Neonatal Bacterial Meningitis

The predominant pathogens are the following:

• Group B streptococcus (GBS)

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

• Listeria monocytogenes

Other reported pathogens include enterococci, nonenterococcal group D streptococci, alpha-hemolytic streptococci, Staphylococcus aureus, coagulase-negative staphylococci, gram-negative enteric organisms (eg, Klebsiella species, Enterobacter species, Citrobacter diversus), Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae.

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 central nervous system (CNS) from a contiguous otic focus (eg, otitis media).

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 (because movement of inflamed meninges is painful), is more specific for the diagnosis. A bulging fontanelle or nuchal rigidity occurs in only approximately 20% of infants; the younger the patient, the less common are these findings (1). Cranial nerve abnormalities (particularly those involving the 3rd, 6th, and 7th nerves) may also be present.

Meningitis due to group B streptococcus (GBS meningitis) 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 months 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 sakazakii, are likely to cause cysts and abscesses. Pseudomonas aeruginosa, E. coli K1, and Serratia species 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.

• Cerebrospinal fluid (CSF) cell counts, glucose and protein levels, Gram stain, and culture

• Polymerase chain reaction (PCR) testing

• Sometimes ultrasound or CT or MRI of the brain

Definitive diagnosis of neonatal bacterial meningitis is made by CSF examination. Lumbar puncture (LP), which should be performed in any neonate suspected of having sepsis or meningitis. However, LP can be difficult to perform in a neonate, and there is some risk of the procedure causing hypoxia. Poor clinical condition (eg, respiratory distress, shock, thrombocytopenia) may increase risk. A needle with a trocar should be used for LP to avoid introducing epithelial rests and subsequent development of epitheliomas.

Low glucose, elevated protein, and elevated white blood cell count in CSF suggest bacterial meningitis. Normal CSF values are controversial and in part age-related. In general, both term and preterm infants without meningitis have ≤ 10 to 14 white blood cells/mcL (0.010 to 0.014 × 10⁹/L) in their CSF, one-fifth of which may be polymorphonuclear leukocytes. CSF protein levels in the absence of meningitis are more variable; term infants have levels of < 110 to 160 mg/dL (0.1 to 1.6 g/L), whereas preterm infants have levels up to 210 mg/dL (2.1 g/L). 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 (1, 2). If LP is delayed, CSF results are less reliable; however, even after clinical condition improves, the presence of inflammatory cells and abnormal glucose and protein levels in CSF days after illness onset can suggest meningitis.

The CSF should also be cultured, even if bloody or acellular. In some instances, particularly if CSF is obtained after initiation of antibiotics (pretreatment), multiplex PCR panels may provide additional diagnostic value. Repeating the CSF analysis helps guide duration of therapy and predict prognosis. LP may be repeated at 24 to 48 hours if clinical response is questionable; at 24 to 48 hours in neonates with GBS meningitis and at 72 hours when gram-negative organisms are involved. LP should not be repeated at the end of therapy if the neonate is doing well.

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

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

Without treatment, the mortality rate for neonatal bacterial meningitis approaches 100%.

With treatment, the mortality rate for neonatal bacterial meningitis is 5 to 20%.

Prognosis is determined by birth weight, organism, and clinical severity. For organisms that cause vasculitis or brain abscess (necrotizing meningitis), the mortality rate may approach 75%.

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 hours 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.

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.