Neonatal Bacterial Meningitis

Neonatal Bacterial 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 common 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. Usually, 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 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.

Diagnosis


CSF glucose and protein levels, Gram stain, and culture
Sometimes brain CT or MRI

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 chemistries 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 30% 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 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 infants 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).

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, an 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 gram-negative neonatal bacterial meningitis is 15 to 20%, and for gram-positive (eg, GBS) it is 6 to 10%. 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 Some Trade Names
OMNIPEN
PRINCIPEN
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plus gentamicin Some Trade Names
GARAMYCIN
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, cefotaxime Some Trade Names
CLAFORAN
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, or both, followed by culture-specific drugs

Empiric antibiotic therapy: Initial empiric treatment depends on patient age and is still debated. Most experts recommend ampicillin Some Trade Names
OMNIPEN
PRINCIPEN
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plus an aminoglycoside, a 3rd-generation cephalosporin (eg, cefotaxime Some Trade Names
CLAFORAN
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), or both. Ampicillin Some Trade Names
OMNIPEN
PRINCIPEN
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is active against organisms such as GBS, enterococci, and Listeria. Gentamicin Some Trade Names
GARAMYCIN
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provides synergy and added efficacy against these organisms and adequate gram-negative coverage. Cephalosporins provide adequate gram-negative coverage but do not provide synergy with ampicillin Some Trade Names
OMNIPEN
PRINCIPEN
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for gram-positive organisms and may allow for some resistant 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 Some Trade Names
VANCOCIN
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plus an aminoglycoside with or without a 3rd-generation cephalosporin. Antibiotics are adjusted when results of CSF culture and sensitivities are known. The results of the Gram stain should not change antibiotic therapy.

Organism-specific antibiotic therapy: The recommended initial treatment for GBS meningitis in neonates < 1 wk of age is penicillin G Some Trade Names BICILLINWYCILLINClick for Drug Monograph 100,000 to 150,000 units/kg IV q 8 h or ampicillin Some Trade Names OMNIPENPRINCIPENClick for Drug Monograph 100 mg/kg IV q 8 h, plus gentamicin Some Trade Names GARAMYCINClick for Drug Monograph 4 mg/kg IV once/day if the infant is 32 to 35 wk gestational age or 5 mg/kg IV once/day if the infant is > 35 wk gestational age. If clinical improvement occurs or sterilization of CSF is documented, gentamicin Some Trade Names
GARAMYCIN
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can be stopped.

For enterococci or L. monocytogenes, treatment is generally ampicillin Some Trade Names
OMNIPEN
PRINCIPEN
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plus gentamicin Some Trade Names
GARAMYCIN
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.

In gram-negative bacillary meningitis, treatment is difficult. The traditional regimen of ampicillin Some Trade Names
OMNIPEN
PRINCIPEN
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plus an aminoglycoside results in a 15 to 20% mortality rate, with a high rate of sequelae in survivors. A 3rd-generation cephalosporin (eg, cefotaxime Some Trade Names
CLAFORAN
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) should be strongly considered in neonates with proven 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, except for initial empiric therapy, 3rd-generation cephalosporins are generally not used routinely, because certain gram-negative organisms are induced to produce β-lactamase, 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.

Adjunctive measures: 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 to treat neonatal meningitis. Corticosteroids are not used in treatment of neonatal meningitis. Patients should be closely monitored for neurologic complications during the first 2 yr of life.