Download Group B Streptococcal Disease: From Trials and

IDSA LECTURE
Group B Streptococcal Disease: From Trials
and Tribulations to Triumph and Trepidation
Anne Schuchat
Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, Atlanta
Group B streptococci garnered attention during the 1970s when they surpassed Escherichia coli and Staphylococcus aureus
to become the principal causes of sepsis in early infancy. During the 1980s, several clinical trials demonstrated that administration of antimicrobial agents during labor could interrupt vertical transmission and prevent invasive disease in the first
week of life (i.e., early-onset disease). However, prophylaxis was not widely used during the next 10 years. On the basis of
efforts by clinician-researchers, professional organizations, community-based parent advocacy groups, and the public health
community, consensus recommendations for group B streptococcal prophylaxis were finally issued in 1996. By the end of
1999, the incidence of early-onset disease in selected counties within the United States had decreased by 70%, and the gap
between black and white persons with disease narrowed by 75%. This recent triumph leaves the professional community
treading lightly, alert to the need to monitor for unintended consequences that may threaten recent progress.
Research on group B streptococci began at approximately the
same time that Dr. Joseph Smadel completed his medical training (in 1931) and started his research career in rickettsial and
viral diseases, and like Dr. Smadel, group B streptococci also
has a Rockefeller connection. That institution was home to Dr.
Rebecca Lancefield, whose career at Rockefeller spanned 7 decades. In 1933, she reported development of the grouping system for hemolytic streptococci [1]; this landmark work permitted differentiation of group A streptococci (Streptococcus
pyogenes), which was the major pathogen associated with puerperal sepsis at the time, from group B streptococci (Streptococcus agalactiae), which were initially identified in postpartum specimens obtained after uncomplicated deliveries [2]. The
organism was initially considered to be a commensal, but by
the end of the decade, Fry [3] reported fatal human sepsis associated with group B streptococci. By the 1960s, numerous re-
Received 31 January 2001; revised 28 March 2001; electronically published 10 August
2001.
This article is a shortened and edited version of the 24th Annual Joseph E. Smadel Lecture,
which was presented at the 38th Annual Meeting of the Infectious Diseases Society of
America, held in New Orleans in September 2000.
Reprints or correspondence: Dr. Anne Schuchat, Respiratory Diseases Branch, Div. of
Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, Mailstop C-23,
Atlanta, GA 30333 ([email protected]).
Clinical Infectious Diseases 2001; 33:751–6
2001 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2001/3306-0001$03.00
ports had linked neonatal infections with this organism [4–6].
However, during the 1970s, the magnitude of disease and attention to group B streptococci changed dramatically when
separate reports from Baker et al. [7], Franciosi et al. [8], and
Barton et al. [9] announced that group B streptococci had
emerged as the leading cause of neonatal sepsis in nurseries
around the United States. I will focus on the most recent chapters of the group B streptococci story, which took place from
the 1980s through the end of the 20th century, a time during
which attention to group B streptococcal disease shifted its
focus from trials and tribulations to triumph and trepidation.
Approximately 10%–35% of women are asymptomatic carriers of group B streptococci in the genital and gastrointestinal
tracts [10]. At birth, 1 in 2 infants who are born to colonized
mothers will themselves be colonized on the skin or mucosal
surfaces [11]. Approximately 98% of colonized newborns are
without symptoms, but 1%–2% develop early-onset disease, in
which sepsis, pneumonia, or meningitis occur during the first
week of life. The vast majority of early-onset infections are
evident within hours of birth. During the 1970s, ∼50% of infants who developed early-onset group B streptococcal infection
died of their illness, and many patients who survived meningitis
had permanent neurological sequelae. However, by the 1980s,
improved recognition of symptoms, prompt treatment, and
other improvements in neonatal care reduced the fatality rate
to ∼15%. The fatality rate remains higher among infants who
IDSA LECTURE • CID 2001:33 (15 September) • 751
are born prematurely, and such infants also remain at higher
risk of long-term consequences of intrauterine infection, such
as cerebral palsy and chronic lung disease. Therefore, with the
overall improvements in the survival rates, the clinical community turned attention to research on disease prevention. Researchers explored administration of antimicrobial agents to
women during pregnancy [12] and to babies after delivery [13],
but the most promising results involved use of antibiotic prophylaxis intrapartum, which is defined here as after onset of
labor or rupture of the amniotic membranes.
TRIALS
Investigators conducted a number of clinical trials of intrapartum antimicrobial prophylaxis, although not all were randomized or used prospectively enrolled control subjects [14–
21]. For efficiency, most studies used inclusion criteria that
focused on higher-risk women, such as those who had been
detected as prenatal carriers of group B streptococci or those
with heavy density of colonization, which was determined on
the basis of first-generation methods for the rapid identification
of group B streptococci after rupture of the membranes or
preterm labor. Investigators measured the effect of intrapartum
antimicrobial prophylaxis against neonatal colonization—a surrogate for disease risk—as well as against laboratory-confirmed,
early-onset group B streptococcal disease. One study used postpartum maternal febrile illness as a secondary end point [18].
The trials consistently demonstrated that intrapartum antimicrobial prophylaxis interrupts maternal transmission of the
organism to the child [14–19], and the trials that were sufficiently large demonstrated that intrapartum antimicrobial prophylaxis reduces the incidence of early-onset group B streptococcal disease in newborns [18, 20, 21]. The trial by Boyer
and Gotoff [18] deserves particular mention, because it was
considered by many to be pivotal. The main study was a randomized controlled trial of treatment with ampicillin versus
placebo for women who had been identified as prenatal carriers
of group B streptococci (on the basis of vaginal and rectal swab
samples obtained for culture at 26–28 weeks’ gestation) and
who had a threatened delivery at !37 weeks’ gestation or had
an interval of 112 h between rupture of the amniotic membranes and delivery. This trial, which was funded by the National Institutes of Health, was halted after an interim analysis
revealed significant protection among ampicillin recipients. The
decision was based on ethical concerns regarding the withholding of intervention from control subjects any longer. After
results were published in the New England Journal of Medicine
in 1986, one might have expected wide-scale adoption of this
apparently successful intervention strategy.
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TRIBULATIONS
What was the immediate impact of the family of prevention
trials? During the 1980s, there was no large-scale surveillance
for early-onset group B streptococcal infections, so data regarding group B streptococcal disease from this period are limited to reports from a few major hospitals. Group B streptococci
continued to be the principal cause of early-onset neonatal
sepsis in large hospitals around the country. Even in institutions
in which trials had been conducted, intrapartum prophylaxis
was not initially adopted. Barriers to implementation included
the complexity of the interventions that had been tested—some
relied on cumbersome intrapartum detection tests and others
used prenatal cultures, which were considered far from perfect.
Clinicians with faith in biotechnology probably thought that a
simple and accurate detection method would be available soon
and that prevention could wait. But a perfect detection method
was not revealed during the next decade [22], and the accuracy
of prenatal cultures could be optimized with attention to timing
and site of specimen collection [23–25] as well as microbiological technique used in processing cultures [26]. The magnitude of disease caused by group B streptococci was not well
appreciated outside a small number of clinical centers, which
limited the priority given to this condition by the general medical and public health communities. Complicating the situation
further, there was diffused responsibility for group B streptococcal disease among clinicians: pediatric caregivers bore the
burden of treatment of newborns with life-threatening infections, but obstetrical caregivers who were responsible for intrapartum care had to implement prevention strategies. Public
pressure for prevention of group B streptococcal disease was
largely absent during the 1980s.
During the 1990s, a number of forces converged on the group
B streptococcal front. Public advocacy groups formed in the
United States (e.g., the Group B Strep Association and the Jesse
Cause) and Canada (Canadian Group B Strep Association); their
efforts led to local and national media attention. Economic analyses suggested that a number of intervention strategies were likely
to save money, compared with the staggering costs of caring for
ill newborns with group B streptococcal infections as well as
those with long-term sequelae of newborn infection [27–30].
Several state legislatures considered bills related to prevention of
group B streptococcal infection, which was one of the avenues
that had been addressed by the parents’ groups. The California
assembly passed a bill in 1995 that mandated the health department there to hold a consensus conference, the results of
which would guide California policy and clinical recommendations on this issue. Some parents sought a voice through political channels, and others sought legal settlements; the issue
reached prominence that was sufficient for step-by-step guidance
for these cases to appear in the legal journal Trial [31].
Finally, in 1996, consensus recommendations for the prevention of group B streptococcal disease were issued by the 2 key
professional organizations, the American College of Obstetricians
and Gynecologists [32] and the American Academy of Pediatrics
[33], together with the Centers for Disease Control and Prevention (CDC) [34]. The consensus guidelines urged institutions
and caregivers to adopt a prevention strategy for group B streptococcal disease and recommended the following 2 appropriate
approaches as acceptable alternatives (table 1): the screeningbased strategy and the risk-based strategy. Even though the proportion of cases that would be preventable by use of the screening-based strategy was theoretically greater [35], the relative
effectiveness of the 2 strategies in practice was not clear. Because
the screening-based strategy is more complex—it requires prenatal measures, accurate laboratory testing, and communication
from laboratories to labor and delivery—it may be less effective
in practice than it is in theoretical estimates.
In Contemporary Ob/Gyn, the guidelines were heralded and
clinicians were warned, “If you don’t heed the CDC recommendations and a baby you delivered develops a group B streptococcal infection, it will be just a matter of where they place
the decimal point in the out-of-court settlement” [36]. The
critical issue at this point was whether practitioners would actually implement the guidelines and what consequences implementation would yield. In contrast to the situation during
which the first prevention trials were published, by this point,
the United States did have a large-scale surveillance system in
place poised to monitor impact.
TRIUMPH
Hospital authorities and practitioners alike viewed the consensus
recommendations as a new standard. The proportion of hospitals
that adopted prevention policies regarding group B streptococci
increased from 13% in 1992 to nearly 60% in 1997 [37]. From
1993 through 1998, the incidence of early-onset group B strepTable 1.
tococcal disease decreased by 65%, whereas the incidence of
invasive group B streptococcal disease in adults and of late-onset
disease in infants who were 7–90 days of age remained stable
[38]. In 1993, the rate of early-onset disease among African
American persons was nearly twice that of white infants; by 1998,
this gap in incidence had narrowed by 75%. There was a direct
association between implementation of a new prevention policy
and a decrease in the incidence of disease: hospitals with new or
revised policies in 1996 had approximately half the incidence of
disease in 1997 that they had in earlier years, whereas hospitals
with no policy in 1996 had no significant decrease in the number
of cases by 1997 [39]. The incidence of disease continued to
decrease from 1997 through 1999, but the proportion of hospitals
that had implemented policies did not continue to increase during this time period [40]. An explanation for this discrepancy is
the finding that, by 1999, more hospitals had introduced systemwide features, such as standing orders, to promote compliance with policies that they had already adopted [40]. Individual
practitioners were even more likely than institutions to have
policies; many hospitals claimed that their policy was to encourage obstetrical caregivers to implement prevention policies
[41, 42]. Although practitioners in some areas were more likely
to have adopted the screening-based approach, in others, the
risk-based strategy predominated [41]. There were also geographic differences in implementation of appropriate screening
methods in clinical laboratories [43]. CDC is currently collaborating with investigators in 8 states where active surveillance
for group B streptococcal disease is ongoing on special projects
to track actual compliance with the screening-based and riskbased strategies and to compare the relative effectiveness of these
approaches.
TREPIDATION
The good news regarding disease prevention and practice
changes must be tempered with concern about unintended
Strategies for prevention of early-onset group B streptococcal (GBS) disease.
Approach
Prenatal component
Intrapartum component
Screening-based strategy
Obtain vaginal and rectal swab specimens at
35–37 weeks’ gestation and inoculate in selective broth media; assess history of previous infant with group B streptococcal disease and
presence of GBS bacteriuria during current
pregnancy.
Offer intrapartum penicillina to women with GBS identified on prenatal cultures, previous infant with GBS
disease, GBS bacteriuria during this pregnancy, or
unknown screening results and threatened delivery
at gestation of !37 weeks, rupture of membranes
for ⭓18 h, or intrapartum temperature of 138C.
Risk-based strategy
Determine history of previous infant with group B
streptococcal disease and presence of GBS
bacteriuria during current pregnancy.
Offer intrapartum penicillina to women with previous
infant with GBS disease, GBS bacteriuria during
this pregnancy, threatened delivery at gestation
of !37 weeks, rupture of membranes for ⭓18 h,
or intrapartum temperature of 138C.
a
Penicillin was recommended as first-line agent with ampicillin as acceptable alternative; clindamycin or erythromycin were recommended for women who
were allergic to penicillin.
IDSA LECTURE • CID 2001:33 (15 September) • 753
consequences. A critical component of success in control of
group B streptococcal disease is the use of antimicrobial prophylaxis during labor and delivery. Implementation of prevention guidelines appears to double the rates of use of antibiotics
during labor. While the guidelines were being developed, authorities voiced concern about adverse effects of increased use
of antibiotics, such as severe anaphylactic reactions or the possible emergence of antimicrobial resistance in either group B
streptococci or other perinatal pathogens. One unanticipated
problem was a shortage of iv penicillin G, the drug of choice
for prophylaxis, which occurred in 1999 after a main supplier
in the United States halted production because of manufacturing irregularities [44]. A national survey of obstetriciangynecologists suggested that two-thirds of the providers who
had been using penicillin as their first-line prophylaxis agent
were affected by the shortage; they usually substituted use of
a broader-spectrum agent during the interim period [42]. Although the increased demand for group B streptococcal prophylaxis that grew out of the consensus recommendations was
not the cause of the sudden shortage, the problem points to
the tenuous state of generic drug availability and highlights a
major concern for infectious disease practitioners.
Resistance has been a concern as well. As of 2001, no penicillin-resistant isolates of group B streptococci have been detected. However, resistance to erythromycin and clindamycin
has become relatively common in both genital tract isolates and
invasive strains [45–47]. Additional concerns relate to the potential for increased antibiotic use to lead to more infections
caused by pathogens other than group B streptococci, by filling
the niche vacated by this organism. Escherichia coli is the second-most-common cause of neonatal sepsis in the first week
of life, after group B streptococci, and sepsis due to ampicillinresistant E. coli has a worse clinical outcome than does sepsis
due to group B streptococci [48, 49]. A small study from California found that, when the number of cases of sepsis due to
group B streptococci decreased in 1 hospital, the number of
cases of other types of early-onset sepsis actually increased [50].
In a larger observational study from Australia, rates of sepsis
caused by organisms other than group B streptococci decreased
significantly during the period when the incidence of group B
streptococcal sepsis dropped [51]. CDC’s Active Bacterial Core
surveillance (ABCs) is tracking all causes of early-onset sepsis
in a few states; no increase in the incidence of infection with
E. coli or of other infections has been detected to date. The
possibility that other infections—in particular, those due to
resistant pathogens—will emerge suggests the need for continued surveillance.
To determine whether additional opportunities for prevention of group B streptococcal disease exist, CDC’s ABCs, part
of the Emerging Infections Program Network, has been tracking
detailed information on early-onset cases that have occurred
754 • CID 2001:33 (15 September) • IDSA LECTURE
Figure 1. Incidence (cases per 100,000 population; bars) and casefatality ratio (%; line) of invasive group B streptococcal disease by age
group (years), United States, 1999. From the Active Bacterial Core surveillance of the Emerging Infections Program Network, estimated population of 25,844,605 for 1999. See also http://www.cdc.gov/ncidod/dbmd/
abcs.
in recent years, despite the prevention guidelines. A review of
1300 cases from 1998 and 1999 in a population with ∼300,000
births annually found that approximately one-fifth of cases
occurred despite administration of intrapartum antibiotics
[52]. These cases may represent antibiotic failures; however, in
some instances, administration of antibiotics earlier during labor might have been more effective. Only 35% of case-mothers
had been screened prenatally for group B streptococcal colonization, and only 44% of case-mothers had a risk factor evident at the time of labor. Forty percent of case-mothers presented with none of the risk-based criteria for prophylaxis and
without having been screened for group B streptococcal colonization. Recent cases represent a mixture of missed opportunities for prevention, protocol failures, and cases that would
not be preventable even under perfect implementation of prophylaxis strategies.
PROGRESS AND PRIORITIES
During 1999, an estimated 1600 cases of early-onset group B
streptococcal disease occurred in the United States. On the basis
of disease burden in the era before prevention standards, an
estimated 4500 cases and 225 deaths due to early-onset group
B streptococcal disease were prevented in 1999. The decrease
in the incidence of disease resulted from provision of penicillin—an antibiotic that has been available for more than half
a century—to selected women during childbirth by means of
a strategy that had been demonstrated to be effective a decade
before it was widely accepted as a standard of care. Behind the
statistics lies the message that biotechnological breakthroughs
are not always needed to make major differences in health.
Sometimes what is needed is a decision that the problem is
worth addressing.
Today, the antimicrobial prophylaxis strategies are making a
difference, but they may not be the ultimate solution to prevention of group B streptococcal infection. They were proposed
as interim strategies while development of more comprehensive
tools continues. Antimicrobial prophylaxis will not prevent all
cases of early-onset disease. Prenatal cultures are not always
predictive of colonization at delivery, and antibiotics are not
100% effective. Intrapartum prophylaxis has not reduced the
occurrence of late-onset group B streptococcal disease and does
not prevent stillbirths, miscarriages, or preterm deliveries attributable to group B streptococci [53]. In addition, the sustainability of frequent use of antimicrobial agents for prophylaxis during labor is not assured; potential risks of this
approach, such as emergence of problems with resistance and
adverse effects, may eventually outweigh the current benefits.
Additional syndromes, such as invasive group B streptococcal
disease in nonpregnant adults, will not be addressed through
this strategy. Adults, primarily those with chronic medical conditions or the elderly, now experience most of the illness and
death caused by this pathogen (figure 1) [54]. These concerns
motivate continued interest and activity in evaluation of group
B streptococcal vaccines.
A few lessons learned from the past 2 decades of perinatal
group B streptococcal disease may be generalizable to other
health concerns. It is essential that research trials are linked to
subsequent clinical practice. The tribulations that are a common part of public health can be exploited if we learn to use
controversy as a springboard to forging consensus. Triumphs
may be rare, but when they occur, they should not only be
celebrated but they should be used to convert skeptics to the
idea that change is possible. The future may be filled with
trepidation, but if we expect the unexpected, we can be better
prepared to respond to it effectively.
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References
1. Lancefield RC. A serological differentiation of human and other groups
of hemolytic streptococci. J Exp Med 1933; 57:571–95.
2. Lancefield RC, Hare R. The serological differentiation of pathogenic
and non-pathogenic strains of hemolytic streptococci from parturient
women. J Exp Med 1935; 61:335–49.
3. Fry RM. Fatal infections by haemolytic streptococcus group B. Lancet
1938; 1:199–201.
4. Hood M, Janney A, Dameron G. Beta hemolytic streptococcus group
B associated with problems of perinatal period. Am J Obstet Gynecol
1961; 82:809–18.
5. Rantz LA, Kirby WMM. Hemolytic streptococcus bacteremia: report
of thirteen cases with special reference to serologic groups of etiologic
organisms. N Engl J Med 1942; 227:730–3.
6. Eickhoff TC, Klein JO, Daly AK, Ingall D, Finland M. Neonatal sepsis
and other infections due to group B beta-hemolytic streptococci. N
Engl J Med 1964; 271:1221–8.
7. Baker CJ, Barrett FF, Gordon RC, Yow MD. Suppurative meningitis
23.
24.
25.
26.
27.
28.
due to streptococci of Lancefield group B: a study of 33 infants. J
Pediatr 1973; 82:724–9.
Franciosi RA, Knostman JD, Zimmerman RA. Group B streptococcal
neonatal and infant infections. J Pediatr 1973; 82:707–18.
Barton LL, Feigin RD, Lins R. Group B beta hemolytic streptococcal
meningitis in infants. J Pediatr 1973; 82:719–23.
Regan JA, Klebanoff MA, Nugent RP. The epidemiology of group B
streptococcal colonization in pregnancy. Vaginal Infections and Prematurity Study Group. Obstet Gynecol 1991; 77:604–10.
Baker CJ, Edwards MS. Group B streptococcal infections. In: Remington J, Klein JO, eds. Infectious diseases of the fetus and newborn
infant. 4th ed. Philadelphia: WB Saunders, 1995:980–1054.
Gardner SE, Yow MD, Leeds LJ, Thompson PK, Mason EO, Clark DJ.
Failure of penicillin to eradicate group B streptococcal colonization in
the pregnant woman: a couple study. Am J Obstet Gynecol 1979; 135:
1062–5.
Siegel JD, McCracken GHJ, Threlkeld N, DePasse BM, Rosenfeld CR.
Single-dose penicillin prophylaxis of neonatal group B streptococcal
disease. Lancet 1982; 1:1426–30.
Allardice JG, Baskett TF, Seshia MMK, Bowman N, Malazdrewicz R.
Perinatal group B streptococcal colonization and infection. Am J Obstet
Gynecol 1982; 142:617–20.
Yow MD, Mason EO, Leeds LJ, Thompson PK, Clark DJ, Gardner SE.
Ampicillin prevents intrapartum transmission of group B streptococcus. JAMA 1979; 241:1245–7.
Easmon CSF, Hastings MJG, Deeley J, Bloxham B, Rivers RPA, Marwood R. The effect of intrapartum chemoprophylaxis on the vertical
transmission of group B streptococci. Br J Obstet Gynaecol 1983; 90:
633–5.
Matorras R, Garcia-Perea A, Madero R, Usandizaga JA. Maternal colonization by group B streptococci and puerperal infection: analysis of
intrapartum chemoprophylaxis. Eur J Obstet Gynecol Reprod Biol
1990; 38:203–7.
Boyer KM, Gotoff SP. Prevention of early-onset neonatal group B
streptococcal disease with selective intrapartum chemoprophylaxis. N
Engl J Med 1986; 314:1665–9.
Morales WJ, Lim D. Reduction of group B streptococcal maternal and
neonatal infections in preterm pregnancies with premature rupture of
membranes through a rapid identification test. Am J Obstet Gynecol
1987; 157:13–6.
Garland SM, Fliegner JR. Group B streptococcus and neonatal infections: the case for intrapartum chemoprophylaxis. Aust NZ J Obstet
Gynaecol 1991; 31:119–22.
Tuppurainen N, Hallman M. Prevention of neonatal group B streptococcal disease: intrapartum detection and chemoprophylaxis of heavily colonized parturients. Obstet Gynecol 1989; 73:583–7.
Baker CJ. Inadequacy of rapid immunoassays for intrapartum detection
of group B streptococcal carriers. Obstet Gynecol 1996; 88:51–5.
Boyer KM, Gadzala CA, Kelly PD, Burd LI, Gotoff SP. Selective intrapartum chemoprophylaxis of neonatal group B streptococcal earlyonset disease. II. Predictive value of prenatal cultures. J Infect Dis
1983; 148:802–9.
Badri MS, Zawaneh S, Cruz AC, et al. Rectal colonization with group
B streptococcus: relation to vaginal colonization of pregnant women.
J Infect Dis 1977; 135:308–12.
Yancey MK, Schuchat A, Brown LK, Ventura VL, Markenson GR. The
accuracy of late antenatal screening cultures in predicting genital group
B streptococcal colonization at delivery. Obstet Gynecol 1996; 88:811–5.
Hillier S, Schuchat A. Preventing neonatal group B streptococcal disease: the role of the clinical microbiology laboratory. CMNEEJ 1997;
19:113–6.
Strickland DM, Yeomans ER, Hankins GDV. Cost effectiveness of intrapartum screening and treatment for maternal group B streptococci
colonization. Am J Obstet Gynecol 1990; 163:4–8.
Mohle-Boetani J, Schuchat A, Plikaytis BD, Smith D, Broome CV.
Comparison of prevention strategies for neonatal group B streptococcal
IDSA LECTURE • CID 2001:33 (15 September) • 755
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
infection: a population-based economic analysis. JAMA 1993; 270:
1442–8.
Yancey MK, Duff P. An analysis of the cost-effectiveness of selected
protocols for the prevention of neonatal group B streptococcal infection. Obstet Gynecol 1994; 83:367–71.
Rouse DJ, Goldenberg RL, Cliver SP, Cutter GR, Mennemeyer ST, Fargason CA. Strategies for the prevention of early-onset neonatal group B
streptococcal sepsis: a decision analysis. Obstet Gynecol 1994; 83:483–94.
McLaughlin GE. Investigating the group B strep case. Trial 1998; May:
42–5.
American College of Obstetricians and Gynecologists Committee on
Obstetric Practice (ACOG). Prevention of early-onset group B streptococcal disease in newborns [ACOG committee opinion]. Washington
DC: ACOG, 1996.
American Academy of Pediatrics Committee on Infectious Diseases
and Committee on Fetus and Newborn. Revised guidelines for prevention of early-onset group B streptococcal (GBS) infection. Pediatrics
1997; 99:489–96.
Centers for Disease Control and Prevention. Prevention of perinatal
group B streptococcal disease: a public health perspective. MMWR
Morb Mortal Wkly Rep 1996; 45(RR-7):1–24.
Rosenstein N, Schuchat A. Opportunities for prevention of perinatal
group B streptococcal disease: a multistate surveillance analysis. Neonatal GBS Disease Study Group. Obstet Gynecol 1997; 90:901–6.
Queenan JT. GBS prevention: national guidelines at last. Contemp Ob/
Gyn 1996; 41:8–11.
Centers for Disease Control and Prevention. Adoption of hospital policies for prevention of perinatal group B streptococcal disease: United
States, 1997. MMWR Morb Mortal Wkly Rep 1998; 47:665–70.
Schrag S, Zywicki S, Farley MM, et al. Group B Streptococcal disease
in the era of intrapartum antibiotic prophylaxis, 1993–1998. N Engl J
Med 2000; 342:15–20.
Factor SH, Whitney CG, Zywicki S, Schuchat A. Effects of hospital
policies on the 1996 group B streptococcal consensus guidelines. ABC
Surveillance Team. Obstet Gynecol 2000; 95:377–82.
Centers for Disease Control and Prevention. Hospital-based policies
for prevention of perinatal group B streptococcal disease: United States,
1999. MMWR Morb Mortal Wkly Rep 2000; 49:936–40.
Centers for Disease Control and Prevention. Adoption of perinatal
group B streptococcal disease prevention recommendations by prenatal-care providers: Connecticut and Minnesota, 1998. MMWR Morb
Mortal Wkly Rep 2000; 49:228–32.
756 • CID 2001:33 (15 September) • IDSA LECTURE
42. Watt JP, Schuchat A, Erickson K, Honig JE, Gibbs R, Schulkin J. Group
B streptococcal disease prevention practices of obstetrician-gynecologists. Obstet Gynecol 2001; 98:7–13.
43. Centers for Disease Control and Prevention. Laboratory practices for
prenatal group B streptococcal screening and reporting B: Connecticut,
Georgia, and Minnesota, 1997–1998. MMWR Morb Mortal Wkly Rep
1999; 48:426–8.
44. Centers for Disease Control and Prevention. Notice to readers: shortage
of intravenous penicillin G: United States. MMWR Morb Mortal Wkly
Rep 1999; 48:974.
45. Pearlman MD, Pierson CL, Faix RG. Frequent resistance of clinical
group B streptococci isolates to clindamycin and erythromycin. Obstet
Gynecol 1998; 92:258–61.
46. Fernandez M, Hickman ME, Baker CJ. Antimicrobial susceptibilities
of group B streptococci isolated between 1992 and 1996 from patients
with bacteremia or meningitis. Antimicrob Agents Chemother 1998;
42:1517–9.
47. Morales WJ, Dickey SS, Bornick P, Lim DV. Change in antibiotic resistance of group B streptococcus: impact on intrapartum management.
Am J Obstet Gynecol 1999; 181:310–4.
48. Schuchat A, Zywicki S, Dinsmoor MJ, et al. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter
case-control study. Pediatrics 2000; 105:21–6.
49. Gladstone IM, Ehrenkranz RA, Edberg SC, Baltimore RS. A ten-year
review of neonatal sepsis and comparison with the previous fifty-year
experience. Pediatr Infect Dis J 1990; 9:819–25.
50. Towers CV, Carr MH, Padilla G, Asrat T. Potential consequences of
widespread antepartal use of ampicillin. Am J Obstet Gynecol 1998;
179:879–83.
51. Isaacs D, Royle JA. Intrapartum antibiotics and early onset neonatal
sepsis caused by group B Streptococcus and by other organisms in
Australia. Australasian Study Group for Neonatal Infections. Pediatr
Infect Dis J 1999; 18:524–8.
52. Centers for Disease Control and Prevention. Early-onset group B streptococcal disease: United States, 1998–1999. MMWR Morb Mortal Wkly
Rep 2000; 49:793–6.
53. Regan JA, Klebanoff MA, Nugent RP, et al. Colonization with group
B streptococci in pregnancy and adverse outcome. Am J Obstet Gynecol
1996; 174:1354–60.
54. Jackson LA, Hilsdon R, Farley M, et al. Risk factors for group B streptococcal disease in adults. Ann Intern Med 1995; 123:415–20.