Prevention of Perinatal Group B DISCLOSURE A Public Health Perspective

A Public Health Perspective
Prevention of
Perinatal Group B
Streptococcal Disease
The Disease
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GBS Disease in Infants
Group B Streptococcus or Streptococcus agalactiae, is a gram positive
bacterium that causes invasive disease primarily in infants, pregnant or
postpartum women, and older adults, with the highest incidence among
young adults.
GBS emerged as an important pathogen in the 1970s
GBS is the leading infectious cause of morbidity and mortality among
infants in the US.
Before Testing
– Over 7500 cases of GBS newborn sepsis and meningitis annually
– 1600 seriously ill
– Case – fatality rate of 5% - 20%
– 300 deaths
• As a result of prevention efforts, incidence of GBS has declined
dramatically over the past 15 years, from 1.7 cases/1000 live births to
0.34-0.37 cases/1000 live births.
• Perinatal GBS disease burden
– neonatal illness/death, long-term disability
maternal morbidity
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• Neonatal direct costs -- $300 million/yr
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Neonatal GBS Disease
A Schuchat. Clin Micro Rev 1998;11:497-513.
Maternal to Infant
GBS colonized mother
10%-30% pregnant women are colonized
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A Schuchat. Clin Micro Rev 1998;11:497-513.
Early-onset sepsis,
pneumonia, meningitis
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Perinatal Environments
Intrauterine infection can result
Transplacental passage of pathogens
including viral infections (e.g., rubella,
cytomegalovirus [CMV], herpes
simplex, hepatitis, mumps), bacterial
infections (e.g., syphilis, tuberculosis,
Listeria, Salmonella infections) and
protozoal infections (e.g.,
toxoplasmosis, malaria).
Infection may also ascend through the
Infection may occur secondary to
contact with hospital nursery
personnel and equipment after birth or
with household members.
Organisms in hospital nurseries include
enteroviruses, herpes simplex,
respiratory syncytial virus and
parainfluenza viruses.
The infant is colonized with
organisms that reside in the
maternal cervicovaginal canal.
Common organisms include
streptococci, Escherichia coli, and
other aerobic and anaerobic enteric
The neonate may be exposed to
Chlamydia, gonococci, herpes
simplex viruses and CMV, if mother
Possible association between early
onset and certain obstetric
procedures, i.e. internal fetal
monitoring devices, > 5 or six digital
vaginal exams after onset of labor
or ROM.
• When to culture?
– culture at delivery -- too late
– prenatal cultures predict delivery status
Heavy colonization, which is defined as culture of GBS
from the direct plating rather than from selective broth
only, is associated with higher risk for early-onset
disease. GBS identified in clean-catch urine specimens
during any trimester is considered a surrogate for heavy
maternal colonization and is associated with a higher
risk for early onset GBS disease.
GBS Maternal Colonization
• The gastrointestinal tract serves as the primary reservoir for
GBS and is the likely source of vaginal colonization.
• In addition to maternal colonization with GBS, other factors
that increase the risk for early-onset disease include:
• Gestational age < 37 weeks
• Longer duration of ROM
• Intra-amniotic infection
• Young maternal age
• African Americans and nonsmokers
• Previous delivery of an infant with invasive GBS disease
• In a 1985 report of predictors of early onset disease, women with
gestation <37 weeks, membrane rupture of >12 hours, or intrapartum
temperature >99.5 F (>37.5 C) had a 6.5 times the risk for having and
infant with early-onset GBS disease compared with women who had
none of these risk factors.
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Current Estimates of Annual GBS EarlyOnset Disease in the U.S.
(2001 provisional, from ABCs/EIP Network)
~4,400 cases prevented per year
1720 cases still occurring annually
70 - 90 deaths
Remains leading infectious cause
of neonatal morbidity and mortality
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Factors and Clinical Signs/Symptoms Associated
with Neonatal Sepsis
Early Onset of Symptoms
• Maternal infection during the
perinatal period
• Prolonged rupture of the
• Difficult or prolonged labor
• Maternal fever, pyuria and foul smelling
amniotic fluid
• If > 24 hrs since ruptured or amnionitis
• Infant hypoxia and staining of the
meconium as a sign of fetal/neonatal stress
• Increased risk of infection
• Prematurity and/or low birth
• Low Apgar score or the need for • Hypoxia, hypoperfusion, aspiration or the
resuscitation at birth
need for intubation
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Factors associated with early-onset
GBS disease: multivariable analysis
GBS screening
0.46 (0.36-0.60)
Prolonged ROM (> 18 h)
1.41 (0.97-2.06)
Pre-term delivery
1.50 (1.07-2.10)
Black race
1.87 (1.45-2.43)
Maternal age <20 y
2.22 (1.59-3.11)
Previous GBS infant
5.54 (1.71-17.94)
Intrapartum fever
5.36 (3.60-7.99)
Late onset of Sepsis
• Male > Females
• Routes for infections are
provided by e.g.,
meningomyelocele or sinus tracts
• Sex
• Congenital anomalies
• Prolonged stay in neonatal
• Increase the risk for infection
intensive care unit
• Procedures
• Use of monitoring electrodes,
umbilical catheters, chest tubes,
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etc. increase infection risk
Signs and Symptoms of
Sepsis in the Neonate
Temperature Change from the
normal range
• Hyperthermia
• Hypothermia
Hematological symptoms including
bleeding problems
Central Nervous System symptoms
• Lethargy
• Irritability
• Seizures
Pulmonary symptoms
• Cyanosis
• Dyspnea
• Periodic breathing
1. History and physical examination
2. Blood, urine and CSF samples should be obtained, examined and cultured.
3. Laboratory tests useful in making the diagnosis include:
a. Peripheral WBCs
Range of White Blood Cells (x 1000/mm3) for normal infants
Ratio of
immature to
1.8 - 6
0 - 1.1
1 day
7.2 - 14.5
0 - 1.3
< 0.15
5 days
1.8 - 5.4
0 - 0.5
< 0.12
28 days
1.8 - 5.4
0 - 0.5
< 0.12
Cardiovascular symptoms
• Tachycardia or bradycardia
• Hypotension
• Shock
Gastrointestinal symptoms
• Abdominal distention
• Anorexia
• Vomiting
• Diarrhea
Hepatic symptoms
• Hepatomegaly
• Jaundice
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Schrag et al, NEJM , 347:233-9
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Factors and Clinical Signs/Symptoms Associated
with Neonatal Sepsis
Adjusted RR (95% CI)
b. Counterimmunoelectrophoresis (CIE) or latex agglutination (LA)
c. Other tests, when used individually, are unreliable indicators of
neonatal sepsis. A combination of a complete leukocyte count,
microerythrocyte sedimentation rate, and C-reactive protein may be
more accurate than any single test.
< 0.16
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Prevention of Perinatal GBS Disease
• Intrapartum antibiotics
Prevention &
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– Highly effective at preventing early-onset
disease in women at risk of transmitting
GBS to their newborns
• Challenge: How best to identify women at
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First U.S. Consensus Recommendations
(CDC '96, ACOG '96, AAP '97)
Screening-based approach:
35-37 wks culture, offer intrapartum antibiotic
prophylaxis (IAP) to GBS carriers and to preterm
unless neg. culture result available
Sensitivity and Specificity
of Late Antenatal Cultures
Risk-based approach:
IAP to preterm, membrane rupture>18 hours, or
intrapartum fever (T>38C)
Both strategies also give IAP to women with GBS
bacteriuria, or previous infant with GBS disease
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Yancey et al., OB GYN 1996;88:811-5.
Prevention Strategy Using
GBS by Culture Site
Screening-Based Approach
Risk factors:
• Previous infant w/GBS disease
• GBS bacteriuria this pregnancy
• Delivery < 37 wks gestation
Collect rectal & vaginal swab at 35-37 wks
GBS+ Offer
Not done, incomplete, or
results unknown
* P <0.05 both vs. vaginal only
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Risk factors:
• Intrapartum fever > 38C
• ROM > 18 hrs
No intrapartum prophylaxis needed
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CDC Guidelines
• Routine screening for group B
streptococcus during pregnancy prevents
more cases of early-onset disease than the
risk-based approach.
• Screening group: 18% of carriers had
no risk factor
CDC 2002 Guidelines
• UNIVERSAL prenatal screening
– 35-37 weeks
MMWR August 16, 2002 Vol 51 – RR 11
Schrag. et al. 2002 N Engl J Med 347:233-239
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Intrapartum Antibiotic
Prophylaxis (IAP)
• Recommended for some
pregnant women
Indications for IAP under
universal prenatal screening
• Previous infant with invasive GBS disease
• GBS bacteriuria during current pregnancy
• Positive GBS screening culture during current
pregnancy (unless a planned cesarean delivery, in the
absence of labor or amniotic membrane rupture)
• Unknown GBS status AND any of the following:
• Delivery at <37 weeks’ gestation
• Amniotic membrane rupture 18 hours
• Intrapartum temperature 100.4°F ( 38.0 °C)
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Intrapartum prophylaxis
NOT indicated
Previous pregnancy with a positive GBS screening culture
(unless a culture was ALSO positive during the current
Planned cesarean delivery performed in the absence of
labor or membrane rupture (regardless of maternal GBS
culture status)
Negative vaginal and rectal GBS screening culture
during the current pregnancy, regardless of
intrapartum risk factors
Threatened Preterm Delivery
• Suggested algorithm for management of
threatened preterm delivery (labor or rupture
of membranes at <37 weeks’ gestation)
which does not proceed rapidly to delivery:
– Culture and start IV antibiotics
– Culture negative at 48 hrs: stop antibiotics
– Culture positive: no data on duration of
antibiotics before active labor, when active
labor begins give IAP
– Culture negative and undelivered within 4
wks: re-screen
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Algorithm for screening for GBS colonization and use of intrapartum
prophylaxis for women with PPROM
Pt admitted with s/s PTL
Obtain vaginal-rectal swab for GBS culture and start
GBS prophylaxis
Patient entering labor?
Patient entering true labor?
Continue GBS prophylaxis
until delivery
Cont. Abx per
standard of care if
receiving for latency
Continue Abx until
Discontinue GBS prophylaxis
Continue Abx. For
48 hrs. if receiving
for GBS prophylaxis
Obtain GBS culture results
Obtain GBS culture results
Not available prior to labor
onset and patient still preterm
GBS prophylaxis of true
No GBS prophylaxis at onset of
true labor, repeat vaginal-rectal
culture if patient reaches 35-37
weeks gestation and has not yet
Recommednd regimen for intrapartum antibiotic prophylaxis for
prevention of early-onset group B streptococcal disease
• Penicillin G
– 5 million units IV load, then 2.5 million units
IV every 4h until delivery
Patient allergic to Penicillin?
• Ampicillin
– 2 g IV load, then 1g IV every 4h until delivery
– acceptable alternative, but broader spectrum
may select for resistant organisms
No GBS prophylaxis at
onset of true labor, repeat
vaginal-rectal culture if
patient reaches 35-37
weeks gestation and has
not yet delivered
GBS prophylaxis at
onset of labor
Intrapartum Antibiotic
Prophylaxis (IAP)
Not Available prior to
labor onset
PCN G, 5 million units IV
initial dose, then 2.5-3.0
million units every 4 hours
until delivery
Or Ampicillin, 2 g IV initial
dose, then 1 g IV every 4 hrs
until delivery
Patient with a history of
any of the following
after receiving PCN or a
Respiratory distress
Cefazolin, 2g IV initial
dose, then 1g IV every 8
hrs until delivery
Isolate susceptible to
clindamycin and
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Penicillin allergies
• Patient should be assessed to determine whether at
high risk for anaphylaxis
• Non-PCN drugs have
– increased resistance
• 3–15% for clindamycin
• 7–25% for erythromycin
– poor transplacental delivery
• susceptibility testing (for clindamycin and
erythromycin) should be performed on prenatal
GBS isolates from penicillin-allergic women at
high risk for anaphylaxis
PCN allergies
• Not at risk of anaphylaxis:
– Cefazolin 2g IV loading dose, then 1g q 8 hours until
• At Risk of anaphylaxis
– Clindamycin, 900 mg IV every 8 hours until delivery
– OR
– Erythromycin, 500 mg IV every 6 hours until delivery
• GBS resistant to Clinda & Erythro
– Vancomycin should be reserved for penicillin-allergic
women at high risk for anaphylaxis.
– Vancomycin 1g IV every 12 hours until delivery
(Obstet Gynecol 2008;111:356–64)
Timing of Intrapartum
Ampicillin and Transmission
of GBS
Sample Algorithm for Secondary prevention of early-onset
GBS disease among newborns
Signs of Neonatal Sepsis
• Full diagnostics evaluation
Antibiotic therapy
Maternal chorioamnionitis
• Limited evaluation
•Antibiotic therapy
GBS prophylaxis indicated for mother
•Routine clinical care
Mother received intravenous
penicillin, ampicillin, or cefazolin
for >/=4 hours before delivery?
Observation for
>/= 48 hrs.
• >/= 37 wks. and duration
•of membrane rupture < 18 hrs
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De Cueto et al., OB GYN 1998;91:112-4.
Sample Diagnostic
Evaluation of Infants Born
to Mothers with IAP
• Full Evaluation
CBC & differential
Blood culture
+/- Chest X-ray
+/- Lumbar puncture
• Limited Evaluation
– CBC & differential
– Blood culture
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Observation for
>/= 48 hrs.
• <37 wks. and duration
•of membrane rupture >/= 18 hrs
Limited evaluation
Observation for > 48 hrs.
CDC’s Recommendations
for Prenatal GBS Cultures
Optimize cultures:
• Site: vagina and rectum
– single swab or two swabs
– through anal sphincter
• Timing: 35 to 37 weeks
• Collection: NOT by speculum
– self collection an option
• Processing: selective broth medium
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Key GBS Resources
• Centers for Disease Control and Prevention
(CDC). Prevention of perinatal GBS disease:
revised guidelines. Morbidity and Mortality
Weekly Report, volume 51, no. RR-11, August 16,
CDC's GBS Internet page
– Endorsed by American Academy of
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GBS Resources
• American College of Obstetricians and
Gynecologists (ACOG). December 2002.
Prevention of Early-Onset Group B
Streptococcal Disease in Newborns.
Committee Opinion, # 279
• ACNM Position statement
• Schrag et. al, NEJM 2002; Vol. 347 (4):233-239
• Gibbs, Schrag, Schuchat. Perinatal Infections Due
to Group B Streptococci. Obstetrics &
Gynecology 2004;104:1062-1076
• Larsen, Sever. Group B Streptococcus and
pregnancy: a review. American Journal of
Obstetrics and Gynecology in press
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• Public Health Foundation
• GBS Association home page
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