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 Overview of Meningitis Meningitis is inflammation of the meninges and subarachnoid space. It may result from infections, other disorders, or reactions to drugs. Severity and acuity vary. Findings typically include... read more . For acute bacterial meningitis in older children and adults, see Acute Bacterial Meningitis Acute Bacterial Meningitis Acute bacterial meningitis is rapidly progressive bacterial infection of the meninges and subarachnoid space. Findings typically include headache, fever, and nuchal rigidity. Diagnosis is by... read more , and in children < 3 months see Neonatal Bacterial Meningitis Neonatal Bacterial Meningitis Neonatal bacterial meningitis is inflammation of the meninges due to bacterial invasion. Signs are those of sepsis, central nervous system irritation (eg, lethargy, seizures, vomiting, irritability... read more . For viral meningitis, including in infants and children, see Viral Meningitis Viral Meningitis Viral meningitis tends to be less severe than acute bacterial meningitis. Findings include headache, fever, and nuchal rigidity. Diagnosis is by cerebrospinal fluid (CSF) analysis. Treatment... read more . (See also 1 General references 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... read more and 2 General references 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... read more .)
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.
In infants who have not received routine immunizations, common causes of bacterial meningitis include
Neisseria meningitidis Meningococcal Diseases Meningococci (Neisseria meningitidis) are gram-negative cocci that cause meningitis and meningococcemia. Symptoms, usually severe, include headache, nausea, vomiting, photophobia, lethargy... read more
(especially serogroup B, but occasionally groups A, C, Y, or W135)
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 of Bacterial Meningitis in Infants
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.
Cerebrospinal fluid (CSF) analysis
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 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
Overview of Enterovirus Infections Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more (eg, in infants with meningitis during the late
summer and autumn months in the US), herpes simplex virus
Neonatal Herpes Simplex Virus (HSV) Infection Neonatal herpes simplex virus infection is usually transmitted during delivery. A typical sign is vesicular eruption, which may be accompanied by or progress to disseminated disease. Diagnosis... read more
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.
Symptoms and signs of bacterial meningitis may also be caused by other CNS infections, including
viral meningitis Viral Meningitis Viral
meningitis tends to be less severe than acute bacterial meningitis. Findings include headache, fever, and nuchal rigidity. Diagnosis is by cerebrospinal fluid (CSF) analysis. Treatment... read more (typically enteroviral or, in young infants, parechoviral),
neonatal HSV infection
Neonatal Herpes Simplex Virus (HSV) Infection Neonatal herpes simplex virus infection is usually transmitted during delivery. A typical sign is vesicular eruption, which may be accompanied by or progress to disseminated disease. Diagnosis... read more
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.
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.
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.
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.
Specific Therapy for Bacterial Meningitis in Infants Over 3 Months of Age Once Identification and Susceptibility Results Are Known
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. |
Recommended Dosages of Antimicrobial Drugs for Infants and Children With Bacterial Meningitis
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 |
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 of bacterial meningitis involves vaccination and sometimes chemoprophylaxis.
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.
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
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.
Recommended Chemoprophylaxis for High-Risk Contacts* of Children With Meningococcal or Haemophilus influenzae Type b Meningitis
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 Chemoprophylaxis for meningitis 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. |
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.
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