Group B StreptococciA Newborn’s Greatest Threat?

Tracy Bumsted, MD, MPH

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

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.

History• Isolated in 1887• 1935 - 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.

Microbiology

Facultative Gram-Positive Diplococci

Can grow on variety of

bacteriologic media

ClassificationBeta-hemolysis – differentiates Groups of

Streptococci with different group-specific antigens within the cell wall.

S. pnemoniae

S. Pyogenes (GAS)

S. Agalactiae (GBS)

Further Classification of GBS• Serotypes – based on type-specific capsular

polysaccharides• GBS polysaccharides:

– Glucose, Galactose, Glucosamine and– N-acetylneuraminic acid (sialic acid)

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%

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)

Screening Pregnant Women

• Test at 35-37 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)

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

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

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

Infant Colonization• Infants acquire GBS via vertical

transmission– Ascending route through ruptured membranes

Infant Colonization• Infants acquire GBS via vertical

transmission– Contact with GBS in the genital tract during

delivery

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.

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

Risk of Infant Disease

Asymptomatic colonized mother

Vertical transmissionin utero or during birth

Newborn Ill

50%

1 - 2%>90% by 12 hours of lifeResp sx’s predominate: Apnea, Grunting, Tachypnea, Cyanosis

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.

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

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

Infant Factors Affecting EOD• Neutrophils

• Primary defense againstextracellular bacterialpathogens

• Impaired migration to achemotactic stimulus

• Storage pools quickly depleted in neonates with invasive infection, leading to profound neutropenia, more pronounced in premature infants

Infant Factors Affecting EOD• Macrophages

• First effector cell to encounter pathogens

• Alveolar macrophage in lung

• Diminished migration to site of infection

Infant Factors Affecting EODHumoral ImmunityComplement Pathway

– Impaired opsonization

Passive placental transfer of IgG– Increases dramatically in final 8 weeks of pregnancy

Disease Manifestations• Bacteremia/Sepsis: 27-87% 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

Time Frame of GBS InfectionsEarly-Onset

DiseaseLate-Onset

DiseaseLate, 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%

SepsisMeningitisOsteoarthritisCellulitis/Adenitis

Late Late-Onset Disease?

• Seen more in association with immunodeficiency (HIV, transient hypogammaglobulinemia)

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

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

Other Pearls

• Neutropenia = ANC <1800ANC = WBC x (%segs+bands+metamyelos)

• I:T ratio = (%bands+metas) / (segs+band+metas)Elevated I:T ratio = >0.3

Laboratory Evaluation

• BCx

• CBC with manual differential

• CXR• LP

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

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 needECMO.

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

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.

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