Group B Streptococcus (GBS)

Epidemiology / Background                     

Group B strep (GBS, or Streptococcus agalactaie) is an encapsulated, gram-positive, beta-hemolytic diplococcus that colonizes the GI or GU tracts of 15-40% of pregnant women. Although usually asymptomatic in adults, GBS infection in neonates causes sepsis leading to pneumonia, meningitis, shock, or even death. 

GBS disease is classified based on the time of onset. Early-onset GBS disease occurs before 7 days of life, and is acquired in utero or during the delivery process. Late-onset GBS  occurs after 7 days of life and is typically acquired in the community.

Identifying pregnant women who are colonized with GBS and giving intrapartum antibiotics significantly decreases the risk of early-onset GBS sepsis in the neonate. Guidelines issued by the AAP and ACOG have dramatically reduced the number of early-onset GBS infections over the past 20 years, from about 1.7 per 1,000 live-births in 1990 to less than 0.5 per 1,000 live births in 2008.

Figure 1. Incidence of early- and late-onset invasive group B streptococcal (GBS) disease --- Active Bacterial Core surveillance areas, 1990--2008, and activities for prevention of GBS disease.

Abbreviations: ACOG = American College of Obstetricians and Gynecologists and AAP = American Academy of Pediatrics.  Source: Adapted from Jordan HT, Farley MM, Craig A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease. Pediatr Infect Dis J 2008;27:1057--64.

* Incidence rates for 2008 are preliminary because the live birth denominator has not been finalized.

Prevention
                     

Identifying pregnant women who are colonized with GBS and giving intrapartum antibiotics significantly decreases the risk of early onset GBS disease in the neonate. The following screening and prevention measures are currently recommended:

Screening:

• Pregnant women should be screened for GBS infection at 35-37 weeks gestation using rectal and vaginal swabs.

Indications for Prophylaxis:

• The following women should receive intrapartum antibiotic prophylaxis:

• GBS-positive in preceding 5 weeks
• GBS status unknown with 1 or more intrapartum risk factors:
• Gestation < 37 weeks
• Rupture of membranes > 18 hours
• Temperature > 38 C
• GBS bacteriuria during current pregnancy
• History of a previous infant with GBS disease
                    

Adequate Prophylaxis:

Adequate prophylaxis involves antibiotic treatment for at least 4 hours prior to delivery. If given for less than 4 hours, this is considered inadequate prophylaxis.  

Antibiotics proven to be effective include:

• Penicillin (5 million units initial IV dose, then 2.5-3 million units q4 hours until delivery)
• Ampicillin (2g initial IV dose, then 1g IV q4 hours until delivery)
• Cefazolin (2g initial IV dose, then 1g IV q8 hours until delivery)
                          

Often, penicillin-allergic patients will be treated with either clindamycin (900mg IV q8 hours until delivery) or vancomycin (1g IV q12 hours until delivery). However, these antibiotics have not been proven effective and are NOT considered adequate prophylaxis.

Presentation
             

GBS generally presents as sepsis and is classified based on the time of onset:

Presentations can include:

• Shock: temperature instability, hypotension, bradycardia, multiorgan system failure
• Pneumonia: tachypnea, grunting, nasal flaring, retractions, decreased breath sounds, cyanosis
• Meningitis: seizures, lethargy, coma, bulging anterior fontanelle, focal cranial nerve signs
• Osteoarthritis and soft-tissue infection: pain, swelling, overlying warmth & erythema, may be manifestations of late-onset disease.

Differential
                 

Because the symptoms of GBS sepsis are non-specific, there is a broad differential including:

1. Perinatal asphyxia
2. Aspiration pneumonia (amniotic fluid, meconium, gastric contents)
3. Hyaline membrane disease
4. Other agents causing pneumonia or sepsis (e.g. E. coli, HSV)
5. Congenital heart disease
6. Hypoglycemia
7. Adrenal insufficiency
8. Organic acidosis
9. Urea cycle disorders
10. Intracranial hemorrhage
11. Neonatal purpura fulminans
12. Severe anemia
13. Congenital leukemia

Workup
             

The workup for GBS sepsis is based on the infant’s presentation and risk factors. Infants presenting with signs of sepsis should undergo a full diagnostic workup, including a blood culture, CBC, CXR, and LP.

Asymptomatic infants with risk factors for early-onset disease should be managed based on the algorithm below.

Figure 2. Algorithm for secondary prevention of early-onset group B streptococcal (GBS) disease among newborns.

* Full diagnostic evaluation includes a blood culture, a complete blood count (CBC) including white blood cell differential and platelet counts, chest radiograph (if respiratory abnormalities are present), and lumbar puncture (if patient is stable enough to tolerate procedure and sepsis is suspected).

† Antibiotic therapy should be directed toward the most common causes of neonatal sepsis, including intravenous ampicillin for GBS and coverage for other organisms (including Escherichia coli and other gram-negative pathogens) and should take into account local antibiotic resistance patterns.

§ Consultation with obstetric providers is important to determine the level of clinical suspicion for chorioamnionitis. Chorioamnionitis is diagnosed clinically and some of the signs are nonspecific.

¶ Limited evaluation includes blood culture (at birth) and CBC with differential and platelets (at birth and/or at 6--12 hours of life).

** See table 3 for indications for intrapartum GBS prophylaxis.

†† If signs of sepsis develop, a full diagnostic evaluation should be conducted and antibiotic therapy initiated.

§§ If ≥37 weeks' gestation, observation may occur at home after 24 hours if other discharge criteria have been met, access to medical care is readily available, and a person who is able to comply fully with instructions for home observation will be present. If any of these conditions is not met, the infant should be observed in the hospital for at least 48 hours and until discharge criteria are achieved.

¶¶ Some experts recommend a CBC with differential and platelets at age 6--12 hours.

Treatment

If sepsis is suspected, or if there is a history of maternal chorioamnionitis, empiric antibiotics should be started. For early-onset disease, a typical regimen includes ampicillin and an aminoglycoside. For late-onset disease, typically ampicillin or nafcillin is used with a third-generation cephalosporin. The duration of treatment varies based on the infectious source:

Prognosis

Mortality from GBS infection is 5%. Complications in 12-30% of those surviving include cortical blindness, spasticity, and global intellectual disability. Deafness, motor deficits, and minor intellectual disability may also occur.

Ongoing Research

One major area of study surrounding GBS is vaccine development. There are nine major GBS serotypes, each with a unique capsular polysaccharide. Researchers have succeeded in creating vaccines against individual serotypes, but are still searching for a common antigen that might be used for a universal GBS vaccine. Currently researchers are analyzing GBS genomic sequences to identify viral proteins common to all nine serotypes that might serve as candidate antigens for vaccine development.

References

1. Baker CJ. Chemoprophylaxis for the prevention of neonatal group B streptococcal disease. Up-To-Date article. Accessed 2013 Feb 3.
2. Committee on Infectious Diseases and Committee on Fetus and Newborn. Recommendations for the Prevention of Perinatal Group B Streptococcal (GBS) Disease. Pediatrics. 2011-1466; published ahead of print August 1, 2011. http://pediatrics.aappublications.org/content/early/2011/07/28/peds.2011...
3. Gotoff, Samuel P. Group B Streptococcal Infections. Pediatrics in Review. 2002;23;381
4. Johri AK, Paoletti LC, Glaser P, Dua M, Sharma PK, Grandi G, et al. Group B Streptococcus: global incidence and vaccine development. Nat Rev Microbiol. 2006;4:932–942.
5. Jordan HT, Farley MM, Craig A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease. Pediatr Infect Dis J 2008;27:1057—64
6. Puopolo KM and Baker CJ. Group B streptococcal infection in neonates and young infants. Up-To-Date article. Accessed 2013 Feb 3.
7. Verani JR, McGee L, Schrag SJ. Prevention of Perinatal Group B Streptococcal Disease. Revised Guidelines from CDC, 2010. 2010 Nov 19. 59(RR10);1-32. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htm?s_cid=rr5910a1_w#Fig1.