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Bacterial meningitis in children older than one

month: Treatment and prognosis


Author: Sheldon L Kaplan, MD
Section Editor: Morven S Edwards, MD
Deputy Editor: Carrie Armsby, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2024. | This topic last updated: Aug 29, 2023.

INTRODUCTION

Children with suspected bacterial meningitis require urgent evaluation and


management, including prompt administration of appropriate antimicrobial therapy
( table 1). The mortality rate of untreated bacterial meningitis approaches 100
percent. Even with optimal therapy, morbidity and mortality may occur. Neurologic
sequelae are common among survivors.

The treatment and prognosis of bacterial meningitis in infants and children older than
one month will be reviewed here. Other aspects of bacterial meningitis in pediatric
patients are discussed separately:

● Clinical features, evaluation, and diagnosis (see "Bacterial meningitis in children


older than one month: Clinical features and diagnosis")
● Bacterial meningitis in neonates (see "Bacterial meningitis in the neonate: Clinical
features and diagnosis" and "Bacterial meningitis in the neonate: Treatment and
outcome" and "Bacterial meningitis in the neonate: Neurologic complications")
● Neurologic complications (see "Bacterial meningitis in children: Neurologic
complications" and "Bacterial meningitis in children: Dexamethasone and other
measures to prevent neurologic complications")
● Pathophysiology (see "Pathogenesis and pathophysiology of bacterial
meningitis")
PRETREATMENT EVALUATION

If possible, the pretreatment evaluation of children with suspected bacterial


meningitis should include ( table 1):

● Complete history and physical examination


● Blood tests (eg, complete blood count with differential, serum chemistries,
coagulation studies, and inflammatory markers)
● Blood cultures
● Cerebrospinal fluid (CSF) studies (cell count and differential, glucose, protein)
● CSF Gram stain and culture

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


deteriorating clinical status or the need for neuroimaging, blood culture should be
obtained before the administration of antibiotic therapy ( table 1).

The pretreatment evaluation of infants and children with suspected bacterial


meningitis is discussed in greater detail separately. (See "Bacterial meningitis in
children older than one month: Clinical features and diagnosis", section on
'Evaluation'.)

GENERAL MANAGEMENT

Setting of care — Children who are suspected of having bacterial meningitis based
upon the results of the initial evaluation (including history, physical examination,
laboratory tests, and cerebrospinal fluid [CSF] examination) should be admitted to the
hospital for ongoing management. The level of inpatient care (ward versus pediatric
intensive care unit) is determined by the severity of illness. Admission to a pediatric
intensive care unit is appropriate for children with hemodynamic instability (ie, septic
shock), significant respiratory compromise, prolonged or recurrent seizures, severely
depressed mental status, rapidly deteriorating clinical status, or other potentially life-
threatening complications.

Supportive measures — General supportive measures include:


● Appropriate respiratory support for patients with hypoxia or labored breathing
(see "Initial assessment and stabilization of children with respiratory or
circulatory compromise")

● Establishing venous access (see "Vascular (venous) access for pediatric


resuscitation and other pediatric emergencies")

● Appropriate hemodynamic support for children presenting with signs of shock


(see "Septic shock in children in resource-abundant settings: Rapid recognition
and initial resuscitation (first hour)")

● Treatment of metabolic disturbances such as hypoglycemia, electrolyte


abnormalities, and acidosis if present (see "Approach to hypoglycemia in infants
and children", section on 'Treatment' and "Approach to the child with metabolic
acidosis", section on 'Treatment')

● Treatment of seizures if present (see "Seizures and epilepsy in children: Initial


treatment and monitoring")

Fluid management — Careful management of fluid and electrolyte balance is an


important aspect of supportive therapy. Both over- and underhydration are
associated with adverse outcomes [1]. Hypotonic fluids (eg, one-half or one-quarter
normal saline) should be avoided because they deliver too much free water, which
contributes to hyponatremia and can exacerbate cerebral edema.

The approach to initial fluid management depends on hemodynamic stability, volume


status, and whether there is evidence of syndrome of inappropriate secretion of
antidiuretic hormone (SIADH; eg, serum sodium <130 mEq/L):

● Shock – Children who are in shock should receive volume resuscitation with
isotonic fluid to maintain blood pressure and cerebral perfusion. The
management of septic shock in children is discussed separately. (See "Septic
shock in children in resource-abundant settings: Rapid recognition and initial
resuscitation (first hour)".)
● Hypovolemia without shock – Children who are volume depleted, but not in
shock, should receive volume repletion with isotonic fluids with careful and
frequent attention to fluid status. Daily weight, urine output, and serum
electrolytes should be monitored. (See "Treatment of hypovolemia (dehydration)
in children in resource-abundant settings".)

● SIADH – For children without signs of shock or hypovolemia who have evidence
of SIADH (eg, serum sodium <130 mEq/L), we suggest moderate fluid restriction
(ie, two-thirds to three-quarters of maintenance). Daily weight, urine output,
serum electrolytes, and, if indicated, serum and urine osmolalities should be
carefully monitored. Fluid administration can be liberalized gradually once serum
sodium is >135 mEq/L. Most children can receive maintenance fluid intake within
24 to 48 hours of hospitalization. SIADH is common in children with bacterial
meningitis. In one study, 10 percent of children with pneumococcal meningitis
had initial serum sodium values <130 mEq/L [2]. (See "Treatment of
hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion
(SIADH) and reset osmostat", section on 'Fluid restriction'.)

● Normovolemia without SIADH – Children without signs of shock, hypovolemia,


or SIADH (eg, those with normal perfusion, normal serum sodium [≥135 mEq/L],
and without signs of volume overload) can receive isotonic fluids at a
maintenance rate (calculator 1 and calculator 2). However, fluid status and serum
electrolytes should be reassessed regularly since SIADH can develop subsequent
to the initial presentation. (See "Maintenance intravenous fluid therapy in
children".)

Dexamethasone — The role of dexamethasone therapy to prevent hearing loss and


other neurologic complications of bacterial meningitis in children is uncertain. This
issue is discussed separately. (See "Bacterial meningitis in children: Dexamethasone
and other measures to prevent neurologic complications", section on
'Dexamethasone'.)

Monitoring — Children who are being treated for bacterial meningitis should be
monitored carefully for complications (eg, seizures, signs of elevated intracranial
pressure, development of infected subdural effusions), particularly during the first
two to three days of treatment when complications are most likely to occur [3].

● 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

Infection control — All patients admitted to the hospital with meningitis should be
placed on standard precautions [4-6]. (See "Infection prevention: Precautions for
preventing transmission of infection", section on 'Standard precautions'.)

In addition, droplet precautions are recommended for patients with suspected


Neisseria meningitidis and Haemophilus influenzae type b (Hib) meningitis until they
have received 24 hours of effective therapy [4,5]. 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.

ANTIBIOTIC THERAPY

Avoidance of delay — Antibiotic therapy should be initiated immediately after


lumbar puncture (LP) is performed if the clinical suspicion for meningitis is high
( table 1). Delay in the administration of appropriate antibiotics can have a
deleterious effect on outcome for patients who are deteriorating rapidly.

If neuroimaging is to be performed before LP, antibiotic therapy should be initiated


immediately after blood culture is obtained, before neuroimaging is performed.
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. (See "Bacterial meningitis in children older than one
month: Clinical features and diagnosis", section on 'Cerebrospinal fluid culture'.)
Treatment principles — There are two general principles of antibiotic therapy for
bacterial meningitis:

● Bactericidal effect – 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
[7,8]. This principle is supported by clinical observations of poor outcomes in
patients receiving bacteriostatic therapy (eg, clindamycin, tetracycline) [9].

● Drug entry into CSF – Treatment of bacterial meningitis requires adequate


concentration of antibiotics in the CSF. Most drugs reach 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.

Inflammation increases the permeability of the blood-brain barrier, which can


increase the peak concentration of drugs in the CSF. This was illustrated in one
study that sequentially monitored CSF and serum penicillin levels in children with
bacterial meningitis. The mean CSF:serum ratio two hours after administration of
the same intravenous (IV) 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 [10]. (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 parenteral antibiotics. Oral antibiotics are not
appropriate for treatment of bacterial meningitis, since the dose and tissue levels
tend to be considerably lower than with parenteral agents.

Empiric therapy — The organism causing bacterial meningitis seldom is known at


the outset of therapy. As a result, the initial empiric treatment plan is based upon the
most likely pathogens and local susceptibility patterns.

● Empiric regimen – The empiric regimen should include coverage for


meningococcus and penicillin-resistant pneumococcus, the two most common
causes of bacterial meningitis in infants and children. (See "Bacterial meningitis in
children older than one month: Clinical features and diagnosis", section on
'Epidemiology'.)

For most patients, we suggest the following regimen [5,6]:

• Vancomycin 60 mg/kg/day IV (maximum dose 4 g/day) in four divided doses,


plus

• Ceftriaxone 100 mg/kg/day IV (maximum dose 4 g/day) in two divided doses,


or cefotaxime (where available) 300 mg/kg/day IV (maximum dose 12 g/day) in
three or four divided doses

We suggest twice-daily ceftriaxone dosing rather than once daily to avoid the
possibility of inadequate treatment in the event of dosing errors, delayed doses,
or missed doses [3].

For children in whom cephalosporins or vancomycin are contraindicated (eg,


severe allergy), consultation with a pediatric infectious diseases specialist is
advised.

Additional coverage may be warranted in the following circumstances ( table 2):

• Immune deficiency, neurosurgery, or medical device – Children with immune


deficiency, recent neurosurgery, penetrating head trauma, or anatomic defects
may require additional empiric coverage, as summarized in the table
( table 2).

• Adjunctive dexamethasone – Some experts suggest the addition of rifampin to


the empiric regimen if dexamethasone is administered [11]. (See "Bacterial
meningitis in children: Dexamethasone and other measures to prevent
neurologic complications", section on 'Antibiotic regimen'.)

• Unusual pathogen on Gram stain – The CSF Gram stain may provide important
clues for the need to broaden empiric therapy to cover for less common or
unusual organisms. However, empiric antibiotics should not be narrowed
based upon CSF Gram stain results, because Gram stain results are subject to
observer misinterpretation [11]; broad-spectrum antimicrobial therapy should
be continued until CSF culture results are available.

● Duration of empiric therapy – The duration of empiric therapy depends upon


the culture results, CSF parameters, and clinical concern for bacterial meningitis:

• Positive culture – Once culture results are available, treatment should be


modified based on the specific pathogen isolated in CSF and/or blood culture.
(See 'Specific therapy' below.)

• Negative culture with normal CSF profile – For children who have a normal
CSF profile and negative blood and CSF cultures, we usually discontinue
antimicrobial therapy if cultures remain sterile after 48 to 72 hours of
incubation.

• Negative culture with CSF pleocytosis – For children with CSF pleocytosis
whose blood and CSF cultures remain negative after 48 to 72 hours, the
decision to continue or discontinue empiric antibiotic therapy is individualized
based upon the clinical status of the child and level of clinical concern for
bacterial meningitis. Consultation with a pediatric infectious diseases specialist
is advised if the clinician is uncertain how to manage such children. Important
considerations include:

- CSF cultures may be negative in children who received antibiotic therapy


before CSF examination (see "Bacterial meningitis in children older than
one month: Clinical features and diagnosis", section on 'Cerebrospinal fluid
culture')

- Negative CSF culture does not preclude the development of meningitis


hours or days after the LP; if clinical signs suggest meningitis, repeat LP
may be warranted

- Molecular tests can help to identify the specific pathogen in some cases
(see "Bacterial meningitis in children older than one month: Clinical
features and diagnosis", section on 'Molecular methods')
- Nonbacterial causes of CSF pleocytosis should also be considered (see
"Bacterial meningitis in children older than one month: Clinical features
and diagnosis", section on 'Differential diagnosis' and "Viral meningitis in
children: Clinical features and diagnosis", section on 'Distinguishing viral
from bacterial meningitis')

Specific therapy — Once the causative agent and its in vitro antimicrobial
susceptibility pattern are known, empiric antimicrobial therapy can be altered
accordingly. The following sections discuss the choice of antimicrobial regimen
according to the isolated pathogen. Guidance on treatment duration is provided
below. (See 'Treatment duration' below.)

Streptococcus pneumoniae — The therapeutic options for pneumococcal


meningitis are summarized in the table ( table 3) and discussed in the following
sections [6]. The increasing prevalence of antibiotic-resistant S. pneumoniae has
important implications for the treatment of pneumococcal meningitis, as discussed
below. (See "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics" and
"Streptococcus pneumoniae: Microbiology and pathogenesis of infection".)

● Penicillin-susceptible isolates – In children with penicillin-susceptible isolates


(minimum inhibitory concentration [MIC] ≤0.06 mcg/mL), treatment consists of
[6]:

• Penicillin G 300,000 units/kg/day intravenously (IV) in four to six divided doses,


or

• High-dose ceftriaxone or cefotaxime (ie, same dose as for empiric therapy)

● Penicillin-nonsusceptible, cephalosporin-susceptible isolates – In children


with isolates that are penicillin-nonsusceptible (intermediate or resistant; MIC
>0.06 mcg/mL) but susceptible to ceftriaxone and cefotaxime (MIC ≤0.5 mcg/mL),
treatment consists of high-dose ceftriaxone or cefotaxime [6]. Ceftriaxone and
cefotaxime can attain levels of only 3 to 8 mcg/mL in the CSF and achieve reliable
bactericidal activity only if the MIC is ≤0.5 mcg/mL [12].
● Cephalosporin-nonsusceptible isolates – In children with isolates
nonsusceptible to ceftriaxone and cefotaxime (intermediate [MIC = 1 mcg/mL] or
resistant [MIC ≥2 mcg/mL]), treatment consists of:

• Vancomycin 60 mg/kg/day IV (maximum dose 4 g/day) in four divided doses,


plus

• High-dose ceftriaxone or cefotaxime

• Rifampin (20 mg/kg/day IV in two divided doses) may be added in selected


circumstances (as described below)

Treatment with extended-spectrum cephalosporins alone is generally not


sufficient for isolates with intermediate susceptibility to ceftriaxone or cefotaxime
(MIC = 1 mcg/mL) [6]. In the context of central nervous system infections, isolates
with MICs ≥2 mcg/mL are considered resistant ( table 4).

Rifampin may be added to the regimen (if the isolate is susceptible) in the
following settings [6]:

• If the isolate has a high MIC for cephalosporins (≥4 mcg/mL)


• If the patient appears to be failing vancomycin
• If repeat cerebrospinal fluid culture is not sterile (see 'Repeat lumbar puncture'
below)
• If the patient was treated with dexamethasone

● Other antimicrobials – Other antibiotics that are rarely used in the treatment of
resistant pneumococcal meningitis include meropenem and respiratory
fluoroquinolones (eg, moxifloxacin, levofloxacin, gemifloxacin) [13].

Meropenem is effective in vitro but should not be used for monotherapy [13].

Fluoroquinolones are not routinely recommended for use in children due to the
potential risk of musculoskeletal toxicity. However, for serious infections such as
meningitis, it is reasonable to use a systemic fluoroquinolone when no safe or
effective alternative exists. (See "Fluoroquinolones", section on 'Children'.)
Chloramphenicol also has been used for patients with an allergy to penicillin and
cephalosporin. Unfortunately, many penicillin-resistant strains are somewhat
resistant to chloramphenicol killing (despite in vitro tests that show inhibition)
and treatment failures of meningitis caused by penicillin-resistant S. pneumoniae
have occurred when chloramphenicol was used [14].

Neisseria meningitidis — The preferred agents for meningococcal meningitis are


third-generation cephalosporins (eg, ceftriaxone 100 mg/kg/day IV in two divided
doses [maximum 4 g/day] or cefotaxime [where available] 225 to 300 mg/kg/day IV
[maximum dose 12 g/day] in three or four divided doses). High-dose penicillin G
(300,000 units/kg/day in four divided doses) is an alternative low-cost option.
However, the susceptibility of the isolate to penicillin should be documented before
switching to penicillin since beta-lactamase-producing N. meningitidis isolates have
been reported [15,16]. Patients treated with penicillin should receive antimicrobial
chemoprophylaxis to eradicate nasopharyngeal carriage prior to discharge.
Treatment of meningococcal meningitis is discussed in greater detail separately. (See
"Treatment and prevention of meningococcal infection", section on 'Antibiotic
therapy'.)

Haemophilus influenzae — Meningitis due to H. influenzae is usually treated with a


third-generation cephalosporin such as ceftriaxone (100 mg/kg/day IV in two divided
doses [maximum dose 4 g/day]) or cefotaxime (where available; 200 mg/kg/day IV in
three or four divided doses [maximum dose 12 g/day]). Ampicillin is appropriate only
if the infecting pathogen has been shown to be beta-lactamase negative. Patients
with meningitis due to H. influenzae type b who are treated with agents other than
ceftriaxone or cefotaxime should receive antibiotic chemoprophylaxis prior to
discharge [17]. Treatment of H. influenzae meningitis and postexposure
chemoprophylaxis are discussed in greater detail separately. (See "Epidemiology,
clinical manifestations, diagnosis, and treatment of Haemophilus influenzae", section
on 'Directed treatment' and "Prevention of Haemophilus influenzae type b infection",
section on 'Postexposure chemoprophylaxis'.)

Listeria monocytogenes — The preferred regimen for treatment of meningitis due


to L. monocytogenes in infants and children consists of ampicillin (300 mg/kg/day IV
in four divided doses [maximum dose 12 g/day]) plus gentamicin (7.5 mg/kg/day IV in
three divided doses) ( table 5). The usual treatment duration is 21 to 28 days
(gentamicin may not need to be continued for the entire duration). (See "Treatment
and prevention of Listeria monocytogenes infection", section on 'Preferred regimen'.)

Group B streptococcus (GBS) — The preferred agents for treatment of GBS


(Streptococcus agalactiae) meningitis are penicillin G (450,000 to 500,000 units/kg/day
IV in four divided doses) or ampicillin (300 mg/kg/day IV in three divided doses). The
usual treatment duration is 14 to 21 days. Treatment of GBS is discussed separately.
(See "Group B streptococcal infection in neonates and young infants", section on
'Definitive therapy'.)

Staphylococcus aureus — Meningitis caused by S. aureus is uncommon in children


unless there is an underlying anatomic defect (eg, dermal sinus), immune
dysfunction, or implanted device (eg, CSF drain or shunt). Management of CSF shunt
infections is discussed separately. (See "Infections of cerebrospinal fluid shunts",
section on 'Treatment'.)

Antimicrobial therapy for S. aureus meningitis is as follows:

● MSSA – The standard therapy for methicillin-susceptible S. aureus (MSSA)


meningitis is nafcillin or oxacillin (both are dosed at 150 to 200 mg/kg/day IV in
four doses [maximum 12 g/day]) [11,18]. Treatment duration is typically 14 days.

● MRSA – The preferred therapy for methicillin-resistant S. aureus (MRSA)


meningitis is vancomycin (60 mg/kg/day IV in four divided doses [maximum dose
4 g/day]) [11,18,19]. Treatment duration is at least 14 days. Some experts
recommend adding rifampin to vancomycin if the isolate is susceptible to
rifampin (20 mg/kg/day orally or IV in two divided doses [maximum dose 600
mg/day]).

Alternative agents for MRSA meningitis include ceftaroline (45 mg/kg/day in three
divided doses), trimethoprim-sulfamethoxazole (TMP-SMX; 10 to 12 mg/kg of the
TMP component and 50 to 60 mg/kg of the SMX component per day in four
divided doses) or linezolid (in patients <12 years old: 30 mg/kg/day IV in three
divided doses [maximum dose 1200 mg/day]; in patients ≥12 years old: 600 mg IV
twice per day) [11,18,19]:

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


into the CSF [20-23]. Rapid penetration has been demonstrated in children and
adolescents [23]. 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 [18,24].

Treatment of invasive MSSA and MRSA infections in children is discussed in greater


detail separately. (See "Staphylococcus aureus in children: Overview of treatment of
invasive infections", section on 'Definitive antimicrobial therapy'.)

Gram-negative rods (GNRs) — Consultation with a pediatric infectious diseases


specialist is advised for children with meningitis caused by a GNR. Choices for IV
therapy are outlined here and discussed in greater detail separately. (See "Infections
of cerebrospinal fluid shunts".)

● Enteric GNR – The usual treatment regimen for susceptible isolates consists of an
extended-spectrum cephalosporin (eg, ceftriaxone 100 mg/kg/day IV in two
divided doses [maximum dose 4 g/day] or cefotaxime [where available] 200 to
300 mg/kg/day IV in four divided doses [maximum dose 12 g/day]) plus an
aminoglycoside (eg, gentamicin 7.5 mg/kg/day IV in three divided doses) [25]. The
aminoglycoside often can be discontinued after the first five to seven days, once
the CSF is documented to be sterile.

● Pseudomonas aeruginosa – Ceftazidime (150 mg/kg/day IV in three divided


doses [maximum dose 6 g/day]) or cefepime (150 mg/kg/day IV in three divided
doses [maximum dose 6 g/day]) are the most effective cephalosporins for
treating susceptible P. aeruginosa infections [26]. For ceftazidime-resistant
strains, meropenem (120 mg/kg/day IV in three divided doses [maximum dose 6
g/day]) is an effective treatment.
● Extended-spectrum beta-lactamase (ESBL)-producing organisms –
Meropenem (120 mg/kg/day IV in three divided doses [maximum dose 6 g/day])
is the agent of choice in the treatment of meningitis caused by susceptible ESBL-
producing GNRs [27,28].

Repeat LP should be performed two to three days after starting therapy to assess the
efficacy of treatment. (See 'Repeat lumbar puncture' below.)

Occasionally, IV therapy alone is insufficient and intraventricular administration


of an antibiotic (typically an aminoglycoside) is necessary to sterilize the CSF.
Intraventricular therapy should be undertaken in consultation with specialists
in pediatric infectious diseases and neurosurgery. This issue is discussed in
greater detail separately. (See "Infections of cerebrospinal fluid shunts",
section on 'Adjunctive intraventricular antibiotics in selected cases'.)

Treatment duration — The duration of antimicrobial therapy depends upon the


causative organism and clinical course. We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [4-6,11]:

● S. pneumoniae – 10 to 14 days
● N. meningitidis – 5 to 7 days
● H. influenzae – 7 to 10 days
● L. monocytogenes – 21 to 28 days
● S. aureus – At least two weeks
● Gram-negative bacilli – Three weeks or a minimum of two weeks beyond the first
sterile CSF culture, whichever is longer

Limited observational and clinical trial data suggest that in carefully selected cases, a
shorter duration of therapy may be equally efficacious and may reduce hospital
duration and health care costs [29-31]. However, due to the limitations of these data,
as described below, we view the findings as preliminary and continue to suggest
organism-specific durations of therapy, as outlined above.

A 2009 meta-analysis of five randomized trials (383 children) found that treatment for
4 to 7 days resulted in rates of cure similar to treatment for 7 to 14 days (odds ratio
1.24, 95% CI 0.73-2.11) [30]. However, the trials included in the meta-analysis had
important limitations, including lack of blinding in all five trials, small number of
patients, and relatively short follow-up. In addition, there was considerable variability
in the distribution of causative organisms in the different trials, with the most
common being S. pneumoniae, N. meningitidis, and H. influenzae type b (Hib). In a
subsequent multicenter trial in resource-limited countries involving >1000 children
with bacterial meningitis (S. pneumoniae in 33 percent, Hib in 26 percent, N.
meningitidis in 7 percent, and no identified cause in 33 percent), outcomes were
generally similar among children treated with ceftriaxone for 5 versus 10 days [29].
There were two cases of relapse in the 5-day group versus none in the 10-day group,
and there were nine meningitis-related deaths (2 percent) in the 5-day group versus
six (1 percent) in the 10-day group. While these differences were not statistically
significant, the study may have been underpowered to detect important differences.
Furthermore, the setting, methodology, and lack of organism-specific outcome
information preclude generalizability to resource-abundant settings [29,32].

Outpatient therapy — In selected patients, a portion of parenteral antibiotic therapy


may be administered in the outpatient setting [11,33]. In our practice, we very rarely
complete antimicrobial therapy for bacterial meningitis at home; however, it may be a
reasonable option for some patients if all of the following criteria are met [34]:

● Patient is clinically stable and afebrile for at least 24 to 48 hours.

● Patient has completed at least six days of inpatient therapy – Serious adverse
complications of meningitis are uncommon after three or four days of therapy,
particularly in children who are clinically well and afebrile [35].

● Patient has normal or nearly normal neurologic function (no focal findings and no
seizure activity).

● There is no concern for complications of meningitis on neuroimaging (eg, no


abscess or subdural collection).

● Patient is able to take fluids by mouth.


● Patient has reliable venous access (ie, a peripherally inserted central catheter or
tunneled central venous catheter).

● Caregivers are reliable and have transportation and a telephone.

If the outpatient regimen will be different from the regimen given in the hospital, we
suggest that the first dose be supervised in the hospital to ensure that the patient
tolerates it. Home antibiotic therapy should be administered by a qualified home
health nursing professional or a caregiver who has received proper instruction. If the
family is not comfortable administering the antibiotics, arrangements can be made to
administer antibiotics in the office. In addition, the patient should be examined daily
by a clinician (eg, visiting nurse, primary care provider). If any concerns arise
(recurrence of fever, new neurologic findings), the patient should be referred for
further evaluation.

Potential advantages of completing therapy in the outpatient setting are that it


decreases the risk of nosocomial infection, improves quality of life for the patient and
family, and decreases health care costs [34,36]. Risks include the potential for missed
doses, administration errors, catheter-related complications, adverse drug events,
and risks posed by provision of care by caregivers who may lack formal medical
training. Careful patient selection and close monitoring are keys to the success and
safety of this approach [34,36,37].

Additional details regarding outpatient parenteral antibiotic therapy are provided


separately. (See "Outpatient parenteral antimicrobial therapy".)

RESPONSE TO THERAPY

The response to therapy is monitored with clinical and laboratory parameters (eg,
fever curve, resolution of symptoms and signs, normalization of inflammatory
markers) and by neuroimaging.

Duration of fever — Fevers typically last three to six days after initiating adequate
therapy [3]. Fever lasts >5 days in approximately 10 to 15 percent of patients [3,38];
secondary fever (eg, recurrence of fever after being afebrile for at least 24 hours)
occurs in approximately 15 to 20 percent [3,38].

Causes of persistent or secondary fever include [3]:

● Inadequate treatment
● Development of nosocomial infection (eg, infected intravenous [IV] catheters,
urinary tract infection, viral infection); nosocomial infection is more often
associated with secondary fever than with persistent fever
● Discontinuation of dexamethasone (see "Bacterial meningitis in children:
Dexamethasone and other measures to prevent neurologic complications",
section on 'Adverse effects')
● Development of a suppurative complication (pericarditis, pneumonia, arthritis,
subdural empyema ( image 1 and picture 1))
● Drug fever (a diagnosis of exclusion)

In patients with persistent or secondary fever, suppurative and nosocomial


complications should be carefully sought. The evaluation typically includes repeat
blood culture, complete blood count, C-reactive protein, and urinalysis. The need for
repeat evaluation of the cerebrospinal fluid (CSF) should be considered on an
individual basis. 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 individual's host response to infection is
responsible for the prolonged fever.

Repeat blood culture — As discussed above, repeat blood culture may be warranted
in patients with persistent or secondary fever. In addition, for patients who had a
positive blood culture at initial evaluation, blood culture 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.

Repeat lumbar puncture — Reexamination of the CSF is warranted in the following


circumstances:
● Poor clinical response – Patients who have a poor clinical response despite 24 to
36 hours of appropriate antimicrobial therapy should undergo repeat lumbar
puncture (LP) [11]. This is particularly important in the following settings:

• Children with cephalosporin-resistant pneumococcal meningitis

• Children with high bacterial burden in CSF (eg, sheets of bacteria on Gram
stain)

• 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) (see "Bacterial meningitis in
children: Dexamethasone and other measures to prevent neurologic
complications", section on 'Adverse effects')

● Gram-negative bacillary meningitis – Patients with gram-negative bacillary


meningitis should undergo repeat LP two to three days after beginning treatment
to document that the CSF is sterile and to determine treatment duration.

● Persistent or recurrent fever – Repeat LP also may be indicated in children with


persistent or recurrent fever. The decision to perform repeat LP in this setting is
individualized, as discussed above. (See 'Duration of fever' above.)

Reexamination of the CSF in these settings informs decisions about extending


duration of therapy and/or changing the antibiotic regimen. Extension of the duration
of therapy is indicated if any of the following are noted:

● CSF cultures from the repeat LP grow a pathogenic organism


● CSF examination at the conclusion of the standard treatment duration shows >30
percent neutrophils
● CSF examination at the conclusion of the standard treatment duration shows CSF
glucose of <20 mg/dL (or <20 percent of the blood glucose level)

Neuroimaging — Neuroimaging (with computed tomography or magnetic resonance


imaging) may be indicated during the course of treatment to assess for complications
such as subdural empyema, brain abscess, cerebral vascular thrombosis, or
hydrocephalus. Indications for neuroimaging may include [39]:

● Focal neurologic signs or prolonged obtundation

● Unexplained persistent fever

● Increasing head circumference in young infants

● Seizures occurring >72 hours after the start of treatment

● Persistently positive CSF cultures despite appropriate antibiotic therapy

● Persistent elevation of CSF neutrophils (>30 to 40 percent) at the completion of


standard duration of therapy

● Gram-negative meningitis in young infants – Neuroimaging is usually performed


sometime during treatment to evaluate for hydrocephalus and other
complications of the meningitis (see "Bacterial meningitis in children: Neurologic
complications" and "Hydrocephalus in children: Clinical features and diagnosis",
section on 'Neuroimaging')

● Meningitis caused by the organism with a propensity to cause abscess (eg,


Citrobacter, Cronobacter, Streptococcus anginosus)

In addition, imaging is warranted in children who experience recurrent meningitis to


evaluate the possibility of a communication between the nasal passage or ear and the
meninges [40].

PROGNOSIS

Mortality — Reported mortality rates among children with bacterial meningitis range
from 0 to 15 percent, depending upon the setting, era, and infecting organism [41-
47]. In resource-abundant settings, mortality rates associated with bacterial
meningitis are approximately 4 to 5 percent [44,45]. Reported mortality rates in
resource-limited countries are approximately 8 to 10 percent [44].
Case-fatality rates according to the organism isolated are as follows
[2,41,42,44,48,49]:

● H. influenzae type b (Hib) – 4 to 5 percent


● N. meningitidis – 7 percent
● S. pneumoniae – 7 to 15 percent

The risk of mortality is increased in children who are comatose or in shock at the time
of admission and in those who require mechanical ventilation [42,50,51].

Neurologic sequelae — Persistent neurologic sequelae are common in children who


survive an episode of bacterial meningitis. The most common sequelae include
hearing loss, seizures, intellectual disability, and spasticity and/or paresis. This is
discussed in greater detail separately. (See "Bacterial meningitis in children:
Neurologic complications".)

Prognostic factors — Factors related to the outcome of bacterial meningitis in


children include [42,52-58].

● Level of consciousness at the time of admission – In an analysis of data from


654 children with bacterial meningitis, the Glasgow Coma Score (GCS) ( table 6)
at admission was the strongest independent predictor of death or severe
neurologic sequelae at the time of hospital discharge [53]. The likelihood of death
from severe neurologic disability increased with decreasing GCS (approximately
10-fold higher risk with GCS 7 to 9 and approximately 30-fold higher risk with GCS
≤6).

● Etiologic agent – The risk of death or neurologic sequelae is higher in children


with pneumococcal meningitis than with meningococcal or Hib meningitis
[42,50].

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 [42,56,59].
● Seizures – 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
[42]. In a series of children with Hib meningitis, seizures were associated with
subtle cognitive and learning problems [60].

● Cerebrospinal fluid (CSF) glucose concentration – Decreased CSF glucose


concentration (<20 mg/dL [1.1 mmol/L]) at the time of admission appears to be
associated with increased risk of hearing loss [42,54,55].

● Delayed sterilization of the CSF – 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
[61].

● Underlying conditions – Children with underlying immunodeficiency,


malnutrition, malignancy, or preexisting neurologic disease have a higher risk of
death or neurologic sequelae [57,58].

FOLLOW-UP

Hearing evaluation — Hearing evaluation should be performed at the time of or


shortly after discharge from the hospital [62,63]. Hearing may be assessed by pure
tone audiometry; auditory brainstem response 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 hearing
loss. (See "Hearing loss in children: Screening and evaluation".)

Developmental screening — Young children who have been treated for meningitis
are at risk for developmental delay. Developmental surveillance should continue
throughout childhood. (See "Developmental-behavioral surveillance and screening in
primary care".)
Evaluation for immunodeficiency — Children who develop pneumococcal
meningitis with a vaccine serotype ( table 7) despite having received at least one
dose of pneumococcal conjugate vaccine and those who develop Haemophilus
influenzae type b (Hib) meningitis despite two or more doses of the Hib vaccine may
have an underlying immunodeficiency. In such cases, an evaluation of the child’s
immune status with serum immunoglobulin levels and human immunodeficiency
virus (HIV) testing can be considered [6,64]. Infections caused by pneumococcal
serotype 3 are an exception to this since pneumococcal conjugate vaccines are less
protective against this serotype.

In one study of 163 children who underwent immune evaluation after being
diagnosed with invasive pneumococcal disease (87 percent had meningitis), 10
percent were found to have an underlying primary immunodeficiency [64]. However,
in another study that included 28 children who underwent immune evaluation
because they developed invasive pneumococcal disease despite receiving ≥2 doses of
pneumococcal conjugate vaccine, only one child was found to have an
immunodeficiency [65].

PREVENTION

Chemoprophylaxis — Chemoprophylaxis in the following clinical settings is


discussed separately:

● N. meningitidis – Chemoprophylaxis is indicated in close contacts of patients with


meningococcal meningitis ( table 8). This is discussed in a separate topic review.
(See "Treatment and prevention of meningococcal infection", section on
'Antimicrobial chemoprophylaxis'.)

● H. influenzae type b (Hib) – Chemoprophylaxis may be indicated for certain close


contacts of a child with Hib meningitis, depending upon individual circumstances.
This is discussed in a separate topic review. (See "Prevention of Haemophilus
influenzae type b infection", section on 'Postexposure chemoprophylaxis'.)
● S. pneumoniae – 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 "Overview of the management and prognosis of sickle
cell disease", section on 'Infection prevention' and "Prevention of infection in
patients with impaired splenic function", section on 'Antibiotic prophylaxis'.)

● Basilar skull fractures – 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. The available evidence
does not support the routine use of antibiotics prophylactically to prevent
meningitis in this setting [66]. Furthermore, the majority of CSF leaks resolve
spontaneously within one week of injury. However, the incidence of bacterial
meningitis rises substantially if a leak persists past seven days and prophylactic
antibiotics may be appropriate in some cases, particularly if the leak cannot be
repaired in a timely manner. (See "Skull fractures in children: Clinical
manifestations, diagnosis, and management", section on 'Basilar skull fractures'.)

Vaccines — Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately:

● S. pneumoniae (see "Pneumococcal vaccination in children")


● N. meningitidis (see "Meningococcal vaccination in children and adults")
● Hib (see "Prevention of Haemophilus influenzae type b infection")

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and


regions around the world are provided separately. (See "Society guideline links:
Bacterial meningitis in infants and children".)

INFORMATION FOR PATIENTS


UpToDate offers two types of patient education materials, "The Basics" and "Beyond
the Basics." The Basics patient education pieces are written in plain language, at the
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 email these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword[s] of interest.)

● Basics topics (see "Patient education: Meningitis in children (The Basics)" and
"Patient education: Bacterial meningitis (The Basics)")

● Beyond the Basics topic (see "Patient education: Meningitis in children (Beyond
the Basics)")

SUMMARY AND RECOMMENDATIONS


● General supportive management – Children with suspected bacterial
meningitis should be admitted to the hospital for ongoing management.
Supportive management of children with bacterial meningitis includes ( table 1)
(see 'General management' above):

• Appropriate respiratory and hemodynamic support for patients with


respiratory compromise or shock (see "Initial assessment and stabilization of
children with respiratory or circulatory compromise")

• Careful management of fluid and electrolyte balance (see 'Fluid management'


above)
• Monitoring for complications (eg, seizures, signs of elevated intracranial
pressure, development of infected subdural effusions) (see 'Monitoring' above)

• Expert opinion differs on the use of dexamethasone in children with suspected


meningitis; this issue is discussed separately (see "Bacterial meningitis in
children: Dexamethasone and other measures to prevent neurologic
complications")

● Empiric antibiotic therapy – For most patients older than one month with
suspected meningitis, we suggest vancomycin plus high doses of a third-
generation cephalosporin (eg, ceftriaxone, cefotaxime) rather than other
regimens (Grade 2C). This combination provides coverage for antibiotic-resistant
Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae
(type b [Hib] and non-type b), which are the most common causes of bacterial
meningitis in children. Additional coverage may be warranted in select
circumstances, as summarized in the table ( table 2). Empiric antibiotic therapy
should be initiated immediately after lumbar puncture (LP) is performed if the
clinical suspicion for meningitis is high ( table 1). (See 'Empiric therapy' above
and 'Avoidance of delay' above.)

● Specific therapy – Once the causative agent and its in vitro antimicrobial
susceptibility pattern are known, empiric antimicrobial therapy can be altered
accordingly. The duration of antimicrobial therapy depends upon the causative
organism and the clinical course. (See 'Specific therapy' above and 'Treatment
duration' above.)

● Response to therapy – The response to therapy is monitored with clinical and


laboratory parameters (eg, fever curve, resolution of symptoms and signs,
normalization of inflammatory markers). Fevers typically last three to six days
after initiating adequate therapy. Repeat LP and/or neuroimaging may be
warranted in some patients (see 'Response to therapy' above):

• Repeat LP – Reexamination of cerebrospinal fluid (CSF) is indicated for patients


with gram-negative bacillary meningitis (to document that the CSF is sterile)
and in patients who have a poor clinical response despite 24 to 36 hours of
appropriate antimicrobial therapy. Repeat LP also may be warranted in
patients with persistent or recurrent fever. (See 'Repeat lumbar puncture'
above.)

• Neuroimaging – Neuroimaging may be indicated during the course of


treatment to assess for complications such as subdural empyema, brain
abscess, cerebral vascular thrombosis, or hydrocephalus. Indications for
neuroimaging may include focal neurologic signs, prolonged obtundation,
increasing head circumference, seizures occurring >72 hours after the start of
treatment, persistently positive CSF cultures, or persistent CSF neutrophilia
despite appropriate antibiotic therapy. (See 'Neuroimaging' above.)

● Prognosis – The mortality rate for children with bacterial meningitis in resource-
abundant settings is approximately 4 to 5 percent. Neurologic complications are
common among survivors. The most common sequelae include hearing loss,
seizures, intellectual disability, and spasticity and/or paresis. (See 'Prognosis'
above and "Bacterial meningitis in children: Neurologic complications".)

● Follow-up – 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.)

● Chemoprophylaxis – Chemoprophylaxis is indicated for certain close contacts of


patients with meningococcal ( table 8) and Hib meningitis. (See "Prevention of
Haemophilus influenzae type b infection", section on 'Postexposure
chemoprophylaxis' and "Treatment and prevention of meningococcal infection",
section on 'Antimicrobial chemoprophylaxis'.)
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