Bacterial Meningitis in Infants Over 3 Months of Age

25/4/22, 20:40 Bacterial Meningitis in Infants Over 3 Months of Age - Pediatrics - MSD Manual Professional Edition
MSD MANUAL
Professional Version
Bacterial Meningitis in Infants Over

3 Months of Age
By Geoffrey A. Weinberg , MD, Golisano Children’s Hospital
Last full review/revision Sep 2021| Content last modified Sep 2021
Bacterial meningitis in infants is a serious infection of the meninges and subarachnoid space. Infants
may present with nonspecific symptoms and signs (eg, lethargy, irritability, poor feeding, fever or
hypothermia). Diagnosis is by cerebrospinal fluid analysis. Treatment is with antimicrobials and, for
selected infants, dexamethasone.
For an overview of meningitis, see Overview of Meningitis. For acute bacterial meningitis in older
children and adults, see Acute Bacterial Meningitis, and in children < 3 months see Neonatal Bacterial
Meningitis. For viral meningitis, including in infants and children, see Viral Meningitis. (See also 1 and
2.)
General references
1. Weinberg GA, Stone RT: Bacterial infections of the nervous system. In Swaiman's Pediatric
Neurology: Principles and Practice, 6th ed., edited by Swaiman KF, Ashwal S, Ferriero DM, Schor NF,
Finkel RS, Gropman AL, Pearl PL, and Shevell MI. Philadelphia, Elsevier, 2018, pp. 883–894.
2. Committee on Infectious Diseases, American Academy of Pediatrics: Red Book: 2021–2024 Report of
the Committee on Infectious Diseases, ed. 32, edited by Kimberlin DW, Barnett ED, Lynfield R, and
Sawyer MH. Itasca, American Academy of Pediatrics, 2021.
Etiology of Bacterial Meningitis in Infants

The etiology and incidence of bacterial meningitis are closely related to age and whether the infants
have received routine immunization with the Haemophilus influenzae type b conjugate vaccine and
the Streptococcus pneumoniae conjugate vaccine.
In infants who have not received routine immunizations, common causes of bacterial meningitis
include
S. pneumoniae (many serotypes; particularly in infants with no record of S. pneumoniae
conjugate vaccination)
Neisseria meningitidis (especially serogroup B, but occasionally groups A, C, Y, or W135)
H. influenzae type b (particularly in infants with no record of H. influenzae type b conjugate
vaccination)
Other etiologies of bacterial meningitis in infants and children > 3 months of age have been reported
but are very rare. Listeria monocytogenes, Streptococcus agalactiae, and Escherichia coli cause disease in
infantsp< 3 months of age; they rarely
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Bacterial Meningitis in Infants Over 3 Months of Age - Pediatrics - MSD Manual Professional Edition
The younger the patient, the less specific are the symptoms and signs of meningitis.
The initial manifestations of bacterial meningitis may be an acute febrile illness with respiratory or
gastrointestinal symptoms followed only later by signs of serious illness. About 33 to 50% of neonates
have a bulging anterior fontanelle, but only rarely do they have nuchal rigidity or other classic
meningeal signs (eg, Kernig sign or Brudzinski sign) typically present in older children. In children < 12
months, the absence of nuchal rigidity must not be used to exclude meningitis.
Pearls & Pitfalls

In children < 12 months, the absence
of nuchal rigidity must not be used to
exclude meningitis. However, if
present, nuchal rigidity should not be
ignored.
As bacterial meningitis progresses, children develop central nervous system (CNS) manifestations,
sometimes very rapidly. The degree of CNS derangement ranges from irritability to coma. As many as
15% of children who have bacterial meningitis are comatose or semicomatose at the time of
hospitalization. Seizures sometimes occur with bacterial meningitis but in only about 20% of children
—typically those who are already toxic, obtunded, or comatose. Infants who are alert and appear
normal after a brief, non-focal seizure with fever are unlikely to have bacterial meningitis (see also
Febrile Seizures).
Papilledema is very uncommon in children of any age with bacterial meningitis. When papilledema is
present, other causes of papilledema should be sought; bacterial meningitis progresses so quickly
that there is usually insufficient time for papilledema to develop.
Diagnosis of Bacterial Meningitis in Infants

Cerebrospinal fluid (CSF) analysis
In general, lumbar puncture should be done whenever the diagnosis of meningitis is known or
suspected in an infant.
However, lumbar puncture may be delayed for the following reasons:
Clinically important cardiorespiratory compromise (most often in young infants)
Signs of significantly increased intracranial pressure, including retinal changes; altered pupillary
responses; hypertension, bradycardia, and respiratory depression (Cushing triad); and focal
neurologic signs
Suspected intracranial injury, including presence of visible injuries, particularly to the head, or
history suggestive of nonaccidental injury
Infection at the site of lumbar puncture
Suspicion or history of bleeding disorders (eg, hemophilia, severe thrombocytopenia)
In these circumstances, blood cultures should be done and antibiotics should be given empirically
without doing the lumbar puncture. In cases of suspected increased intracranial pressure,
arrangements should be made for a neuroimaging study (eg, cranial CT with and without contrast
enhancement, cranial ultrasonography) during or immediately after antibiotics administration. If the
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CSF is sent for analysis typically cell count protein glucose Gram stain culture and in selected
CSF is sent for analysis, typically cell count, protein, glucose, Gram stain, culture, and, in selected
infants, polymerase chain reaction (PCR) tests for enteroviruses (eg, in infants with meningitis during
the late summer and autumn months in the US), herpes simplex virus, or parechovirus.
Simultaneously, a blood sample should be drawn and sent to have the CSF:blood glucose ratio
determined.
Typical CSF findings in bacterial meningitis include
High white blood cell (WBC) count (> 500/mcL [0.5 × 109/L] often to as high as 10,000 WBC/mcL
[10 × 109/L], with a predominance of polymorphonuclear leukocytes [> 80%])
Elevated protein (> 100 mg/dL [1 gm/L])
Low glucose (< 40 mg/dL [2.2 mmol/L], often < 10 mg/dL [0.56 mmol/L], and CSF:blood glucose
ratio typically < 0.33)
Gram stain often shows organisms in the CSF in bacterial meningitis. Although findings may vary
somewhat, infants who have bacterial meningitis very rarely have completely normal CSF at
examination.
Infants also should have 2 sets of blood cultures (if possible; minimum 1 set of aerobic and anaerobic
culture bottles), serum electrolytes, complete blood count and differential, and a urinalysis and urine
culture.
Differential diagnosis
Symptoms and signs of bacterial meningitis may also be caused by other CNS infections, including
viral meningitis (typically enteroviral or, in young infants, parechoviral), neonatal HSV infection (almost
exclusively in the infant < 1 month of age), pediatric HSV encephalitis, and brain abscess. Other causes
of CNS infections that affect older children and adults (eg, Lyme neuroborreliosis; fungal meningitis;
tuberculous meningitis; Bartonella infection; chemical meningitis resulting from use of nonsteroidal
anti-inflammatory drugs, trimethoprim/sulfamethoxazole, or IV immune globulin; cancer) rarely occur
in children < 12 months and should be distinguishable based on history, physical examination, and
examination of the CSF.
In these other causes of meningitis, CSF findings most often include < 500 WBC/mcL (0.5 × 109/L) with
< 50% polymorphonuclear leukocytes, protein < 100 mg/dL (1 g/L), normal glucose, and a negative
Gram stain for organisms.
Prognosis for Bacterial Meningitis in Infants

Among older infants and children, the mortality rate with bacterial meningitis is about 5 to 10%, and
neurologic morbidity (eg, sensorineural hearing loss, intellectual disability, spasticity and paresis,
seizure disorder) occurs in 15 to 25%. Sensorineural deafness is most common after pneumococcal
meningitis.
In older infants and children, mortality rates vary from 3 to 5% when the cause is H. influenzae type b,
5 to 10% when the cause is N. meningitidis, and 10 to 20% when the cause is S. pneumoniae.
Treatment of Bacterial Meningitis in Infants

Antimicrobial therapy
As soon as bacterial meningitis is diagnosed (actually or presumptively), IV access should be secured
and appropriate antimicrobial drugs (and possibly corticosteroids) should be given.
Empiricp antimicrobial therapy for p infants > 3 monthsyis directed at the common pathogens:
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Ceftriaxone or cefotaxime plus
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Vancomycin
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Cefotaxime and ceftriaxone are extremely effective against the organisms that usually cause bacterial
meningitis in infants > 3 months. The major difference between these drugs is that ceftriaxone has a
much longer serum half-life than cefotaxime. Vancomycin is given because some pneumococcal
strains in certain areas are not susceptible to 3rd-generation cephalosporins. In areas (and
institutions) where most pneumococci are susceptible to penicillin, vancomycin may not be necessary,
particularly if no gram-positive cocci are seen on the CSF Gram stain; decision to withhold vancomycin
should typically be made in consultation with an infectious disease specialist.
Once the infecting organism is identified, more specifically targeted drugs are used; for example,
vancomycin may no longer be required.
Organism-specific antimicrobial therapy
After immediate empiric antimicrobial drugs have been started, results of CSF and/or blood cultures
are used to select a more specifically targeted drug while waiting for microbial identification and
susceptibility test results. (See table Specific Therapy for Bacterial Meningitis in Infants Over 3 Months
of Age Once Identification and Susceptibility Results Are Known and see table Recommended Dosages
of Antimicrobial Drugs for Infants and Children With Bacterial Meningitis.)
If S. pneumoniae is suspected (eg, because gram-positive cocci in pairs are seen on a Gram stain of
the CSF), the empiric vancomycin should be continued until susceptibility test results are available.
Vancomycin is stopped if the isolate is susceptible to penicillin or the 3rd-generation cephalosporins;
if the isolate is not susceptible, vancomycin is continued (and some clinicians add rifampin). Because
dexamethasone can decrease the CSF penetrance (and thus effectiveness) of vancomycin, some
experts advise that either dexamethasone should not be given or, if given, that rifampin be added
concurrently.
Disease caused by N. meningitidis is treated reliably with penicillin G or ampicillin at high doses, or
alternatively by a 3rd-generation cephalosporin. If penicillin or ampicillin therapy is used, it is followed
by a 2-day course of twice-daily rifampin to clear the carrier state and prevent relapse (rifampin is not
necessary if a 3rd-generation cephalosporin is used to complete therapy).
If H. influenzae type b is suspected or proved, disease may be treated reliably with either
ceftriaxone or cefotaxime; ampicillin may be used only if the isolate is proved susceptible. If ampicillin
therapy is used, it is followed by a 4-day course of once-daily rifampin to clear the carrier state and
prevent relapse (rifampin is not necessary if a 3rd-generation cephalosporin is used to complete
therapy).
Specific antimicrobial therapy for other rare infections (eg, S. agalactiae, E. coli, L. monocytogenes, S.
aureus) should be selected in consultation with an infectious disease specialist.
TABLE
Specific Therapy for Bacterial Meningitis in Infants Over 3 Months of

Age Once Identification and Susceptibility Results Are Known
Pathogen Therapy
Penicillin MIC ≤ 0.06 mcg/mL and ceftriaxone

or cefotaxime MIC ≤ 0.5 mcg/mL: Penicillin G
or ampicillin for 10–14 days; ceftriaxone or
cefotaxime also acceptable
Penicillin MIC ≥ 0.12 mcg/mL and ceftriaxone
Streptococcus
p pneumoniae p or cefotaxime
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MIC = minimum inhibitory concentration.
Penicillin G or ampicillin for 7 days (must be
TABLE
Recommended Dosages of Antimicrobial Drugs for Infants and

Children With Bacterial Meningitis
Drug Infants and Children
Ampicillin 50–75 mg/kg every 6 hours
Cefotaxime 50–75 mg/kg every 6 hours
40–50 mg/kg every 12 hours

Ceftriaxone or
80–100 mg/kg every 24 hours
50,000–66,667 units/kg every 4 hours

Penicillin G or
75,000–100,000 units/kg every 6 hours
if i 0 k 2h
Corticosteroids for bacterial meningitis

The use of corticosteroids (eg, dexamethasone) as adjunctive therapy in bacterial meningitis has been
studied for decades and continues to be controversial. The beneficial effects of corticosteroids in
reducing neurologic morbidity appear to vary with the age of the patient (child or adult), the specific
bacterial etiology, and even whether the patient lives in an industrialized country or in the developing
world.
At present, evidence suggests that dexamethasone reduces hearing impairment in infants and
children living in industrialized countries who have bacterial meningitis caused by H. influenzae type b.
The effectiveness of dexamethasone in meningitis caused by other organisms remains unproved,
although some studies of adults in industrialized countries with meningitis caused by S. pneumoniae
report improved neurologic outcomes and reduced mortality. Dexamethasone does not appear to
benefit children or adults with bacterial meningitis who live in developing countries, nor does it seem
to benefit neonates with meningitis.
Thus, dexamethasone 0.15 mg/kg IV should be given before, or within 1 hour after, antimicrobial
therapy in children > 6 weeks of age with meningitis caused by H. influenzae type b. The drug is
continued every 6 hours for 4 days in confirmed H. influenzae type b meningitis. Some experts also
recommend using this same dexamethasone regimen in children with pneumococcal meningitis who
are > 6 weeks of age.
For optimal efficacy, dexamethasone must be started at the time of diagnosis; this is not always
possible, unless the Gram stain of the fluid or epidemiologic factors (eg, disease contact history) can
yield an immediate etiologic diagnosis. In regions where children have been given routine H.
influenzae type b and pneumococcal conjugate vaccines, bacterial meningitis caused by these
organisms will be rare. For these reasons, along with the conflicting evidence regarding the benefits of
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Prevention of BacterialClick
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Prevention of bacterial meningitis involves vaccination and sometimes chemoprophylaxis.

Vaccination
A conjugate pneumococcal vaccine effective against 13 serotypes, including > 90% of the
pneumococcal serotypes that cause meningitis in infants, is recommended for all children beginning
at 2 months of age (see Table: Recommended Immunization Schedule for Ages 0–6 Years). For further
information, see current Advisory Committee on Immunization Practices (ACIP) pneumococcal vaccine
recommendations and the Centers for Disease Control and Prevention's child and adolescent
immunization schedule for ages 18 years or younger, United States, 2021.
Routine vaccination with an H. influenzae type b conjugate vaccine also is highly effective and begins
at age 2 months. For further information, see current ACIP Haemophilus influenzae vaccine
recommendations.
The ACIP recommends that infants > 6 weeks who are at high risk of meningococcal disease receive a
meningococcal conjugate vaccine. For infants not at high risk, routine meningococcal conjugate
vaccination is recommended at age 11 or 12 years (see Table: Recommended Immunization Schedule
for Ages 7–18 Years). High-risk infants include those who
Have HIV infection
Have functional or anatomic asplenia (including patients with sickle cell disease)
Have persistent complement component pathway deficiencies
Complement inhibitor use (eg, eculizumab, ravulizumab)
Are traveling to or reside in a high-risk area (eg, sub-Saharan Africa, Saudi Arabia, or during the
Hajj)
Exposure to an outbreak attributable to a vaccine serogroup
Two serogroup B meningococcal vaccines have been approved by the ACIP for use in children ≥ 10
years of age who are at high risk of meningococcal group B disease (same categories as above);
routine meningococcal B vaccination is not yet currently given. For further information, see current
ACIP meningococcal vaccine recommendations.
Chemoprophylaxis for meningitis
Antimicrobial chemoprophylaxis is necessary for
N. meningitidis meningitis: All close contacts
H. influenzae meningitis: Selected close contacts
Contacts of children who have meningitis caused by other bacteria do not require chemoprophylaxis.
For meningococcal meningitis, close contacts have a risk of infection that may be 25 to 500 times
higher than that of the general population. Close contacts are defined as
Household members, especially children < 2 years of age
Child care center contacts exposed in the 7 days before symptom onset
Anyone directly exposed to the patient’s oral secretions (eg, through kissing, sharing
toothbrushes or utensils, mouth-to-mouth resuscitation, endotracheal intubation, endotracheal
tube management) in the 7 days before symptom onset
Not every health care practitioner who has cared for an infant with meningitis is considered a close
contact. Health care personnel should receive chemoprophylaxis only if they were managing the
patient's airway or were directly exposed to the patient's respiratory secretions. Chemoprophylaxis
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should be given as soon as possible (ideally within 24 hours of identification of the index patient);
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Haemophilus influenzae Type b Meningitis). For young children, oral rifampin or injectable ceftriaxone
Haemophilus influenzae Type b Meningitis). For young children, oral rifampin or injectable ceftriaxone
is preferred.
For H. influenzae type b meningitis, the risk of infection in contacts is lower than with meningococcal
disease but can be substantial in young, unvaccinated infant or toddler contacts residing in the
household of an index patient. Also, household contacts may be asymptomatic carriers of H.
influenzae type b. Close contacts are defined more explicitly than for meningococcal prophylaxis
because caretakers who spend time in the household but do not live there may nevertheless have
become colonized with H. influenzae type b. Thus for this organism, household contacts are defined
as the following:
People who live with the index patient
People who have spent ≥ 4 hours with the index patient for ≥ 5 of the 7 days preceding the index
patient's hospital admission
Chemoprophylaxis is then recommended for each member of a household, as just defined, if that
household also has
At least 1 contact < 4 years who is incompletely immunized or unimmunized
A child < 12 months who has not completed the primary Hib conjugate immunization series
An immunocompromised child (regardless of previous immunization status)
Complete immunization against H. influenzae type b is defined as having had at least 1 dose of Hib
conjugate vaccine at age ≥ 15 months, or 2 doses between 12 months and 14 months, or the 2- or 3-
dose primary series for children < 12 months with a booster dose at ≥ 12 months.
In addition, if a preschool or child care center has had ≥ 2 cases of invasive Hib disease within 60 days
among its attendees, many experts recommend chemoprophylaxis for all attendees and staff to
eliminate asymptomatic nasal carriage regardless of immunization status.
Close contacts most at risk of secondary infection are children < 4 years who are incompletely
immunized against H. influenzae type b. Chemoprophylaxis should be given < 24 hours after
identification of the index patient; chemoprophylaxis given > 2 weeks after exposure is likely of little
to no value. Oral rifampin or injectable ceftriaxone is preferred, and ciprofloxacin is acceptable for
older contacts (see Table: Recommended Chemoprophylaxis for High-Risk Contacts* of Children With
Meningococcal or Haemophilus influenzae Type b Meningitis).
TABLE
Recommended Chemoprophylaxis for High-Risk Contacts* of

Children With Meningococcal or Haemophilus influenzae Type b
Meningitis
Drug and
Age Dosage Duration
Indication
Rifampin† (for
Neisseria
meningitidis)
5 mg/kg IV or orally
< 1 month 2 days
every 12 hours
10 mg/kg IV or
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Key Points
Infants with bacterial meningitis may first present with nonspecific symptoms and signs
(eg, of upper respiratory or gastrointestinal illness) but then decompensate rapidly.
The most common bacterial causes of meningitis are Streptococcus pneumoniae, Neisseria
meningitidis, and Haemophilus influenzae type b.
If meningitis is suspected, do lumbar puncture (unless contraindication exists) and give
empiric antimicrobial therapy (and possibly dexamethasone) as soon as possible.
Empiric antimicrobial therapy in infants > 3 months is with cefotaxime or ceftriaxone,
plus vancomycin.
Provide antimicrobial chemoprophylaxis to select contacts of patients with N.
meningitidis meningitis or H. influenzae meningitis.
More Information
The following are some English-language resources that may be useful. Please note that THE MANUAL
is not responsible for the content of these resources.
Advisory Committee for Immunization Practices (ACIP): Current pneumococcal vaccine
recommendations
ACIP: Current meningococcal vaccine recommendations
ACIP: Current Haemophilus influenzae vaccine recommendations
Centers for Disease Control and Prevention (CDC): Child and adolescent immunization schedule for
ages 18 years or younger, United States, 2021
© 2022 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
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25/4/22, 20:40 Bacterial Meningitis in Infants Over 3 Months of Age - Pediatrics - MSD Manual Professional Edition

Bacterial Meningitis in Infants Over

Etiology of Bacterial Meningitis in Infants

Symptoms and Signs ofClick

Pearls & Pitfalls

Diagnosis of Bacterial Meningitis in Infants

Prognosis for Bacterial Meningitis in Infants

Treatment of Bacterial Meningitis in Infants

Specific Therapy for Bacterial Meningitis in Infants Over 3 Months of

Penicillin MIC ≤ 0.06 mcg/mL and ceftriaxone

Recommended Dosages of Antimicrobial Drugs for Infants and

Drug Infants and Children

Ampicillin 50–75 mg/kg every 6 hours

Cefotaxime 50–75 mg/kg every 6 hours

40–50 mg/kg every 12 hours

50,000–66,667 units/kg every 4 hours

Corticosteroids for bacterial meningitis

Prevention of bacterial meningitis involves vaccination and sometimes chemoprophylaxis.

Recommended Chemoprophylaxis for High-Risk Contacts* of

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