Introduction
Group B streptococcus (GBS), is the gram positive aerobic diplococcus Streptococcus
agalactiae, and is found in pairs or in chains. The bacterium is encapsulated in a
polysaccharide coating. The Lancefield classification system distinguishes different
streptococci by the specific carbohydrate antigen; GBS has Lancefield group B antigen.
There are nine serotypes of GBS; in the United States, serotype Ia, Ib, II, III, and V
account for approximately 95% of all cases. Serotype III is most prevalent in early-onset
meningitis and late-onset disease in neonates. Early onset disease is defined by infection
at > 7 days of life, and late-onset disease from 7 days to 3 months. Approximately 80% of
early–onset is due to vertical transmission from mother to infant during labor, and usually
presents as sepsis and pneumonia within the first 24 hours, with 5 – 10% of cases
presenting as meningitis.
Approximately 10 – 30% of pregnant women are colonized with GBS. Risk factors for
colonization during pregnancy include diabetes, age < 20 years, less than four
pregnancies, African-American or Hispanic ethnicity, and low maternal serum antibody
specific to GBS serotype. Obstetric risk factors include intrapartum fever, prolonged
rupture of membranes, GBS bacteriuria, previous infant affected by GBS disease, and
delivery < 37 weeks gestation.
In GBS culture positive women, the mean rate of transmission risk is 50%, with a range
of 29% to 85%. Of those infants who become colonized, 1-4
Background
In the 1970s, GBS was identified as the leading cause of neonatal sepsis, with
approximately 7500 cases per year prior to recommended prevention protocols.5 Neonatal
mortality rates were reported as high as 50%, with annual cost approaching $300 million.
Morbidity from this disease included blindness, hearing loss, mental retardation, and
cerebral palsy. 3,6 With studies in the late 1970s and 1980s demonstrating the
effectiveness of intrapartum antibiotic regimens in decreasing neonatal cases,7-9 in the
United States, similar guidelines were proposed by the American Academy of Pediatrics
(AAP) and American College of Obstetricians and Gynecologists (ACOG) in 1992,
followed by guidelines from the Centers for Disease Control and Prevention (CDC). 10-12
The 1996 CDC guidelines offered two strategies, one a risk based approach, the other a
screen based approach using cultures; these were endorsed by the AAP and ACOG.
Risk Based Screening versus Culture Based Screening
The risk based strategy recommended chemoprophylaxis for intrapartum risk factors
associated with early-onset disease: delivery at < 37 weeks gestation, an intrapartum
maternal temperature of 100.4 F (38.0 C), or rupture of membranes  18 hours. The
screen based strategy promoted universal screening of all pregnant women between the
35 – 37 weeks gestation with vaginal and rectal swabs for GBS colonization, with
colonized women receiving antibiotics intrapartum. Under both strategies, women with
GBS bacteriuria or a history of a previous infant with early onset GBS disease were also
to receive intrapartum antibiotic therapy.
The effect of the guidelines resulted in more hospital drafting formal policies for
antibiotic use, noting a change in the incidence of early onset disease in those institutions
with policies, and increased provider use of one or both strategies.13-16 With these
changes, the incidence of both early-onset and late-onset GBS disease continued to
decline, from an 1.7 cases per 1000 live births in 1993 to 0.45 cases per 1000 live births
in 1999.16,17 However, based on surveillance of several areas in the US, these
recommendations were revised in 2002.18 A summary of these differences include:
1) Universal culture based screening for vaginal and rectal GBS colonization
of all pregnant women between 35 – 37 weeks gestation
2) An update for prophylaxis regimens for penicillin allergic women, with
women stratified into 3 groups:
a) women not at high risk for anaphylaxis receiving cefazolin
b) women at high risk for anaphylaxis with GBS susceptible
to clindamycin or erythromycin receiving these antibiotics
c) women at high risk for anaphylaxis with GBS resistant to
clindamycin or erythromycin, or unknown sensitivities
receiving vancomycin
3) GBS colonized women undergoing elective cesarean sections without
rupture of membranes or labor are recommended to not receive antibiotic
prophylaxis
4) A proposed algorithm for managing patients with threatened preterm
labor, with the recognition that there may be appropriate alternatives
a) GBS negative women do not need antibiotic prophylaxis
b) GBS carriers should receive IV penicillin for  hours, to
be continued for > 48 hours at the discretion of the
physician; antibiotics to be restarted when the patient is in
labor
c) Women without culture results should under vaginal/rectal
cultures, and be started on antibiotics. If cultures are
negative, the antibiotics should be stopped; if the cultures
are positive, recommendations under 4b should be followed
5) Detailed instructions on the appropriate technique for obtaining cultures,
appropriate transport and culturing methods including the use of selective
medias to enhance isolation of GBS, and susceptibility testing with other
antibiotics for patients who are penicillin allergic
6) An updated algorithm for the management of newborns exposed to
antibiotic prophylaxis
The guidelines also stress that many recommendations are unchanged:
1) Penicillin is the first line agent, while ampicillin is an acceptable
alternative
2) Women with unknown culture results in labor should be managed
according to the risk based strategy
3) Women with vaginal and rectal cultures negative for GBS colonization do
not need antibiotic prophylaxis even if obstetrical risk factors develop
4) GBS bacteriuria in the current pregnancy or a history of a previous child
with GBS disease should receive intrapartum antibiotic prophylaxis
5) With the exception of GBS bacteriuria, asymptomatic colonization should
be treated only intrapartum
Although the CDC acknowledges that both risk and culture based strategies worked to
reduce early-onset disease, this shift to a culture based strategy is based series of studies,
including a study by Schrag et al reporting a direct comparison of both strategies and
controlling for risk factors.18,19 Schrag and colleagues reviewed > 5100 deliveries from a
surveillance area containing > 600,000 deliveries between 1998 and 1999. They noted
312 cases of early onset disease, or an incidence rate of 0.5 cases per 1000 live births. Of
these infected infants, 62% did not have clinical risk factors. Similarly, 18% of women
with positive GBS cultures also did not have clinical risk factors. For this group, women
who didn’t receive antibiotics had an incidence rate of 1.3 cases per 1000 live births.
When compared to rate of 5.1 cases per 1000 live births in the era prior to prevention, the
efficacy of preventing early onset GBS is 88%. They also noted that 89% of women in
the screened protocol who had indications for intrapartum antibiotics received
intrapartum antibiotics, compared to only 61% of women in the risk based protocol
receiving antibiotics despite having a risk factor. In summary, their data demonstrates
that more patients in a culture based strategy received antibiotics than those with risk
factors, and that the culture based approach captured more patients at risk by identifying
those women who were colonized but without risk factors.
Consequences of the Revised CDC Guidelines: Concerns for Adverse Reactions to
Antibiotics, Emergence of Resistant GBS, and Rise of Non-GBS Pathogens
While minor reactions can occur as high as 10%, anaphylaxis is a rare event, estimated
incidence of 4 per 10,000 – 100,000. With its use intrapartum, anaphylaxis can be
addressed in a rapid fashion, and its risk is outweighed by the risk of neonatal GBS
disease. 19
At this time, there have no reports of GBS resistant to penicillin or ampicillin. There
reports, however, of erythromycin and/or clindamycin resistant GBS, with ranges of 7 –
25% resistance to erythromycin, and 3 – 15% for clindamycin. While it is recommended
that penicillin sensitive GBS should be considered sensitive to the first generation
cephalosporin cefazolin, there also a report of resistance to the second generation
cephalosporin cefoxitin.
Another concern with the implementation of antibiotic use to combat GBS disease is the
concern for the emergence of antibiotic resistance in other organisms responsible for
neonatal sepsis. While some studies have suggested no increase non-GBS organisms
causing neonatal disease, others have suggested that there are increases in vaginal flora
with resistant organisms, leading to increased exposure to neonates. Others have
suggested caution in interpreting resistance information, but all are in agreement that
continued surveillance is imperative. 18-28
Future Goals
Work by Yancey et al demonstrated that GBS cultures taken 1 – 5 weeks prior to
delivery, starting at 35 – 36 weeks gestation had a positive predictive value of 88%; at 6
weeks or greater, positive antenatal cultures were only 43% positive at the time of
delivery. However, a more recent study noted only a 67% positive predictive value. 23,28
This has led to research to pursue rapid GBS testing to further target the at risk
population. Ultimately, vaccination is seen as the next advance. However, a vaccination
also has concerns to address, such as vaccine duration, distribution and implementation to
the population, and continued surveillance to monitor for changes in serotypes within a
population. 18
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