Group B Streptococci A 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.

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

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

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 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

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 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

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

Infant Factors Affecting EOD Humoral Immunity Complement 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 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

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 <1800 ANC = 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 need ECMO.

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