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Bacterial Meningitis in Infants Over 3 Months of Age

By

Geoffrey A. Weinberg

, MD, University of Rochester School of Medicine and Dentistry

Last full review/revision Mar 2020| Content last modified Mar 2020
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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.

Etiology

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 infants < 3 months of age; they rarely are the etiology in extremely premature infants who have survived to become > 3 months of age. Staphylococcus aureus meningitis may occur in infants who have had trauma or neurologic surgery.

Symptoms and Signs

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

  • 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) during or immediately after antibiotics administration. If the results of the imaging study suggest it is safe, lumbar puncture may be done. However, it is not necessary to routinely do CT before lumbar puncture in young children with suspected meningitis; herniation of the brain is rare in young children with bacterial meningitis, even though all patients with meningitis have some degree of increased intracranial pressure.

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) or herpes simplex virus (eg, infants < 3 months of age). 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), 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 gm/L), normal glucose, and a negative Gram stain for organisms.

Prognosis

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

  • 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.

Empiric antimicrobial therapy for infants > 3 months is directed at the common pathogens: pneumococci, meningococci, and H. influenzae type b.

A typical drug regimen includes

  • Ceftriaxone or cefotaxime plus

  • Vancomycin

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
icon

Specific Therapy for Bacterial Meningitis in Infants Over 3 Months of Age Once Identification and Susceptibility Results Are Known

Pathogen

Therapy

Streptococcus pneumoniae

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 or cefotaxime MIC ≤ 0.5 mcg/mL: Ceftriaxone or cefotaxime for 10–14 days

Penicillin MIC ≥ 0.12 mcg/mL and ceftriaxone or cefotaxime MIC ≥ 1.0 mcg/mL: Ceftriaxone or cefotaxime, plus vancomycin with or without rifampin for 10–14 days

Neisseria meningitidis

Penicillin G or ampicillin for 7 days (must be followed by rifampin to eliminate carrier state)

Alternatives: Ceftriaxone or cefotaxime

Haemophilus influenzae type b

Ceftriaxone or cefotaxime for 10 days

Alternative: Ampicillin if isolate is susceptible (must be followed by rifampin to eliminate carrier state)

MIC = minimum inhibitory concentration.

Table
icon

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

Ceftriaxone

40–50 mg/kg every 12 hours

or

80–100 mg/kg every 24 hours

Penicillin G

50,000–66,667 units/kg every 4 hours

or

75,000–100,000 units/kg every 6 hours

Rifampin

10 mg/kg every 12 hours

Vancomycin

10–15 mg/kg every 6 hours

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 dexamethasone therapy, many pediatric infectious disease experts no longer routinely give corticosteroids to infants with meningitis.

Prevention

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.

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 (eg, with sickle cell disease)

  • Have persistent complement component pathway deficiencies

  • Are traveling to a high-risk area (eg, sub-Saharan Africa, Saudi Arabia during the hajj)

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 should be given as soon as possible (ideally within 24 hours of identification of the index patient); chemoprophylaxis given > 2 weeks after exposure is likely of little to no value. Rifampin, ceftriaxone, and ciprofloxacin are appropriate drugs depending on the age of the contact (see Table: Recommended Chemoprophylaxis for High-Risk Contacts* of Children With Meningococcal or 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
icon

Recommended Chemoprophylaxis for High-Risk Contacts* of Children With Meningococcal or Haemophilus influenzae Type b Meningitis

Drug and Indication

Age

Dosage

Duration

Rifampin† (for Neisseria meningitidis)

< 1 month

5 mg/kg IV or orally every 12 hours

2 days

≥ 1 month

10 mg/kg IV or orally every 12 hours (maximum 600 mg orally every 12 hours)

2 days

Rifampin† (for H. influenzae)

< 1 month

10 mg/kg IV or orally once a day

4 days

≥ 1 month

20 mg/kg IV or orally once a day (maximum 600 mg orally once a day)

4 days

Ceftriaxone (for either pathogen)

< 15 years

125 mg IM

Single dose

≥ 15 years

250 mg IM

Single dose

Ciprofloxacin‡ (for either pathogen)

> 1 month

20 mg/kg orally (maximum 500 mg)

Single dose

* See text for definitions of high-risk close contacts.

Rifampin is not recommended for pregnant women.

Ciprofloxacin is not routinely recommended for children < 18 years; however, it may be used for certain children > 1 month if risks and benefits have been assessed. If fluoroquinolone-resistant strains of meningococci have been identified in a community, ciprofloxacin should not be used for chemoprophylaxis.

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.

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