1. Group B Streptococci A Newborn’s Greatest Threat?
Tracy Bumsted, MD, MPH

2. Scanning electron micrograph shows a human neutrophil binding to and phagocytosing group B streptococci that have been opsonized with a monoclonal antibody and complement.

3. A few frightening facts…
Many women carry GBS asymptomatically.
Infected newborns can get really sick, really fast and die.
Newborns are immunocompromised.
GBS are smart.

4. History
Isolated in 1887
Known to be associated with pregnancy and early newborn sepsis.
1960’s – Increasing newborn infections attributed to GBS.
1970’s – GBS emerged as predominant organism causing sepsis & meningitis in newborns.
1990’s – Increased use of maternal abx in labor
2002 – ACOG guideline for screening & chemoprophylaxis for GBS+ mothers.

5. Can grow on variety of bacteriologic media
Microbiology
Facultative Gram-Positive Diplococci
Can grow on variety of bacteriologic media

6. Classification
Beta-hemolysis – differentiates Groups of Streptococci with different group-specific antigens within the cell wall.
S. Pyogenes (GAS)
S. Agalactiae (GBS)
S. pnemoniae

7. Further Classification of GBS
Serotypes – based on type-specific capsular polysaccharides
GBS polysaccharides:
Glucose, Galactose, Glucosamine and
N-acetylneuraminic acid (sialic acid)

8. Epidemiology
Prior to maternal intrapartum chemoprophylaxis became widespread, attack rates for GBS disease in infants was 0.2 to 5.4 per 1000 live births (80% early-onset disease).
After maternal intrapartum chemoprophylaxis, this has dropped >65%

9. Maternal Colonization
25-30% all women
Higher rates for women:
Younger than 20 years of age
Black (36.7%) > White > Asian (14%)
Lower educational level
Lower rates for women:
Multiparous (>2 pregnancies)

10. Screening Pregnant Women
Test at weeks gestation, swab:
Distal vagina >>> cervix
Rectum – often the only source that is +
Sensitivity >95%
Asymptomatic bacteriuria (>100K cfu/ml) is a surrogate for high genital innoculum and marker of increased risk of Early-Onset Disease (EOD)

11. Intrapartum Maternal Chemoprophylaxis
Can prevent vertical transmission of GBS from colonized mothers to their neonates (51 9% in one study)
Can prevent EOD (6  0% in one study)
Maternal febrile morbidity
No impact demonstrated on LOD

12. Intrapartum Maternal Chemoprophylaxis
If GBS+ by culture, or +risk factors:
Chemoprophylaxis begins at hospital admission for delivery or at ROM
IV Penicillin G 5 million U x 1, then 2.5 million U IV q4 hours until delivery
If pen-allergic, can use IV clinda or ancef

13. Intrapartum Maternal Chemoprophylaxis
Risk Factors for increased EOD:
Previous delivery of infant with GBS disease
GBS bacteriuria during pregnancy
Preterm labor or ROM <37 weeks gestation
ROM >18 hours before delivery
Intrapartum fever (>38), suspicion of chorio

14. Infant Colonization Infants acquire GBS via vertical transmission
Ascending route through ruptured membranes

15. Infant Colonization Infants acquire GBS via vertical transmission
Contact with GBS in the genital tract during delivery

16. Infant Colonization
Single factor most clearly associated with likelihood of vertical transmission and subsequent neonatal colonization is the number of organisms (inoculum) in the maternal genital tract.

17. Risk Factors for Infant EOD
Must have vertical transmission
Heavily colonized mother
Preterm labor <37 weeks gestation
PROM
ROM >18 hours before delivery any gestation
Intrapartum maternal fever >38; chorioamnionitis

18. Risk of Infant Disease 50% 1 - 2% Asymptomatic colonized mother
Vertical transmission
in utero or during birth
Newborn Ill
50%
1 - 2%
>90% by 12 hours of life
Resp sx’s predominate: Apnea, Grunting, Tachypnea, Cyanosis

19. Maternal Factors Affecting Vertical Transmission
Bacterial inoculum in genital tract
Preterm labor (?caused by heavy inoculum)
Maternal antibody to the serotype-specific polysaccharide capsule of colonizing strain
?younger mothers may not have this antibody so cannot passively protect their fetuses.

20. Bacterial Factors Affecting Vertical Transmission and EOD
Adherance to epithelium: Sticky fingers
Vaginal
Chorioamniotic membranes
Infant lung
(after infant aspirates infected
maternal amniotic fluid)
Infant endothelial cells

21. Bacterial Factors Affecting Vertical Transmission and EOD
Capsular polysaccharide
Thought to confer virulence by interfering with opsonophagocytosis
Presence of the terminal sialic acid residue:
Prevents deposition of C3
Prevents activation of the alternative complement pathway (primary pathway used by human host when type-specific Ab is lacking)
Interferes with leukotriene B and C5a, potent neutrophil chemoattractants

22. Infant Factors Affecting EOD
Neutrophils
Primary defense against
extracellular bacterial
pathogens
Impaired migration to a
chemotactic stimulus
Storage pools quickly depleted in neonates with invasive infection, leading to profound neutropenia, more pronounced in premature infants

23. Infant Factors Affecting EOD
Macrophages
First effector cell to
encounter pathogens
Alveolar macrophage in lung
Diminished migration to site
of infection

24. Infant Factors Affecting EOD
Humoral Immunity
Complement
Pathway
Impaired
opsonization
Passive placental transfer of IgG
Increases dramatically in final 8 weeks of pregnancy

25. Disease Manifestations
Bacteremia/Sepsis: % EOD
Meningitis: 6-15% EOD, often no WBC in CSF
Pneumonia: “common”
Septic Arthritis: mean age 20 days; hips, LE
Osteomyelitis: 5% of LOD, mean age 9 days; proximal humerus, femur
Cellulitis/Adenitis: 2% LOD; mean age 5 weeks; face & neck swelling, LAD

26. Time Frame of GBS Infections
Early-Onset Disease
Late-Onset Disease
Late, Late-Onset Disease
<7 days; mean 8 hours, median 1 hour
7-89 days; mean 36 days, median 27 days
90 days and later
Sepsis 40-55%
Pneumonia 30-45%
Meningitis 6-15%
Sepsis 55%
Meningitis 35%
Osteoarthritis 5%
Cellulitis/Adenitis 2%
Sepsis
Meningitis
Osteoarthritis
Cellulitis/Adenitis

27. Late Late-Onset Disease?
Seen more in association with immunodeficiency (HIV, transient hypogammaglobulinemia)

28. Other Pearls
10-38% of newborns with GBS meningitis have negative BCx so CSF is important to determine meningeal involvement
24% of infants with cellulitis/adenitis who had LPs grew GBS from CSF

29. Other Pearls
CBC of septic babies can show leukopenia, neutropenia or leukocytosis
Increased I:T ratio – immature:total neutrophils has been shown to be a reliable index for distinguishing resp distress caused by GBS vs. a non-infectious etiology

30. Other Pearls Neutropenia = ANC <1800
ANC = WBC x (%segs+bands+metamyelos)
I:T ratio = (%bands+metas) / (segs+band+metas)
Elevated I:T ratio = >0.3

31. Laboratory Evaluation
BCx
CBC with manual
differential
CXR LP

32. Empiric Treatment Ampicillin IV 300 mg/kg/day Gentamicin
If neonate if getting empiric vanco, should also give ampicillin because vanco does not penetrate CSF well without inflammation
Fluid resuscitation for poor perfusion/acidosis

33. Empiric Treatment
Transfer to DNCC for prompt, supportive care of respiratory failure and shock
Surfactant to improve gas exchange for infected premature neonates
May develop persistant
pulmonary HTN and need
ECMO.

34. Sobering Prognosis Faster time to dx and tx improves outcomes
Mortality 2-8% all cases
Mortality >20% premature babies
Sepsis survivors: some PVL with ND sequelae
Meningitis survivors: 20-30% permanent neurologic sequelae (MR, blindness, spasticity, paresis)
Bone/Joint infx: most are excellent with early surgical intervention

35. Got It? Get It? Good. GBS is a common colonizing organism.
Maternal, Infant and Bacterial factors all affect transmission and development of disease.
Infants usually present with respiratory symptoms, but also can have lethargy, poor feeding, abdominal distention, pallor, tachycardia and jaundice.
Fever usually in term newborns; Hypothermia in preterm babies.

36. Got It? Get It? Good.
Many clinical manifestations, especially in late-onset disease.
Get full ROS lab evaluation.
Treat with amp and gent, plus supportive care.
Prognosis can be poor, especially with delayed diagnosis.
Prevention is possible