[Federal Register Volume 59, Number 240 (Thursday, December 15, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-30806]
[[Page Unknown]]
[Federal Register: December 15, 1994]
_______________________________________________________________________
Part IV
Department of Health and Human Services
_______________________________________________________________________
Centers for Disease Control and Prevention
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Prevention of Group B Streptococcal Diseases: A Public Health
Perspective; Notice
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
Prevention of Group B Streptococcal Disease: A Public Health
Perspective
AGENCY: Centers for Disease Control and Prevention (CDC), Public Health
Service, Health and Human Services.
ACTION: Notice.
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SUMMARY: This notice is a request for review and comment of the draft
document, Prevention of Group B Streptococcal Disease: A Public Health
Perspective. The draft document was prepared by the Childhood and
Respiratory Diseases Branch, Division of Bacterial and Mycotic
Diseases, National Center for Infectious Diseases, CDC, with input from
multiple reviewers.
DATES: Written comments on the draft document must be received on or
before February 13, 1995.
ADDRESSES: Comments should be submitted in writing to the Centers for
Disease Control and Prevention (CDC), Attention: GBS Recommendations
Review Committee, Mailstop C-09, 1600 Clifton Road, NE., Atlanta, GA
30333. The Federal Register containing this draft document may be
viewed and photocopied at most libraries designated as U.S. Government
Depository Libraries and at many other public and academic libraries
that receive the Federal Register throughout the country. In addition,
copies of this Federal Register notice document can be obtained by
calling (404) 639-2215.
FOR FURTHER INFORMATION CONTACT: Cynthia Whitney M.D., or Anne Schuchat
M.D., telephone (404) 639-2215 or FAX (404) 639-3970.
SUPPLEMENTARY INFORMATION: The purpose of this document is to summarize
the literature on group B streptococcal disease in newborns and to
recommend a prevention strategy for clinicians providing obstetric
care.
Dated: December 9, 1994.
Claire V. Broome,
Deputy Director, Centers for Disease Control and Prevention (CDC).
Appendix--
Prevention of Group B Streptococcal Disease: A Public Health
Perspective
Executive Summary
This document contains a summary of the literature on the
epidemiology and prevention options for neonatal group B
streptococcal (GBS) disease and proposes recommendations for
prevention of early-onset neonatal disease.
Neonatal GBS disease has become the major infectious cause of
illness and death among newborns since its emergence in the 1970s.
An estimated 7600 episodes of invasive GBS disease, primarily sepsis
and meningitis, occur in newborns each year in the United States;
approximately 80% of these episodes represent early-onset disease,
occurring within the first week of life. Early-onset disease occurs
in newborns through vertical transmission from a mother who carries
GBS in her anorectum or genital tract. Several obstetric factors
have been identified that indicate a high risk of a newborn
developing early-onset GBS disease; the most important include
prolonged or premature rupture of membranes, premature gestational
age, and maternal chorioamnionitis, which is manifest by intrapartum
fever.
Administering intravenous penicillin or ampicillin to mothers
during labor and delivery is an effective way of preventing early-
onset GBS disease. Several strategies have been proposed to select
which women should receive intrapartum chemoprophylaxis. Many
intrapartum chemoprophylaxis strategies are cost-effective, but they
vary in their simplicity, the proportion of disease prevented, and
the number of women who receive intrapartum chemoprophylaxis.
Where possible, we recommend the following strategy, which will
prevent the majority of early-onset disease and limit the use of
antimicrobials to about 5% of all deliveries, thus minimizing
maternal side effects and the emergence of antimicrobial-resistant
organisms. This strategy identifies women who are colonized with GBS
through prenatal screening cultures at 26 to 28 weeks and restricts
intrapartum chemoprophylaxis to colonized women who develop one or
more of the following risk factors: intrapartum fever, prolonged
rupture of membranes (12 hours), and premature onset of
labor or membrane rupture (<37 weeks). In addition, all women who
have previously delivered an infant with GBS disease should receive
intrapartum chemoprophylaxis. This strategy requires appropriate
methods for specimen collection and laboratory processing because
culture methods substantially affect the ability to recover
organisms. We recognize that this strategy is most applicable to
women who are compliant with recommended prenatal care schedules and
in settings where prenatal screening is practical. Women who do not
receive prenatal care or whose GBS culture status is unknown should
receive intrapartum chemoprophylaxis if one of the stated risk
factors is present without regard to culture status.
An alternate strategy, for practices in which prenatal screening
for GBS colonization is not done, is to give intrapartum
antimicrobials to all women who develop one of the above obstetric
risk factors (intrapartum fever, prolonged rupture of membranes, and
premature onset of labor or membrane rupture) and to women who have
previously delivered an infant with GBS disease. This strategy may
require giving antimicrobials to up to 25% of deliveries, however,
and those who employ this strategy should monitor for side effects
of antimicrobial agents and for infections caused by antimicrobial-
resistant organisms in their patient population.
Effectively implementing prevention strategies require
communication among clinicians, microbiology laboratory personnel,
delivery ward staff, and patients to ensure that cultures are
properly collected, that the results are available at delivery, and
that high-risk women receive appropriate intrapartum
chemoprophylaxis. The majority of early-onset GBS disease and nearly
all deaths can be prevented with currently available methods.
Despite this, however, continued efforts are needed to simplify
prevention strategies, through development of highly sensitive and
rapid antigen detection tests or an effective vaccine, and to
monitor the impact of current prevention efforts.
Introduction
During the last 2 decades, group B streptococcus (GBS) has
emerged as a major infectious cause of neonatal morbidity and
mortality. During this time, studies of the epidemiology and risk
factors for GBS disease in newborns have contributed to advances in
the development and evaluation of prevention strategies for this
illness. This report will (1) review the epidemiology of GBS disease
and summarize options for prevention of GBS disease in newborns, and
(2) propose guidelines for screening and the use of intrapartum
chemoprophylaxis for prevention of neonatal GBS disease.
Background
GBS, or Streptococcus agalactiae, is a gram-positive coccus that
causes invasive disease primarily in newborns, pregnant women, and
adults with underlying medical conditions. In infants, GBS disease
is characterized as either early-onset (occurring in infants <7 days
old) or late-onset (occurring in infants 7 days old).
Disease in infants most commonly occurs as bacteremia, pneumonia, or
meningitis (1). Approximately 25% of neonatal GBS disease occurs in
premature infants (2).
GBS infection in pregnant women includes urinary tract
infection, chorioamnionitis, endometritis, and wound infection;
stillbirths and premature delivery have also been attributed to GBS
(1). In nonpregnant adults, skin or soft tissue infection,
bacteremia, genitourinary infection, and pneumonia are the most
common manifestations of disease (2, 3).
The case-fatality rate for GBS disease is estimated as 5-20% for
newborns (1, 2) and 15-32% (2-4) for adults. A recent multistate
active surveillance system in a population of 10 million persons (2)
found that 6% of early-onset GBS infections resulted in death. This
case-fatality rate is lower than those reported previously (1, 5),
particularly the rates of 15-50% observed in series from the 1970s
(6-8). This reduction in deaths most likely resulted from
improvements in neonatal care (9, 10).
Epidemiology
Colonization
The gastrointestinal tract is the major human reservoir of GBS,
with the genitourinary tract the most important site of secondary
spread (1). Colonization rates may vary among ethnic groups,
geographic locales, and by age, but rates are similar for pregnant
and nonpregnant women (1, 11-13). Five percent to 40% of all
pregnant women are colonized with GBS in the vagina or rectal area
(11, 14, 15). Of all infants born to colonized parturients, about 1-
2% will develop early-onset invasive disease (1).
The isolation rate of GBS from clinical specimens depends on a
variety of factors. Culturing specimens from both the anorectum and
the vagina increases the likelihood of GBS isolation by 5-27% over
vaginal culture alone (14-16). The use of selective media, or broth
containing antimicrobials to inhibit competing organisms, is
particularly important because it can increase the yield of
screening cultures by as much as 50% (17, 18).
Incidence of Neonatal Disease
Recently, multistate, population-based methods of case-finding
have been used to estimate the incidence of neonatal GBS disease in
the United States. Age- and race-adjusted projections to the entire
U.S. population suggested that in 1990, there were 7600 episodes
(incidence 1.8 per 1000 live births) and 310 deaths due to GBS
disease among infants 90 days of age (2). Early-onset
infections accounted for approximately 80% of neonatal GBS
infections (2). Long-term neurologic sequelae may result from
meningitis or complications of severe sepsis, but the incidence and
cost of these sequelae are not known.
Risk Factors
Studies have identified a number of obstetric, maternal, and
neonatal factors that increase the likelihood that early-onset GBS
disease will occur in a newborn. Deliveries in which premature onset
of labor, prolonged rupture of membranes, intrapartum fever, or
multiple gestation (5, 19-22) occurs are more likely to be
complicated by GBS early-onset disease. The incidence of GBS disease
also is higher among infants born to mothers who are <20 years old,
of black race, or who have a high inoculum of GBS in genital
cultures, GBS bacteriuria during pregnancy, or low levels of anti-
GBS capsular antibody, or who previously delivered an infant with
GBS disease (5, 7, 23-25). Risk factors identified for neonates
include low birth weight and heavy surface colonization with GBS (7,
26).
Determinants of late-onset GBS disease are not well documented.
Some evidence suggests that late-onset disease may be acquired
through either vertical or nosocomial transmission (5, 27, 28),
although acquisition of disease in the community also is possible
(13).
Review of Prevention Strategies
Almost half of invasive GBS disease occurs in newborns (2);
therefore, efforts to prevent GBS disease have concentrated on this
group. Research has focused on inducing protective immunity in the
newborn (active and passive immunization) or eradicating
colonization with GBS from the mother and/or newborn
(chemoprophylaxis).
Immunization
Several studies have suggested that susceptibility to neonatal
GBS disease is, in part, due to a deficiency of maternal
anticapsular antibody (25, 29). Active maternal immunization holds
promise for prevention of peripartum maternal disease and neonatal
disease by transplacental transfer of protective IgG antibodies
(30). Several vaccines designed to induce antibodies against the
polysaccharide capsule of GBS are now being developed.
Theoretically, these vaccines also could be used to prevent GBS
disease in nonpregnant adults.
The potential impact of effective vaccines may be limited
because of reduced transplacental transport of protective antibody
before 32-34 weeks gestation and because of possible difficulty in
delivering the vaccine, particularly to those at highest risk such
as teenage and nulliparous women.
Chemoprophylaxis
Efficacy Studies
Administering antimicrobials to pregnant women before the onset
of labor or rupture of membranes is not likely to prevent neonatal
GBS disease. In one study, asymptomatic pregnant women colonized
with GBS were given oral antimicrobials in the third trimester; over
30% of those treated were still colonized at delivery, and there was
no significant difference in carriage of the organism at delivery
between treated and untreated groups (31). Another study showed that
nearly 70% of colonized women who were treated in the third
trimester were colonized at delivery even when their sex partners
had also been treated (32).
Postnatal chemoprophylaxis with intramuscular penicillin given
to infants just after birth also has been studied. Only one
prospective, randomized, controlled study has been published in
which blood cultures were obtained from all newborns before
chemoprophylaxis was given (33). In this study, which enrolled only
low-birth-weight infants, there were no differences between treated
and untreated groups in the incidence of early- or late-onset GBS
disease or in mortality. Another study suggested that postnatal
chemoprophylaxis with penicillin may decrease neonatal illness due
to GBS (34, 35). However, there was no significant effect on overall
mortality, and mortality associated with penicillin-resistant
pathogens was higher in the penicillin-treated group than the
control group (1.0 vs 0.4 per 1000 live births, p = 0.06) (35).
Since the majority of neonatal infections are acquired in utero (1),
antimicrobials given to neonates, while useful for treatment, are
unlikely to prevent GBS disease.
Intrapartum chemoprophylaxis (i.e., administration of
antimicrobials after onset of labor or membrane rupture but before
delivery) is the most promising method to prevent both early-onset
disease and maternal illness due to GBS. Antimicrobial regimens that
have been used for intrapartum chemoprophylaxis are shown in Table
1. Several studies have shown that intrapartum chemoprophylaxis
decreases neonatal colonization (36-40) and early-onset invasive
disease (39-42) when given to unselected pregnant women colonized
with GBS. Other studies examined the use of intrapartum
chemoprophylaxis for selected women colonized with GBS who were at
increased risk for delivering an infant with GBS disease. The only
prospective, randomized, controlled clinical trial using this
approach focused on pregnant women colonized with GBS who
experienced either preterm labor or membrane rupture (<37 weeks
gestation) or prolonged rupture of membranes (>12 hours) (43). In a
preliminary study of the obstetric population in the same community,
the incidence of early-onset GBS disease in this high risk group was
8-fold higher than in colonized women without any of these risk
factors (44, 45). In the intrapartum chemoprophylaxis trial,
colonized mothers with preterm labor or prolonged rupture of
membranes were randomized to receive intravenous ampicillin or no
chemoprophylaxis. Infants delivered to mothers in the treatment (85
infants) and control groups (79 infants) differed significantly with
respect to neonatal colonization (9% vs 51%, p<0.001) and early-
onset invasive disease (0% vs 6%, p<0.02). Postpartum maternal
febrile illness was also significantly reduced in the treatment
group (p<0.04). The authors (Boyer and Gotoff) estimated that this
strategy would prevent at least 50 percent of early-onset GBS
infections in their population.
Other studies also have documented the protective efficacy of
intrapartum chemoprophylaxis given to GBS carriers in selected high-
risk groups. These included women with heavy genital colonization
(46, 47) and with preterm prolonged rupture of membranes (48). A
summary of published studies of the efficacy of intrapartum
chemoprophylaxis is presented in Table 2. A recent meta-analysis of
seven trials, which included studies of all carriers and carriers
with risk factors, estimated a 30-fold reduction in early-onset GBS
disease with intrapartum chemoprophylaxis (49).
Identification of Carriers
Most of the studies of intrapartum chemoprophylaxis have
evaluated its impact on subsets of women who had been identified as
GBS carriers. Although the GBS carriage rate in pregnancy does not
change with trimester (11, 13), the duration of carriage is
unpredictable (13), and prenatal screening cultures will not
correctly identify all women with intrapartum GBS carriage. The
later in pregnancy that cultures are performed, the better the
correlation with intrapartum culture results. However, scheduling
routine cultures very late in pregnancy will miss women who deliver
prematurely. In one study, only 7.4% of women with a negative
culture at 26-28 weeks were found to carry GBS at delivery when
selective (antimicrobial-containing) broth medium was used and
cultures were obtained from both the vagina and anorectum (15). The
same large study showed that a single positive GBS culture during
pregnancy was 67% predictive of a positive culture at delivery; the
estimated sensitivity and specificity were 70.0% and 90.4%,
respectively (15). Follow-up of over 5000 deliveries by women who
had prenatal cultures for GBS found that 14 (88%) of the 16 infants
who developed early-onset GBS disease were born to mothers who were
detected prenatally as carriers (45).
Optimal identification of GBS carriers is dependant on
technique. The correlation of prenatal culture results with
intrapartum GBS carriage is likely to be substantially reduced when
screening does not incorporate appropriate sites (rectum and
vagina), timing (26 weeks gestation or later), and culture medium
(selective broth). Since cultures from the vagina and rectum are
more sensitive than cervical cultures (12), pelvic examination or
visualization of the cervix by speculum examination is not required
for collection of screening cultures.
Selection Criteria
Based on their randomized clinical trial, Boyer and Gotoff
recommended intrapartum chemoprophylaxis for those women identified
as GBS carriers through prenatal cultures who subsequently developed
one of the following signs: rupture of membranes >12 hours, onset of
labor or membrane rupture at <37 weeks, or intrapartum fever
[>37.5 deg.C](43). The American Academy of Pediatrics (AAP)
supported the use of this strategy and added the following
indications for intrapartum chemoprophylaxis: previous delivery of
an infant with GBS disease and multiple gestation pregnancy in a GBS
carrier (50).
Minkoff and Mead proposed an approach to GBS prevention that
focused on prevention of disease associated with prematurity (51).
This proposal suggested giving intrapartum antimicrobials to women
who were either colonized with GBS or whose colonization status was
unknown at the time of presentation with preterm labor or preterm
rupture of membranes. However, strategies designed to prevent
infection only in preterm deliveries would have limited impact since
fewer than 30% of infants with GBS disease are born prematurely (2).
A pragmatic approach to determining the need for antimicrobial
prophylaxis was recently advocated by the American College of
Obstetricians and Gynecologists (ACOG, 52, 53). This strategy
consists of using intrapartum antimicrobials for all women with one
or more of the following conditions: preterm labor (<37 weeks),
preterm premature rupture of membranes (<37 weeks), prolonged
rupture of membrane (>18 hours), previous child affected by
symptomatic GBS infection, or maternal fever during labor (53). This
strategy is simpler than protocols requiring either prenatal or
intrapartum identification of GBS carriage, although its impact on
disease has not been evaluated in clinical practice. In addition,
the strategy may lead to an increase in perinatal infections with
penicillin-resistant organisms as a result of large-scale use of
antimicrobials.
There have been no clinical trials directly comparing efficacy
among suggested prevention strategies. Finding a statistically
significant difference in efficacy may not be feasible; a recent
article estimated that 100,000 women would be required for each arm
of a randomized prospective trial comparing the efficacy of
universal screening and selective intrapartum chemoprophylaxis with
treatment based on risk factors alone (54). This limitation on
directly comparing the efficacy of several prevention strategies is
reflected in a recent national consensus statement by the Society of
Obstetricians and Gynaecologists of Canada and the Canadian
Paediatric Society, which recommended use of either the AAP (Boyer
and Gotoff) strategy or the ACOG approach and underscored the need
for further prevention research (55).
Adverse Effects
Because a substantial proportion of pregnant women are colonized
with GBS, administration of intrapartum chemoprophylaxis to all GBS
carriers is likely to cause an unacceptably high number of adverse
reactions. It has been estimated--assuming a GBS colonization rate
of 25%, 4 million deliveries in the United States annually, and a
rate of fatal anaphylaxis to penicillin of 0.001%--that giving
intrapartum antimicrobials to all women who are GBS carriers would
result in about 10 deaths per year from anaphylaxis (56). Another
0.7 to 10% of women given prophylaxis would be expected to have less
severe reactions (57). Severe complications can occur in the fetus
even when maternal anaphylaxis is relatively mild (58). In addition,
widespread antimicrobial use is known to increase the risk for
emergence of antimicrobial-resistant organisms. GBS isolates have
not yet developed clinically important resistance to penicillin, but
infections with penicillin-tolerant GBS have been described (59-61).
Development of antimicrobial-resistance in other peripartum
pathogens is an even greater threat. McDuffie et al. report four
episodes of adverse perinatal outcome due to antimicrobial-resistant
Enterobacteriaceae among women treated with ampicillin or
amoxicillin for premature rupture of membranes (62).
Restricting antimicrobials to selected populations at increased
risk for delivering a newborn with GBS disease would decrease the
likelihood of adverse reactions and antimicrobial resistant
organisms. The strategy proposed by Boyer and Gotoff (giving
intrapartum ampicillin to women identified prenatally as GBS
carriers who have rupture of membranes >12 hours, labor or membrane
rupture at <37 weeks, or intrapartum fever [>37.5 deg.C]) would
require administering antimicrobials to 4.6% of the obstetric
population served by their urban hospital (43). The approach
suggested by Minkoff and Mead (giving antimicrobials to women with
either labor or membrane rupture at <37 weeks gestation who are
intrapartum carriers of GBS or whose GBS status is unknown) was
estimated to require prophylaxis for 8.9 percent of parturients
(51). Strategies that treat all GBS carriers (42) or all women with
obstetric risk factors (e.g., prolonged membrane rupture,
prematurity) (52) are estimated to require administering
antimicrobials in over 20% of deliveries; this level of
antimicrobial use could lead to unacceptable numbers of serious
adverse reactions and contribute to the emergence of antimicrobial-
resistant organisms.
Implementation Issues
Despite the encouraging results of efficacy studies, routine GBS
screening and selective intrapartum chemoprophylaxis have not been
widely adopted in the obstetric community (53, 63). Practical
problems include logistic concerns related to screening for GBS
colonization and concern about the cost-effectiveness of
implementing chemoprophylaxis.
A strategy based on detecting colonization by prenatal screening
and using these results to guide selective intrapartum
chemoprophylaxis would not be effective for persons receiving no
prenatal care or in persons whose prenatal records are not available
to caregivers at the time of delivery. Ideally, GBS carriage would
be determined at the time of labor onset or at rupture of membranes.
However, since identification of GBS by culture takes 24-48 hours,
intrapartum culture results would not be available in time for
intervention in the majority of deliveries. Rapid detection of GBS
antigen from vaginal specimens may identify GBS carriers when
prenatal screening is not available (64). Although rapid tests for
detection of GBS are very specific and many recently developed tests
can be performed in less than 1 hour, the sensitivity of rapid
detection tests has been variable, and, often, unacceptably low (15-
74%) (64). Some rapid detection kits appear to be sensitive for
detecting women who are heavily colonized. Three studies have
confirmed the efficacy of intrapartum chemoprophylaxis given to
women identified by rapid detection techniques as GBS carriers (46-
48). However, since many infants with neonatal GBS disease are born
to women who are lightly colonized (48, 65), using currently
available rapid detection techniques to identify women for
prophylaxis would prevent only a minority of GBS cases.
The cost-effectiveness of selective intrapartum chemoprophylaxis
for the prevention of GBS disease has been studied using population-
based rates of disease (66). The approach recommended by Boyer and
Gotoff was shown to be cost-effective at the current rates of
disease. The cost per case prevented (<35,000 dollars) was similar
to maternal screening and intervention programs for other perinatal
diseases such as congenital syphilis (67). Four other studies also
have suggested that selective intrapartum chemoprophylaxis is cost-
effective for the prevention of neonatal GBS disease (45, 68-70).
Two additional problems related to implementation of
chemoprophylaxis should be mentioned. Clinicians have been concerned
about adopting a strategy that will inevitably have failures (52).
This concern may be influenced by the complexity of communicating
GBS risk information to women during pregnancy or by medicolegal
considerations. Increasing intrapartum antimicrobial use may have a
substantial impact on management of the newborn (71, 72). Some
pediatricians routinely perform additional diagnostic tests on
infants whose mothers received intrapartum antimicrobials or observe
these infants longer, leading to prolonged hospital stays for many
low-risk newborns (71). The American Academy of Pediatrics has
recommended that management of newborns whose mothers received
intrapartum antimicrobials be based on clinical manifestations and
the infant's estimated gestational age (50).
Some of the challenges of instituting a prevention strategy are
illustrated in two recent reports. Pylipow et al initiated selective
intrapartum chemoprophylaxis in their hospital in response to an
increased rate of early-onset GBS disease (72). They enrolled 2040
women, 16.3% of whom were colonized with GBS. Among women colonized
at delivery, 122 (37%) had at least one obstetric risk factor.
However, 33 of these women did not receive intrapartum
chemoprophylaxis because of failure to follow the protocol (N=17),
birth less than 1 hour after arriving at the hospital (n=9),
negative prenatal culture but positive culture at delivery (n=4), or
no prenatal care (n=3). Eleven infants had early-onset GBS disease;
two had received one dose of intrapartum chemoprophylaxis and were
asymptomatic, and nine were born to carriers with risk factors who
did not receive intrapartum chemoprophylaxis. No affected infants
were born to colonized women without risk factors or to women whose
prenatal screening culture was negative for GBS. One woman who
received intrapartum chemoprophylaxis developed a rash and transient
hypotension and was delivered by cesarean section because of
transient fetal bradycardia. The study suggested that selective
intrapartum chemoprophylaxis was effective in preventing early-onset
GBS disease, that the infants of colonized women without labor
complications are at low risk of disease, and that administering
intrapartum antimicrobials is not without risks. The second report,
by Gibbs et al (73), also illustrates that a prevention strategy
employing selective intrapartum chemoprophylaxis is not easily
implemented. In this study, which was conducted in an academic
setting, 80.3% of 142 women who had positive GBS screening cultures
and who developed risk factors at delivery received intrapartum
antimicrobials. Reasons for those failing to receive appropriate
treatment included failure to follow protocol, marginal indications
for chemoprophylaxis, or patient refusal. The study is ongoing but
early results suggest a downward trend in the rate of disease.
Conclusions
Group B streptococcal disease continues to be a major cause of
illness and death among newborns despite clinical advances in the
last 2 decades. Major risk factors for early-onset neonatal GBS
disease include prolonged rupture of membranes, intrapartum fever,
prematurity, GBS bacteriuria during pregnancy, and previous delivery
of an infant with GBS disease (5, 20, 22-24). Studies have shown
that much early-onset neonatal disease can be prevented by
prophylactic antimicrobials given during labor, and that prenatal
screening--by culture at 26 to 28 weeks gestation of both the vagina
and rectum using selective broth media--can detect the majority of
women who will be colonized with GBS at delivery (45). A growing
body of evidence suggests that it is more costly to treat GBS-
infected newborns than to prevent the infection, and that well-
implemented prevention programs can substantially reduce illness and
death due to GBS (45, 66, 68-70). As with any prevention program,
prevention programs for GBS must be implemented carefully; failure
to use optimal culture methods can seriously compromise the efficacy
of screening strategies, and nonselective approaches to
antimicrobial prophylaxis may result in excessive antimicrobial use
which entails risk. A recent survey of Georgia obstetric care
providers suggests that there is some confusion among practitioners
over currently published prevention recommendations; only 9% of
those who obtained screening cultures followed recommended
procedures and 32% gave antimicrobials prenatally when carriage was
detected even though 93% stated they knew such treatment is
ineffective (74).
Of the options outlined above, a program of universal prenatal
screening and intrapartum chemoprophylaxis for carriers with
obstetric risk factors has several features supporting its use for
preventing early-onset GBS disease. This strategy relies on
currently available technology, minimizes potential adverse effects
associated with antimicrobials, has been validated through a
randomized controlled trial, and is least likely to contribute to
selection of antimicrobial-resistant microorganisms. This strategy
is cost-effective at the current rate of disease in the United
States (66). However, it uses prenatal screening as a method to
identify women with GBS carriage and would miss those women who have
not received any prenatal care and some women whose carriage of GBS
is not detected by prenatal culture. In addition, the use of
prenatal screening cultures could result in overuse of
antimicrobials if clinicians give intrapartum chemoprophylaxis to
GBS carriers who do not develop risk factors at the time of delivery
or if antimicrobials are given before delivery or rupture of
membranes.
Determining when to use intrapartum antimicrobials solely on the
basis of obstetric criteria (e.g., prematurity, prolonged membrane
rupture, or intrapartum fever) (53) may be helpful for women who
have not had the benefits of prenatal care or in settings where
prenatal screening is not feasible. Such a program would require
giving antimicrobials to a larger proportion of women in labor than
a program based on prenatal screening and selective
chemoprophylaxis, and is likely to cause excessive adverse reactions
and selection of antimicrobial-resistant organisms. Institutions
that choose this empiric approach are encouraged to monitor its
effectiveness and quantify adverse outcomes associated with the
strategy for review in the medical literature. The impact of
intrapartum chemoprophylaxis on management of low risk newborns also
need to be evaluated.
A program of universal prenatal screening for GBS, although it
may be the best option available now, is not a permanent solution to
the problem of neonatal GBS disease. A more sensitive rapid
screening test for GBS that could accurately detect women who carry
GBS at the time of delivery would avoid the need for prenatal
screening. Sensitive intrapartum testing would also permit detection
of GBS carriage among women without adequate prenatal care. Since an
intrapartum test might detect a higher proportion of women who carry
the organism at delivery and avoid detecting women who only carry
the organism earlier in pregnancy, intrapartum use of a sensitive
rapid detection test could make a prevention program more simple and
more efficient. Development of a vaccine against GBS that is highly
immunogenic in women and permits transplacental transfer of
protection to the fetus would also eliminate the need for prenatal
screening.
Since incidence may vary widely, State or local health
departments or groups of affiliated hospitals should consider
establishing surveillance systems for neonatal GBS disease or
reviewing data from existing systems to identify the current
magnitude of disease and provide further information for evaluating
the effectiveness of prevention measures. In hospital settings,
prevention programs should monitor the occurrence of adverse
reactions to chemoprophylaxis, the emergence of perinatal infections
due to antimicrobial resistant organisms, and the impact of
obstetric antimicrobial use on pediatric management protocols. Only
through enhanced communication among obstetric care providers,
pediatricians, laboratory personnel, infection control
practitioners, infectious disease clinicians, and local and State
health departments can programs for prevention of this serious
disease succeed. Open communication between clinicians and patients
is also an important component of GBS disease prevention. An
informational brochure for pregnant women on GBS is available
through CDC (CRDB/DBMD, National Center for Infectious Diseases,
Mailstop C-09; Atlanta, GA 30333). The following recommendations for
the prevention of GBS disease will need periodic reappraisal to
incorporate advances in technology or other refinements in
prevention strategies.
Recommendations
(1) Screen all pregnant women at 26-28 weeks gestation for
anogenital GBS colonization (figure 1). Screen for GBS colonization
at the first opportunity thereafter if it is not possible to screen
at 26-28 weeks. Screening earlier in pregnancy is not recommended
because of poor correlation with intrapartum carriage. Information
systems should be developed and monitored to assure that prenatal
culture results are available at the time and place of delivery.
(2) Use culture techniques that maximize the likelihood of GBS
recovery. Speculum examination is not necessary for specimen
collection. A single swab or two separate swabs of the distal vagina
and anorectum inoculated into selective broth medium and then
subcultured onto solid medium appears to be optimal. A standard
culture swab may be used, but the sample should be identified for
the laboratory as specifically for GBS culture; in this screening
culture, there is no need for the laboratory to culture for other
organisms. Appropriate selective broth media are commercially
available. A laboratory procedure to maximize recovery of GBS is
detailed in Table 3.
(3) Do not use oral antimicrobials to treat women who are found
to be colonized with GBS during prenatal screening. Such treatment
is not effective in eliminating carriage or preventing neonatal
disease.
(4) Give intrapartum chemoprophylaxis to women with a history of
previously giving birth to an infant with early-onset GBS disease;
prenatal screening is not necessary for these women.
(5) Give intrapartum chemoprophylaxis to pregnant women
identified as GBS carriers who meet at least one of the following
criteria: a) Intrapartum fever (T37.5 deg.C) not clearly
attributable to an extrauterine source; b) onset of labor or
membrane rupture before 37 weeks gestation; or c) rupture of
membranes longer than 12 hours.
(6) For women without prenatal care, in settings in which
prenatal screening cultures are not done, or if GBS culture results
are unknown, assume the patient carries GBS and administer
intrapartum antimicrobials to women who have the criteria listed in
5a-c (figure 2). Screening cultures for GBS colonization may be
performed upon admission to the hospital for delivery; intrapartum
antimicrobials may be stopped if cultures are complete and are
negative for GBS.
(7) Use intravenous penicillin G (5 million units every 6 hours)
or ampicillin (2 grams initially followed by 1 gram every 4-6 hours)
until delivery for intrapartum chemoprophylaxis. Clindamycin or
erythromycin may be used for women allergic to penicillin, although
the efficacy of these drugs for GBS disease prevention has not been
measured in controlled trials. (Note: women with clinical diagnoses
of chorioamnionitis may require other treatment regimens.)
(8) Treat women found to have symptomatic or asymptomatic GBS
bacteriuria during pregnancy at the time of diagnosis. Although data
related to this issue are limited, intrapartum chemoprophylaxis
could be considered for women with a history of GBS bacteriuria
during the pregnancy, even if other risk factors are absent.
(9) Routine use of prophylactic antimicrobials for infants born
to mothers who received intrapartum antimicrobials is not
recommended. However, therapeutic use of antimicrobials is
appropriate for those infants suspected clinically of having GBS
disease or other acute infection. Additional research is needed to
determine algorithms for assessing sepsis in infants born to mothers
who receive intrapartum antimicrobials.
Table 1.--Summary of Antimicrobial Regimens Used for Intrapartum Chemoprophylaxis for GBS Disease
----------------------------------------------------------------------------------------------------------------
Reference Antimicrobial Dose and schedule Comments
----------------------------------------------------------------------------------------------------------------
Yow\36\................ Ampicillin............. 500 mg IV every 6 hrs.. 30/34 received only one dose before
delivery.
Allardice\41\.......... Ampicillin............. 500 mg IV every 6 hrs..
Easmon\37\............. Benzyl penicillin...... 600 mg IM every 8 hrs.. Erythromycin 100 mg IM for penicillin-
allergic women.
Matorras\39\........... Ampicillin............. 500 mg IV every 6 hrs.. 46/57 received only one dose before
delivery.
Garland\42\............ Penicillin............. 1 mU IV every 6 hrs....
Boyer\43\.............. Ampicillin............. 2 g IV load then 1 g IV Mean duration of prophylaxis 5.4 hrs.
every 4 hrs.
Tuppurainen\47\........ Penicillin G........... 5 mU IV every 6 hrs.... If labor lasted >18 hrs, then
penicillin V 1 mU PO every 8 hrs
after initial IV therapy.
Morales\48\............ Ampicillin............. 1 g IV every 6 hrs.....
Morales\46\............ Ampicillin............. 1 g IV every 6 hrs..... Ampicillin levels measured in 8
mother-infant pairs.
----------------------------------------------------------------------------------------------------------------
IV = Intravenous, IM = Intramuscular, PO = By mouth.
Table 2.--Summary of Trials Employing Intrapartum Chemoprophylaxis for Prevention of Neonatal Colonization and Early-onset Group B Streptococcal Disease
--------------------------------------------------------------------------------------------------------------------------------------------------------
Neonatal colonization Early-onset disease
Reference Study design, Case selection -----------------------------------------------------------------------------------------
control selection criteria IC No IC P value IC No IC P value
--------------------------------------------------------------------------------------------------------------------------------------------------------
Yow\36\............. R Random........... I.................. 0/34 14/24 0.001 0/34 0/24 NA
Allardice\41\....... P/R Nonrandom...... I.................. 4/57 62/136 <0.01 0/57 9/136 0.06
Easmon\37\.......... P Random........... PC................. 0/38 17/49 0.001 ND ND NA
Matorras\39\........ P Random........... I or PC............ 2/60 24/65 <0.01 0/60 3/65 0.14
Garland\42\......... P Nonrandom........ PC................. ND ND NA 16/NG 27/NG NG
Boyer\43\........... P Random........... PC and Pre/PROM.... 8/85 40/79 0.001 0/85 5/79 0.02
P Nonrandom........ PC and Pre/PROM.... 5/82 102/233 <0.01 0/82 7/233 0.02
Tuppurainen\47\..... P Random........... Heavy PC........... ND ND NA 1/88 10/111 0.03
Morales\48\......... P/R Nonrandom...... Light I and PPROM.. ND ND NA 0/29 6/37 0.03
P/R Nonrandom...... Heavy I and PPROM.. ND ND NA 0/7 7/11 0.01
Morales\46\......... P Random........... Light PC........... 0/98 35/98 <0.01 0/98 0/98 NA
Heavy PC........... 0/37 24/30 <0.01 0/37 3/30 0.09
--------------------------------------------------------------------------------------------------------------------------------------------------------
Legend--Table 2
IC=Intrapartum chemoprophylaxis, R=Retrospective, I=Intrapartum colonization, NA=not applicable, P/R=Prospective case selection, retrospective control
selection, P=Prospective, PC=Prenatal colonization, ND=not done, NG=Not given, Pre/PROM=Preterm labor (gestation <37 weeks) or prolonged rupture of
membranes (<12 hours), PPROM=Preterm prolonged rupture of membranes.
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TN15DE94.014
BILLING CODE 4163-18-C
Table 3.--Procedure for Collection and Processing of Clinical Specimens
for Culture of GBS
(1) Obtain one or two swab(s) of the vaginal introitus and anorectum.
(2) Inoculate both swabs together into Todd-Hewitt broth supplemented
with either colistin (10 g/ml) and nalidixic acid (15 g/ml), or with gentamicin (8 g/ml) and nalidixic acid (15
g/ml).
(3) Incubate cultures for 18 to 24 hours. If turbidity is observed,
subculture the broth culture growth to sheep blood agar plate. If no
turbidity is present, incubate in broth for another 24 hours before
discarding.
(4) Inspect and identify organisms suggestive of GBS (beta hemolytic or
nonhemolytic, gram-positive and catalase negative). If GBS is not
identified after incubation for 18 to 24 hours on sheep blood agar
plate, reincubate and inspect at 48 hours to identify suspected
organisms.
(5) Various latex agglutination tests or the CAMP test may be employed
for specific identification.
BILLING CODE 4163-18-P
TN15DE94.015
BILLING CODE 4163-18-C
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Abstracts of the 34th ICAAC 1994:14 (Abstract J23).
[FR Doc. 94-30806 Filed 12-14-94; 8:45 am]
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