Bacterial meningitis in the neonate: Treatment and outcome

Authors:
Morven S Edwards, MD
Carol J Baker, MD
Section Editors:
Sheldon L Kaplan, MD
Leonard E Weisman, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Literature review current through: Feb 2018. | This topic last updated: Jul 27,
2017.

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.

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
●Management of cardiovascular instability or shock
●Prevention of hypoglycemia
●Control of seizures
 ●Provision of oxygen and mechanical ventilator support
●Nutritional support

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].

Empiric 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).

When the results of the CSF and blood cultures, including antimicrobial susceptibilities,
are available, antimicrobial therapy is adjusted as indicated.

Empiric 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.

Common pathogens — Likely pathogens vary somewhat based upon age and
whether the neonate remains hospitalized since birth or is admitted from the
community:

●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 empiric 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, if available) can be used if L.
monocytogenes or enterococci are unlikely. Adding cefotaxime to the regimen
broadens empiric 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.
●If meningitis resulting from a gram-negative organism is strongly suspected (eg,
when the CSF Gram stain reveals gram-negative bacilli), the empiric regimen of
ampicillin and an aminoglycoside should be expanded to include cefotaxime. If
cefotaxime is not available, ceftazidime or meropenem may be substituted. (See
'If cefotaxime is unavailable' below.)
Late-onset — Initial empiric 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 (usually gentamicin) plus cefotaxime.
Alternatives to cefotaxime in the event of a shortage are discussed below.
Antibiotic coverage generally should 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].
In one survey of febrile infants <90 days old who presented to an emergency
department (ED), nearly 80 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 — If cefotaxime is unavailable, alternative agents include

ceftazidime and ceftriaxone [16]; however, ceftriaxone should not be used in neonates
with clinically significant hyperbilirubinemia or those receiving concurrent intravenous
(IV) calcium (including parenteral nutrition). Meropenem is another alternative,
particularly if there is concern for infection due to a multidrug-resistant (MDR) gram-
negative organism. 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, empiric 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.

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 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 (eg, cefotaxime or ceftazidime)
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 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.

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
●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

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 puncture 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 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.

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, including whether there is a noninfectious explanation for
the pleocytosis (eg, IVH).
●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.
●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.

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.

Adjunctive therapies for neonatal sepsis, which is a prelude to neonatal meningitis, are
discussed separately.

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 [30,32,33].
●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).
●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.
●Sterilization of the CSF is a criterion for discontinuing combination therapy for
some pathogens (eg, GBS, Listeria).

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.

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.

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 better 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.
●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.
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].

FOLLOW-UP — Long-term follow-up for survivors of neonatal meningitis includes

monitoring of hearing, vision, and developmental status. Hearing should be evaluated
by evoked response audiometry within four to six weeks of completion of therapy [45].

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.

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.
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].
●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].

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].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored

guidelines from selected countries and regions around the world are provided
separately.

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.
●Neonates with bacterial meningitis should receive initial care in an intensive
care unit (ICU).
●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.
●We recommend suspected neonatal meningitis be treated initially with empiric
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). The choice of the initial empiric regimen is 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):
•For early-onset meningitis (ie, within the first three to six days of age), an
appropriate empiric regimen includes ampicillin plus an aminoglycoside
(usually gentamicin). When the CSF Gram stain reveals gram-negative
 bacilli, the empiric regimen should be expanded to include cefotaxime (if
available).
•For late-onset meningitis (ie, after the first week of life), appropriate empiric
antibiotic regimens are as follows:
-For neonates admitted from the community, the regimen includes
ampicillin plus an aminoglycoside (usually gentamicin) plus cefotaxime
(if available).
-For infants who continue to be hospitalized from birth, the regimen
includes vancomycin plus an aminoglycoside (usually 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.
•If cefotaxime is unavailable, alternative agents include ceftazidime and
ceftriaxone. Ceftriaxone should not be used in neonates with clinically
significant hyperbilirubinemia or those receiving concurrent IV calcium
(including parenteral nutrition).
•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, empiric antimicrobial therapy should be altered accordingly.
●The duration of antimicrobial therapy depends upon the causative organism
and the clinical course.
●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.
●Lumbar puncture (LP) should be repeated 24 to 48 hours after initiation of
antimicrobial therapy to document sterilization of the CSF.
●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.
 ●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.
●Long-term follow-up for survivors of neonatal meningitis includes monitoring of
hearing, visual acuity, and developmental status.

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