Meningitis, Neonatal

Neonatal meningitis is inflammation of the meninges due to bacterial invasion in the 1st 90 days of life. Signs are those of sepsis, CNS irritation—lethargy, seizures, vomiting, irritability, nuchal rigidity, a bulging or full fontanelle—and cranial nerve abnormalities. Diagnosis is by lumbar puncture. Treatment is with antibiotics.

Neonatal 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 25% of neonates with sepsis and occasionally occurs in isolation.

Etiology

Group B streptococcus (GBS—predominantly type III), Escherichia coli (particularly those strains containing the K1 polysaccharide), and Listeria monocytogenes account for 75% of neonatal meningitis.

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

Neonatal meningitis most frequently results from the bacteremia that occurs with neonatal sepsis; the higher the colony count in the blood culture, the higher is the risk for meningitis. 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 associated with neonatal sepsis (eg, temperature instability, respiratory distress, jaundice, apnea) are manifest. CNS signs (eg, lethargy, seizures [particularly focal], vomiting, irritability) more specifically suggest meningitis. A bulging or full fontanelle occurs in about 25% and nuchal rigidity in only 15%. Cranial nerve abnormalities (particularly those involving the 3rd, 6th, and 7th nerves) may also be present.

Meningitis due to GBS may occur in the 1st wk of life, accompanying early-onset neonatal sepsis and frequently presenting as a pneumonic illness. Usually, however, GBS meningitis occurs after this period (most commonly in the 1st 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 meningitis, particularly when caused by gram-negative enteric bacilli. Organisms that cause meningitis together with severe vasculitis, particularly C. diversus and Enterobacter sakazakii , are likely to produce 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 increase from abscess or hydrocephalus, or rupture of an abscess into the ventricular system.

Diagnosis

Definitive diagnosis is made by CSF examination via 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 for hypoxia. Poor clinical condition (eg, respiratory distress, shock, thrombocytopenia) makes LP risky. If LP is delayed, the neonate should be treated as though meningitis were present. Even when the clinical condition improves, the presence of inflammatory cells in CSF and abnormal chemistries 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% of neonates with negative blood cultures have positive CSF cultures. 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). Some experts believe that a repeat LP at 24 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 age-related. In general, for LBW infants up to 4 wk of age, 40 WBCs/μL (1⁄2 of which may be PMNs), a protein level of 220 mg/dL, and a glucose level of 50 mg/dL (2.8 mmol/L) are considered the upper limits of normal. For term infants, these limits are 20 WBCs/μL (with 1⁄2 PMNs), a protein level of 170 mg/dL, and a glucose level of 50 mg/dL (2.8 mmol/L). The CSF glucose concentration depends largely on serum glucose concentration and may normally be as low as 20 to 30 mg/dL (1.1 to 1.7 mmol/L), therefore, serum glucose should be measured before LP so the ratio of CSF:serum glucose levels can be determined (< 50% is abnormal).

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, Gram stain or culture is positive, ventricular pressure is increased, and ventricles are dilated. When ventriculitis or brain abscess is suspected, an MRI or CT scan with contrast may aid diagnosis.

Prognosis

Without treatment, the mortality rate from neonatal meningitis approaches 100%. With treatment, prognosis is determined by birth weight, organism, and clinical severity. Mortality rate for gram-negative neonatal meningitis is 20 to 30% and for gram-positive (eg, GBS), 10 to 20%. For organisms that produce vasculitis, meningitis, and brain abscess (necrotizing meningitis), the mortality rate may approach 75%. Neurologic sequelae (eg, hydrocephalus, hearing loss, mental retardation) 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 1st 24 h of antimicrobial therapy. Those from gram-negative bacillary meningitis remain positive for an average of 3 1⁄2 days.

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

Treatment

Empiric treatment is begun with ampicillin plus cefotaxime. 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. Until the diagnosis of meningitis is confirmed, ill neonates with hospital-acquired infection should initially receive vancomycin plus an aminoglycoside different from the one previously used, or a 3rd-generation cephalosporin. Antibiotics are adjusted when results of the LP are available and culture and sensitivities are known.

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 mg/kg IV q 8 h, plus gentamicin 2.5 mg/kg IV q 8 h. If clinical improvement occurs or sterilization of CSF is documented, gentamicin Some can be stopped.

For enterococci or L. monocytogenes, treatment is generally ampicillin plus gentamicin.

In gram-negative bacillary meningitis, treatment is difficult. The traditional regimen of ampicillin
plus an aminoglycoside results in a 20 to 30% mortality rate, with a high rate of sequelae in survivors. A 3rd-generation cephalosporin should be strongly considered in neonates with proved gram-negative meningitis (or sepsis) or those convincingly septic. If antibiotic resistance is a concern, both an aminoglycoside and a 3rd-generation cephalosporin may be used until sensitivities are known. However, these drugs are generally not used routinely, because certain gram-negative organisms are induced to produce β-lactamase by 3rd-generation cephalosporins, resulting in rapid development of resistance.

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.

Because meningitis may be considered part of the continuum of neonatal sepsis, the adjunctive measures used in treating neonatal sepsis (see Infections in Neonates: Other treatment) should also be used in neonatal meningitis. Patients should be closely followed for neurologic complications during the 1st 2 yr of life.

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