1. Early-onset Group B Streptococcal Disease Prevention: For Clinicians Overview of CDC Prevention Guidelines, National Center for Immunization and Respiratory Diseases Division of Bacterial Diseases November 19, 2010
This presentation will provide an overview of early-onset Group B streptococcal disease prevention for Clinicians with a focus on CDC’s 2010 prevention guidelines
Image: CDC logo (Centers for Disease Control and Prevention) and HHS logo (Department of Health and Human Services)
National Center for Immunization & Respiratory Diseases
Division of Bacterial Disease

2. Background on Group B Streptococcal (GBS) Disease and Prevention
This section will provide background on Group B streptococcal disease, also known as GBS disease, and prevention.

3. Group B Streptococcus Gram positive, beta hemolytic bacteria
Common colonizer of human gastrointestinal and genitourinary tracts
Recognized as causing disease in humans in the 1930s
Causes serious disease in young infants, pregnant women and older adults
Emerged as most common cause of sepsis and meningitis in infants <3 months in the 1970s
Group B Streptococcus
Group B Streptococcus is a gram positive, beta hemolytic bacteria.
It is a common colonizer of the human gastrointestinal and genitourinary tracts.
It was first recognized as causing disease in humans in the 1930s.
It can cause serious disease in young infants, pregnant women and older adults.
It emerged as the most common cause of sepsis and meningitis in young infants in the 1970s

4. GBS Disease in Infants Before Prevention Efforts
Early-onset: 0-6 days of life
Late onset: 7-89 days of life
GBS Disease In Infants Before Prevention Efforts
This slide shows the distribution of infant GBS disease by age of onset.
The data are taken from a study that was summarized in a review by Schuchat and published in Clin Micro Rev in 1998, Volume 11, pages The data represent cases detected in the 1980s, before prevention efforts.
Among infants under 90 days of age, the risk of GBS disease was not evenly distributed.
The graph shows that 77.5% of GBS cases in infants were among those less than 1 week old.
Cases occurring within the first week of life are called early-onset disease. Cases in infants 7-89 days of life are called late-onset.
A Schuchat. Clin Micro Rev 1998;11:

5. Early-onset GBS Disease (EOGBS)
Leading infectious cause of neonatal sepsis in U.S.
Annual incidence in 2008: 0.28 cases / 1,000 live births
Estimated 1,200 cases in 2008
Clinical presentation
Typically symptoms appear on day 0 or day 1 of life
Respiratory distress, apnea, signs of sepsis most common symptoms
Bacteremia most common form of disease (app. 80% of cases)
Pneumonia and meningitis less common
Case fatality rate
1970s: As high as 50%
4-6% in recent years
Early-onset GBS Disease
Early-onset GBS disease is the leading infectious cause of neonatal sepsis in the U.S.
Early-onset GBS disease annually causes cases / 1,000 live births
Early-onset GBS disease causes an estimated 1,200 cases of neonatal sepsis per year.
Clinical presentation
Typically symptoms appear on day 0 or day 1 of life
Symptoms often include respiratory distress, apnea, signs of sepsis.
Bacteremia most common form of Early-onset GBS disease (app. 80% of cases)
Pneumonia and meningitis are less common forms of Early-onset GBS disease.
Case fatality rate for Early-onset GBS disease
1970s: As high as 50%
4-6% in recent years

6. Photo courtesy of Dr. Carol Baker
NEONATAL GBS CLINICAL SLIDES
This is one of two slides that demonstrates the potential severity of neonatal GBS disease.
Here is an 18-hour-old-infant with GBS bacteremia and pneumonia.
In this photo, the infant’s condition has stabilized, but the infant remains on mechanical ventilation and vasopressors.
In cases of severe disease infants may require extracorporeal membrane oxygenation (ECMO), which is a temporizing, supportive treatment to effectively bypass severely diseased lungs while they are given time to heal from infection.
Photo courtesy of Dr. Carol Baker, Baylor College of Medicine, Houston, TX
Photo courtesy of Dr. Carol Baker
Baylor College of Medicine, Houston, TX

7. NEONATAL GBS CLINICAL SLIDES
This slide shows the kind of vascular compromise that can result from GBS sepsis, with extensive purpura on the legs and perineum on this 2-day-old term male infant.
This infant was born to a mother with no clinical risk factors for GBS; however, on the second day of life, the infant developed apnea, shock, disseminated intravascular coagulopathy (DIC) and peripheral gangrene and subsequently died.
Photo courtesy of Dr. Carol Baker, Baylor College of Medicine, Houston, TX
Photo courtesy of Dr. Carol Baker Baylor College of Medicine, Houston, TX

8. GBS Maternal Colonization
GBS Carriers
10% - 30% of women
Higher proportion in African Americans and nonsmokers
GBS usually live in gastrointestinal tract but can spread to the genital tract
No symptoms or signs on examination
Colonization comes and goes over months
Not a sexually transmitted infection
Risk factor for early-onset disease: GBS colonization during labor and delivery
Prenatal cultures late in pregnancy can predict delivery status
GBS MATERNAL COLONIZATION
At any given time, between 10 and 30 percent of women are colonized with GBS.
The rate is higher among African Americans and among nonsmokers.
GBS usually live in the gastrointestinal tract but can spread to the genital tract.
GBS colonization in the gastrointestinal and genital tracts of women is most often asymptomatic and does not require treatment.
Since there are no clinical signs of colonization, you cannot tell who is a GBS carrier by doing a physical exam or taking a history.
GBS colonization is a dynamic condition, GBS colonization may come and go over months.
If a woman is colonized with GBS at one point in time that does not mean that she will be colonized several months later.
This is important to recognize because prevention of GBS disease depends on identifying women who are likely to be colonized at the time of delivery.
GBS not a sexually transmitted infection
Maternal vaginal colonization with GBS at the time of labor and delivery is an important risk factor for neonatal early-onset disease. Prenatal cultures of samples taken from the vagina and rectum late in pregnancy can predict colonization status at delivery.

9. Mother to Infant Transmission of GBS
GBS colonized mother
Non-colonized newborn
50%
Colonized newborn
Asymptomatic
98%
Early-onset sepsis, pneumonia, meningitis 2%
MATERNAL-TO-INFANT TRANSMISSION
Most Group B Streptococcal Disease cases among newborns result from mother-to-infant transmission during labor and delivery.
Many women are asymptomatically colonized by group B streptococcus in the genital and gastrointestinal tracts.
Colonization is not altered by or dependent on pregnancy.
About half the infants born to colonized mothers are themselves colonized on the skin and mucosal surfaces as a result of passage through the birth canal or as a result of GBS ascending into the amniotic fluid.
The majority of colonized infants, 98%, are asymptomatic.
About 2% will develop early-onset disease, presenting with sepsis, pneumonia or meningitis in the first few days of life.

10. Additional Risk Factors for Early-onset GBS Disease
Obstetric risk factors:
Preterm delivery
Prolonged rupture of membranes
Infection of the placental tissues or amniotic fluid / fever during labor
GBS in the mother’s urine during pregnancy (marker for heavy colonization)
Previous infant with GBS disease
Low maternal levels of anti-GBS antibodies
Demographic risk factors
African American
Young maternal age
ADDITIONAL RISK FACTORS FOR EARLY-ONSET GBS DISEASE
There are certain other risk factors which increase the chance that an infant will be afflicted with the disease.
Obstetric risk factors include preterm delivery (defined as delivery at less than 37 weeks), prolonged rupture of membranes (defined in various studies as more than 12, 18 or 24 hours), and infection of the placental tissues or amniotic fluid, which can manifest as a fever during labor.
Other risk factors include symptomatic or asymptomatic GBS bacteriuria, having delivered a previous infant with GBS disease, immunologic risk factors such as a low level of antibody to GBS capsular polysaccharide, and demographic risk factors such as African-American race and young maternal age at delivery.

11. Prevention of Early-onset GBS Disease
Intrapartum antibiotics (IAP)
Highly effective at preventing early-onset disease in women at risk of transmitting GBS to their newborns
Efficacy in clinical trials: 100%
Effectiveness in observational studies: 86-89%
Challenge: How best to identify women who should receive IAP?
PREVENTION OF PERINATAL GBS DISEASE
In the 1980s, it was discovered that intrapartum antibiotics, abbreviated as IAP, are highly effective in preventing mothers at risk from transmitting GBS to their newborns. The efficacy in a clinical trial was 100% and in observational studies the effectiveness ranged from 86-89%.
The challenge since this discovery has been how to best identify women who should receive IAP.

12. 1996 Consensus Guidelines for GBS Prevention
Screening-based approach:
Vaginal-rectal culture at wks
IAP for GBS carriers
IAP for preterm delivery (unless negative culture result available)
Risk-based approach :
No vaginal-rectal culture
IAP for preterm deliveries, membrane rupture>18 hours, or intrapartum fever (T>38˚C)
Both strategies - IAP to women with:
GBS bacteriuria during pregnancy
Previous infant with GBS disease
1996 Consensus Guidelines for GBS Prevention
The 1996 Consensus Guidelines for GBS prevention outlined two approaches for identifying women in need of IAP.
Screening-based approach:
Vaginal-rectal culture at wks
IAP for GBS carriers
IAP for preterm delivery (unless negative culture result available)
Risk-based approach :
No vaginal-rectal culture
IAP for preterm deliveries, membrane rupture>18 hours, or intrapartum fever (T>38C)
Both strategies - IAP to women with:
GBS bacteriuria during pregnancy
Previous infant with GBS disease

13. Rate of Early- onset GBS Disease in the 1990s, United States
Group B Strep Association formed
1st ACOG & AAP
statements
CDC draft
guidelines published
Consensus
guidelines
RATE OF EARLY- AND LATE-ONSET GBS DISEASE IN THE 1990s, U.S.
This slide plots the incidence of early-onset GBS disease in areas covered by the multi-state, population-based Active Bacterial Core surveillance system from 1989 to 2000.
The white line represents early-onset GBS disease.
The incidence of early-onset GBS disease in the United States since 1993 declined 70% (from 1.7 cases per 1,000 live births in 1993 to 0.45 cases per 1,000 live births in 1999) , coinciding with increased prevention activities.
The graph shows that in 2000 the rates had plateaued at 0.5 cases per 1,000 live births.
This graph was originally published by Schrag in New England Journal of Medicine, 2000, 342:
Schrag, New Engl J Med : 15-20

14. Screening for GBS Protects More Infants from Early-onset GBS than Relying on Risk Factors
Infants whose mothers are screened for GBS are less than half as likely to develop early-onset GBS disease as mothers who are not screened
Screening identifies colonized women without obstetric risk factors (18% of all deliveries in 1990s)
Screening for GBS Protects More Infants from Early-onset GBS than Relying on Risk Factors
Infants whose mothers are screened for GBS are less than half as likely to develop early-onset GBS disease as mothers who are not screened.
Screening identifies colonized women without obstetric risk factors (18% of all deliveries in 1990s).
These data were originally published by Schrag et al. in the New England Journal of Medicine, 2002, 347:
Schrag et al, NEJM 2002, 347:233-9

15. 2002 GBS Guidelines: Key Changes
Single strategy for identifying candidates for IAP: universal screening by culture at wks
IAP agents for penicillin-allergic
Cefazolin, except for women at high risk of anaphylaxis
No routine IAP for planned cesarean deliveries
GBS screening and IAP for threatened preterm deliveries
More detail on specimen collection and handling
Neonatal management
Addition of chorioamnionitis
2002 Guidelines: Key Changes
The early-onset GBS disease prevention guidelines were updated in 2002.
Single strategy for identifying candidates for IAP: universal screening by culture at wks
IAP agents for penicillin-allergic
Ideally, cefazolin, except for women at high risk of anaphylaxis
No routine IAP for planned cesarean deliveries
GBS screening and IAP for threatened preterm deliveries
More detail on specimen collection and handling
Neonatal management
Addition of chorioamnionitis

16. Implementation and Impact of Early-onset GBS Disease Prevention Guidelines
This section will cover the implementation and impact of early-onset GBS disease prevention guidelines.

17. Proportion of Women Screened for GBS Colonization
A multi-state retrospective cohort study was conducted to assess the implementation of the 2002 guidelines for preventing early-onset GBS disease.
This study involved the review of ~7,600 L&D records from a sample of ~800,000 live births for
The study indicated that 85% women were being screened for GBS colonization by
This was a marked increase from the 48% of women screened in There was an increase in the proportion of individuals screened in all of the areas studied.
98% of the women screened had a GBS screening result available at labor
However, when data from all groups was pooled, black and Hispanic women had a slightly lower rate of screening than women who were not black or Hispanic
This graph was originally published by Van Dyke et al. in the New England Journal of Medicine, 2009, 360:
Proportion of women screened increased from 48% to 85%
98% of women screened had available result at labor
Van Dyke et al., NEJM :

18. Proportion of Women with an Indication for GBS IAP Who Received GBS IAP
The study on implementation of the 2002 guidelines for preventing early-onset GBS disease also indicated that 85% of women who had an indication for GBS IAP received it in
This was a marked increase from the 74% of women who had an indication for GBS IAP and then received it in There was an increase in the proportion of individuals with an indication who received IAP in all of the areas studied.
This graph was originally published by Van Dyke et al. in the New England Journal of Medicine, 2009, 360:
Proportion of women with an indication for IAP who then received IAP increased from 74% to 85%
Van Dyke et al., NEJM :

19. Rate of Early- and Late-Onset GBS, 1990-2008
Early-onset GBS
Late-onset GBS
RATE OF EARLY- AND LATE-ONSET GBS DISEASE , U.S.
This graph plots the incidence of early-and late-onset GBS disease in the ABCs areas from 1989 to 2008.
The yellow line represents late-onset disease in this graph.
Even with the implementation of guidelines recommending GBS prophylaxis, late-onset GBS disease rates have remained stable since 1990 at approximately 0.3 cases per 1,000 live births.
The white line represents early-onset disease.
The incidence of early-onset GBS disease in the United States since 1993 has declined 84% (from 1.7 cases per 1,000 live births in 1993 to 0.28 cases per 1,000 live births in 2008) , coinciding with increased prevention activities.
These data are from Active Bacterial Core surveillance, part of the CDC’s Emerging Infections Program.
Before national prevention policy
Transition
Universal screening
Source: Active Bacterial Core surveillance / Emerging Infections Program

20. Early-onset GBS Disease in the U.S., 2000-2008
Universal screening
Early-onset GBS Disease in the US,
This slide shows a graph plotting the incidence of early-onset GBS disease in the ABCs areas from 2000 to 2008.
During this time period, there was a 46% decrease in early-onset GBS disease.
The most notable decline was during , the year following the publication of revised early-onset GBS prevention guidelines.
These data are from Active Bacterial Core surveillance, part of the CDC’s Emerging Infections Program.
Source: Active Bacterial Core surveillance / Emerging Infections Program

21. Rate of Early-onset GBS Disease by Race and Gestational Age, 2000-2007
Universal screening
Black <37 wks
White <37 wks
Some groups, particularly pre-term and black infants, remain disproportionately affected by early-onset GBS disease.
This graph plots the incidence of early-onset invasive GBS disease in black neonates < 37 and ≥37 weeks gestational age and white neonates < 37 and ≥37 weeks gestational age in areas under surveillance through the Active Bacterial Core surveillance system.
Between 2000 and 2007, rates of early-onset GBS disease decreased among both black (30% reduction) and white infants (49% reduction) born at ≥37 weeks gestational age
However, between 2000 and 2007 rates among both black and white infants born at <37 weeks essentially remained the same or increased.
Also, among infants born at a gestational age <37 weeks, rates of early-onset GBS disease were 3.8 times higher among black infants than among white infants
These data are from Active Bacterial Core surveillance, part of the CDC’s Emerging Infections Program.
Black >37 wks
White >37 wks
Source: Active Bacterial Core surveillance / Emerging Infections Program

22. Implementation Challenges
Missed prevention opportunities among infants born preterm
50% screened prior to admission
Only 18% of GBS unknown screened on admission
Preterm 20% less likely to receive IAP when indicated than term
Receipt of ≥4 hours IAP protective (78% effective, 95% CI 44-91)
Penicillin-allergic women
Only 14% at low risk for anaphylaxis received cefazolin
70% at low risk for anaphylaxis received clindamycin even though
<5% had susceptibility testing
No data on efficacy/effectiveness of clindamycin to prevent EOGBS
Implementation Challenges
Missed prevention opportunities among infants born preterm
50% screened prior to admission
18% of GBS unknown screened on admission
Preterm 20% less likely to receive IAP when indicated than term
Receipt of ≥4 hours IAP protective (78% effective, 95% CI 44-91)
Penicillin-allergic women
Only 14% at low risk for anaphylaxis received cefazolin
70% at low risk for anaphylaxis received clindamycin even though
<5% had susceptibility testing
No data on efficacy/effectiveness of clindamycin to prevent EOGBS
These data were originally published by Van Dyke in New England Journal of Medicine, 2009, 360:
Van Dyke et al., N Engl J Med Jun 18;360(25):

23. GBS Resistance: Clindamycin and Erythromycin All Ages, 2001-2008*
47.7%
25.6%
24.8%
11.4%
GBS Resistance: Clindamycin and Erythromycin for All Ages,
The lack of erythromycin/clindamycin susceptibility testing is important because resistance among GBS isolates to clindamycin or erythromycin is a significant and growing problem.
Resistance to clindamycin and erythromycin increased among GBS isolates between 2001 and 2008.
The percent of isolates resistant to clindamycin increased from 11.4% n 2001 to 24.8% in 2008.
The percent of isolates resistant to erythromycin increased from 25.6% n 2001 to 47.7% in 2008.
These data are based on isolates from Colorado, Georgia, Maryland, Minnesota, New York, and Oregon data were excluded since only early-onset isolates were tested.
These data are from Active Bacterial Core surveillance, part of the CDC’s Emerging Infections Program
*Isolates are from CO, GA, MD, MN, NY, and OR data excluded since only early-onset isolates were tested.
Source: Active Bacterial Core surveillance / Emerging Infections Program

24. Potential Unintended Consequences of GBS Prevention Guidelines
Adverse drug reactions
Anaphylaxis among women receiving GBS IAP very rare
Two studies reviewing >12,000 births found one non-fatal case
Four published case reports in U.S. since 1996
Impact on non-GBS sepsis
Stable or decreasing rates in most studies
E.coli sepsis may be increasing among pre-term infants, but trends not consistent across studies
Health services utilization for neonates
Studies conducted during reported increased, stable, or decreased use of health services for neonates whose mothers received IAP
No studies on the impact of the 2002 guidelines
Potential Unintended Consequences of GBS Prevention Guidelines
Adverse drug reactions
Anaphylaxis among women receiving GBS IAP very rare.
Two studies reviewing >12,000 births found one non-fatal case.
Four published case reports in the U.S. since 1996.
Impact on non-GBS sepsis
Stable or decreasing rates in most studies.
E.coli sepsis may be increasing among pre-term infants, but trends are not consistent across studies.
Health services utilization for neonates
Studies conducted during reported increased, stable, or decreased use of health services for neonates whose mothers received IAP.
No studies have reported on the impact of the 2002 guidelines.

25. 2010 GBS Guidelines Organizations Endorsing CDC’s 2010 GBS Guidelines
American College of Obstetricians and Gynecologists
American Academy of Pediatrics
American College of Nurse-Midwives
American Academy of Family Physicians
American Society for Microbiology
Organizations Endorsing the 2010 GBS Guidelines
American Congress of Obstetricians and Gynecologists
American Academy of Pediatrics
American College of Nurse-Midwives
American Academy of Family Physicians
American Society for Microbiology

26. 2010 GBS Guidelines: Methods
Key stakeholders convened late 2008
American Academy of Pediatrics, American Academy of Family Physicians, American College of Nurse-midwives, American College of Obstetricians and Gynecologists, Centers for Disease Control and Prevention, Society for Hospital Epidemiology of America, American Society for Microbiology, microbiologists, pharmacologists, state health departments, parent organizations
Reviewed relevant data
Identified areas of guidelines that needed changes or clarifications
Made evidence-based revisions to guidelines
GBS Guidelines Revision
In order to address the implementation challenges in the guidelines for preventing early-onset GBS disease, key stakeholders convened in late These included:
American Academy of Pediatrics, American Academy of Family Physicians, American College of Nurse-Midwives, American College of Obstetricians and Gynecologists, Centers for Disease Control and Prevention, Society for Hospital Epidemiology of America, American Society for Microbiology, microbiologists, pharmacologists, state health departments, parent organizations
Reviewed relevant data
Published literature and ‘grey’ literature
Data from on-going surveillance and research
Identified areas of guidelines that needed changes or clarifications
Made evidence-based revisions to guidelines

27. The Recommendations MMWR, Vol 59 (RR-10)
THE RECOMMENDATIONS: MMWR, VOLUME 59 (RR-10)
This slide shows the front cover of the 2010 revised GBS prevention guidelines. The entire document has been published by MMWR in Volume 59, RR-10.

28. Key Prevention Strategies Remain Unchanged in 2010
Universal screening of pregnant women for GBS at weeks gestational age
Intrapartum antibiotic prophylaxis for:
GBS positive screening test
GBS colonization status unknown with
Delivery <37 weeks
Temperature during labor >100.4˚ F (>38.0˚ C)
Rupture of membranes >18 hours
Previous infant with GBS disease
GBS in the mother’s urine during current pregnancy
Penicillin preferred drug for IAP
Ampicillin acceptable alternative
Cefazolin preferred for penicillin-allergic at low risk of anaphylaxis
PREVENTION OF PERINATAL GBS DISEASE
The key prevention strategies remain unchanged in the 2010 guidelines
Universal screening of pregnant women at weeks gestational age.
Women should later receive intrapartum antibiotic prophylaxis against GBS if they had:
a GBS + screening culture;
an unknown GBS colonization status with delivery before 37 weeks, a temperature during labor greater than or equal to 100.4˚F or 38.0˚C, or rupture of membranes for more than 18 hours;
a previous infant with GBS disease;
or GBS bacteriuria during the current pregnancy.
Penicillin is the preferred drug for IAP, although ampicillin is an acceptable alternative.
Cefazolin is the preferred option for penicillin allergic women with a low risk of anaphylaxis with penicillin.
Nonetheless, there are important changes in the 2010 GBS guidelines. I will now review the key points that clinicians need to know about GBS prevention, highlighting areas of changes in 2010.

29. Identification of Candidates for IAP in the 2010 GBS Guidelines
This section will cover identification of candidates to receive IAP in the 2010 GBS prevention recommendations.

30. Indications for Intrapartum GBS Prophylaxis
Previous infant with invasive GBS disease
GBS bacteriuria during current pregnancy
Positive GBS screening test during current pregnancy
Unknown GBS status AND any of the following:
Delivery at <37 weeks’ gestation
Amniotic membrane rupture 18 hours
Intrapartum temperature 100.4°F ( 38.0 °C)
Indications for IAP under universal prenatal screening
Previous infant with invasive GBS disease
GBS bacteriuria during any trimester of the current pregnancy
Positive GBS screening test in late gestation during current pregnancy (unless a planned cesarean delivery, in the absence of labor or amniotic membrane rupture)
Unknown GBS status AND any of the following:
Delivery at <37 weeks’ gestation
Amniotic membrane rupture 18 hours
Intrapartum temperature 100.4°F ( 38.0 °C)

31. Intrapartum GBS Prophylaxis Not Indicated
Colonization with GBS during a previous pregnancy
Unless another indication during the current pregnancy
GBS bacteriuria during a previous pregnancy
Negative vaginal and rectal GBS screening test during the current pregnancy
Regardless of intrapartum risk factors
Cesarean delivery performed before labor onset on a woman with intact amniotic membranes
Regardless of maternal GBS test status
Regardless of gestational age
Intrapartum prophylaxis NOT indicated Colonization with GBS during a previous pregnancy
Unless another indication during the current pregnancy
GBS bacteriuria during a previous pregnancy
Negative vaginal and rectal GBS screening test late in gestation during the current pregnancy
Regardless of intrapartum risk factors
Cesarean delivery performed before labor onset on a woman with intact amniotic membranes
Regardless of maternal GBS test status
Regardless of gestational age. The clarification that the recommendations for cesarean deliveries performed before labor onset on women with intact amniotic membranes apply to women delivering at any gestational age is new in the 2010 guidelines.

32. Bacteriuria GBS in urine during pregnancy
GBS found in urine of 2%-7% of pregnant women
Marker of heavy vaginal-rectal colonization
Risk factor for early-onset GBS disease in the newborn
Antibiotic treatment of GBS bacteriuria during pregnancy does not eliminate GBS from the genitourinary and gastrointestinal tracts, and recolonization after a course of antibiotics is typical
Clinicians must inform laboratories when submitted urine specimens are from pregnant women
Women with symptomatic or asymptomatic GBS urinary tract infections detected during pregnancy should be treated according to current standards of care
Women with GBS isolated from the urine at any time during the current pregnancy should receive IAP
Bacteriuria
GBS in urine during pregnancy
GBS found in urine of 2%-7% of pregnant women.
Marker of heavy vaginal-rectal colonization.
Risk factor for early-onset GBS disease in the newborn.
Antibiotic treatment of GBS bacteriuria during pregnancy does not eliminate GBS from the genitourinary and gastrointestinal tracts, and recolonization after a course of antibiotics is typical.
Clinicians must inform laboratories when submitted urine specimens are from pregnant women.
Women with symptomatic or asymptomatic GBS urinary tract infections detected during pregnancy should be treated according to current standards of care.
Women with GBS isolated from the urine at any time during the current pregnancy should receive IAP.

33. Prenatal GBS Sample Collection
Site: vagina and rectum
Single swab or two swabs
Lower 1/3 of vagina
Through anal sphincter
Collection: NOT by speculum
Self collection an option
Timing: 35 to 37 weeks
Transport: Nonnutritive transport medium
Examples - Stuart’s or Amies
With or without charcoal
Results most sensitive if processed within 24 hours of collection
Results most sensitive if refrigerated before processing
CDC’S RECOMMENDATIONS FOR PRENATAL GBS CULTURES
All women who do not have GBS bacteriuria during the current pregnancy or a previous infant with invasive GBS disease should undergo prenatal screening.
Every effort should be made to optimize the yield from the tests.
Includes sampling both the vagina and the rectum at the appropriate time.
Sample collection can be done with either a single swab or with two swabs, but if two are used, both can go into a single nonnutritive transport medium.
The vaginal swab should sample the lower one third of the vagina.
Specimens should come from the lower third of the vagina, and the rectal swab should pass through the anal sphincter.
Samples should NOT be collected with a speculum.
Self-collected cultures from both vaginal and rectal sites can be an alternative to sample collected by clinicians, and patients may prefer to be offered this option.
Samples should be collected during the 35th to 37th week of pregnancy.
Specimens should be transported in a nonnutritive transport medium. Examples include Stuart’s or Amies medium with or without charcoal.
Specimens in transport media will remain viable at room temperature for up to 4 days, however,
Results are most sensitive when the sample is processed within 24 hours of collection.
Results are most sensitive when the sample is refrigerated prior to processing.

34. Antimicrobial Susceptibility Testing for Penicillin-Allergic Women at High Risk of Anaphylaxis
Many isolates from invasive GBS disease are resistant to clindamycin or erythromycin
Resistance to erythromycin is associated frequently but not always with resistance to clindamycin
Some isolates susceptible to clindamycin but resistant to erythromycin may have inducible clindamycin resistance
Antimicrobial susceptibility testing should be performed on antenatal GBS isolates from penicillin-allergic women at high risk for anaphylaxis
Should include testing for inducible resistance (e.g. D-zone test)
Specimens from penicillin allergic women at high risk for anaphylaxis should be clearly labeled
Antibiotic susceptibility testing
Many isolates from invasive GBS disease are resistant to clindamycin or erythromycin:
Resistance to erythromycin is associated frequently but not always with resistance to clindamycin.
Some isolates that are susceptible to clindamycin but resistant to erythromycin may have inducible clindamycin resistance
Antimicrobial susceptibility testing should be performed on antenatal GBS isolates from penicillin-allergic women at high risk for anaphylaxis, and should include testing for inducible resistance (e.g. D-zone test).
Specimens from penicillin allergic women at high risk for anaphylaxis should be clearly labeled as being from penicillin allergic women.

35. Intrapartum testing for GBS
Nucleic acid amplification tests (NAAT) such as PCR an option for intrapartum GBS testing for women who are GBS unknown at labor onset and have no risk factors
Lower sensitivity for direct specimens (no enrichment)
Positive result: Administer IAP
Negative result and patient does not develop intrapartum temperature100.4°F ( 38.0 °C) or have ROM ≥18 hours: No IAP
Negative result and patient develops intrapartum temperature 100.4°F ( 38.0 °C) or has ROM ≥18 hours: Administer IAP
Additional slides on changes affecting laboratories in the 2010 GBS prevention guidelines can be found at:
Intrapartum testing for GBS in 2010 guidelines
Can do nucleic acid amplification tests (or NAAT) such as PCR for women who are GBS unknown at labor onset and have no risk factors
Studies have found PCR for GBS to have a lower sensitivity when performed on direct specimens (no enrichment first)
Positive result: Administer IAP
Negative result and patient does not develop intrapartum fever or have ROM ≥18 hours: No IAP
Negative result and patient develops intrapartum fever or has ROM ≥18 hours: Administer IAP
Additional slides on changes affecting laboratories in the 2010 GBS prevention guidelines can be found at:

36. This slide shows an algorithm with many more choices for laboratory processing of prenatal specimens in the 2010 guidelines than in the 2002 guidelines.
Additional slides on changes affecting laboratories in the 2010 GBS prevention guidelines can be found at:

37. Threatened Preterm Delivery
Separate algorithms are presented for GBS prophylaxis in the setting of threatened preterm delivery, one for spontaneous preterm labor (PTL) and one for preterm premature rupture of membranes (pPROM)
Women with PTL or pPROM should all receive:
Screening on admission for GBS if GBS status unknown
Antibiotics for GBS prophylaxis
Antibiotics to prolong latency in pPROM can serve as GBS IAP if certain criteria are met
Ampicillin 2 g IV followed by 1 g IV every 6 hours for 48 hours
Delivery occurs while the mother is receiving that antibiotic regime
2010 GBS Prevention Guidelines Changes: Obstetric Management
Separate algorithms are presented for GBS prophylaxis in the setting of threatened preterm delivery, one for spontaneous preterm labor (PTL) and one for preterm premature rupture of membranes (pPROM).
Women with PTL or pPROM should all receive:
Screening on admission for GBS if GBS status unknown
Antibiotics for GBS prophylaxis
Antibiotics to prolong latency in pPROM can serve as GBS IAP if certain criteria are met.
These criteria include:
That the treatment is Ampicillin 2 g IV followed by 1 g IV every 6 hours for 48 hours and,
The delivery occurs while the mother is receiving that antibiotic regime.

38. This slide shows algorithms for providing GBS intrapartum prophylaxis for women with preterm labor.

39. This slide shows algorithms for providing GBS intrapartum prophylaxis for women with preterm premature rupture of membranes.

40. Antibiotic Selection in the 2010 GBS Guidelines
This section will cover antibiotic selection in the 2010 GBS guidelines.

41. Antibiotics for IAP Penicillin the first-line agent for IAP
Dosage: 5 million IU IV then million IU IV every 4 hours
Revised dose ( million IU) consistent with available penicillin formulations
Ampicillin an acceptable alternative
Antibiotics for intrapartum antibiotic prophylaxis
Penicillin is the first-line agent for IAP.
Recommended dose is 5 million IU IV then million IU IV every 4 hours
Revised dose to be consistent with commercially available penicillin formulations and avoid need for pharmacies to specially mix doses
Ampicillin is an acceptable alternative.

42. Data on Antibiotics for Intrapartum GBS Prophylaxis
Data from clinical trials, observational studies, and pharmacokinetics studies indicate that penicillin and ampicillin given as intrapartum prophylaxis are effective in preventing early-onset GBS disease.
Data from observational and pharmacokinetics studies indicate that cefazolin is probably effective as GBS intrapartum prophylaxis.
In contrast, there are no similar data available for clindamycin, erythromycin, or vancomycin.

43. Antibiotics for IAP in Women Allergic to Penicillin
Cefazolin best option for a woman allergic to penicillin but not at high risk for anaphylaxis
Drugs with less evidence for effectiveness (e.g. clindamycin, vancomycin) only for women at high risk of anaphylaxis
High risk for anaphylaxis defined as history of anaphylaxis, angioedema, respiratory distress or urticaria following penicillin
Erythromycin no longer included as option
Antibiotics for intrapartum antibiotic prophylaxis in penicillin-allergic women
Ampicillin is an acceptable alternative.
For women who are allergic to penicillin, cefazolin is the best option for a woman who is not at high risk for anaphylaxis
Drugs with less evidence for effectiveness as GBS IAP, such as clindamycin and vancomycin, should only be used if a woman has a high risk of anaphylaxis to penicillin
High risk for anaphylaxis is defined as a history of anaphylaxis, angioedema, respiratory distress, or urticaria following administration of a penicillin or a cephalosporin.
Erythromycin is no longer included as an option in the 2010 GBS gudielines

44. Antibiotics for IAP in Women Allergic to Penicillin
Women at high risk for anaphylaxis following penicillin or a cephalosporin may receive CLINDAMYCIN for GBS IAP if:
Their GBS isolate is susceptible to clindamycin and erythromycin OR
Their GBS isolate is susceptible to clindamycin but resistant to erythromycin and testing for inducible resistance is negative
Women at high risk for anaphylaxis following penicillin or a cephalosporin may receive VANCOMYCIN for GBS IAP if:
Their GBS isolate is intrinsically resistant to clindamycin OR
Their GBS isolate shows inducible resistance to clindamycin OR
Their GBS isolate’s susceptibility to clindamycin and erythromycin is unknown
Antibiotics for IAP in Penicillin Allergic Women: Modifications in 2010 Guidelines
Women at high risk for anaphylaxis following penicillin or a cephalosporin may receive CLINDAMYCIN for GBS IAP if:
Their GBS isolate is susceptible to clindamycin and erythromycin OR
Their GBS isolate is susceptible to clindamycin but resistant to erythromycin and testing for inducible resistance is negative.
Women at high risk for anaphylaxis following penicillin or a cephalosporin may receive VANCOMYCIN for GBS IAP if:
Their GBS isolate is intrinsically resistant to clindamycin OR
Their GBS isolate shows inducible resistance to clindamycin OR
Their GBS isolate’s susceptibility to clindamycin and erythromycin is unknown

45. 2010 GBS Guidelines: Algorithm for Selecting IAP Regimens
This slide shows an algorithm with recommended regimens for intrapartum antibiotic prophylaxis for prevention of early-onset GBS disease.

46. Newborn Management in the 2010 GBS Guidelines
This section will cover newborn management in the 2010 GBS guidelines.

47. Revised Neonatal Management Algorithm
Applies to all newborns
Regardless of whether mother received IAP
Management based on clinical appearance, risk factors (maternal chorioamnionitis, prolonged rupture of membranes, preterm), and adequacy of IAP if indicated for mother
Adequate IAP clarified
≥4 hours of IV penicillin, ampicillin, or cefazolin before delivery
All other agents or durations are considered inadequate for purposes of neonatal management
Aims to reduce unnecessary evaluations and antibiotics in newborns at relatively low risk for early-onset GBS disease
The revised neonatal management algorithm applies to all newborns, regardless of whether mother received IAP
Management is based on clinical appearance, risk factors (maternal chorioamnionitis, prolonged rupture of membranes, preterm), and adequacy of IAP if indicated for mother
The definition of adequate IAP is clarified as ≥4 hours of IV penicillin, ampicillin, or cefazolin before delivery.
All other agents or durations are considered inadequate for purposes of neonatal management.
This is because there are no data from clinical trials, observational studies, or pharmacokinetics studies available that show that intrapartum prophylaxis with other agents is effective in preventing early-onset GBS disease. In contrast, data are available for penicillin, ampicillin, and cefazolin indicating their effectiveness in preventing early-onset GBS disease.
The revised algorithms aims to reduce unnecessary evaluations and antibiotics in newborns at relatively low risk for early-onset GBS disease

48. This slide shows an algorithm for the secondary prevention of early-onset GBS disease among newborns.

49. Recommended Management: 2002 vs. 2010
This slide explains how responses to various clinical scenarios differs between the 2002 and the 2010 guidelines.
The 2002 guidelines offered no guidance on how to manage a newborn with signs of sepsis whose mother had not received IAP. The 2010 guidelines recommend that the infant receive antibiotics as well as a full diagnostic evaluation consisting of a complete blood count with differential and platelets, blood culture, chest radiograph (if respiratory abnormalities are present), and lumbar puncture (if the patient is stable enough to tolerate procedure and sepsis is suspected). Therapy for the infant should include antimicrobial agents active against GBS (including intravenous ampicillin) as well as other organisms that might cause neonatal sepsis, such as E.Coli.
The 2002 guidelines offered no guidance on how to manage a well-appearing newborn whose mother had chorioamnionitis. The 2010 guidelines recommend that the infant receive a limited diagnostic evaluation consisting of a blood culture (at birth), and a complete blood count with differential and platelets as well as antibiotic treatment.
The 2002 guidelines offered no guidance on how to manage a well-appearing newborn whose mother was GBS+ but did not receive IAP. The 2010 guidelines outline several options that depend on the infant’s gestational age and on how long the mother had rupture of membranes.
The 2002 guidelines offered no guidance on how to manage a well-appearing newborn whose mother had an indication for IAP but received clindamycin or vancomycin. The 2010 guidelines outline several options that depend on the infant’s gestational age and on how long the mother had rupture of membranes.
The 2002 guidelines recommended that all well-appearing newborns whose mothers had an indication for IAP and received less than 4 hours worth of ampicillin, penicillin, or cefazolin receive a limited diagnostic evaluation. The 2010 guidelines outline several options that depend on the infant’s gestational age and on how long the mother had rupture of membranes.
The 2002 guidelines recommended that all well-appearing newborns born during the 35th or 36th week of pregnancy whose mothers had an indication for IAP and received at least 4 hours worth of ampicillin, penicillin, or cefazolin receive a limited diagnostic evaluation. The 2010 guidelines suggest that these infants do not routinely require diagnostic evaluations but should be observed for at least 48 hours.

50. What Can You Do to Help?
Make sure your OB, Peds, FP, Midwife, and Microbiology colleagues know the new guidelines are out
Check to see if your lab is following the new guidelines for laboratory methods
Form a committee to plan steps needed for implementation in your facility
What Can You Do to Help?
Make sure your OB, Peds, Family Practice, Midwife, and Microbiology colleagues know the new guidelines are out.
Check to see if your lab is following the new guidelines for laboratory methods.
Form a committee to plan steps needed for implementation in your facility.

51. Early-onset GBS Disease Web Resources
Centers for Disease Control and Prevention
American College of Obstetricians and Gynecologists
American Academy of Pediatrics
American College of Nurse-Midwives
American Academy of Family Physicians
American Society for Microbiology
Group B Strep Association
GBS WEB RESOURCES
Listed on this slide are a few of the key resources available for the prevention of early-onset GBS disease.
American Academy of Pediatrics,
American College of Nurse-midwives,
American College of Obstetricians and Gynecologists,
American Society for Microbiology,
Centers for Disease Control and Prevention,
The Group B Strep Association ( a non-profit community-based organization, has a home page with linkages to both CDC and ACOG’s web sites, as well as other resources for parents.

52. Acknowledgments
GBS Technical Team: Kathryn Arnold, Barbara Stoll, Yun Wang, Carol Baker, Carrie Byington, Richard Polin, Ronald Gibbs, Jeanne Jordan, Sarah Kilpatrick, Geraldine Hall, Tekoa King, Ruth Lynfield, Marti Perhach, Laura Riley, Pablo Sanchez, Pamela Simms, Julie Wood, Rex Astles, Bernard Beall, Roberta Carey, Janine Corey, Tarayn Fairlie, Lee Hampton, Denise Jamieson, Melissa Lewis, Lesley McGee, Michael Miller, Christine Olson, Alison Patti, Stephanie Schrag, Jennifer Verani, Emily Weston, Cynthia Whitney, Elizabeth Zell
ACKNOWLEDGEMENTS
GBS Technical Working Group: Kathryn Arnold, Barbara Stoll, Yun Wang, Carol Baker, Carrie Byington, Richard Polin, Ronald Gibbs, Jeanne Jordan, Sarah Kilpatrick, Geraldine Hall, Tekoa King, Ruth Lynfield, Marti Perhach, Laura Riley, Pablo Sanchez, Pamela Simms, Julie Wood, Rex Astles, Bernard Beall, Roberta Carey, Janine Corey, Tarayn Fairlie, Lee Hampton, Denise Jamieson, Lesley McGee, Melissa Lewis, Michael Miller, Christine Olson, Alison Patti, Stephanie Schrag, Jennifer Verani, Emily Weston, Cynthia Whitney, Elizabeth Zell

53. Image: CDC logo (Centers for Disease Control and Prevention) and HHS logo (Department of Health and Human Services)
National Center for Immunization & Respiratory Diseases
Division of Bacterial Disease