Neonatal Meningitis Treatment & Management

Although evaluation and treatment of perinatal infection often begins before birth, discussion of antenatal interventions is beyond the scope of this review. However, early initiation of antimicrobial drugs is essential; a confirmed diagnosis of meningitis seldom is established before treatment is started.

Aggressive antimicrobial intervention is lifesaving in neonates with suspected meningitis. Because distinguishing viral from bacterial meningitis is difficult early in the clinical course, a combination of agents is often necessary, providing coverage for both types of infection. The duration of therapy for bacterial and herpes simplex virus (HSV) meningitis with an appropriate agent is typically 14-21 days.

Although there is a consensus that acyclovir is the preferred antiviral therapy, there remains some disagreement with respect to what constitutes optimal antibacterial therapy. The combination of ampicillin and gentamicin is a common regimen. Resistance of E coli to ampicillin has been reported; this may be related to increased use of intrapartum antibiotic prophylaxis. ^[36]

In treating meningitis, many centers administer cefotaxime in addition to or instead of gentamicin, particularly when gram-negative infections are suspected. Cefotaxime is also often used rather than gentamicin when there are concerns regarding renal function, given the potential nephrotoxicity of the latter. However, the use of cefotaxime has been linked to the emergence of cephalosporin-resistant strains of several gram-negative species. ^[37] Antimicrobial resistance may be even more problematic in developing countries; resistance of E coli and Klebsiella species to ampicillin, gentamicin, and cephalosporins is on the rise. ^[38]

The choice of an antibiotic regimen should be based on the likely pathogen, the local patterns of antibacterial drug sensitivities, and the policies of the hospital.

Corticosteroids have been shown to reduce long-term sequelae, particularly hearing loss, in older infants with Haemophilus influenzae type B meningitis and S pneumoniae infection. However, use of corticosteroids is not recommended for neonates with meningitis. ^[39]

Supportive care is focused on supporting blood pressure to maintain adequate cerebral perfusion and preventing secondary brain injury. Meticulous fluid management is important to minimize cerebral edema and to respond to inappropriate antidiuretic hormone (ADH) secretion. The syndrome of inappropriate ADH secretion (SIADH) may cause hyponatremia and hypo-osmolality, which may increase lethargy and seizures while further increasing intracranial pressure (ICP).

Management of seizures is a common challenge in neonates with meningitis. Phenobarbital and phenytoin remain the current drugs of choice, with benzodiazepines utilized as adjunctive therapy. Respiratory dysfunction, disseminated intravascular coagulation (DIC), and nutritional deficiencies should be managed by experienced neonatologists.

Assessment of response to therapy

Lumbar puncture, especially for cerebrospinal fluid (CSF) culture and sensitivity, should be repeated 24-48 hours after the initial study to monitor the course of the infection and guide further treatment decisions. If the patient has persistent infection in the lumbar CSF or clinical deterioration that is not explained by other complications, imaging studies to investigate for abscess formation should be performed. A diagnostic tap of the lateral ventricle should be considered to assess for ventriculitis if no focal abscess is noted on imaging. Ventriculitis may occur, especially with gram-negative bacteria, in the absence of pleocytosis in the lumbar CSF or with sterile CSF.

Given the high sensitivity and specificity of polymerase chain reaction (PCR) assay for HSV, a negative HSV-PCR result in the initial CSF sample is an acceptable end point for discontinuance of empiric acyclovir treatment. However, if any clinical data continue to suggest HSV, consider a full course of treatment despite the negative HSV-PCR result. At some centers, lumbar puncture is repeated 3 weeks after completion of therapy for PCR-proven HSV meningitis to confirm that the virus has been eradicated.

Infants with partially treated bacterial meningitis should be managed on a case-by-case basis in accordance with their clinical presentation. These infants should be observed for at least 48 hours after treatment is discontinued.

C-reactive protein levels can be useful in identifying the presence of a systemic anti-inflammatory response and can be used serially to track the response to treatment.

Ventriculostomy with external drainage may be required in cases where acute hydrocephalus develops secondary to obstruction of CSF flow.

Administration of intraventricular antibiotics is recommended in cases of ventriculitis, but is no longer recommended as a routine treatment for gram-negative meningitis.

The use of intrapartum antibiotic prophylaxis in pregnant mothers who are positive for group B streptococcal (GBS) colonization on screening or have risk factors for GBS colonization has reduced the incidence of neonatal early-onset GBS meningitis from approximately 1.8 cases to 0.3 cases per 1000 live births. ^[9] Screening and risk factor assessment should be included universally in routine prenatal care.

Cesarean delivery decreases, but does not eliminate, transmission of HSV from the mother’s genital tract to the neonate in cases of known infection. Suppressive antiviral therapy for HSV-infected women during the third trimester may prevent recurrent infectious episodes and thereby minimize the infant’s exposure to the virus during delivery. ^[16]

Because of the potential for hearing loss, neonates with meningitis should undergo brainstem auditory evoked response (BAER) testing at 4-6 weeks after discharge. ^[40] Survivors of neonatal meningitis require long-term surveillance not only for disorders of hearing but also for disorders of vision, motor, or cognitive function.

Developmental delay is a frequent complication of neonatal meningitis. Early intervention services should be employed to maximize developmental gains.

Recommendations for specific microbial therapy based on isolated pathogen and susceptibility testing ^[46]

Recommended dosages of antimicrobial therapy based on age 

In the event that these complications manifest after antibiotic therapy, neurosurgical intervention may be required for the aggressive treatment during the acute stage of bacterial meningitis. Patients with these complications are assessed by neuroimaging (CT scan, MRI, cranial ultrasonography) to confirm lesions and the need for neurosurgery. ^[44]

Clinical features assessed prior to surgical intervention:

• Pretreatment duration
• Initial clinical presentation
• Disturbance of consciousness
• Focal neurologic deficits
• Initial CSF findings
• Leukocyte count
• Lactate level
• Sugar
• Protein
• Positive blood culture
• Clinical course after antimicrobial treatment
• Prolonged/secondary fever
• Persistent focal features
• Prolonged disturbance of consciousness
• Late/intractable seizures
• Repeated CSF testing

  • Leukocyte count
  • Lactate level
  • Sugar
  • Protein
• Positive culture

Despite advances in antimicrobial therapy, mortality and morbidity remains high in neonatal meningitis. In infants that have unsatisfactory responses to antibiotic treatment, there are a number of complicated manifestations that arise.

Clinical presentation of complications includes ^[44] : 

• Prolonged or secondary fever
• Intractable seizures
• Late seizures
• Depressed level of consciousness
• Prolonged disturbance of consciousness
• Persistent focal signs
• Frontal bulging
• Syndrome of inappropriate antidiuretic hormone (SIADH)
• Brain infarction
• Subdural effusions

In addition to neurologic complications, cerebrovascular complications also occur with infantile bacterial meningitis. With the development of cerebrovascular complications, there is an onset of mechanisms that are involved.

Detrimental mechanisms that contribute to cerebrovascular complications include ^[45] :

• Loss of cerebrovascular autoregulation
• Strangulation of vessels that transverse exudates at the base of the brain
• Development of vasculitis
• Inflammation
• Spasms
• Constriction
• Thrombosis
• Meningeal inflammatory exudate in subarachnoid space
• Obstruction of outflow and absorption of CSF
• Infiltration of cerebral vasculature

The sequela of cerebrovascular complications often leads to cerebral infarction. This further leads to cerebral ischemia, seizures, hydrocephalus, and other complications of pathogeneses. 

Listeria monocytogenes and Escherichia coli are bacteria found in contaminated foods that can cause neonatal meningitis. ^[43] By avoiding certain foods and safely preparing produce, pregnant mothers can reduce the risk of neonatal meningitis caused by these bacteria.

Foods to avoid that may be contaminated by listeria include:

• Soft cheeses made with unpasteurized milk
• Smoked seafood that is not canned or shelf-stable
• Raw (unpasteurized) milk

Foods that must be safely prepared to prevent the growth of listeria and E. coli include:

• Raw sprouts
• Melons
• Hot dogs, deli meat, and cold cuts