A Review of Pediatric

Bacterial Meningitis

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P
ediatric bacterial meningitis is ABSTRACT: Pediatric bacterial meningitis is a medical
a severe, life-threatening infec- emergency requiring immediate initiation of treatment.
tion of the membranes (menin- Although the United States and other developed countries
ges) surrounding the brain and spinal have seen a decline in pediatric meningitis, bacterial
cord. The infection may be associated meningitis continues to cause high morbidity and mortality
with long-term, potentially devastating globally. Vaccinations (Haemophilus influenzae type b,
sequelae even when it is aggressively pneumococcal, and meningococcal) have significantly
managed. Compared with viral men- reduced the risk of bacterial meningitis in developed
ingitis, which frequently is self-limit- countries. The treatment of bacterial meningitis depends
ing and has a good prognosis, bacterial on the suspected or known causative organism. Treatment
meningitis carries a higher risk of often incorporates a third-generation cephalosporin or
morbidity and mortality. According penicillin plus vancomycin. Dexamethasone may be added
to the CDC, 4,100 cases of bacterial to prevent neurologic sequelae such as hearing loss.
meningitis were reported in the United Despite aggressive therapy, many patients will experience
States from 2003 to 2007, and approx- long-term neurologic complications.
imately 500 deaths occurred annually
during this period.1 It is estimated that factors such as age, immune function laboratory capacity in certain regions
the peak incidence of bacterial men- and immunization status, and geo- and underreporting lead to a significant
ingitis occurs in children younger than graphical location.2-4 The two most variability in incidence.6 The incidence
2 months and that at least 75% of common pathogens in the United States has been reported to be 5 to 10 cases
cases occur in those younger than 5 are Streptococcus pneumoniae and Neis- per 100,000 population in high-income
years.2-4 seria meningitidis.2-4 Globally, Hae- countries; however, the incidence also
mophilus influenzae type b (Hib) is a varies with age.5 Population-based
Etiology major cause of meningitis. This is in surveillance reported 80.69 cases per
There are several causative organisms contrast to the U.S. and other developed 100,000 population in patients less
for meningitis in infants and children countries, where the routine immuni- than 2 months.4
(TABLE 1). The etiology depends on zation of infants with the Hib-conju- The incidence of pediatric menin-
Amy M. Pick, PharmD, BCOP
gate vaccine has greatly reduced the gitis has declined substantially with
Associate Professor of Pharmacy Practice incidence of Hib-related meningitis.5 the introduction of vaccines against
Desirae C. Sweet, 2016 PharmD Candidate the three most common bacterial
Kimberley J. Begley, PharmD Epidemiology pathogens.2,7,8
Assistant Professor of Pharmacy Practice The global incidence and burden of
Creighton University
School of Pharmacy and Health Professions
bacterial meningitis are difficult to Hib: The serotype b of H influenzae
Omaha, Nebraska determine. Worldwide, the lack of is a respiratory pathogen that was once

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U.S. Pharmacist • May 2016 • www.uspharmacist.com
 PEDIATRIC BACTERIAL MENINGITIS
the leading cause of pediatric bacterial meningitis globally. tion schedule. There are concerns with serogroup B N
Today, the frequency of Hib in children has declined meningitidis meningitis, which currently does not have a
dramatically with the routine administration of the Hib vaccine because of its poorly immunogenic capsule.2
conjugate polysaccharide vaccine, which was introduced Other causative organisms, particularly in infants,
in the 1990s.2 include Group B streptococcus (GBS) and Listeria mono-
cytogenes. GBS is categorized as early-onset (developing at
S pneumoniae: The 7-valent pneumococcal conjugate age <7 days) or late-onset (developing at age >7 days).8
vaccine (PCV) was incorporated into the infant immuni- Pregnant women are screened for GBS colonization and,
zation schedule in 2000, and since that time the incidence if the patient tests positive, maternal intrapartum antibiot-
of pneumococcal meningitis in children in the U.S. has ics are initiated during labor to prevent the transmission
declined by 55% to 60%.9 Despite this, S pneumoniae of GBS to the fetus. The CDC and the American College
remains the most frequent cause of bacterial meningitis of Obstetricians and Gynecologists have developed recom-
in children. One reason is that more than 91 distinct mendations and guidelines for the prevention of GBS.11,12
serotypes of pneumococcus have been identified.2 In addi- L monocytogenes accounted for 3.4% of cases of bacterial
tion, there has been an increase in non-PCV serotypes meningitis (adults and children) from 1998 to 2007.8 A
that cause invasive disease. This led to the development 36% decline in Listeria occurred during this time period,
of PCV13 for use in infants and the use of 23-valent likely owing to a reduction in food-borne Listeria con-
polysaccharide vaccine in older children and adults.2 tamination.8

N meningitidis: N meningitidis is a gram-negative diplococ- Pathogenesis and Predisposing Factors

cus that is responsible for invasive meningococcal disease. The pathogenesis of pediatric bacterial meningitis is unclear.5
The incidence is bimodal, with an increase in infants Meningitis-causing pathogens typically cross the blood-
younger than 1 year and in teenagers and young adults.10 brain barrier (BBB) after colonization of the nasopharynx.
In the U.S., the serogroups B, C, and Y are involved in The mechanism of penetration depends on the organism
bacterial meningitis.2 The incidence of N meningitidis involved. The BBB also exhibits increased permeability
serogroup C and Y bacterial meningitis has decreased during a meningeal infection. Certain factors increase a
because of the routine immunization of 11- to 18-year-olds person’s risk of bacterial meningitis, including exposure to
with the quadrivalent meningococcal glycoconjugate vac- the infection (i.e., meningococcal) or having a recent upper
cine. Although this vaccine is approved for use in children respiratory tract infection.4
aged 2 to 10 years, it is not part of the routine immuniza-
Clinical Features
Table 1. Most Common Bacterial The clinical presentation of bacterial meningitis is often
nonspecific and depends on the patient’s age. Children
Pathogens According to Age with meningitis may present with fever and signs of a
Age Group Bacterial Pathogens meningeal inflammation, such as severe and persistent
0-1 mo (neonate) GBS (Streptococcus agalactiae) headache, stiff and painful neck (nuchal rigidity), vomit-
Escherichia coli ing, and confusion.4,13 The degree of signs and symptoms
Listeria monocytogenes often depends on the duration of the illness. Some less
1-3 mo GBS common symptoms include sluggishness, photophobia,
E coli skin rash, and dizzy spells. Petechiae and purpura are most
L monocytogenes commonly associated with N meningitidis and often begin
Streptococcus pneumoniae
Neisseria meningitidis
in the lower extremities.4,5,10
Two clinical signs that may be present in patients with
3 mo-3 y S pneumoniae meningitis are Kernig and Brudzinski. A positive Kernig
N meningitidis
GBS
sign is when the patient is lying in the supine position
E coli with the hips and knees flexed at 90° and is unable to
L monocytogenes extend the knee beyond 135° without pain.4 A positive
3-10 y S pneumoniae Brudzinski sign is when severe neck stiffness causes the
N meningitidis patient’s hips and knees to flex when the neck is flexed.4
Clinicians should keep in mind that the Kernig and
10-19 y N meningitidis
Brudzinski signs, as well as nuchal rigidity, are not present
GBS: group B streptococcus. Source: References 2, 4, 5.
in most cases of meningitis in adults and children.13

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 PEDIATRIC BACTERIAL MENINGITIS
Generalized seizures occur in approximately 20% to CSF fluid has a high WBC count and a positive Gram
30% of patients prior to or within 48 hours of admis- stain has a poorer outcome.
sion.14 Although patients may have temporary neurologic Molecular techniques such as polymerase chain reac-
deficits, these deficits resolve in most patients, and they tion may be helpful in the diagnosis and resolution of
are not at high risk for epilepsy. Patients at high risk for bacterial meningitis.14,15 A rapid antigen-agglutination
epilepsy are those with permanent neurologic deficits test may also be used in diagnosis.13 This option covers
secondary to bacterial meningitis. a wide range of organisms, such as Neisseria meningococ-
cal serogroups, S pneumoniae, H influenzae, and E coli,
Complications but it is less sensitive. Because false-positive results have
Two types of complications can occur in bacterial men- been reported with this method, many institutions do
ingitis: systemic and neurologic. Systemic complications not use it.13 The rapid antigen-agglutination test may be
in children include septic shock, disseminated intravas- most useful in patients who have been pretreated with
cular coagulation, acute respiratory distress syndrome, antimicrobial therapy and whose CSF and Gram stain
and septic or reactive arthritis. Even with treatment, there cultures are negative.
are significant long-term neurologic effects. At least 1 in The Bacterial Meningitis Score (BMS) may be used to
5 people with bacterial meningitis has long term neuro- determine the likelihood of bacterial and nonbacterial
logic sequelae.13 Neurologic sequelae include sensorineu- meningitis in infants and children older than 2 months.4
ral hearing loss (reported in 11% of patients), seizures, Criteria include positive CSF Gram stain, incidence of a
motor problems, hydrocephalus, and many other cogni- seizure with illness, blood neutrophil count exceeding
tive and behavioral problems.4,7 S pneumoniae meningi- 10,000 cells/mm3, CSF neutrophil count greater than
tis has one of the highest rates of long-term complications. 10,000 cells/mm3, and CSF protein exceeding 80 mg/dL.
The severity of the illness often contributes to the higher Patients at low risk for bacterial meningitis have a
mortality and likelihood of long-term neurologic sequelae.2,7 score of 0, meaning that they lack the above criteria. A
Corticosteroids, which are discussed in the TREATMENT score of 1 point suggests that nonbacterial (aseptic)
section, are often administered to lessen the risk of neu- meningitis is less likely, and a score of >2 suggests that
rologic damage. bacterial meningitis is more likely. A meta-analysis reported
the BMS has a sensitivity of 99.3% and a specificity of
Diagnosis 62.1%.4 The BMS may be helpful for determining the
The diagnosis of pediatric bacterial meningitis involves patient’s risk of bacterial meningitis.
laboratory blood tests and analysis of cerebrospinal fluid
(CSF). Blood tests should include a CBC, electrolyte Treatment
panel, C-reactive protein, and coagulation factors. Principles of Antimicrobial Therapy: Empiric therapy is
Diagnosis relies on CSF analysis. The Infectious selected based on the common bacteria causing the
Diseases Society of America (IDSA) bacterial meningitis meningitis. Once the pathogen is identified, specific
guidelines recommends that lumbar puncture (LP) be treatment may be made based on the known organism.
performed on children with expected meningitis.15 There Additional considerations in selecting treatment depend
are certain exceptions, including patients who are immu- on the drug’s ability to penetrate the BBB. Certain
nocompromised or have a history of selected neurologic characteristics of antimicrobials that permit easier pen-
conditions (i.e., CSF shunts, CNS trauma, or neurosur- etration across the BBB include low molecular weight,
gery).15 In these cases, the patient should first receive a simple chemical structure, high lipid solubility, low degree
CT scan of the head and have normal findings confirmed of protein binding, and low degree of ionization. For
prior to LP. The clinician should weigh the risk versus instance, vancomycin tends to have better penetration
benefit of performing LP in a pediatric patient. Regard- when the BBB is significantly damaged. Whether the
less of when the LP occurs, antibiotic treatment should antibiotic has concentration-dependent (aminoglycosides
be initiated immediately.15 and fluoroquinolones) or time-dependent (vancomycin
CSF analysis assists in the appropriate diagnosis of and beta-lactams) killing properties should also be con-
meningitis.15 A Gram stain of CSF fluid also is per- sidered. Antibiotics should be carefully deescalated once
formed.15 The Gram stain is positive in about 90% and the organism has been identified.15
80% of children with pneumococcal and meningococcal
meningitis, respectively.14 In H influenzae and Listeria Antibiotics: Globally, numerous organizations have treat-
meningitis, the Gram stain is positive in about 50% and ment guidelines for bacterial meningitis, including the
30% of patients, respectively. Generally, a patient whose IDSA, the Canadian Paediatric Society, the National

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 PEDIATRIC BACTERIAL MENINGITIS

Table 2. Antibiotic Recommendations for Bacterial Meningitis

Bacterial Recommended Treatment
Organism Antibiotics (IV) Duration (days)
Streptococcus pneumoniae Vancomycin + 3rd-generation cephalosporin (cefotaxime or ceftriaxone) 10-14
Neisseria meningitidis 3rd-generation cephalosporin (cefotaxime or ceftriaxone) 5-10
or
Penicillin G or ampicillin (depending on sensitivities)
Haemophilus influenzae 3rd-generation cephalosporin (cefotaxime or ceftriaxone) 7-10
Listeria monocytogenes Ampicillin or penicillin G ± aminoglycoside 14-21
GBS Ampicillin or penicillin G ± aminoglycoside 14-21
Escherichia coli Third-generation cephalosporin (cefotaxime or ceftriaxone) 21
GBS: group B streptococcus.
Source: References 2, 15, 19, 20, 21.

Institute for Health and Care Excellence, and the Men- of Pediatrics (AAP) recommends initiating vancomycin
ingitis Research Foundation.15-18 The 2004 IDSA guideline with cefotaxime or ceftriaxone in all children aged 1 month
on bacterial meningitis is currently being updated, with and older with suspected meningitis and then deescalating
publication expected in the autumn of 2016. Most of the once the organism is identified.20 The IDSA guideline also
recommendations provided here are from the IDSA guide- recommends the addition of vancomycin whenever S
line, although there is minimal variation between the pneumoniae is suspected.15 Rifampin, which has excellent
various organizations. CSF penetration, may be used in cases of cephalosporin-
The initiation of empiric therapy for the management resistant pneumococcal meningitis.2 Penicillin resistance
of bacterial meningitis should occur immediately follow- has also been reported to occur with N meningitides; for
ing LP or when meningitis is suspected.15 Treatment is on this reason, penicillins are avoided and third-generation
an inpatient basis. Selection of empiric therapy depends cephalosporins are first-line therapy for meningococcal
on the most prevalent organisms for each age group (TABLES meningitis.
2 and 3), as well as on local resistance patterns. General The duration of treatment has not been fully elucidated.
recommendations often include a third-generation ceph- A meta-analysis examining the duration of antibiotics did
alosporin, such as ceftriaxone or cefotaxime. Ampicillin not find conclusive evidence to support either long or
or penicillin G may be used against susceptible organisms. short courses of antibiotics in the treatment of pediatric
Pediatric dosing recommendations for selected antibiotics bacterial meningitis.15,19,21 The current recommendations
are summarized in TABLE 4. are based more on experience than on scientific evidence.
Drug resistance is a concern in the treatment of several TABLE 2 lists treatment durations.
organisms. Because of increasing apprehension regarding
multidrug-resistant strains of S pneumoniae, penicillin is Corticosteroids
not recommended for empiric therapy.2,15,19 Instead, Despite antibiotic therapy, patients with meningitis are
vancomycin is often added to the empiric regimen with at risk for long-term neurologic complications. There is
a third-generation cephalosporin. The American Academy some evidence that the use of anti-inflammatory agents
such as corticosteroids may reduce brain injury.2,15 Cor-
ticosteroids decrease inflammation and the release of
Table 3. Empiric Therapy cytokines, including tumor necrosis factor-alpha. Dexa-
According to Age methasone is the most common corticosteroid used to
Age Group Options for Antibiotics (IV) prevent or minimize the neurologic complications of
0-1 mo Ampicillin + gentamycin meningitis. The data, however, are conflicting. Initial
or trials suggested an advantage for dexamethasone used
Ampicillin + cefotaxime adjunctively to decrease neurologic sequelae (particularly
≥1-23 mo Vancomycin + cefotaxime or ceftriaxone hearing loss), with the greatest benefit in cases of Hib
meningitis. A 2015 Cochrane review found limited evi-
≥24 mo-50 y Vancomycin + cefotaxime or ceftriaxone
dence from two trials that suggested reductions in death
Source: References 2, 15, 19, 20, 21.
and hearing loss with use of adjuvant corticosteroids, and

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 PEDIATRIC BACTERIAL MENINGITIS
appropriate fluid status, moderate
Table 4. Recommended Pediatric fluid restriction (generally two-
Dosing of Selected Antibiotics thirds or three-fourths of their daily
maintenance) should be considered.
Antibiotic IV Daily Dosage Maximum Daily Dosage
Pediatric patients with meningitis
Ampicillin 200-400 mg/kg per day in 4 divided doses 12 g/day may have excess total and extracel-
Cefepime 150 mg/kg per day in 3 divided doses 6 g/day lular water, increased secretion of
Cefotaxime 225-300 mg/kg per day in 3 or 4 divided doses 12 g/day
the antidiuretic hormone, mild
systemic hypertension, and
Ceftazidime 150 mg/kg per day in 3 divided doses 6 g/day
increased intracranial pressure. In
Ceftriaxone 100 mg/kg per day in 2 divided doses 4 g/day initiating hydration, it is important
Gentamicin 7.5 mg/kg per day IV in 3 divided doses Adjust according to to rule out inappropriate secretion
serum peak and trough of antidiuretic hormone.
concentrations
Meropenem 120 mg/kg per day IV in 3 divided doses 6 g/day Chemoprophylaxis
Penicillin G 250,000-300,000 U/kg per day in 4 or 6 24 million U/day
Chemoprophylaxis may be con-
divided doses sidered to reduce the risk of
person-to-person transmission of
Vancomycin 60 mg/kg per day IV in 4 divided doses 4 g/day
meningitis (i.e., siblings and other
Source: References 2, 15, 19.
home contacts).1 Rifampin may
be prescribed to close contacts to
there was no advantage for reducing neurologic sequelae.22 reduce the transmission of Hib and meningococcal
Currently, the IDSA guideline recommends that adjunc- meningitis.1,14 Vaccination is recommended for children
tive corticosteroids be used in infants and children with who are unvaccinated and eligible for the Hib vaccine.
Hib infections, with initiation 10 to 20 minutes prior to For the meningococcal infection, adults and pediatric
the first antibiotic.15 Corticosteroids should not be given patients may receive rifampin or ceftriaxone. Cipro-
to patients who have already received antimicrobial ther- floxacin 500 mg orally as a single dose is another option
apy, owing to a lack of benefit. Although the IDSA guide- for adults, but it is not recommended for pediatric patients
line does not provide recommendations for pneumococcal owing to the potential for cartilage damage.14 Unvacci-
meningitis, the AAP suggests that dexamethasone be nated children and close contacts older than 2 years who
considered in patients aged 6 weeks and older after weigh- have been exposed to meningococcus A, C, Y, or W135
ing the risks and benefits.15 There is no evidence support- should receive the quadrivalent meningococcal vaccina-
ing the routine use of adjunctive corticosteroids in menin- tion. Refer to the CDC Immunization Schedules for the
gococcal meningitis. most up-to-date recommendations (www.cdc.gov/vaccines/
Several dosing regimens of dexamethasone have been schedules). Chemoprophylaxis is not indicated for pneu-
used. The most common dosage is 0.15 mg/kg every 6 mococcal meningitis. Generally, healthcare workers do
hours for 4 days.15,19 Dexamethasone should be given prior not require chemoprophylaxis.
to or simultaneously with the first dose of antibiotics. An
auditory assessment should be performed at discharge and Conclusion
1 month afterward. Pediatric bacterial meningitis is often fatal if treatment
Other limited agents are being used for the anti-inflam- is delayed. Pharmacists should be aware of the signs and
matory treatment of pediatric bacterial meningitis. Glyc- symptoms to assist in the timely diagnosis of meningitis
erol, a hyperosmolar diuretic, has also been used as adjunc- in pediatric patients. If meningitis is suspected, an exam-
tive treatment; its low cost and oral administration are ination of the CSF via LP should be performed in eli-
advantages, but more data are needed in order to recom- gible patients to determine the organism involved. Imme-
mend this agent for the prevention of neurologic sequelae.2 diate initiation of antibiotics and supportive care is
essential for reducing the morbidity and mortality of
Supportive Care meningitis. Even with treatment, patients may have
The management of meningitis includes the administration long-term neurologic sequelae. Pharmacists should rec-
of IV fluids.19,23 The patient’s fluid and electrolyte balance ommend the discussed vaccinations knowing that they
should be assessed. If patient is in shock or hypovolemic, may reduce the risk of meningitis.
rehydration should be provided. If the patient has an References available online at www.uspharmacist.com.

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U.S. Pharmacist • May 2016 • www.uspharmacist.com
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