The incidence of neonatal bacterial meningitis is approximately one-fourth of that of neonatal sepsis with a median range of 0.2 to 0.5 cases per 1,000 live births. The rates vary according to nursery and predisposing maternal and infant risk factors. A preponderance of male infants with meningitis caused by gram-negative enteric bacilli exists, but the ratio of male-to-female cases is comparable with that for group B streptococcus. The incidence of meningitis in low-birth-weight infants is approximately three times that of infants with birth weights greater than 2,500 g. Other risk factors associated with an increased incidence of neonatal bacteremia and meningitis include premature or prolonged rupture of membranes, maternal fever or chorioamnionitis, and traumatic delivery. Group B streptococcus and Listeria monocytogenes may cause early-onset and late-onset disease. Late-onset infections (after 7 days of life) are more often associated with meningitis.

Group B streptococci (40% to 55% of cases) and Escherichia coli (15% to 20% of cases) are the two most frequent pathogens causing meningitis (Box 72.1). Listeria monocytogenes is an important but much less frequently encountered pathogen. In some institutions, nonenterococcal group D streptococci cause a substantial proportion of meningitis cases. Enterobacter species, Klebsiella species, Salmonella species, and other gram-negative bacilli are infrequently encountered. Staphylococcus species and Candida species can cause meningitis in premature infants who are subject to invasive supportive management and monitoring devices. Common pathogenic organisms of meningitis in older infants and children (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b) are infrequent causes of meningitis in neonates. Group A streptococcus, once a major pathogen of neonatal sepsis and meningitis in the early 20th century, is now only occasionally seen in infants.

Most cases of meningitis result from hematogenous dissemination. Factors that predispose to bacteremia also predispose to meningitis; as many as one-third of infants with bacteremia develop meningitis. Rarely, meningitis is secondary to extension from infected skin through the soft tissues and skull (e.g., infected cephalhematoma). Infants with congenital malformations of the neural tube such as meningomyeloceles can be infected by direct spread from skin surfaces.

The choroid plexus may be the port of entry to the cerebrospinal fluid (CSF) because ventriculitis is present in at least 70% of cases of neonatal gram-negative enteric meningitis; ventricles probably are the initial site of infection and serve as a reservoir for spread of infection throughout the subarachnoid space.

Many organisms causing meningitis in the newborn possess specific surface antigens. The K1 polysaccharide of E. coli is present in 75% to 85% of strains isolated from neonates with meningitis. The BIII polysaccharide of group B streptococci is recovered from 30% of early-onset and 90% of late-onset strains causing neonatal meningitis. Type IVb strains of L. monocytogenes account for most meningitis cases.

The K1 antigen of E. coli confers resistance to phagocytosis and does not activate the alternate complement pathway. Immunochemical similarities exist between glycopeptides of the brain containing sialic acid and the capsular polysaccharide of E. coli K1 strains. However, specific antibodies to the K1 antigen appear to be highly protective against sepsis and meningitis. Delayed clearance of E. coli because of decreased phagocytosis may allow replication of the organism in the blood to a concentration of 1,000 or more organisms per milliliter, a concentration associated with an increased incidence of meningitis.

The capsular polysaccharide of serotype III of the group B streptococci seems to mediate resistance to phagocytosis; strains expressing this antigen adhere to buccal epithelial cells of neonates better than to those of adults. The presence of type-specific antibodies is necessary for opsonization of type Ia, II, and III strains, and high concentrations appear to confer resistance to the newborn infant. Phagocytosis of the organism is normal in the presence of type III polysaccharide, but chemiluminescence of neutrophils is decreased when exposed to this antigen; however, this decrease in chemiluminescence has also been found with other pathogens.

The pathogenesis of late-onset disease caused by group B streptococci is unclear. In most instances, serotype III is the infecting pathogen. Predisposing risk factors usually are absent. A history of preceding respiratory tract infection is present in
many patients. This infection may alter the nasopharyngeal epithelium and facilitate invasion by the streptococci.

Interleukin-1 beta and tumor necrosis factors are detectable in the CSF of almost all infants with bacterial meningitis and are considered important mediators of the inflammation within the central nervous system. High levels of interleukin-1 beta or prolonged persistence of detectable levels of this mediator are associated with a poorer outcome.

Brain abscesses occur in 70% of cases of Enterobacter sakazakii meningitis, whereas other gram-negative enteric bacilli cause abscesses in less than 10% of infants. Hematogenous spread is the most likely source of dissemination.

The clinical manifestations of meningitis in the newborn infant are often nonspecific and indistinguishable from those of sepsis. Meningitis should always be considered when bacteremia is suspected. The cardinal signs of meningitis in older children, such as stiff neck and Kernig and Brudzinski signs, are absent in most infants.

The most frequent signs are temperature instability, respiratory distress, irritability, lethargy, and poor feeding or vomiting. Seizures occur in 40% of newborn infants with meningitis. Other signs include a bulging fontanelle, hyperactivity or hypoactivity, alteration of the level of consciousness, tremor, twitching, apnea, stiff neck or opisthotonos, hemiparesis, and cranial nerve palsy. Some patients present with a severe protracted state of shock. Patients with group B streptococcal infection also may present with hydrocephalus without other signs of infection.

The pathologic findings of meningitis in neonates are similar to those found in older children. A diffuse purulent leptomeningitis is almost always found and is more pronounced at the base of the brain. In the acute phase of the illness, brain edema is frequently present, but cerebral herniation is uncommon. Vasculitis is common with resultant thrombosis and possibly infarct of brain tissue. Brain abscesses can develop in these areas and can involve multiple lobes. Ventriculitis is present in three-fourths of infants, and hydrocephalus develops in approximately one-third. Subdural effusions occur rarely in the neonate. Leukomalacia with porencephaly can develop as a result of tissue anoxia.

The diagnosis of meningitis is based on examination and culture of the CSF. In most instances, a lumbar puncture should be performed at the time of the sepsis workup. In a recent study, one-third of the very low-birth-weight infants with proven bacterial meningitis had sterile blood cultures, reemphasizing the importance of lumbar puncture in the evaluation of infants with suspected sepsis. However, in a critically ill child, the lumbar puncture can be postponed until the cardiorespiratory condition is stable. Although CSF cultures may be sterile in the infant who has received antibiotics before diagnosis, examination of the CSF for cellular and biochemistry values and for antigen detection is almost always indicative of meningitis.