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Print | Back Treatment and prognosis of acute bacterial meningitis in children older than one month of age Author Sheldon L Kaplan MD Section Editors Morven S Edwards MD Douglas R Nordli Jr MD Deputy Editor Mary M Torchia MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete Literature review current through Aug 2013 | This topic last updated Apr 2 2013

INTRODUCTION mdash Suspected bacterial meningitis is a medical emergency and immediate

diagnostic steps must be taken to establish the specific cause so that appropriate

antimicrobial therapy can be initiated The mortality rate of untreated bacterial meningitis

approaches 100 percent and even with optimal therapy morbidity and mortality may occur

Neurologic sequelae are common among survivors

The treatment and prognosis of bacterial meningitis in infants and children older than one

month will be reviewed here The pathogenesis epidemiology clinical features and diagnosis

of acute bacterial meningitis and the treatment and prognosis of bacterial meningitis in

neonates (lt1 month of age) and adults are discussed separately (See Pathogenesis and

pathophysiology of bacterial meningitis and Clinical features and diagnosis of acute

bacterial meningitis in children older than one month of age and Treatment and outcome of

bacterial meningitis in the neonate and Initial therapy and prognosis of bacterial meningitis

in adults and Treatment of bacterial meningitis caused by specific pathogens in adults)

GENERAL PRINCIPLES mdash There are a number of general principles of antibiotic therapy in

patients with bacterial meningitis The most important initial issues are avoidance of delay in

administering therapy and the choice of drug regimen

Avoidance of delay mdash Antibiotic therapy should be initiated immediately after lumbar

puncture (LP) is performed if the clinical suspicion for meningitis is high (algorithm 1) Delay in

the administration of appropriate antibiotics can have a deleterious effect on outcome for

patients who are deteriorating rapidly

If computed tomography (CT) scan is to be performed before LP antibiotic therapy should be

initiated immediately after blood cultures are obtained Although the administration of

antimicrobial therapy before LP may affect the yield of cerebrospinal fluid (CSF) Gram stain

and culture pathogens other than meningococcus usually can be identified in the CSF up to

several hours after the administration of antibiotics [1-3] (See Clinical features and diagnosis

of acute bacterial meningitis in children older than one month of age section on

Interpretation of CSF in pretreated patients)

Antibiotic regimen mdash There are two general principles of antibiotic therapy for bacterial

meningitis [4]

The agent(s) used must be bactericidal against the infecting organism

The agent(s) used must be able to penetrate past the blood-brain barrier to reach a

sufficient concentration in the CSF

Bactericidal agents mdash Since the CSF is a site of impaired humoral immunity a fundamental

principle of therapy of bacterial meningitis is that antibiotics must achieve a bactericidal effect

within CSF to result in optimal microbiologic cure [56] This principle is supported by clinical

observations of poor outcomes in patients receiving bacteriostatic therapy (eg clindamycin

tetracycline) [7] as well as direct experimental evidence in which bactericidal antibiotic

therapy resulted in optimal microbiologic cure and survival in animals with pneumococcal

meningitis [8]

Chloramphenicol is a bacteriostatic drug for most enteric Gram-negative rods however it

usually is bactericidal for Haemophilus influenzae Neisseria meningitidis and Streptococcus

pneumoniae and has been used extensively and successfully to treat meningitis caused by

these organisms

Drug entry into CSF mdash Treatment of bacterial meningitis requires adequate concentration of

antibiotics in the CSF Most drugs reach peak concentrations in the CSF that are only 10 to

20 percent of peak concentrations in the serum This is because the blood-brain barrier

blocks macromolecule entry into the CSF with small lipophilic molecules penetrating most

easily

The peak concentration of drugs in CSF increases with inflammation of the blood-brain

barrier This was illustrated in one study that sequentially monitored CSF and serum penicillin

levels in children with bacterial meningitis The mean CSFserum ratio two hours after

administration of the same intravenous dose of penicillin was 42 percent on the first day of

therapy but fell to less than 10 percent on the 10th day when the inflammatory changes had

subsided [9] (See Cerebrospinal fluid Physiology and utility of an examination in disease

states section on Blood-brain barrier)

Because of the general limitation in antibiotic penetration into the CSF all patients should be

treated with intravenous antibiotics Oral antibiotics should be avoided since the dose and

tissue levels tend to be considerably lower than with parenteral agents One exception can be

made for chloramphenicol which has been administered successfully by the oral route to

treat H influenzae type b (Hib) meningitis in children [10]

Choice of regimen mdash The choice of regimen depends upon whether the pathogen is known

since regimens for empiric therapy pose a different set of management issues than do those

used to treat known pathogens (See Empiric therapy below and Specific therapy below)

PRETREATMENT EVALUATION mdash If possible the pretreatment evaluation of children with

suspected bacterial meningitis should include a complete history and physical examination

cerebrospinal fluid (CSF) examination (cell count and differential glucose protein Gram stain

and culture) complete blood count (CBC) with differential and platelet count two aerobic

blood cultures serum electrolytes glucose blood urea nitrogen and creatinine evaluation of

clotting function is especially indicated if petechiae or purpuric lesions are noted (algorithm 1)

In cases in which the performance of a lumbar puncture (LP) is delayed by rapidly

deteriorating clinical status or the need for neuroimaging blood cultures should be obtained

before the administration of antibiotic therapy (algorithm 1)

The pretreatment evaluation of infants and children with suspected bacterial meningitis is

discussed in greater detail separately (See Clinical features and diagnosis of acute bacterial

meningitis in children older than one month of age section on Evaluation)

IMMEDIATE MANAGEMENT mdash Immediate management of children with suspected bacterial

meningitis includes [11]

Assurance of adequate ventilation and cardiac perfusion (see Initial assessment and

stabilization of children with respiratory or circulatory compromise)

Initiation of hemodynamic monitoring and support at the same time as obtaining

appropriate laboratory studies (blood and cerebrospinal fluid [CSF]) (see

Pretreatment evaluation above)

Establishment of venous access (see Vascular (venous) access for pediatric

resuscitation and other pediatric emergencies)

Administration of fluids as necessary to treat septic shock if present (see Systemic

inflammatory response syndrome (SIRS) and sepsis in children Definitions

epidemiology clinical manifestations and diagnosis)

Administration of dexamethasone if warranted after assessment of potential benefits

and risks before or immediately after the first dose of antimicrobial therapy (see

Dexamethasone and other measures to prevent neurologic complications of

bacterial meningitis in children section on Dexamethasone)

Administration of the first dose of empiric antibiotics (vancomycin [15 mgkg] plus

either cefotaxime [100 mgkg] or ceftriaxone [50 mgkg]) (see Empiric regimen

below)

Administration of glucose (025 gkg) for documented hypoglycemia (serum glucose

concentration less than 40 mgdL [22 mmolL]) (see Approach to hypoglycemia in

infants and children section on Glucose therapy)

Treatment of acidosis and coagulopathy if present (see Systemic inflammatory

response syndrome (SIRS) and sepsis in children Definitions epidemiology clinical

manifestations and diagnosis and Disseminated intravascular coagulation in infants

and children)

SUPPORTIVE CARE

Fluid management mdash Careful management of fluid and electrolyte balance is an important

aspect of supportive therapy Both over- and under-hydration are associated with adverse

outcomes [12]

Children who are in shock should receive sufficient quantities of isotonic fluid to maintain

blood pressure and cerebral perfusion [13] The management of septic shock in children is

discussed separately (See Systemic inflammatory response syndrome (SIRS) and sepsis in

children Definitions epidemiology clinical manifestations and diagnosis)

Children who are hypovolemic but not in shock should be rehydrated with careful and

frequent attention to fluid status Body weight urine volume and specific gravity and serum

electrolytes should be monitored regularly (See Treatment of hypovolemia (dehydration) in

children)

For children who are neither in shock nor hypovolemic we suggest moderate fluid restriction

(1200 mLm2 per day) initially especially if the serum sodium is less than 130 mEqL until

evidence of inappropriate secretion of antidiuretic hormone can be excluded Body weight

urine volume and specific gravity serum electrolytes and if indicated serum and urine

osmolalities should be carefully monitored Fluid administration can be liberalized gradually

as the serum sodium reaches 135 mEqL Most children can receive maintenance fluid intake

within 24 hours of hospitalization

Monitoring mdash Children who are being treated for bacterial meningitis should be monitored

carefully for complications (eg increased intracranial pressure seizure activity development

of infected subdural effusions) particularly during the first two to three days of treatment

when complications are most likely to occur [13-15]

Heart rate blood pressure and respiratory rate should be monitored regularly with a

frequency appropriate to the care setting

A complete neurologic examination should be performed daily rapid assessment of

neurologic function should be performed several times per day for the first several

days of treatment

Head circumference should be measured daily in children younger than 18 months

EMPIRIC THERAPY mdash The organism causing bacterial meningitis seldom is known at the

outset of therapy as a result an empiric treatment plan usually needs to be formulated An

awareness of the most likely pathogens knowledge of local susceptibility patterns and

assessment of the degree of urgency are necessary to devise an optimal empiric treatment

strategy Once culture results are available treatment should be modified to follow the

guidelines for specific pathogens (See Specific therapy below)

Major pathogens mdash The two most common causes of bacterial meningitis in infants and

children who have received a full series of H influenzae type b (Hib) and pneumococcal

conjugate vaccines are S pneumoniae and N meningitidis [16] Among S pneumoniae

isolates antibiotic resistance remains a concern In developing countries that do not routinely

immunize against Hib Hib continues to be a frequent cause of meningitis [17] (See Clinical

features and diagnosis of acute bacterial meningitis in children older than one month of age

section on Epidemiology)

Group B streptococcus Escherichia coli and Listeria monocytogenes are important causes in

infants younger than three months (See Clinical features and diagnosis of acute bacterial

meningitis in children older than one month of age section on Epidemiology and Clinical

features and diagnosis of bacterial meningitis in the neonate section on Etiology)

Empiric regimen mdash The empiric regimen should include coverage for penicillin-resistant S

pneumoniae and N meningitidis the two most common causes of bacterial meningitis in

infants and children Additional coverage for other organisms may be indicated in children

with immune deficiency recent neurosurgery penetrating head trauma and anatomic

defects The cerebrospinal fluid (CSF) Gram stain may provide important clues for the need to

add additional antibiotics to cover for more unusual organisms Broad-spectrum antimicrobial

therapy should be continued until CSF culture results are available because Gram stain

results are subject to observer misinterpretation [18] (See Special circumstances below)

An appropriate empiric regimen (ie one that covers antibiotic-resistant S pneumoniae N

meningitidis and Hib) includes high doses of a third-generation cephalosporin (eg

cefotaxime ceftriaxone) and vancomycin [19]

Cefotaxime 300 mgkg per day intravenously (IV) (maximum dose 12 gday) in 3 or 4

divided doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2

divided doses plus

Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses

If ceftriaxone is used we suggest twice daily dosing to avoid the possibility of inadequate

treatment in the event of dosing errors delayed doses or missed doses [13] Some experts

suggest the addition of rifampin to the empiric regimen if dexamethasone is administered [18]

(See Pneumococcal meningitis in children section on Empiric therapy)

Consultation with an expert in pediatric infectious diseases is recommended for children in

whom cephalosporins or vancomycin are contraindicated

Use of dexamethasone mdash Issues related to neurologic sequelae after bacterial meningitis

and the possible role of dexamethasone therapy to minimize these complications are

discussed separately (See Neurologic complications of bacterial meningitis in children and

Dexamethasone and other measures to prevent neurologic complications of bacterial

meningitis in children section on Dexamethasone)

The decision to use dexamethasone in children with suspected bacterial meningitis must be

individualized Factors to be weighed in this decision include

The etiologic agent

The ability to administer dexamethasone before or within 1 hour of the first dose of

antibiotic therapy

The empiric antibiotic regimen

The potential adverse effects

The American Academy of Pediatrics (AAP) Committee on Infectious Diseases suggests that

dexamethasone therapy may be beneficial in children with Hib meningitis if given before or at

the same time as the first dose of antimicrobial therapy [20] The AAP Committee on

Infectious Diseases suggests that dexamethasone therapy be considered for infants and

children older than six weeks with pneumococcal meningitis after weighing the potential risks

and benefits [21]

In accordance with the AAP Committee on Infectious Diseases we recommend adjunctive

therapy with dexamethasone for children with Hib meningitis We suggest that decisions

regarding the use of dexamethasone in children with pneumococcal meningitis or in those in

whom bacterial meningitis is suspected but the etiology unknown be individualized

depending upon careful analysis of the potential risks and benefits The author of this topic

review usually does not administer dexamethasone to children with suspected pneumococcal

or meningococcal meningitis In the same patients other experts may choose to use

dexamethasone (See Pneumococcal meningitis in children section on Dexamethasone)

Regimen mdash If the decision is made to use dexamethasone dexamethasone should be given

before or concurrently with the first dose of the antimicrobial agent(s) it is probably of no

benefit if given more than 1 hour later [18] The regimen for dexamethasone is

Dexamethasone 015 mgkg per dose every 6 hours for 2 to 4 days [13] Two days of

dexamethasone appear to be as effective as and less toxic than longer courses [22]

Special circumstances mdash The treatment of bacterial meningitis in children with immune

deficiency recent neurosurgery anatomic defects penetrating head trauma CSF leak and

during epidemics requires consultation with an expert in pediatric infectious diseases

Immune deficiency mdash Vancomycin plus either cefotaxime or ceftriaxone given as described

above are reasonable empiric coverage for most children with an underlying defect in host

defense (See Empiric regimen above)

If a Gram-negative rod is observed on Gram stain of the CSF the addition of an

aminoglycoside (eg gentamicin amikacin) to these two agents is recommended (See Gram-

negative rods below)

Gentamicin 75 mgkg per day IV in 3 divided doses or

Amikacin 15 to 22 5 mgkg per day IV (maximum dose 15 gday) in 3 divided doses

Peak and trough serum concentrations must be monitored when aminoglycosides are used

[23]

Cancer and neutropenia mdash In a retrospective case series of 40 cases of bacterial or fungal

meningitis in 36 neutropenic pediatric cancer patients (two-thirds of whom had recent

neurosurgery a central nervous system [CNS] device or CSF leak) S pneumoniae and

Staphylococcus aureus were the two most common isolates [24] Empiric therapy in such

patients should be based upon the Gram stain results Initial therapy typically includes

vancomycin plus an aminoglycoside plus either cefotaxime or ceftriaxone If there is any

concern about Pseudomonas aeruginosa or an increased risk for infection caused by an

extended-spectrum beta-lactamase (ESBL)-producing organism meropenem may be

warranted as an alternative to cefotaxime or ceftriaxone

T cell defects mdash S pneumoniae and L monocytogenes are the most likely causes of

bacterial meningitis in patients with defective cell-mediated immunity [25] To address these

pathogens the empiric regimen for children with defects in T cell immunity should include

vancomycin plus either cefotaxime or ceftriaxone dosed as recommended above and high-

dose ampicillin (see Empiric regimen above) The dose of ampicillin is as follows

Ampicillin 300 to 400 mgkg IV per day (maximum dose 10 to 12 gday) in 4 or 6

divided doses

Recent neurosurgery mdash In addition to the usual nosocomial pathogens that may complicate

any surgical procedure coagulase-negative staphylococci (such as Staphylococcus

epidermidis) and S aureus are important causes of meningitis in patients who have had

recent neurosurgery Patients who undergo operations that involve a prosthetic device such

as a ventricular shunt or drain are clearly at risk for developing infection (See Infections of

central nervous system shunts and other devices)

Patients who have undergone recent neurosurgery also are at increased risk for meningitis

with enteric Gram-negative rods such as E coli and Klebsiella species as well as P

aeruginosa (See Epidemiology and clinical features of gram-negative bacillary meningitis)

Empiric therapy in this setting usually consists of a combination of a third-generation

cephalosporin and vancomycin In addition an aminoglycoside (eg gentamicin amikacin)

should be added if Gram-negative bacilli are noted on CSF Gram stain

Alternative regimens include

Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus

Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses

or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses

or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses

The local antibiogram can help to guide which of the agents directed against Gram-

negative organisms might be most appropriate (eg a high rate of resistance to

ceftazidime suggests meropenem is a better choice)

Recent placement of CSF shunt mdash In infants and children who have had recent placement

of a CSF shunt vancomycin plus either cefotaxime or ceftriaxone are recommended [18]

Anatomic defects mdash Children with anatomic defects (eg dermal sinus (picture 1) urinary

tract anomalies) are at increased risk for meningitis with S aureus or coagulase-negative

staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See

Epidemiology and clinical features of gram-negative bacillary meningitis)

Empiric therapy in children with anatomic defects should include vancomycin plus either

cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)

In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative

bacilli are noted on CSF Gram stain

Gentamicin 75 mgkg per day IV in 3 divided doses or

Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses

Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis

with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic

Gram-negative bacilli including P aeruginosa [18]

Empiric therapy in this setting usually consists of a combination of vancomycin plus an

extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an

aminoglycoside [18]

Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus

Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses

or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses

or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses

plus

Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per

day IV (maximum dose 15 gday) in 3 divided doses

CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for

presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this

setting Pneumococcal meningitis in these patients is usually less severe than that caused by

hematogenous invasion and the prognosis is somewhat better Nevertheless because of the

possibility of an isolate highly resistant to penicillin such patients should be treated with a

third-generation cephalosporin plus vancomycin until culture results return This regimen

also will cover H influenzae which rarely causes meningitis in patients with dural defects

(See Empiric regimen above)

Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N

meningitidis is suspected is discussed separately (See Treatment and prevention of

meningococcal infection)

SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility

pattern are known empiric antimicrobial therapy can be altered accordingly

S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail

separately (See Pneumococcal meningitis in children section on Overview of treatment)

Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles

are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S

pneumoniae meningitis is 10 to 14 days

N meningitidis mdash Meningococcal meningitis is best treated with penicillin

Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6

divided doses

A third-generation cephalosporin is an effective alternative to penicillin for children with

penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins

and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)

Possible regimens include

Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided

doses or

Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses

For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a

recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin

is another option

Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4

divided doses

Although scattered cases of N meningitidis resistant to penicillin have been reported such

strains are rare Relative resistance to penicillin occurs more commonly but does not have an

impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and

prevention of meningococcal infection section on Penicillin)

A five- to seven-day duration of therapy is adequate for meningococcal meningitis and

eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin

nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis

Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to

eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the

organism to contacts (See Treatment and prevention of meningococcal infection section on

Antimicrobial chemoprophylaxis)

H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-

resistant H influenzae type b (Hib) meningitis [2030-32]

Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses

or

Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses

Ampicillin is effective for susceptible strains

Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6

divided doses

For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is

one option Chloramphenicol is another

Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided

doses

Cefuroxime should not be used to treat Hib meningitis because it is associated with less

rapid sterilization of the CSF and a greater incidence of hearing loss [3031]

Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization

persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients

who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital

discharge to prevent transmission of the organism to contacts For patients who are treated

with chloramphenicol rifampin therapy should be delayed until chloramphenicol is

discontinued since concomitant administration of rifampin may reduce serum concentrations

of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on

Antibiotic prophylaxis of close contacts)

L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and

gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has

poor CSF penetration it is used for synergy [35]

Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided

doses plus

Gentamicin 75 mgkg per day IV in 3 divided doses

Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients

[36] The dose for TMP-SMX is as follows

TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX

component per day in 4 divided doses

Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent

in vitro activity against L monocytogenes It may prove to be useful for listeria infections but

has not yet been approved for this indication Other antibiotics are less effective against L

monocytogenes

The usual duration of therapy for Listeria meningitis is 14 to 21 days

Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus

agalactiae) meningitis is discussed separately (See Group B streptococcal infection in

neonates and young infants section on Treatment)

S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is

nafcillin or oxacillin [1837]

Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or

Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)

The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin

[183738]

Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some

experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses

(maximum dose 600 mgday) to vancomycin either orally or by intravenous

administration

Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]

TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX

component per day in 4 divided doses or

Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day

maximum dose 1200 mgday

Inflammation of the meninges does not appear to affect penetration of linezolid into

the CSF [39-42] Rapid penetration has been demonstrated in children and

adolescents [42] However CSF concentrations are variable and correlation of CSF

and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some

case reports document successful linezolid treatment of staphylococcal meningitis

[3743]

Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated

with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside

often can be discontinued after the first week once the CSF cultures have been documented

to be sterile Consultation with an expert in pediatric infectious diseases is recommended for

children with meningitis caused by a Gram-negative rod One suggested regimen is as

follows

Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided

doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided

doses plus

Gentamicin 75 mgkg per day IV in 3 divided doses

Organisms such as P aeruginosa often are resistant to many commonly used antibiotics

Ceftazidime has been the most consistently effective cephalosporin in the treatment of P

aeruginosa infections including meningitis [45]

Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses

Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US

Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and

adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-

negative rods [47] and is the agent of choice in the treatment of meningitis caused by

extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is

dosed as follows

Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses

A repeat CSF sample should be obtained for culture two to three days into therapy to help

assess the efficacy of treatment

In addition we suggest repeating the CSF analysis near the end of therapy particularly in

young infants to determine whether treatment may be discontinued CSF findings suggestive

of the need for continued therapy include

Percentage of neutrophils gt30 percent or

CSF glucose concentration lt20 mgdL

Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for

several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken

in consultation with specialists in pediatric infectious diseases and neurosurgery (See

Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and

intraventricular therapy)

DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the

causative organism and the clinical course

Positive CSF culture mdash There is limited evidence from high-quality studies to guide the

duration of treatment for bacterial meningitis We suggest the following durations of therapy

for uncomplicated meningitis caused by the following organisms [2027]

S pneumoniae ndash 10 to 14 days

N meningitidis ndash 5 to 7 days

H influenzae type b (Hib) ndash 7 to 10 days

L monocytogenes ndash 14 to 21 days

S aureus ndash at least 2 weeks

Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile

culture whichever is longer [14]

A multicenter trial in resource-limited countries found that outcomes were similar among

children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae

N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid

(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days

of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or

placebo The setting methodology and lack of organism-specific outcome information

preclude generalizability to resource-rich settings [4950] We continue to suggest organism-

specific durations of therapy as outlined above

Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be

administered in the outpatient setting [1851] Advantages of completion of therapy in the

outpatient setting include decreased risk of nosocomial infection improved quality of life and

decreased cost of therapy [3352-54] Several observational studies have shown that with

careful selection and close monitoring completion of antimicrobial therapy in the outpatient

setting can be safe and effective [52-54]

One group of investigators used the following criteria for outpatient antimicrobial therapy in

children [52]

Completion of at least six days of inpatient therapy serious adverse complications of

meningitis are exceedingly rare after three or four days of therapy particularly in

children who are clinically well and afebrile [141551]

Afebrile for at least 24 to 48 hours before initiation of outpatient therapy

No significant neurologic dysfunction or focal findings

No seizure activity

Clinical stability

Ability to take fluids by mouth

First dose of outpatient antibiotic is administered in the hospital

Outpatient antibiotic therapy is administered in the office or emergency department

setting or by qualified home health nursing

Daily examination is performed by a clinician

Parents are reliable and have transportation and a telephone

Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the

duration of antibiotic therapy is individualized depending upon the remainder of the CSF

evaluation blood culture result and clinical status

For those who have a normal CSF profile and negative blood and CSF culture we

usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours

of incubation

For those who have a CSF pleocytosis and positive blood culture but negative CSF

culture treat for meningitis caused by the organism isolated from the blood culture

(ie management is the same as if the CSF culture was positive for the same

organism)

For those who have a CSF pleocytosis negative blood culture and negative CSF

culture we individualize the duration of meningitic doses of antimicrobial therapy

based on clinical parameters Consultation with a specialist in pediatric infectious

diseases is suggested if the clinician is uncertain how to manage such children

RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever

curve resolution of symptoms and signs) Repeat examination of the spinal fluid and

neuroimaging may be necessary in some patients In children who had a positive blood

culture at initial evaluation blood cultures should be repeated to document sterility of the

blood stream The follow-up blood culture is usually obtained when it is known that the initial

blood culture is positive

In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or

increased head circumference neurologic complications (eg subdural empyema cerebral

vascular thrombosis ventricular dilation brain abscess) should be considered and

neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in

children)

Duration of fever mdash The duration of fever is typically four to six days after the initiation of

adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of

patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24

hours) occurs in approximately 16 percent [5557]

Persistence of fever beyond eight days and secondary fever have a number of causes

including [2355]

Inadequate treatment

Development of nosocomial infection (eg infected intravenous catheters urinary tract

infection viral infection) nosocomial infection is more often associated with

secondary fever than with persistent fever [52]

Discontinuation of dexamethasone

Development of a suppurative complication (pericarditis pneumonia arthritis

subdural empyema)

Drug fever (a diagnosis of exclusion)

In patients with persistent or secondary fever suppurative and nosocomial complications

should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)

considered on an individual basis [51] In many cases a specific cause of prolonged fever

cannot be determined In the patient who is improving daily but has unexplained fever despite

careful evaluation it is thought that the individuals host response to infection is responsible

for the prolonged fever

Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have

a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This

is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for

children with pneumococcal meningitis who were treated with dexamethasone (since

dexamethasone may interfere with the ability of the clinician to assess clinical response such

as resolution of fever)

Re-examination of the CSF also may be indicated in children with persistent or recurrent

fever as discussed above (See Duration of fever above)

In addition re-examination of the CSF is necessary after two to three days of treatment for

Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-

negative rods above)

Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if

organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF

examination Extension of duration of treatment also is indicated if CSF examination at the

conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose

of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]

Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance

imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis

in the following circumstances (see Neurologic complications of bacterial meningitis in

children) [5155]

Focal neurologic signs increasing head circumference or prolonged obtundation

irritability or seizures (gt72 hours after the start of treatment)

Persistently positive CSF cultures despite appropriate antibiotic therapy

Persistent elevation of CSF neutrophils at the completion of standard duration of

therapy (more than 30 to 40 percent)

Recurrent meningitis (to evaluate the possibility of a communication between the

nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has

been reported to be a relatively easy noninvasive method of delineating anatomic

abnormalities in children with recurrent meningitis [58]

In addition neuroimaging of infants with Gram-negative meningitis sometime during their

treatment is recommended to detect hydrocephalus or other complications of the meningitis

[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known

as Cronobacter) meningitis (See Gram-negative rods above)

PROGNOSIS

Mortality mdash Case fatality rates for meningitis in children older than one month in the United

States range from 0 to 15 percent depending upon the infecting organism and when the

survey was performed [161960-63] Among 2780 children in the United States with bacterial

meningitis between 2001 and 2006 mortality was 42 percent [62]

A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a

mortality rate of 48 percent in developed countries and 81 percent in developing countries

[61] The mortality rate in developed countries varied by organism ranging from 38 percent

for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S

pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study

(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States

[19] (See Pneumococcal meningitis in children section on Mortality)

Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive

an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in

children section on Incidence)

The possible role of dexamethasone therapy in mitigating neurologic complications of

bacterial meningitis is discussed separately (See Dexamethasone and other measures to

prevent neurologic complications of bacterial meningitis in children section on Efficacy)

Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children

include level of consciousness at the time of admission etiologic agent prolonged or

complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed

sterilization of the CSF and nutritional status as discussed below [192364-69]

Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children

with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only

independent predictor of death or neurologic sequelae [64]

Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children

with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]

(See Pneumococcal meningitis in children section on Mortality)

The risk of hearing impairment is also related to etiologic agent Hearing loss occurs

in approximately 31 percent of children with pneumococcal meningitis 11 percent of

children with meningococcal meningitis and 6 percent of children with Hib meningitis

[196771]

Seizures ndash In a multicenter pneumococcal meningitis surveillance study the

occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial

therapy was associated with increased risk of neurologic sequelae [19] In a series of

children with Hib meningitis seizures were associated with subtle cognitive and

learning problems [72]

CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11

mmolL]) at the time of admission appears to be associated with hearing loss

[196566]

Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently

positive culture 16 to 18 hours after the initiation of therapy) is associated with

adverse outcomes including moderate to profound sensorineural hearing loss

seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]

Nutritional status ndash Malnutrition is associated with increased morbidity and mortality

[6869] In a multicenter study of 482 Latin American children with bacterial

meningitis the risk of death was increased among those who were underweight

(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight

respectively) [69] The risk of severe neurologic sequelae was also increased in

severely underweight children (OR 5 95 CI 16-16)

FOLLOW-UP

Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after

discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked

response audiometry may be used in young children or those who cannot cooperate with pure

tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation

suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing

impairment in children)

Development mdash Young children who have been treated for meningitis are at risk for

developmental delay Those who are younger than three years of age may be eligible to

receive Early Intervention Services in the United States (eligibility criteria vary by state)

Appropriate referrals should be made as indicated Developmental surveillance should

continue throughout childhood (See Developmental-behavioral surveillance and screening in

primary care section on When to perform developmental-behavioral screening)

PREVENTION

Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard

precautions [202127] (See General principles of infection control section on Standard

precautions)

In addition droplet precautions are recommended for patients with N meningitidis and H

influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy

[2027] Patients should be in private rooms and hospital personnel should wear a face mask

when they are within 3 feet (1 meter) of the patient

Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of

patients with meningococcal and Hib meningitis is discussed separately (See Treatment

and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and

Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close

contacts)

Although it does not have a role in preventing the spread of pneumococcal meningitis

chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in

children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic

patient section on Antibiotic prophylaxis and Overview of the management of sickle cell

disease section on Infection prevention)

Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid

(CSF) leaks and predispose patients to meningitis because of the potential for direct

communication of bacteria in the upper respiratory tract with the central nervous system

There is no evidence that antibiotics given prophylactically are efficacious for preventing

meningitis [74]

Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial

meningitis in children are discussed separately

S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate

vaccines in children and Pneumococcal (Streptococcus pneumoniae)

polysaccharide vaccines in children section on Indications)

N meningitidis (see Meningococcal vaccines and Patient information Vaccines for

children age 7 to 18 years (Beyond the Basics))

Hib (see Prevention of Haemophilus influenzae infection section on Immunization

and Patient information Vaccines for infants and children age 0 to 6 years (Beyond

the Basics))

INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education

materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are

written in plain language at the 5th to 6th grade reading level and they answer the four or five

key questions a patient might have about a given condition These articles are best for

patients who want a general overview and who prefer short easy-to-read materials Beyond

the Basics patient education pieces are longer more sophisticated and more detailed These

articles are written at the 10th to 12th grade reading level and are best for patients who want

in-depth information and are comfortable with some medical jargon

Here are the patient education articles that are relevant to this topic We encourage you to

print or e-mail these topics to your patients (You can also locate patient education articles on

a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)

Basics topics (see Patient information Meningitis in children (The Basics) and

Patient information Bacterial meningitis (The Basics))

Beyond the Basics topic (see Patient information Meningitis in children (Beyond the

Basics))

SUMMARY AND RECOMMENDATIONS

Immediate and supportive care

Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is

performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance

of delay above)

The pretreatment evaluation of children with suspected bacterial meningitis should

include a complete history and physical examination cerebrospinal fluid (CSF)

examination (cell count and differential glucose protein Gram stain and culture)

complete blood count (CBC) with differential and platelet count blood cultures serum

electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is

indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment

evaluation above)

Immediate management of children with suspected bacterial meningitis includes

assessment and stabilization of ventilation and perfusion and initiation of

hemodynamic monitoring and support while obtaining appropriate laboratory studies

and establishing venous access Empiric antibiotic therapy and dexamethasone if

warranted should be administered as soon as possible after lumbar puncture

Hypoglycemia acidosis and coagulopathy should be treated as necessary (See

Immediate management above)

For children who are neither in shock nor dehydrated we suggest moderate fluid

restriction (1200 mLm2 per day) until evidence of inappropriate secretion of

antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)

Antibiotic and dexamethasone therapy

We recommend that the empiric regimen for infants and children older than one

month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus

pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade

1A) (See Major pathogens above and Empiric regimen above)

An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum

dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per

day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or

ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses

(See Empiric regimen above)

We recommend the use of dexamethasone for children with Hib meningitis (Grade

1A) (See Use of dexamethasone above and Dexamethasone and other measures

to prevent neurologic complications of bacterial meningitis in children section on

Dexamethasone)

Decisions regarding the use of dexamethasone in children with pneumococcal

meningitis or in whom bacterial meningitis is suspected but the etiology unknown

must be individualized after careful analysis of the potential risks and benefits The

author of this topic review usually does not administer dexamethasone to children

with suspected pneumococcal or meningococcal meningitis In the same patients

other experts may choose to use dexamethasone (See Use of dexamethasone

above and Pneumococcal meningitis in children section on Dexamethasone and

Dexamethasone and other measures to prevent neurologic complications of

bacterial meningitis in children section on Dexamethasone)

We recommend not using dexamethasone if more than one hour has elapsed since

the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone

above and Dexamethasone and other measures to prevent neurologic complications

of bacterial meningitis in children section on Dexamethasone)

The empiric regimen may need to be broadened in infants and children with immune

deficiency recent neurosurgery penetrating head trauma and anatomic defects

Patients with these conditions should be managed in consultation with a specialist in

pediatric infectious diseases (See Special circumstances above)

Once the causative agent and its in vitro antimicrobial susceptibility pattern are

known empiric antimicrobial therapy can be altered accordingly (See Specific

therapy above)

The duration of antimicrobial therapy depends upon the causative organism and the

clinical course (See Duration of therapy above)

Response to treatment

The response to therapy is monitored clinically (eg fever curve resolution of

symptoms and signs) Repeat examination of the spinal fluid may be necessary in

some patients (See Response to therapy above)

Re-examination of CSF is indicated for patients who have a poor clinical response

despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for

children with third-generation cephalosporin-resistant pneumococcal meningitis and

for children with pneumococcal meningitis who were treated with dexamethasone In

addition re-examination of the CSF is necessary after two to three days of treatment

for Gram-negative bacillary meningitis to determine appropriate duration of therapy

(See Repeat CSF analysis above and Gram-negative rods above)

Neuroimaging is indicated in infants and children with signs or symptoms of

complications andor recurrent meningitis (See Neuroimaging above)

Prognosis and follow-up

The overall mortality for bacterial meningitis in infants and children is approximately 5

percent in developed countries and 8 percent in developing countries (See Mortality

above)

Neurologic sequelae including deafness intellectual disability spasticity andor

paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic

sequelae above)

Children who have been treated for bacterial meningitis should undergo hearing

evaluation at the time of or shortly after discharge They should also be followed

closely for other neurologic sequelae including gross motor and cognitive impairment

(See Follow-up above)

Antibiotic prophylaxis

Chemoprophylaxis is recommended for certain contacts of patients with

meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus

influenzae infection section on Antibiotic prophylaxis of close contacts and

Treatment and prevention of meningococcal infection section on Antimicrobial

chemoprophylaxis)

Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19