Despite the development of effective vaccines, useful tools for rapid identification of pathogens and potent antimicrobial drugs, neonatal meningitis continues to contribute substantially to neurological disability worldwide.
The persistence of neonatal meningitis results from increases in the numbers of infants surviving premature delivery and from limited access to medical resources in developing countries. In addition, the absence of specific clinical findings makes diagnosis of meningitis more difficult in neonates than in older children and adults. Moreover, a wide variety of pathogens are seen in infants as a consequence of the immaturity of their immune systems and intimate exposure to possible infection from their mothers.
This review focuses on common presentations of treatable bacterial and viral meningitis in the neonatal period, defined as the period from birth to 44 weeks after conception. Common central nervous system (CNS) infections caused by bacteria and viruses (eg, herpes simplex virus [HSV]) are emphasized. Meningitides caused by HIV and fungi are excluded, as are those caused by other organisms implicated in congenital CNS damage (eg, cytomegalovirus [CMV] and Toxoplasma).
Neonates are at greater risk for sepsis and meningitis than other age groups are because of the following deficiencies in humoral and cellular immunity and in phagocytic function:
Inefficiency in the neonates’ alternative complement pathway compromises their defense against encapsulated bacteria 
T-cell defense and mediation of B-cell activity are also compromised
Deficient migration and phagocytosis by neutrophils contribute to neonatal vulnerability to pathogens of even low virulence 
Common bacterial pathogens
Among US neonates, group B streptococci (GBS) are the most commonly identified causes of bacterial meningitis, implicated in roughly 50% of all cases. Escherichia coli accounts for another 20%. Thus, identification and treatment of maternal genitourinary infections is an important prevention strategy.  Listeria monocytogenes is the third most common pathogen, accounting for 5-10% of cases; it is unique in that it exhibits transplacental transmission. 
Studies suggest that in underdeveloped countries, gram-negative bacilli—specifically, Klebsiella organisms and E coli —may be more common than GBS. In a series from Africa and South Asia, Tiskumara et al noted that 75% of cases of late-onset meningitis were due to gram-negative bacilli.  In a review of studies from Asia, Africa, and Latin America, Zaidi et al reported that the most common organisms were Klebsiella species, E coli, and Staphylococcus aureus. 
With the widespread use of intrapartum antibiotic prophylaxis since 1996 in developed countries, the incidence of early-onset GBS infection has decreased, whereas the incidence of late-onset disease has remained fairly constant.  However, from 2003 to 2006, the Centers for Disease Control and Prevention (CDC) reported a slight increase in early-onset disease in the United States, particularly in the African American population; the reasons for this are unclear. 
Herpes simplex virus
As many as 95% of viral infections caused by HSV result from intrapartum transmission, with occasional postnatal exposure occurring through oropharyngeal shedding or cutaneous shedding of virus by parents or hospital contacts. Late presentation in the second postnatal week is more commonly seen than early presentation of disseminated disease.
As cases of neonatal enteroviral sepsis and aseptic meningitis come to be more frequently recognized, reporting and identification of more virulent serotypes as they affect infants are likely to play a growing role.  As many as 12% of neonates may be infected with this family of viruses. Although many of these babies are asymptomatic, enterovirus may be responsible for as many as 3% of neonates who present with a sepsislike picture.  More recently, human parechovirus-3 has been implicated in an increasing number of neonates with meningitis. While related to the enterovirus family, this pathogen is not detected with enteroviral polymerase chain reaction (PCR) studies performed on cerebrospinal fluid (CSF). [13, 14]
Enterobacter sakazakii has been identified as an emerging pathogen in neonates. This bacterium is most typically associated with the ingestion of contaminated reconstituted formula. It has been reported with increasing frequency in the past few years, prompting the US Food and Drug Administration (FDA) to publish warnings of possible contamination of dried formula. 
In industrialized countries, the incidence of bacterial meningitis is approximately 0.3 per 1000 live births.  The incidence of HSV meningitis is estimated to be 0.02-0.5 cases per 1000 live births.  Because of testing limitations, the worldwide incidence of neonatal meningitis is difficult to determine with accuracy. However, a study of neonatal infections in Asia (based on data collected from China, Hong Kong, India, Iran, Kuwait, and Thailand) reported estimated incidences of neonatal meningitis that ranged from 0.48 per 1000 live births in Hong Kong to 2.4 per 1000 live births in Kuwait.  Another publication that looked at neonatal infections in Africa and South Asia reported figures ranging from 0.8 to 6.1 per 1000 live births. 
These numbers are believed to underestimate the true incidence of neonatal meningitis in underdeveloped countries, given the lack of access to health care facilities in these areas.
Survivors of neonatal meningitis are at significant risk for moderate to severe disability. Some 25-50% have significant problems with language, motor function, hearing, vision, and cognition [18, 3] ; 5-20% have future epilepsy. [19, 20] Survivors are also more likely to have subtle problems, including visual deficits, middle-ear disease, and behavioral problems.  As many as 20% of children identified as normal at 5-year follow-up may have significant educational difficulties lasting into late adolescence. 
Poor prognostic indicators include low birth weight, prematurity, significant leukopenia or neutropenia, high levels of protein in the cerebrospinal fluid (CSF), delayed sterilization of the CSF, and coma. [1, 2] Seizures lasting longer than 72 hours and the need for inotropes predict moderate-to-severe disability or death with 88% sensitivity and 99% specificity. 
In developed countries, mortality from bacterial meningitis among neonates declined from almost 50% in the 1970s to less than 10% in the late 1990s. However, a corresponding decrease in morbidity rate did not occur. 
In a prospective sample of more than 1500 neonates surviving to the age of 5 years, the prevalence of motor disabilities (including cerebral palsy) was 8.1%, that of learning disability was 7.5%, that of seizures was 7.3%, and that of hearing problems was 25.8%.  No problems were reported in 65% of babies who survived GBS meningitis and in 41.5% of those who survived E coli meningitis.
Mortality among neonates with HSV infection of the CNS is 15%. Of these cases, 25-40% will have culture-proven CSF infection. The 2 HSV serotypes (HSV-1 and HSV-2) carry the same risk of mortality. However, HSV-2 is more commonly associated with morbidity, including cerebral palsy, mental retardation, seizures, microcephaly, and ophthalmic defects.  Although the use of acyclovir has reduced the morbidity and mortality associated with HSV infection, neurological sequelae are likely in 50% of neonates with HSV meningitis. 
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