
LP also should be performed in children with bacteremia and meningeal signs or persistent
fever (even if they have no meningeal signs), since bacteremia can progress to meningitis
within hours [12,27]. In addition, repeat LP may be warranted in a child whose initial CSF
culture was negative but in whom clinical signs of meningitis persist [10].
Contraindications to LP include cardiopulmonary compromise, signs of increased
intracranial pressure, papilledema, altered respiratory effort, focal neurologic signs, and
skin infection over the site for LP. (See "Lumbar puncture: Indications, contraindications,
technique, and complications in children", section on 'Contraindications' and 'Predisposing
factors' above.)
It is essential that antimicrobial therapy not be delayed if there is a contraindication to or
inability to perform an LP, or if the LP is delayed by the need for cranial imaging. In any of
these situations, blood cultures should be obtained and empiric antibiotics administered as
soon as is possible (before the imaging study in children who require imaging) (algorithm
1). (See 'Initiation of empiric therapy' below and 'Imaging' below.)
Examination of the CSF should include cell count and differential, glucose and protein
concentration, Gram stain, and culture. Cytocentrifugation of CSF enhances the likelihood
that laboratory personnel will detect bacteria on Gram-stained specimens. CSF cultures
should be performed in all cases of suspected bacterial meningitis, regardless of the cell
count. Early in the disease process, the CSF culture may be positive in the absence of
pleocytosis [12,28].
Interpretation of CSF Certain laboratory findings are characteristic of bacterial
meningitis and are present in most cases (table 3). These include CSF pleocytosis with a
predominance of neutrophils, elevated CSF protein, decreased CSF glucose, the presence of
an organism on CSF Gram stain, and isolation of a pathogenic organism from the CSF and
blood culture.
However, because CSF and blood cultures may be obtained at different points in time
during the evolution of the disease process, varying combinations of positive or negative
cultures of blood and CSF and the presence or absence of pleocytosis are possible [10].
Early in the course (after bacterial invasion but before the inflammatory response), the CSF
culture may be positive in the absence of pleocytosis [12,28]. In some cases, pleocytosis is
present and culture of the blood reveals a pathogen, but culture of the CSF does not. A
negative culture of the CSF does not preclude the development of meningitis hours or days
after LP; if clinical signs suggest meningitis, repeat LP may be warranted [10,12].
Cell count The CSF white blood cell (WBC) count in acute bacterial meningitis is
typically >1000 WBC/microL, with a predominance of neutrophils (table 3) [14]. However,
early in the course, few or no WBCs may be present. A CSF WBC count >6/microL is
considered abnormal in children older than three months of age [14], and >9 WBCs/microL
is considered abnormal for infants 29 to 90 days [29,30].
A traumatic LP can cause small amounts of bleeding into the CSF that can interfere with
interpretation of the CSF cell count. Certain formulas can be used to aid in the
interpretation of the cell count when the LP is traumatic. When the CSF is not grossly
bloody, we subtract 1 WBC for every 1000 RBCs/microL. However, none of the formulas
to "correct" the CSF WBC can be used with total confidence to exclude meningitis when
the LP is traumatic [31,32]. Children in whom the LP is traumatic should be treated
presumptively for meningitis pending results of CSF culture. (See "Bacterial meningitis in
children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)
The presence of a single neutrophil in the CSF is considered abnormal [10,12]. However,
this finding is not pathognomonic for bacterial meningitis; patients with aseptic meningitis
can have 30 to 90 percent neutrophils on their initial CSF examination [10]. (See "Viral
meningitis: Clinical features and diagnosis in children", section on 'CSF studies'.)
Similarly, neither the presence nor quantity of bands (immature neutrophils) in the CSF
helps to distinguish bacterial from viral meningitis [33].
Glucose and protein The CSF glucose in acute bacterial meningitis is <40 mg/dL in
more than one-half of cases (table 3) [14]. In addition, the ratio of the CSF to blood glucose
concentration is usually depressed (<0.6 ) [34].
The CSF protein in acute bacterial meningitis typically ranges from 100 to 500 mg/dL
(table 3) [14]. The CSF protein concentration may be increased in children with traumatic
LP because of the increased protein concentration in plasma and the release of proteins
from lysed red blood cells (RBC) [35]. In children with traumatic LP the CSF protein
concentration may be corrected by subtracting 1 mg/dL for every 1000 RBCs/microL
[10,35].
Gram stain The presence of an organism on CSF Gram stain can suggest the bacterial
etiology one day or more before culture results are available. The absence of organisms on
Gram stain does not exclude the diagnosis [36]. The probability of visualizing bacteria
depends upon the number of organisms present [37] and is increased by cytocentrifugation.
Broad-spectrum antimicrobial therapy should be continued until CSF culture results are
available, because Gram stain results are subject to observer misinterpretation [38]. (See
"Bacterial meningitis in children older than one month: Treatment and prognosis", section
on 'Empiric therapy'.)
An organism is visualized on CSF Gram stain in approximately 90 percent of children with
pneumococcal meningitis [21] and 80 percent of children with meningococcal meningitis
[39]. In contrast, the Gram stain is positive in only one-half of patients with gram-negative
bacillary meningitis and one-third of patients with listeria meningitis [40,41].
Characteristic morphologic features of the common pathogens for bacterial meningitis in
children are as follows:
Gram-positive diplococci suggest S. pneumoniae (picture 2)
Gram-negative diplococci suggest N. meningitidis (picture 3)
Small pleomorphic gram-negative coccobacilli suggest Hib (picture 4)
Gram-positive cocci or coccobacilli suggest group B streptococcus (picture 5)
Gram-positive rods and coccobacilli suggest L. monocytogenes (picture 6)
Culture Isolation of a bacterial pathogen from the CSF culture confirms the diagnosis of
bacterial meningitis. However, a negative culture of the CSF at a particular point in time
does not preclude the development of meningitis hours or days later [12,28].
In one review of 128 children with bacterial meningitis, CSF cultures were positive in 97
percent of patients who received neither oral nor parenteral antibiotics, 67 percent of
patients who received oral antibiotics, and 56 percent of patients who received parenteral
antibiotics before CSF cultures were obtained [42].
Rapid diagnostic tests Bacterial antigen tests should be reserved for cases in which the
initial CSF Gram stain is negative and CSF culture is negative at 48 hours of incubation
[43]. Polymerase chain reaction (PCR) of CSF and blood is most helpful for documenting
meningococcal disease in the patient with negative cultures [44].
Interpretation of CSF in pretreated patients Prior administration of antimicrobial agents,
particularly oral antibiotics, tends to have minimal effects on CSF cytology [25,45-48].
However, CSF chemistry results in pretreated patients must be interpreted with caution. In
a retrospective review of 231 children with bacterial meningitis in the post-Hib and
pneumococcal conjugate vaccine era, 85 children received antibiotics before LP [48].
Receipt of antibiotics for 12 hours before LP was associated with increased median CSF
glucose concentration (48 versus 29 mg/dL [2.66 versus 1.6 mmol/L]) and decreased
median CSF protein concentration (121 versus 178 mg/dL [1.21 versus 1.78 g/L]) [48].
Although the use of antimicrobial therapy before LP affects the CSF culture and perhaps
the Gram stain [25,42,47], conventional teaching has been that a pathogen still can be
identified in the CSF in the majority of patients up to several hours after the administration
of antibiotics [25]. However, a review of 128 children with bacterial meningitis specifically
addressed this question and found that the time interval between antibiotic administration
and negative CSF cultures may be shorter than appreciated for children who receive
parenteral antibiotics [42]:
Among children with meningococcal meningitis who were treated with a parenteral dose
of an extended-spectrum cephalosporin, three of nine LPs were sterile within one hour
(occurring as early as 15 minutes), and all were sterile by two hours.
Sterilization of the CSF was slower with pneumococcal meningitis. The first negative
culture was obtained four hours after administration of antibiotics, and five of seven were
negative by 10 hours.
Additional cultures Culture of other sites should be obtained as indicated [10].
Gram stain and culture of petechial or purpuric lesions may identify the causative agent
[10].
Urine cultures should be obtained in infants (<12 months of age) who present with fever
and nonspecific symptoms and signs of meningitis, since urinary tract infection may be the
primary source of the meningitis pathogen in such patients [10,49]. However, it is common
to note a CSF pleocytosis in infants with urinary tract infection and sterile CSF cultures
[49-53]. In such cases, the CSF pleocytosis may be related to a viral meningitis [54] or an
innate response to bacteria or bacterial products [55,56]. (See "Evaluation and management
of fever in the neonate and young infant (less than three months of age)" and "Fever
without a source in children 3 to 36 months of age".)

Urine cultures also should be obtained in children with anomalies of the urinary tract and in
immunocompromised patients. (See 'Predisposing factors' above.)

If possible, urine for culture should be obtained before antimicrobial therapy is
administered. However, therapy should not be withheld if an adequate specimen cannot be
promptly obtained [10].
In patients with concomitant otitis media, Gram-stained smear of middle ear fluid
(obtained by needle aspiration) may permit immediate identification of the likely pathogen
and may be helpful if the Gram-stained smear of the CSF is equivocal [10].
Cultures of the nose and throat are not helpful in identifying the etiology of bacterial
meningitis [10].
Other tests Other tests for the diagnosis of bacterial meningitis have limited availability
and/or undetermined utility for early diagnosis, as illustrated below.
Despite its increasingly broad use, serum C-reactive protein is not a reliable indicator of
severe infection [57].
In retrospective cohorts, elevated serum procalcitonin (>0.5 ng/mL) appears to be helpful
in distinguishing bacterial from viral meningitis, but additional data are necessary before
procalcitonin can be included in clinical decision rules [58].
The presence of tumor necrosis factor may distinguish bacterial from viral meningitis
[59], but this assay is not generally available.
The presence of IL-1 or IL-10 also may correlate with meningitis, but whether these
indicators are sensitive and specific enough to accelerate the diagnosis remains to be
determined [60].
The possibility of an immune deficiency should be considered in children who develop Hib
meningitis or pneumococcal meningitis with a serotype contained in the pneumococcal
vaccine despite having received at least three doses of the respective conjugate vaccines. In
such children, we suggest that quantitative immunoglobulins and complement activity be
obtained and that the peripheral blood smear be examined for Howell-Jolly bodies (picture
7). The presence of Howell-Jolly bodies most frequently indicates either absence of the
spleen (eg, surgical removal) or splenic hypofunction. If an unusual organism, such as S.
aureus or another organism that commonly colonizes the skin, is isolated, a direct
connection to the skin via a sinus tract should be sought [61]. An overview of primary
immunodeficiencies and an approach to the diagnosis of splenic dysfunction are found
elsewhere. (See "Primary humoral immune deficiencies: An overview" and "Approach to
the adult patient with splenomegaly and other splenic disorders", section on 'Hyposplenism
and asplenia'.)
IMAGING It is not uncommon for lumbar puncture (LP) to be delayed while a
computed tomographic (CT) scan is performed to exclude an intracranial process that
would contraindicate an LP. Although concerns exist about herniation following LP in
children, a review of the literature found that herniation was unlikely in children with
bacterial meningitis unless they had focal neurologic findings or coma; furthermore, a
normal CT does not absolutely exclude subsequent herniation [62,63].
Indications for imaging before LP in children with suspected bacterial meningitis include
(algorithm 1) [38]:
Coma
The presence of a cerebrospinal fluid (CSF) shunt
History of hydrocephalus
Recent history of CNS trauma or neurosurgery
Papilledema
Focal neurologic deficit (with the exception of palsy of cranial nerve VI [abducens nerve]
or VII [facial nerve])
In children who require neuroimaging before LP, blood cultures should be obtained and
empiric antibiotics administered before imaging (algorithm 1) [38]. LP should be
performed as soon as possible after neuroimaging provided that neuroimaging has not
revealed any contraindications.
DIAGNOSIS Acute bacterial meningitis should be suspected in children who present
with fever and signs of meningeal inflammation. In infants, the clinical manifestations may
include fever, hypothermia, lethargy, respiratory distress, jaundice, poor feeding, vomiting,
diarrhea, seizures, restlessness, irritability, and/or bulging fontanel [10,16]. In older
children, clinical manifestations may include fever, headache, photophobia, nausea,
vomiting, confusion, lethargy, and/or irritability [10,14]. Previous receipt of oral antibiotics
does not affect the clinical presentation of acute bacterial meningitis. (See 'Presentation'
above.)
Isolation of a bacterial pathogen from the cerebrospinal fluid (CSF) (by culture or other
diagnostic techniques) confirms the diagnosis of bacterial meningitis. Isolation of bacteria
from blood cultures in a patient with CSF pleocytosis also confirms the diagnosis, even if
the CSF culture remains negative.
Supportive findings include CSF pleocytosis with a predominance of neutrophils, decreased
CSF glucose concentration (or ratio of CSF to blood glucose), elevated CSF protein, and
isolation of the same pathogen from blood culture (table 3). However, because CSF and
blood cultures may be obtained at different points in time during the evolution of the
disease process, varying combinations of positive or negative cultures of blood and CSF
and the presence or absence of pleocytosis are possible [10,12]. (See 'Laboratory
evaluation' above.)
The CSF culture may be negative in children who received antibiotic therapy before CSF
examination. In such children, increased CSF cell count with a predominance of
neutrophils, elevated CSF protein concentration, and/or decreased CSF glucose
concentration usually are sufficient to establish the diagnosis of bacterial meningitis [25,45-
47]; blood cultures and/or rapid diagnostic tests may help to identify the pathogenic
organism. (See 'Interpretation of CSF in pretreated patients' above.)
DIFFERENTIAL DIAGNOSIS The clinical and laboratory findings of bacterial
meningitis overlap with those of meningitis caused by viruses, mycobacteria, fungi, or
protozoa (table 3). Other processes that can mimic bacterial meningitis include central
nervous system (CNS) abscess, bacterial endocarditis with embolism, subdural empyema,
and brain tumor [14,18]. Differentiation of these disorders from bacterial meningitis
requires careful examination of cerebrospinal fluid (CSF) and neuroimaging.
CSF pleocytosis The Bacterial Meningitis Score (BMS) is a clinical prediction rule for
children with CSF pleocytosis (CSF white blood cell [WBC] count 10 cells/microL) that
classifies children who have not been pretreated with antibiotics at very low risk of
bacterial meningitis if they lack all of the following [64]:
Positive CSF Gram stain
CSF absolute neutrophil count (ANC) 1000 cells/microL
CSF protein of 80 mg/dL
Peripheral blood ANC of 10,000 cells/microL
History of seizure before or at the time of presentation
In a meta-analysis of data from eight validation studies (one of which was prospective)
including 5312 patients, bacterial meningitis was diagnosed in 23 percent [65]. The BMS
missed nine patients with bacterial meningitis: three were younger than two months, three
had petechiae or purpura, and three were older than two months and did not have petechiae
or purpura; the six patients who were older than two months all had N. meningitidis. In
pooled analysis, the sensitivity and specificity of the BMS for bacterial meningitis were
99.3 percent (95% CI 98.7-99.7 percent) and 62.1 percent (60.5 to 63.7 percent),
respectively.
These findings suggest that the BMS may be used in conjunction with clinical judgment to
identify children with CSF pleocytosis who are at very low risk of bacterial meningitis and
to assist clinical decision making. To avoid misclassification, the BMS should not be used
in children who are younger than two months, immunocompromised, ill-appearing, have
been pretreated with antibiotics, have petechiae or purpura on examination, have a
ventriculoperitoneal shunt, or have recently had neurosurgery [64,65].
Normal CSF findings In a review of 650 children (0 to 12 years) who underwent lumbar
puncture (LP) for evaluation of possible meningitis, CSF findings were normal in 57
percent of patients [18]. Indications for LP included fever; headache; vomiting; nuchal
rigidity; first episode of convulsion with fever; and encephalopathic, toxic, or septic
appearance. The incidence of normal CSF varied according to age, occurring in 83 percent
of infants 0 to 8 weeks, 65 percent of children 8 weeks to 24 months, 53 percent of children
2 to 5 years, and 37 percent of children 5 to 12 years.
Common conditions among children with normal CSF findings included:
Right-sided pneumonia
Otitis media (most presented with fever and irritability)
Pharyngitis/tonsillitis
Upper respiratory infection with cervical adenopathy
Viral infection/ herpangina (predominantly in children <5 years)
Gastroenteritis
Additional causes of nuchal rigidity that should be considered in children evaluated for
meningitis who have normal CSF findings include retropharyngeal abscess, cervical spine
arthritis or osteomyelitis, spinal injury, and oculogyric crisis, esophageal foreign body,
idiosyncratic reaction to phenothiazine, and various toxins (tetanus, black widow spider
bites, scorpion stings) [66,67]. (See appropriate topic reviews).
Additional causes of CNS symptoms in infants include anaphylaxis, seizure, head trauma,
and stroke. (See appropriate topic reviews).
INITIATION OF EMPIRIC THERAPY Empiric therapy for bacterial meningitis should
be initiated immediately after the results of lumbar puncture (LP) are received or
immediately after the LP is performed.
It is essential that antimicrobial therapy not be delayed if there is a contraindication to or
inability to perform an LP. If LP is delayed by the need for cranial imaging, blood cultures
should be obtained and empiric antibiotic therapy administered before the imaging study
(algorithm 1). (See 'Imaging' above.)
Empiric treatment consists of bactericidal agent(s) that achieve significant levels in the
cerebrospinal fluid (CSF), usually a third-generation cephalosporin and vancomycin. More
specific treatment can be instituted when the etiologic agent is identified. (See "Bacterial
meningitis in children older than one month: Treatment and prognosis", section on 'Empiric
therapy'.)
Children in whom bacterial meningitis is suspected, or in whom bacterial meningitis cannot
be excluded, based upon initial CSF findings should be admitted to the hospital.
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, The Basics and Beyond the Basics. The Basics patient education pieces are
written in plain language, at the 5
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grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10
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in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)
Basics topics (see "Patient information: Meningitis in children (The Basics)" and "Patient
information: Bacterial meningitis (The Basics)")
Beyond the Basics topic (see "Patient information: Meningitis in children (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
Streptococcus pneumoniae and Neisseria meningitidis are the most common causes of
bacterial meningitis in infants and children older than one month of age. (See 'Causative
organisms' above.)
Certain host factors may predispose to bacterial meningitis with a particular organism
(table 2). Additional risk factors for bacterial meningitis include exposure to someone with
meningococcal or Haemophilus influenzae type b (Hib) meningitis, cochlear implantation
device, recent neurosurgical procedure, or anatomic defect (dermal sinus or urinary tract
anomaly). (See 'Predisposing factors' above.)
Most patients with bacterial meningitis present with fever and symptoms and signs of
meningeal inflammation (movie 1A-B). However, the clinical manifestations of bacterial
meningitis are variable and nonspecific; no single sign is pathognomonic. (See 'Clinical
features' above.)
Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps
must be taken to establish the specific cause (algorithm 1). (See 'Evaluation' above.)
The laboratory evaluation of children with suspected meningitis should include a
complete blood count with differential and platelet count, two aerobic blood cultures, and
serum electrolytes, glucose, blood urea nitrogen, and creatinine. Evaluation of clotting
function is especially indicated if petechiae or purpuric lesions are noted. (See 'Blood tests'
above.)
A lumbar puncture should be performed on any child in whom, after careful history and
physical examination, the diagnosis of meningitis is suspected unless specific
contraindications to lumbar puncture are present. Examination of the cerebrospinal fluid
(CSF) should include cell count and differential, glucose and protein concentration, Gram
stain, and culture. (See 'CSF examination' above.)
If there is a contraindication to or inability to perform a lumbar puncture or if the lumbar
puncture is delayed by the need for cranial imaging, blood cultures should be obtained and
empiric antibiotics administered as soon as possible. (See 'CSF examination' above.)
Laboratory findings characteristic of bacterial meningitis include CSF pleocytosis with a
predominance of neutrophils, elevated CSF protein, decreased CSF glucose, the presence of
an organism on CSF Gram stain, and isolation of a pathogenic organism from the CSF
and/or blood culture (table 3). (See 'Interpretation of CSF' above.)
Isolation of a bacterial pathogen from the CSF (by culture or other diagnostic techniques)
confirms the diagnosis of bacterial meningitis. (See 'Diagnosis' above.)
In children who were treated with antibiotics before CSF was obtained, increased CSF
cell count, elevated CSF protein concentration, and/or decreased CSF glucose concentration
usually are sufficient to establish the diagnosis of meningitis; blood cultures and/or rapid
diagnostic tests may help to identify the pathogenic organism. (See 'Interpretation of CSF
in pretreated patients' above.)
Empiric therapy for bacterial meningitis (a third-generation cephalosporin and
vancomycin) should be initiated immediately after the results of lumbar puncture are
received or immediately after the lumbar puncture is performed if the clinical suspicion for
bacterial meningitis is high. (See 'Initiation of empiric therapy' above and "Bacterial
meningitis in children older than one month: Treatment and prognosis", section on 'Empiric
therapy'.)
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