21/1/2016 Bacterial meningitis in the neonate: Treatment and outcome

Official reprint from UpToDate ®

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Bacterial meningitis in the neonate: Treatment and outcome

Authors Section Editors Deputy Editor

Morven S Edwards, MD Sheldon L Kaplan, MD Carrie Armsby, MD, MPH
Carol J Baker, MD Leonard E Weisman, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2015. | This topic last updated: Jan 18, 2016.

INTRODUCTION — Bacterial meningitis is more common in the first month than at any other time of life [1].
Despite advances in infant intensive care, neonatal meningitis remains a devastating disease.

The mortality rate has declined from almost 50 percent in the 1970s to contemporary rates of less than 10
percent [2-5]. However, morbidity from neonatal meningitis is relatively unchanged [6]. Survivors remain at high
risk for neurologic sequelae and lifelong impairment as a result of infectious insult to their developing brains
[3,5].

The treatment and outcome of bacterial meningitis in the neonate (age <1 month) will be discussed here. The
clinical features, diagnosis, and complications are discussed separately, as is bacterial meningitis in older
children. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis" and "Bacterial meningitis in
the neonate: Neurologic complications" and "Bacterial meningitis in children older than one month: Clinical
features and diagnosis" and "Bacterial meningitis in children older than one month: Treatment and prognosis"
and "Bacterial meningitis in children: Neurologic complications".)

SUPPORTIVE CARE — Initial care for all neonates with meningitis should be provided in an intensive care
setting. Although there are no data to quantify the impact of supportive care measures, adequate oxygenation,
prevention of hypoglycemia, effective anticonvulsant therapy, control of intracranial hypertension, and prevention
of fluctuations in cerebral blood flow are considered crucial parts of the management of neonates with bacterial
meningitis [7].

Supportive measures for neonates with meningitis may include:

● Fluid maintenance (see "Fluid and electrolyte therapy in newborns")

● Prevention of hypoglycemia (see "Management and outcome of neonatal hypoglycemia")

● Control of seizures (see "Treatment of neonatal seizures")

● Provision of oxygen and mechanical ventilator support (see "Mechanical ventilation in neonates")

● Nutritional support (see "Parenteral nutrition in infants and children")

ANTIMICROBIAL THERAPY

Overview — Appropriate broad spectrum antimicrobial therapy with agents that have adequate cerebrospinal
fluid (CSF) penetration is indicated if the initial CSF evaluation is suggestive of bacterial meningitis (eg,
organism present on Gram-stained smear, increased CSF white blood cell count, increased CSF protein,
decreased CSF glucose) and should be initiated as soon as possible [8]. (See "Bacterial meningitis in the
neonate: Clinical features and diagnosis", section on 'Interpretation of CSF'.)

Empirical therapy for nonbacterial infections also can be indicated for some neonates pending definitive
evaluation (eg, acyclovir for herpes simplex virus in neonates who have mucocutaneous vesicles or clinical or
CSF findings suggesting herpes simplex virus). (See "Neonatal herpes simplex virus infection: Clinical features
and diagnosis", section on 'Clinical manifestations' and "Neonatal herpes simplex virus infection: Management
and prevention", section on 'Acyclovir therapy'.)

When the results of the CSF and blood cultures, including antimicrobial susceptibilities, are available,
antimicrobial therapy is adjusted as indicated. (See 'Specific therapy' below.)

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Empirical therapy — The initial choice of antimicrobials for suspected bacterial meningitis in the neonate is
based on the infant's age, likely pathogens, and the susceptibility patterns of gram-negative organisms causing
late-onset infections in infants with continuous care in a particular nursery. (See "Bacterial meningitis in the
neonate: Clinical features and diagnosis", section on 'Etiology'.)

● In neonates zero through three days of age, the most common bacterial pathogens are group B
Streptococcus (GBS), Escherichia coli, other enteric bacilli, and Listeria monocytogenes. Uncommon
pathogens include other streptococci, including groups A, C, or G, viridans streptococci and enterococci,
non-typeable Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae.

● In neonates four days of age or older, other gram-negative organisms must be considered in addition to
GBS, E. coli, and other enterics, including Serratia marcescens, Pseudomonas aeruginosa, and
Citrobacter koseri, as well as L. monocytogenes.

● In continuously hospitalized neonates seven days of age or older, a wide range of potential gram-positive
organisms must be considered in addition to antimicrobial-resistant gram-negative organisms, such as
Acinetobacter, Stenotrophomonas, multiple-drug-resistant Klebsiella, and other enterics.

● In neonates admitted from the community, meningitis due to Staphylococcus aureus is not a concern; in
hospitalized very low birth weight infants, late-onset S. aureus meningitis has been documented, albeit
rarely [9,10].

Early-onset

● Initial empirical therapy for suspected bacterial meningitis within the first three to six days of age is
ampicillin and an aminoglycoside, usually gentamicin.

● An alternative regimen of ampicillin and an expanded spectrum third-generation cephalosporin (such as

cefotaxime) can be used if L. monocytogenes or enterococci are unlikely. Adding cefotaxime to the
regimen broadens empirical coverage for gram-negative organisms. High rates of ampicillin resistance
among E. coli isolates and a link between maternal intrapartum ampicillin and E. coli resistance have been
reported in very low birth weight (VLBW) infants (birth weight [BW] <1500 g) but not near term or term
infants [11].

In the neonatal intensive care unit (NICU) setting, cephalosporin use should be restricted to neonates with
suspected bacterial meningitis based on CSF parameters and/or clinical findings. When use of cefotaxime
is routine (eg, when it is used more broadly for all neonates treated for "rule out sepsis"), rapid emergence
of cephalosporin-resistant strains (especially Enterobacter cloacae, Klebsiella pneumoniae, and Serratia
species) can occur [12]. The choice of empiric antibiotic coverage for suspected sepsis in preterm and
term neonates is discussed in detail separately. (See "Treatment and prevention of bacterial sepsis in the
preterm infant", section on 'Empiric antibiotic therapy' and "Management and outcome of sepsis in term
and late preterm infants", section on 'Initial empiric therapy'.)

● If meningitis resulting from a gram-negative organism is strongly suspected (eg, when the CSF Gram stain
reveals gram-negative bacilli), the empirical regimen of ampicillin and an aminoglycoside should be
expanded to include cefotaxime. If cefotaxime is not available, meropenem may be substituted.

Late-onset — Initial empirical therapy for suspected bacterial meningitis after the first week of life depends
upon the preliminary CSF findings and whether the neonate remains hospitalized since birth or has been
discharged from the birth hospital and is admitted from the community.

● Neonates admitted from the community – For neonates admitted from the community who are strongly
suspected to have bacterial meningitis based on CSF parameters and/or clinical findings, the initial
empiric regimen consists of ampicillin plus an aminoglycoside plus cefotaxime. Antibiotic coverage
should generally not be narrowed based on the Gram stain results because they are subject to observer
misinterpretation. Empiric broad-spectrum therapy should be continued pending confirmation of the
organism and susceptibility results [13]. (See 'Specific therapy' below.)

In one survey of febrile infants <90 days old who presented to an emergency department (ED), nearly 80

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percent of infants with meningitis had ampicillin-resistant pathogens [14]. The authors recommended that
the initial regimen contain ampicillin and gentamicin plus a third-generation cephalosporin because of the
risk of GBS and L. monocytogenes infection in this age group, as well as for treatment of cefotaxime-
susceptible gram-negative enteric organisms. We agree with these recommendations.

● Neonates hospitalized since birth – For infants who remain hospitalized since birth, late-onset sepsis
without meningitis is initially treated with vancomycin and an aminoglycoside. When lumbar puncture
(LP) suggests meningitis, cefotaxime should be added to provide an extended spectrum for gram-negative
enterics and for optimal activity in the CSF against pneumococci. Cefotaxime should also be added when
the LP cannot be performed due to clinical instability. Ampicillin should be added to a vancomycin-
aminoglycoside regimen if L. monocytogenes is suspected (eg, on the basis of the Gram stain), because
vancomycin concentrations in the CSF are not bactericidal for these organisms [15].

If cefotaxime is unavailable [16] or if there is concern for infection due to a multidrug-resistant (MDR) gram-
negative organism, meropenem rather than cefotaxime is the preferred choice for empirical therapy. The
determination of whether to provide empiric therapy for MDR organisms is based upon susceptibility patterns of
gram-negative organisms at the particular NICU. MDR gram-negatives remain uncommon in NICUs in the United
States but Enterobacteriaceae infections resistant to extended spectrum beta-lactams are an emerging problem
in older infants and children [17].

Specific therapy — Once the causative agent and the in vitro antimicrobial susceptibility results are known,
empirical antimicrobial therapy should be altered accordingly. Guidelines for the treatment of the most common
causative organisms of neonatal meningitis are provided below.

Group B Streptococcus — GBS is uniformly susceptible to penicillin and ampicillin. The combination of
penicillin or ampicillin plus an aminoglycoside can be employed until sterility of the bloodstream and CSF has
been documented. This recommendation is based on the improved in vitro synergy and in vivo efficacy in animal
models of infection when these combinations are compared with penicillin or ampicillin alone [18-24]. Penicillin
G monotherapy should be given when clinical and microbiologic responses have been documented to complete
a 14- to 21-day course of therapy. (See "Group B streptococcal infection in neonates and young infants",
section on 'Antimicrobial therapy'.)

The dose for penicillin varies depending upon the age of the neonate:

● Infants ≤7 days of age: 250,000 to 450,000 U/kg per day intravenously (IV) divided every eight hours

● Infants >7 days of age: 450,000 to 500,000 U/kg per day IV divided every six hours

Ampicillin is an acceptable alternative. The dose for ampicillin varies depending upon the age of the neonate:

● Infants ≤7 days: 200 to 300 mg/kg per day IV divided every eight hours

● Infants >7 days: 300 to 400 mg/kg per day IV divided every six hours

Gram-negative enteric bacteria — Ampicillin is the antimicrobial of choice for neonatal meningitis
resulting from ampicillin-susceptible strains of E. coli.

Ampicillin-resistant E. coli and other gram-negative organisms usually are treated with a combination of an
expanded-spectrum cephalosporin, generally cefotaxime (or ceftazidime in the case of P. aeruginosa) initially in
combination with an aminoglycoside, usually gentamicin. Once sterility of the CSF is documented, the
aminoglycoside can be discontinued and the appropriate beta-lactam continued to complete a minimum of 21
days or 14 days of therapy after the CSF is sterile, whichever is longer.

The prevalence of antimicrobial resistance among K. pneumoniae has increased markedly since the 1990s [25].
The hospital microbiology laboratory should provide assistance for appropriate testing of gram-negative
organisms for MDR patterns.

Meropenem is recommended for treatment of infections caused by most MDR enteric organisms. Although
there are limited data documenting the optimal dose and tolerance of meropenem in neonates, meropenem
should be administered for the entire course of therapy for neonates with meningitis that is caused by MDR

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gram-negative organisms.

For infants >3 months of age, the dose of meropenem is 40 mg/kg every 8 hours. Meropenem is not approved in
the United States for the treatment of meningitis in infants <3 months of age. However, when there are no other
treatment options, we use a dose of 20 to 40 mg/kg every 8 to 12 hours, with the lower dose for infants with
renal impairment or immaturity of renal function.

Listeria — The combination of ampicillin and gentamicin is more effective than ampicillin alone in vitro and in
animal models of infection, and it is appropriate for initial therapy. When the CSF has been sterilized and the
infant has improved clinically, a 14- to 21-day course of treatment can be completed with ampicillin
monotherapy. (See "Treatment, prognosis, and prevention of Listeria monocytogenes infection", section on
'Antibiotic regimens'.)

Coagulase-negative staphylococci — Vancomycin is the antimicrobial of choice for proven meningitis

caused by coagulase-negative staphylococci. These organisms rarely invade the meninges except as a
complication of bacteremia accompanying intraventricular hemorrhage (IVH) in VLBW infants (BW <1500 g) or
as a result of surgical manipulations or placement of a ventriculoperitoneal shunt. Such infections invariably are
of late onset.

The dose of vancomycin is 20 mg/kg per dose; the dosing interval varies depending upon gestational age (GA)
as follows [26]:

● <30 weeks gestation: every 18 hours

● 30 to 37 weeks gestation: every 12 hours
● >37 weeks gestation: every 8 hours

Sterilization of the CSF usually is achieved promptly after initiation of vancomycin. If the CSF is persistently
positive, consideration should be given to adding rifampin (5 mg/kg every 12 hours) to vancomycin for synergy.

Duration

Positive CSF culture — The duration of antimicrobial therapy depends upon the causative organism and
the clinical course:

● A 14-day course is sufficient for neonates with uncomplicated meningitis caused by GBS or other gram-
positive organisms, such as L. monocytogenes or Enterococcus

● A longer course of therapy is required for neonates with GBS meningitis who have a complicated course
(see "Bacterial meningitis in the neonate: Neurologic complications")

● A 21-day course is the minimum for neonates with meningitis resulting from E. coli or other gram-
negative pathogens [12]

● Prolonged treatment, sometimes for as long as eight weeks, may be required for neonates with
ventriculitis, abscesses, or multiple areas of infarction with resulting encephalomalacia (see "Bacterial
meningitis in the neonate: Neurologic complications")

Negative CSF culture — The duration of antibiotic therapy for neonates with negative cultures must be
determined on an individual clinical basis:

● For neonates with clinically suspected bacterial meningitis (with or without CSF pleocytosis) but with
negative blood and CSF cultures (obtained before antibiotic therapy), we suggest discontinuation of
antimicrobials after 48 to 72 hours of negative cultures.

● For neonates with CSF pleocytosis and bacteremia, but a negative CSF culture (obtained before antibiotic
therapy), we usually continue meningeal doses of antimicrobial therapy for 10 days for gram-positive
bacteremia (eg, GBS) and 14 days for gram-negative bacteremia.

Lumbar punture delayed — For neonates in whom the CSF evaluation was delayed because of clinical
instability, meningeal doses of antimicrobial therapy should be continued until the LP can be safely performed.
The administration of antibiotics for several hours or days before CSF evaluation may result in negative CSF
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culture. In most cases, other CSF parameters, (eg, cell count and protein concentration), will be sufficiently
abnormal to permit accurate diagnosis of meningitis if it is present. (See "Bacterial meningitis in the neonate:
Clinical features and diagnosis", section on 'Interpretation of CSF'.)

The total duration of therapy depends upon the CSF evaluation and blood culture result:

● Those who have a CSF pleocytosis and positive blood culture are treated for 10 days for gram-positive
bacteremia (eg, GBS) and 14 days for gram-negative bacteremia.

● For those who have a CSF pleocytosis and negative blood culture, we individualize the duration of
meningitic doses of antimicrobial therapy based on clinical parameters and likelihood that there is a
noninfectious explanation for the pleocytosis (such as IVH). (See "Bacterial meningitis in the neonate:
Clinical features and diagnosis", section on 'Differential diagnosis'.)

● For those who have a normal CSF profile, and negative blood and CSF cultures, we usually discontinue
antimicrobial therapy when cultures are sterile after 48 to 72 hours.

Antibiotic exposure prior to evaluation — Exposure to antibiotics prior to the evaluation, through
maternal intrapartum antibiotic prophylaxis (IAP) or antibiotics given to the neonate for other reasons, may
influence the interpretations of the results:

● Maternal IAP – Compared with infants whose mothers did not receive IAP, infants whose mothers did
receive IAP are more likely to be healthy-appearing, less likely to be critically ill, and less likely to be
infected [27]. Neonates whose mothers received IAP and have a clinical course that suggests neonatal
sepsis or meningitis are treated in the same manner as infants with proven sepsis or meningitis. (See
'Positive CSF culture' above.)

● Infants receiving antibiotics for other reasons – Infants who are receiving prophylactic antibiotics (eg,
for vesicoureteral reflux) or antibiotics for other reasons at the time of CSF evaluation are treated in the
same manner as infants in whom the CSF evaluation was delayed. (See 'Lumbar punture delayed' above.)

ADJUNCTIVE THERAPY — There is evidence from experimental models that immune modulation may
positively impact the outcome of neonatal meningitis. However, none of the modalities investigated thus far has
been sufficiently characterized for their use to be included in the routine management of neonatal meningitis.

The effect of dexamethasone to diminish the risk of neurologic sequelae in neonatal meningitis was evaluated in
a small, randomized trial that did not have a placebo arm [28]. The administration of dexamethasone did not
significantly affect mortality or neurologic outcome at two years of age, and dexamethasone therapy is not
currently recommended. (See "Bacterial meningitis in children: Dexamethasone and other measures to prevent
neurologic complications".)

Adjunctive therapies for neonatal sepsis, which is a prelude to neonatal meningitis, are discussed separately.
(See "Management and outcome of sepsis in term and late preterm infants", section on 'Adjunctive therapies'.)

MONITORING RESPONSE TO THERAPY

Ongoing evaluation — The response to antimicrobial and supportive therapy and the potential development of
complications are monitored clinically through repeat neurologic evaluations, evaluation of the cerebrospinal fluid
(CSF), and by neuroimaging. In bacteremic infants, a blood culture should be performed to document sterility of
the blood stream. The follow-up blood culture is usually obtained when it is known that the initial blood culture is
positive.

Repeat lumbar puncture — Lumbar puncture (LP) should be repeated routinely at 24 to 48 hours after
initiation of antimicrobial therapy to document CSF sterilization [13,26]. Gram-positive bacteria usually clear
rapidly (within 24 hours) from the CSF after initiation of appropriate antimicrobial therapy, whereas gram-negative
may persist for several days in severe cases [29,30].

Reevaluation of the CSF 24 to 48 hours after initiation of antimicrobial therapy is important for several reasons
[26,31]:

● Delayed sterilization of the CSF is associated with an increased risk of developing neurologic sequelae
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[30,32,33]. (See 'Prognostic factors' below.)

● The persistent identification of organisms on a Gram-stained smear may be an early indication of

inadequacy of antimicrobial therapy (eg, the organism is not susceptible to the concentration of antibiotic
that is attained in the CSF). (See 'Coagulase-negative staphylococci' above.)

● Persistence of viable organisms more than 48 hours after initiation of antimicrobial therapy is an indication
for diagnostic neuroimaging because it can indicate a purulent focus (eg, obstructive ventriculitis, multiple
small vessel thrombi) that can require additional intervention or increased duration of antimicrobial therapy.
(See "Bacterial meningitis in the neonate: Neurologic complications".)

● Sterilization of the CSF is a criterion for discontinuing combination therapy for some pathogens (eg, GBS,
Listeria). (See 'Specific therapy' above.)

In uncomplicated neonatal meningitis, the CSF culture obtained 24 to 48 hours after initiation of therapy is
sterile. However, as indicated above, a positive culture obtained 24 to 48 hours after initiation of therapy raises a
concern for ventriculitis. The additional evaluation and management of infants with possible ventriculitis is
individualized and should be undertaken in consultation with specialists in pediatric infectious diseases and
pediatric neurosurgery. (See "Bacterial meningitis in the neonate: Neurologic complications", section on
'Ventriculitis'.)

Neuroimaging — Neuroimaging is indicated to assist in defining the potential complications of neonatal

meningitis and typically is performed late in the course of therapy to provide the best prognostic information.
(See "Bacterial meningitis in the neonate: Neurologic complications".)

In addition, it is our practice to perform magnetic resonance imaging (MRI) 48 to 72 hours before the anticipated
end of therapy in all neonates with confirmed bacterial meningitis, even those with an apparently uncomplicated
course. We prefer MRI over contrast-enhanced computed tomography (CT) because MRI provides added detail,
optimizes assessment of injury to white matter, and avoids radiation exposure [34]. If there are focal findings
that require extension of the course of antimicrobial therapy, treatment can be continued without interruption.

● Cranial sonography – Early in the course of infection, cranial sonography is the most useful and
practical neuroimaging technique. It is most helpful for assessing ventricular size and the presence of
intraventricular hemorrhage. Cranial sonography also can demonstrate ventriculitis, echogenic sulci,
abnormal parenchymal echogenicities, and extracerebral fluid collections [35,36]. In addition, because
sonography can be performed at the bedside, it can be useful in defining the progression of complications
in infants with prolonged seizure activity or focal neurologic deficits. (See "Bacterial meningitis in the
neonate: Neurologic complications".)

● Magnetic resonance imaging or computed tomography – Similar to ultrasonography, early in the

treatment course, MRI and CT with contrast enhancement can demonstrate the degree of cerebral edema,
obstruction to CSF flow, infarction, abscess, and subdural fluid collections [37]. Later in the treatment
course, contrast-enhanced MRI or CT is useful in detecting cerebral abscesses, persistent cerebritis,
areas of infarct or encephalomalacia, and degree of cerebral cortical and white matter atrophy. These
findings may influence duration of antimicrobial therapy and/or the need for early intervention services.
(See "Bacterial meningitis in the neonate: Neurologic complications".)

Contrast-enhanced neuroimaging (MRI or CT) is integral to the care of all neonates with meningitis caused
by organisms that have a propensity for formation of intracranial abscesses. These include Citrobacter
koseri, S. marcescens, Proteus mirabilis, and Enterobacter sakazakii (now known as Cronobacter) [38-
44]. (See "Bacterial meningitis in the neonate: Neurologic complications", section on 'Brain abscess'.)

FOLLOW-UP — Long-term follow-up for survivors of neonatal meningitis includes monitoring of hearing, visual
acuity, and developmental status. Hearing should be evaluated by evoked response audiometry within four to six
weeks of completion of therapy [45]. (See "Hearing impairment in children: Evaluation".)

Survivors of neonatal meningitis are at risk for developmental delay and may be eligible to receive early
intervention services in the United States (eligibility criteria vary by state). Appropriate referrals should be made
as indicated. Developmental surveillance should continue throughout childhood. (See "Developmental-behavioral
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surveillance and screening in primary care", section on 'When to perform developmental-behavioral screening'.)

OUTCOME

Mortality and disability — Neonatal meningitis is a devastating disease. Advances in infant intensive care
have helped to reduce mortality, which is approximately 10 percent [2,3,5,46], but survivors remain at high risk
for neurologic sequelae and lifelong impairments, as illustrated below [3,5,46]. Approximately 20 percent of
survivors have severe disability and another 35 percent have mild to moderate disability. (See "Bacterial
meningitis in the neonate: Neurologic complications".)

In a review of 101 infants with gestational age (GA) ≥35 weeks admitted to a Canadian tertiary-care center in
Canada with a diagnosis of neonatal bacterial meningitis (established by culture of the pathogen from the
cerebrospinal fluid [CSF]) between 1979 and 1998, 13 infants died [47]. Mortality declined from 17.4 percent to 9
percent between 1979 and 1988, and 1989 and 1998. Among survivors, 17 had moderate or severe disability at
one year of age. Moderate or severe disability was defined as severe cerebral palsy (CP) (severe impairment of
daily activities), moderate to severe developmental delay (Bayley score <2 standard deviations [SD] for age),
blindness, and/or deafness.

In a survey comparing five-year outcome between a cohort of children born in England and Wales who had
neonatal meningitis (bacterial, viral, or fungal) in 1996 to 1997 (15 percent had birth weight [BW] <2000 g) with
control groups of neonates hospitalized for other reasons and patients from general practice, more patients with
neonatal meningitis had serious disability at five years than did hospital or general practice controls (23 percent,
7 percent, and 2 percent, respectively) [3]. Between 1985 and 1996, mortality declined from 22 to 6.6 percent,
but the incidence of serious disability (defined as multiple impairments, intellectual impairment, moderate or
severe sensorineural hearing loss or visual impairment, epilepsy, neuromotor disability hydrocephalus, or
inability to attend mainstream school) was unchanged (25.5 percent in 1985 and 23.5 percent in 1996)
[3,48,49].

Outcomes vary according to the causative organism and the infant's BW:

● Gram-positive infections – In case series from the late 1990s from Europe and early 2000s from the
United States, the mortality rates of group B streptococcal (GBS) meningitis were 22 and 6 percent,
respectively [50,51]. Long-term neurologic sequelae occur in as many as 40 percent of survivors of GBS
meningitis. Among 43 survivors of GBS meningitis between 1998 and 2006 who underwent follow-up
examination at age 3 through 12 years, 24 (56 percent) demonstrated age-appropriate development, eight
(19 percent) had severe impairment (eg, cognitive skills >2 SD below the mean in at least one domain,
severe neurologic or functional impairment), and 11 (25 percent) had mild-to-moderate impairment (eg,
cognitive skills within 1 to 2 SD below the mean in any domain, academic underachievement, evidence of
mild neurologic or functional impairment) [52]. These outcomes are little changed from those reported two
decades earlier [53]. (See "Group B streptococcal infection in neonates and young infants", section on
'Outcome'.)

● Gram-negative infections – In one review of 72 neonates with gram-negative meningitis from 1969 to
1989, the mortality rate was 17 percent. Among the 44 survivors, 55 percent had central nervous system
(CNS) sequelae [32]. CNS sequelae included developmental delay in 32 percent, seizure disorder in 30
percent, cerebral palsy in 25 percent, and hearing loss in 16 percent [32].

● Very low birth weight infants – One review compared clinical outcomes in 64 very low birth weight
(VLBW) infants (BW <1500 g) who had neonatal meningitis (including Candidal meningitis) from 1977
through 1995 and VLBW infants without meningitis [54]. After controlling for BW, intraventricular
hemorrhage (IVH), chronic lung disease, and social risk factors, survivors of meningitis had an increased
risk of major neurologic abnormality (odds ratio [OR] 2.27 [95% CI 1.02-5.05]). Major neurologic
abnormality included CP, hypertonia, hypotonia, shunt-dependent hydrocephalus (without other neurologic
abnormality), blindness, deafness, and mental developmental index <70 at 20 months of age.

In a large cohort study of extremely low birth weight (ELBW; BW <1000 g) infants, those with neonatal
meningitis were more likely than uninfected infants to have cerebral palsy, neurodevelopmental
impairment, and low mental developmental index scores [55].

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Prognostic factors — Factors predictive of death or serious adverse sequelae from bacterial meningitis include:

● LBW (birth weight <2500 g) or preterm birth (<37 weeks gestation) [4,56,57]

● History of symptoms for >24 hours before hospitalization

● Leukopenia (WBC <5000/microL) and neutropenia at presentation [4,47,53]

● Seizures occurring more than 72 hours after hospitalization

● Focal neurologic deficits

● Requirement for mechanical ventilatory support or inotropes [47,53,58]

● Delayed sterilization of the CSF [30,32,33,59]

In a retrospective study, 22 percent of survivors of GBS meningitis had neurologic sequelae evident at hospital
discharge; the most common sequelae were persistent seizure disorder, followed by hypertonicity and
dysphagia [51]. In multivariate analysis, only seizures that persisted after admission predicted sequelae at
discharge. In another study, low voltage background pattern and electrographic seizure activity on amplitude
integrated electroencephalogram were predictive of poor outcome in 13 survivors of GBS meningitis [50].

Neuroimaging findings of meningeal inflammation are not related to neurologic outcome, but the presence and
size of parenchymal lesions (eg, thrombi, encephalomalacia) do have prognostic significance. In particular,
abscess formation is associated with neurologic sequelae [36].

SUMMARY AND RECOMMENDATIONS

● Bacterial meningitis in the neonate is a devastating disease. Advances in infant intensive care have helped
to reduce mortality, but survivors remain at high risk for neurologic sequelae and lifelong impairments. (See
'Introduction' above.)

● Neonates with bacterial meningitis should receive initial care in an intensive care unit (ICU). (See
'Supportive care' above.)

● Antimicrobial therapy for neonatal meningitis is indicated if the results of the cerebrospinal fluid (CSF)
evaluation are suggestive of bacterial meningitis. Appropriate broad spectrum antimicrobial therapy with
agents that have adequate CSF penetration should be initiated as soon as possible. (See "Bacterial
meningitis in the neonate: Clinical features and diagnosis", section on 'Laboratory features' and
'Antimicrobial therapy' above.)

● The initial choice of antimicrobials for suspected bacterial meningitis in the neonate is empirical, based on
the infant's age, likely pathogens, and the susceptibility patterns of gram-negative organisms in a
particular nursery or neonatal intensive care unit (NICU). We recommend suspected neonatal meningitis
be treated initially with empirical antibiotic therapy that provides broad coverage for the most likely
pathogens (group B Streptococcus [GBS] and gram-negative enteric organisms, including Escherichia
coli) (Grade 1B). (See 'Empirical therapy' above.)

The empiric regimen for early-onset (ie, within the first three to six days of age) meningitis consists of
ampicillin and an aminoglycoside (typically gentamicin). When the CSF Gram stain reveals gram-negative
bacilli, the empirical regimen should be expanded to include cefotaxime. (See 'Early-onset' above.)

Empiric antibiotic regimens for late-onset (ie, after the first week of life) meningitis are as follows (see
'Late-onset' above):

• For neonates admitted from the community, we suggest ampicillin plus an aminoglycoside (typically
gentamicin) plus cefotaxime.

• For infants who continue to be hospitalized from birth, we suggest vancomycin plus an
aminoglycoside (typically gentamicin) plus cefotaxime. If GBS or L. monocytogenes is suspected
(eg, on the basis of the Gram stain), ampicillin should be added to the regimen.

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• If multidrug-resistant (MDR) gram-negative rods are a concern (based on the susceptibility patterns in
the particular NICU), meropenem should be substituted for cefotaxime.

● Once the causative agent and its in vitro antimicrobial susceptibility pattern are known, empirical
antimicrobial therapy should be altered accordingly. (See 'Specific therapy' above.)

● The duration of antimicrobial therapy depends upon the causative organism and the clinical course. (See
'Duration' above and "Bacterial meningitis in the neonate: Neurologic complications".)

● The response to antimicrobial and supportive therapy and the potential development of complications are
monitored clinically, through repeat neurologic examinations, evaluation of the CSF, and by neuroimaging.
Neurologic complications must be considered in the neonate with neonatal meningitis who fails to improve
clinically after 24 to 48 hours of appropriate antibiotic therapy. (See 'Monitoring response to therapy' above
and "Bacterial meningitis in the neonate: Neurologic complications".)

● We suggest repeat lumbar puncture (LP) 24 to 48 hours after initiation of antimicrobial therapy to
document sterilization of the CSF. (See 'Repeat lumbar puncture' above.)

● Neuroimaging is indicated in neonates with signs suggesting neurologic complications. In addition, we

perform magnetic resonance imaging (MRI) 48 to 72 hours before the anticipated discontinuation of
antimicrobial therapy in all neonates with bacterial meningitis, even in those with an apparently
uncomplicated course. (See 'Neuroimaging' above.)

● The mortality of neonatal bacterial meningitis is approximately 10 percent. Approximately 20 percent of

survivors have severe disability and another 35 percent have mild to moderate disability. Long-term
neurologic sequelae are somewhat more frequent after gram-negative neonatal meningitis than after group
B streptococcal neonatal meningitis. (See 'Outcome' above.)

● Long-term follow-up for survivors of neonatal meningitis includes monitoring of hearing, visual acuity, and
developmental status. (See 'Follow-up' above.)

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Topic 6016 Version 20.0

Disclosures

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21/1/2016 Bacterial meningitis in the neonate: Treatment and outcome
Disclosures: Morven S Edw ards, MD Grant/Research/Clinical Trial Support: Pfizer Inc. [Group B Streptococcus].
Consultant/Advisory Boards: Novartis Vaccines [Group B Streptococcus]. Carol J Baker, MD Consultant/Advisory Boards: Pfizer
[Group B streptococcal, Serogroup B Meningococcal (vaccines)]. Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support:
Pfizer [S. pneumoniae (PCV13, Linezolid)]; Cubist [S. aureus (Tedizolid)]; Forest Lab [Osteomyelitis (Ceftaroline)]. Consultant/Advisory
Boards: Pfizer [S. pneumoniae (PCV13, Linezolid); S. aureus (vaccine development)]; Theravance [S. aureus (Telavancin)]. Leonard
E Weism an, MD Grant/Research/Clinical Trial Support: Vax-Immune [Ureaplasma diagnosis, vaccines, and antibodies].
Consultant/Advisory Boards: Glaxo-Smith Kline [Malaria vaccine]; NIAID [Staphylococcus aureus (Mupirocin)]. Patent Holder: Baylor
College of Medicine [Ureaplasma diagnosis, vaccines, antibodies, process for preparing biological samples]. Equity Ow nership/Stock
Options: Vax-Immune [Ureaplasma diagnosis, vaccines, and antibodies]. Carrie Arm sby, MD, MPH Nothing to disclose.
Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately
referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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