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Neonatal Bacterial Meningitis

by Mary T. Caserta, MD

(see also Meningitis.)

Neonatal bacterial meningitis is inflammation of the meninges due to bacterial invasion. Signs are those of sepsis, CNS irritation (eg, lethargy, seizures, vomiting, irritability [particularly paradoxical irritability], nuchal rigidity, a bulging or full fontanelle), and cranial nerve abnormalities. Diagnosis is by lumbar puncture. Treatment is with antibiotics.

Neonatal bacterial meningitis occurs in 2/10,000 full-term and 2/1,000 low-birth-weight (LBW) neonates, with a male predominance. It occurs in about 15% of neonates with sepsis and occasionally occurs in isolation.

Etiology

The predominant pathogens are

  • Group B streptococcus (GBS—predominantly type III)

  • Escherichia coli (particularly those strains containing the K1 polysaccharide)

  • Listeria monocytogenes

Enterococci, nonenterococcal group D streptococci, α-hemolytic streptococci, and other gram-negative enteric organisms (eg, Klebsiella sp, Enterobacter sp, Citrobacter diversus) also are pathogens. Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae have been reported as causes.

Neonatal bacterial meningitis most frequently results from the bacteremia that occurs with neonatal sepsis; the higher the colony count in the blood culture, the higher the risk of meningitis. Neonatal bacterial meningitis may also result from scalp lesions, particularly when developmental defects lead to communication between the skin surface and the subarachnoid space, which predisposes to thrombophlebitis of the diploic veins. Rarely, there is direct extension to the CNS from a contiguous otic focus (eg, otitis media).

Symptoms and Signs

Frequently, only those findings typical of neonatal sepsis (eg, temperature instability, respiratory distress, jaundice, apnea) are manifest. CNS signs (eg, lethargy, seizures [particularly focal], vomiting, irritability) more specifically suggest neonatal bacterial meningitis. So-called paradoxical irritability, in which cuddling and consoling by a parent irritates rather than comforts the neonate, is more specific for the diagnosis. A bulging or full fontanelle occurs in about 25% and nuchal rigidity in only 15%. The younger the patient, the less common are these findings. Cranial nerve abnormalities (particularly those involving the 3rd, 6th, and 7th nerves) may also be present.

Meningitis due to GBS may occur in the first week of life, accompanying early-onset neonatal sepsis and frequently manifesting initially as a systemic illness with prominent respiratory signs. Often, however, GBS meningitis occurs after this period (most commonly in the first 3 mo of life) as an isolated illness characterized by absence of antecedent obstetric or perinatal complications and the presence of more specific signs of meningitis (eg, fever, lethargy, seizures).

Ventriculitis frequently accompanies neonatal bacterial meningitis, particularly when caused by gram-negative enteric bacilli. Organisms that cause meningitis together with severe vasculitis, particularly C. diversus and Cronobacter (formerly Enterobacter) sakazakii, are likely to cause cysts and abscesses. Pseudomonas aeruginosa, E. coli K1, and Serratia sp also may cause brain abscesses. An early clinical sign of brain abscess is increased intracranial pressure (ICP), commonly manifested by vomiting, a bulging fontanelle, and sometimes enlarging head size. Deterioration in an otherwise stable neonate with meningitis suggests progressive increased ICP caused by abscess or hydrocephalus, or rupture of an abscess into the ventricular system.

Pearls & Pitfalls

  • Classic signs of meningitis are uncommon; a bulging or full fontanelle occurs in only about 25% of neonates and nuchal rigidity occurs in only 15% of neonates.

Diagnosis

  • CSF cell counts, glucose and protein levels, Gram stain, and culture

  • Sometimes ultrasonography or CT or MRI of the brain

Definitive diagnosis is made by CSF examination via lumbar puncture (LP), which should be done in any neonate suspected of having sepsis or meningitis. However, LP can be difficult to do in a neonate, and there is some risk of hypoxia. Poor clinical condition (eg, respiratory distress, shock, thrombocytopenia) makes LP risky. If LP is delayed, the neonate should be treated as though meningitis is present. Even when the clinical condition improves, the presence of inflammatory cells and abnormal glucose and protein levels in CSF days after illness onset can still suggest the diagnosis. A needle with a trocar should be used for LP to avoid introducing epithelial rests and subsequent development of epitheliomas. The CSF, even if bloody or acellular, should be cultured. About 15 to 35% of neonates with negative blood cultures have positive CSF cultures depending on the population studied. LP should be repeated at 24 to 48 h if clinical response is questionable and at 72 h when gram-negative organisms are involved (to ensure sterilization). Repeating the CSF analysis helps guide duration of therapy and predict prognosis. Some experts believe that a repeat LP at 24 to 48 h in neonates with GBS meningitis has prognostic value. LP should not be repeated at the end of therapy if the neonate is doing well.

Normal CSF values are controversial and in part age-related. In general, both term and preterm infants without meningitis have 20 WBCs/μL (one fifth of which may be PMNs) in their CSF. CSF protein levels in the absence of meningitis are more variable; term infants have levels of < 100 mg/dL, whereas preterm infants have levels up to 150 mg/dL. CSF glucose levels in the absence of meningitis are > 75% of the serum value measured at the same time. These levels may be as low as 20 to 30 mg/dL (1.1 to 1.7 mmol/L). Bacterial meningitis has been identified by culture in neonates with normal CSF indices, showing that normal CSF values do not exclude a diagnosis of meningitis.

Ventriculitis is suspected in a neonate not responding appropriately to antimicrobial therapy. The diagnosis is made when a ventricular puncture yields a WBC count greater than that from the LP, by a positive Gram stain or culture, or by increased ventricular pressure. When ventriculitis or brain abscess is suspected, ultrasonography or MRI or CT with contrast may aid diagnosis; dilated ventricles also confirm ventriculitis.

Prognosis

Without treatment, the mortality rate for neonatal bacterial meningitis approaches 100%. With treatment, prognosis is determined by birth weight, organism, and clinical severity. Mortality rate for treated neonatal bacterial meningitis is 5 to 20. For organisms that cause vasculitis or brain abscess (necrotizing meningitis), the mortality rate may approach 75%. Neurologic sequelae (eg, hydrocephalus, hearing loss, intellectual disability) develop in 20 to 50% of infants who survive, with a poorer prognosis when gram-negative enteric bacilli are the cause.

Prognosis also depends partly on the number of organisms present in CSF at diagnosis. The duration of positive CSF cultures correlates directly with the incidence of complications. In general, CSF cultures from neonates with GBS are usually sterilized within the first 24 h of antimicrobial therapy. Those from gram-negative bacillary meningitis remain positive longer, with a median of 2 days.

GBS meningitis has a mortality rate significantly lower than that of early-onset GBS sepsis.

Treatment

  • Empiric ampicillin plus gentamicin, cefotaxime, or both, followed by culture-specific drugs

Empiric antibiotic therapy

Initial empiric treatment depends on patient age and is still debated. For neonates, many experts recommend ampicillin plus an aminoglycoside. A 3rd-generation cephalosporin (eg, cefotaxime) is also added until culture and sensitivity results are available if meningitis due to a gram-negative organism is suspected. However, resistance may develop more rapidly when cefotaxime is used routinely, and prolonged use of 3rd-generation cephalosporins is a risk factor for invasive candidiasis. Ampicillin is active against organisms such as GBS, enterococci, and Listeria. Gentamicin provides synergy and added efficacy against these organisms. Cephalosporins provide adequate gram-negative coverage but do not provide synergy with ampicillin for gram-positive organisms.

Hospitalized neonates who previously received antibiotics (eg, for early-onset sepsis) may have resistant organisms; fungal disease may also be considered in a septic-appearing neonate after prolonged hospitalization. Ill neonates with hospital-acquired infection should initially receive vancomycin plus an aminoglycoside with or without a 3rd-generation cephalosporin depending on the concern for meningitis.

Antibiotics are adjusted when results of CSF culture and sensitivities are known. The results of the Gram stain should not be used to adjust coverage before culture results are available.

Organism-specific antibiotic therapy

The recommended initial treatment for GBS meningitis in neonates < 1 wk of age is penicillin G 100,000 to 150,000 units/kg IV q 8 h or ampicillin 100 to 150 mg/kg IV q 8 h. Additionally, gentamicin 3 mg/kg IV once/day is given for synergy if neonates are < 35 wk gestational age or 4 mg/kg IV once/day is given if neonates are > 35 wk gestational age. If clinical improvement occurs or sterilization of CSF is documented, gentamicin can be stopped.

For enterococci or L. monocytogenes, treatment is generally ampicillin plus gentamicin for the entire course.

In gram-negative bacillary meningitis, treatment is difficult. The traditional regimen of ampicillin plus an aminoglycoside results in a 15 to 20% mortality rate, with a high rate of sequelae in survivors. Instead, a 3rd-generation cephalosporin (eg, cefotaxime) should be used in neonates with proven gram-negative meningitis. If antibiotic resistance is a concern, both an aminoglycoside and a 3rd-generation cephalosporin or extended-spectrum β-lactam (eg, meropenem) may be used until sensitivities are known.

Parenteral therapy for gram-positive meningitis is given for a minimum of 14 days, and for complicated gram-positive or gram-negative meningitis, a minimum of 21 days.

Adjunctive measures

Because meningitis may be considered part of the continuum of neonatal sepsis, the adjunctive measures used in treating neonatal sepsis (see Other treatment) should also be used to treat neonatal meningitis. Corticosteroids are not used in treatment of neonatal meningitis. Patients should be closely monitored for neurologic complications during early childhood, including for sensorineural hearing loss.

Key Points

  • The most common causes are GBS, E. coli, and L. monocytogenes.

  • Manifestations are often nonspecific (eg, temperature instability, respiratory distress, jaundice, apnea).

  • Although CNS signs (eg, lethargy, seizures, vomiting, irritability) may be present, classic findings such as a bulging or full fontanelle and nuchal rigidity are not common.

  • CSF culture is critical because some neonates with meningitis have normal CSF indices (eg, WBC count, protein and glucose levels).

  • Begin empiric treatment with ampicillin, gentamicin, and cefotaxime followed by culture-specific drugs.

  • Corticosteroids are not used in neonatal meningitis.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • GENOPTIC
  • CLAFORAN
  • No US brand name
  • VANCOCIN
  • MERREM

* This is a professional Version *