**7. Laboratory tests**

age, transfer of maternal circulating antibodies through placenta occurs only in minute quantities. Neutrophil reserves of a neonate can easily become exhausted, since they are 20–30% of

The causative agent of neonatal meningitis is usually transmitted to fetus vertically during labor. When the etiology is bacterial, histopathologic findings of meningitis in newborns are similar, irrespective of the specific agent. Another similarity is observed in the inflammatory responses of newborns, older children, and adults, the only exception being the paucity of plasma cells and lymphocytes in the subacute phase of meningeal reactions in newborns. The most common finding is purulent exudate in meninges and ependymal surfaces of ventricles. Perivascular inflammation is also observed in some patients. This may further proceed to arteritis of various degrees with phlebothrombosis and thrombophlebitis in the subependymal region. Hydrocephalus and encephalopathy were detected in half of the infants died from meningitis. Unlike older infants (3–12 months of age), subdural effusion is rare in neonates. Interleukin-1β is present in high concentrations in the meninges and brain tissue of the infants

Clinical findings of neonatal meningitis are similar to those of neonatal sepsis with or without meningitis. It is not possible to predict with physical examination alone whether the infant has sepsis, meningitis or both. The most common (60%) finding is the alteration in body temperature. This alteration may become manifest as either fever (>38°C) or hypothermia (<36°C). Fever is usually observed in term infants, whereas preterms have a stronger tendency to develop hypothermia [3]. Skin vesicles should suggest HSV in the etiology of meningitis,

**Finding Frequency (%)**

**Table 1.** Physical examination findings found in neonatal meningitis and their frequencies [1, 3].

Alteration in body temperature (either hypothermia or hyperthermia) 60 Irritability or lethargy 60 Seizures 20–50 Bulging of fontanel 25 Nuchal rigidity 15 Poor feeding 50 Dyspnea 33–50 Apnea 10–30 Jaundice 28 Diarrhea 20

that of an average adult [15].

88 Selected Topics in Neonatal Care

who have succumbed to the infection [16].

**6. Physical examination**

First tests to be performed include complete blood count with differentials and cultures (urine and blood). Detection of growth in urine culture could be a reflection of metastatic dissemination of the organism to the bladder, thus cannot be relied upon as a locator of infection in young infants [1].

Lumbar puncture (LP) is an irreplaceable diagnostic tool in neonatal meningitis. Cerebrospinal fluid (CSF) obtained through LP should be examined directly and as Gram- and Giemsastained smears under microscope, cultured, and, if needed, sent for polymerase chain reaction. Direct microscopy should be performed as soon as possible, because the later it is performed, the more likely the erythrocytes and leukocytes undergo cellular lysis and escape detection. LP should ideally precede the initiation of antimicrobial therapy, but if, delayed for any reason, such as deteriorating clinical status of the patient, empirical antibiotic therapy should be started immediately.

Interpretation of CSF findings is more difficult in neonates than in older children, since the glucose, protein concentrations, and cell count of CSF are higher due to the high permeability of the blood-brain barrier (**Table 2**).


**Table 2.** Means and normal ranges of cerebrospinal parameters in neonates [12].

Many experts accept 20–30/μL as the cutoff value for pleocytosis. Decreased CSF glucose, increased CSF protein, and pleocytosis may indicate either bacterial or viral (especially HSV) meningitis. If only one of these parameters is in the normal range, this cannot be accepted as an evidence against the presence of meningitis. If all three parameters are normal, then it can be presumed that meningitis is not present; nevertheless, keeping in mind that completely normal CSF findings may be observed during the very early course of neonatal meningitis, the most prudent approach would be to repeat LP after 24–72 h in such borderline cases. If the infant had meningitis, pleocytosis and other abnormalities consistent with meningitis would be detected in CSF obtained in this second LP [3]. Ample number of erythrocytes in CSF may be interpreted as a clue to HSV meningitis if the physician is sure that the LP was not traumatic. Pleocytosis is more marked in bacterial and Gram-negative meningitides than in viral and Gram-positive meningitides [1].

abnormalities, resistant infection, and clinical deterioration. MR is the most precise tool for the diagnosis of complications, like sinus vein thrombosis, ventriculitis, and subdural depos-

Neonatal Meningitis

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http://dx.doi.org/10.5772/intechopen.69601

History of premature or prolonged labor, intrauterine scalp monitorization, traumatic birth,

Physical signs may be subtle in neonatal meningitis, in which either fever or hypothermia may be the only clue to diagnosis. Pleocytosis under direct microscopy or the presence of bacteria in Gram smear suggests meningitis. Definitive diagnosis is made with the isolation

The differential diagnosis includes other causes of neonatal seizures, partially treated meningitis, intracranial abscess, intracranial hemorrhage, intracranial aneurysm, cerebral vein

In the meningitides with the onset in the first 3–6 days of life, the empirical therapy should be ampicillin + cefotaxime, ampicillin + gentamicin, or, if there is a very high probability that the causative organism is Gram negative, as in the case of detection of Gram-negative bacilli on

After the first 3–6 days of life, ampicillin + gentamicin + cefotaxime for infants from outside of a healthcare facility, and vancomycin + gentamicin + cefotaxime for previously or currently hospitalized newborns would be appropriate choices [1, 10]. If *L. monocytogenes* grows in CSF or is suspected as the pathogen from the Gram smear, it is advisable to add ampicillin to vancomycin + gentamicin combination, because CSF concentrations of vancomycin are not

Dexamethasone therapy, which is used for older children, is not recommended for neonatal

Acyclovir (20 mg/kg/dose, every 8 h, for 14–21 days) should be administered to all neonates

For newborns whose CSF shows growth of a pathogen, the duration of therapy should be 14 days for Gram-positive organisms and 21 days for Gram negatives if neither any complication nor resistance to therapy is present. If a growth is detected in blood culture but not in CSF, while CSF shows signs of inflammation, a therapy duration of 10 days for Gram-positive organisms and 14 days for Gram negatives would suffice. Empirical antimicrobial therapy

with HSV disease, regardless of manifestations and clinical findings [21].

its. Electroencephalography has no diagnostic value in neonatal meningitis [12].

and maternal peripartum infection should be noted.

thrombosis, head trauma, and congenital metabolic diseases.

smear, it should be ampicillin + gentamicin + cefotaxime [10].

Dosages of recommended drugs are depicted in **Table 3**.

**8. Diagnosis**

of causative organism in CSF.

**9. Management**

bactericidal for Listeria [10].

meningitis [1, 10].

CSF protein concentrations higher than 100 mg/dL in term infants and 150 mg/dL in preterm neonates are consistent with bacterial meningitis. CSF protein may also be found to be high in parameningeal infections like brain abscess, congenital infections, and intracranial hemorrhage [3].

The glucose concentration is said to be consistent with bacterial meningitis if it is below 30 mg/dL in term newborns and 20 mg/dL in preterm infants. CSF glucose to serum glucose ratio is not a reliable indicator of meningitis in the first 28 days of life, because newborns often receive intravenous glucose infusions and serum glucose concentrations can rise abruptly with stress [3]. In case of a bloody tap, assessing the CSF leucocyte count by correcting it with respect to that of the peripheral blood is not recommended in that it decreases the sensitivity and provides only a slight increase in specificity. When LP is traumatic, the wisest thing to do is to assume the patient as if she/he had meningitis and start empirical therapy [17]. Since sitting position with the legs flexed provides the widest interspinous spaces and it is sufficiently safe, it should be favored for sick neonates whenever the infant's condition permits a spinal tap [18].

Although, as noted above, signs of sepsis and meningitis intertwine in the newborn period, some neonatologists consider that it is unnecessary to perform LP on neonates evaluated for sepsis, especially those with early neonatal sepsis [19, 20]. Blood cultures are negative in onethird of neonates with meningitis who are very low birth weight and born over 34 weeks of gestation [1]. Thus, in case LP is not performed, a significant portion of neonates with meningitis would not get a correct diagnosis and would not be observed for the likely complications of meningitis; for that reason, the author is in favor of the opinion that LP should always be performed as soon as the infant becomes clinically stable and can tolerate the procedure if it has not been possible to be performed at the first suspicion of meningitis. It should be kept in mind that findings of CSF inflammation last for a considerably long duration (days, sometimes weeks), which allows the clinician diagnose or exclude the diagnosis of meningitis.

Ultrasonography is valuable in the follow-up, especially for the cases, in which hydrocephalus has developed as a complication of meningitis. If the disadvantage of radiation exposure is left aside, computed tomography can accelerate the decision making of ventriculostomy in cases of hydrocephalus and surgical drainage in patients with cranial abscesses. Magnetic resonance (MR) is the imaging modality of choice in conditions, such as focal neurologic abnormalities, resistant infection, and clinical deterioration. MR is the most precise tool for the diagnosis of complications, like sinus vein thrombosis, ventriculitis, and subdural deposits. Electroencephalography has no diagnostic value in neonatal meningitis [12].
