[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]


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Part IV





Department of Health and Human Services





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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.

-----------------------------------------------------------------------

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.                                                                                  


BILLING CODE 4163-18-P

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]
BILLING CODE 4163-18-P