CONDITION • Updated 03 Nov 2023

Bacterial Meningitis in Children

Overview and Recommendations

Background

● Bacterial meningitis is a life-threatening medical, neurologic, and sometimes neurosurgical

emergency caused by a bacterial infection of the meninges leading to tissue inflammation.
● Risk factors for meningitis include exposure to pathogens, reduced host immunity, young age,
and implanted medical devices in the central nervous system.
● Infection occurs when bacteria breech the host's natural defenses and enter the central ner-
vous system by hematogenous spread or direct extension from a contiguous site.
● Age may determine which pathogens are most likely; the most common include Streptococcus
agalactiae (group B Streptococcus), Listeria monocytogenes, Streptococcus pneumoniae, Neisseria
meningitidis, Haemophilus influenzae type b and nontypeable H. influenzae, Escherichia coli, and
Klebsiella.
● Vaccination is the most effective means of meningitis prevention.

Evaluation

● Clinical presentation of meningitis in infants and children may include:

⚬ symptoms of fever, lethargy, poor feeding, irritability, vomiting, headache, confusion,
seizure, and neck stiffness
⚬ signs such as bulging fontanelle, petechial or purpuric rash (if meningococcemia present),
nuchal rigidity, Kernig and Brudzinski signs, and shock
● Initial testing for suspected meningitis
⚬ Draw blood for culture, complete blood count with differential, glucose, and C-reactive pro-
tein or procalcitonin level (if available).
⚬ Perform a lumbar puncture (LP) to diagnose meningitis unless it will delay antibiotic ther-
apy or is contraindicated due to increased intracranial pressure from an alternate cause.
– Check opening pressure and perform Gram stain, culture and sensitivities, cell count and
differential, protein, and glucose.
– Consider polymerase chain reaction (PCR) testing on cerebrospinal fluid (CSF).
– Consider herpes simplex virus (especially in neonates) and enteroviral PCR testing.
● Suspect meningitis in children with suspicious clinical presentation and abnormal CSF find-
ings, including:
⚬ positive Gram stain
⚬ elevated opening pressure based on age
⚬ elevated white blood cell count with neutrophil predominance (may vary from < 100
cells/mm3 to > 10,000 cells/mm3)
⚬ glucose < 40 mg/dL (0.56 mmol/L)
⚬ protein > 58 mg/dL (may not be accurate in neonates)
● Diagnosis is confirmed with positive CSF cultures or CSF polymerase chain reaction for specific
pathogen.

Management
● Start antimicrobial therapy once cerebrospinal fluid (CSF) analysis or the clinical presentation
(when lumbar puncture is delayed or contraindicated) suggests the diagnosis of bacterial
meningitis.
● Empiric antibiotic choice depends on the likely pathogens, which are based on age and Gram
stain results.
⚬ Dosing and interval will vary by age.
⚬ Adjust antibiotics based on culture and antimicrobial sensitivities of any isolated pathogen.
⚬ Duration of therapy varies by organism.
⚬ Consider using IV antibiotics for the entire duration of therapy.
● For suspected of confirmed Haemophilus influenza type B meningitis, give dexamethasone
0.15 mg/kg IV, if possible, 10-20 minutes before and no later than with the first antibiotic
dose; repeat every 6 hours for 2-4 days (Strong recommendation). It may not be recom-
mended for use in neonates (Weak recommendation). Use in pneumococcal meningitis is
controversial.
● Fluid and electrolyte management is determined by the clinical situation, as children are
prone to shock as well as dehydration, elevated intracranial pressure, and hyponatremia from
the syndrome of inappropriate antidiuretic hormone.
● Give rifampin 20 mg/kg (maximum 600 mg) orally once daily for 4 days prior to discharge for
children ≥ 1 month old with H. influenza type B meningitis that did not receive cefotaxime or
ceftriaxone during treatment (dose for infants < 1 month old is not established, but some ex-
perts recommend lowering the dose to 5 mg/kg every 12 hours).
● Follow-up of children with meningitis includes:
⚬ audiologic evaluation preferably prior to discharge then followed by regular hearing
evaluations
 ⚬ developmental, behavioral, and neurologic evaluations for the first year following infection
● Chemoprophylaxis for contacts of children with H. influenza and meningococcal meningitis
should be done in conjunction with the local health department, ideally within 24 hours, but
no later than 14 days after diagnosis of index patient.

Algorithms

Related Topics
● Sepsis in Children
● Sepsis Treatment in Children
● Late-onset Neonatal Sepsis
● Bacterial Meningitis in Adults
● Meningococcal Disease

General Information

Description
● potentially life-threatening bacterial infection of the meninges that can result in serious neu-
rologic sequelae; considered a medical emergency 2 ,4

Epidemiology

Incidence/Prevalence

● annual incidence is highest in neonates at reported 40 per 100,000 5

● incidence decreasing among children living in areas with widespread use of Haemophilus b
conjugate vaccine, pneumococcal vaccine, and meningococcal vaccine 2 ,3 ,4

STUDY
⚬ SUMMARY
decreased incidence of bacterial meningitis in regions with vaccination programs
against Streptococcus pneumoniae and Haemophilus influenzae
 POPULATION-BASED SURVEILLANCE: N Engl J Med 2011 May 26;364(21):2016
Details
– based on population-based study of 17.4 million persons from the Emerging Infections
Programs Network from 1998 to 2007
– 3,188 patients had bacterial meningitis
– overall incidence of meningitis decreased from 2 per 100,000 persons from 1998 to 1999
to 1.38 per 100,000 persons from 2006 to 2007
– annual incidence of bacterial meningitis in United States in 2006-2007
● at age < 2 months - 80.7 per 100,000 persons
● at age 2-23 months - 6.9 per 100,000 persons
● at age 2-10 years - 0.56 per 100,000 persons
● at age 11-17 years - 0.43 per 100,000 persons
– Reference - N Engl J Med 2011 May 26;364(21):2016

STUDY
● SUMMARY
incidence of pneumococcal meningitis in children in Utah, United States from 2001 to 2010
COHORT STUDY: Pediatrics 2013 Sep;132(3):421
Details
⚬ based on retrospective cohort study of children < 18 years old presenting to major pedi-
atric hospital in Utah, United States from 1997 to 2010
⚬ 68 patients had culture-confirmed pneumococcal meningitis, including 22 before licensure
of PCV7 vaccine in 2000, and 46 after
⚬ incidence of pneumococcal meningitis before PCV7 was 0.78 per 100,000 patients
⚬ incidence of pneumococcal meningitis from 2001 to 2010 (after PCV7 vaccine licensure)
– 0.57 per 100,000 patients overall
– 4.47 per 100,000 children aged 0-23 months
– 0.14 per 100,000 patients due to PCV7 serotypes
⚬ despite significant postlicensure decrease in meningitis due to PCV7 serotypes, overall inci-
dence of pneumococcal meningitis did not decrease significantly because of 46% increase
in incidence of meningitis due to non-PCV7 serotypes
⚬ Reference - Pediatrics 2013 Sep;132(3):421

STUDY
● SUMMARY
annual incidence of bacterial meningitis 0.38 per 1,000 live births in infants < 90 days old
in United Kingdom and Ireland from 2010 to 2011
POPULATION-BASED SURVEILLANCE: Clin Infect Dis 2014 Nov 15;59(10):e150
Details
 ⚬ based on population-based surveillance of bacterial meningitis in infants < 90 days old in
United Kingdom and Ireland from July 2010 to July 2011
⚬ annual incidence of bacterial meningitis per 1,000 live births
– 0.38 overall (364 cases)
– 0.16 due to group B Streptococcus (150 cases)
– 0.04 due to Escherichia coli (41 cases)
⚬ other causative pathogens included S. pneumoniae in 28 cases, Neisseria meningitidis in 23
cases, Listeria monocytogenes in 11 cases, other gram-positive bacteria in 24 cases, and
other gram-negative bacteria in 24 cases
⚬ Reference - Clin Infect Dis 2014 Nov 15;59(10):e150

STUDY
● SUMMARY
prevalence of meningococcal carriage peaks around age 19 years
SYSTEMATIC REVIEW: Lancet Infect Dis 2010 Dec;10(12):853
Details
⚬ based on systematic review of observational studies
⚬ systematic review of 110 studies reporting pharyngeal carriage of all meningococcal
serogroups in defined age groups
⚬ 82 studies with 143,114 persons were included in meta-analysis
⚬ prevalence of asymptomatic Neisseria meningitidis carriers
– 4.5% in infants
– 7.7% in children aged 10 years
– 23.7% in persons aged 19 years
– 13.1% in persons aged 30 years
– 7.8% in persons aged 50 years
⚬ Reference - Lancet Infect Dis 2010 Dec;10(12):853

Risk Factors

● medical-related risk factors

⚬ infants, especially those born to group B strep-positive mother (see Group B streptococcal
infection in infants less than 3 months old)
⚬ immunodeficiency or immunosuppression due to various causes such as immunoglobulin
deficiencies, terminal complement deficiencies, HIV infection, asplenia 2 ,3 ,4 ,5
⚬ absence of opsonic or bactericidal antibody is a major risk factor in most cases of meningi-
tis due to group B streptococci, Escherichia coli, Haemophilus influenzae type b, Streptococcus
pneumoniae, and Neisseria meningitidis 2
⚬ basilar skull fracture or penetrating trauma 1
● prematurity, low birth weight, and younger age

STUDY
⚬ SUMMARY
among neonates and infants aged < 90 days presenting with fever without apparent
source, age ≤ 21 days associated with increased risk of bacterial meningitis
COHORT STUDY: Pediatr Infect Dis J 2015 May;34(5):494
Details
– based on prospective cohort study
– 2,362 infants < 90 days old with fever without apparent source were evaluated
– indications for lumbar puncture (LP) included ≥ 1 of the following
● unwell clinical appearance or clinical findings suggestive of bacterial meningitis
● age < 21 days
● abnormal blood test results including leukocytes < 5,000/mcL or > 15,000/mcL, neu-
trophils > 10,000/mcL, C-reactive protein > 20 mg/L, or procalcitonin ≥ 0.5 ng/mL
– 639 had LP and cerebrospinal fluid (CSF) analysis, including 70.1% ≤ 21 days old
– diagnosis of bacterial meningitis defined as detection of a bacterial pathogen in CSF
(with or without associated pleocytosis) or in blood culture accompanied by pleocytosis
– 11 infants diagnosed with bacterial meningitis
– prevalence of bacterial meningitis higher with age ≤ 21 days compared to age > 21 days,
2.8% vs. 0.1% (odds ratio 9.14 [95% CI 6.95-12.02)
– of 378 well-appearing infants who were > 21 days old and had LP for CSF analysis, none
were diagnosed with bacterial meningitis, regardless of whether they had abnormal
blood tests
– Reference - Pediatr Infect Dis J 2015 May;34(5):494

STUDY
⚬ SUMMARY
gestational age < 37 weeks and birth weight < 2,500 g may each be associated with in-
creased risk of bacterial meningitis in infants < 90 days old
COHORT STUDY: Clin Infect Dis 2014 Nov 15;59(10):e150
Details
– based on population-based cohort study in United Kingdom and Ireland
– 364 infants < 90 days old with bacterial meningitis were analyzed
– 25 infants died of meningitis
– increased risk of bacterial meningitis associated with
● gestational age < 37 weeks (p < 0.001) (incidence rate ratio [RR] 4.62, 95% CI 3.6-6
compared to ≥ 37 weeks)
● birth weight < 2,500 g (p < 0.001)
⚬ incidence RR 3.1 (95% CI 2.2-4.3) for 1,500-2,499 g compared to ≥ 2,500 g
 ⚬ incidence RR 16 (95% CI 12-22) for < 1,500 g compared to ≥ 2,500 g
– Reference - Clin Infect Dis 2014 Nov 15;59(10):e150
● environmental risk factors
⚬ living in dormitory setting 2
⚬ travel, especially to sub-Saharan Africa (Centers for Disease Control and Prevention -
Bacterial Meningitis 2015 Dec 17 )
⚬ lack of immunization 5
⚬ ear, nose, or throat infections, including 2
– otitis media
– sinusitis
– acute mastoiditis
– pansinusitis
● pansinusitis with extension causing meningitis and epidural abscess in 11-year-old girl
in case report (Pediatr Emerg Care 2009 Apr;25(4):267)
● nosocomial risk factors
⚬ presence of ventriculoperitoneal shunt 1
⚬ cochlear implants 2 ,5
– patients with cochlear implants are at an increased risk of bacterial meningitis due to
several factors including
● cochleovestibular malformations (especially inner ear anomalies such as common
cavity, enlarged vestibular aqueduct, and incomplete partition types I-III) which may
lead to cerebrospinal fluid (CSF) leakage with or without surgery
● age - more common in infants and children, especially if history of acute otitis media
● clinical factors such as immunocompromised, history of head trauma, or otic capsule
fracture
● surgical factors such as
⚬ size and location of cochleostomy and whether cochleostomy is adequately cov-
ered following insertion procedure
⚬ accidental trauma from electrode placement that may result in microfracturing of
modiolus and spiral lamina, and consequent mixing of perilymph and CSF
⚬ dislodgement and activation of latent bacterial colonies due to instrumentation of
middle ear
⚬ direct central nervous system inoculation through dura exposure when performing
a mastoidectomy or when drilling a well for receiver-stimulator
● hematogenous seeding of cochlear implant
– Reference - Curr Opin Otolaryngol Head Neck Surg 2014 Oct;22(5):359
 – 283 cases of meningitis after cochlear implantation reported to Centers for Disease
Control and Prevention (CDC) since 2002 (Otol Neurotol 2012 Jan;33(1):93)
⚬ postneurosurgery 1
●

Table 1: Predisposing Risk Factors by Common Bacterial Pathogens

Common Bacterial Predisposing Risk Factors

Pathogen

Streptococcus Lack of immunization, cerebrospinal fluid leak, cochlear im-

pneumoniae plant, nephrotic syndrome, asplenia, sickle-cell disease, HIV
infection, otitis, sinusitis, immunodeficiency, diabetes
mellitus

Neisseria meningitidis Terminal complement deficiency, freshman living in dormi-

tory, outbreaks, travel to "meningitis belt"

Haemophilus influenzae Lack of immunization, asplenia, sickle-cell disease, HIV infec-

type b tion, otitis, sinusitis

Listeria monocytogenes Immunodeficiency, diabetes mellitus

Reference - 2 .

Etiology and Pathogenesis

Causes

Table 2: Common Bacterial Pathogens by Age

Age Common Bacterial Pathogens

< 1 month ● Streptococcus agalactiae (group B Streptococcus) 1 ,2 ,3 ,4

● Escherichia coli 1 ,2 ,3 ,4
● Listeria monocytogenes 1 ,2 ,4
 Age Common Bacterial Pathogens

● Klebsiella species 1
● Streptococcus pneumoniae 4

1-3 months ● S. pneumoniae 1 ,2 ,3

● Neisseria meningitidis 1 ,2 ,3
● Group B streptococci 1 ,2
● E. coli 1 ,2
● L. monocytogenes 2
● Haemophilus influenzae type b 1 ,2 and nontypeable H.
influenzae*

3-23 months ● S. pneumoniae 1 ,2 ,4

● N. meningitidis 1 ,2 ,4
● H. influenzae type b 1 ,2 ,4 and nontypeable H.
influenzae*
● Group B streptococci*

2-5 years ● S. pneumoniae 1 ,2 ,4

● N. meningitidis 1 ,2 ,4
● H. influenzae type b 2 ,4 and nontypeable H. influenzae*

6-21 years ● S. pneumoniae 1 ,2

● N. meningitidis 1 ,2

* Based on 3,155 patients with bacterial meningitis in United States 1998-2007 (N Engl J Med 2011 May
26;364(21):2016), but notation of group B streptococci may be related to use of age range 2-23 months in
this study.
Table 3: Common Bacterial Pathogens in Children with Cerebrospinal Fluid Shunts

Shunt Infection Common Bacterial Pathogens

First infection ● Coagulase-negative Staphylococcus

● Methicillin-sensitive Staphylococcus aureus
● Methicillin-resistant S. aureus
● Haemophilus influenzae nontypeable
● H. influenzae type b
● Enterobacter or other gram-negative bacteria
● Streptococcus including Enterococcus
● Propionibacterium acnes

Repeat infection ● Coagulase-negative Staphylococcus species

● S. aureus
● Streptococcus viridans
● Gram-negative bacteria

Reference - Clin Infect Dis 2017 Feb 14 early online, Pediatr Infect Dis J 2011 Sep;30(9):731.

STUDY
● SUMMARY
> 90% of repeat shunt infections are gram-positive organisms, often with similar organ-
isms to previous infection
CASE SERIES: Pediatr Infect Dis J 2011 Sep;30(9):731
Details
⚬ based on case series
⚬ 31 children (80% were < 6 months old at initial shunt placement) with ≥ 2 cerebrospinal
fluid shunt infections were assessed
⚬ gram-positive organisms were present in 93% of second and 94% of third shunt infections
– 58% of second shunt infections were Gram-stain concordant with initial infection
– 78% of third shunt infections were Gram-stain concordant with second infection
 ⚬ Reference - Pediatr Infect Dis J 2011 Sep;30(9):731

Pathogenesis

● although much of the pathogenesis of community-acquired bacterial meningitis is not well

understood, four main steps have been described
⚬ colonization - bacteria that cause meningitis often first colonize respiratory tract mucous
membranes
⚬ invasion into blood stream - pathogens may enter the bloodstream by traversing through
cells (transcellularly) or between cells (pericellularly)
⚬ survival in bloodstream - immune evasion is required for bloodstream survival
⚬ entry into subarachnoid space - most commonly occurs following bacteremia, but direct
entry into central nervous system is possible
⚬ Reference - Handb Clin Neurol 2014;121:1361
● mechanisms of central nervous system entry
⚬ bacteria enter central nervous system by hematogenous spread or direct extension from
contiguous site, including
– in neonate - pathogens from maternal genital secretions
– in infants and children - often due to organisms colonizing upper respiratory tract
– other routes of infection include
● direct communication with cerebrospinal fluid (CSF), such as with
⚬ trauma
⚬ CSF leaks
⚬ cochlear implants
⚬ ventriculoperitoneal (VP) shunt
⚬ congenital dura defects such as dermal sinus or meningomyelocele
● extension from suppurative parameningeal focus
– Reference - Pediatr Clin North Am 2005 Jun;52(3):795
⚬ meningitis-causing pathogens cross blood-brain barrier transcellularly, pericellularly, or by
means of infected phagocytes 2
● bacterial multiplication in subarachnoid space ultimately causes release of proinflammatory
mediators, breakdown of blood-brain barrier, and recruitment of leukocytes to subarachnoid
space (Lancet 2016 Dec 17;388(10063):3036)
● pathogenic processes and associated clinical findings
⚬ phase 1 - bacterial invasion results in release of pro-inflammatory cytokines and conse-
quent inflammation of subarachnoid space causing fever and headache
 ⚬ phase 2 - cytokines and other chemical mediators induce subpial encephalopathy causing
meningismus and confusion; reduced CSF glucose may develop
⚬ phase 3 - breakdown in blood-brain barrier and transendothelial migration of leukocytes
occur; cerebral edema develops causing impaired consciousness, elevated CSF pressure,
increased CSF protein, and focal symptoms
⚬ intermediate events - impaired cerebral blood flow, rising intracranial pressure, and vas-
culitis causing obtundation, seizures, focal neurologic symptoms and signs (such as cranial
nerve palsies)
⚬ late events - focal neuronal injury causing paralysis, cognitive impairment, coma, and possi-
bly death in untreated cases
⚬ Reference - Eur J Neurol 2008 Jul;15(7):649, correction can be found in Eur J Neurol 2008
Aug;15(8):880

History and Physical

Clinical Presentation

● clinical features are variable, nonspecific, depend on age, duration of illness, and host re-
sponse to infection; in some cases, may be absent 2 ,4
⚬ common non-specific symptoms and signs
– fever
– nausea or vomiting
– unwell appearance
– lethargy
– irritability
– signs or breathing difficulty
– refusing food and drink
– headache
– muscle and joint pain
⚬ less common, non-specific symptoms and signs
– chills
– abdominal pain
– vomiting
– sore throat
⚬ more specific signs and symptoms
– non-blanching rash
– stiff neck
– back rigidity
 – bulging fontanelle
– photophobia
– Kernig's sign
– Brudzinski's sign
– unconsciousness
– paresis
– focal neurological deficit including cranial nerve involvement and abnormal pupils
– altered mental state
– seizures
● infants on numerous occasions may not have classic signs of meningitis which include 4
⚬ neck stiffness
⚬ bulging fontanelle or
⚬ high-pitched cry)
● recognize signs of shock and manage urgently 4
⚬ capillary refill time more than 2 seconds
⚬ unusual skin color
⚬ toxic state
⚬ altered mental state/decreased level of consciousness
⚬ tachycardia and/or hypotension
⚬ leg pain
⚬ poor urine output
⚬ respiratory symptoms or breathing difficulty
⚬ cold hands/feet
● recognize signs suggesting increased intracranial pressure (lumbar puncture contraindicated)
4

⚬ reduced or fluctuating level of consciousness (Glasgow Coma Scale score < 9 or a drop of 3
or more)
⚬ relative bradycardia and hypertension
⚬ focal neurological signs
⚬ abnormal posture or posturing
⚬ papilledema
⚬ poorly responsive, dilated, or unequal pupils
⚬ abnormal 'doll's eye' movements

STUDY
● SUMMARY
common signs and symptoms alone have limited utility in diagnosing bacterial meningitis
in children
 SYSTEMATIC REVIEW: Pediatrics 2010 Nov;126(5):952
Details
⚬ based on systematic review
⚬ systematic review of 10 cohort studies evaluating accuracy of clinical features to predict
bacterial meningitis in 5,006 children
⚬ performance analyses of each clinical feature included 1-5 studies depending on the clinical
feature
⚬ following clinical features had high specificity for bacterial meningitis in children (ranged
from 90%-100%), but sensitivity too low to rule out bacterial meningitis in children without
clinical feature
– neck stiffness or bulging fontanelle
– history of seizure in child outside of febrile convulsions age range
– petechiae
– jaundice
– toxic or moribund appearance
– Kernig sign
⚬ Reference - Pediatrics 2010 Nov;126(5):952, commentary can be found in Evid Based Med
2011 Jun;16(3):89

History

Medication History

● ask about recent or current antibiotic treatment 1 ,2

● ask about immunization status 2

Past Medical History (PMH)

● ask about history of 2 ,5

⚬ recent infections (such as otitis, sinusitis)
⚬ skull or meningeal defects (Pediatr Clin North Am 2005 Jun;52(3):795)
⚬ immunosuppression
⚬ splenectomy or functional asplenia such as sickle cell disease
⚬ terminal complement deficiency
⚬ penetrating trauma
⚬ cochlear implants
⚬ epidural abscess (Eur J Neurol 2008 Jul;15(7):649)
⚬ cerebrospinal fluid shunt or any other recent neurosurgical procedures
⚬ previous meningitis infection
● in neonates and young infants, ask about birth history including
⚬ prematurity
⚬ low birth weight
⚬ maternal group B Streptococcus status in neonates, whether it was treated with antibiotics,
and timing of antibiotics prior to delivery
⚬ maternal herpes simplex virus infection in infants < 2 months old (Pediatr Rev 2008
Dec;29(12):417)
⚬ Reference - Clin Microbiol Infect 2015 Oct;21(10):910
Family History (FH)

● ask about family history of 4 ,5

⚬ complement deficiency
⚬ meningococcal disease
⚬ recurrent or serious bacterial infections

Social History (SH)

● ask about
⚬ ill contacts in daycare setting, at school, or among friends or family 2
⚬ communal living situation such as dormitory 2
⚬ travel history (Eur J Neurol 2008 Jul;15(7):649)
⚬ secondhand smoke exposure (BMC Public Health 2012 Dec 10;12:1062)
● in endemic regions, assess for tick exposure for Lyme disease (Pediatrics 2006 Jan;117(1):e1)
● in adolescents, ask if they are sexually active for risk of HIV infection 1

Physical

General Physical

● general physical should include hourly (or in cases of shock, continuous) assessments of heart
rate, respiratory rate, oxygen saturations, blood pressure, temperature, perfusion (capillary
refill), and neurological functioning 3 ,4
● signs may include 2 ,4
⚬ signs of increased intracranial pressure such as
– bulging fontanelle in infants
– Cushing triad - late and ominous sign
● some references describe Cushing triad as hypertension, bradycardia, and irregular
respirations (Cheyne-Stokes breathing)
 ● some references describe Cushing triad as hypertension, bradycardia, and widened
pulse pressure (difference between systolic and diastolic blood pressure)
⚬ fever
⚬ lethargy
⚬ irritability
● if ventriculoperitoneal shunt present, examine proximal port or reservoir and shunt tract
looking for redness or swelling (Clin Infect Dis 2017 Feb 14 early online)
Skin

● petechial or purpuric rash 4

⚬ more common with concomitant meningococcemia (usually involves trunk or extremities)
⚬ can occur with other bacterial and nonbacterial causes including
– other bacterial meningitis
– bacterial endocarditis
– bacteremia
– systemic viral infection

● jaundice may be seen in infants (Handb Clin Neurol 2014;121:1361)

HEENT

● assess for
⚬ bulging fontanelle in infants 2
⚬ papilledema 3 ,4
⚬ cranial nerve palsy 1

Neck

● nuchal rigidity may be present, more common in older children 2 ,4

Abdomen

● possible omphalitis in infant (Acta Paediatr 2006 May;95(5):519)

Back

● sacral dimple or other defect may suggest dermal sinus tract (Neurosurg Clin N Am 1995
Apr;6(2):359)

Neuro

● assess for focal neurologic findings or asymmetry in neurological exam 2

● signs of meningeal irritation 2
⚬ unreliable for diagnosing or ruling out meningitis
⚬ less common in children < 12 months old
⚬ Kernig sign (flexing hip and extending knee to elicit pain in back and legs)
⚬ Brudzinski sign (passive flexion of neck elicits flexion of hips)

● measure head circumference in children with open fontanelles (Pediatr Rev 2008
Dec;29(12):417)

Diagnosis

Making the Diagnosis

● diagnosis of bacterial meningitis may be difficult as clinical features in infants and children are
2
varied, non-specific, and can be subtle or even absent
● definitive diagnosis based on clinical suspicion and identification of bacteria likely to cause
meningitis by either 1
⚬ cerebrospinal fluid (CSF) cultures (positive in 70%-85% of patients not pretreated with
antibiotics)
⚬ CSF polymerase chain reaction (PCR) for specific pathogens
● presumptive diagnosis based on clinical suspicion with
⚬ positive CSF Gram stain
 ⚬ abnormal CSF findings if no specific organism identified - findings may include 1
– elevated opening pressure
– cloudy appearance
– elevated white blood cell (WBC) count
● typically 1,000-5,000 cells/mm3
● may vary from < 100 cells/mm3 to > 10,000 cells/mm3
– neutrophil predominance, typically 80%-95% (about 10% of patients may have lympho-
cyte predominance of > 50% lymphocytes or monocytes)
– glucose < 40 mg/dL (2.22 mmol/L) (but not accurate in neonates)
– elevated protein (nearly 100% of patients, but not accurate in neonates)
– pretreatment blood culture positive for organism consistent with meningitis
⚬ CSF findings may not be reliable in children with CSF shunts and drains
● in children for whom antibiotics were started before establishing diagnosis, increased WBC
count and protein in CSF may be sufficient for diagnosis 2

Differential Diagnosis

● aseptic meningitis 2
⚬ viral meningitis
– enterovirus
● coxsackievirus
● echovirus
– measles, mumps
– varicella
– West Nile virus infection and other arbovirus infections
– cytomegalovirus (CMV)
– Epstein-Barr virus (EBV)
– congenital parvovirus B19 infection
⚬ fungal meningitis
– cryptococcal meningitis
– invasive candidiasis
⚬ spirochetal
– neurosyphilis 5
– Lyme disease (neuroborreliosis) due to infection by Borrelia burgdorferi
⚬ mycobacterial
– tuberculosis in children (see also tuberculous meningitis
 – atypical mycobacteria
● inflammatory (noninfectious) conditions
⚬ sarcoidosis
⚬ systemic lupus erythematosus (SLE)
⚬ Behcet disease
● acute sinusitis
● encephalitis
● hemorrhagic meningeal irritation
⚬ subarachnoid hemorrhage
⚬ subdural hematoma
● other less common etiologies to consider include
⚬ drugs including nonsteroidal anti-inflammatory drugs, IV immunoglobulin, and
trimethoprim/sulfamethoxazole 5
⚬ lymphocytic choriomeningitis virus (LCMV), human herpes virus 6 (HHV6), and HIV
⚬ Mollaret syndrome (benign recurrent lymphocytic meningitis; see also Herpes simplex en-
cephalitis) 5
⚬ brucellosis
⚬ ehrlichiosis
⚬ autoimmune disease (such as lupus and Sjogren syndrome)
⚬ vasculitis (Kawasaki disease)
5
⚬ central nervous system abscess
⚬ neoplastic meningitis 5
5
⚬ leptomeningeal carcinomatosis
⚬ parasitic meningitis 5
⚬ primary amebic meningoencephalitis (rare disease caused by Naegleria fowleri)
– 24 fatal cases (between 1989 and 2000) reported in United States related to children
swimming in natural waters in areas with higher temperatures, only 3 survivors docu-
mented (MMWR Morb Mortal Wkly Rep 2003 Oct 10;52(40):962)
– 6 fatal cases in Arizona, Florida, and Texas, United States in 2007, including 5 boys aged
10-14 years (MMWR Morb Mortal Wkly Rep 2008 May 30;57(21):573)

Testing Overview
1, 4
● if bacterial meningitis suspected
⚬ collect blood samples for
– blood cultures
 – complete blood count
– serum glucose
– C-reactive protein or procalcitonin
⚬ perform lumbar puncture (LP) unless contraindicated
– do not delay treatment if there will be a delay in LP
– if clinical presentation is consistent with CNS mass lesion or other cause of increased in-
tracranial pressure, head computed tomography (CT) scan may be indicated prior to LP
to rule space-occupying lesion
⚬ testing of CSF sample includes
– Gram stain (IDSA Grade A-III)
– culture
– white blood cell count and differential
– glucose and protein
– polymerase chain reaction (PCR) may help identify underlying pathogen especially in
cases with negative Gram stain, negative culture, or early treatment with antibiotics have
been given
1, 4
⚬ obtain specimens for cultures before starting antibiotics if possible
⚬ in child with unexplained petechial rash and fever or history of fever, also obtain blood gas
and coagulation screen 4

Clinical Prediction Rules

● no clinical prediction rule has been established as standard of care across practice guidelines
● for other related prediction rules in neonates and infants, see Fever Without Apparent Source
in Infants and Young Children
● bacterial meningitis score (BMS)
⚬ BMS reported to be most specific tool for differentiating aseptic and bacterial meningitis,
but not widely used 2 ,5
⚬ BMS (also called Nigrovic rule) ranges from 0 to 6 based on
– 2 points if Gram stain of cerebrospinal fluid (CSF) shows bacteria
– 1 point if CSF protein > 80 mg/dL (0.8 g/L)
– 1 point if peripheral absolute neutrophil count > 10,000 cells/mm3
– 1 point if CSF absolute neutrophil count > 1,000 cells/mm3
– 1 point if seizure before or at time of presentation
– Reference - Pediatrics 2002 Oct;110(4):712

STUDY
⚬ SUMMARY
 BMS score of zero (none of 5 predictors) may have 99.7% negative predictive value to
rule out bacterial causes of meningitis in children DynaMed Level 2
SYSTEMATIC REVIEW: Arch Dis Child 2012 Sep;97(9):799
Details
– based on systematic review limited by clinical heterogeneity
– systematic review of 8 validation studies assessing efficacy of BMS to identify bacterial
etiologies in 4,896 children with meningitis
– studies differed in inclusion criteria, exclusion criteria, and definition of meningitis
– exclusion criteria varied by study and included
● traumatic lumbar puncture
● antibiotics within 72 hours prior to lumbar puncture
● purpura
● critical illness
● other bacterial infections necessitating inpatient antibiotic therapy
● presence of ventricular shunt device or previous neurosurgery
● immunosuppression
● active tuberculosis or Lyme disease
– 1,242 children (23%) had bacterial meningitis
– overall BMS rating comparing very low risk (score of 0) vs. not very low risk (≥ 1) had
● sensitivity of 99.3% (95% CI 98.7-99.7%) in all studies
● specificity of 62.1% (95% CI 60.5%-63.7%) in all studies
● to rule out bacterial meningitis BMS score of zero had
⚬ negative predictive value 99.6% (95% CI 99.3%-99.9%)
⚬ negative likelihood ratio 0.01 (95% CI 0.01-0.02)
● to predict bacterial meningitis BMS score of ≥ 1 had
⚬ positive predictive value 28.1% (95% CI 22.6%-33.9%)
⚬ positive likelihood ratio 2.6 (95% CI 2.5-2.7)
– of 9 children with bacterial meningitis and BMS of zero
● 3 were < 2 months old
● 3 (all ≥ 8 months old) had petechial or purpuric rash at presentation
● remaining 3 had Neisseria meningitidis meningitis
– Reference - Arch Dis Child 2012 Sep;97(9):799

Blood Tests
● if bacterial meningitis is suspected 1 ,4
⚬ before starting antimicrobial treatment obtain blood sample for culture emergently
 ⚬ perform
– C-reactive protein measurement
– white blood cell count with differential
– blood glucose measurement
● blood testing findings 1 ,4
⚬ white blood cell (WBC) count is often increased with left shift
⚬ inflammatory markers
– C-reactive protein (CRP) concentration is not diagnostic and should not be used alone to
determine need for antibiotics
● elevated CRP and WBC count plus nonspecifically abnormal CSF suggests bacterial
meningitis
● normal CRP has high negative predictive value for bacterial meningitis (IDSA Grade B-
II), but normal CRP and white blood cell count does not rule out bacterial meningitis
– procalcitonin (PCT)
● elevated levels associated with severe bacterial infections
● unable to make recommendation for use due to lack of test availability (IDSA Grade C-
II)

STUDY
● SUMMARY
blood procalcitonin ≥ 0.5 ng/mL might distinguish bacterial from viral causes in
children with meningitis DynaMed Level 2

SYSTEMATIC REVIEW: Clin Pediatr (Phila) 2016 Jul;55(8):749

Details
⚬ based on systematic review limited by heterogeneity
⚬ systematic review of 8 studies assessing efficacy of procalcitonin to differentiate
between bacterial and viral meningitis with 616 children aged 0-14 years
– CRP also assessed in 6 of these studies with 542 children aged 0-14 years
– all studies used LUMItest procalcitonin chemiluminescence assay
– reference standards for diagnosis of bacterial meningitis included positive find-
ings on at least 1 of
– direct cerebrospinal fluid examination
– Gram stain
– bacterial culture
– latex agglutination
– polymerase chain reaction
⚬ variation among studies included
 – cutoff values for markers
– procalcitonin varied from 0.2 ng/mL to 3.3 ng/mL
– CRP varied from 1 mg/dL to 20 mg/dL
– definition of viral meningitis
⚬ efficacy of procalcitonin 0.5 ng/mL cutoff in 5 studies with 432 children
– sensitivity 97% (95% CI 92%-99%)
– specificity 88% (95% CI 84%-92%)
– diagnostic odds ratio 190 (95% CI 69-521)
⚬ Reference - Clin Pediatr (Phila) 2016 Jul;55(8):749
⚬ polymerase chain reaction (PCR) testing for Neisseria meningitidis 4
– use early blood samples as these are more likely to detect the bacteria when present
– negative blood PCR testing for N. meningitidis does not rule out disease

Imaging Studies

● head computed tomography (CT) indicated in some cases prior to lumbar puncture to rule out
mass lesion or another cause of increased intracranial pressure 1 ,3 ,4
● obtain head CT before performing an LP in children with 1 ,2 ,3 ,4
⚬ papilledema
⚬ focal neurologic deficit
⚬ abnormal level of consciousness (Glasgow Coma Scale < 9 or a decrease of ≥ 3 points)
⚬ immunocompromised state
⚬ history of selected central nervous system diseases including those associated with
– cerebrospinal (CSF) shunt
– hydrocephalus
– trauma
– prior neurosurgery
– space-occupying lesion
● provide antibiotics prior to head CT, as diagnosis may be delayed 1 ,4
● CT may detect signs of elevated intracranial pressure but a negative result should not be used
to determine whether to perform lumbar puncture 4
● head CT or magnetic resonance imaging with gadolinium may be indicated after starting treat-
ment for
⚬ non-response to antibiotics including
– persistently abnormal CSF indices, including failure to sterilize 3
 – persistent signs or symptoms (> 72 hours after start of treatment) including impaired
consciousness, excessive irritability, seizures , increasing head circumference in child < 2
years, intensification of headache
⚬ specific patients including
– newborn infants (Pediatr Clin North Am 2005 Jun;52(3):795)
– children with cerebrospinal fluid shunts and drains or other healthcare-associated ven-
triculitis and meningitis (IDSA Strong recommendation, Moderate-quality evidence) (Clin
Infect Dis 2017 Feb 14 early online)
– meningitis due to bacteria other than Streptococcus pneumoniae or Neisseria meningitidis
– immunized child with meningitis due to pneumococcal serotype included in pneumococ-
cal vaccine
⚬ Reference - Med Mal Infect 2009 Jun;39(6):356

Cerebrospinal Fluid (CSF) Analysis

Lumbar Puncture (LP)

● perform LP if meningitis suspected unless contraindicated 1 ,2 ,3 ,4

● when to delay or not perform LP
⚬ if clinical presentation is consistent with CNS mass lesion or other cause of increased in-
tracranial pressure, cranial imaging by head computed tomography (CT) scan may be indi-
1
cated prior to LP
⚬ do not delay treatment to perform CT scan 4
⚬ CT findings and decision to proceed with LP 4
– if CT has evidence of increased intracranial pressure, do not perform LP
– otherwise use clinical judgement, not CT results, to assess if LP can be safely performed
4
⚬ contraindications to LP
– increased intracranial pressure due to mass lesion
– ventricular obstruction
– local infection at puncture site for LP
– suspicion of epidural abscess
– spreading or extensive purpura
– anticoagulation, coagulopathies, or platelet count < 100 × 109/L
– active seizure (LP should be delayed until patient stabilized)
– shock
– cardiorespiratory compromise related to position patient must assume to undergo
procedure
– underlying cardiorespiratory compromise
● LP technique
⚬ positioning of patient important to success of procedure
⚬ important to determine what testing and volume of CSF is needed before performing LP
⚬ record CSF pressure during lumber puncture 2
⚬ see Lumbar puncture (LP) for details
Cerebrospinal Fluid (CSF) Analysis

● recommendations for diagnostic CSF testing 1 ,3 ,4 ,2

⚬ CSF evaluation should be prepared within 4 hours of presentation to guide adjunctive
steroid therapy
⚬ perform Gram stain for all patients with suspected bacterial meningitis (IDSA Grade A-III)
⚬ following tests help identify underlying pathogen
– white blood cell (WBC) count and differential
– glucose and protein levels
– culture plus susceptibility testing if positive
⚬ non-culture diagnostic tests
– consider non-culture testing if
● antibiotic treatment started prior to examination of CSF
● early identification of pathogens is desired
● initial CSF gram stain is negative with negative culture at 72 hour incubation
– polymerase chain reaction (PCR) and other nucleic acid amplification testing to identify
pathogen; panels using nucleic acid-based testing to identify multiple pathogens from a
single sample are available
● broad-based PCR may be useful to exclude bacterial meningitis or influence decisions
to start or discontinue antibiotics (IDSA Grade B-II)
● enteroviral PCR may reduce length of hospital stay, use of antibiotics, and ancillary di-
agnostic testing (IDSA Grade B-II)
– other non-culture tests include
● latex agglutination
● immunochromatography
– select testing depending on clinical setting
● herpes simplex virus PCR for neonates with suspected herpes simplex virus (Emerg
Med Clin North Am 2007 Nov;25(4):1087)
● tuberculosis testing in high-risk children 3
● repeating LP for CSF analysis 1
 ⚬ repeat LP and CSF analysis for children not responsive to antimicrobial therapy after 48
hours (IDSA Grade A-III)
⚬ repeat LP for neonates with meningitis due to gram-negative bacilli to document CSF steril-
ization (IDSA Grade A-III)
⚬ consider repeating in infants with meningitis due to group B Streptococcus 3 or meningitis
due to uncommon bacteria (Med Mal Infect 2009 Jun;39(6):356)
⚬ perform repeat lumbar puncture in neonates with 4
– deterioration in clinical condition
– reemergent or persistent fever
– persistently abnormal inflammatory markers
– new clinical findings (especially neurological findings)
Cerebrospinal Fluid (CSF) Test Findings

General Findings

● normal values for opening pressure

⚬ 1-10 cm H2O in young children
⚬ 6-20 cm H2O in children > 8 years old
⚬ Reference - Am Fam Physician 2003 Sep 15;68(6):1103
● CSF may appear cloudy if significant concentrations of white or red blood cells (RBC), bacteria,
or protein present 1
● CSF findings in children with CSF shunts and drains or other healthcare-associated ventriculi-
tis and meningitis may not be reliable
⚬ abnormalities of CSF cell count, glucose, and/or protein may not be reliable indicators for
presence of infection (IDSA Weak recommendation, Moderate-quality evidence)
⚬ normal CSF cell count, glucose, and protein may not reliably exclude infection (IDSA Weak
recommendation, Moderate-quality evidence)
⚬ negative CSF Gram stain does not exclude presence of infection, especially in children who
have received previous antimicrobial therapy (IDSA Strong recommendation, Moderate-
quality evidence)
⚬ Reference - Clin Infect Dis 2017 Feb 14 early online

STUDY
● SUMMARY
neonatal meningitis can occur without bacteremia or abnormal CSF parameters
COHORT STUDY: Pediatrics 2006 Apr;117(4):1094
Details
⚬ based on cohort study
 ⚬ 9,111 neonates at least 34 weeks estimated gestational age from 150 neonatal intensive
care units had report of first lumbar puncture reviewed
⚬ 95 (1%) had culture-confirmed meningitis
⚬ 62% of patients with meningitis had concomitant positive blood culture
⚬ use of CSF parameters to predict culture-proven meningitis
– CSF WBC > 0 cells/mm3 had 97% sensitivity and 11% specificity
– CSF WBC > 21 cells/mm3 had 79% sensitivity and 81% specificity
– CSF glucose and CSF protein not diagnostically useful
⚬ Reference - Pediatrics 2006 Apr;117(4):1094
CSF White Blood Cell Count and Differential

● WBC count typically elevated in bacterial meningitis 1 ,2

⚬ usually in the range of 1,000-5,000 cells/mm3
⚬ can be as low as < 100 cells/mm3 or as high as > 10,000 cells/mm3
● CSF white blood cell levels that indicate need for initiating antibiotics 4
⚬ ≥ 20 cells/mm3 in neonates (or lower if other signs and symptoms of bacterial meningitis
are present)
⚬ ≥ 5 cells/mm3 or ≥ 1 neutrophil/mm3 in older children, regardless of other CSF variables
● age-specific CSF WBC reference values in young infants
⚬ based on ranges below 95% CI in cohort of 1,064 infants ≤ 56 days old having LP
⚬ ≤ 19 cells/mcL (0.02 cells/mm3) in infants ≤ 28 days old
⚬ ≤ 9 cells/mcL (0.01 cells/mm3) in infants aged 29-56 days
⚬ Reference - Pediatrics 2010 Feb;125(2):257
● neutrophil predominance usually present (80%-95%), but about 10% of patients have lympho-
cyte predominance initially (> 50% lymphocytes or monocytes) 1
● analysis after traumatic LP

STUDY
⚬ SUMMARY
in presence of traumatic LP, adjustment of CSF WBC count using WBC:RBC ratios may
increase specificity, but reduce sensitivity of pleocytosis for diagnosis of bacterial
meningitis in infants < 60 days old DynaMed Level 2

COHORT STUDY: Ann Emerg Med 2017 May;69(5):622

Details
– based on retrospective cohort study
– 20,319 infants ≤ 60 days old had LP to assess for central nervous system infection
 ● 2,880 infants (14%) had traumatic LP (CSF RBC > 10,000 cells/mm3, with no upper limit
to identify possible peripheral blood sample)
● bacterial meningitis (positive CSF culture) in 162 (0.93%) of infants with nontraumatic
tap and 33 (1.1%) of infants with traumatic tap
– mean CSF RBC:WBC ratio for traumatic taps was 877:1 by linear regression analysis
– meningitis was suspected if pleocytosis was present (defined as CSF WBC count > 20
cells/mm3 in neonates 0-28 days old and > 10 cells/mm3 in infants 29-60 days old)
– for detection of bacterial meningitis in traumatic taps
● uncorrected CSF WBC counts had 88% sensitivity, 22% specificity, and 99% NPV
● CSF WBC counts corrected using 877:1 ratio had 67% sensitivity, 67% specificity, and
99% negative predictive value
● CSF WBC counts corrected using 1,000:1 ratio had 67% sensitivity, 63% specificity, and
99% negative predictive value
● CSF WBC counts corrected using 500:1 ratio had 61% sensitivity, 82% specificity, and
99% negative predictive value
– Reference - Ann Emerg Med 2017 May;69(5):622

STUDY
⚬ SUMMARY
CSF WBC count may increase by 1 cell/mm3 for every 2,500-5,000 cells/mm3 of CSF
RBCs in infants < 6 months old without meningitis DynaMed Level 2

COHORT STUDY: Pediatr Infect Dis J 2013 Oct;32(10):1150

Details
– based on retrospective cohort study
– 495 infants < 6 months old with meningitis ruled-out after LP to assess for bacterial
meningitis
– 130 infants (26.3%) had traumatic LP (CSF RBC > 1,000 cells/mm3)
– both CSF WBC and CSF protein increased with traumatic tap
– mean CSF RBC:WBC ratio for traumatic taps
● 2,500:1 cells/mm3 in term infants
● 5,000:1 cells/mm3 in infants < 37 weeks gestational age
– there was significant variation in observed/predicted (CSF RBC:WBC ratio/peripheral
RBC:WBC ratio) ratios
– Reference - Pediatr Infect Dis J 2013 Oct;32(10):1150

Gram Staining and CSF Culture

● Gram staining 1 ,2 ,4
⚬ recommended for all patients with suspected meningitis (IDSA Grade A-III)
 ⚬ identifies causative bacteria in about 60%-90% of patients with community-acquired bacte-
rial meningitis and reported to have ≥ 97% specificity
⚬ likelihood of visualizing bacteria
– increased with cytospin techniques
– depends on pathogen
● 90% for Streptococcus pneumoniae
● 86% for Haemophilus influenzae
● 75% for Neisseria meningitidis
● 50% gram-negative bacilli
● about 30% for Listeria monocytogenes
– decreased by about 20% if antimicrobial given before LP

● CSF culture
⚬ positive CSF cultures reported in 70%-85% of bacterial meningitis in patients not on antimi-
crobial therapy 1
⚬ if CSF culture negative in children treated with antibiotics before LP, elevated CSF protein
and WBC count usually sufficient for meningitis diagnosis 2
● review of CSF specimen evaluation for N. meningitidis, S. pneumoniae, and H. influenzae in bac-
terial meningitis can be found at CDC 2011 Laboratory Methods for the Diagnosis of
Meningitis
CSF Glucose and Protein

● CSF glucose concentration ≤ 40 mg/dL (2.2 mmol/L) reported in 50%-60% of children with bac-
terial meningitis 1
● CSF:serum glucose ratio 1
⚬ ≤ 0.4 reported to have 80% sensitivity and 98% specificity in children > 2 months old
⚬ ≤ 0.6 considered abnormal in neonates
● CSF protein elevated in most children with bacterial meningitis 1 ,2 ,5
● CSF protein concentrations (normal ranges may vary by laboratory)
⚬ normal levels
– in newborns, up to 150 mg/dL (1.5 g/L)
 – by age 6-12 months, levels reach that seen in adults and range from 18 mg/dL to 58
mg/dL (0.18 g/L to 0.58 g/L)
⚬ in bacterial meningitis, mean CSF protein concentration 418 mg/dL (4.18 g/L) range 21
mg/dL to 2,220 mg/dL (0.21 g/L to 22.2 g/L)
⚬ may be adjusted for increased protein caused by traumatic tap (subtract 1 mg/dL [0.01 g/L]
protein per 1,000 RBC/mm3)
⚬ Reference - Am Fam Physician 2003 Sep 15;68(6):1103

STUDY
● SUMMARY
CSF protein may help distinguish bacterial from viral cause in children with meningitis
DynaMed Level 2

COHORT STUDY: J Pediatr 2006 Jul;149(1):72

Details
⚬ based on retrospective cohort study with wide confidence intervals
⚬ 167 children (median age 5 years) hospitalized for meningitis were assessed for preadmis-
sion emergency department CSF (protein, glucose, WBCs, neutrophils) and blood (C-reac-
tive protein [CRP], procalcitonin, WBCs, neutrophils) test results
⚬ 21 children (12.6%) had bacterial meningitis
⚬ bacterial meningitis associated with CSF protein ≥ 0.5 g/L (odds ratio 108, 95% CI 15-772,
86% sensitivity, 78% specificity)
⚬ all children with bacterial meningitis had elevated procalcitonin or elevated CSF protein
⚬ Reference - J Pediatr 2006 Jul;149(1):72

CSF Polymerase Chain Reaction (PCR) Testing

● broad-based PCR may be useful to exclude diagnosis of bacterial meningitis or identify bacte-
ria, especially if culture and Gram stain are negative (IDSA Grade B-II) 1 , 2 , 4
● enteroviral PCR may reduce length of hospital stay, use of antibiotics, and ancillary diagnostic
testing (IDSA Grade B-II) 1
● CSF samples may be submitted for
⚬ specific PCR testing, such as N. meningitidis and S. pneumoniae 4
⚬ multiplex PCR testing for a panel of bacteria, viruses, and fungi (Adv Biomed Res 2013;2:7)
● FilmArray Meningitis/Encephalitis (ME) Panel nucleic acid-based test FDA approved for simul-
taneous detection of 14 pathogens from a single sample of cerebrospinal fluid in patients
with suspected meningitis or encephalitis
⚬ simultaneously tests for 14 bacterial, viral and yeast pathogens
– bacteria identified include Escherichia coli K1, Haemophilus influenzae, Listeria monocyto-
genes, Neisseria meningitidis, Streptococcus agalactiae, and Streptococcus pneumoniae
 – viruses identified include cytomegalovirus, enterovirus, herpes simplex virus 1, herpes
simplex virus 2, human herpesvirus 6, human parechovirus, and varicella zoster virus
– yeasts identified include Cryptococcus neoformans and Cryptococcus gattii
⚬ test does not detect all causes of central nervous system infections or provide information
about antimicrobial susceptibility
– standard cerebrospinal fluid bacterial and fungal cultures should still be obtained due to
● possibility of false negative and false positive results
● need for bacterial growth for drug susceptibility testing following positive results
– false negative results may occur when the concentration of organisms in the CSF speci-
men is below the limit of detection
⚬ Reference - FDA Press Release 2015 Oct 8
● CSF sample PCR testing up to 96 hours after hospital admission may yield useful information 4

STUDY
● SUMMARY
real-time quantitative PCR may be more sensitive than culture for detection of S. pneumo-
niae, N. meningitidis, and H. influenzae meningitis DynaMed Level 2
DIAGNOSTIC COHORT STUDY: Sci Rep 2016 Dec 23;6:39784
DIAGNOSTIC COHORT STUDY: BMC Infect Dis 2013 Jan 22;13:26
Details
⚬ based on 2 diagnostic cohort studies without reliable reference standard
⚬ 266 patients (12% adults) with suspected bacterial meningitis had CSF testing by culture,
Gram stain, and direct bacterial antigen testing by latex agglutination (traditional methods)
and real-time quantitative PCR for S. pneumoniae, N. meningitidis, and Haemophilus
influenzae
– 47 (17.7%) had known bacterial cause for meningitis including 35 with S. pneumoniae, N.
meningitidis, or H. influenzae

Rate of Bacterial Identification by Test

Organism T Positive Detected by Seen on Detected

ot Culture Latex Gram Stain by qPCR
al Agglutinatio
n

Streptococc 17 41% 54% of 11 50% of 16 100% of 16

us tested examined tested
 Organism T Positive Detected by Seen on Detected
ot Culture Latex Gram Stain by qPCR
al Agglutinatio
n

pneumo-
niae

Neisseria 13 8% 29% of 7 25% of 12 92%

meningitidis tested tested

Haemophilu 5 40% 50% of 2 25% 100%

s influenzae tested

● sensitivity of Gram stain and real-time PCR was not significantly affected by prior an-
tibiotic use
– Reference - Sci Rep 2016 Dec 23;6:39784
⚬ 451 patients median age 11 years old (range 0-78 years) with suspected bacterial meningi-
tis had CSF testing by Gram stain, culture, and real-time PCR for S. pneumoniae, N. meningi-
tidis, and H. influenzae
– 80 (17.7%) had culture isolation of 1 of the 3 pathogens (40 S. pneumoniae, 36 N. meningi-
tidis, and 4 H. influenzae), and 113 (25.1%) were real-time PCR positive (51 S. pneumoniae,
57 N. meningitidis, and 5 H. influenzae)
– reference standards included culture results, composite reference standard (Gram stain
or culture), and latent class analysis (pooled comparative data used to estimate relative
sensitivities and specificities of diagnostic methods in absence of reference standard)
– estimates of efficacies for diagnosis of S. pneumoniae, N. meningitidis, or H. influenzae
meningitis using latent class analysis (with disease prevalence of 21.5%)

Efficacy by Test

Organism(s) Bacterial Gram Stain Real-time PCR

Culture

Streptococcus ● Sensitivity 81% ● Sensitivity 98% ● Sensitivity 96%

pneumoniae, (95% CI (95% CI (95% CI
Neisseria meningi- 73%-89%) 95%-100%) 91%-100%)
tidis, or
 Organism(s) Bacterial Gram Stain Real-time PCR
Culture

Haemophilus in- ● Specificity ● Specificity 99% ● Specificity 94%

fluenzae 99.7% (95% CI (95% CI (95% CI
meningitis 99%-100%) 97%-100%) 92%-97%)

S. pneumoniae ● Sensitivity 85% ● Sensitivity 98% ● Sensitivity 96%

only (95% CI (95% CI (95% CI
75%-96%) 91%-100%) 91%-100%)
● Specificity ● Specificity 99% ● Specificity 99%
100% (95% CI (95% CI (95% CI
99.9%-100%) 98%-100%) 97%-99.7%)

N. meningitidis ● Sensitivity 78% ● Sensitivity 99% ● Sensitivity 96%

only (95% CI (95% CI (95% CI
65%-90%) 95%-100%) 89%-100%)
● Specificity ● Specificity ● Specificity 97%
99.8% (95% CI 99.6% (95% CI (95% CI
99%-100%) 99%-100%) 95%-98%)

– Reference - BMC Infect Dis 2013 Jan 22;13:26

Cerebrospinal Fluid (CSF) Testing Not Routinely Recommended

● latex agglutination 1 ,2 ,5
⚬ latex agglutination may not be clinically useful as it more often identifies children with posi-
tive culture and bacterial meningitis, and does not appear to accurately identify children
with negative culture and bacterial meningitis
⚬ not recommended for routine use (IDSA Grade D-II) due to studies showing false-positives
and failure of positive result to alter clinical decisions (test has reported sensitivity of 70%
and specificity of 99.4%)
⚬ may be useful for patients with negative CSF Gram stain (IDSA Grade C-II), especially for
negative Gram stain and CSF culture in patients pretreated with antibiotics (IDSA Grade B-
III)
⚬ reported sensitivities for detecting antigens for common meningeal pathogens
– 78%-100% for Haemophilus influenzae type b
– 67%-100% for Streptococcus pneumoniae
– 69%-100% for Streptococcus agalactiae
 – 50%-93% for Neisseria meningitidis
⚬ positive latex agglutination test establishes diagnosis of bacterial meningitis caused by spe-
cific pathogen, but negative test cannot rule out bacterial meningitis
● CSF lactate concentration 1
⚬ develops during bacterial meningitis due to tissue anoxia
⚬ not recommended for patients with suspected community-acquired bacterial meningitis
(IDSA Grade D-III)
⚬ in postoperative neurosurgical patient, consider initiation of empirical antimicrobial ther-
apy for CSF lactate concentration ≥ 4 mmol/L (36 mg/dL), pending other study results (IDSA
Grade B-II)
1
● limulus lysate assay not recommended for routine use (IDSA Grade D-II)

Management

Management Overview

● bacterial meningitis is a neurologic emergency, and therapy should be started as soon as pos-
1
sible after diagnosis is considered to be likely
● start antimicrobial therapy once cerebrospinal fluid (CSF) obtained for analysis, and diagnosis
of meningitis seems likely
⚬ empiric antibiotics indicated if lumbar puncture delayed such as when computed tomogra-
phy scan is required or when meningitis is purulent even if CSF Gram stain is negative 1
⚬ empiric antibiotic choice depends on likely pathogens (based on age and risk factors)
⚬ see recommended doses of antibiotics once specific antibiotic selected
⚬ dexamethasone is recommended if Haemophilus influenza type B meningitis is suspected
and should be given prior to or within 20-30 minutes of antibiotic dose; it is not recom-
mended for use in neonates (IDSA Grade A-I)
⚬ modify treatment based on susceptibility testing and/or isolation of bacterial pathogen;
recommendations on choice of specific antimicrobial agent based on knowledge of in vitro
susceptibility and relative penetration into CSF in presence of meningeal inflammation 1
⚬ recommended duration of antibiotic therapy depends on organism isolated (IDSA Grade A-
III)
⚬ empiric antibiotics
– in infants < 3 months old
● give IV cefotaxime plus either amoxicillin or ampicillin immediately
● ceftriaxone may be used as an alternative to cefotaxime (with or without ampicillin or
amoxicillin), however ceftriaxone should not be given to premature babies or babies
 with jaundice, hypoalbuminemia, or acidosis as it may exacerbate hyperbilirubinemia
– in children and adolescents ≥ 3 months old, give IV ceftriaxone immediately
⚬ use IV antibiotics for duration of treatment course in most children, although selected pa-
tients may finish therapy with outpatient antibiotics after ≥ 6 days of inpatient antibiotic
therapy (IDSA Grade A-III)
● chemoprophylaxis for close contacts for specific indications based on pathogen and contact's
age, immune status, and degree of contact with index case
● adjunctive therapies to reduce risk for neurologic sequelae
⚬ IV maintenance fluids
⚬ dexamethasone 0.15 mg/kg IV every 6 hours for 2-4 days (give first dose 10-20 minutes be-
fore or with first antibiotic dose) (IDSA Grade A-I)
– recommended in suspected or confirmed H. influenzae type b meningitis (IDSA Grade A-I)
and controversial in pneumococcal meningitis (IDSA Grade C-II)
– do not give to infants or children who have already received antibiotic therapy (IDSA
Grade A-I)
– insufficient evidence to recommend adjunctive dexamethasone in neonates with bacte-
rial meningitis (IDSA Grade C-I)
● follow-up should include hearing and neurobehavioral evaluation within 1 month and every 3
months for 1 year

Treatment Setting
● primary care physician should transfer patients with suspected bacterial meningitis to nearest
healthcare facility as soon as possible; do not delay transfer to start parenteral antibiotics 4
● if urgent transfer is not possible, initiate parenteral antibiotics in patients with suspected bac-
terial meningitis 4

Fluid and Electrolytes

● fluid management recommendations for suspected or confirmed bacterial meningitis 4

⚬ assess infant or child for
– signs of shock
– signs of dehydration
– elevated intracranial pressure
⚬ if patient is dehydrated, give enteral fluids or feeds or IV isotonic fluids such as sodium
chloride 0.9% with glucose 5%
⚬ only restrict fluids in presence of
– raised intracranial pressure
 – increased antidiuretic hormone secretion (SIADH)
⚬ give full-volume maintenance fluids to maintain electrolyte balance and avoid
hypoglycemia
⚬ give enteral feeds as maintenance fluids as tolerated
⚬ if IV maintenance fluid is needed give isotonic fluids such as
– sodium chloride 0.9% with glucose 5%
– glucose 10% and added sodium chloride for maintenance in neonates
⚬ monitor fluid administration and urine output to ensure adequate hydration and avoid
overhydration
⚬ monitor electrolytes and blood glucose at least daily while child is receiving IV fluids
⚬ in presence of elevated intracranial pressure or evidence of shock, initiate emergency man-
agement for these conditions and discuss ongoing fluid management with a pediatric
intensivist
● fluid restriction in children with syndrome of inappropriate antidiuresis (SIAD)
⚬ no evidence that fluid restriction reduces cerebral edema
⚬ may result in hypovolemia, decreased systemic blood pressure, and compromised cerebral
perfusion
⚬ Reference - Pediatr Clin North Am 2005 Jun;52(3):795

STUDY
● SUMMARY
maintenance fluids may reduce risk of neurologic sequelae compared to restricted fluids in
children and adolescents with acute bacterial meningitis DynaMed Level 2

COCHRANE REVIEW: Cochrane Database Syst Rev 2016 Nov 4;(11):CD004786

Details
⚬ based on Cochrane review of trials with unclear blinding of outcome assessors
⚬ systematic review of randomized trials comparing different fluid volumes for initial man-
agement of acute bacterial meningitis
⚬ 3 trials with 420 patients met inclusion criteria; age ranged from 1 month to 16 years
⚬ all trials compared maintenance fluids to restricted fluids
– maintenance fluids defined as 100 mL/kg/day for first 10 kg of body weight, 50 mL/kg for
second 10 kg, and 20 mL/kg for over 20 kg as expressed breast milk or other milk feed,
divided into feeds given every 3 hours were compared to 60% of maintenance fluids for
48 hours in 1 trial with 357 children
– maintenance fluids defined as 110 mL/kg for first 10 kg of body weight, 50 mL/kg for
next 10 kg, and 25 mL/kg for subsequent weight were compared to 65% of maintenance
fluids IV in 1 trial with 50 children
– maintenance fluids defined as 100 mL/kg for first 10 kg of body weight, 50 mL/kg for
next 10 kg, and 20 mL/kg for each kg over 20 kg (plus replacement fluids for any esti-
 mated deficit over 24 hours) were compared to 67% of maintenance fluids IV in 1 trial
with 13 patients (not included in analyses for neurologic sequelae or mortality)
⚬ comparing maintenance fluids to restricted fluids
– maintenance fluids associated with
● nonsignificant decrease in risk of acute severe neurologic sequelae (risk ratio 0.67,
95% CI 0.41-1.08) in analysis of 2 trials with 407 children
● decrease in spasticity and seizures up to 14 days and severe neurologic sequelae up
to 3 months in 1 trial with 357 children
– no significant difference in mortality in analysis of 2 trials with 407 children
⚬ Reference - Cochrane Database Syst Rev 2016 Nov 4;(11):CD004786

Medications

Antibiotics

Empiric Antibiotic Treatment

● empiric antibiotic choice based on age and risk factors with modification if Gram stain positive
2

● start empiric antibiotics if either 1

⚬ meningitis is purulent, even if CSF Gram stain is negative
⚬ lumbar puncture delayed such as when computed tomography scan is required
● Infectious Diseases Society of America recommendations for empiric treatment 1
⚬ for neonates (IDSA Grade A-III)
– aged 0-7 days, IV antibiotic regimens (1 of 2 regimens)
● ampicillin 150 mg/kg/day in divided doses every 8 hours plus cefotaxime 100-150
mg/kg/day in divided doses every 8-12 hours
● ampicillin 150 mg/kg/day in divided doses every 8 hours plus aminoglycoside (gen-
tamicin or tobramycin 5 mg/kg/day in divided doses every 12 hours or amikacin 15-20
mg/kg/day in divided doses every 12 hours)
– aged 8-28 days, IV antibiotic regimens (1 of 2 regimens)
● ampicillin 200 mg/kg/day in divided doses every 6-8 hours plus cefotaxime 200
mg/kg/day in divided doses every 6-8 hours
● ampicillin 200 mg/kg/day in divided doses every 6-8 hours plus aminoglycoside (gen-
tamicin or tobramycin 7.5 mg/kg/day in divided doses every 8 hours or amikacin 30
mg/kg/day in divided doses every 8 hours)
 – smaller doses and longer intervals of administration may be advisable for very low-birth-
weight neonates (< 2,000 g)
⚬ for infants and children ≥ 1 month old, IV antibiotic regimen (IDSA Grade A-III)
– standard (use both)
● vancomycin 60 mg/kg/day in divided doses every 6 hours
● ceftriaxone 80-100 mg/kg/day in divided doses every 12-24 hours or cefotaxime 225-
300 mg/kg/day in divided doses every 6-8 hours
– if patient treated with dexamethasone - consider adding rifampin 10-20 mg/kg/day
(maximum 600 mg/day) in divided doses every 12-24 hours if pneumococcal meningitis
suspected
– if Listeria monocytogenes considered - add ampicillin 300 mg/kg/day in divided doses ev-
ery 6 hours to standard regimen
⚬ for special considerations, IV antibiotic regimens (IDSA Grade A-III) (see below for recom-
mended dosing by age)
– healthcare-associated ventriculitis and meningitis, including CSF shunt
● vancomycin plus antipseudomonal beta-lactam (cefepime, ceftazidime, or
meropenem) (IDSA Strong recommendation, Low-quality evidence)
● aztreonam or ciprofloxacin may be used instead of antipseudomonal beta-lactam in
children with demonstrated anaphylaxis to beta-lactam antimicrobial agents and con-
traindications to meropenem (IDSA Strong recommendation, Low-quality evidence)
● in children colonized or infected at another site with a highly antimicrobial-resistant
pathogen, adjust empiric regimen to treat for this pathogen (IDSA Strong recommen-
dation, Low-quality evidence)
● adjust antibiotics based on pathogen, if identified
● Reference - Clin Infect Dis 2017 Feb 14 early online
– basilar skull fracture - vancomycin plus ceftriaxone or cefotaxime
– penetrating head trauma or postneurosurgery - vancomycin plus cefepime, ceftazidime,
or meropenem
⚬ acyclovir 20 mg/kg IV every 8 hours if suspected neonatal herpes (Pediatrics 2013
Feb;131(2):e635)
● National Institute for Health and Care Excellence (NICE) recommendations for antibiotics 4
⚬ in infants and children with suspected meningitis or meningococcal disease
– in infants < 3 months old
● give IV cefotaxime plus either amoxicillin or ampicillin immediately
● ceftriaxone may be used as an alternative to cefotaxime (with or without ampicillin or
amoxicillin), however ceftriaxone should not be given to premature babies or babies
 with jaundice, hypoalbuminemia, or acidosis as it may exacerbate hyperbilirubinemia
– in children > 3 months old with suspected bacterial meningitis, give IV ceftriaxone
immediately
– in children with suspected meningococcal disease, give ceftriaxone IV without delay
– in children who have a recent travel history or have had prolonged or multiple exposure
to antibiotics in past 3 months, give adjunctive vancomycin
– do not give calcium-containing infusions with ceftriaxone; give cefotaxime instead
– in children with suspected tuberculosis meningitis, use antibiotic treatment appropriate
for tuberculous meningitis
– in children with suspected herpes simplex meningoencephalitis, give appropriate antivi-
ral treatment
⚬ in children with unconfirmed bacterial meningitis (diagnosis based on clinical suspicion)
– in infants < 3 months old, give cefotaxime plus either ampicillin or amoxicillin for ≥ 14
days and consider continuation of antibiotic course and consultation with pediatric in-
fectious disease expert in complicated cases
– in infants and children > 3 months old with uncomplicated disease, give IV ceftriaxone
for ≥ 10 days depending on symptoms and signs and course of illness
Treatment Based on Isolated Pathogen and Susceptibility Testing

Streptococcus Pneumoniae

● revised definition of Streptococcus pneumoniae susceptibility breakpoints for penicillin

Table 4: Susceptibility Category by Minimum Inhibitory Concentration (MIC)

Susceptible Intermediate Resistant

Meningitis, IV ≤ 0.06 mcg/mL Not applicable ≥ 0.12 mcg/mL

penicillin

Not meningitis, IV ≤ 2 mcg/mL 4 mcg/mL ≥ 8 mcg/mL

penicillin

Not meningitis, ≤ 0.06 mcg/mL 0.12-1 mcg/mL ≥ 2 mcg/mL

oral penicillin

⚬ Reference - MMWR Morb Mortal Wkly Rep 2008 Dec 19;57(50):1353

● IDSA recommends treatment based on penicillin minimal inhibitory concentration (MIC) 1 (see
below for recommended dosing by age)
⚬ treat for 10-14 days (IDSA Grade A-III)
⚬ MIC < 0.1 mcg/mL
– penicillin G or ampicillin (IDSA Grade A-III)
– alternatives - ceftriaxone, cefotaxime, or chloramphenicol (IDSA Grade A-III)
⚬ MIC 0.1-1 mcg/mL
– ceftriaxone or cefotaxime (IDSA Grade A-III)
– alternatives - cefepime or meropenem (IDSA Grade B-II)
⚬ MIC ≥ 2 mcg/mL (or cefotaxime or ceftriaxone MIC ≥ 1 mcg/mL)
– vancomycin plus ceftriaxone or cefotaxime (IDSA Grade A-III)
– consider addition of rifampin if ceftriaxone MIC > 2 mcg/mL (IDSA Grade A-III)
– alternatives - moxifloxacin or gatifloxacin (systemic gatifloxacin not available in United
States) (IDSA Grade B-II), have not been studied in neonates and children with bacterial
meningitis
Neisseria Meningitidis

● IDSA recommends treating for 7 days based on penicillin MIC (IDSA Grade A-III) 1 (see below
for recommended dosing by age)
⚬ MIC < 0.1 mcg/mL
– penicillin G or ampicillin
– alternatives - ceftriaxone, cefotaxime, or chloramphenicol
⚬ MIC 0.1-1 mcg/mL
– ceftriaxone or cefotaxime
– alternatives - chloramphenicol, fluoroquinolone (recommended dose not reported for
infants and children), or meropenem
● meningococcal resistance patterns 2 ,3
⚬ 30%-80% of N. meningitidis may have reduced or no susceptibility to penicillin
⚬ third-generation cephalosporin resistance is uncommon

Listeria Monocytogenes

● IDSA recommends 1 (see below for recommended dosing by age)

⚬ treat for ≥ 21 days (IDSA Grade A-III)
⚬ ampicillin or penicillin G (IDSA Grade A-III)
⚬ consider addition of aminoglycoside to penicillin G (IDSA Grade A-III)
 ⚬ alternatives - trimethoprim-sulfamethoxazole (IDSA Grade A-III) or meropenem (IDSA Grade
B-III)
● National Institute for Health and Care Excellence recommends IV amoxicillin or ampicillin for
4
21 days plus gentamicin for at least first 7 days
Streptococcus Agalactiae (Group B Streptococcus)

● IDSA recommends 1 (see below for recommended dosing by age)

⚬ treat for 14-21 days (IDSA Grade A-III)
⚬ ampicillin or penicillin G (IDSA Grade A-III)
⚬ consider addition of aminoglycoside to penicillin G (IDSA Grade A-III)
⚬ alternatives - ceftriaxone or cefotaxime (IDSA Grade B-III)
● NICE recommends IV cefotaxime for ≥ 14 days and consider continuation of antibiotic course
and consultation with pediatric infectious disease expert in complicated cases 4

Escherichia Coli

● IDSA recommends (for E. coli and other Enterobacteriaceae) 1 (see below for recommended
dosing by age)
⚬ treat for 21 days (IDSA Grade A-III)
⚬ third-generation cephalosporin (ceftriaxone or cefotaxime) (IDSA Grade A-II)
⚬ alternatives - aztreonam (recommended dose not reported for infants and children), fluo-
roquinolone (recommended dose not reported for infants and children), meropenem,
trimethoprim-sulfamethoxazole, ampicillin (IDSA Grade A-III)
⚬ in vitro susceptibility test results must guide specific antimicrobial choice (IDSA Grade A-III)

Haemophilus Influenzae

● IDSA recommends 1 (see below for recommended dosing by age)

⚬ treat for 7 days (IDSA Grade A-III)
⚬ beta-lactamase negative (IDSA Grade A-III)
– ampicillin
– alternatives - ceftriaxone, cefotaxime, cefepime, chloramphenicol, or fluoroquinolone
(recommended dose not reported for infants and children)
⚬ beta-lactamase positive
– third-generation cephalosporin (ceftriaxone or cefotaxime) (IDSA Grade A-I)
– alternatives - cefepime (IDSA Grade A-I), chloramphenicol (IDSA Grade A-III), or fluoro-
quinolone (recommended dose not reported for infants and children) (IDSA Grade A-III)
Other Bacterial Pathogens

● Pseudomonas aeruginosa - IDSA recommends 1 (see below for recommended dosing by age)
⚬ treat for 21 days (IDSA Grade A-III)
⚬ in vitro susceptibility test results must guide specific antimicrobial choice (IDSA Grade A-III)
⚬ cefepime or ceftazidime (IDSA Grade A-II)
⚬ alternatives - aztreonam (recommended dose not reported for infants and children),
ciprofloxacin (recommended dose not reported for infants and children), meropenem
(IDSA Grade A-III)
⚬ consider addition of aminoglycoside to any of the above (IDSA Grade A-III)
● Staphylococcus aureus - IDSA recommends (see below for recommended dosing by age)
⚬ methicillin susceptible 1
– nafcillin or oxacillin (IDSA Grade A-III)
– alternatives - vancomycin (IDSA Grade A-III) or meropenem (IDSA Grade B-III)
⚬ methicillin resistant
– vancomycin(IDSA Grade A-II)
● dosing 15 mg/kg IV every 6 hours for 14 days (IDSA Grade B-II)
● target trough concentration of 15-20 mcg/mL (IDSA Grade B-III)
– alternatives
● linezolid 10 mg/kg orally or IV every 8 hours (maximum 600 mg/dose) (IDSA Grade B-
III) or 600 mg orally or IV twice daily if ≥ 12 years old
● sulfamethoxazole-trimethoprim (no data so recommended dose and route not
reported)
– Reference - Infectious Diseases Society of America (IDSA) clinical practice guideline on
treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in adults and
children (Clin Infect Dis 2011 Feb 1;52(3):e18), correction can be found in Clin Infect Dis
2011 Aug 1;53(3):319, commentary can be found in Clin Infect Dis 2011 Jun
15;52(12):1468, Clin Infect Dis 2011 Jul 1;53(1):98, Clin Infect Dis 2011 Aug 1;53(3):308,
Clin Infect Dis 2015 Apr 15;60(8):1290
– see also Methicillin-resistant Staphylococcus aureus (MRSA)
● Staphylococcus epidermidis - IDSA recommends 1 (see below for recommended dosing by age)
⚬ vancomycin (IDSA Grade A-III)
⚬ consider addition of rifampin to vancomycin (IDSA Grade A-III)
⚬ alternatives - linezolid (recommended dose not reported) (IDSA Grade B-III)
● Enterococcus species - IDSA recommends 1 (see below for recommended dosing by age)
 ⚬ ampicillin susceptible - ampicillin plus gentamicin (IDSA Grade A-III)
⚬ ampicillin resistant - vancomycin plus gentamicin (IDSA Grade A-III)
⚬ ampicillin and vancomycin resistant - linezolid (recommended dose not reported) (IDSA
Grade B-III)
Dosing and Drug-specific Information

● recommended dose of IV antibiotics is based on patient age, renal and hepatic function, and
whether an infection is healthcare associated

Table 5: IDSA Recommended Doses of IV Antibiotics (Assuming Normal Renal and

Hepatic Function)

Drug Neonates Aged 0- Neonates Aged 8- Infants and

7 Days* 28 Days* Children > 28
Days Old

Amikacin (monitor 15-20 mg/kg/day 30 mg/kg/day in di- 20-30 mg/kg/day

serum peak and in divided doses vided doses every in divided doses
trough levels) every 12 hours 8 hours every 8 hours

Ampicillin 150 mg/kg/day in 200 mg/kg/day in 300 mg/kg/day in

divided doses ev- divided doses ev- divided doses ev-
ery 8 hours ery 6-8 hours ery 6 hours (up to
400 mg/kg/day for
healthcare-associ-
ated infections)

Aztreonam** NA NA 120 mg/kg/day in

divided doses ev-
ery 6-8 hours

Cefepime NA NA 150 mg/kg/day in

divided doses ev-
ery 8 hours

Cefotaxime 100-150 150-200 225-300

mg/kg/day in di- mg/kg/day in di- mg/kg/day in di-
 Drug Neonates Aged 0- Neonates Aged 8- Infants and
7 Days* 28 Days* Children > 28
Days Old

vided doses every vided doses every vided doses every

8-12 hours 6-8 hours 6-8 hours***

Ceftazidime 100-150 150 mg/kg/day in 150 mg/kg/day in

mg/kg/day in di- divided doses ev- divided doses ev-
vided doses every ery 8 hours ery 8 hours (200
8-12 hours mg/kg/day for
healthcare-associ-
ated infections)

Ceftriaxone NA NA 80-100 mg/kg/day

once daily or in di-
vided doses every
12 hours***

Ciprofloxacin** NA NA 30 mg/kg/day in
divided doses ev-
ery 8-12 hours

Chloramphenicol 25 mg/kg/day once 50 mg/kg/day once 75-100 mg/kg/day

daily daily or in divided in divided doses
doses every 12 every 6 hours
hours

Gentamicin or 5 mg/kg/day in di- 7.5 mg/kg/day in 7.5 mg/kg/day in

Tobramycin as ad- vided doses every divided doses ev- divided doses ev-
junctive therapy 12 hours ery 8 hours ery 8 hours
(monitor serum
peak and trough
levels)

Linezolid** NA NA < 12 years old: 30

mg/kg/day in di-
 Drug Neonates Aged 0- Neonates Aged 8- Infants and
7 Days* 28 Days* Children > 28
Days Old

vided doses every

8 hours

≥ 12 years old: 20
mg/kg/day in di-
vided doses every
12 hours

Meropenem NA NA 120 mg/kg/day in

divided doses ev-
ery 8 hours

Nafcillin 75 mg/kg/day in di- 100-150 200 mg/kg/day in

vided doses every mg/kg/day in di- divided doses ev-
8-12 hours vided doses every ery 6 hours
6-8 hours

Oxacillin 75 mg/kg/day in di- 150-200 200 mg/kg/day in

vided doses every mg/kg/day in di- divided doses ev-
8-12 hours vided doses every ery 6 hours
6-8 hours

Penicillin G 0.15 million 0.2 million 0.3 million

units/kg/day in di- units/kg/day in di- units/kg/day in di-
vided doses every vided doses every vided doses every
8-12 hours 6-8 hours 4-6 hours

Rifampin NA 10-20 mg/kg/day 10-20 mg/kg/day

in divided doses once daily or in di-
every 12 hours vided doses every
12 hours (maxi-
mum dose 600
mg/day)***
 Drug Neonates Aged 0- Neonates Aged 8- Infants and
7 Days* 28 Days* Children > 28
Days Old

Trimethoprim- NA NA 10-20 mg/kg/day

sulfamethoxazole (based on
trimethoprim com-
ponent) in divided
doses every 6-12
hours

Vancomycin 20-30 mg/kg/day 30-45 mg/kg/day 60 mg/kg/day in

in divided doses in divided doses divided doses ev-
every 8-12 every 6-8 hours ery 6 hours (goal
hours(goal trough (goal trough 15-20 trough 15-20
15-20 mcg/mL) mcg/mL) mcg/mL)

Abbreviations: IDSA, Infectious Diseases Society of America; NA, not applicable.

* Consider smaller doses and longer intervals between doses for very low-birth-weight infants (< 2,000
g).

** Recommended dosing for healthcare-associated ventriculitis or meningitis.

*** Upper dosing range recommended for healthcare-associated infections.

Reference -

Clin Infect Dis 2004 Nov 1;39(9):1267, Clin Infect Dis 2017 Mar 15;64(6):e34.

● aminoglycosides 2
⚬ CSF penetration variable or poor, even with meningeal inflammation
⚬ monotherapy for bacterial meningitis contraindicated
● carbapenems 1
⚬ imipenem associated with potential for seizure activity (reported as 33% in children with
bacterial meningitis); IDSA recommends against use in most patients with bacterial menin-
gitis (IDSA Grade D-II)
⚬ meropenem may not be useful alternative agent for treatment of pneumococcal isolates
highly resistant to penicillin and cephalosporins (IDSA Grade D-II); highly resistant isolates
may also confer intermediate susceptibility or resistance to meropenem
 ⚬ meropenem-containing regimen may be best for meningitis caused by gram-negative
bacilli that produce extended spectrum beta-lactamases or that may hyperproduce beta-
lactamases (for example, Enterobacter species, Citrobacter species, Serratia marcescens)
⚬ meropenem has similar clinical and microbiological outcomes to those of third-generation
cephalosporins (cefotaxime or ceftriaxone) and can be used as an alternative for treatment
of bacterial meningitis (IDSA Grade A-I)
● cephalosporins
⚬ third-generation cephalosporins are the preferred drugs of choice for empiric treatment of
H. influenzae meningitis due to emergence of beta-lactamase–producing strains 1

STUDY
⚬ SUMMARY
third-generation cephalosporins may be as effective as older antibiotic regimens for
empiric treatment of acute bacterial meningitis in adults and children DynaMed Level 2

COCHRANE REVIEW: Cochrane Database Syst Rev 2007 Oct 17;(4):CD001832

Details
– based on Cochrane review of trials with methodologic limitations
– systematic review of 19 randomized trials comparing ceftriaxone or cefotaxime to older
antibiotic regimens (ampicillin-chloramphenicol or chloramphenicol alone) as empiric
therapy for acute bacterial meningitis in 1,496 adults and children
– unclear allocation concealment in 18 trials, blinding not reported in 1 additional trial
– all trials conducted in 1980s except 3 (1993, 1996, and 2005)
– largest trial with 510 patients had majority of weight (33.8%) in analyses it was included
in (mortality and treatment failure)
– no significant difference between groups in
● mortality in analysis of 19 trials
● deafness in analysis of 10 trials with 501 patients
● treatment failure (either death or deafness) in analysis of 19 trials
● neutropenia (in 10 trials with 472 patients) or skin rash (in 8 trials with 533 patients)
– third-generation cephalosporins associated with
● reduced risk of positive cerebrospinal fluid (CSF) cultures at 10-48 hours after start of
treatment (risk difference [RD] -6%, 95% CI -11% to 0%) in analysis of 12 trials with 442
patients
● increased risk of diarrhea (RD 8%, 95% CI 3%-13%) in analysis of 12 trials with 750 pa-
tients, results limited by significant heterogeneity
– Reference - Cochrane Database Syst Rev 2007 Oct 17;(4):CD001832 (review updated
2011 Aug 22)
● chloramphenicol - associated with increasing resistance to H. influenzae; third-generation
cephalosporins are preferred instead for empiric therapy 1
● fluoroquinolones 1
⚬ due to significant rates of fluoroquinolone resistance, role of fluoroquinolones is limited
and susceptibility testing should be considered before use
⚬ use only for meningitis caused by multidrug-resistant gram-negative bacilli, or when patient
has not responded to or cannot receive standard antimicrobial therapy (IDSA Grade A-III)
⚬ gatifloxacin and moxifloxacin
– should only be used as alternative agents in patients with bacterial meningitis (IDSA
Grade B-III)
– have not been studied in newborns and children with bacterial meningitis; should only
be considered in these patients if not responding to standard therapy
● rifampin 1
⚬ should only be added if organism is susceptible and there is delay in expected clinical or
bacteriologic response (IDSA Grade A-III)
⚬ should be combined with vancomycin in patients with CSF shunt infection caused by
staphylococci, especially if shunt cannot be removed (IDSA Grade A-III)
● vancomycin
⚬ CSF penetration may be decreased in absence of meningeal inflammation or with use of
dexamethasone 2
⚬ not recommended in patients with bacterial meningitis caused by isolates that are suscep-
tible to other agents (IDSA Grade E-II) due to reports of clinical failure
⚬ even in patients with meningitis caused by highly penicillin- and cephalosporin-resistant
strains, vancomycin should be combined with third-generation cephalosporin (IDSA Grade
A-III) and should not be used as single agent 1
⚬ consider intrathecal administration in patients not responding to parenteral administration
(IDSA Grade B-III) 1
⚬ maintain serum trough concentration about 15-20 mcg/mL (IDSA Grade B-III) 1

STUDY
● SUMMARY
addition of intraventricular gentamicin to IV gentamicin plus ampicillin may increase
mortality in neonates with gram-negative meningitis and ventriculitis DynaMed Level 2
RANDOMIZED TRIAL: Cochrane Database Syst Rev 2012 Jul 11;(7):CD004496
Details
⚬ based on Cochrane review of small randomized trial
 ⚬ systematic review of randomized or quasi-randomized trials comparing intraventricular an-
tibiotics with or without IV antibiotics vs. IV antibiotics only in neonates with bacterial
meningitis
⚬ review identified 1 randomized trial comparing intraventricular antibiotics (gentamicin) plus
IV antibiotics (ampicillin plus gentamicin) vs. IV antibiotics alone in 52 infants with meningi-
tis and ventriculitis
– cause of meningitis was gram-negative enteric bacilli in all infants
– all-cause mortality 42.9% with combination treatment vs. 12.5% with IV antibiotics only
(p = 0.034, NNH 3)
– no significant difference in duration of culture positivity of CSF
⚬ Reference - Cochrane Database Syst Rev 2012 Jul 11;(7):CD004496
Duration of Treatment

● duration of treatment based on pathogen, clinical presentation, and infection setting (such as
healthcare associated infections)

Table 6: IDSA Recommended Duration of Therapy*

Pathogen and/or Clinical Presentation Duration

Streptococcus pneumoniae 10-14 days

Neisseria meningitidis 7 days

Listeria monocytogenes ≥ 21 days

Streptococcus agalactiae (Group B Streptococcus) 14-21 days

Escherichia coli 21 days

Haemophilus influenzae 7 days

Pseudomonas aeruginosa 21 days

Staphylococcus aureus 14 days (methi-

cillin resistant)
 Pathogen and/or Clinical Presentation Duration

Healthcare-associated Infections

Coagulase-nega- No or minimal CSF pleocytosis, normal 10 days

tive staphylococ- CSF glucose, and few clinical
cus or symptoms/systemic features
Propionibacterium
acnes Significant CSF pleocytosis, CSF hypoglyc- 10-14 days
orrhachia, or clinical symptoms/systemic
features

Staphylococcus aureus 10-14 days

Gram-negative bacilli 10-14 days**

Patients with repeatedly positive CSF cultures on appropriate an- 10-14 days after
timicrobial therapy last positive
culture

Abbreviations: CSF, cerebral spinal fluid; IDSA, Infectious Diseases Society of America.

* Duration of therapy is not standardized and should be individualized based on treatment response.

** Some experts suggest treatment duration of 21 days.

Reference -

Clin Infect Dis 2011 Feb 1;52(3):e18, Clin Infect Dis 2004 Nov 1;39(9):1267, Clin Infect Dis 2017 Mar
15;64(6):e34.

⚬ short and long duration ceftriaxone may have similar efficacy in children with bacterial
meningitis

STUDY
⚬ SUMMARY
4-7 days of ceftriaxone may be as effective as 7-14 days in children with bacterial
meningitis DynaMed Level 2
RANDOMIZED TRIAL: Arch Dis Child 2009 Aug;94(8):607
Details
– based on systematic review of randomized trials with methodologic limitations
 – systematic review of 5 randomized trials with 426 children aged 3 weeks to 16 years
comparing 4 to 7-day course vs. 7 to 14-day course of ceftriaxone
– all trials lacked blinding and included mainly patients with uncomplicated bacterial
meningitis with either favorable initial prognosis and/or highly susceptible pathogens
– comparing short vs. long course of ceftriaxone, no significant differences in
● clinical success (84% vs. 81% in 5 trials with 383 patients)
● long-term neurologic complications (7% vs. 11% in 5 trials with 367 patients)
● long-term hearing impairment (12% vs. 19% in 4 trials with 241 patients)
● total adverse events (2 trials with 122 patients)
● secondary nosocomial infections (2 trials with 139 patients)
– Reference - Arch Dis Child 2009 Aug;94(8):607, commentary can be found in Evid Based
Med 2010 Feb;15(1):6

STUDY
⚬ SUMMARY
5 days of ceftriaxone may be as effective as 10 days in children with bacterial meningitis
DynaMed Level 2

RANDOMIZED TRIAL: Lancet 2011 May 28;377(9780):1837

Details
– based on randomized trial terminated early with unclear stopping rule
– 1,027 children aged 2 months to 12 years with bacterial meningitis received ceftriaxone
80-100 mg/kg/day for 5 days then randomized to ceftriaxone 80-100 mg/kg/day for 5
days vs. placebo and followed for 190 days
– all patients had culture-confirmed bacterial meningitis caused by S. pneumoniae, H. in-
fluenzae type B, or N. meningitidis
– trial terminated early after enrollment of 1,027 of planned 1,400 children due to no sig-
nificant differences between treatments
– comparing short course vs. long course of ceftriaxone
● meningitis-related mortality 2% vs. 1% (not significant)
● hearing loss in 21% vs. 21% (not significant)
● vision loss in 1% vs. 2% (not significant)
● neurological sequelae in 4% vs. 6% (not significant)
– no significant differences in bacteriological failure or relapse
– Reference - Lancet 2011 May 28;377(9780):1837, editorial can be found in Lancet 2011
May 28;377(9780):1809

Outpatient Antibiotic Therapy

● IDSA recommends antibiotics IV for duration of treatment course 1

● IDSA recommends that selected patients may be discharged to finish antibiotic therapy as
outpatient if (IDSA Grade A-III) 1
⚬ inpatient antibiotic therapy for ≥ 6 days
⚬ improving condition or clinical stability
– no fever for ≥ 24-48 hours prior to starting outpatient treatment
– no seizure activity, significant neurologic dysfunction, or focal findings
– ability to take fluids by mouth
⚬ discharge plan includes healthcare visits, lab monitoring, and emergency plan
⚬ adequate home resources
– access to home healthcare for antimicrobial administration
– daily availability of physician
– reliable access route and infusion device if needed
– patient and/or family compliance with plan
– safe environment with access to phone, utilities, refrigerator, and food
● see Approach to Rational Antibiotic Use in the Outpatient Setting
Corticosteroids

● dexamethasone may reduce associated cerebral edema, increased intracranial pressure, al-
tered cerebral blood flow, cerebral vasculitis, and neuronal injury by decreasing inflammatory
response, but does not reverse damage that occurred prior to treatment 1 ,3 ,4
● recommendations for administration of dexamethasone vary 1 ,4
⚬ Infectious Diseases Society of America (IDSA)
– recommends dexamethasone in suspected or confirmed H. influenzae type b meningitis
(IDSA Grade A-I)
– considers dexamethasone controversial in suspected or confirmed pneumococcal
meningitis (IDSA Grade C-II)
– do not give to infants or children who have already received antibiotic therapy; give dex-
amethasone 10-20 minutes before or with first antibiotic dose (IDSA Grade A-I)
– recommended in suspected or confirmed H. influenzae type b meningitis (IDSA Grade A-I)
and controversial in pneumococcal meningitis (IDSA Grade C-II)
– insufficient evidence to recommend adjunctive dexamethasone in neonates with bacte-
rial meningitis (IDSA Grade C-I)
– dosing: 0.15 mg/kg IV every 6 hours for 2-4 days
⚬ National Institute for Health and Care Excellence (NICE)
– recommends dexamethasone in infants and children > 3 months old with suspected or
confirmed bacterial meningitis if LP reveals any of the following
 ● frankly purulent CSF
● elevated CSF white blood cell count with protein concentration > 1 g/L
● CSF white blood cell count > 1,000/mcL
● bacteria on Gram stain
– give within 4 hours of starting antibiotics and do not start if > 12 hours
– dosing: 0.15 mg/kg (maximum dose 10 mg) IV 4 times daily for 4 days

STUDY
● SUMMARY
adjuvant dexamethasone may reduce severe hearing loss but not mortality in children with
acute bacterial meningitis in high-income countries DynaMed Level 2

COCHRANE REVIEW: Cochrane Database Syst Rev 2015 Sep 12;(9):CD004405

Details
⚬ based on Cochrane review of trials with methodologic limitations
⚬ systematic review of 25 randomized trials comparing adjuvant corticosteroids vs. placebo
in 4,121 adults or children with acute bacterial meningitis
⚬ 18 trials enrolled children < 16 years, most evaluated dexamethasone
⚬ dexamethasone dose ranged from 0.4 to 1.5 mg/kg/day and duration ranged from 2 to 4
days
⚬ all trials included in analysis of high-income countries had ≥ 1 limitation including
– unclear allocation concealment
– no intention-to-treat analysis
⚬ for outcome of severe hearing loss in patients < 16 years old
– adjuvant steroids associated with decreased risk in analysis of 11 trials with 1,144 chil-
dren in high-income countries
● risk ratio (RR) 0.52 (95% CI 0.35-0.78)
● NNT 14-42 with severe hearing loss in 11% of placebo group
– no significant difference in risk in analysis of 3 trials with 387 children in low-income
countries
– in analysis by causative organism
● adjuvant steroids associated with decreased risk of severe hearing loss (RR 0.34, 95%
CI 0.2-0.59) in subgroup with H. influenzae infection (756 children from 10 trials)
● no significant difference in subgroup with non-H. influenzae infection (860 children
from 13 trials)
⚬ no significant difference between groups in mortality in analysis of 18 trials with 2,511 chil-
dren (results similar in high- and low-income countries)
⚬ Reference - Cochrane Database Syst Rev 2015 Sep 12;(9):CD004405 (review updated 2018
Nov 7)
STUDY
● SUMMARY
insufficient evidence to determine whether adjuvant corticosteroids reduce mortality or
hearing loss in neonates with bacterial meningitis
COCHRANE REVIEW: Cochrane Database Syst Rev 2015 Nov 11;(11):CD010435
Details
⚬ based on Cochrane review
⚬ systematic review of 2 randomized or quasi-randomized trials comparing adjuvant corticos-
teroids vs. placebo or no adjuvant treatment in 132 neonates with bacterial meningitis
⚬ comparing dexamethasone 0.15 mg/kg every 6 hours for 2 days plus ceftriaxone and
Amikacin (meropenem for severely ill patients) (doses not stated) vs. antibiotics alone in 1
randomized trial with 80 neonates in India
– mortality prior to hospital discharge 12.5% vs. 40% (p < 0.05, NNT 4)
– hearing loss at 4-10 weeks after discharge in 17% vs. 42% (p = 0.039, NNT 4)
⚬ comparing dexamethasone 0.15 mg/kg every 6 hours for 4 days plus cefotaxime (dose not
stated) vs. cefotaxime alone in 1 quasi-randomized trial with 52 neonates in Jordan
– mortality prior to hospital discharge 22.2% vs. 28% (not significant)
– hearing loss at age 2 years in 10% vs. 5.6% (not significant)
⚬ Reference - Cochrane Database Syst Rev 2015 Nov 11;(11):CD010435

DYNAMED COMMENTARY

The evidence for adjuvant corticosteroids is insufficient to draw a conclusion as the 2 included trials
evaluated different durations of treatment (yielding different results for mortality) and assessed
hearing loss at different times posttreatment without subgroup analysis by specific bacteria.

Other Adjuvant Medication

STUDY
● SUMMARY
addition of acetaminophen to standard treatment may not decrease mortality and may in-
crease risk of neurological sequelae other than hearing loss in children with acute bacterial
meningitis DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2021 Nov 23;11:CD013437
Details
⚬ based on Cochrane review of trials with methodologic limitations
⚬ systematic review of 8 randomized trials evaluating noncorticosteroid adjuvant therapies in
1,425 children and adults with acute bacterial meningitis
 ⚬ noncorticosteroid adjuvant therapies included acetaminophen, immunoglobulins, heparin,
pentoxifylline, and combination of succinic acid, inosine, nicotinamide, and riboflavin
mononucleotide
⚬ 3 trials compared acetaminophen vs. placebo in 1,274 children ≥ 2 months old receiving
standard treatment; all trials had unclear blinding of outcome assessors
⚬ acetaminophen was given rectally or orally at initial loading dose of 30-35 mg/kg followed
by 20 mg/kg every 6 hours, with duration ranging from 42 hours to 4 days
⚬ neurological sequelae other than hearing loss was defined as health consequences of in-
fection that involve central nervous system including seizure disorder, focal neurological
deficit, ataxia, paresis, or psychomotor impairment
⚬ no significant differences in
– mortality (risk ratio [RR] 0.94, 95% CI 0.81-1.09) in analysis of 3 trials with 1,274 children
– any hearing loss (≥ 40 decibels [dB]) or severe hearing loss (≥ 60 dB) in analyses of 2 tri-
als with 901 children
⚬ acetaminophen plus standard treatment associated with increased risk of neurological se-
quelae other than hearing loss
– short-term (up to 6 weeks after hospital discharge) in analysis of 2 trials with 1,096
children
● RR 1.99 (95% CI 1.4-2.81)
● NNH 7-31 with neurological sequelae other than hearing loss in 8% of standard treat-
ment alone group
– long-term (between 6 weeks after hospital discharge and last reported time point) in
analysis of 2 trials with 901 children
● RR 2.32 (95% CI 1.34-4.04)
● NNH 8-77 with neurological sequelae other than hearing loss in 3.8% of standard
treatment alone group
⚬ Reference - Cochrane Database Syst Rev 2021 Nov 23;11:CD013437

STUDY
● SUMMARY
addition of glycerol to ceftriaxone might reduce risk of neurologic disability and hearing
loss but not mortality in patients with acute bacterial meningitis DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2018 Feb 6;(2):CD008806
Details
⚬ based on Cochrane review with statistical limitations and without significant difference in
high-quality trial
⚬ systematic review of 5 randomized trials evaluating addition of glycerol to ceftriaxone in
1,451 patients with acute bacterial meningitis
 ⚬ 4 trials included children < 16 years old and 1 trial included adults and adolescents > 14
years old
⚬ statistical limitations include confidence interval that cannot exclude differences that may
be clinically important for mortality and heterogeneity for risk of neurological disability
⚬ comparing glycerol with or without steroids to placebo
– glycerol with or without steroids associated with
● nonsignificant decrease in risk of neurological disability (risk ratio [RR] 0.73, 95% CI
0.53-1) in analysis of 5 trials with 1,270 patients
● reduced risk of hearing impairment in analysis of 5 trials with 922 patients
⚬ RR 0.64 (95% CI 0.44-0.93)
⚬ NNT 14-110 with hearing loss in 13% of placebo group
⚬ no significant difference in risk of hearing impairment in 1 high-quality trial
– no significant differences in
● mortality (RR 1.08, 95% CI 0.9-1.3) in analysis of 5 trials with 1,272 patients
● risk of seizures in analysis of 4 trials with 1,090 patients, results limited by significant
heterogeneity
⚬ Reference - Cochrane Database Syst Rev 2018 Feb 6;(2):CD008806

STUDY
● SUMMARY
glycerol 1.5 g/kg orally every 6 hours for 48 hours reduces risk of severe neurologic seque-
lae but not hearing impairment DynaMed Level 1

RANDOMIZED TRIAL: Clin Infect Dis 2007 Nov 15;45(10):1277

Details
⚬ based on randomized trial
⚬ 654 children aged 2 months to 16 years with bacterial meningitis in 6 Latin American coun-
tries were treated with ceftriaxone 80-100 mg/kg IV once daily for 7-10 days and random-
ized to treatment every 6 hours for 48 hours with 1 of 4 adjuvant regimens
– IV dexamethasone 0.15 mg/kg plus oral placebo
– IV dexamethasone 0.15 mg/kg plus oral 85% glycerol 1.5 g/kg (1.5 mL/kg)
– IV placebo plus oral glycerol 1.5 g/kg
– IV placebo plus oral placebo
⚬ severe neurologic sequelae (defined as blindness, quadriparesis or quadriplegia, hydro-
cephalus requiring a shunt, or severe psychomotor retardation) in
– 14% with placebo
– 5% with glycerol (p = 0.01, NNT 12)
– 6% with glycerol plus dexamethasone (p = 0.033, NNT 13)
– 7% with dexamethasone (p = 0.072)
 ⚬ no significant effect on death or deafness seen with any adjuvant medication
⚬ Reference - Clin Infect Dis 2007 Nov 15;45(10):1277, editorial can be found in Clin Infect Dis
2007 Nov 15;45(10):1287
● complications are treated with medications used in patients without bacterial meningitis
⚬ vasoactive agents (such as dopamine or dobutamine) as needed to maintain normal blood
pressure
⚬ antipyretics, high-dose barbiturate therapy, or mannitol may be used to reduce increased
intracranial pressure (Pediatr Clin North Am 2005 Jun;52(3):795)
⚬ antiseizure medications (such as benzodiazepines, phenytoin, or phenobarbital) to control
or prevent seizures
⚬ Reference -Pediatr Clin North Am 2005 Jun;52(3):795

Surgery and Procedures

● patient may require surgical management of complications and associated conditions
including
⚬ drainage of
– persisting sinus abscess
– mastoiditis
– brain abscess
⚬ repair of breach causing persistent cerebrospinal fluid otorrhea or rhinorrhea (some
breaches may heal spontaneously)
⚬ tympanocentesis for otitis media
⚬ treatment of elevated intracranial pressure
⚬ removal of dermal sinus tract if causing recurrent meningitis
⚬ References - Med Mal Infect 2009 Jun;39(6):356, J Pediatr Neurosci 2012 Jan;7(1):47

Management of Cerebrospinal Fluid Shunt Infections

● Infectious Diseases Society of America (IDSA) 2017 clinical practice guideline for healthcare-as-
sociated ventriculitis and meningitis
⚬ recommendations for treatment of children who develop bacterial meningitis directly from
shunt (not by hematogenous dissemination)
– give appropriate antimicrobial therapy for 10-14 days, depending on the organism (IDSA
Strong recommendation, Low-quality evidence)
– shunt removal and placement of an external ventricular drain
● remove all components of an infected cerebrospinal fluid (CSF) shunt and replace
with an external ventricular drain (combined with IV antimicrobial therapy) (IDSA
Strong recommendation, Moderate-quality evidence)
 ● remove an infected CSF drain (IDSA Strong recommendation, Moderate-quality
evidence)
● external drainage catheter allows monitoring of CSF and continued treatment of hy-
drocephalus until infection clears
– consider intraventricular antimicrobial therapy for children with poor response to sys-
temic antimicrobial therapy alone (IDSA Strong recommendation, Low-quality evidence)
● clamp drain for 15-60 minutes after antimicrobial therapy administered if given via a
ventricular drain (IDSA Strong recommendation, Low-quality evidence)
● adjust dosages and intervals of intraventricular antimicrobial therapy based on
⚬ achieving cerebrospinal fluid antimicrobial concentrations of 10-20 times the mini-
mal inhibitory concentration (MIC) of causative microorganism (IDSA Strong recom-
mendation, Low-quality evidence)
⚬ ventricular size (IDSA Strong recommendation, Low-quality evidence)
⚬ daily output from ventricular drain (IDSA Strong recommendation, Low-quality
evidence)
– monitoring response to treatment
● children should be monitored based on clinical parameters (IDSA Strong recommen-
dation, Low-quality evidence)
● monitor CSF cultures to ensure that they become negative (IDSA Strong recommenda-
tion, Low-quality evidence)
● perform additional CSF analysis in children with no definitive clinical improvement to
ensure improvement of CSF parameters and negative cultures (IDSA Strong recom-
mendation, Low-quality evidence)
● do not monitor daily CSF cultures and analysis if not using external CSF drains for
treatment of shunt infection, unless clinically indicated (IDSA Strong recommendation,
Low-quality evidence)
⚬ Reference - Clin Infect Dis 2017 Feb 14 early online
● see also Central Nervous System Device Infections

Consultation and Referral

● referral may be required to
⚬ ear, nose, and throat specialist for conditions that may require surgical intervention
including
– tympanocentesis for otitis media or acute mastoiditis
– surgery for acute mastoiditis
– drainage for cases of persisting sinus abscess or prolonged sepsis
– surgery for persistent cerebrospinal fluid otorrhea or rhinorrhea
 ⚬ neurosurgeon for intracerebral complications or evaluation of possible ventricular shunt
infection
● consult infectious disease/immunologist for children with
⚬ prior serious infection in patient or patient's siblings
⚬ recurrent meningitis
⚬ meningitis with resistant organisms
⚬ adequate immunization and meningitis due to serotype included in vaccine
⚬ infection due to uncommon pathogens (for example, Neisseria meningitidis serotypes Y,
W135, X, or Z)
● neurosurgical consult may also be needed if recurrent bacterial meningitis related to dermal
sinus tract associated with dermoid or epidermoid cyst
● References - Med Mal Infect 2009 Jun;39(6):356, J Pediatr Neurosci 2012 Jan;7(1):47

Other Management

● closely monitor respiratory rate, heart rate, blood pressure, temperature, and consciousness
level hourly (or more frequently) for 4-6 hours after presentation to emergency room in pa-
tients with unexplained petechial rash and fever (or history of fever) but no high-risk clinical
manifestations 4
● advise parents or caregivers of children assessed as being at low risk of meningococcal
meningitis and discharged after initial observation to return to hospital if patient appears ill 4
● National Institute for Health and Care Excellence (NICE) recommends monitoring and correct-
ing metabolic disturbances in infants and children with suspected bacterial meningitis and
meningococcal septicemia, including 4
⚬ electrolyte abnormalities, especially hyponatremia and hypokalemia
⚬ hypoglycemia
⚬ acidosis
⚬ hypocalcemia
⚬ hypomagnesemia
⚬ coagulopathy
⚬ anemia
● NICE recommendations for respiratory support in infants and children with suspected bacte-
rial meningitis 4
⚬ in self-ventilating children with respiratory distress, give 15-L face mask oxygen via a reser-
voir rebreathing mask
⚬ if there is loss of airway patency, start airway-opening maneuvers and bag-valve mask ven-
tilation in preparation for tracheal intubation
 ⚬ tracheal intubation should be performed by a healthcare provider with expertise in pedi-
atric airway management
⚬ children with suspected or confirmed bacterial meningitis are at risk of sudden deteriora-
tion during intubation including aspiration, pulmonary edema, or worsening shock
⚬ children should be on strict no food or drink-by-mouth precautions
⚬ facilities should be able to readily administer fluid boluses and/or appropriate vasoactive
drugs
⚬ facilities should have access to a healthcare provider experienced in management of criti-
cally ill children
⚬ indications for tracheal intubation and mechanical ventilation include
– threatened or actual loss of airway patency (including loss of gag reflex)
– clinical observation of increasing work of breathing
– signs of respiratory failure such as
● impaired mental status
● continuing shock following infusion of 40 mL/kg of resuscitation fluid
● signs of elevated intracranial pressure
– need for any form of assisted ventilation, such as bag-valve mask ventilation
– hypoventilation or apnea
● see also Elevated Intracranial Pressure in Adults

Follow-up

● National Institute for Health and Care Excellence recommendations for follow-up before dis-
charge 4
⚬ discuss with caregivers
– access to further care immediately after discharge and future care
– potential long-term effects of their condition and likely patterns of recovery
– contact details of patient support organizations such as meningitis charities that can of-
fer support
⚬ perform formal audiological assessment as soon as possible, preferably before discharge,
and within 4 weeks of being able to be tested
⚬ consider urgent assessment for cochlear implants for children with a severe or profound
deafness as soon as they are fit to undergo testing
⚬ at 4-6 weeks after discharge, pediatrician should review results of hearing test and discuss
possible other associated morbidities including
– orthopedic complications due to damaged bones and joints
– skin complications
– psychosocial problems
 – neurological and developmental problems
– renal failure
● United Kingdom Health Protection Agency (HPA) recommendations
⚬ measure anti-Haemophilus influenzae type B (Hib) antibodies in fully vaccinated index cases
< 10 years old around 4 weeks after infection and give additional dose of a Hib-containing
vaccine given if antibody levels are < 1 mg/mL (HPA Recommendation)
⚬ if not possible to measure anti-Hib antibody levels or there is concern child may be lost to
follow-up, give additional dose of a Hib-containing vaccine to index cases > 12 months old
and < 10 years old, irrespective of Hib vaccination status
⚬ children with Hib vaccine failure should also have total immunoglobulin levels and sub-
classes measured, and be carefully assessed for evidence of an immune deficiency
⚬ Reference - National Health Services England 2013 Jul PDF

STUDY
● SUMMARY
otoacoustic emissions before hospital discharge may be highly sensitive as screening test
for hearing impairment in children with bacterial meningitis DynaMed Level 2

DIAGNOSTIC COHORT STUDY: Pediatrics 1998 Dec;102(6):1364

Details
⚬ based on diagnostic cohort study without blinding of otoacoustic emissions test result from
auditory brainstem response (ABR) test result
⚬ 124 children aged 6 weeks to 15 years with bacterial meningitis had audiologic assessment
prior to hospital discharge (otoacoustic emissions and ABR, otoscopy, and tympanometry)
⚬ ABR used as reference standard (hearing loss defined as ABR threshold ≥ 30 decibels [dB])
⚬ 1 investigator performed and analyzed all tests
⚬ among 110 children who had both otoacoustic emissions and ABR
– 7 (6.3%) had ABR threshold ≥ 30 dB, including 2 children with sensorineural hearing loss
and 5 with conductive hearing loss
– otoacoustic emissions predicted hearing loss with 100% sensitivity, 91% specificity, 44%
positive predictive value, and 100% negative predictive value
⚬ Reference - Pediatrics 1998 Dec;102(6):1364

Complications and Prognosis

Complications
● sepsis 4
● complications may develop before diagnosis or after several days of treatment, including
⚬ shock 4
 – can be associated with disseminated intravascular coagulation (DIC)(Pediatr Clin North
Am. 2005 Jun;52(3):795-810)

⚬ gangrene of distal extremities can occur in patients with fulminant hemorrhagic meningo-
coccal meningitis (CMAJ 2010 Jan 12;182(1):E18)
● syndrome of inappropriate antidiuretic hormone secretion (SIADH) (Pediatr Clin North Am.
2005 Jun;52(3):795-810)
● neurological sequelae 2 ,4
⚬ early or late focal neurologic findings may occur in 10%-15% of patients and may include
– hemiparesis
– quadriparesis
– facial palsy
– visual field defects
– Reference - Lancet 2003 Jun 21;361(9375):2139
⚬ seizures in up to one-third of children with bacterial meningitis
– most episodes are generalized
– focal seizures have worse prognosis
– seizures that are difficult to control or persist > 4 days after diagnosis and seizures that
arise for first time late in hospital course associated with neurologic sequelae

STUDY
⚬ SUMMARY
intracranial hemorrhage may be more common and seizures less common in neonates
with bacterial meningitis and low birth weight
COHORT STUDY: Arq Neuropsiquiatr 2007 Dec;65(4B):1149
Details
– based on retrospective cohort study
– 87 neonates ≤ 29 days old admitted to neonatal intensive care unit with bacterial menin-
gitis were assessed for outcome based on birth weight (< 2,500 g vs. ≥ 2,500 g)
– comparing infants with birth weight < 2,500 g vs. ≥ 2,500 g
● seizures in 11.8% vs. 41.5% (p = 0.003)
● intracranial hemorrhage in 26.5% vs. 9.6% (p = 0.035)
● no significant differences in other complications
 – Reference - Arq Neuropsiquiatr 2007 Dec;65(4B):1149
● hydrocephalus occasionally seen in children with suboptimal or delayed treatment, more
common in younger infants (Pediatr Clin North Am. 2005 Jun;52(3):795-810)
● subdural effusion in > 30%
⚬ more common with Haemophilus influenzae and pneumococcal meningitis (compared to
meningococcal)
⚬ more common in children < 2 years old
⚬ usually resolves spontaneously without permanent neurologic abnormalities
⚬ Reference - Pediatr Clin North Am. 2005 Jun;52(3):795-810
● brain abscess may rarely occur, especially in neonates with Citrobacter diversus or Proteus
species (Pediatr Clin North Am. 2005 Jun;52(3):795-810)
● ventriculitis (inflammation of ventricular system, may be associated with ventricular dilatation
and formation of intraventricular adhesions and septae) (Pediatr Radiol 2008 Feb;38(2):129)
● elevated intracranial pressure 4
● brain herniation associated with diagnostic lumbar puncture in patients with elevated in-
tracranial pressure 1
● joint involvement
⚬ direct invasion of joint by microorganism, usually H. influenzae type b (early occurrence
typical)
⚬ immune complex-mediated event affecting several joints, most frequently seen with
meningococcal infections (usually presents after fourth day of treatment)
⚬ Reference - Lancet 2003 Jun 21;361(9375):2139
● renal failure 4

Prognosis

Mortality

● reported overall mortality 14.8% 5

STUDY
● SUMMARY
overall mortality 8% in infants < 90 days old in United Kingdom and Ireland from 2010 to
2011
POPULATION-BASED SURVEILLANCE: Clin Infect Dis 2014 Nov 15;59(10):e150
Details
⚬ based on population-based surveillance of bacterial meningitis in infants < 90 days old in
United Kingdom and Ireland from July 2010 to July 2011
 ⚬ overall mortality 8%
⚬ pneumococcal meningitis mortality 19% vs. group B Streptococcus meningitis mortality 5%
(p = 0.04)
⚬ mortality 17% in preterm infants vs. 4% in term infants (p = 0.0002)
⚬ Reference - Clin Infect Dis 2014 Nov 15;59(10):e150

STUDY
● SUMMARY
birth weight may not affect mortality in neonates with bacterial meningitis DynaMed Level 2

COHORT STUDY: Arq Neuropsiquiatr 2007 Dec;65(4B):1149

Details
⚬ based on retrospective cohort study
⚬ 87 neonates ≤ 29 days old admitted to neonatal intensive care unit with bacterial meningi-
tis were assessed for outcome based on birth weight (< 2,500 g vs. ≥ 2,500 g)
⚬ death in 11.5% overall (10 infants) not significantly associated with birth weight
⚬ Reference - Arq Neuropsiquiatr 2007 Dec;65(4B):1149

STUDY
● SUMMARY
meningitis reported to account for 8% of in-hospital mortality occurring in children in
Angola
CROSS-SECTIONAL STUDY: Trop Doct 2008 Jan;38(1):66
Details
⚬ based on cross-sectional study of 1,322 randomly selected children hospitalized in Angola
from December 2004 to May 2005
⚬ death in 18% (237 children aged 0-11 years)
⚬ 8% of deaths (19 children) were due to meningitis
⚬ Reference - Trop Doct 2008 Jan;38(1):66

● 13% overall case-fatality rate in retrospective cohort study of 68 children < 18 years old with
laboratory-confirmed pneumococcal meningitis in Utah from 1997 to 2010 (Pediatrics 2013
Sep;132(3):421)

STUDY
● SUMMARY
mortality risk may vary by serotype in bacteremic patients with invasive pneumococcal
disease
SYSTEMATIC REVIEW: Clin Infect Dis 2010 Sep 15;51(6):692
Details
⚬ based on systematic review
⚬ meta-analysis of 9 studies of serotype-specific disease outcomes in 8,253 patients with
pneumococcal pneumonia and meningitis
 ⚬ relative risk of mortality in patients with bacteremic pneumonia (referent was serotype 14)
– increased risk of mortality in patients infected with
● serotype 3 (risk ratio [RR] 1.9, 95% CI 1.54-2.35)
● serotype 6A (RR 1.39, 95% CI 1.02-1.91)
● serotype 6B (RR 1.59, 95% CI 1.2-2.11)
● serotype 9N (RR 1.53, 95% CI 1.16-2.02)
● serotype 19F (RR 2.22, 95% CI 1.71-2.88)
– reduced risk of mortality in patients infected with
● serotype 1 (RR 0.48, 95% CI 0.37-0.63)
● serotype 7F (RR 0.58, 95% CI 0.43-0.79)
● serotype 8 (RR 0.68, 95% CI 0.5-0.94)
⚬ no significant difference in risk of mortality by serotype among patients with meningitis
⚬ Reference - Clin Infect Dis 2010 Sep 15;51(6):692
Long-term Sequelae

● hearing impairment common in children after bacterial meningitis and frequency depends on
organism 2 , 5
⚬ 22%-35% after Streptococcus pneumoniae meningitis
⚬ 5%-10% after Haemophilus influenzae or Neisseria meningitidis meningitis

STUDY
⚬ SUMMARY
hearing loss in 14%-31% of children with meningitis
COHORT STUDY: Arch Otolaryngol Head Neck Surg 1999 May;125(5):509
COHORT STUDY: Arch Otolaryngol Head Neck Surg 2006 Sep;132(9):941
Details
– based on 2 retrospective cohort studies
– 432 children with meningitis were evaluated
● 13.7% developed hearing loss, including 46 children with stable sensorineural hearing
loss and 13 children with progressive or fluctuating hearing loss
● fluctuation of hearing function often required > 1 year to stabilize
● significant risk factors for hearing loss
⚬ increased intracranial pressure noted on computed tomography
⚬ male sex
⚬ low glucose levels in cerebrospinal fluid
⚬ S. pneumoniae as causative organism
⚬ nuchal rigidity
● Reference - Arch Otolaryngol Head Neck Surg 1999 May;125(5):509
 – 171 children with bacterial meningitis in tertiary pediatric hospital were evaluated
● 134 patients with audiologic testing during initial hospitalization were analyzed
● 41 (30.6%) had at least unilateral mild sensorineural hearing loss
● significant predictors for hearing loss
⚬ S. pneumoniae meningitis (35.9% rate compared to 23.9% with N. meningitidis
meningitis)
⚬ length of hospitalization
⚬ development of seizures
⚬ elevated cerebrospinal fluid protein
⚬ decreased cerebrospinal fluid glucose
● Reference - Arch Otolaryngol Head Neck Surg 2006 Sep;132(9):941

STUDY
⚬ SUMMARY
hearing loss in 7% of school-aged children surviving non-H. influenzae type B bacterial
meningitis
COHORT STUDY: Pediatrics 2003 Nov;112(5):1049
Details
– based on cohort study
– 628 school-aged children who survived non-H. influenzae type B bacterial meningitis
were evaluated
– 7% had sensorineural hearing loss (> 25 decibels [dB])
– all cases of hearing loss occurred in subset of children with ≥ 1 risk factor
– risk factors were duration of symptoms > 2 days before admission, absence of pe-
techiae, cerebrospinal fluid glucose level ≤ 0.6 mmol/L, S. pneumoniae infection, and
ataxia
– Reference - Pediatrics 2003 Nov;112(5):1049

● cognitive impairment and developmental delay common after bacterial meningitis 2 , 5

STUDY
⚬ SUMMARY
neuropsychological and behavioral complications can persist for at least 12 years
COHORT STUDY: Arch Dis Child 2000 Aug;83(2):111
Details
– based on prospective cohort study
– 109 children aged 3 months to 14 years who survived bacterial meningitis and had com-
pleted a survey 7 years later, evaluated at 12 years, and compared with 96 original
controls
 – children with history of meningitis had higher risk for any disability (odds ratio 4.7, 95%
CI 2.2-9.6)
– children with acute neurological complications had higher risk for chronic sequelae
– Reference - Arch Dis Child 2000 Aug;83(2):111

STUDY
⚬ SUMMARY
bacterial meningitis in early childhood may increase risk of low IQ
SYSTEMATIC REVIEW: PLoS One 2017;12(8):e0175024
Details
– based on systematic review of observational studies
– systematic review of 26 case-control and 13 cohort studies evaluating IQ and develop-
ment in patients with meningitis
● 34 studies evaluated IQ and 12 studies evaluated developmental delay
● most studies evaluated effect of meningitis in early childhood, only 1 study evaluated
meningitis in adolescence and 1 in adults
● 36 studies evaluated different causes of bacterial meningitis and 3 evaluated viral
meningitis
– compared to controls without history of meningitis, bacterial meningitis associated with
● increased risk of having IQ < 70 points (relative risk 4.99, 95% CI 3.17-7.86) in analysis
of 10 studies
● lower IQ (weighted mean difference 6.08 points, 95% CI 2-10 points) in analysis of 5
studies, results limited by significant heterogeneity
– similar results in analyses of meningitis caused by Haemophilus influenzae b in 6 studies,
Neisseria meningitides in 4 studies, and Streptococcus pneumoniae in 1 study
– Reference - PLoS One 2017;12(8):e0175024

STUDY
⚬ SUMMARY
bacterial meningitis during childhood associated with lower educational achievement
and economic self-sufficiency at age 35 years
COHORT STUDY: JAMA 2013 Apr 24;309(16):1714
Details
– based on retrospective cohort study
– 2,784 patients aged 35 years diagnosed with meningococcal, pneumococcal, or H. in-
fluenzae meningitis at < 12 years old were compared to 11,136 matched controls in
Denmark
– 48% of patients had meningococcal meningitis, 16% of patients had pneumococcal
meningitis, and 36% of patients had H. influenzae meningitis
– comparing patients with meningococcal meningitis vs. controls
 ● high school education in 41.5% vs. 52.5% (p < 0.05)
● higher education in 29.3% vs. 37.2% (p < 0.05)
● economic self-sufficiency in 90.3% vs. 94.1% (p < 0.05)
● disability pension in 3.7% vs. 2.3% (not significant)
– comparing patients with pneumococcal meningitis vs. controls
● high school education in 42.6% vs. 52.8% (p < 0.05)
● higher education in 28.1% vs. 37% (p < 0.05)
● economic self-sufficiency in 84% vs. 94.6% (p < 0.05)
● disability pension in 10% vs. 1.3% (p < 0.05)
– comparing patients with H. influenzae meningitis vs. controls
● high school education in 47.7% vs. 53.2% (p < 0.05)
● higher education in 33.5% vs. 40% (p < 0.05)
● economic self-sufficiency in 90.6% vs. 94.9% (p < 0.05)
● disability pension in 6.2% vs. 2.5% (p < 0.05)
– no significant differences in higher education, economic self-sufficiency, or disability
pension comparing siblings of patients with meningitis to siblings of matched controls
– Reference - JAMA 2013 Apr 24;309(16):1714

STUDY
⚬ SUMMARY
bacterial meningitis in infancy associated with poor academic performance
COHORT STUDY: Arch Dis Child 2007 Nov;92(11):959
Details
– based on cohort study
– 461 teenagers who had bacterial meningitis in infancy were compared to 289 matched
controls in England and Wales
– comparing teenagers with bacterial meningitis in infancy vs. controls
● 7.8% vs. 0% were in special schools
● 25.4% vs. 6.6% did not pass any General Certificate of Secondary Education exams
(school-leaving exams) (p < 0.05)
● 47.8% vs. 25.4% failed to achieve national educational standard of 5 passes at Grade
C (p < 0.05)
– Reference - Arch Dis Child 2007 Nov;92(11):959, editorial can be found in Arch Dis Child
2007 Nov;92(11):945

STUDY
● SUMMARY
meningitis associated with long-term sequelae in 42% of neonates
SYSTEMATIC REVIEW: Lancet 2012 Feb 4;379(9814):445
 Details
⚬ based on systematic review of 153 studies evaluating long-term sequelae after intrauterine
and neonatal insults in 22,161 neonates
⚬ 11 studies evaluated long-term sequelae after meningitis in 501 neonates
⚬ meningitis associated with long-term sequelae in 42%
– impaired cognition, general developmental delay, or learning difficulties in 100%
– cerebral palsy in 21%
– deaf or hearing loss in 12%
– impaired vision or blind in 40%
– epilepsy in 11%
⚬ Reference - Lancet 2012 Feb 4;379(9814):445, editorial can be found in Lancet 2012 Feb
4;379(9814):392, commentary can be found in Evid Based Med 2013 Feb;18(1):37

STUDY
● SUMMARY
bacterial meningitis associated with neuropsychological sequelae and mortality in African
children
SYSTEMATIC REVIEW: BMC Med 2009 Sep 14;7:47
Details
⚬ based on systematic review
⚬ 37 observational studies representing 21 African countries included 6,029 children aged 1
month to 15 years with laboratory-confirmed bacterial meningitis
⚬ 10 studies conducted during a meningitis epidemic

In-hospital Complication Rate

Neuropsychological Median Case Fatality

Sequelae Ratio

Streptococcus pneumoniae 25% 35%

Haemophilus influenzae 25% 25%

type b

Neisseria meningitidis 7% 4%

⚬ patients surviving initial hospitalization had follow-up ranging from 3 to 60 months in 10

studies
– 0%-18% mortality
 – 3%-47% had neuropsychological sequelae
⚬ Reference - BMC Med 2009 Sep 14;7:47

STUDY
● SUMMARY
serious neurologic sequelae appear common in survivors of childhood pneumococcal
meningitis
COHORT STUDY: Pediatrics 2013 Sep;132(3):421
Details
⚬ based on retrospective cohort study
⚬ 68 children < 18 years old with laboratory-confirmed pneumococcal meningitis in Utah,
United States from 1997 to 2010
⚬ 13% (9 children) died
⚬ neurologic outcomes in 59 survivors at median 3-year follow-up
– neurologic sequelae in 63%
– most common or serious neurologic sequelae included
● severe developmental delay in 39%
● persistent seizures at 1 year in 32%
● sensorineural hearing loss in 29%
● quadriplegia in 12%
● cortical blindness in 12%
⚬ Reference - Pediatrics 2013 Sep;132(3):421

STUDY
● SUMMARY
long-term sequelae of childhood bacterial meningitis include behavioral and/or intellec-
tual disorders, hearing changes, and neurologic deficits
SYSTEMATIC REVIEW: Pediatr Infect Dis J 2011 Jan;30(1):3
Details
⚬ based on systematic review
⚬ systematic review of 24 studies evaluating long-term (≥ 5-year follow-up) sequelae in 1,433
survivors of childhood bacterial meningitis
⚬ 49.2% had 1 or more long-term sequelae
⚬ reported sequelae included
– behavioral and/or intellectual disorders (45%)
– hearing changes (6.7%)
– gross neurologic deficits (14.3%)
⚬ Reference - Pediatr Infect Dis J 2011 Jan;30(1):3

STUDY
● SUMMARY
meningitis during infancy associated with significant persistent morbidity
COHORT STUDY: BMJ 2001 Sep 8;323(7312):533
Details
⚬ based on prospective cohort study
⚬ 1,717 children with meningitis in first year of life and 1,485 controls surveyed at 5 years
⚬ 92% vs. 94% follow-up
⚬ 1.8% mortality in meningitis cases within 5 years
⚬ comparing meningitis cases vs. controls (all results significant at p < 0.001)
– learning difficulties in 7.5% vs. 1.1%
– neuromotor disabilities in 8.1% vs. 0.9%
– seizure disorders in 7.3% vs. 2.7%
– hearing problems in 25.8% vs. 13.7%
– ocular or visual disorders in 13.7% vs. 3.9%
– speech and/or language problems in 15.6% vs. 4.5%
– behavioral problems in 11.9% vs. 3.3%
– severe neuromotor disabilities in 5.3% vs. 0.1%
– severe disability in 5.8% vs. 0.07%
– moderate disability in 9.8% vs. 1.4%
– mild disorder in 29.1% vs. 19.8%
⚬ Reference - BMJ 2001 Sep 8;323(7312):533, editorial can be found in BMJ 2001 Sep
8;323(7312):523, commentary can be found in ACP J Club 2002 Mar-Apr;136(2):71, Evid
Based Nurs 2002 Apr;5(2):59

Prognostic Factors

● risk factors for mortality and morbidity include 1 ,2 ,3 , 5

⚬ age 0-28 days
⚬ living in low-income country
⚬ gram-negative bacilli
⚬ Streptococcus pneumoniae
⚬ antimicrobial-resistant organism
⚬ incomplete information about pathogen
⚬ increased illness severity on presentation (for example, low Glasgow Coma Score or use of
inotropes)
⚬ low cerebrospinal fluid (CSF) white blood cell count with positive Gram stain
⚬ delayed administration of antimicrobial therapy
⚬ delayed CSF sterilization (> 24 hours after initiation of antimicrobial therapy) is risk factor
for subsequent neurologic sequelae
⚬ seizures associated with poorer prognosis, including
 – seizures lasting > 4 days after diagnosis
– seizures with first occurrence late in course of disease
– focal seizures

STUDY
● SUMMARY
Glasgow Coma Score on admission may be independent predictor of outcome in infants
and children with bacterial meningitis DynaMed Level 2

RANDOMIZED TRIAL: Clin Infect Dis 2008 Apr 15;46(8):1248

Details
⚬ based on post hoc analysis of randomized trial
⚬ 654 children aged 2 months to 16 years with bacterial meningitis in 6 Latin American coun-
tries enrolled in randomized trial evaluating adjuvant treatment with glycerol, dexametha-
sone, both, or placebo were assessed for findings at time of hospital admission
⚬ outcome measures were
– death
– death or severe neurologic sequelae (defined as blindness, quadriplegia, hydrocephalus
requiring shunt, or severe psychomotor retardation)
– death or any neurologic sequelae (defined as hemiparesis, monoparesis, paraparesis,
moderate psychomotor retardation, or ataxia)
⚬ only independent predictor of all 3 outcomes was Glasgow Coma Score

Odds Ratios Compared to Glasgow Coma Score of 13-15

Glasgow Coma Death Death or Severe Death or Any

Score Neurologic Neurologic
Sequelae Sequelae

10-12 3.1 (95% CI 1.1-9) 3.5 (95% CI 1.5- 3.7 (95% CI 1.8-
8.3) 7.5)

7-9 3.3 (95% CI 0.93- 11 (95% CI 3.7-31) 5.7 (95% CI 2-17)

11.6)

≤6 9 (95% CI 2.3-36) 29 (95% CI 6.8- 13 (95% CI 2.8-59)

122)

⚬ Reference - Clin Infect Dis 2008 Apr 15;46(8):1248

STUDY
● SUMMARY
seizures, coma, or use of inotropes may predict death or neurosensory impairment in
neonatal bacterial meningitis DynaMed Level 2
COHORT STUDY: Pediatrics 2000 Sep;106(3):477
Details
⚬ based on retrospective cohort study
⚬ 101 infants ≤ 28 days old with bacterial meningitis were followed to age 1 year
⚬ outcomes included
– death in 13 infants
– moderate or severe disability (defined as severe cerebral palsy, moderate-to-severe de-
velopmental delay, blindness, or deafness) in 17 infants
⚬ clinical factors at 12 hours or 96 hours after admission associated with death or disability
– seizures
– coma
– use of inotropes
– leukopenia
⚬ Reference - Pediatrics 2000 Sep;106(3):477

Prevention and Screening

Prevention

● vaccination is most effective means of meningitis prevention 2 ,3

⚬ vaccination for Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis
has significantly reduced incidence of meningitis
⚬ routine immunization schedule includes
– Haemophilus B conjugate vaccine and pneumococcal vaccine series with first dose at
age 2 months
– meningococcal vaccine series (serogroup A, C, W, and Y) with age-appropriate meningo-
coccal conjugate vaccine with first dose at age 11-12 years
⚬ additionally meningococcal serogroup B vaccine series may be given based on clinical deci-
sion to children, adolescents, and young adults aged 11-23 years not at increased risk for
meningococcal disease
⚬ meningococcal groups A, B, C, W, and Y pentavalent vaccine (Penbraya) is FDA approved for
active immunization to prevent invasive disease caused by Neisseria meningitidis
serogroups A, B, C, W, and Y in patients aged 10-25 years (FDA Approval Letter 2023 Oct 20
, FDA Product Information 2023 Oct )
 ⚬ different timing or schedules, or additional doses are needed for high-risk children and
adolescents, such as certain chronic diseases, immunocompromise, or functional or
anatomic asplenia
⚬ see Immunizations in children and adolescents for details
● chemoprophylaxis for contacts of patients with meningitis
⚬ collaboration with local department of health essential in identifying all persons who
should receive chemoprophylaxis
⚬ for invasive pneumococcal disease
– American Academy of Pediatrics (AAP) does not recommend antimicrobial chemopro-
phylaxis, regardless of immunization status
– Reference - American Academy of Pediatrics Red Book , 31st ed. 2018:550-561 (re-
quires subscription)
⚬ for Haemophilus influenzae type b (Hib) - guidelines vary
– American Academy of Pediatrics chemoprophylaxis recommendations
● chemoprophylaxis recommended for all household contacts if household has
⚬ ≥ 1 contact < 4 years old who is not immunized or only partially immunized
⚬ a child < 12 months old who has not completed the primary Hib series
⚬ an immunocompromised child, regardless of that child's age or Hib immunization
status
● chemoprophylaxis also recommended for all preschool and child care center contacts
if ≥ 2 cases of Hib have occurred within 60 days
● index cases who are < 2 years old and do not receive ≥ 1 dose of cefotaxime or ceftri-
axone should receive rifampin prophylaxis at the end of therapy for invasive infection
● rifampin 20 mg/kg (maximum 600 mg) orally once daily for 4 days recommended for
index cases and appropriate contacts ≥ 1 month old (dose not established in infants <
1 month old)
● Reference - American Academy of Pediatrics Red Book , 31st ed. 2018:550-561 (re-
quires subscription)
– United Kingdom Health Protection Agency (HPA) recommendations
● chemoprophylaxis recommended for
⚬ index cases < 10 years old with confirmed or probable Hib disease, give before hos-
pital discharge (HPA Indication)
– probable Hib disease is child with epiglottitis where H. influenza was isolated
from a sterile site
– also update Haemophilus B conjugate vaccine
 ⚬ index cases of any age with confirmed or probable invasive Hib disease if there is a
vulnerable person in household (HPA Indication)
– can be given any time during hospital admission
– vulnerable person is any child < 10 years old or an immunosuppressed or as-
plenic person of any age
⚬ all household contacts of index case with confirmed or probable invasive Hib dis-
ease if there is a vulnerable person in household (HPA Recommendation)
– give chemoprophylaxis as soon as Hib diagnosis confirmed in index case (HPA
Recommendation)
– if H. influenzae serotype results delayed (> 48 hours), give antibiotic prophylaxis
immediately if index case considered probable case or if subsequent serotype
results within 4 weeks confirm Hib infection (HPA Indication)
– household contact is any individual who had prolonged close contact with index
case in household setting ≤ 7 days before onset of illness
⚬ pregnant and breastfeeding women if vulnerable person among household con-
tacts (HPA Indication)
⚬ outbreak (≥ 2 cases of Hib disease within 120 days) in preschool or primary school
setting
– offer chemoprophylaxis to all room contacts, including staff (HPA
Recommendation)
– also update Hib vaccine in children (HPA Recommendation)
● consider offering prophylaxis to close contacts in preschool or primary school settings
where levels of contact can be defined and approach those in household
● dosing
⚬ rifampin 20 mg/kg (maximum 600 mg) once daily for 4 days for adults and children
> 3 months old is treatment of choice for eliminating carriage in index case and
among household contacts (HPA Strong recommendation)
⚬ rifampin 10 mg/kg once daily for 4 days for infants < 3 months old (HPA Strong
recommendation)
⚬ alternatives
– ceftriaxone IV or intramuscular recommended as alternative to rifampin (HPA
Recommendation)
– 50 mg/kg once daily for 2 days in children < 12 years old
– 1,000 mg once daily for 2 days in patients ≥ 12 years old
– ciprofloxacin orally twice daily for 5 days (HPA Indication)
– 500 mg in patients > 12 years old
– 250 mg in children aged 5-12 years
 – 125 mg in children aged 2-4 years
– azithromycin orally 10 mg/kg (maximum 500 mg) once daily for 3 days (HPA
Indication)
● Reference - National Health Services England 2013 Jul PDF
⚬ for meningococcal disease
– Centers for Disease Control and Prevention (CDC) recommendations for antimicrobial
chemoprophylaxis for prevention and control of meningococcal disease
● indications
⚬ close contacts
– household members
– child care center contacts
– direct exposure to patient's oral secretions
⚬ consider prophylaxis for travelers who had direct contact with respiratory secre-
tions from index patient or if seated directly next to index patient on flight lasting ≥
8 hours
● start antimicrobial chemoprophylaxis as soon as possible
⚬ ideally < 24 hours after diagnosis in index patient
⚬ starting > 14 days after onset of illness in index patient probably not useful
● oropharyngeal or nasopharyngeal cultures not useful in determining need for
chemoprophylaxis
● antibiotic selection
⚬ rifampin
– newborns < 1 month old - 5 mg/kg orally every 12 hours for 2 days
– children ≥ 1 month old - 10 mg/kg orally every 12 hours for 2 days
⚬ ceftriaxone
– children < 15 years old - 125 mg intramuscularly as single dose
– patients ≥ 15 years old - 250 mg intramuscularly as single dose
⚬ ciprofloxacin not usually recommended for patients < 18 years old , but may be
used for chemoprophylaxis in children when no acceptable alternative
● Reference - MMWR Recomm Rep 2013 Mar 22;62(RR-2):1
– American Academy of Pediatrics has similar recommendations for chemoprophylaxis as
CDC, except
● ciprofloxacin for children ≥ 1 month old - 20 mg/kg (maximum 500 mg) orally as single
dose also listed an antibiotic option
 ● azithromycin 10 mg/kg (maximum 500 mg) as single dose also listed as antibiotic op-
tion, but not recommended routinely
● chemoprophylaxis also indicated in contacts who frequently slept in same dwelling as
index patient during 7 days before onset of illness
● Reference - American Academy of Pediatrics Red Book , 31st ed. 2018:550-561 (re-
quires subscription)
● see also Group B streptococcal infection in infants less than 3 months old for guidelines on
prevention of perinatal group B streptococcal disease

STUDY
● SUMMARY
Hib and pneumococcal conjugate vaccine (PCV) associated with decreased meningitis-re-
lated morbidity and mortality in children in low- and middle-income countries
DynaMed Level 2

SYSTEMATIC REVIEW: BMC Public Health 2013;13 Suppl 3:S21

Details
⚬ based on systematic review of mostly observational studies
⚬ systematic review of 20 studies (4 randomized trials and 16 observational studies) evaluat-
ing effect of Hib and PCV on meningitis-related morbidity and mortality in children < 5
years old in low- and middle-income countries
⚬ Hib conjugate vaccine associated with dose-dependent decrease in meningitis-related
morbidity
– 1 dose associated with nonsignificant decrease in risk of meningitis-related morbidity
(risk ratio [RR] 0.64, 95% CI 0.38-1.06) in analysis of 4 studies
– decreased risk of meningitis-related morbidity with multiple doses
● 2 doses (RR 0.09, 95% CI 0.03-0.27) in analysis of 4 studies
● 3 doses (RR 0.06, 95% CI 0.02-0.22) in analysis of 5 studies
– consistent results in 2 individual trials
⚬ 3 doses of PCV associated with nonsignificant decrease in vaccine-serotype meningitis-re-
lated morbidity (RR 0.16, 95% CI 0.02-1.2) in analysis of 2 trials
⚬ estimated preventable fraction of childhood meningitis mortality
– 38%-43% with 3 doses of Hib conjugate vaccine
– 28%-35% with 3 doses of PCV
⚬ Reference - BMC Public Health 2013;13 Suppl 3:S21

STUDY
● SUMMARY
introduction of 13-valent pneumococcal conjugate vaccine (PCV13) may reduce rate of
meningitis due to specific pneumococcal serotypes but does not appear to be associated
with an overall reduction in rate of pneumococcal meningitis DynaMed Level 2

BEFORE AND AFTER STUDY: Clin Infect Dis 2015 Sep 1;61(5):767
Details
⚬ based on before-and-after study
⚬ 1,207 episodes of invasive pneumococcal disease between 2007 and 2013 in United States
were evaluated
– 645 occurred in 2007-2009 before introduction of PCV13
– 168 occurred in 2010 (transition year)
– 394 occurred in 2011-2013 after introduction of PCV13
⚬ 173 episodes (14%) identified as pneumococcal meningitis
– 76 occurred in 2007-2009
– 69 occurred in 2011-2013
⚬ comparing before vs. after introduction of PCV13, among patients with meningitis
– PCV13 serotype identified in 54% vs. 27% (p = 0.001)
– isolates with ceftriaxone minimum inhibitory concentration ≥ 1 mcg/mL 13% vs. 3% (p =
0.03)
– hemiparesis occurred in 1% vs. 12% (p = 0.01)
⚬ no other significant differences identified in clinical course or outcome among patients with
meningitis
⚬ Reference - Clin Infect Dis 2015 Sep 1;61(5):767, editorial can be found in Clin Infect Dis
2015 Sep 1;61(5):776

● prevention of bacterial meningitis in children with cerebrospinal fluid (CSF) shunts and drains

STUDY
⚬ SUMMARY
antibiotic-impregnated shunt catheters associated with reduced incidence of shunt in-
fection in children with hydrocephalus DynaMed Level 2

BEFORE AND AFTER STUDY: J Neurosurg 2005 Aug;103(2 Suppl):131

Details
– based on retrospective before-and-after study
– 211 children with hydrocephalus were treated with CSF shunt insertion with total 353
shunt insertion procedures
– of 208 shunt procedures placed before October 2002 with nonimpregnated catheters,
25 (12%) had shunt infection
– of 145 shunt procedures placed after October 2002 with antibiotic-impregnated
catheters, 2 (1.4%) had shunt infection
– Reference - J Neurosurg 2005 Aug;103(2 Suppl):131, commentary can be found in J
Neurosurg 2006 Feb;104(2 Suppl):153
 STUDY
⚬ SUMMARY
multidisciplinary program may reduce incidence of meningitis in patients with ventric-
ular and lumbar cerebrospinal fluid drains DynaMed Level 2
BEFORE AND AFTER STUDY: J Neurosurg 2010 Feb;112(2):345
Details
– based on retrospective before-and-after study of patients who had external ventricular
or lumbar cerebrospinal fluid drains placed
– 43 patients evaluated before program implementation and 112 patients evaluated after
program implementation
– multidisciplinary program included
● increased awareness
● focused standard operating procedures
● diagnostic and therapeutic algorithm
● timely administration of prophylaxis
● improvement of drainage system
– infection rate 37% before implementation vs. 9% after implementation (p < 0.0001)
– Reference - J Neurosurg 2010 Feb;112(2):345

STUDY
● SUMMARY
interventions recommended in pneumococcal disease clusters include prompt use of
amoxicillin or azithromycin chemoprophylaxis, pneumococcal vaccination for close con-
tacts, and implementation of infection control measures
SYSTEMATIC REVIEW: Lancet Infect Dis 2011 Feb;11(2):119
Details
⚬ based on systematic review of 28 identified cluster reports
⚬ antibiotics to close contacts reduced risk of pneumococcal disease in 1 study
⚬ no further cases seen following rifampicin chemoprophylaxis in 3 of 4 clusters
⚬ no further cases seen following penicillin chemoprophylaxis in 4 of 5 clusters
⚬ no further cases seen following use of infection control measures in 7 of 8 clusters
⚬ pneumococcal polysaccharide vaccine appears to have about 2-week delayed benefit
⚬ Reference - Lancet Infect Dis 2011 Feb;11(2):119

Screening
● not applicable

Guidelines and Resources

Guidelines
United States Guidelines

● Infectious Diseases Society of America (IDSA) guideline on management of bacterial meningi-

tis can be found in Clin Infect Dis 2004 Nov 1;39(9):1267, summary can be found in Am Fam
Physician 2005 May 15;71(10):2003 , commentary can be found in Clin Infect Dis 2005 Apr
1;40(7):1061

● Infectious Diseases Society of America (IDSA) clinical practice guideline on nosocomial ventri-
culitis and meningitis can be found in Clin Infect Dis 2017 Feb 14 early online
● American Academy of Pediatrics (AAP) policy statement on cochlear implants in children: sur-
gical site infections and prevention and treatment of acute otitis media and meningitis can be
found in Pediatrics 2010 Aug;126(2):381, reaffirmed January 2018

United Kingdom Guidelines

● National Institute for Health and Care Excellence (NICE) guideline on management of bacterial
meningitis and meningococcal septicaemia in children and young people < 16 years old in pri-
mary and secondary care can be found at NICE 2015 Feb:CG102 PDF , summary can be
found in BMJ 2010 Jun 28;340:c3209, commentary can be found in BMJ 2010 Aug 24;341:c4466

● National Institute for Health and Care Excellence (NICE) guideline on antibiotics for prevention
and treatment of neonatal infection can be found at NICE 2021 Apr:NG195 PDF

Canadian Guidelines

● Canadian Paediatric Society (CPS) guideline on management of suspected and confirmed bac-
terial meningitis in Canadian children older than 1 month of age can be found in Paediatr
Child Health 2014 Mar;19(3):141 [English] or full-text [French], updated December 2018

European Guidelines

● European Federation of Neurological Societies (EFNS) guideline on management of commu-

nity-acquired bacterial meningitis in older children and adults can be found in Eur J Neurol
2008 Jul;15(7):649, correction can be found in Eur J Neurol 2008 Aug;15(8):880
● Société de Pathologie Infectieuse de Langue Française (SPILF) guideline on acute bacterial
meningitis (except newborn and nosocomial meningitis) can be found in Med Mal Infect 2009
Jun;39(6):356 or in Rev Neurol (Paris) 2009 Sep;165 Spec No 3:F205 [French]

Australian and New Zealand Guidelines

● Queensland Health Primary Clinical Care Manual: Paediatrics can be found at Queensland
Health 2023 PDF .
● New South Wales (NSW) Ministry of Health clinical practice guidelines on acute management
of bacterial meningitis in infants and children (fourth edition) can be found at NSW 2014 Jul 15
PDF
African Guidelines

● Federation of Infectious Diseases Societies of Southern Africa (FIDSSA) guideline on manage-

ment of acute meningitis in children and adults in South Africa can be found in South Afr J
Epidemiol Infect 2013;28(1):5 PDF

Review Articles
● review can be found in Handb Clin Neurol 2014;121:1361
● review can be found in Expert Rev Anti Infect Ther 2013 Oct;11(10):1079
● review can be found in Expert Opin Pharmacother 2012 Oct;13(15):2189
● review can be found in Paediatr Drugs 2011 Dec 1;13(6):385
● review of aseptic and bacterial meningitis: evaluation, treatment, and prevention can be
found in Am Fam Physician 2017 Sep 1;96(5):314
● review of community-acquired bacterial meningitis can be found in Curr Opin Infect Dis 2017
Feb;30(1):135
● review of treatment of bacterial meningitis can be found in Lancet 2012 Nov
10;380(9854):1693
● review of neonatal meningitis can be found in Clin Perinatol 2015 Mar;42(1):29
● review of neonatal meningitis can be found in Trop Med Int Health 2011 Jun;16(6):672, com-
mentary can be found in Trop Med Int Health 2012 Feb;17(2):260
● review of lumbar puncture indications and interpretation can be found in Semin Perinatol
2012 Dec;36(6):445
● review of cerebrospinal fluid specimen evaluation for N. meningitidis, S. pneumoniae, and H. in-
fluenzae in bacterial meningitis can be found at 2016 CDC Apr 15
● review of dilemmas in diagnosis of acute community-acquired bacterial meningitis can be
found in Lancet 2012 Nov 10;380(9854):1684, editorial can be found in Lancet 2012 Nov
10;380(9854):1623
● review of effect of vaccines on bacterial meningitis worldwide can be found in Lancet 2012
Nov 10;380(9854):1703
● review of diagnosis, initial management, and prevention of meningitis can be found in Am
Fam Physician 2010 Dec 15;82(12):1491
● review of clinical decision rules for evaluating meningitis can be found in Curr Opin Neurol
2009 Jun;22(3):288
● review of pediatric neurocritical care can be found in Paediatr Anaesth 2014 Jul;24(7):717
● review of care of asplenic patient can be found in N Engl J Med 2014 Jul 24;371(4):349
● Laboratory Methods for the Diagnosis of Meningitis Caused by Neisseria meningitidis,
Streptococcus pneumoniae, and Haemophilus influenzae can be found at CDC 2011 Dec

MEDLINE Search

● to search MEDLINE for (Bacterial meningitis) with targeted search (Clinical Queries), click ther-
apy , diagnosis , or prognosis

Patient Information
● handout on meningitis from American Academy of Family Physicians or in Spanish
● handout on meningitis from KidsHealth or in Spanish
● handout on meningococcal vaccines from American Academy of Pediatrics or in Spanish

● information on meningococcal disease from Centers for Disease Control and Prevention
or in Spanish
● Patient UK
⚬ checklist of meningitis symptoms PDF
⚬ handout on meningitis PDF

References

General References Used

The references listed below are used in this DynaMed topic primarily to support background informa-
tion and for guidance where evidence summaries are not felt to be necessary. Most references are in-
corporated within the text along with the evidence summaries.

1. Tunkel AR, Hartman BJ, Kaplan SL, et al. Infectious Diseases Society of America (IDSA) practice
guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004 Nov 1;39(9):1267-
84, summary can be found in Am Fam Physician 2005 May 15;71(10):2003 , commentary
can be found in Clin Infect Dis 2005 Apr 1;40(7):1061.

2. Kim KS. Acute bacterial meningitis in infants and children. Lancet Infect Dis. 2010 Jan;10(1):32-
42, commentary can be found in Lancet Infect Dis 2010 Sep;10(9):596.
3. Le Saux N, Canadian Paediatric Society, Infectious Diseases and Immunization Committee.
Guidelines for the management of suspected and confirmed bacterial meningitis in Canadian
children older than one month of age. Paediatr Child Health. 2014 Mar;19(3):141-52 [English]
or full-text [French], updated December 2108 .
4. National Institute for Health and Care Excellence (NICE). Meningitis (bacterial) and meningo-
coccal septicaemia in under 16s: recognition, diagnosis and management. NICE 2015
Feb:CG102 PDF .
5. Mount Hillary R, Boyle Sean D. Aseptic and bacterial meningitis: Evaluation, treatment, and
prevention. Am Fam Physician 2017 Sep 1;96(5):314.

Recommendation Grading Systems Used

● Infectious Diseases Society of America (IDSA) 2017 uses Grading of Recommendations,

Assessment, Development, and Evaluation (GRADE) system for recommendations
⚬ strength of recommendation
– Strong recommendation - most people should receive recommended course of action
– Weak recommendation - be prepared to help people make a decision that is consistent
with their own values/decision aids and shared decision making
⚬ quality of evidence
– High - further research is very unlikely to change confidence in the estimate of effect
– Moderate - further research is likely to have an important impact on confidence in the
estimate of effect and may change the estimate
– Low - further research is very likely to have an important impact on confidence in the es-
timate of effect and is likely to change the estimate
– Very low - any estimate of effect is very uncertain
⚬ Reference - IDSA clinical practice guideline for healthcare-associated ventriculitis and
meningitis (Clin Infect Dis 2017 Feb 14 early online)
● International Diseases Society of America (IDSA) 2004 grading system for recommendations
⚬ strength of recommendations
– Grade A - good evidence to support a recommendation for use; should always be
offered
– Grade B - moderate evidence to support a recommendation for use; should generally be
offered
– Grade C - poor evidence to support a recommendation; optional
– Grade D - moderate evidence to support a recommendation against use; should gener-
ally not be offered
 – Grade E - good evidence to support a recommendation against use; should never be
offered
⚬ quality of evidence
– Level I - evidence from ≥ 1 properly randomized, controlled trial
– Level II - evidence from ≥ 1 well-designed clinical trial, without randomization; from co-
hort or case-controlled analytic studies (preferably from > 1 center); from multiple time-
series; or from dramatic results from uncontrolled experiments
– Level III - evidence from opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
⚬ Reference - IDSA practice guidelines for the management of bacterial meningitis (Clin Infect
Dis 2004 Nov 1;39(9):1267)

● Infectious Diseases Society of America (IDSA) grading system for recommendations:

⚬ Strength of recommendation grades:
– Grade A - good evidence to support recommendation for or against use
– Grade B - moderate evidence to support recommendation for or against use
– Grade C - poor evidence to support recommendation
⚬ Quality of evidence ratings:
– I - evidence from ≥ 1 properly randomized, controlled trial
– II - evidence from ≥ 1 well-designed nonrandomized clinical trial; from cohort or case-
controlled analytic studies (preferably from > 1 center); from multiple time series; or
from dramatic results from uncontrolled studies
– III - evidence from opinions of respected authorities, based on clinical experience, de-
scriptive studies, or reports of expert committees
⚬ Reference - IDSA clinical practice guideline on treatment of methicillin-resistant
Staphylococcus aureus infections in adults and children (Clin Infect Dis 2011 Feb;52(3):e18),
correction can be found in Clin Infect Dis 2011 Aug 1;53(3):319, commentary can be found
in Clin Infect Dis 2015 Apr 15;60(8):1290

● United Kingdom Health Protection Agency (HPA) grading system for recommendations
⚬ Strong recommendation - based on > 2 consistent, well-conceived, well-executed studies
with control groups or longitudinal measurements
⚬ Recommendation - based on > 1 well-conceived, well-executed, controlled or time-series
study; or > 3 studies with more limited execution
⚬ Indication - based on previous scientific observation and theoretic rationale, but case-con-
trolled or prospective studies do not exist
⚬ Not recommended - based on published literature recommending against practice
⚬ Reference - National Health Services England 2013 Jul PDF
● Scottish Intercollegiate Guidelines Network (SIGN) grades of recommendation
⚬ Grade A
– ≥ 1 high-quality meta-analysis, systematic review of randomized trials, or randomized
trial with very low risk of bias and directly applicable to target population, or
– body of evidence consisting principally of well-conducted meta-analyses, systematic re-
views of randomized trials, or randomized trials with low risk of bias directly applicable
to target population, and demonstrating overall consistency of results
⚬ Grade B
– body of evidence including studies rated as high-quality systematic reviews of case-con-
trol or cohort studies, and high-quality case-control or cohort studies with very low risk
of confounding or bias and high probability that relation is causal and which are directly
applicable to the target population, and with overall consistency of results, or
– extrapolated evidence from studies described in Grade A
⚬ Grade C
– body of evidence including well-conducted case-control or cohort studies with low risk of
confounding or bias and moderate probability that relation is causal and which are di-
rectly applicable to target population and overall consistency of results, or
– extrapolated evidence from studies described in Grade B
⚬ Grade D
– nonanalytic studies such as case reports, case series, expert opinion, or
– extrapolated evidence from studies described in Grade C
⚬ Good Practice Point (GPP) - recommended best practice based on clinical experience of
guideline development group
⚬ Reference - SIGN national clinical guideline on management of invasive meningococcal dis-
ease in children and young people (SIGN 2008 May PDF ), summary can be found in BMJ
2008 Jun 14;336(7657):1367, commentary can be found in BMJ 2008 Jun 14;336(7657):1370,
BMJ 2008 Jun 28;336(7659):1453

Synthesized Recommendation Grading System for DynaMed Content

● The DynaMed Team systematically monitors clinical evidence to continuously provide a syn-
thesis of the most valid relevant evidence to support clinical decision-making (see 7-Step
Evidence-Based Methodology ).
● Guideline recommendations summarized in the body of a DynaMed topic are provided with
the recommendation grading system used in the original guideline(s), and allow users to
quickly see where guidelines agree and where guidelines differ from each other and from the
current evidence.
● In DynaMed content, we synthesize the current evidence, current guidelines from leading au-
thorities, and clinical expertise to provide recommendations to support clinical decision-mak-
ing in the Overview & Recommendations section.
● We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)
to classify synthesized recommendations as Strong or Weak.
⚬ Strong recommendations are used when, based on the available evidence, clinicians
(without conflicts of interest) consistently have a high degree of confidence that the desir-
able consequences (health benefits, decreased costs and burdens) outweigh the undesir-
able consequences (harms, costs, burdens).
⚬ Weak recommendations are used when, based on the available evidence, clinicians be-
lieve that desirable and undesirable consequences are finely balanced, or appreciable un-
certainty exists about the magnitude of expected consequences (benefits and harms).
Weak recommendations are used when clinicians disagree in judgments of relative benefit
and harm, or have limited confidence in their judgments. Weak recommendations are also
used when the range of patient values and preferences suggests that informed patients are
likely to make different choices.
● DynaMed synthesized recommendations (in the Overview & Recommendations section) are
determined with a systematic methodology:
⚬ Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological
expertise and ≥ 1 with content domain expertise) aware of the best current evidence for
benefits and harms, and the recommendations from guidelines.
⚬ Recommendations are phrased to match the strength of recommendation. Strong recom-
mendations use "should do" phrasing, or phrasing implying an expectation to perform the
recommended action for most patients. Weak recommendations use "consider" or "sug-
gested" phrasing.
⚬ Recommendations are explicitly labeled as Strong recommendations or Weak recom-
mendations when a qualified group has explicitly deliberated on making such a recom-
mendation. Group deliberation may occur during guideline development. When group de-
liberation occurs through DynaMed Team-initiated groups:
– Clinical questions will be formulated using the PICO (Population, Intervention,
Comparison, Outcome) framework for all outcomes of interest specific to the recom-
mendation to be developed.
– Systematic searches will be conducted for any clinical questions where systematic
searches were not already completed through DynaMed content development.
– Evidence will be summarized for recommendation panel review including for each out-
come, the relative importance of the outcome, the estimated effects comparing inter-
vention and comparison, the sample size, and the overall quality rating for the body of
evidence.
 – Recommendation panel members will be selected to include at least 3 members that to-
gether have sufficient clinical expertise for the subject(s) pertinent to the recommenda-
tion, methodological expertise for the evidence being considered, and experience with
guideline development.
– All recommendation panel members must disclose any potential conflicts of interest
(professional, intellectual, and financial), and will not be included for the specific panel if
a significant conflict exists for the recommendation in question.
– Panel members will make Strong recommendations if and only if there is consistent
agreement in a high confidence in the likelihood that desirable consequences outweigh
undesirable consequences across the majority of expected patient values and prefer-
ences. Panel members will make Weak recommendations if there is limited confidence
(or inconsistent assessment or dissenting opinions) that desirable consequences out-
weigh undesirable consequences across the majority of expected patient values and
preferences. No recommendation will be made if there is insufficient confidence to
make a recommendation.
– All steps in this process (including evidence summaries which were shared with the
panel, and identification of panel members) will be transparent and accessible in sup-
port of the recommendation.
⚬ Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in
recommendation drafting or development, with explicit confirmation that Strong recom-
mendations are adequately supported.
⚬ Recommendations are published only after consensus is established with agreement in
phrasing and strength of recommendation by all editors.
⚬ If consensus cannot be reached then the recommendation can be published with a nota-
tion of "dissenting commentary" and the dissenting commentary is included in the topic
details.
⚬ If recommendations are questioned during peer review or post publication by a qualified
individual, or reevaluation is warranted based on new information detected through sys-
tematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

● DynaMed topics are created and maintained by the DynaMed Editorial Team and Process
.
● All editorial team members and reviewers have declared that they have no financial or other
competing interests related to this topic, unless otherwise indicated.
● DynaMed content includes Practice-Changing Updates, with support from our partners,
McMaster University and F1000.
Special Acknowledgements

● DynaMed topics are written and edited through the collaborative efforts of the above individ-
uals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medi-
cal practice. Recommendations Editors are actively involved in development and/or evaluation
of guidelines.

● Editorial Team role definitions

Topic Editors define the scope and focus of each topic by formulating a set of clinical
questions and suggesting important guidelines, clinical trials, and other data to be
addressed within each topic. Topic Editors also serve as consultants for the internal
DynaMed Editorial Team during the writing and editing process, and review the final topic
drafts prior to publication.

Section Editors have similar responsibilities to Topic Editors but have a broader role that
includes the review of multiple topics, oversight of Topic Editors, and systematic
surveillance of the medical literature.

Recommendations Editors provide explicit review of Overview and Recommendations

sections to ensure that all recommendations are sound, supported, and evidence-based.
This process is described in "Synthesized Recommendation Grading."

Deputy Editors oversee DynaMed internal publishing groups. Each is responsible for all
content published within that group, including supervising topic development at all
stages of the writing and editing process, final review of all topics prior to publication, and
direction of an internal team.

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