Prevention of Perinatal Group B Streptococcal Disease


Revised Guidelines from CDC

Prepared by
Stephanie Schrag, D. Phil.
Rachel Gorwitz, M.D.
Kristi Fultz-Butts, M.P.H.
Anne Schuchat, M.D.
Division of Bacterial and Mycotic Diseases
National Center for Infectious Diseases
The material in this report was prepared by the National Center for
Infectious Diseases, James M. Hughes, M.D., Director; Division of Bacterial
and Mycotic Diseases, Mitchell L. Cohen, M.D., Director.
Summary
Group B streptococcus (GBS) remains a leading cause of serious neonatal
infection despite great progress in perinatal GBS disease prevention in the
1990s. In 1996, CDC, in collaboration with other agencies, published
guidelines for the prevention of perinatal group B streptococcal disease
(CDC. Prevention of perinatal group B streptococcal disease: a public health
perspective. MMWR 1996;45[RR-7]:1--24). Data collected after the issuance of
the 1996 guidelines prompted reevaluation of prevention strategies at a
meeting of clinical and public health representatives in November 2001. This
report replaces CDC's 1996 guidelines. The recommendations are based on
available evidence and expert opinion where sufficient evidence was lacking.
Although many of the recommendations in the 2002 guidelines are the same as
those in 1996, they include some key changes:
*        Recommendation of universal prenatal screening for vaginal and rectal GBS
colonization of all pregnant women at 35--37 weeks' gestation, based on
recent documentation in a large retrospective cohort study of a strong
protective effect of this culture-based screening strategy relative to the
risk-based strategy
*       Updated prophylaxis regimens for women with penicillin allergy
*       Detailed instruction on prenatal specimen collection and expanded methods
of GBS culture processing, including instructions on antimicrobial
susceptibility testing
*       Recommendation against routine intrapartum antibiotic prophylaxis for
GBS-colonized women undergoing planned cesarean deliveries who have not
begun labor or had rupture of membranes
*       A suggested algorithm for management of patients with threatened preterm
delivery
*       An updated algorithm for management of newborns exposed to intrapartum
antibiotic prophylaxis
Although universal screening for GBS colonization is anticipated to result
in further reductions in the burden of GBS disease, the need to monitor for
potential adverse consequences of intrapartum antibiotic use, such as
emergence of bacterial antimicrobial resistance or increased incidence or
severity of non-GBS neonatal pathogens, continues, and intrapartum
antibiotics are still viewed as an interim strategy until GBS vaccines
achieve licensure.

Introduction

Group B streptococcus (GBS) emerged as the leading infectious cause of
neonatal morbidity and mortality in the United States in the 1970s (1--4).
Initial case series reported case-fatality ratios as high as 50%. In the
early 1980s, clinical trials demonstrated that administering antibiotics
during labor to women at risk of transmitting GBS to their newborns could
prevent invasive disease in the first week of life (i.e., early-onset
disease) (5). As a result of the collaborative efforts of clinicians,
researchers, professional organizations, parent advocacy groups, and the
public health community in the 1990s, recommendations for intrapartum
prophylaxis to prevent perinatal GBS disease were issued in 1996 by the
American College of Obstetricians and Gynecologists (ACOG) (6) and CDC (7),
and in 1997 by the American Academy of Pediatrics (8).
Those guidelines recommended the use of one of two prevention methods, a
risk-based approach or a culture-based screening approach. Providers using
the risk-based method identify candidates for intrapartum chemoprophylaxis
according to the presence of any of the following intrapartum risk factors
associated with early-onset disease: delivering at <37 weeks' gestation,
having an intrapartum temperature >100.4ºF (>38.0ºC), or rupture of
membranes for >18 hours. The screening- based method recommends screening of
all pregnant women for vaginal and rectal GBS colonization between 35 and 37
weeks' gestation. Colonized women are then offered intrapartum antibiotics
at the time of labor. Under both strategies, women with GBS bacteriuria
during their current pregnancy, or who previously gave birth to an infant
with early-onset GBS disease are candidates for intrapartum antibiotic
prophylaxis.
Before active prevention was initiated, an estimated 7,500 cases of neonatal
GBS disease occurred annually (9). Despite striking declines in disease
incidence coinciding with increased prevention activities in the 1990s, GBS
disease remains a leading infectious cause of morbidity and mortality among
newborns in the United States (10,11). Moreover, since the release of the
1996 guidelines, new data are available to evaluate the effectiveness of the
screening approach relative to the risk-based approach and to resolve some
of the clinical challenges of implementing prevention.
In light of these new data, in November 2001, CDC consulted with multiple
partners to revise the 1996 guidelines for the prevention of perinatal group
B streptococcal disease, using an evidence-based approach where possible and
scientific opinion when sufficient data were lacking ( Table 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#tab1> ). These updated guidelines
replace CDC's 1996 guidelines. They are intended for the following groups:
providers of prenatal, obstetric, and pediatric care; supporting
microbiology laboratories, hospital administrators and managed care
organizations; childbirth educators; public health authorities; and
expectant parents and their advocates.

Differences and similarities between current and previous guidelines

Following are major differences in the new guidelines:
*       Recommendation of universal prenatal culture-based screening for vaginal
and rectal GBS colonization of all pregnant women at 35--37 weeks' gestation
*       Updated prophylaxis regimens for women with penicillin allergy
*       Detailed instruction on prenatal specimen collection and expanded methods
of GBS culture processing, including instructions on susceptibility testing
*       Recommendation against routine intrapartum antibiotic prophylaxis for
GBS-colonized women undergoing planned cesarean deliveries who have not
begun labor or had rupture of membranes
*       A suggested algorithm for management of patients with threatened preterm
delivery
*       An updated algorithm for management of newborns exposed to intrapartum
antibiotic prophylaxis
Although important changes have been instituted, many recommendations remain
the same:
*       Penicillin remains the first-line agent for intrapartum antibiotic
prophylaxis, with ampicillin an acceptable alternative.
*       Women whose culture results are unknown at the time of delivery should be
managed according to the risk-based approach; the obstetric risk factors
remain unchanged (i.e., delivery at <37 weeks' gestation, duration of
membrane rupture >18 hours, or temperature >100.4ºF [>38.0ºC]).
*       Women with negative vaginal and rectal GBS screening cultures within 5
weeks of delivery do not require intrapartum antimicrobial prophylaxis for
GBS even if obstetric risk factors develop (i.e., delivery at <37 weeks'
gestation, duration of membrane rupture >18 hours, or temperature >100.4ºF
[>38.0ºC]).
*       Women with GBS bacteriuria in any concentration during their current
pregnancy or who previously gave birth to an infant with GBS disease should
receive intrapartum antimicrobial prophylaxis.
*       In the absence of GBS urinary tract infection, antimicrobial agents should
not be used before the intrapartum period to treat asymptomatic GBS
colonization.

Background


Early Infancy and Pregnancy-Related Infections

GBS causes severe invasive disease in young infants. The majority of
infections in newborns occur within the first week of life and are
designated early-onset disease. Late-onset infections occur in infants aged
>1 week, with most infections evident in the first 3 months of life. Young
infants with invasive GBS disease usually present with sepsis or pneumonia,
and less often contract meningitis, osteomyelitis, or septic arthritis. The
proportion of infants with meningitis is higher among those with late-onset
infections. When neonatal infections caused by GBS appeared in the 1970s, as
many as 50% of patients died. During the 1990s, the case-fatality ratio of
early- and late-onset disease was 4% (10) because of advances in neonatal
care.
Intrauterine infection of the fetus results from ascending spread of GBS
from the vagina of a colonized woman who is typically asymptomatic. Fetal
aspiration of infected amniotic fluid can lead to stillbirth, neonatal
pneumonia, or sepsis. Infants can also become infected with GBS during
passage through the birth canal, although the majority of infants who are
exposed to the organism through this route become colonized on skin or
mucous membranes but remain asymptomatic.
In pregnant women, GBS can cause clinical infections, but most women have no
symptoms associated with genital tract colonization. Urinary tract
infections caused by GBS complicate 2%--4% of pregnancies (12,13). During
pregnancy or the postpartum period, women can contract amnionitis,
endometritis, sepsis, or rarely, meningitis caused by GBS (14--19).
Fatalities among women with pregnancy-associated GBS disease are extremely
rare.

GBS Colonization

The gastrointestinal tract serves as the natural reservoir for GBS and is
the likely source of vaginal colonization. Vaginal colonization is unusual
in childhood but becomes more common in late adolescence (20). Approximately
10% to 30% of pregnant women are colonized with GBS in the vagina or rectum
(21). GBS colonization can be transient, chronic, or intermittent. Maternal
intrapartum GBS colonization is a major risk factor for early-onset disease
in infants, and vertical transmission of GBS from mother to fetus primarily
occurs after the onset of labor or membrane rupture. However, colonization
early in pregnancy is not predictive of neonatal sepsis (22). Culture
screening of both the vagina and rectum for GBS late in gestation during
prenatal care can detect women who are likely to be colonized with GBS at
the time of delivery and are thus at higher risk of perinatal transmission
of the organism (23).
Classic epidemiologic studies conducted during the 1980s revealed that women
with prenatal GBS colonization were >25 times more likely than women with
negative prenatal cultures to deliver infants with early-onset GBS disease
(24). Researchers used prenatal cultures as the basis for identifying
candidates for intrapartum antimicrobial chemoprophylaxis; clinical trials
identified reductions in vertical transmission of the organism, as measured
by infant colonization (25,26) or by protection against early-onset disease
(5,27). Heavy colonization, defined as culture of GBS from direct plating
rather than only from selective broth, is associated with higher risk for
early-onset disease. GBS identified in clean-catch urine specimens is
considered a surrogate for heavy maternal colonization and also is
associated with a higher risk for early-onset GBS disease (12,13); it has
been included among indications for intrapartum antibiotic prophylaxis.

GBS Culture-Based Screening Methods

Numerous studies have documented that the accuracy of prenatal screening
cultures in identifying intrapartum colonization status can be enhanced by
careful attention to the timing of cultures, the anatomic sites swabbed, and
the precise microbiologic methods used for culture and detection of
organisms ( Box 1 <http://www.cdc.gov/mmwr/preview/mmwrhtml/#box1> ).
Collection of cultures between 35 and 37 weeks' gestation is recommended to
improve the sensitivity and specificity of detection of women who remain
colonized at the time of delivery (23,28). Swabbing both the lower vagina
and rectum (i.e., through the anal sphincter) increases the yield
substantially compared with sampling the cervix or sampling the vagina
without also swabbing the rectum (29). Studies have indicated that when
women in the outpatient clinic setting collect their own screening
specimens, with appropriate instruction, GBS yield is similar to when
specimens are collected by a health-care provider (30). Although swabbing
both sites is recommended and use of two swabs can be justified, both swabs
should be placed in a single broth culture medium because the site of
isolation is not important for clinical management and laboratory costs can
thereby be minimized. Because vaginal and rectal swabs are likely to yield
diverse bacteria, use of selective enrichment broth is recommended ( Box 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#box1> ) to maximize the isolation
of GBS and avoid overgrowth of other organisms. When direct agar plating is
used instead of selective enrichment broth, as many as 50% of women who are
GBS carriers have false-negative culture results (31).

Additional Risk Factors for Perinatal GBS Disease

In addition to colonization with GBS, other factors increase the risk for
early-onset disease. These include gestational age <37 completed weeks,
longer duration of membrane rupture, intraamniotic infection, young maternal
age, black race, Hispanic ethnicity, and low maternal levels of anticapsular
antibody (32--37). In a 1985 report of predictors of early-onset disease
(24), women with gestation <37 weeks, membrane rupture of >12 hours, or
intrapartum temperature >99.5ºF (37.5ºC) had 6.5 times the risk of having an
infant with early-onset GBS disease compared with women with none of those
factors. Of note, women who had one of these risk factors but who had
negative prenatal screening cultures were at relatively low risk for
early-onset GBS disease (attack rate 0.9 per 1,000 births) compared with
women who were colonized prenatally but had none of the risk factors (attack
rate 5.1 per 1,000 births) (24). In a risk-based strategy promoted during
the 1990s as an alternative to prenatal culture-based screening approaches,
prematurity (gestation <37 weeks), intrapartum fever (temperature >100.4ºF
or 38ºC), or duration of membrane rupture >18 hours were used as clinical
indications for intrapartum prophylaxis. Previous delivery of an infant with
invasive GBS disease may increase the risk of early-onset disease in
subsequent deliveries (38,39), and intrapartum treatment of such women in
subsequent pregnancies has been promoted. By contrast, colonization with GBS
in a previous pregnancy is not considered an indication for intrapartum
prophylaxis in subsequent pregnancies; rather, women require evaluation for
prenatal colonization in each pregnancy. Because colonization is transient,
the predictive value of culture-based screening is too low to be clinically
useful when performed more than 5 weeks before delivery (28); thus, many
women with GBS colonization during one pregnancy will no longer be colonized
during subsequent pregnancies.

Impact and Implementation of the 1996 Guidelines


Declines in Perinatal GBS Disease Incidence in the Era of Chemoprophylaxis

Before the widespread use of intrapartum antibiotics, the incidence of
invasive neonatal GBS disease ranged from 2 to 3 cases per 1,000 live births
(9,40). Active, population-based surveillance in selected states in 1990,
when GBS prevention was still rarely implemented, projected an incidence of
1.8 cases per 1,000 live births in the United States (early-onset disease:
1.5/1,000; late-onset: 0.35/1,000) (9).
Coinciding with active prevention efforts in the 1990s, the incidence of
early-onset disease declined by 70% to 0.5 cases per 1,000 live births in
1999 ( Figure 1 <http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig1> ).
Projections from active surveillance data for 1999 from the Active Bacterial
Core surveillance/Emerging Infections Program Network (ABCs)(41) estimate
that intrapartum antibiotics prevented nearly 4,500 early-onset cases and
225 deaths that year (10,11). Other countries that have adopted perinatal
GBS disease prevention guidelines similar to the United States have seen
comparable declines in early-onset disease incidence (42--44). Recent
estimates of early-onset disease incidence in the United States suggest a
slight increase in incidence from 1999 to 2000, consistent with a plateau in
the impact of prevention efforts ( Figure 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig1> ).
The incidence of invasive GBS infections among pregnant women in the United
States declined by 21% from 0.29 per 1,000 live births in 1993 to 0.23 in
1998 (10), suggesting that increased use of intrapartum antibiotics also
prevented some cases of maternal GBS amnionitis and endometritis. In
contrast, the rate of late-onset disease remained fairly constant throughout
the 1990s ( Figure 1 <http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig1> ).
Although intrapartum chemoprophylaxis for women with heavy GBS colonization
may prevent a portion of late-onset disease, the stable incidence of
late-onset disease during a period when use of intrapartum antibiotics was
increasing suggests that this intervention is not effective against
late-onset disease.

Implementation of Chemoprophylaxis Strategies After the Release of the 1996
Guidelines

Declines in perinatal GBS disease incidence in the 1990s suggest that
prevention strategies have been implemented successfully. Several studies
have explored directly the challenges of implementation and extent of
compliance with recommendations. Surveys of prenatal care providers in
Connecticut and Minnesota in 1998 found that over 80% had a GBS prevention
policy (Connecticut, 95%; Minnesota, 85%) (45). In Minnesota, family
physicians were less likely to have a policy than were
obstetrician/gynecologists and certified nurse midwives (45). A national
survey of ACOG members in 2000 found that 98% of respondents had a GBS
prevention policy; 75% of respondents reported using a version of the
culture-based screening approach (46). Providers in all three surveys scored
well on questions about their knowledge of the screening and risk-based
strategies (45,46).
In hospitals that established or revised policies for GBS prevention shortly
after the release of the 1996 guidelines, rates of early-onset GBS disease
declined by 1997 (47). By 1999, although only 63% of hospitals in a
multistate survey of hospitals in the ABCs areas had a formal GBS prevention
policy (48), having a hospital policy was no longer associated with changes
in incidence of GBS disease, likely because a high proportion of individual
practitioners had adopted policies by this time.
Several studies of single institutions or health maintenance organizations
have evaluated adherence of hospital personnel to GBS guidelines ( Table 2
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#tab2> ). Among hospitals with a
risk-based policy, intrapartum antibiotics were administered in 40%--80% of
preterm deliveries or deliveries with prolonged rupture of membranes ( Table
2 <http://www.cdc.gov/mmwr/preview/mmwrhtml/#tab2> ) (49--53). Among
hospitals with a culture-based screening policy, close to 90% of delivering
women had documented GBS screening, and close to 90% of GBS-positive women
received intrapartum antibiotics ( Table 2
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#tab2> ) (42,51,54--59).
Correct laboratory processing of culture specimens ( Box 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#box1> ) plays a critical role in
successful implementation of the screening policy. A survey of clinical
laboratories in selected counties of three states in 1997--1998 found that
only a proportion of laboratories were using the recommended selective broth
media to process GBS cultures (Georgia, 39% of laboratories; Minnesota, 42%;
Connecticut, 62%), suggesting that this may be an area in need of
improvement (31).
Although surveys of practitioners and laboratories and reports from single
hospitals help monitor implementation of GBS prevention guidelines, a recent
CDC-sponsored review of labor and delivery records in selected counties of
eight states in the ABCs areas in 1998 and 1999 sheds light on actual
provider practices 2 to 3 years after the release of the 1996 guidelines
(60). In this population, GBS screening was documented in 52% of deliveries,
although this varied widely, from 24% in selected counties of Oregon to 70%
in Maryland. Among screened women, 24% were GBS positive, consistent with
carriage rates reported in earlier studies; 89% of GBS- positive women
received intrapartum antibiotics. The median time of GBS culture collection
was at 35.6 weeks' gestation, consistent with the recommendation of 35--37
weeks' gestation. Among unscreened women, 24% had at least one intrapartum
risk factor; however, only 61% of women with at least one risk factor
received intrapartum antibiotics. Preterm delivery (<37 weeks' gestation)
was the most common indication for which intrapartum antibiotics were not
administered. Thus, this multistate record review confirmed trends in
adherence identified in reports from single hospitals ( Table 2
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#tab2> ).

Maximizing Prevention by Chemoprophylaxis


Effectiveness of the Risk-Based Approach Versus the Screening Approach

Despite dramatic declines in GBS incidence in the United States in the
1990s, GBS remains a leading cause of newborn morbidity and mortality,
resulting in an estimated 1,600 early-onset cases and 80 deaths annually.
Although alternatives to intrapartum antibiotics such as a vaccine may
become available in the future, intrapartum chemoprophylaxis remains the
most effective available intervention against perinatal GBS disease.
However, debate about the most effective strategy for identifying candidates
for intrapartum chemoprophylaxis continues.
When the 1996 guidelines were issued, data regarding the relative
effectiveness of the risk-based and screening approaches were not available.
Theoretical predictions based on population estimates of the proportion of
early-onset GBS cases without obstetric risk factors (approximately 45% in
the preprevention era [61]) suggested that the screening-based approach
would lead to greater declines in disease incidence than the risk-based
approach (61,62). However, because implementation of the risk-based approach
has been viewed as simpler than the screening-based approach, which requires
correct specimen collection at the prenatal clinic, appropriate laboratory
processing, and timely reporting of results to delivery staff, the actual
effectiveness of these strategies is unknown. Consequently, since 1996, both
approaches have been recommended as equally acceptable pending further data
(6--8).
Although observational data are now available suggesting that each strategy
can lead to reduced incidence of early-onset GBS disease (49,50,63--65), the
strategies have not been directly compared by clinical trial because of the
large sample size required. A series of single hospital analyses finding
benefits of screening over the risk-based approach (51,56,59,66) were
limited by sequential use of the strategies and inability to control for
potential confounders. A recent CDC-sponsored multistate study provided the
first large-scale direct comparison of the strategies (60). By incorporating
population-based surveillance for early-onset GBS disease into a sample
survey of a population of over 600,000 live births, this analysis found that
the screening approach was >50% more effective than the risk-based approach
at preventing perinatal GBS disease.
The protective effect of the screening approach was robust and persisted
after controlling for risk factors associated with early-onset GBS disease
(e.g., preterm delivery, prolonged membrane rupture, young maternal age,
black race). The benefit of screening stemmed from two main factors. First,
by identifying GBS-colonized women who did not present with obstetric risk
factors, screening reached more of the population at risk than did the
risk-based approach. Among the cohort of screened women, 18% of all
deliveries were to mothers who were colonized with GBS but did not have
obstetric risk factors. The efficacy of intrapartum antibiotics in
preventing early-onset GBS disease among infants in this cohort was close to
90%, suggesting that chemoprophylaxis of GBS-positive women without
obstetric risk factors resulted in significant prevention of early-onset
disease.
Women who were GBS positive in the screening cohort were also more likely to
receive intrapartum antibiotics than were women with obstetric risk factors
in the risk cohort. Although improvements in implementation of the
risk-based approach would lead to further decline in disease, this would not
be as great as with universal screening (60).
Finally, because the effectiveness of screening in this study was based on
actual implementation of this strategy in clinical practice in 1998 and
1999, further improvements in screening implementation (e.g., improvements
in specimen collection and the methods used for processing cultures) are
expected to result in further benefits.

Rationale for a Universal Prenatal Screening Strategy to Detect GBS Status

The new availability of category II evidence ( Table 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#tab1> ) for a large protective
effect of prenatal GBS screening compared with the risk-based approach
provides the foundation for a recommendation of universal prenatal GBS
screening ( Figure 2 <http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig2> ).
Statewide prevention activities in some ABCs areas further demonstrate that
culture-based screening can be successfully implemented in a variety of
settings and institutions. For example, a health department-led survey of
clinical laboratories in Connecticut followed by rapid feedback of survey
results found that the proportion of laboratories in Connecticut using the
correct media for processing GBS screening cultures increased from 62% in
1997 to 92% in 1998 (67) and 100% in 2000. Moreover, coinciding with an
active prevention campaign launched by the state health department that
advocated the screening-based approach, the incidence of early-onset GBS
disease in Connecticut declined from 0.6 cases per 1,000 live births in 1996
(68) to 0.2 cases per 1,000 live births in 1999.
From the standpoint of implementation, universal screening has two
additional benefits over the dual recommendations of 1996. Communication of
the public health messages associated with a single strategy is simpler than
communicating and educating about multiple strategies. Additionally,
screening has clear indicators that facilitate evaluation of implementation
(e.g., documentation of GBS test, timing of test, rates of GBS positivity)
(58) compared with the risk-based approach, in which evidence of prevention
implementation cannot be assessed for approximately 75% of deliveries
because they have no intrapartum risk factors.
Cost-effectiveness analyses of the screening- and risk-based strategies
(62,69--73) have indicated that although the initial costs associated with
specimen collection and processing make the screening strategy more
expensive than the risk-based approach, the overall cost savings due to
disease prevention do not differ importantly between strategies.
Additionally, multistate review of labor and delivery records in 1998 and
1999 suggests that perfect implementation of the screening- or risk-based
strategies will result in a comparable proportion of deliveries in which
women receive intrapartum antibiotic prophylaxis for GBS (24% for both
strategies) (60,74). Thus, the strategies cannot be distinguished in terms
of the proportion of deliveries that will be exposed to intrapartum
antibiotics.

Adverse Effects and Unintended Consequences of Chemoprophylaxis

Potential adverse or unintended effects of GBS prevention efforts that have
raised concern include allergic or anaphylactic reactions to agents used for
intrapartum antibiotic prophylaxis, emergence of GBS strains resistant to
standard therapies, and increasing incidence of serious neonatal infections
caused by pathogens other than GBS, including antimicrobial-resistant
strains. Because of the increasing emergence of bacterial resistance to
antimicrobial agents in both nosocomial and community settings, assessment
of the impact and continued effectiveness of interventions based on
antimicrobial prophylaxis is critical.

Antibiotic Allergies Including Anaphylaxis

Anaphylaxis associated with GBS chemoprophylaxis occurs but is sufficiently
rare that any morbidity associated with anaphylaxis is greatly offset by
reductions in the incidence of maternal and neonatal invasive GBS disease.
Anaphylaxis-related mortality is likely to be a rare event since women
receiving intrapartum antibiotics will be in hospital settings where rapid
intervention is readily available. Estimates of the rate of anaphylaxis
caused by penicillin range from 4/10,000 to 4/100,000 recipients.
Additionally, as many as 10% of the adult population have less severe
allergic reactions to penicillin (75). Anaphylaxis associated with GBS
prophylaxis was reported in the early 1990s (76); since the release of the
1996 guidelines, an additional report of a nonfatal case of anaphylaxis
associated with GBS chemoprophylaxis has been published (77). In a CDC
multistate sample of over 5,000 live births, a single, nonfatal anaphylactic
reaction was noted among the 27% of deliveries in which intrapartum
antibiotics were administered (60). In that case, a single dose of
penicillin was administered approximately 4 hours before a preterm cesarean
delivery, and an anaphylactic reaction occurred shortly after the mother
received a single dose of a cephalosporin following umbilical cord clamping.

Resistance in GBS

GBS isolates with confirmed resistance to penicillin or ampicillin have not
been observed to date (78--83). Penicillin remains the agent of choice for
intrapartum antibiotic prophylaxis. Ampicillin is an acceptable alternative,
but penicillin is preferred because it has a narrower spectrum of
antimicrobial activity and may be less likely to select for resistant
organisms. The efficacy of both penicillin (27) and ampicillin (5) as
intrapartum agents for the prevention of early-onset neonatal GBS disease
has been demonstrated in clinical trials. Although the intramuscular route
of administration for penicillin has been evaluated (25), intravenous
administration is the only route of administration recommended for
intra-partum chemoprophylaxis to prevent perinatal GBS disease, regardless
of the antimicrobial agent used, because of the higher intraamniotic
concentrations achieved with this method.
In contrast, the proportions of GBS isolates with in vitro resistance to
clindamycin and erythromycin have increased since 1996. The prevalence of
resistance among invasive GBS isolates in the United States and Canada
ranged from 7% to 25% for erythromycin and from 3% to 15% for clindamycin in
reports published between 1998 and 2001(79--81,84). Resistance to
erythromycin is frequently but not always associated with clindamycin
resistance. Resistance of GBS isolates to cefoxitin, a second-generation
cephalosporin sometimes used as a component of broad-spectrum coverage for
chorioamnionitis, has also been reported (85); cefoxitin resistance has
similarly been observed among invasive GBS isolates collected from 1996 to
2000 as part of CDC's active surveillance. Whether in vitro resistance of
GBS has direct clinical implications remains unclear (86). Despite emerging
resistance to some drug classes, minimum inhibitory concentrations of
cefazolin, a first-generation cephalosporin available in an intravenous
formulation, were low (<0.5 µg/ml) among a sample of invasive U.S. isolates
from 1996 to 2000 (87), suggesting that GBS isolates are currently
susceptible to this agent. Although NCCLS guidelines do not specify
susceptibility breakpoints for cefazolin, they recommend that all isolates
susceptible to penicillin be considered susceptible to cefazolin (88).
In light of the increasing prevalence of resistance to clindamycin,
erythromycin, or both, recommended strategies for providing intrapartum
antibiotic prophylaxis to penicillin-allergic women are updated ( Box 2
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#box2> ). Because the efficacy of
recommended alternatives to penicillin or ampicillin has not been measured
in controlled trials, and because some of the recommended alternatives have
a broad spectrum of activity and may be more complicated and costly to
administer, verification of a reported history of penicillin allergy is
important. Patients with reported penicillin allergy should then be assessed
to determine their risk for anaphylaxis. Persons at high risk for
anaphylaxis are those who have had immediate hypersensitivity reactions to
penicillin (e.g., anaphylaxis, angioedema, or urticaria) or who have a
history of asthma or other conditions that would make anaphylaxis more
dangerous (89,90). An estimated 10% of persons with penicillin allergy also
have immediate hypersensitivity reactions to cephalosporins (90). Among
penicillin-allergic women not at high risk for anaphylaxis, cefazolin,
because of its narrow spectrum of activity and ability to achieve high
intraamniotic concentrations, is the agent of choice for intrapartum
chemoprophylaxis.
For penicillin-allergic women at high risk for anaphylaxis, testing of GBS
isolates from prenatal screening for susceptibility to clindamycin and
erythromycin is recommended if feasible ( Box 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#box1> ). One of these agents
should be employed for intrapartum GBS prophylaxis if the screening isolate
is susceptible to both agents.
Vancomycin should be reserved for penicillin-allergic women at high risk for
beta-lactam anaphylaxis when clindamycin or erythromycin are not options
because of in vitro resistance or unknown susceptibility of a prenatal
isolate. Vancomycin use is generally restricted because of emerging
vancomycin resistance among some gram-positive organisms (e.g.,
vancomycin-resistant enterococcus and vancomycin-resistant Staphylococcus
aureus). An estimated 13.8 million hospitalized patients received vancomycin
therapy in 1998 (91). If penicillin allergy occurs in approximately 10% of
adults, and 25% of parturients are colonized with GBS prenatally,
approximately 100,000 of the 4 million annual deliveries would require
prophylaxis with vancomycin in the absence of clindamycin and erythromycin
susceptibility testing of GBS prenatal isolates. This represents a 7%
increase in the number of patients exposed to vancomycin. The total grams of
vancomycin used annually would increase by less than 1% if all
penicillin-allergic colonized women received vancomycin prophylaxis.

Increased Incidence or Resistance in Non-GBS Pathogens

Decreases in the incidence of early-onset GBS sepsis have not usually been
accompanied by increases in incidence of early-onset sepsis caused by other
pathogens, including those that are antibiotic resistant. Most studies,
including population-based multicenter studies, have found stable (59,92,93)
or decreasing (43) rates of non-GBS early-onset sepsis during a period of
increasing use of intrapartum antibiotic prophylaxis for GBS ( Table 3
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#tab3> ). This is true both for
overall non-GBS sepsis and for neonatal sepsis caused by Escherichia coli,
the second leading bacterial cause of neonatal sepsis after GBS (93,94).
Some single hospital studies have found increased rates or case counts of
neonatal sepsis caused by E. coli, gram-negative organisms in general, or
ampicillin-resistant pathogens (64,94,95), but these increases appear to be
limited to preterm or low-birth-weight infants. An increasing proportion of
E. coli neonatal sepsis cases caused by ampicillin-resistant organisms was
observed in two studies (92,94), but again was limited to preterm or
low-birth-weight infants. Furthermore, the proportion of community-acquired
E. coli infections that are ampicillin resistant has been increasing (96),
suggesting that trends in antimicrobial resistance should not be attributed
to GBS prophylaxis.
An association between intrapartum antibiotic exposure and ampicillin
resistance in cases of E. coli or other non-GBS early-onset sepsis has been
observed in several studies (36,94,95, 97,98). These reports established
that infections caused by antibiotic-resistant organisms were more
frequently preceded by antibiotic use than were infections caused by
susceptible organisms, and that more doses or longer duration of
anti-biotics before delivery increased the chance that a neonatal infection,
if it occurred, would be caused by an antibiotic-resistant organism. These
studies, however, were not designed to assess whether intrapartum antibiotic
use increased the rate of antibiotic-resistant infections. Moreover,
findings from these studies are consistent with intrapartum antibiotics
inducing resistance among initially susceptible organisms, but also with
intrapartum antibiotics preventing antibiotic-susceptible infections and
having no impact on antibiotic-resistant infections, resulting in a net
decrease in the total rate of infection.
The reported increases in antibiotic-resistant early-onset infections in a
few studies are not of sufficient magnitude to outweigh the benefits of
intrapartum antibiotic prophylaxis to prevent perinatal GBS disease.
However, to assure early detection of increases in the rate of disease or
deaths caused by organisms other than GBS, continued surveillance of
neonatal sepsis caused by organisms other than GBS is needed.

Clinical Challenges


GBS Bacteriuria During Pregnancy

The presence of GBS bacteriuria in any concentration in a pregnant woman is
a marker for heavy genital tract colonization. Therefore, women with any
quantity of GBS bacteriuria during pregnancy should receive intrapartum
chemoprophylaxis. Vaginal and rectal screening at 35--37 weeks is not
necessary for these women. GBS can cause both symptomatic and asymptomatic
urinary tract infections, which should be diagnosed and treated according to
current standards of care for urinary tract infections in pregnancy. Women
with GBS urinary tract infections during pregnancy should receive
appropriate treatment at the time of diagnosis as well as intrapartum GBS
prophylaxis. Laboratory personnel should report any presence of GBS
bacteriuria in specimens obtained from pregnant women. For this to occur,
labeling of urine specimens to indicate that they were obtained from a
pregnant woman is imperative.

Planned Cesarean Delivery

Because GBS can cross intact amniotic membranes, a cesarean delivery does
not prevent mother-to-child transmission of GBS. Moreover, because cesarean
delivery itself is associated with health risks for mother and newborn, GBS
colonization of the mother is not an indication for cesarean delivery, and
cesarean delivery should not be used as an alternative to intrapartum
antibiotic prophylaxis for GBS prevention.
However, although a risk does exist for transmission of GBS from a colonized
mother to her infant during a planned cesarean delivery performed before
onset of labor in a woman with intact amniotic membranes, it is extremely
low, based on a retrospective study at a single hospital (99) and a review
of CDC active, population-based surveillance data from the 1990s. Thus, in
this specific circumstance, in which the risk for disease is extremely low,
the individual risks to a mother and her infant from receiving intrapartum
antibiotic prophylaxis may balance or outweigh the benefits. Intrapartum
antibiotic prophylaxis to prevent perinatal GBS disease is, therefore, not
recommended as a routine practice for women undergoing planned cesarean
deliveries in the absence of labor or amniotic membrane rupture, regardless
of the GBS colonization status of the mother. Patients expected to undergo
planned cesarean deliveries should nonetheless still undergo routine vaginal
and rectal screening for GBS at 35--37 weeks because onset of labor or
rupture of membranes may occur before the planned cesarean delivery. In rare
situations in which patients or providers opt for intrapartum prophylaxis
before planned cesarean deliveries, administration of antibiotics at the
time of incision rather than at least 4 hours before delivery may be
reasonable (100).

Threatened Preterm Delivery

Because preterm (at <37 weeks' gestation) delivery is an important risk
factor for early-onset GBS disease, and because timing of delivery can be
difficult to assess, management of intrapartum prophylaxis for women with
threatened preterm delivery can be challenging. Assessing the need for
intrapartum prophylaxis for these women can also be difficult because GBS
screening is recommended at 35 to 37 weeks' gestation, and culture results
are not always available when labor or rupture of membranes occur preterm.
A suggested approach to GBS chemoprophylaxis in the context of threatened
preterm delivery is outlined ( Figure 3
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig3> ). Because insufficient
data are available to suggest a single course of management, other
management strategies developed by individual physicians or institutions may
be appropriate alternatives. The algorithm suggests that if GBS screening
culture results from the current pregnancy are not available and if onset of
labor or rupture of membranes occurs before 37 weeks' gestation with a
substantial risk for preterm delivery (as assessed by the woman's
health-care provider), intrapartum antibiotic prophylaxis for GBS should be
provided pending culture results. For women not yet screened for GBS, a
vaginal and rectal specimen for GBS culture should be obtained if time
permits. If a negative culture result within the previous 4 weeks is on
record, or if the clinician determines that labor can be successfully
arrested and preterm delivery averted, antibiotics for GBS prophylaxis
should not be initiated. Because recent clinical trials suggest that
antibiotics administered during pregnancy may be associated with adverse
neonatal outcomes, such as necrotizing enterocolitis or increased need for
supplementary oxygen, without evident benefit for preterm labor or preterm
premature rupture of membranes (101,102), antibiotics should be reserved for
instances in which a significant risk for preterm delivery is present.
No data are available on which to recommend a specific duration of
antibiotic administration for GBS-positive women with threatened preterm
delivery when delivery is successfully postponed. Management strategies
based on scientific opinion have been proposed (100); without further data,
the management approach is left to the discretion of the individual
provider. Regardless of management strategy chosen, these women should also
receive intrapartum antibiotic chemoprophylaxis for GBS when labor likely to
proceed to delivery occurs or recurs.
Previous data (28) suggest that the accuracy of GBS screening cultures in
predicting colonization status at delivery is greatest if the cultures are
collected within 5 weeks of delivery. Therefore, if a woman is screened
early for GBS because of threatened preterm delivery but does not deliver
within 4 weeks, she should be screened again for GBS colonization and
managed according to the result of the repeated screening culture ( Figure 3
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig3> ).

Obstetric Procedures for GBS-Colonized Women

Questions have arisen regarding whether certain obstetric procedures, such
as digital vaginal examinations, intrauterine fetal monitoring, and membrane
stripping or sweeping to hasten the onset of labor, should be performed on
GBS-colonized women. Asymptomatic GBS colonization is not an indication to
perform any of these procedures. When such procedures are indicated for
other reasons, evidence is currently not sufficient to recommend that
particular procedures should be avoided because of increased risk of
peripartum or perinatal infection. Although some obstetric procedures
(frequent vaginal examinations after onset of labor or membrane rupture
[17,36,103--105], intrauterine fetal monitoring [104,106,107], and
mechanical cervical ripening devices [108]) have been significantly
associated with peripartum or perinatal infectious outcomes, most studies to
date have been limited by an inability to randomly allocate women to
treatment groups and have yielded conflicting results. Moreover, because
many studies were performed before GBS prevention was widely implemented,
GBS colonization status was often not known and intrapartum chemoprophylaxis
was less common. A meta-analysis of available studies examining the use of
membrane stripping among women of undetermined GBS colonization status (109)
found no significant increases in overall peripartum or perinatal infection
rates among women who underwent this procedure and their infants compared
with those who did not.

Management of Newborns Exposed to Intrapartum Prophylaxis

On the basis of information available since the publication of the 1996
guidelines, a modified approach for empiric management of newborns born to
women who receive intrapartum antibiotics to prevent early-onset GBS disease
or to treat suspected chorioamnionitis is provided ( Figure 4
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig4> ). Variations in the
algorithm that incorporate individual circumstances or institutional
preferences may be appropriate. The modified approach contains the following
changes:
*       If a woman receives intrapartum antibiotics for treatment of suspected
chorioamnionitis, her newborn should have a full diagnostic evaluation and
empiric therapy pending culture results, regardless of clinical condition at
birth, duration of maternal antibiotic therapy before delivery, or
gestational age at delivery (110). Empiric therapy for the infant should
include antimicrobial agents active against GBS as well as other organisms
that might cause neonatal sepsis (e.g., ampicillin and gentamicin).
*       When clinical signs in the infant suggest sepsis, a full diagnostic
evaluation should include a lumbar puncture, if feasible. Blood cultures can
be sterile in as many as 15% of newborns with meningitis (111--113), and the
clinical management of an infant with abnormal cerebrospinal fluid (CSF)
findings differs from that of an infant with normal CSF. If a lumbar
puncture has been deferred for a neonate receiving empiric antibiotic
therapy, and the therapy is continued beyond 48 hours because of clinical
instability, CSF should be obtained for cell count, glucose, protein, and
culture.
*       In addition to penicillin or ampicillin, initiation of intrapartum
antibiotic prophylaxis with cefazolin at least 4 hours before delivery can
be considered adequate, based on achievable amniotic fluid concentrations of
cefazolin (114). Although other agents may be substituted for penicillin if
the woman has a history of penicillin allergy (Box 2), the effectiveness of
these agents in preventing early-onset GBS disease has not been studied and
no data are available to suggest the durations before delivery of these
regimens that can be considered adequate.
*       Based on the demonstrated effectiveness of intrapartum antibiotic
prophylaxis at preventing early-onset GBS disease (65) and data indicating
that clinical onset occurs within the first 24 hours of life in over 90% of
infants who contract early-onset GBS disease (115), hospital discharge as
early as 24 hours after delivery may be reasonable under certain
circumstances. Specifically, a healthy-appearing infant who is >38 weeks'
gestation at delivery and whose mother received >4 hours of intrapartum
antibiotic prophylaxis before delivery may be discharged home as early as 24
hours after delivery, assuming that other discharge criteria have been met
and that a person able to comply fully with instructions for home
observation will be present. A key component of following instructions is
the ability of the person observing to communicate with health-care
providers by telephone and to transport the child promptly to an appropriate
health-care facility if clinical signs of sepsis develop. If these
conditions are not met, the infant should remain in the hospital for at
least 48 hours of observation and until criteria for discharge are achieved.
Investigations since 1996 lend additional support to several components of
the algorithm. A retrospective study of over 250,000 live births (115) found
that administration of intrapartum antibiotic prophylaxis did not change the
clinical spectrum of neonatal illness or delay the onset of clinical signs
among infants who contracted GBS disease despite prophylaxis. Thus, the
algorithm targets infants born to mothers with suspected chorioamnionitis
and infants with signs of sepsis for full diagnostic evaluation and empiric
therapy. Also, new evidence indicates that 4 or more hours of intrapartum
ampicillin or penicillin administered according to recommended dosing
intervals ( Box 2 <http://www.cdc.gov/mmwr/preview/mmwrhtml/#box2> )
significantly reduces vertical transmission of GBS (116) and risk of
early-onset GBS disease (65). Thus, although the American Academy of
Pediatrics 1997 guidelines suggested 2 or more doses as a threshold for
prophylaxis adequacy for infants >35 weeks' gestation (8), the revised
algorithm continues to use >4 hours, administered according to recommended
dosing intervals, as the benchmark for optimal prevention of early-onset GBS
disease. Moreover, a review of pregnancies at a West Coast health
maintenance organization using the GBS culture-based screening strategy
found that among women who received intrapartum antibiotic prophylaxis, 50%
received prophylaxis at least 4 hours before delivery, whereas only 14%
received at least 2 doses of intrapartum antibiotics (58); this indicates
that duration of prophylaxis is a more practical target than number of
doses, in addition to being associated with efficacy.
One objective of developing an algorithm for management of newborns was to
minimize unnecessary evaluation and antimicrobial treatment of infants whose
mothers received intrapartum prophylaxis. Although early provider surveys
indicated that pediatricians and neonatologists were more likely to conduct
diagnostic evaluations and initiate empiric anti-biotics for an infant whose
mother received intrapartum antibiotic prophylaxis (117--119), more recent
data indicate that implementation of GBS prevention strategies has not
resulted in increased use of health services for neonates (120), and in some
circumstances, when GBS prophylaxis increased a decrease occurred in the
proportion of neonates who received laboratory evaluations (58).
Intrapartum antibiotic prophylaxis is the method of choice for preventing
neonatal early-onset GBS disease. In the event that intrapartum antibiotics
are not given despite an indication (e.g., delivery occurred precipitously
before antibiotics could be administered to a GBS-positive woman),
sufficient data are not available on which to recommend a single management
strategy for the newborn. Some centers provide intramuscular penicillin to
asymptomatic infants within 1 hour of birth, based on results of
observational studies showing declines in early-onset GBS disease coincident
with a policy of universal administration of intramuscular penicillin to all
newborns (121).

Future Prevention Technology


Rapid Tests to Detect GBS Colonization Status

Rapid tests for detection of GBS colonization at the time of onset of labor
or rupture of amniotic membranes might obviate the need for prenatal
culture-based screening if their sensitivity and specificity are comparable
to culture in selective broth media and they yield results rapidly enough to
permit administration of adequate intrapartum antibiotic prophylaxis to
women detected as carriers. Currently available rapid tests detect GBS
antigen from swab specimens. These tests are insufficiently sensitive to
detect light colonization, and therefore are not adequate to replace
culture-based prenatal screening (122,123) or to use in place of the
risk-based approach when culture results are unknown at the time of labor.
An adequate rapid intrapartum test must be as sensitive as culture
(minimally 85% compared with culture of vaginal and rectal swabs inoculated
into selective broth media), rapid so that results are available to
clinicians in time for antibiotics to be given before delivery, and
convenient for integration into routine laboratory use. Even a highly
sensitive rapid detection test would not be adequate if results were not
available to clinicians 24 hours a day, 7 days a week. Alternatives to
culturing vaginal and rectal swab specimens at 35--37 weeks' gestation using
recommended procedures should be validated to show sensitivity similar to
recommended culture methods.
A rapid intrapartum test possessing the attributes described above offers
the advantage of ascertaining GBS colonization status before delivery among
women who have had no pre-natal care. Although such tests might initially be
introduced selectively in certain facilities with sufficient demand and
capability, a general recommendation for their use would require the
capacity for effective implementation in a wide range of hospital settings.
Drawbacks of rapid tests include delays in administration of intrapartum
antibiotic prophylaxis while test results are pending and lack of an isolate
for susceptibility testing, which is of particular concern for
penicillin-allergic women. Additionally, until rapid tests are universally
used, missed opportunities for GBS screening may occur among women who
receive prenatal care at institutions relying on intrapartum rapid tests but
who deliver at institutions where such tests are not yet available.
In a study of 112 pregnant women at an academic hospital in Quebec, a new,
not yet commercially available fluorogenic polymerase chain reaction assay
was 97% sensitive and 100% specific when compared with vaginal and rectal
cultures collected at admission for delivery. Test results in this study
were available within 45 minutes of specimen collection (124). Further
studies are needed to determine whether this type of test can be adapted for
use outside the research setting. If appropriate techniques for rapid
detection of GBS become commercially available, they may be integrated into
the currently recommended screening strategy.

Vaccines To Prevent GBS Disease

Improved use of intrapartum antimicrobial prophylaxis has resulted in a
substantial reduction in early-onset GBS disease, but it is unlikely to
prevent most late-onset neonatal infections, GBS-related stillbirths, or
prematurity, and does not address GBS disease in nonpregnant adults.
Immunization of women during or before pregnancy could prevent peripartum
maternal disease and protect infants from perinatally acquired infection by
transplacental transfer of protective IgG antibodies (125,126). This would
eliminate the need for prenatal GBS screening and intrapartum antimicrobial
prophylaxis, along with associated costs and concerns regarding the
potential adverse effects of intrapartum antibiotic use discussed
previously.
Serotype-specific antibodies to GBS capsular polysaccharide, although rare
in populations of unvaccinated women, have been shown to protect against
disease (32,127). Phase 1 and 2 clinical trials among healthy, nonpregnant
adults of monovalent protein-conjugate vaccines containing capsular
polysaccharide antigens of GBS disease-associated serotypes have shown these
vaccines to be well tolerated and immunogenic (128--130). One challenge of
demonstrating vaccine efficacy in preventing early-onset GBS disease is that
the sample size required for clinical trials may be prohibitively large.
Identification of surrogate immunologic measures of clinical efficacy may
thus be important (131,132). Surrogate information on clinical vaccine
efficacy may also be gained by measuring the impact of multivalent conjugate
vaccines on vaginal GBS colonization (132,133).
Anticipated difficulties in making vaccine available to pregnant women have
resulted in consideration of other target populations for vaccine
administration, including adolescent girls (134), women of childbearing age,
and infants (135). The duration of protection that could be afforded by
vaccination is unknown; one or more booster doses might be required,
potentially complicating vaccine delivery. Shifts in the GBS serotypes
causing disease have provided an additional challenge to vaccine development
(133) and may necessitate modification of vaccine serotype composition over
time.

Research Priorities and Tools To Aid Prevention

Technological advances that aid the implementation of a universal screening
strategy will further prevention efforts. In addition to development of
reliable rapid tests that can be performed in a wide range of labor and
delivery settings, methods of simplifying prenatal culture procedures, e.g.,
the development of media with a reliable color indicator to signal presence
of GBS, might improve accuracy of prenatal culture results and facilitate
prenatal culture processing at clinical laboratories with limited technical
capacity. Media that have been developed for this purpose, such as Granada
(136,137) or GBS medium (138), should be further evaluated to determine if
sensitivity and specificity are comparable to recommended methods, which
consist of culture in selective broth media followed by GBS-specific
identification.
Although universal prenatal GBS culture-based screening is likely to result
in substantial further declines in the incidence of early-onset disease,
intrapartum chemoprophylaxis is not a permanent or comprehensive strategy
for GBS disease prevention. Because vaccines under development hold promise
to prevent a larger portion of the burden of GBS disease with a simpler and
sustainable intervention, further work on GBS vaccine development and
support of phase 3 clinical trials are warranted (139).
Until a safe, effective, and economical vaccine achieves licensure, it will
be important to continue to monitor for potential adverse effects of
chemoprophylaxis, with an emphasis on tracking key sentinel events signaling
a need for revision of the guidelines. Such sentinel events include the
emergence of penicillin resistance among GBS, which to date has not been
detected, and an increase in the incidence of disease or deaths due to
neonatal pathogens other than GBS that offsets the burden of early-onset
disease prevented by chemoprophylaxis. Monitoring for the latter will
require long-term surveillance of a large population of term and preterm
births (140).
Because GBS carriage is common among delivering women in the United States,
continued surveillance for GBS disease and evaluation of prevention
implementation remains important to minimize missed opportunities for
prevention. States are encouraged to monitor incidence of GBS disease, to
promote activities that enhance perinatal GBS disease prevention and
education, and to assess progress toward national objectives for disease
reduction, such as Healthy People 2010, which sets a target of reducing the
incidence of early-onset GBS disease in all racial and ethnic groups to 0.5
cases per 1,000 live births (141). Practical tools to assist with monitoring
for missed opportunities for perinatal GBS prevention within hospitals have
been published (142); additional prevention information and tools for
providers, patients and clinical microbiologists are available at
http://www.cdc.gov/groupbstrep, http://www.acog.org, http://sales.acog.com,
http://www.aap.org, and
http://www.health.state.mn.us/divs/dpc/ades/invbact/strepb.htm.

Recommendations

The following updated recommendations for the prevention of GBS disease are
based on critical appraisal of multistate population-based observational
data and several studies from individual institutions that have been
completed since publication of previous CDC (7), ACOG (6), and AAP (8)
recommendations. They replace previous recommendations from CDC. The
strength (indicated by a letter) and quality (indicated by a roman numeral)
of evidence supporting each recommendation are shown in parentheses,
according to the evidence-based rating system outlined in Table 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#tab1> .
Obstetric-care practitioners, in conjunction with supporting laboratories
and labor and delivery facilities, should adopt the following strategy for
the prevention of perinatal GBS disease based on prenatal screening for GBS
colonization. The risk-based approach is no longer an acceptable alternative
except for circumstances in which screening results are not available before
delivery (AII).
*       All pregnant women should be screened at 35--37 weeks' gestation for
vaginal and rectal GBS colonization ( Figure 2
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig2> ) (AII). At the time of
labor or rupture of membranes, intrapartum chemoprophylaxis should be given
to all pregnant women identified as GBS carriers (AII). Colonization during
a previous pregnancy is not an indication for intrapartum prophylaxis in
subsequent deliveries. Screening to detect GBS colonization in each
pregnancy will determine the need for prophylaxis in that pregnancy.
*       Women with GBS isolated from the urine in any concentration (e.g., 103)
during their current pregnancy should receive intrapartum chemoprophylaxis
because such women usually are heavily colonized with GBS and are at
increased risk of delivering an infant with early-onset GBS disease (BII).
Labels on urine specimens from prenatal patients should clearly state the
patient's pregnancy status to assist laboratory processing and reporting of
results. Prenatal culture-based screening at 35--37 weeks' gestation is not
necessary for women with GBS bacteriuria. Women with symptomatic or
asymptomatic GBS urinary tract infection detected during pregnancy should be
treated according to current standards of care for urinary tract infection
during pregnancy.
*       Women who have previously given birth to an infant with invasive GBS
disease should receive intrapartum chemoprophylaxis; prenatal culture-based
screening is not necessary for these women (BII).
*       If the result of GBS culture is not known at the onset of labor,
intrapartum chemoprophylaxis should be administered to women with any of the
following risk factors: gestation <37 weeks, duration of membrane rupture
>18 hours, or a temperature of >100.4º F (>38.0ºC) (AII). Women with known
negative results from vaginal and rectal GBS screening cultures within 5
weeks of delivery do not require prophylaxis to prevent GBS disease even if
any of the intrapartum risk factors develop.
*       Women with threatened preterm (<37 weeks' gestation) delivery should be
assessed for need for intrapartum prophylaxis to prevent perinatal GBS
disease. An algorithm for management of women with threatened preterm
delivery is provided ( Figure 3
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig3> ). Other management
approaches, developed by individual physicians or institutions, may be
appropriate (CIII).
*       Culture techniques that maximize the likelihood of GBS recovery are
required for prenatal screening ( Box 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#box1> ). Collection of specimens
for culture may be conducted in the outpatient clinic setting by either the
patient, with appropriate instruction, or health-care provider (BII). This
involves swabbing the lower vagina and rectum (i.e., through the anal
sphincter). Because lower vaginal as opposed to cervical cultures are
recommended, cultures should not be collected by speculum examination.
Specimens should be placed in a nonnutritive transport medium (e.g., Amies
or Stuart's without charcoal). Specimen labels should clearly identify that
specimens are for group B streptococcal culture. If susceptibility testing
is ordered for penicillin-allergic women ( Box 2
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#box2> ), specimen labels should
also identify the patient as penicillin allergic and should specify that if
GBS is isolated, it should be tested for susceptibility to clindamycin and
erythromycin. Specimens should be inoculated into a selective broth medium
(examples of appropriate commercially available media include Trans-Vag
Broth supplemented with 5% defibrinated sheep blood or LIM broth), incubated
overnight, and subcultured onto solid blood agar medium (AII). Methods of
testing prenatal isolates from penicillin-allergic women for susceptibility
to clindamycin and erythromycin are outlined ( Box 1
<http://www.cdc.gov/mmwr/preview/mmwrhtml/#box1> ). Laboratories should
report culture results (positive and negative) and susceptibility testing
results to the anticipated site of delivery (when known) and to the
health-care provider who ordered the test.
*       Health-care providers should inform women of their GBS screening test
result and the recommended interventions. In the absence of GBS urinary
tract infection, antimicrobial agents should not be used before the
intrapartum period to treat
*       GBS colonization. Such treatment is not effective in eliminating carriage
or preventing neonatal disease and may cause adverse consequences (DI).
*       GBS-colonized women who have a planned cesarean delivery performed before
rupture of membranes and onset of labor are at low risk for having an infant
with early-onset GBS disease. These women should not routinely receive
intrapartum chemoprophylaxis for perinatal GBS disease prevention (CII).
*       For intrapartum chemoprophylaxis, the following regimen is recommended for
women without penicillin allergy (Box 2): penicillin G, 5 million units
intravenously initial dose, then 2.5 million units intravenously every 4
hours until delivery (AII). Because of its narrow spectrum of activity,
penicillin is the preferred agent. An alternative regimen is ampicillin, 2 g
intravenously initial dose, then 1 g intravenously every 4 hours until
delivery (AI).
*       Intrapartum chemoprophylaxis for penicillin-allergic women takes into
account increasing resistance to clindamycin and erythromycin among GBS
isolates (Box 2). During prenatal care, history of penicillin allergy should
be assessed to determine whether a patient is at high risk for anaphylaxis,
i.e., has a history of immediate hyper-sensitivity reactions to penicillin
(e.g., anaphylaxis, angioedema, or urticaria) or history of asthma or other
conditions that would make anaphylaxis more dangerous (89). Women who are
not at high risk for anaphylaxis should be given cefazolin, 2 g
intravenously initial dose, then 1 g intravenously every 8 hours until
delivery (BIII). For women at high risk for anaphylaxis, clindamycin and
erythromycin susceptibility testing, if available, should be performed on
isolates obtained during GBS prenatal carriage screening. Women with
clindamycin- and erythromycin-susceptible isolates should be given either
clindamycin, 900 mg intravenously every 8 hours until delivery; OR
erythromycin, 500 mg intravenously every 6 hours until delivery. If
susceptibility testing is not possible, susceptibility results are not
known, or isolates are resistant to erythromycin or clindamycin, the
following regimen can be used for women with immediate penicillin
hypersensitivity: vancomycin, 1 g intravenously every 12 hours until
delivery (CIII).
*       Routine use of antimicrobial prophylaxis for newborns whose mothers
received intrapartum chemoprophylaxis for GBS infection is not recommended.
However, therapeutic use of these agents is appropriate for infants with
clinically suspected sepsis. An updated algorithm for management of infants
born to mothers who received intrapartum chemoprophylaxis for GBS infection
is provided ( Figure 4 <http://www.cdc.gov/mmwr/preview/mmwrhtml/#fig4> ).
This revised algorithm is not an exclusive approach to management; variation
that incorporates individual circumstances or institutional preferences may
be appropriate (CIII).
*       Local and state public health agencies, in conjunction with appropriate
groups of hospitals, are encouraged to establish surveillance for
early-onset GBS disease and to take other steps to promote perinatal GBS
disease prevention and education to reduce the incidence of early-onset GBS
disease in their states. Efforts to monitor the emergence of perinatal
infections caused by other organisms are also encouraged.
Before full implementation of this strategy can be expected in all
health-care settings, all members of the health-care team will need to
improve protocols for isolation and reporting of GBS culture results, to
improve information management to ensure communication of screening results,
and to educate medical and nursing staff responsible for prenatal and
intrapartum care. Within institutions, such efforts may take several months.
Even with ideal implementation, cases of early-onset GBS disease will
continue to occur. Tools to help promote prevention and educate parents of
infants with early-onset GBS disease are available at
http://www.cdc.gov/groupbstrep. Additional tools available to assist with
prevention implementation are available at http://www.acog.org,
http://sales.acog.com, http://www.aap.org and
http://www.health.state.mn.us/divs/dpc/ades/invbact/strepb.htm
<http://http://www.health.state.mn.us/divs/dpc/ades/invbact/strepb.htm>
Multiple copies of educational materials published by CDC are available at
the Public Health Foundation, 1220 L St., NW Suite 350, Washington, DC
20005, telephone 877-252-1200, or online at http://www.phf.org.

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Consultants
Kathryn Arnold, M.D., Georgia Division of Public Health, Atlanta, Georgia;
Carol Baker, M.D., American Academy of Pediatrics/ Committee on Infectious
Diseases, Elk Grove Village, Illinois; Gina Burns, M.S., Group B Strep
Association, Chapel Hill, North Carolina; Richard Facklam, Ph.D., CDC,
Atlanta, Georgia; Monica Farley, M.D., Infectious Diseases Society of
America, Alexandria, Virginia; Theodore G. Ganiats, M.D., American Academy
of Family Physicians, Leawood, Kansas; Ronald Gibbs, M.D., Infectious
Diseases Society of Obstetricians and Gynecologists, Washington, D.C.; Paul
Heath, M.D., U.K. GBS Prevention Working Group, London, England; James H.
Jorgensen, Ph.D., Health Science Center at San Antonio, University of Texas,
San Antonio, Texas; William Kanto, M.D., American Academy of
Pediatrics/Committee on Fetus and Newborn, Elk Grove Village, Illinois;
Shelene Keith, Jesse Cause Foundation--Saving the Babies from Group B Strep,
Port Huenme, California; Tekoa King, M.P.H., American College of Nurse
Midwives, Washington, D.C.; Feng Ying Lin, M.D., National Institute of Child
Health and Development, National Institutes of Health, Bethesda, Maryland;
Ruth Lynfield, M.D., Minnesota Department of Health, Minneapolis, Minnesota;
Martin McCaffrey, M.D., Naval Medical Center, San Diego, California; Elliot
Philipson, M.D., Cleveland Clinic, Cleveland, Ohio; Lisa Porter, M.Ed.,
Jacksonville, Florida; Laura Riley, M.D., American College of Obstetricians
and Gynecologists, Washington, D.C.; Donna Russell, M.S., Washington
Department of Health, Renton, Washington; Pam Sims, Pharm. D., Samford
University, Birmingham, Alabama; Carol A. Spiegel, Ph.D., University of
Wisconsin, Madison, Wisconsin; Barbara Stoll, M.D., Emory University School
of Medicine, Atlanta, Georgia; Beth H. Stover, Healthcare Infection Control
Practices Advisory Committee, CDC, Atlanta, Georgia; Cynthia Whitney, M.D.,
CDC, Atlanta, Georgia; Michael K. Yancey, M.D., Tripler Army Medical Center,
Honolulu, Hawaii; Elizabeth Zell, M.Stat., CDC, Atlanta, Georgia

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Figure 4
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Edward E. Rylander, M.D.
Diplomat American Board of Family Practice.
Diplomat American Board of Palliative Medicine.