Cover article

Perinatal group B streptococcal disease:
The next generation of prevention

By Anne Schuchat, MD

Increased use of intrapartum antimicrobial prophylaxis since the 1990s has greatly reduced the rate of invasive GBS disease, a major cause of death in newborns. Universal implementation of updated guidelines for disease prevention will accelerate this important trend.

In 2002, the Centers for Disease Control and Prevention (CDC) released updated guidelines for preventing neonatal infections caused by group B Streptococcus (GBS). Although release of these guidelines, developed in consultation with the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG), may seem to many pediatricians like déja vu all over again, they offer the opportunity to improve prevention of GBS infection in a new generation of babies.^1,2 The new guidelines recommend universal prenatal screening cultures for GBS colonization. They represent a major update to earlier recommendations, issued in 1996 and 1997, which offered a risk-based strategy (that does not rely on cultures) as equally acceptable to prenatal screening (which does rely on cultures).^3–5 Because of compelling new data from a 2002 study reporting the superior effectiveness of the screening strategy,⁶ experts concluded that the time has come for universal screening. Pediatricians need to be aware of other key recommendations in the revised guidelines as well as updated resources for educating themselves, their patients, and local health-care institutions about prevention of GBS disease, a leading cause of illness and death in newborns.

Where we were

Three decades ago, pediatricians first noted an increase in severe neonatal sepsis caused by Streptococcus agalactiae, also known as GBS.⁷ Until then, this b-hemolytic gram-positive coccus was less familiar than Streptococcus pyogenes (group A Streptococcus). S pyogenes was a common cause of childhood pharyngitis and scarlet fever and, in the mid 19th century, was responsible for outbreaks of puerperal sepsis (originally referred to as childbed fever). GBS, on the other hand, had been considered a relatively harmless commensal organism, but the high fatality rate associated with neonatal sepsis, pneumonia, and meningitis in the 1970s and 1980s changed this perception, particularly in relation to the vulnerable newborn.⁸

By the 1980s, pediatric researchers showed that providing antibiotics intrapartum to selected women interrupted spread of the bacteria from mother to child.⁹ This led, about 10 years ago, to AAP's release of its first guidelines for preventing early-onset GBS disease through selective chemoprophylaxis.¹⁰ Then, in 1996, AAP, ACOG, and CDC achieved a consensus that prevention strategies represented a standard of care. All three groups recommended use of intrapartum antibiotic prophylaxis for candidates identified by one of two strategies: prenatal screening to identify silent GBS carriers or a risk-based strategy that relied on obstetric complications in labor instead of prenatal culture results. Under both strategies, intrapartum antimicrobial prophylaxis was provided to women who previously had an infant with GBS disease or who had GBS bacteriuria during the current pregnancy.

Before 1993, GBS caused about 7,600 cases of newborn invasive disease annually in the United States, with 6,100 early-onset infections evident in the first week of life.¹¹ Such early-onset disease occurs through vertical transmission during labor or after rupture of amniotic membranes. Risk of early-onset infection was higher among preterm deliveries, African-Americans, and deliveries complicated by amnionitis or prolonged rupture of the membranes. Late-onset infection, which develops from 1 week to 3 months of life, was less common and represented a mixture of vertical and horizontal transmission. A common factor for increased risk of infection is maternal colonization of the vagina or rectum with GBS.

Increased use of intrapartum antibiotic prophylaxis in the 1990s had a striking impact on disease burden (Figure 1, available in the print issue, adapted from MMWR 2002:51(No.RR-11), Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease). By 1998, the incidence of early-onset GBS disease had dropped 65%, representing a major prevention milestone in pediatrics.¹² Recent data suggest, however, that even more can be done.¹³ As a result, the CDC has issued new guidelines, supported and endorsed by AAP and ACOG, to capitalize on the latest scientific results and potentially simplify the information health-care providers and parents need to know.

Where we are now

From 1998 through 2001, the incidence of early-onset GBS disease reached a plateau. Although prophylaxis prevented about 4,400 cases of early-onset infections each year, an estimated 1,720 babies developed early-onset GBS disease in 2001 and 70 to 90 infants died from the disease.¹⁴

To address the possibility of further disease prevention, the CDC collaborated on a study with investigators in eight states that have ongoing active surveillance for GBS disease. This multistate cohort study in a population of more than 600,000 births was designed to evaluate the relative effectiveness of the screening and risk-based strategy. It demonstrated that prenatal screening was over 50% more effective in reducing early-onset GBS disease than the risk-based strategy.⁶ The principal advantage of the screening-based approach is that it reaches women with no obstetric risk factors—and these women make up a large proportion of the population at risk of transmitting GBS infection to their newborns.

Critical reappraisal of available data from this study, as well as from smaller investigations, led to the next generation of prevention recommendations promoting universal prenatal screening (Figure 2, Adapted in the print edition from MMWR 2002:51(No.RR-11), Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease).

A single approach. Unlike earlier guidelines, the new recommendations do not present the risk-based approach as an acceptable alternative for disease prevention (Table 1, Adapted in the print edition from MMWR 2002:51(No.RR-11), Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease).. Rather, the risk-based approach is reserved for two specific situations: the woman who begins labor and who has not been screened for GBS, and the woman for whom no prenatal screening results are available. The new guidelines also update several other issues.

The recommendations call for all pregnant women to undergo prenatal screening at 35 to 37 weeks' gestation, based on swabs collected from the vagina and rectum. Women identified as GBS carriers should receive intrapartum antimicrobial prophylaxis during labor or after membranes have ruptured. Women who delivered a baby with GBS disease in a previous pregnancy also should receive intrapartum antimicrobial prophylaxis—these women do not need to be screened at 35 to 37 weeks' gestation.

Because GBS bacteriuria during pregnancy is an indicator of heavy or dense colonization with GBS, its presence calls for intrapartum antimicrobial prophylaxis and also eliminates the necessity for screening at 35 to 37 weeks' gestation. GBS bacteriuria can cause a urinary tract infection, which should be treated the same way any such infection during pregnancy would be. In addition, the patient should be subject to intrapartum antimicrobial prophylaxis after labor begins or membranes rupture.

As described above, two categories of women are subject to the risk-based strategy because their GBS status is unknown at the time of delivery. These patients should receive intrapartum antimicrobial prophylaxis only in certain circumstances: threatened preterm delivery, membrane rupture lasting 18 hours or longer, or intrapartum temperature of 100.4° F (38° C) or higher.

Recommended agents. Intravenous penicillin is the recommended first-line agent for GBS prophylaxis, with ampicillin an acceptable alternative. GBS strains have become increasingly resistant to clindamycin and erythromycin, the agents previously recommended for prophylaxis in the penicillin-allergic woman. In light of these trends, the new prevention guidelines update antibiotic prophylaxis regimens (Table 2, Adapted in the print edition from MMWR 2002:51(No.RR-11), Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease).

Processing of cultures. The new guidelines also include expanded instructions to assure that microbiology laboratories correctly process culture specimens by, for example, using a recommended selective broth medium. The guidelines also outline the procedure for susceptibility testing of isolates in penicillin-allergic women.

Managing newborns of treated mothers. In addition, the new guidelines update an ongoing concern of pediatricians: how to manage newborns whose mother has received chemoprophylaxis for prevention of early-onset GBS or suspected chorioamnionitis. Concern that antibiotics may mask or delay signs of infection in newborns led some providers to increase diagnostic testing and empiric therapy in such newborns. Regrettably, data on optimal management of newborns exposed to maternal prophylaxis are scarce. Nonetheless, the new guidelines include an algorithm that reflects additional experience showing that early discharge of lower-risk newborns may be reasonable in certain circumstances and data suggesting that ampicillin or penicillin, initiated at least four hours before delivery, provides adequate efficacy against vertical transmission of GBS (Figure 3, Adapted in the print edition from MMWR 2002:51(No.RR-11), Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease). The algorithm also clarifies the use of lumbar puncture, so as to encourage use of this procedure in appropriate circumstances. A significant percentage of cases of neonatal meningitis can be missed with reliance on blood cultures alone. Individual institutions and providers may adapt the algorithm in light of local data and preferences.

Managing late-onset disease. GBS remains fully susceptible to penicillin and ampicillin, and these drugs are appropriate for treating late-onset infection. Newborns are not likely to be allergic to these agents. Resistance to clindamycin and erythromycin is increasing, but these antibiotics are not often used for neonatal sepsis therapy.

Where we want to go

Even perfect implementation of the new GBS prevention guidelines cannot prevent some cases of early-onset GBS disease. In addition, late-onset disease continues to affect about 1,300 infants in the US each year. At present, no evidence exists to support the use of prophylactic antibiotics to reduce the likelihood of these late-onset infections, for which risk factors are unknown. Although intrapartum prophylaxis reduces colonization of GBS in the infant's closest contact, the reduction of vaginal colonization, both in terms of prevalence and potential density, is likely to be transient. In addition, GBS colonization of the gastrointestinal tract is unlikely to be eradicated by the typical one or two doses of intravenous antibiotic prophylaxis. Because infants with late-onset GBS disease may acquire the organism at birth or during the next several weeks, transient reduction of colonization in the mother might not be expected to affect the child. In addition, some babies may acquire the organism from other contacts in the home, hospital, or community.

GBS vaccines, administered either during pregnancy or, potentially, during adolescence, offer the best theoretical approach to preventing both early- and late-onset infections. The resulting maternal antibodies can cross the placenta during pregnancy and circulate in the newborn for a few months after birth—long enough to protect the infant during the period of risk for late-onset infection. (If a woman is vaccinated during adolescence, the antibodies will wane over time before pregnancy, but it is believed that placental transfer would still provide the baby with protection for the first few months of life.) Other preventive possibilities are to define risk factors for late-onset GBS disease (some could be modifiable) and to identify subsets of infants who might benefit from hyperimmune globulin approaches to protection against infection.

Full implementation of universal prenatal screening is likely to produce additional gains in the prevention of early-onset disease while clinical research and vaccine development continue. The Government Performance Results Act set a national target of fewer than 0.3 cases of early-onset disease for every 1,000 births.¹⁵ Similarly, the Healthy People 2010 target is fewer than 0.5 cases of early-onset disease for every 1,000 live births for all racial and ethnic groups.¹⁶ Part of the objective is to eliminate health disparities based on race; the rate of early-onset GBS disease in white people is now at, or below, 0.5 cases for every 1,000 births, according to the CDC, whereas the rate in African-Americans is considerably higher. Reaching these targets requires the collaboration of clinicians, laboratories, administrators, public health workers, and the public in following the updated guidelines and instituting universal prenatal screening for GBS colonization.

What obstacles remain

Many issues related to prevention of GBS disease have not yet been addressed; the possible emergence of antibiotic resistance is especially important.

Effects of increased antibiotic use. Administration of antibiotics during labor and delivery to prevent GBS infection results in increased antibiotic use, the consequences of which require monitoring. One concern is that GBS, the target of preventive antibiotics, may itself develop antibiotic resistance. As of now, GBS remains susceptible to penicillin and to ampicillin.

However, increases in resistance to both clindamycin and erythromycin, agents once recommended for penicillin-allergic women, have led to changes in the recommendations for second-line antibiotic agents. One option, vancomycin, is the last remaining antibiotic to be effective against many gram-positive infections, and overuse of this drug is a national concern. Universal prenatal GBS screening will result in large populations receiving antibiotics and the likelihood that resistance to penicillin eventually will emerge. This likelihood underscores the rationale for considering intrapartum antimicrobial prophylaxis an interim strategy for GBS prevention, to be used only until a vaccine for this infection becomes available for clinical use.

Infection from other neonatal pathogens. Although major reductions in the incidence of early-onset GBS disease already have been detected, some observers fear that infections caused by other neonatal pathogens may be increasing. Thus far, evaluation of early-onset neonatal sepsis trends in the era of intrapartum antibiotic prophylaxis for GBS suggests a net decline in overall early-onset sepsis in the general population.^17–19

Gram-negative infections, however, particularly those caused by ampicillin-resistant Escherichia coli, appear to be increasing in the very low birth-weight or preterm population.^17,20 Community-acquired E coli infection has become increasingly resistant, independent of changes in the use of b-lactam antibiotics in labor and delivery. Continued surveillance will be important to assure that one problem has not been replaced with another.²¹

Lack of proper laboratory procedures. The new guidelines for GBS prevention focus on prenatal screening for colonization, using cultures processed in selective broth medium. This strategy will reach the vast majority of pregnant women, but its success depends on appropriate tests being carried out in clinical microbiology laboratories. Surveys in the late 1990s suggested that many laboratories were using insensitive methods to culture GBS, so increased attention is being paid now to assuring compliance by clinical laboratories.²² These efforts will help assure provider confidence in laboratory results—in particular, in the accuracy of a negative prenatal culture result.

Communication of results from laboratories to clinicians and labor and delivery sites is also a challenge, particularly when a single obstetric practice uses many different laboratories. Furthermore, because not all women receive prenatal care, some will not be screened for GBS before labor. (As mentioned, the new guidelines recommend that women in whom GBS test results are not available should be managed according to the presence of obstetric risk factors.)

The Food and Drug Administration recently approved a real-time polymerase chain reaction test that offers rapid detection of GBS from clinical specimens. The test relies on fairly expensive laboratory equipment and is therefore not widely available. In institutions that have such equipment, however, these tests make it possible to ascertain during labor the GBS colonization status of women who have not had prenatal care.

Insufficient data on newborn management. For pediatricians, an important challenge in this era of intrapartum antibiotic prophylaxis has been to care for infants whose mothers received antibiotics. This is an important area of clinical concern, and additional research is needed. It will be valuable in balancing cost containment and optimal health outcomes, as well as patient preferences.

How to help your patients, hospital, and community

Clinicians continue to be bombarded by practice guidelines, and it can be difficult for individuals and institutions to change practice. GBS prevention is a team sport, and successful implementation requires substantial coordination among players within the health-care environment. Hospitals and managed care organizations can form committees to assure a smooth transition to implementation of the new guidelines.²³ Such committees may benefit from the participation of personnel from obstetrics, pediatrics, microbiology, pharmacy, nursing, infection control, and medical information systems (see "Meeting the challenge of making a transition").

Some institutions have adopted standing orders for use of prophylactic antibiotics in defined circumstances. Others have found creative ways to flag the records of women who are colonized with GBS so that labor and delivery staff can easily recognize candidates for prophylaxis. Institutions have also introduced routine performance monitoring to track the efficacy of programs in ensuring that women get prenatal tests and that positive results are appropriately addressed.

Pediatricians have an important role in educating parents, other clinicians, and institutions in their communities about the importance of putting the new guidelines into practice so as to prevent GBS infections (Table 3). Community-based activities also provide an opportunity to improve prevention of GBS disease. Pediatricians can offer their services to state and local health departments, who will benefit from their expertise. Community groups, such as parent advocacy or disability-awareness organizations, may also be interested in pediatrician perspectives on GBS prevention. Many educational tools are available from the CDC and other organizations (see "The word on GBS prevention—and getting it out").

TABLE 3
What you can do to help prevent GBS infections

Getting it together

The revised 2002 guidelines on perinatal GBS prevention include many changes to earlier guidelines. By putting these new recommendations into practice, health-care providers can build on the gains already achieved since intrapartum antibiotic prophylaxis was begun in the 1990s.

REFERENCES

1. Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Morbid Mortal Weekly Rep 2002;51(RR-11):1

2. American College of Obstetricians and Gynecologists: Prevention of early-onset group B streptococcal disease in newborns. ACOG Committee Opinion 2002;100(279):1405

3. Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease: A public health perspective. MMWR Morbid Mortal Weekly Rep 1996;45 (RR-7):1

4. American College of Obstetricians and Gynecologists Committee on Obstetric Practice: Prevention of early-onset group B streptococcal disease in newborns. ACOG Committee Opinion (No. 173), 1996

5. 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

6. Schrag SJ, Zell ER, Lynfield R, et al: A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002;347:233

7. McCracken GH: Group B streptococci: The new challenge in neonatal infections. J Pediatr 1973;82:703

8. Schuchat A: Epidemiology of group B streptococcal disease in the United States: Shifting paradigms. Clin Microbiol Rev 1998;11:497

9. Boyer KM, Gotoff SP: Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis. N Engl J Med 1986; 314:1665

10. Committee on Infectious Diseases and Committee on Fetus and Newborn: Guidelines for prevention of group B streptococcal (GBS) infection by chemoprophylaxis. Pediatrics 1992;90:775

11. Zangwill KM, Schuchat A, Wenger JD: Group B streptococcal disease in the United States, 1990: Report from a multistate active surveillance system. MMWR Surveillance Summaries 1992;41(SS-6):25

12. 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

13. Centers for Disease Control and Prevention: Early-onset group B streptococcal disease—United States, 1998–1999. MMWR Morbid Mortal Weekly Rep 2000;49:793

14. www.cdc.gov/ncidod/dbmd/abcs/survreports/gbs01_provis.pdf

15. Whittaker JB: The Government Performance and Results Act of 1993: A Mandate for Strategic Planning and Performance Measurement, 1995, Educational Services Institute, Arlington, Va.

16. U.S. Department of Health and Human Services: Healthy People 2010: Understanding and Improving Health, ed 2. Washington, D.C., US Government Printing Office, 2000

17. Hyde TJ, Hilger TM, Reingold A, et al: Trends in incidence and antimicrobial resistance of early-onset sepsis: Population-based surveillance in San Francisco and Atlanta. Pediatrics 2002;110:690

18. Baltimore RS, Huie SM, Meek JI, et al: Early-onset neonatal sepsis in the era of group B streptococcal prevention. Pediatrics 2001;108:1094

19. Isaacs D, Royle JA, Australasian Study Group for Neonatal Infections: Intrapartum antibiotics and early onset neonatal sepsis caused by group B streptococcus and by other organisms in Australia. Pediatr Infect Dis J 1999;18:524

20. Stoll BJ, Hansen N, Fanaroff A, et al: Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med 2002;347:240

21. Moore MR, Schrag SJ, Schuchat A: Effects of intrapartum antimicrobial prophylaxis for prevention of group B streptococcal disease on the incidence and ecology of early-onset neonatal sepsis. Lancet Infectious Diseases 2003;3(4):201

22. Centers for Disease Control and Prevention: Laboratory practices for prenatal group B streptococcal screening and reporting—Connecticut, Georgia, and Minnesota, 1997–1998. MMWR Morbid Mortal Weekly Rep 1999;48:426

23. Davis RL, Hasselquist MB, Cardenas V, et al: Introduction of the new CDC group B streptococcal prevention guideline at a large West Coast health maintenance organization. Am J Obstet Gynecol 2001;184:603

DR. SCHUCHAT is chief, Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention. She has nothing to disclose in regard to affiliations with, or financial interests in, any organization that may have an interest in any part of this article.

Meeting the challenge of making a transition

Committees that have been formed by hospitals and managed care organizations to ensure a smooth transition to implementation of the new guidelines face challenges. Many of the issues such a committee must address—including planning testing and treatment protocols for women with penicillin allergies—focus on prenatal care and obstetrics. Nonetheless, participation by knowledgeable pediatrics staff will ensure presentation of, first, issues of pertinence to the baby and, second, changes in general obstetric management that may influence pediatric care. Questions that implementation committees should address include:

• Is the laboratory able to conduct antimicrobial susceptibility testing for clindamycin and erythromycin?

• If so, how will prenatal care providers label prenatal swabs from penicillin-allergic women to alert microbiology staff to the need for susceptibility testing?

• What agent(s) will be used for penicillin-allergic women at risk of anaphylaxis? If vancomycin will be used for either all penicillin-allergic patients at risk of anaphylaxis, or those with clindamycin or erythromycin resistance, does pharmacy require special notifications or permissions to permit its use?

• Are tools available locally (such as fact sheets, brochures, cards) to facilitate prenatal education regarding labor and delivery plans, particularly for penicillin-allergic women?

• Are tools available locally for parent education about observation and discharge procedures for the infant whose mother had GBS prophylaxis? If early discharge instructions are already developed, do they need to be adapted to incorporate local GBS protocols?

• Can the hospital begin monitoring neonatal sepsis to evaluate the impact of prophylaxis policies on GBS and other pathogens? Will this information be reported to public health authorities, such as local or state health departments?

The word on GBS prevention—and getting it out

The Centers for Disease Control and Prevention Web site page, www.cdc.gov/groupbstrep , offers access to a wealth of information about GBS disease for patients, providers, and laboratories. Click on "Hospital & Health Care Providers" and link to:

• "New Guidelines" for the new guidelines in their entirety, as published in Morbidity & Mortality Weekly Report (2002:51 [No. RR-11])

• "Professional & Patient Resources" for patient handouts, instructions for collecting a genital swab, sample prenatal testing cards for tracking screening results, and a list of readings, among other information. This screen also provides a link to the Web site of the American College of Obstetricians and Gynecologists, from which you can order a patient pamphlet entitled "Group B Streptococcus and Pregnancy." Another link, to the American College of Nurse Midwives site, provides access to a list of frequently asked questions and their answers.

• "Slide Sets & Other Tools" for access to slide presentations on clinical issues and an introduction to the new guidelines and recommendations for laboratory processing of specimens.

• "For More Information" for a list of patient brochures and fliers about GBS that can be ordered from the CDC and reprints of the complete guidelines. Small numbers of print or video materials also can be ordered from GBS Health Communications Specialist, CDC, 1600 Clifton Rd., NE MS A-49, Atlanta, GA 30333, or by fax at 404-371-5434. To order bulk copies of CDC materials, contact the Public Health Foundation at www.phf.org or 877-252-1200 (toll free).

 

Anne Schuchat. Perinatal group B streptococcal disease: The next generation of prevention. Contemporary Pediatrics September 2003;20:40.