Bacterial Meningitis in The Neonate - Treatment and Outcome

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Official reprint from UpToDate®

www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Bacterial meningitis in the neonate: Treatment and

outcome
Authors: Morven S Edwards, MD, Carol J Baker, MD
Section Editors: Sheldon L Kaplan, MD, Joseph A Garcia-Prats, MD
Deputy Editor: Carrie Armsby, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2023. | This topic last updated: Jan 09, 2023.
INTRODUCTION
Bacterial meningitis is more common in the first month than at any other time of life [1].
Despite advances in neonatal intensive care, meningitis in the neonate remains a devastating
disease.
The treatment and outcome of bacterial meningitis in the neonate (age <1 month) will be
discussed here. The clinical features, diagnosis, and complications of bacterial meningitis are
discussed separately, as is bacterial meningitis in older children:
● (See "Bacterial meningitis in the neonate: Clinical features and diagnosis".)

● (See "Bacterial meningitis in the neonate: Neurologic complications".)
● (See "Bacterial meningitis in children older than one month: Clinical features and
diagnosis".)
● (See "Bacterial meningitis in children older than one month: Treatment and prognosis".)
SUPPORTIVE CARE
Initial care for all neonates with meningitis should be provided in an intensive care unit setting.
Supportive care measures are a crucial part of the management of neonates with bacterial
meningitis [2]. These may include:
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● Management of cardiovascular instability or shock ( algorithm 1) (see "Neonatal shock:

Management")
● Provision of oxygen and additional respiratory support as needed (see "Respiratory
support, oxygen delivery, and oxygen monitoring in the newborn" and "Overview of
mechanical ventilation in neonates")
● Careful fluid therapy, avoiding both hypo- and hypervolemia (see "Fluid and electrolyte
therapy in newborns")
● Prevention and management of hypoglycemia (see "Management and outcome of
neonatal hypoglycemia")
● Control of seizures (see "Treatment of neonatal seizures")
● Nutritional support (see "Approach to enteral nutrition in the premature infant" and
"Parenteral nutrition in infants and children")
ANTIMICROBIAL THERAPY
For neonates whose clinical and initial cerebrospinal fluid (CSF) findings are suggestive of
bacterial meningitis (eg, CSF pleocytosis, increased CSF protein and/or decreased CSF glucose,
organism present on Gram stain), broad-spectrum antimicrobial therapy should be initiated as
soon as possible. An appropriate regimen includes agents that have adequate CSF penetration
at appropriate doses to achieve adequate levels in the CSF.
When the results of the CSF and blood cultures, including antimicrobial susceptibilities, are
available, antimicrobial therapy is tailored to the specific pathogen. (See 'Definitive therapy'
below.)
Empiric therapy — The initial choice of antimicrobials for suspected bacterial meningitis in the
neonate is based on the timing of onset (ie, early versus late onset), likely pathogens
( table 1), and local susceptibility patterns within the nursery or neonatal intensive care unit
and within the community. (See "Bacterial meningitis in the neonate: Clinical features and
diagnosis", section on 'Etiology'.)
Often, at the first sign of illness, empiric therapy for neonatal sepsis is initiated as summarized
in the table ( table 2) and discussed separately. (See "Management and outcome of sepsis in
term and late preterm neonates", section on 'Initial empiric therapy'.)
When there is clinical concern for meningitis (eg, critical illness, CSF pleocytosis, organism
present on CSF Gram stain, or other suggestive CSF parameters), the empiric regimen should
be modified as follows:
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● Discontinue the aminoglycoside.
● Add an extended-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime,

or cefepime); ceftriaxone should not be used in neonates, because it displaces bilirubin
from albumin binding sites, which might contribute to kernicterus and may precipitate if
used with intravenous calcium, leading to severe reactions [3,4].
● In addition, for most neonates with CSF pleocytosis and negative CSF Gram stain, empiric
acyclovir therapy for herpes simplex virus is warranted (after performing appropriate
testing), as discussed separately. (See "Neonatal herpes simplex virus infection:
Management and prevention", section on 'Initial antiviral therapy'.)
Adding an expanded-spectrum cephalosporin to the empiric regimen provides optimal activity

in the CSF against ampicillin-resistant gram-negative enteric organisms and pneumococci. High
rates of ampicillin resistance among Escherichia coli isolates and a link between maternal
intrapartum ampicillin prophylaxis and E. coli resistance have been reported in very low birth
weight infants (birth weight <1500 g) [2,5]. However, this not the case in late preterm or term
infants, in whom group B streptococcus (GBS) remains the most likely early-onset pathogen
[2,5]. Ampicillin resistance is a concern in community-acquired late-onset infections in term and
preterm neonates. In one survey of febrile infants <90 days old presenting to an emergency
department, nearly 80 percent of infants with meningitis had ampicillin-resistant pathogens [6].
The authors of the study conclude that the initial regimen should contain both ampicillin and an
expanded-spectrum cephalosporin because of the risk of GBS and Listeria monocytogenes
infection in this age group, as well as for ampicillin-resistant gram-negative enteric organisms.
We agree with this practice.
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 laboratory identification of the organism and susceptibility results (see
'Definitive therapy' below). However, if the Gram stain suggests a pathogen that is not
adequately covered with the empiric regimen, the regimen should be adjusted accordingly. For
example, if initial empiric therapy consists of vancomycin plus an extended-spectrum
cephalosporin and the Gram stain suggests L. monocytogenes, ampicillin should be added. If
meningitis resulting from a multidrug-resistant (MDR) gram-negative organism is strongly
suspected (eg, when the CSF Gram stain reveals gram-negative bacilli and positive screen for
extended-spectrum beta-lactamase), the empiric regimen should substitute meropenem for the
cephalosporin [7].
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In the neonatal intensive care unit setting, ongoing use of an expanded-spectrum

cephalosporin should be restricted to neonates with suspected bacterial meningitis based on
clinical findings and CSF parameters. When use of third- or fourth-generation cephalosporins is
routine (eg, when they are used more broadly for all neonates treated for "rule out sepsis"),
rapid emergence of resistant strains (especially Enterobacter cloacae, Klebsiella pneumoniae, and
Serratia species) can occur [8].
Definitive therapy — Once the causative agent and the in vitro antimicrobial susceptibility
results are known, empiric antimicrobial therapy should be altered accordingly. Guidance for
treating the most common causes of neonatal meningitis is provided below.
Group B streptococcus — GBS is uniformly susceptible to penicillin and ampicillin. Penicillin G

monotherapy is the appropriate definitive therapy once the neonate is improving clinically and
repeat lumbar puncture (LP) documents CSF sterilization (see 'Repeat lumbar puncture' below).
Duration of treatment is 14 to 21 days (see 'Duration' below). Treatment of neonatal GBS
infections, including GBS meningitis, is summarized in the table and discussed in detail
separately ( table 3). (See "Group B streptococcal infection in neonates and young infants",
section on 'Definitive therapy'.)
Escherichia coli and other gram-negative organisms — Ampicillin is the agent of choice for
neonatal meningitis resulting from ampicillin-susceptible strains of E. coli.
Ampicillin-resistant E. coli and other gram-negative organisms usually are initially treated with a
combination of an extended-spectrum cephalosporin (eg, cefotaxime if available) plus an
aminoglycoside, usually gentamicin; the aminoglycoside is discontinued once sterility of the CSF
is documented. Appropriate monotherapy is continued to complete a minimum of 21 days.
The prevalence of antimicrobial resistance among gram-negative isolates has increased

markedly since the 1990s [9]. Resistance in association with production of AmpC beta-
lactamases or extended-spectrum beta-lactamases (ESBLs) occurs primarily, but not exclusively,
in E. coli, Klebsiella species, and Enterobacter species. Carbapenemase-producing gram-negative
organisms, especially Klebsiella pneumoniae, E. coli, and Enterobacter cloacae, have also emerged
but are uncommon in newborn infants [7].
Infections caused by noncarbapenemase-producing MDR enteric organisms are generally

treated with meropenem. Meropenem should be administered for the entire course of therapy
for neonates with meningitis that is caused by MDR gram-negative organisms. The hospital
microbiology laboratory should provide assistance for appropriate testing of carbapenemase-
producing gram-negative organisms for MDR patterns.
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Other pathogens
● 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 in very low birth weight infants (birth weight <1500 g) or as a result of
surgical manipulations or placement of a ventriculoperitoneal shunt. Such infections
invariably are of late onset.
Sterilization of the CSF usually is achieved promptly after initiation of vancomycin unless
shunt material has not been removed. If the CSF is persistently positive, consideration
should be given to adding rifampin (5 mg/kg every 12 hours) to vancomycin for synergy.
However, it is uncertain whether combination therapy truly improves clearance of the
infection. (See "Infections of cerebrospinal fluid shunts and other devices", section on
'Staphylococci'.)
● 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
( table 4). 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 and prevention of Listeria monocytogenes infection", section on 'Antibiotic
therapy'.)
● Staphylococcus aureus – The standard therapy for methicillin-susceptible S. aureus (MSSA)

meningitis is nafcillin or oxacillin [10,11]. Treatment duration is typically 14 days. The
preferred therapy for methicillin-resistant S. aureus (MRSA) meningitis is vancomycin [10-
12]. Treatment duration is at least 14 days. Some experts suggest adding rifampin to
vancomycin for treatment of MRSA infection, but there are no clinical studies to suggest
efficacy. Treatment of MSSA and MRSA infections is discussed in greater detail separately.
(See "Staphylococcus aureus in children: Overview of treatment of invasive infections",
section on 'Definitive antimicrobial therapy'.)
Duration — The duration of antibiotic therapy depends upon the results of CSF and blood
cultures, the clinical course, and whether the neonate was pretreated with antibiotics prior to
the LP.
● Positive CSF culture – The suggested duration of antibiotic therapy for different causative
organisms is as follows:
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• GBS or other gram-positive organisms (eg, L. monocytogenes or Enterococcus) – A 14-day

course is sufficient for neonates with an uncomplicated course [13].
• E. coli or other gram-negative enteric pathogens – A 21-day course is the minimum for
neonates with an uncomplicated course [7].
• A longer course of therapy is required for neonates with meningitis whose course is
complicated. Prolonged treatment, sometimes for as long as eight weeks, may be
required for neonates with ventriculitis, abscesses, or multiple areas of infarction or
hemorrhage with resulting encephalomalacia. (See "Bacterial meningitis in the
neonate: Neurologic complications".)
● Negative CSF culture with positive blood culture and CSF pleocytosis – 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.
● Negative CSF and blood cultures – For neonates in whom cultures were obtained before
antibiotic therapy and both blood and CSF cultures are negative after 48 hours, we
suggest discontinuing antibiotic therapy.
● Pretreated or LP delayed – Some neonates may be exposed to antibiotics prior to

undergoing LP (eg, because the LP is delayed due to clinical instability, because the
mother received intrapartum antibiotic prophylaxis, or because the infant was receiving
antibiotics for another reason [eg, prophylaxis for vesicoureteral reflux]). This can result in
negative CSF culture. However, in most cases, other CSF parameters, (eg, cell count and
protein concentration) will permit accurate diagnosis so long as the LP is not traumatic.
(See "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on
'Interpretation of cerebrospinal fluid'.)
Our approach to managing pretreated neonates is as follows:
• For neonates in whom the LP was delayed because of clinical instability, meningeal
doses of antimicrobial therapy should be continued until the LP can be safely
performed.
• The total duration of therapy in pretreated neonates depends upon the CSF evaluation
and blood culture result:
- Neonates with CSF pleocytosis and positive blood culture are treated for 10 days
for gram-positive infection (eg, GBS) and 14 days for gram-negative infection.
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- For neonates with normal CSF profile and negative blood and CSF cultures, we
usually discontinue antibiotic therapy when cultures are sterile after 48 hours.
- For neonates who have a CSF pleocytosis and negative blood and CSF cultures, 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, intraventricular hemorrhage). (See "Bacterial meningitis in the
neonate: Clinical features and diagnosis", section on 'Differential diagnosis'.)
ADJUNCTIVE THERAPY
Adjunctive immunomodulatory therapy is not a routine part of management of neonatal

meningitis. Though there is evidence from experimental models that immune modulation may
positively impact the outcome of neonatal meningitis, the modalities that have undergone
clinical investigation thus far have either been shown to be ineffective or they have not been
adequately studied.
In particular, we suggest not using glucocorticoid therapy to reduce the risk of neurologic
sequelae in neonatal meningitis. There are limited data on the use of glucocorticoids in this
setting. In a clinical trial involving 52 neonates randomly assigned to dexamethasone plus
antibiotic therapy or antibiotic therapy alone, rates of mortality, neurologic disability, and
hearing loss at two years were similar in both groups [14]. In an observational study of 263
infants <90 days old with bacterial meningitis, glucocorticoid therapy was not associated with
lower mortality; however, only 8 percent of patients in this cohort received glucocorticoids [15].
The role of dexamethasone therapy in older infants and children with bacterial meningitis is
controversial and is discussed separately. (See "Bacterial meningitis in children: Dexamethasone
and other measures to prevent neurologic complications".)
Other adjunctive therapies for neonatal sepsis are discussed separately. (See "Management and
outcome of sepsis in term and late preterm neonates", section on 'Adjunctive therapies' and
"Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section
on 'Adjunct therapy to antibiotics'.)
MONITORING RESPONSE TO THERAPY
Ongoing evaluation — The response to therapy and the potential development of

complications are monitored with:
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● Serial neurologic examinations.
● Assessment of the overall clinical status (eg, vital sign trends, temperature stability, need
for hemodynamic or respiratory support).
● Repeat blood cultures – In bacteremic neonates, a repeat blood culture should be

performed to document sterility of the blood stream. The follow-up blood culture is
usually obtained at the time when the initial blood culture is reported as positive.
● Repeat examination of the cerebrospinal fluid (CSF). (See 'Repeat lumbar puncture' below.)
● Neuroimaging (See 'Neuroimaging' below.)
Most neonates with uncomplicated bacterial meningitis have clinical improvement within 24 to
48 hours of receiving appropriate antibiotic therapy. Clinical deterioration or failure to improve
in this timeframe may suggest development of a complication (eg, obstructive ventriculitis,
subdural effusion, brain abscess, intraventricular hemorrhage) or inadequate antimicrobial
therapy. (See "Bacterial meningitis in the neonate: Neurologic complications".)
Repeat lumbar puncture — We suggest repeating the lumbar puncture (LP) 24 to 48 hours
after initiating antimicrobial therapy for neonates with meningitis caused by group B
streptococcus (GBS), E. coli, other gram-negatives, and Listeria and for neonates with a
complicated course [10,13]. This encompasses the majority of patients with neonatal
meningitis.
Reevaluation of the CSF 24 to 48 hours after initiation of antimicrobial therapy is important for
several reasons [16,17]:
● In severe cases, gram-negative organisms may persist for several days. Delayed
sterilization of the CSF is associated with an increased risk of developing neurologic
sequelae (see 'Outcome' below). This clinical scenario is uncommon with the routine use of
an extended-spectrum cephalosporin as initial empiric therapy. By contrast, gram-positive
bacteria usually clear from the CSF rapidly (within 24 hours) after initiation of appropriate
antimicrobial therapy unless there is high bacterial burden in the CSF.
● The persistent identification of organisms on a Gram stain 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
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focus (eg, obstructive ventriculitis) that can require additional intervention or increased
duration of antimicrobial therapy. (See 'Neuroimaging' below and "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 'Definitive therapy' above and "Group B streptococcal
infection in neonates and young infants", section on 'Definitive therapy'.)
In uncomplicated neonatal meningitis, repeat CSF culture should generally be sterile. A positive
culture obtained 48 hours after initiation of therapy raises a concern for obstructive ventriculitis
or intraventricular hemorrhage. The additional evaluation and management of such infants
should be individualized and undertaken in consultation with specialists in pediatric infectious
diseases and pediatric neurosurgery. (See "Bacterial meningitis in the neonate: Neurologic
complications", section on 'Ventriculitis'.)
Neuroimaging — We 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. Neuroimaging may be warranted earlier in the course for
neonates with signs suggesting neurologic complications. Neurologic complications should be
considered if the neonate fails to improve clinically after 24 to 48 hours of appropriate antibiotic
therapy. (See "Bacterial meningitis in the neonate: Neurologic complications".)
MRI is preferred over contrast-enhanced computed tomography (CT) because MRI provides
better anatomic detail, optimizes assessment of injury to white matter, and avoids radiation
exposure [18]. If there are focal findings that require extension of the course of antimicrobial
therapy, treatment can be continued without interruption.
● Cranial ultrasound – Early in the course of meningitis, cranial ultrasound is the most
practical neuroimaging technique, as it can be performed at the bedside. It is helpful for
assessing ventricular size and the presence of intraventricular hemorrhage. Cranial
ultrasound also can demonstrate ventriculitis, echogenic sulci, abnormal parenchymal
echogenicities, and extracerebral fluid collections [19,20]. In addition, because serial
ultrasound studies can be performed safely at the bedside, it is useful in defining the
progression of complications in infants with prolonged seizure activity or focal neurologic
deficits [21]. (See "Bacterial meningitis in the neonate: Neurologic complications".)
● MRI – Similar to ultrasonography, early in the treatment course, MRI can demonstrate
cerebral edema and ischemic lesions effectively, as well as leptomeningeal enhancement,
ventriculitis, and infarction. Pus within the lateral ventricles can be seen as restricted
diffusion. Later in the treatment course, contrast-enhanced MRI is useful in detecting
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cerebral abscesses, persistent cerebritis, areas of infarction or encephalomalacia, subdural

empyema, hydrocephalus and degree of cerebral cortical, and white matter injury. These
findings may influence duration of antimicrobial therapy and/or the need for early
intervention services [21]. (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, Serratia marcescens, Proteus mirabilis, and
Cronobacter sakazakii [22-27]. (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, vision,
and developmental status. Hearing should be evaluated by auditory brainstem response within
four to six weeks of completion of therapy [28]. (See "Hearing loss in children: Screening and
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 surveillance and screening in primary
care", section on 'Approach to surveillance'.)
OUTCOME
Neonatal meningitis is a devastating disease. Advances in infant intensive care have reduced
mortality, but morbidity remains high.
● Mortality and disability – In the contemporary era, mortality from neonatal meningitis is
approximately 10 percent [1,15,29-33]. However, survivors remain at high risk for
neurologic sequelae and lifelong impairment, as illustrated below [30,32,33].
Approximately 15 to 20 percent of survivors have moderate to severe disability, and
approximately 30 to 35 percent have mild disability. (See "Bacterial meningitis in the
neonate: Neurologic complications".)
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In a review of 101 term and late preterm neonates (ie, gestational ≥35 weeks) diagnosed
with bacterial meningitis between 1979 and 1998, mortality declined from 17 percent in
the early era (1979 to 1988) to 9 percent in the later era (1989 to 1998) [34]. Among
survivors, 19 percent had moderate or severe disability at one year of age (defined as
severe cerebral palsy, moderate to severe developmental delay, blindness, and/or
deafness).
● Prognostic factors – Factors predictive of death or serious adverse sequelae from

bacterial meningitis include [31,32,34-42]:
• Low birth weight (<2500 g) or preterm birth (<37 weeks gestation)

• History of clinical signs for >24 hours before hospitalization
• Leukopenia (white blood cell <5000/microL) and neutropenia at presentation
• Very high cerebrospinal fluid (CSF) protein (>300 mg/dL) and/or very low CSF glucose
(<10 percent of blood glucose value)
• Seizures continuing >72 hours after hospitalization
• Focal neurologic deficits noted during the acute illness
• Requirement for mechanical ventilation or inotropes
• Delayed sterilization of the CSF
Neuroimaging findings of meningeal inflammation are generally not predictive of

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 [20].
● Outcomes in preterm neonates – The outcome is generally worse in preterm low birth
weight infants compared with term infants. In one study of 113 infants with bacterial
meningitis, long-term motor disability (spasticity or paresis) was noted in 27 percent of
preterm infants compared with 10 percent of term infants [32].
Similarly, outcomes for preterm neonates with bacterial meningitis are generally worse
compared with preterm neonates without meningitis. In one study of very low birth
weight infants (birth weight <1500 g), after controlling for birth weight, intraventricular
hemorrhage, chronic lung disease, and social risk factors, survivors of meningitis had a
twofold higher risk of major neurologic disability (eg, cerebral palsy or abnormal tone,
hydrocephalus, blindness, deafness, and severe developmental delay) at 20 months of age
[43]. In a large cohort study of extremely low birth weight (birth weight <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 [44].
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Long-term neurologic outcome in preterm infants is discussed in greater detail separately.

(See "Long-term neurodevelopmental impairment in infants born preterm: Risk
assessment, follow-up care, and early intervention", section on 'Predicting outcome'.)
● Outcomes by causative organism – Outcomes vary according to the causative organism:
• Group B streptococcus (GBS) – Reported mortality rates of neonatal GBS meningitis

range from 5 to 11 percent [37,44-46]. Long-term neurologic sequelae occur in
approximately 20 to 40 percent of survivors.
In a study of 90 neonates diagnosed with GBS meningitis from 1998 through 2006, 5
percent of patients died acutely and an additional 5 percent died by three years of age
[46]. Among the survivors, 56 percent had age-appropriate development, 25 percent
had mild-to-moderate impairment, and 19 percent had severe impairment.
Outcomes of GBS infection in neonates are discussed in greater detail separately. (See
"Group B streptococcal infection in neonates and young infants", section on
'Outcome'.)
• E. coli – In a report of 325 young infants (71 percent were neonates, 35 percent were
preterm) diagnosed with E. coli meningitis from 2001 to 2013, the overall mortality rate
was 9 percent [31]. Mortality was approximately threefold higher in preterm infants
compared with term infants (17 versus 5 percent, respectively). Short-term morbidities
included seizures (13 percent), subdural empyema (6 percent), intraventricular
hemorrhage or hydrocephalus (5 percent), and cerebral venous thrombosis or stroke (3
percent). Long-term morbidities were not described. Preterm birth and severe
hypoglycorrhachia (ie, CSF glucose <10 percent of blood glucose level) were the
strongest predictors of death.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Sepsis in neonates" and
"Society guideline links: Bacterial meningitis in infants and children".)
SUMMARY AND RECOMMENDATIONS
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● Supportive care – Neonates with bacterial meningitis should receive initial care in an
intensive care unit. Supportive care may include (see 'Supportive care' above):
• Management of cardiovascular instability or shock (see "Neonatal shock: Etiology,

clinical manifestations, and evaluation")
• Appropriate respiratory support as needed (see "Respiratory support, oxygen delivery,
and oxygen monitoring in the newborn" and "Overview of mechanical ventilation in
neonates")
• Careful fluid therapy, avoiding both hypo- and hypervolemia (see "Fluid and electrolyte
therapy in newborns")
• Prevention and management of hypoglycemia (see "Management and outcome of
neonatal hypoglycemia")
• Control of seizures (see "Treatment of neonatal seizures")
• Nutritional support (see "Approach to enteral nutrition in the premature infant" and
"Parenteral nutrition in infants and children")
● Empiric antimicrobial therapy – Broad-spectrum antimicrobial therapy should be

initiated as soon as possible in neonates with suspected meningitis. The choice of the
initial empiric regimen is based on the likely pathogens ( table 1) and local susceptibility
patterns. (see 'Empiric therapy' above):
Often, at the first sign of illness, empiric therapy for neonatal sepsis is initiated as
summarized in the table ( table 2) and discussed separately. (See "Management and
outcome of sepsis in term and late preterm neonates", section on 'Initial empiric therapy'.)
For neonates with clinical evidence of meningitis (eg, critical illness, cerebrospinal fluid
[CSF] pleocytosis, organism present on CSF Gram stain, or other suggestive CSF
parameters), we suggest modifying the empiric regimen by substituting an extended-
spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime) for
the aminoglycoside (Grade 2C).
In addition, for most neonates with CSF pleocytosis and negative CSF Gram stain, empiric
acyclovir therapy for herpes simplex virus is warranted (after performing appropriate
testing), as discussed separately. (See "Neonatal herpes simplex virus infection:
Management and prevention", section on 'Initial antiviral therapy'.)
● Definitive antibiotic therapy – Once the causative agent and its in vitro antimicrobial
susceptibility pattern are known, empiric antimicrobial therapy should be altered
accordingly (see 'Definitive therapy' above):
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• Group B streptococcus (GBS) – GBS is uniformly susceptible to penicillin and

ampicillin. Penicillin G monotherapy is the appropriate definitive therapy once clinical
and microbiologic responses have been documented. Duration of treatment is 14 to 21
days. Treatment of neonatal GBS infections, including GBS meningitis, is summarized in
the table and discussed in detail separately ( table 3). (See "Group B streptococcal
infection in neonates and young infants", section on 'Definitive therapy'.)
• Escherichia coli and other gram-negatives – Treatment depends on the susceptibility

pattern. Ampicillin is used for ampicillin-susceptible strains of E. coli. Ampicillin-
resistant organisms usually are initially treated with a combination of an extended-
spectrum cephalosporin plus an aminoglycoside (eg, gentamicin); the aminoglycoside
is discontinued once sterility of the CSF is documented. Infections caused by MDR
AmpC beta-lactamase or extended-spectrum beta-lactamase (ESBL) producing
organisms are treated with meropenem. Treatment for carbapenemase-producing
gram-negative organisms should be based upon susceptibility testing by the
microbiology laboratory. Treatment duration is for a minimum of 21 days.(See
'Escherichia coli and other gram-negative organisms' above and 'Duration' above.)
• Other – Antibiotic regimens for other causes of neonatal meningitis are summarized
above. (See 'Other pathogens' above.)
● Monitoring – The response to therapy and the potential development of complications

are monitored clinically, through serial neurologic examinations, repeat lumbar puncture
(LP), and neuroimaging (see 'Monitoring response to therapy' above):
• Neurologic complications should be considered in the neonate with meningitis who

fails to improve clinically after 24 to 48 hours of appropriate antibiotic therapy. (See
"Bacterial meningitis in the neonate: Neurologic complications".)
• Most neonates should undergo repeat LP 24 to 48 hours after initiation of antibiotic

therapy to document sterilization of the CSF. (See 'Repeat lumbar puncture' above.)
• 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. Neuroimaging may be warranted
earlier in the course for neonates with signs suggesting neurologic complications. (See
'Neuroimaging' above.)
● Outcome – In the modern era, the mortality of neonatal bacterial meningitis is

approximately 10 percent. Approximately 15 to 20 percent of survivors have moderate to
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severe disability, and approximately 30 to 35 percent have mild disability. (See 'Outcome'
above.)
● Follow-up – Long-term follow-up for survivors of neonatal meningitis includes monitoring

of hearing, visual acuity, and developmental milestones. (See 'Follow-up' above.)
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REFERENCES
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incidence and antimicrobial resistance in the era of intrapartum antimicrobial prophylaxis.
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(Eds), American Academy of Pediatrics, 2021. p.311.
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9. Lautenbach E, Patel JB, Bilker WB, et al. Extended-spectrum beta-lactamase-producing
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resistance on outcomes. Clin Infect Dis 2001; 32:1162.
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10. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of
bacterial meningitis. Clin Infect Dis 2004; 39:1267.
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Report of the Committee on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfie
ld R, Sawyer MH (Eds), American Academy of Pediatrics, 2021. p.707.
14. Daoud AS, Batieha A, Al-Sheyyab M, et al. Lack of effectiveness of dexamethasone in
neonatal bacterial meningitis. Eur J Pediatr 1999; 158:230.
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24. Iversen C, Lehner A, Mullane N, et al. Identification of "Cronobacter" spp. (Enterobacter
sakazakii). J Clin Microbiol 2007; 45:3814.
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25. Phan H, Lehman D. Cerebral abscess complicating Proteus mirabilis meningitis in a

newborn infant. J Child Neurol 2012; 27:405.
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28. Harrison GJ. Approach to infections in the fetus and newborn. In: Feigin and Cherry’s Textb
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29. Harvey D, Holt DE, Bedford H. Bacterial meningitis in the newborn: a prospective study of
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years of age. Eur J Pediatr 2005; 164:730.
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32. Ouchenir L, Renaud C, Khan S, et al. The Epidemiology, Management, and Outcomes of
Bacterial Meningitis in Infants. Pediatrics 2017; 140.
33. Holt DE, Halket S, de Louvois J, Harvey D. Neonatal meningitis in England and Wales: 10
years on. Arch Dis Child Fetal Neonatal Ed 2001; 84:F85.
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meningitis. Pediatrics 2000; 106:477.
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meningitis: a twenty-one-year experience. J Pediatr 1993; 122:15.
36. Anderson SG, Gilbert GL. Neonatal gram negative meningitis: a 10-year review, with
reference to outcome and relapse of infection. J Paediatr Child Health 1990; 26:212.
37. Levent F, Baker CJ, Rench MA, Edwards MS. Early outcomes of group B streptococcal
meningitis in the 21st century. Pediatr Infect Dis J 2010; 29:1009.
38. Edwards MS, Rench MA, Haffar AA, et al. Long-term sequelae of group B streptococcal
meningitis in infants. J Pediatr 1985; 106:717.
39. May M, Daley AJ, Donath S, et al. Early onset neonatal meningitis in Australia and New
Zealand, 1992-2002. Arch Dis Child Fetal Neonatal Ed 2005; 90:F324.
40. Franco SM, Cornelius VE, Andrews BF. Long-term outcome of neonatal meningitis. Am J Dis
Child 1992; 146:567.
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41. Greenberg RG, Benjamin DK Jr, Cohen-Wolkowiez M, et al. Repeat lumbar punctures in
infants with meningitis in the neonatal intensive care unit. J Perinatol 2011; 31:425.
42. ter Horst HJ, van Olffen M, Remmelts HJ, et al. The prognostic value of amplitude
integrated EEG in neonatal sepsis and/or meningitis. Acta Paediatr 2010; 99:194.
43. Doctor BA, Newman N, Minich NM, et al. Clinical outcomes of neonatal meningitis in very-
low birth-weight infants. Clin Pediatr (Phila) 2001; 40:473.
44. Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neurodevelopmental and growth impairment
among extremely low-birth-weight infants with neonatal infection. JAMA 2004; 292:2357.
45. Phares CR, Lynfield R, Farley MM, et al. Epidemiology of invasive group B streptococcal
disease in the United States, 1999-2005. JAMA 2008; 299:2056.
46. Libster R, Edwards KM, Levent F, et al. Long-term outcomes of group B streptococcal
meningitis. Pediatrics 2012; 130:e8.
Topic 6016 Version 43.0
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GRAPHICS
Initial evaluation and management of neonatal shock
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O2: oxygen; HR: heart rate; BP: blood pressure; BUN: blood urea nitrogen; LFTs: liver function tests; CBC: com
count; HSV: herpes simplex virus; ECG: electrocardiogram; ID: infectious disease; RBC: red blood cell; PGE1:
CSF: cerebrospinal fluid.
* The amount and rate of infusion may vary depending on the gestational age of the neonate and the suspe
(eg, hypovolemic, distributive, or cardiogenic). An initial fluid bolus of 10 to 20 mL/kg isotonic crystalloid is a
most neonates presenting in shock. However, fluid boluses should be administered cautiously in extremely
(gestational age <28 weeks) or if there is suspicion for a cardiac etiology of shock. Refer to UpToDate's topic
of neonatal shock for additional details.
¶ In neonates presenting with shock, HSV infection should be suspected as a possible etiology if the neonat
exposure to HSV, has examination findings consistent with HSV (mucocutaneous vesicles), and/or has CSF p
addition, the diagnosis should be considered in neonates with concerning findings that are otherwise unexp
include seizures, focal neurologic signs, abnormal neuroimaging, sepsis-like illness (fever or hypothermia, ir
respiratory distress, apnea, abdominal distension, hepatomegaly, ascites), thrombocytopenia, or elevated liv
Refer to separate UpToDate content on neonatal HSV infection for additional details on evaluation and treat
HSV infection.
Δ Empiric antibiotic therapy is provided to all neonates with shock because sepsis is the leading cause of neo
Antimicrobial coverage should include agents active against organisms that most commonly cause neonata
B streptococcus and Escherichia coli). The combination of ampicillin and gentamicin provides adequate cove
organisms until culture results are available. Local antibiotic resistance patterns should also be considered.
suspicion for HSV infection, the empiric antimicrobial regimen should include acyclovir. For additional detail
empiric regimen and duration of therapy, refer to separate UpToDate content on evaluation and treatment o
and HSV.
◊ An adequate response to therapy is signaled by improvement in pulses, skin perfusion (capillary refill <4 s
signs (including rise in BP if initially hypotensive, decrease in HR if initially tachycardic, or rise in HR if initially
resolution of acidosis. For additional details on the goals of therapy and monitoring response, refer to UpTo
evaluation and management of neonatal shock.
§ Vasoactive agents commonly used in the management of neonatal shock include dopamine, epinephrine,
milrinone. The choice is based in part on the type of shock (eg, distributive versus cardiogenic). Dopamine is
vasopressor and inotrope, and it is the most commonly used agent in neonates. Dobutamine is predominan
and it is commonly used for management of neonatal cardiogenic shock. For additional details, refer to UpT
evaluation and management of neonatal shock.
¥ Cardiac disease may be suspected based upon the presence of a murmur or gallop, cyanosis, irregular he
absent femoral pulses, a differential in pre- and post-ductal oxygen saturation, and/or chest radiograph find
cardiomegaly, pulmonary edema).
‡ Primary adrenal insufficiency (eg, congenital adrenal hypoplasia) may be suspected based on physical exa
(ambiguous genitalia) and laboratory findings (hyperkalemia, hyponatremia, hypoglycemia). Secondary or r
insufficiency may be suspected on the basis of shock that is refractory to fluid boluses and vasoactive therap
separate UpToDate content on adrenal insufficiency and neonatal shock for additional details.
† See separate UpToDate topics for additional details of the initial evaluation and management of neonatal
and management of neonatal sepsis, management of suspected cyanotic heart disease, and management o
infants.
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** In some cases, the source of bleeding may be evident based on the history and physical examination (eg
intrapartum hemorrhage, obvious bleeding source on examination such as a subgaleal hematoma). In case
is unclear, additional evaluation may include cranial ultrasound to evaluate for intracranial hemorrhage and
cells in a maternal blood sample (Kleihauer-Betke assay) to assess for fetomaternal hemorrhage.
Graphic 128082 Version 2.0
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Bacterial pathogens in neonatal sepsis and focal neonatal infections
Common
Some less common pathogens*
pathogens*
Early onset ¶
Term and late GBS Enterobacter, Enterococcus, Klebsiella, Listeria,

preterm E. coli nontypeable H. influenzae, other enteric gram-negative
infants bacilli, S. aureus, viridans streptococci
(GA ≥34
weeks)
Preterm E. coli CoNS, Enterobacter, Klebsiella, Listeria, other enteric and

infants GBS nonenteric gram-negative bacilli, S. aureus, viridans
(GA <34 weeks) streptococci
Late onset ¶
Term and late E. coli Enterobacter, Klebsiella, Listeria, N. meningitidis, other

preterm GBS enteric and nonenteric gram-negative bacilli, Salmonella,
infants S. pneumoniae, viridans streptococci
Additional
(GA ≥34 Additional pathogens seen in the NICU setting –
pathogens
weeks) Citrobacter, Enterococcus, Pseudomonas, Serratia
seen in the
NICU setting –
S. aureus,
CoNS
Preterm CoNS Citrobacter, Enterobacter, Enterococcus, Listeria, other

infants S. aureus enteric and nonenteric gram-negative bacilli,
(GA <34 weeks) Pseudomonas, Salmonella, Serratia, viridans streptococci
E. coli
Klebsiella
GBS
Pathogens based on source of infection
Meningitis GBS CoNS, Enterococcus, Listeria, N. meningitides, nontypeable

E. coli H. influenzae, S. aureus, S. pneumoniae, other streptococci
Other gram- (groups A, C, or G and viridans streptococci)
negative
enteric bacilli
Pneumonia GBS C. trachomatis, Citrobacter, Enterobacter, group A

Streptococcus, Klebsiella, Pseudomonas, S. aureus, S.
pneumoniae, Serratia
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Urinary tract E. coli Citrobacter, Enterobacter, Enterococcus, Klebsiella, Proteus

infection Δ Additional pathogens seen in the NICU setting – CoNS, S.
aureus
Skin and soft S. aureus

tissue infection GBS
Group A
Streptococcus
Vascular S. aureus
catheter- CoNS
associated
Enterococcus
infection
Gram-
negatives
Intestinal E. coli
source/NEC Klebsiella
Other enteric
gram-negative
bacilli
Clostridium
spp
Anaerobes (eg,
Bacteroides)
GA: gestational age; GBS: group B Streptococcus; E. coli: Escherichia coli; H. influenzae: Haemophilus
influenzae; S. aureus: Staphylococcus aureus; CoNS: coagulase-negative staphylococci; NICU: neonatal
intensive care unit; N. meningitidis: Neisseria meningitidis; S. pneumoniae: Streptococcus pneumoniae; C.
trachomatis: Chlamydia trachomatis; NEC: necrotizing enterocolitis.
* This table summarizes bacterial pathogens in neonatal sepsis and in focal neonatal infections.
Common pathogens are listed roughly in order of relative frequency within each category; less
common pathogens are listed alphabetically. The list of pathogens within each category is not
exhaustive. This table does not address nonbacterial causes of neonatal infections (eg, herpes
simplex virus, enterovirus, parechovirus, Candida). Refer to separate UpToDate content for
additional information on nonbacterial pathogens.
¶ The definitions of early and late onset vary in different reports. Within UpToDate content, we
generally define early onset as <72 hours after birth and late onset as ≥72 hours. However, some
experts use <7 days versus ≥7 days, respectively, for these definitions. The definitions of early and
late onset as they pertain to GBS disease are somewhat different. Early-onset GBS infection typically
presents within 24 hours of birth but can occur through day 6 after birth. Late-onset GBS typically
occurs at 4 to 5 weeks of age.
Δ Urinary tract infections may not be associated with bacteremia in neonates.

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Suggested antimicrobial regimens in the management of neonatal sepsis in

term and late preterm infants
Antibiotic regimen
Empiric therapy
Early onset (<72 hours) Ampicillin and an aminoglycoside (typically

gentamicin)*
Late onset (≥72 hours) – Admitted from the Preferred regimen – Ampicillin and an
community aminoglycoside (typically gentamicin)*
Alternative – Ampicillin and an expanded-

spectrum cephalosporin (eg, ceftazidime,
cefepime, or cefotaxime [where available])
Late onset (≥72 hours) – Hospitalized since Vancomycin or nafcillin/oxacillin ¶ , and

birth
An aminoglycoside (typically gentamicin)*
Special circumstances:
Suspected meningitis (eg, CSF pleocytosis) Same as above except substitute an expanded-
spectrum cephalosporin (eg, ceftazidime,
cefepime, or cefotaxime [where available]) for
the aminoglycoside Δ
Suspected pneumonia Ampicillin and an aminoglycoside (typically

gentamicin)*
Alternatives:
Ampicillin and expanded-spectrum
cephalosporin, or
Vancomycin and expanded-spectrum
cephalosporin, or
Vancomycin and an aminoglycoside
(typically gentamicin)*
Suspected infection of skin, umbilicus, soft Vancomycin and an aminoglycoside (typically

tissues, joints, or bones (S. aureus is a likely gentamicin)*, or
pathogen)
Vancomycin, nafcillin, and an aminoglycoside
(typically gentamicin)*, or
Vancomycin and an expanded-spectrum

cephalosporin (eg, ceftazidime, cefepime, or
cefotaxime [where available])
Suspected intravascular catheter-related Vancomycin and an aminoglycoside (typically

infection gentamicin)*
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Suspected infection due to organisms Ampicillin, an aminoglycoside (typically

found in the gastrointestinal tract (eg, gentamicin)*, and clindamycin
anaerobic bacteria)
Alternatives:
Ampicillin, an aminoglycoside (typically
gentamicin)*, and metronidazole or
Piperacillin-tazobactam and an
aminoglycoside (typically gentamicin)*
Pathogen-specific therapy
Group B Streptococcus Penicillin G
E. coli – Ampicillin-sensitive Ampicillin
E. coli – Ampicillin-resistant Expanded-spectrum cephalosporin (eg,

ceftazidime, cefepime, or cefotaxime [where
available])
Alternative:
Meropenem
Multidrug-resistant gram-negative bacilli Meropenem

(including ESBL-producing organisms)
L. monocytogenes Ampicillin and gentamicin
MSSA Oxacillin/nafcillin or cefazolin
MRSA Vancomycin
Coagulase-negative staphylococci Vancomycin
This table summarizes our suggested antibiotic regimens for empiric and pathogen-specific therapy
for neonatal sepsis. The initial choice of empiric therapy depends on the neonate's age, likely
pathogens, and presence of an apparent source of infection (eg, skin, joint, or bone involvement).
Local antibiotic susceptibility patterns should also be considered.
CSF: cerebrospinal fluid; E. coli: Escherichia coli; ESBL: extended-spectrum beta-lactamase; L.

monocytogenes: Listeria monocytogenes; MSSA: methicillin-susceptible Staphylococcus aureus; MRSA:
methicillin-resistant Staphylococcus aureus.
* In centers with a high prevalence of gentamicin resistance among gram-negative isolates, an

alternative aminoglycoside (eg, amikacin) may be preferred. Refer to UpToDate's topics on neonatal
sepsis for additional details.
¶ Nafcillin or oxacillin can be used in the empiric regimen in lieu of vancomycin if the neonate is not
critically ill and has a recent negative MRSA screening test.
Δ If there is concern for meningitis caused by a multidrug-resistant gram-negative organism, a

carbapenem such as meropenem is the preferred agent for empiric therapy.
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Antimicrobial therapy for group B streptococcal infections in neonates and

young infants [1-3]
Definitive therapy Duration of

Site(s) of infection
GA <35 weeks GA ≥35 weeks
therapy
PNA ≤7 days PNA ≤7 days

Penicillin G Penicillin G
50,000 50,000
units/kg per units/kg per
dose IV every dose IV every
12 hours 12 hours 10 days
Alternative – Alternative –
Ampicillin 50 Ampicillin 50
mg/kg per mg/kg per
12 hours 8 hours
Bacteremia/sepsis/pneumonia
PNA >7 days PNA >7 days
50,000 50,000
8 hours 8 hours 10 days
mg/kg per mg/kg per
12 hours 8 hours
Meningitis PNA ≤7 days PNA ≤7 days

150,000 150,000
8 hours 8 hours 14 days*
mg/kg per mg/kg per
8 hours 8 hours
PNA >7 days PNA >7 days 14 days*
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125,000 125,000
6 hours 6 hours
mg/kg per mg/kg per
6 hours 6 hours
Other focal infections (dosing is for term infants >7 days old since these infections
typically occur beyond day 7 after birth)
Penicillin G 50,000 units/kg per dose IV

every 8 hours
Cellulitis/adenitis 10 to 14 days
Alternative – Ampicillin 50 mg/kg per dose
IV every 8 hours

every 8 hours
Septic arthritis 14 to 21 days
IV every 8 hours

every 8 hours
Osteomyelitis 21 to 28 days
IV every 8 hours

every 8 hours
Urinary tract infection 10 days
IV every 8 hours
Transition from empiric to definitive therapy should occur once GBS is identified by culture and
clinical improvement is evident. For infants with GBS meningitis, we suggest repeat lumbar puncture
at 24 to 48 hours of therapy to document sterilization of CSF before changing to penicillin or
ampicillin monotherapy. The antibiotic doses listed above are for use in neonates and young infants
weighing ≥1 kg with normal renal function. For additional dosing details, refer to the Lexicomp
pediatric and neonatal drug information monographs included within UpToDate.
GA: gestational age; PNA: postnatal age; IV: intravenous; GBS: group B streptococcus; CSF:
cerebrospinal fluid.
* Complicated central nervous system infections require longer treatment.
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References:
1. American Academy of Pediatrics. Group B streptococcal infections. In: Red Book: 2018 Report of the Committee on
Infectious Diseases, 31st ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics,
Itasca, IL 2018. p.762.
2. Medications. In: Guidelines for Acute Care of the Neonate, 26th Ed, Fernandes CJ, Pammi M, Katakam L (Eds), Baylor
College of Medicine, Houston, TX 2018. p.228.
3. Puopolo KM, Lynfield R, Cummings JJ, et al. Management of Infants at Risk for Group B Streptococcal Disease.
Pediatrics 2019; 144.
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Antibiotic dosing for invasive Listeria infection
Infants and
Infants ≤7 Infants 8 to 28 Infants 29 to 60 days
children >60
days of age days of age of age
days of age
Ampicillin Patients in whom Patients in whom Patients in whom CNS Patients in whom
CNS infection has CNS infection has infection has been CNS infection has
been been documented or not yet been
documented or documented or excluded: documented or
not yet excluded: not yet excluded: 300 mg/kg per day not yet excluded:
300 mg/kg 300 mg/kg IV in 4 divided doses 300 to 400
per day IV in per day IV in Patients in whom CNS mg/kg per day
3 divided 4 divided infection has been IV in 4 to 6
doses doses excluded: divided doses;
Patients in whom Patients in whom 200 mg/kg per day maximum
CNS infection has CNS infection has IV in 4 divided doses dose: 12 g per
been excluded been excluded day
(weight-directed (weight-directed Patients in whom
dosing)*: dosing)*: CNS infection has
Weight ≤2 Weight ≤2 been excluded:
kg: 100 kg: 150
200 mg/kg per
mg/kg per mg/kg per
day IV in 4
day IV in 2 day IV in 2
divided doses;
divided divided
maximum
doses doses
dose: 8 g per
Weight >2 Weight >2 day
kg: 150 kg: 150
mg/kg per mg/kg per
day IV in 3 day IV in 3
divided divided
doses doses
or
Penicillin G Patients in whom Patients in whom Patients in whom CNS Patients in whom
CNS infection has CNS infection has infection has been CNS infection has
been been documented or not yet been
documented or documented or excluded: documented or
not yet excluded: not yet excluded: 400,000 to not yet excluded:
450,000 400,000 to 500,000 units/kg/day 400,000 to
units/kg/day 500,000 IV in 4 divided doses 500,000
IV in 3 units/kg/day Patients in whom CNS units/kg per
divided IV in 4 infection has been day IV in 4
doses excluded: to 6 divided
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Patients in whom divided 200,000 units/kg/day doses;

CNS infection has doses IV in 4 divided doses maximum
been excluded: Patients in whom dose: 24
100,000 CNS infection has million units
units/kg/day been excluded: per day;
IV in 2 150,000 doses
divided units/kg/day >400,000
doses IV in 3 units/kg per
divided day are
doses generally
only used
for infants
<1 year of
age
Patients in whom
CNS infection has
been excluded:
250,000 to
300,000
units/kg/day
IV in 4 to 6
divided
doses;
maximum
dose: 24
million units
per day
plus (if CNS, bloodstream, or other serious infection)
Infants and
Infants ≤60 days of age children >60
days of age
Gentamicin ¶ Gestational age <30 weeks: 7.5 mg/kg per

Postnatal age ≤14 days: 5 mg/kg IV every 48 hours day IV in 3
Postnatal age >14 days: 5 mg/kg IV every 36 hours divided doses
Gestational age 30 to 34 weeks:

Postnatal age ≤10 days: 5 mg/kg IV every 36 hours
Postnatal age >10 to 60 days: 5 mg/kg IV every 24 to 36 hours
Gestational age ≥35 weeks:
Postnatal age ≤7 days: 4 mg/kg IV every 24 hours
Postnatal age >7 to 60 days: 5 mg/kg IV every 24 hours
Dosing in this table is for patients with normal renal function; infant dosing is for patients weighing
≥1 kg. For additional dosing detail, refer to the Lexicomp drug information monographs included
3/29/23, 10:53 PM 6016
within UpToDate.
CNS: central nervous system; IV: intravenously.
* For alternative gestational age-directed dosing, refer to the Lexicomp pediatric drug information
monograph included within UpToDate.
¶ The optimal peak gentamicin levels in listerial infection are not known; the ranges presented are
the opinions of our contributors:
For infants to ≤1 month of age, the desired gentamicin peak is 6 to 12 mcg/mL and the
trough is <2 mcg/mL.
For infants and children >1 month of age, the desired gentamicin peak is 6 to 10 mcg/mL and
the trough is <2 mcg/mL.
For nonpregnant adults, the desired gentamicin peak is 4 to 8 mcg/mL and the trough is <2
mcg/mL (ideally <1 mcg/mL). While the target serum gentamicin peak concentration for
synergy of infections outside the CNS is typically 3 to 4 mcg/mL, many favor higher target
peak concentrations for treatment of gram-positive CNS infections to achieve adequate
concentrations for synergy in the context of limited cerebrospinal fluid penetration; however,
the optimal serum peak concentrations are uncertain. Refer to the UpToDate topic on dosing
of parenteral aminoglycosides for further discussion.
Data from:
American Academy of Pediatrics. Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32nd ed,
Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021.
Medications. In: Guidelines for Acute Care of the Neonate, 26th Ed, Fernandes CJ, Pammi M, Katakam L (Eds), Baylor
College of Medicine, Houston, TX 2018. p.228.
Lexicomp Online. Copyright © 1978-2023 Lexicomp, Inc. All Rights Reserved.
3/29/23, 10:53 PM 6016
Contributor Disclosures
Morven S Edwards, MD Grant/Research/Clinical Trial Support: Pfizer [Group B Streptococcus]. Other
Financial Interest: Texas State University personal services agreement [Chagas disease]. All of the relevant
financial relationships listed have been mitigated. Carol J Baker, MD Consultant/Advisory Boards: Pfizer
[Group B Streptococcus vaccine]; Valneva USA Inc. [Chikungunya vaccine]; VBI Vaccines Inc. [Hepatitis B
vaccine]. All of the relevant financial relationships listed have been mitigated. Sheldon L Kaplan,
MD Grant/Research/Clinical Trial Support: MeMed Diagnostics [Bacterial and viral infections]; Merck
[Staphylococcus aureus]; Pfizer [Streptococcus pneumoniae]. Consultant/Advisory Boards: MeMed
Advisory Board [Diagnostics bacterial and viral infections]. Other Financial Interest: Elsevier [Pediatric
infectious diseases]; Pfizer [PCV13]. All of the relevant financial relationships listed have been
mitigated. Joseph A Garcia-Prats, MD No relevant financial relationship(s) with ineligible companies to
disclose. Carrie Armsby, MD, MPH No relevant financial relationship(s) with ineligible companies to
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Bacterial Meningitis in The Neonate - Treatment and Outcome

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Bacterial Meningitis in The Neonate - Treatment and Outcome

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Bacterial meningitis in the neonate: Treatment and

● (See "Bacterial meningitis in the neonate: Clinical features and diagnosis".)

● Management of cardiovascular instability or shock ( algorithm 1) (see "Neonatal shock:

● Discontinue the aminoglycoside.

● Add an extended-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime,

Adding an expanded-spectrum cephalosporin to the empiric regimen provides optimal activity

In the neonatal intensive care unit setting, ongoing use of an expanded-spectrum

Group B streptococcus — GBS is uniformly susceptible to penicillin and ampicillin. Penicillin G

The prevalence of antimicrobial resistance among gram-negative isolates has increased

Infections caused by noncarbapenemase-producing MDR enteric organisms are generally

● Coagulase-negative staphylococci – Vancomycin is the antimicrobial of choice for proven

● Staphylococcus aureus – The standard therapy for methicillin-susceptible S. aureus (MSSA)

• GBS or other gram-positive organisms (eg, L. monocytogenes or Enterococcus) – A 14-day

● Pretreated or LP delayed – Some neonates may be exposed to antibiotics prior to

Our approach to managing pretreated neonates is as follows:

Adjunctive immunomodulatory therapy is not a routine part of management of neonatal

MONITORING RESPONSE TO THERAPY

Ongoing evaluation — The response to therapy and the potential development of

● Serial neurologic examinations.

● Repeat blood cultures – In bacteremic neonates, a repeat blood culture should be

● Neuroimaging (See 'Neuroimaging' below.)

● The persistent identification of organisms on a Gram stain may be an early indication of

● Persistence of viable organisms more than 48 hours after initiation of antimicrobial

Neuroimaging — We perform magnetic resonance imaging (MRI) 48 to 72 hours before the

cerebral abscesses, persistent cerebritis, areas of infarction or encephalomalacia, subdural

● Prognostic factors – Factors predictive of death or serious adverse sequelae from

• Low birth weight (<2500 g) or preterm birth (<37 weeks gestation)

Neuroimaging findings of meningeal inflammation are generally not predictive of

Long-term neurologic outcome in preterm infants is discussed in greater detail separately.

● Outcomes by causative organism – Outcomes vary according to the causative organism:

• Group B streptococcus (GBS) – Reported mortality rates of neonatal GBS meningitis

SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

• Management of cardiovascular instability or shock (see "Neonatal shock: Etiology,

● Empiric antimicrobial therapy – Broad-spectrum antimicrobial therapy should be

• Group B streptococcus (GBS) – GBS is uniformly susceptible to penicillin and

• Escherichia coli and other gram-negatives – Treatment depends on the susceptibility

● Monitoring – The response to therapy and the potential development of complications

• Neurologic complications should be considered in the neonate with meningitis who

• Most neonates should undergo repeat LP 24 to 48 hours after initiation of antibiotic

• We perform magnetic resonance imaging (MRI) 48 to 72 hours before the anticipated

● Outcome – In the modern era, the mortality of neonatal bacterial meningitis is

● Follow-up – Long-term follow-up for survivors of neonatal meningitis includes monitoring

Use of UpToDate is subject to the Terms of Use.

25. Phan H, Lehman D. Cerebral abscess complicating Proteus mirabilis meningitis in a

Initial evaluation and management of neonatal shock

Graphic 128082 Version 2.0

Bacterial pathogens in neonatal sepsis and focal neonatal infections

Term and late GBS Enterobacter, Enterococcus, Klebsiella, Listeria,

Preterm E. coli CoNS, Enterobacter, Klebsiella, Listeria, other enteric and

Term and late E. coli Enterobacter, Klebsiella, Listeria, N. meningitidis, other

Preterm CoNS Citrobacter, Enterobacter, Enterococcus, Listeria, other

Pathogens based on source of infection

Meningitis GBS CoNS, Enterococcus, Listeria, N. meningitides, nontypeable

Pneumonia GBS C. trachomatis, Citrobacter, Enterobacter, group A

Urinary tract E. coli Citrobacter, Enterobacter, Enterococcus, Klebsiella, Proteus

Skin and soft S. aureus

Δ Urinary tract infections may not be associated with bacteremia in neonates.

Graphic 61061 Version 12.0

Suggested antimicrobial regimens in the management of neonatal sepsis in

Early onset (<72 hours) Ampicillin and an aminoglycoside (typically