# Presentation: 662640

## Perinatal Group B Streptococcal Disease:  Background, Epidemiology, and Overview of Revised CDC prevention guidelines (2002)

**National Center for Infectious Diseases**
**Division of Bacterial and Mycotic Diseases**

**Notes:**
Title :  Perinatal Group B Streptococcal Disease:  Background, Epidemiology, and Overview of Revised CDC prevention guidelines (2002)
Presented by: Centers for Disease Control & Prevention, National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases

## Background on GBS disease and prevention

**Notes:**
Background on GBS Disease and Prevention
Slides in this section provide some background on GBS disease and prevention

## The Disease

- GBS emerged as an important pathogen in the 1970s
- Over 7500 cases of GBS sepsis and meningitis in newborns annually
- Perinatal GBS disease burden
**neonatal illness/death, long-term disability**
**maternal morbidity**
- Neonatal direct costs -- $300 million/yr

**Notes:**
THE DISEASE
Group B streptococcus first emerged as an important pathogen in the 1970s and since has remained the major cause of sepsis in newborns.
In 1990, there were over 15,000 cases of invasive group B streptococcal disease; about half of these occurred in newborns, that is about 7500 neonatal cases a year.
The burden of neonatal group B streptococcus disease extends beyond illness and death, and includes long-term disabilities such as hearing loss, impaired vision, and developmental problems.
Maternal morbidity from GBS includes sepsis, amnionitis, postpartum wound infections, and stillbirths.
Before active prevention, the direct costs of neonatal disease alone in the United States have been estimated at 300 million dollars annually.
This presentation will summarize background on the epidemiology of neonatal group B strep disease, the impact of prevention and the 2002 revised recommendations of the Centers for Disease Control and Prevention (CDC) for prevention of perinatal group B streptococcal disease.

## Invasive GBS Disease Incidence by Age Group and Race (1990)

**MMWR Vol. 41 (No. SS-6) 1992**

**       ****per 1000 births**

**Notes:**
INVASIVE GBS DISEASE INCIDENCE BY AGE GROUP AND RACE
Group B streptococcal disease affects persons of all ages and races.
This slide shows the rates of disease among different age groups from a report in a 1990 study presented in the MMWR Volume 41 in 1992.  This shows the incidence of disease before active prevention.
Infants under 90 days of age have the highest risk of disease, and then the risk falls to its lowest point among older infants and children.
Gradually the risk of GBS increases with age until reaching a second peak among those over the age of 75 years.
This slide also shows that within every age group African-Americans have a higher risk of disease than whites.

## GBS Disease in Infants Before Prevention Efforts

**A Schuchat. Clin Micro Rev 1998;11:497-513.**

**Notes:**
GBS DISEASE IN INFANTS
This slide shows the proportion of GBS disease among infants at different ages.
The data is taken from a study that was summarized in a review by Schuchat and published in Clin Micro Rev in 1998, Volume 11, pages 497-513.  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

## Early-Onset Neonatal GBS Disease Before Prevention Efforts

**A Schuchat. Clin Micro Rev 1998;11:497-513.**

**Notes:**
EARLY-ONSET NEONATAL GBS DISEASE
Among the cases occurring in the first week of life, almost 80% occurred in the first day.
Because the pathogenesis of disease in the first week of life is most likely different from the pathogenesis of cases that occur later, a distinction is made – this presentation discusses prevention aimed at early-onset cases.
This graph shows that babies 0 days old made up 78.5% of neonatal early-onset cases
The data for this slide are summarized in a review by Schuchat in Clin Micro Rev 1998; 11:497-513

## Photo courtesy of Dr. Carol Baker 

**Photo courtesy of Dr. Carol Baker **
- Baylor College of Medicine, Houston, TX

**Notes:**
NEONATAL GBS CLINICAL SLIDES
This is one of three 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

**Photo courtesy of Dr. Carol Baker **Baylor College of Medicine, Houston, TX

**Notes:**
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

## Mother to Infant Transmission

**GBS colonized mother**

**Non-colonized newborn**

**Colonized newborn**

**Asymptomatic**

**Early-onset sepsis, pneumonia, meningitis**

**50%**

**50%**

**98%**

**2%**

**Notes:**
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.

## GBS Maternal Colonization

**GBS Carriers**
**10% - 30% of women**
**higher in African Americans and nonsmokers**
**clinical signs not predictive**
**dynamic condition**
**Risk factor for early-onset disease: GBS colonization at delivery**
**prenatal cultures late in pregnancy can predict delivery status**

**Notes:**
GBS MATERNAL COLINIZATION
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 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 can’t tell who is a GBS carrier by taking a history or doing a physical exam. 
Colonization can be determined by culturing for the bacteria from a swab of the vagina and rectum.
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.
Maternal vaginal colonization with GBS at the time of delivery is an important risk factor for neonatal early-onset disease.  Prenatal cultures taken late in pregnancy can predict colonization status at delivery

## Additional Risk Factors for Early-Onset GBS Disease

- Obstetric: prolonged rupture of membranes, preterm delivery, intrapartum fever
- GBS bacteriuria
- Previous infant with GBS disease
- Demographic (African American race, young age)
- Immunologic (low antibody to GBS capsular polysaccharide)

**Notes:**
ADDITIONAL RISK FACTORS FOR EARLY-ONSET GBS DISEASE
The majority of infants born to mothers who are colonized with GBS will remain perfectly healthy.
There are certain risk factors which increase the chance that an infant will be afflicted with the disease.
Obstetric risk factors include prolonged rupture of  membranes (defined in various studies as more than 12, 18 or 24 hours), preterm delivery (defined as delivery at less than 37 weeks), and maternal intrapartum fever.
Other risk factors include symptomatic or asymptomatic GBS bacteriuria, having delivered a previous infant with GBS disease, demographic risk factors such as African-American race and young maternal age at delivery, and immunologic risk factors such as a low level of antibody to GBS capsular polysaccharide.

## Prevention of Perinatal GBS Disease

**Intrapartum antibiotics**
**Highly effective at preventing early-onset disease in women at risk of transmitting GBS to their newborns**
**Challenge:**** How best to identify women at risk?**

**Notes:**
PREVENTION OF PERINATAL GBS DISEASE
In the 1980s, it was discovered that intrapartum antibiotics are highly effective in preventing mothers at risk from transmitting group B strep to their newborns.
The challenge since this discovery has been how to best identify women who should receive intrapartum antibiotics.

## Rates of Early-Onset GBS Disease by Prenatal Colonization & Risk Factors

**Col: prenatal vag/rect culture**
**RF: risk factors (gest. <37 wks,    ROM >12 hr, fever > 37.5 C)**

**Boyer & Gotoff, Antibiot Chemother 1985.**

**Notes:**
RATES OF EARLY-ONSET GBS DISEASE BY PRENATAL COLONIZATION & RISK FACTORS
A main consideration in development of prevention guidelines was characterizing which women were at risk for delivering infants with early-onset infection
This slide summarizes data from a prospective study conducted in the early 1980s by Boyer and Gotoff (published in Antibiotics and Chemotherapy in 1985) that assessed nearly 5300 infants born over a three-and-a-half year period, none of whom had received intrapartum antibiotics.
The cohort of deliveries was considered in terms of maternal prenatal colonization with group B streptococcus and the presence of an intrapartum risk factor, either pematurity, prolonged rupture of membranes, or intrapartum fever.
The attack rate was quite high among infants born to colonized mothers with one or more risk factors, 40.8 per 1000 births, or about 1 in 25 infants.
Infants born to colonized mothers without a risk factor had the next highest risk of early onset infants with an attack rate of 5.1 per 1000 births.
Infants born to mothers with risk factors who were not prenatally colonized and to mothers who were neither colonized nor had risk factors, had very low attack rates of 0.9 per 1000 births and 0.3 per 1000 births, respectively.

## First U.S. Consensus  Recommendations (CDC '96, ACOG '96, AAP '97)

- Screening-based approach:
-   35-37 wks culture, offer intrapartum antibiotic prophylaxis (IAP) to GBS carriers and to preterm unless neg. culture result available
- or
- Risk-based approach:
-   IAP to preterm, membrane rupture_>_18 hours, or intrapartum fever (T_>_38C)
***Both strategies also give IAP to women with GBS bacteriuria, or previous infant with GBS disease***

**Notes:**
FIRST U.S. CONSENSUS RECOMMENDATIONS (CDC ’96, ACOG ’96, AAP ’97)
In 1996 guidelines were issued by the Centers for Disease Control and Prevention, American College of Obstetricians and Gynecologists, and American Academy of Pediatrics.
These guidelines recommend health care providers and institutions choose between two alternative prevention strategies:
Screening-based approach
Pregnant women should be cultured between 35-37 weeks
Intrapartum antibiotic prophylaxis (IAP) should be offered to women identified as GBS carriers and to women of unknown GBS status at the time of labor who are delivering preterm
Risk-based approach
IAP to preterm, membrane rupture from 18 hrs or more, or for an intrapartum fever of 100.4F or more (38C or more)
Both strategies also give IAP to women with GBS bacteriuria or previous infant with GBS disease

## Implementation and impact of the 1996 consensus guidelines

**Notes:**
Implementation and impact of the 1996 consensus guidelines
Slides in this section outline studies evaluating implementation of the 1996 guidelines and the impact of prevention activities on disease incidence

## GBS Policies in US Hospitals Implementation by Year

**ABCs Hospitals, EIP Network**
**MMWR 1998; 47:665-670**

**ACOG, AAP**
**Guidelines**
**Issued**

**Draft**
**Guidelines**
**Issued**

**Consensus**
**Guidelines **
**Issued**

**Notes:**
GBS POLICIES IN US HOSPITALS IMPLEMENTATION BY YEAR
CDC has an active surveillance network in selected counties of 10 states called the Active Bacterial Core Surveillance (ABCs).  The ABCs participated in a series of projects monitoring GBS prevention implementation in the 1990s.
During the last decade ABCs collected information on the number of hospitals with formal GBS policies.
The bar chart in this slide shows that after the release of the consensus guidelines, there was a noticeable increase in the percent of hospitals with formal GBS policies from 16% of hospitals in 1995 to 58% in 1997.
The data for this chart is from ABCs Hospitals in the EIP Network, published in MMWR 1998: 47;665-670

## Change in incidence of early-onset GBS disease in hospitals w/ and w/out new policies

- P=.26

- P=.006

- Factor, Obstet Gynecol 2000;95:377-82

**Notes:**
Change in incidence of early-onset GBS disease in hospitals w/ and w/out new policies
This slide shows a bar chart documenting the incidence of early-onset GBS cases in 1996 and 1997 in two groups of hospitals: those with a new prevention policy in 1996, and those without a policy in 1996.
Hospitals with a new policy had a significant decline in incidence of early-onset disease (P=0.006) whereas hospitals without policies had no decline (P=0.26)
These results come from a study by S. Factor et al. published in Obstet Gynecol 2000;95:377-82

## Implementation of GBS prevention at hospitals, 1997 v. 1999

|  | 1997 
N=177 | 1999
N=187 | P value |
| --- | --- | --- | --- |
| Formal policy | 58% | 63% | .46 |
| GBS field on L&D forms | 43% | 67% | <0.01 |
| Standing orders for GBS prophylaxis | 37% | 48% | 0.04 |

**ABCs/Emerging Infections Program Network**
**MMWR Oct. 2000 ****49(41);936-940**** **

**Notes:**
IMPLEMENTATION OF GBS PREVENTION AT HOSPITALS, 1997 V. 1999
This slide shows a table summarizing results from a study published in the MMWR (Oct. 2000, Vol. 49(41);936-940 ) by the ABCs/Emerging Infections Program Network. 
In 1997, 177 hospitals were surveyed and 58% had a formal GBS prevention policy, 43% had a specific GBS field on the labor and delivery forms and 37% had standing orders for GBS prophylaxis
In 1999, 187 hospitals were surveyed and 63% had a formal GBS prevention policy, 67% had a GBS field on the labor and delivery forms and 48% had standing orders for GBS prophylaxis
For the latter two observations,  increases from 1997 to 1999 were statistically significant.

## GBS policies among ABCs hospitals vs. individual ACOG members

|  | ABCs hosp policies (n=187) % | ACOG MD policies (n=601) % |
| --- | --- | --- |
| Have GBS policy | 63 | 98 |
| Type of policy:
Screening
Risk-based
Screen, tx all + and tx cult – w/ risk factors | 
53
32
14 | 
31
26
38 |

**Watt, Obstetr Gynecol 2001:98:7-13**

**Notes:**
GBS POLICIES AMONG ABCs HOSPITALS VS. INDIVIDUAL ACOG MEMBERS
This slide shows a table summarizing results of a study published by Watt et al. in Obstet Gynecol 2001:98:7-13
A survey of 187 in ABCs hospitals in 1999 showed that 63% have a GBS policy of which 53% implement the screening-based approach.
A national survey of 601 ACOG physicians in 2000 showed that 98% had a GBS policy.  Among those with policies, 69% used a version of a screening approach and 26% used the risk-based approach.

## Rate of Early- and Late-onset GBS Disease in the 1990s, U.S.

**Rate of Early- and Late-onset GBS Disease in the 1990s, U.S.**

**   **
**   ****Consensus  **
**   ****guidelines**

**  ****1st ACOG & AAP**
**   ****statements**

**Group B Strep Association formed **

**           ****CDC draft **
**guidelines published**

**Schrag, New Engl J Med 2000 ****342: 15-20**** **

**Notes:**
RATE OF EARLY- AND LATE-ONSET GBS DISEASE IN THE 1990s, U.S.
More important than changes in policies are changes in disease incidence.
This slide shows a graph plotting the incidence of early-and late-onset GBS disease in the ABCs areas from 1989 to 2000.
Late-onset disease is represented by the blue line in this graph.
Even with the implementation of guidelines recommending GBS prophylaxis, late-onset disease rates remain stable during the 1990s at approximately 0.3 cases per 1000 live births.
The white line represents early-onset disease.
The incidence of early-onset GBS disease in the United States since 1993 has declined 70% (from 1.7 cases per 1000 live births in 1993 to 0.45 cases per 1000 live births in 1999) , coinciding with increased prevention activities.
As of 2000, the graph shows that the rates have plateaued at 0.5 cases per 1000 live births.  
This graph was originally published by Schrag in New England Journal of Medicine, 2000,  342: 15-20 .

## Rate of Early-Onset Disease by Race, 1993-1998

**Notes:**
RATE OF EARLY-ONSET DISEASE BY RACE, 1993-1998
 This slide shows a graph plotting the incidence of early-onset invasive GBS disease in black Neonates and white Neonates in four active surveillance areas (California, Georgia, Tennessee, and Maryland), 1993 through 1998.
The incidence of early-onset disease declined more steeply among black neonates than among white neonates during this period, and the difference between blacks and whites in the incidence of early-onset disease was reduced by 75 percent.
The Healthy People 2010 objectives, released by the U.S. Department of Health and Human Services, set national objectives for early-onset GBS.  The HP2010 objective is 0.5 cases/1000 births for all races.
In 1998 the rate of early-onset disease in both black neonates (0.8 per 1000 live births) and white neonates (0.5 per 1000 live births) already approached the Healthy People 2010 objective of a reduction in the incidence of early-onset disease to 0.5 case per 1000 live births for all races 
 This data is taken from Schrag, NEJM 2000, 342: 15-20 

## Current Estimates of Annual GBS Early-Onset Disease in the U.S. (2001 provisional, from ABCs/EIP Network)

**1720 cases still occurring annually**** **

**70 - 90 deaths**
**  **

**Remains leading infectious cause of neonatal morbidity and mortality**

**~4,400 cases prevented per year**

**Notes:**
Current Estimates of Annual GBS Early-Onset Disease in the U.S. (2001 provisional, from ABCs/EIP Network)
~4,400 cases prevented per year
1720 cases still occurring annually 
70 - 90 deaths
Remains leading infectious cause of neonatal morbidity and mortality

## Re-evaluation of the 1996 prevention guidelines: Central issues for reconsideration

**Notes:**
Re-evaluation of the 1996 prevention guidelines: Central issues for reconsideration
The next series of slides will address central areas of concern about GBS prevention strategies that were discussed at a CDC meeting in 2001 re-evaluating the 1996 guidelines

## GBS partners meeting to re-evaluate the 1996 guidelines, November 1-2, 2001

- Participants from key organizations (including AAP, ACOG, ACNM, AAFP, IDSOG)

- Objectives

**Consider evidence for risk vs. screening-based approaches**

**Evaluate data on adverse/unintended consequences of prophylaxis**

**Address clinical challenges that have arisen in implementing 1996 guidelines**

**Notes:**
CDC MEETING TO RE-EVALUATE THE 1996 GUIDELINES, NOVEMBER 1-2, 2001
Participants from key organizations (including American Academy of Pediatrics, American College of Obstetricians and Gynecologists, American College of Nurse Midwives, American Academy of Family Physicians, Infectious Disease Society of Obstetricians and Gynecologists)
Objectives:
Consider evidence for risk vs. screening-based approaches
Evaluate data on adverse/unintended consequences of prophylaxis
Address clinical challenges that have arisen in implementing 1996 guidelines

## Risk vs. screening

** ****No randomized trials comparing**
**  ****screening and risk-based approaches**

** ****Observational data suggest efficacy of each**
**  ****approach **

** ****Theoretical predictions suggest strategies**
**  ****may not be equally effective**

**Notes:**
Risk vs. screening
No randomized trials comparing screening and risk-based approaches; sample sizes required for such trials is prohibitive
Observational data suggest efficacy of each approach 
Theoretical predictions suggest strategies may not be equally effective

## Study design

- Multistate, retrospective cohort study using infrastructure of population-based surveillance network

**Study design**

**Study methods**

- Review of randomly selected labor and delivery records from births in 1998 and 1999 in 8 active surveillance areas

- Included all early-onset GBS cases in these
- areas; births without documented GBS screening
- were considered exposed to risk-based approach

**Schrag et al, NEJM 2002, 347:233-9**

**Notes:**
STUDY DESIGN
Multistate, retrospective cohort study using infrastructure of population-based surveillance network
STUDY METHODS
Review of randomly selected labor and delivery records from births in 1998 and 1999 in 8 active surveillance areas
Included all early-onset GBS cases in these areas; births without documented GBS screening were considered exposed to risk-based approach
The results of this study are published in Schrag et al, NEJM 2002, 347:233-9

## ABCs/ Emerging Infection Program Network for GBS surveillance

**Total pop. for 1998/1999 studies: 26 million**
**Approximately 300,000 live births annually**

**Notes:**
ABCs/EMERGING INFECTION PROGRAM NETWORK FOR GBS SURVEILLANCE
This map of the United States shows the surveillance areas that participated in the study
These included selected countires of Oregon, California, Minnesota, Tennessee, Georgia, New York, and the states of Maryland and Connecticut
The population under surveillance in these areas totaled approximately 26 miillion people and 300,000 live births annually.

## Results

-   5144 L&D records representing 629,912 live
-   births were abstracted

-  312 early onset GBS cases occurred in the
-   surveillance areas (incidence: 0.5/1000 live births)

** **52% of all deliveries had prenatal GBS screening

**Schrag et al, NEJM 2002, 347:233-9**

**Notes:**
RESULTS
312 early onset GBS cases occurred in the surveillance areas (incidence: 0.5/1000 live births) in 1998 & 1999
5144 L & D records representing 629,912 live births were abstracted
52% of all deliveries had prenatal GBS screening
These results are from Schrag et al, NEJM 2002, 347:233-9

## Factors associated with early-onset GBS disease: multivariable analysis

| Characteristic | Adjusted RR (95% CI) |
| --- | --- |
| GBS screening | 0.46 (0.36-0.60) |
| Prolonged ROM (> 18 h) | 1.41 (0.97-2.06) |
| Pre-term delivery | 1.50 (1.07-2.10) |
| Black race | 1.87 (1.45-2.43) |
| Maternal age <20 y | 2.22 (1.59-3.11) |
| Previous GBS infant |   5.54 (1.71-17.94) |
| Intrapartum fever | 5.36 (3.60-7.99) |

**Schrag et al, NEJM 2002, 347:233-9**

**Notes:**
FACTORS ASSOCIATED WITH EARLY-ONSET GBS DISEASE:  MULTIVARIABLE ANALYSIS
This table shows the factors significantly associated with early-onset GBS disease in multivariable analysis, as reported by Schrag et al, NEJM 2002, 347:233-9
Prenatal GBS screening was significantly protective.
The relative risk associated with screening was 0.46 (95% CI: 0.36-0.60)
A number of other factors were associated with increased risk of early-onset disease
The relative risk associated with prolonged rupture of membranes (ROM) was 1.41 (95% CI: 0.97-2.06)
The relative risk associated with pre-term delivery was 1.50 (95% CI: 1.07-2.10)
The relative risk associated with Black race was 1.87 (95% CI: 1.45-2.43)
The relative risk associated with maternal age less than 20 was 2.22 (95% CI: 1.59-3.11)
The relative risk associated with previous GBS infant was 5.54 (95% CI: 1.71-17.94)
The relative risk associated with intrapartum fever was 5.36 (95% CI: 3.60-7.99)

## Why is screening more protective than the risk-based approach?

** **

** **

**Broader coverage of at-risk population**

**	**

** ****Antibiotic effectiveness in this cohort, based on**
**   ****birth survey data:  89% (64-97%)**

** ****Captures colonized women without obstetric risk factors**
**    ****(18% of all deliveries)**

**Schrag et al, NEJM 2002, 347:233-9**

**Notes:**
WHY IS SCREENING MORE PROTECTIVE THAN THE RISK-BASED APPROACH?
This study (Schrag et al, NEJM 2002, 347:233-9) showed that screening allowed for a broader coverage of the at-risk population
Screening captures colonized women without obstetric risk factors (18% of deliveries)
Antibiotic effectiveness in this cohort, based on birth survey data was 89% (64-97%)

## Anticipated intrapartum antibiotic use does not differ between strategies

| 
 Reason for IAP | Deliveries (%) |  |
| --- | --- | --- |
|  | Screening cohort | Risk cohort |
| GBS indication | 24 | 24 |
| Other reasons* | 4 | 5 |
| Treatment of screen negative with fever | 2 | -- |
| Total IAP use | 30 | 29 |

*** ****Screening:**** ****based on use in screen negative, no risk factors; Risk: based on use in risk factor negative**

**Schrag et al, NEJM 2002, 347:233-9**

**Notes:**
ANTICIPATED INTRAPARTUM ANTIBIOTICS USE DOES NOT DIFFER BETWEEN STRATEGIES
Data from the study by Schrag et al, NEJM 2002 (347:233-9) shows that the anticipated intrapartum antibiotic use does not differ between the screening and risk based strategies, when the strategies are implemented according to the recommendations.
Under screening an estimated 30% of deliveries will receive intrapartum antibiotics for any reason;  under risk 29% will get intrapartum antibiotics for any reason
Under each strategy 24% of deliveries have indications for GBS prophylaxis.
In the screening cohort, 4% of women received intrapartum antibiotics for others reasons, meaning women with a negative result and no risk factors.
In the risk-based cohort, 5% of women received intrapartum antibiotics for other reasons (eg, no GBS risk factors present).

## Concerns about adverse consequences of intrapartum antibiotics

**Allergies:  anaphylaxis occurs but rarely**
**Resistance: Clindamycin & erythromycin resistance now more common in GBS**
**Changes in incidence or resistance of other pathogens:  data are complex... **

**Notes:**
CONCERNS ABOUT ADVERSE CONSEQUENCES OF INTRAPARTUM ANTIBIOTICS
Allergies:  anaphylaxis occurs but rarely
Resistance: Clindamycin & erythromycin resistance now more common in GBS
Changes in incidence or resistance of other pathogens:  data are complex... 

## Susceptibility of GBS: ABC/EIP Isolates, 1995-2000

**1280 isolates from MN, GA, NY, OR (1173 invasive, 107 colonizing):**
**All susceptible to penicillin, ampicillin, cefotaxime and vancomycin**
**19% erythromycin resistance **
**11% clindamycin resistance**

**Notes:**
SUSCEPTIBILITY OF GBS:  Isolates from the ABCs, 1995-2000
1280 isolates from MN, GA, NY, OR (1173 invasive, 107 colonizing)
All susceptible to penicillin, ampicillin, cefotazime and vancomycin
 19% erythromycin resistance
 11% clindamycin resistance

## What do we know about trends in “other pathogens”?

- Most studies: stable rates of ‘other’ sepsis
- A few hospitals reported increased rates or #s of *E coli,* all gram negs, or amp R infxs
- One multicenter study of very LBW infants found increase in *E coli * rates (Stoll et al)
- Pop-based (multicenter) studies find stable rates of total nonGBS and *E coli *
- % of *E. coli* sepsis w/ amp resistance may be increasing
**Increases restricted to low birth weight or preterm deliveries**

**Notes:**
WHAT DO WE KNOW ABOUT TRENDS IN “OTHER PATHOGENS”?
Most studies find stable rates of sepsis caused by other pathogens
A few single hospitals found increased rates or case counts of E coli, all gram negatives, or of amp R pathogens; one multicenter study of very low birth weight infants found an increased incidence of E. coli in the 1990s (Stoll et al., NEJM 347:240-7)
Other population-based (multicenter) studies find stable rates of total nonGBS and E coli
Proportion of E. coli neonatal sepsis with amp resistance may be increasing
Increases restricted to low birth weight or preterm deliveries; increases may not be related to GBS prophylaxis
See CDC’s revised GBS guidelines (MMWR Aug. 16,2002 (RR-11)) for a detailed review of these studies that includes references

## Ampicillin Susceptibility of E. coli from Early-Onset Sepsis Cases, Full-Term Infants, ABCs, Selected Counties CA and GA, 1998-2000

**N=22, p=0.52, linear trend**
**Hyde et al,  Pediatrics ****2002;110(4):690-5.**

**Ampicillin Susceptibility of *****E. coli***** from Early-Onset Sepsis Cases, Full-Term Infants, ABCs, Selected Counties CA and GA, 1998-2000**

**Notes:**
Ampicillin Susceptibility of E. coli from Early-Onset Sepsis Cases, Full-Term Infants, ABCs, Selected Counties CA and GA, 1998-2000
This bar chart shows a stable trend (P=0.52) in the number of ampicillin resistant E. coli early onset sepsis infections among full term infants in selected counties of CA and GA from 1998-2000. These data are from T. Hyde et al., Pediatrics 2002;110(4):690-5.
In 1998 surveillance detected 8 cases, 4 were ampicillin resistant
In 1999 surveillance detected 8 cases, 3 were ampicillin resistant
In 2000 surveillance detected 6 cases, 2 were ampicillin resistant

## Ampicillin Susceptibility of E. coli  from Early-Onset Sepsis Cases Preterm Infants, ABCs, Selected Counties CA and GA, 1998-2000

**N=37, p=0.02, linear trend**
**Hyde et al,  Pediatrics ****2002;110(4):690-5.**

**Ampicillin Susceptibility of *****E. coli*****  from Early-Onset Sepsis Cases Preterm Infants, ABCs, Selected Counties CA and GA, 1998-2000**

**Notes:**
Ampicillin Susceptibility of E. coli  from Early-Onset Sepsis Cases Preterm Infants, ABCs, Selected Counties CA and GA, 1998-2000
This bar chart shows a significantly increasing trend  (P=0.02) in the number of ampicillin resistant E. coli early onset sepsis infections among preterm infants in Pediatrics 2002;110(4):690-5.
selected counties of CA and GA from 1998-2000. These data are from T. Hyde et al., In 1998 surveillance detected 6 cases, 1 was ampicillin resistant
In 1999 surveillance detected 12 cases, 10 were ampicillin resistant
In 2000 surveillance detected 18 cases, 15 were ampicillin resistant

## Ampicillin resistant E. coli in Women w/ Cystitis, 1992-1996, GHC-Puget Sound

- Gupta et al. JAMA 1999;281;736-8

**Increase significant by linear trend (P <0.001)**

**Notes:**
Ampicillin Resistant E. coli in Women w/ Cystitis, 1992-1996, GHC-Puget Sound
The bar chart in this slide summarizes data from Gupta et al. in JAMA, 1999 on the percent of ampicillin resistant E. coli isolated from women with cystitis from 1992-1996.
The proportion of ampicillin resistant E. coli increased from 26% in 1992 to 34% in 1996.
This shows that ampicillin resistant E. coli has been increasing outside the context of the labor and delivery setting.
Studies investigating whether there are causal links between resistance trends in preterm infants and intrapartum GBS prophylaxis are needed

## What’s new in the 2002 GBS prevention recommendations

**Notes:**
What’s new in the 2002 GBS prevention recommendations
The next series of slides outlines what is new in CDC’s revised perinatal GBS disease prevention guidelines that came out in August, 2002

## The Recommendations 

**The Recommendations**** **
**MMWR, Vol 51**
**(RR-11)**

**Notes:**
THE RECOMMENDATIONS: MMWR, VOLUME 51 (RR-11)
This slide shows the front cover of the 2002 revised group B strep prevention guidelines. The entire document has been published by MMWR in Volume 51, RR-11.

## Areas of change

- Identification of candidates for intrapartum antimicrobial prophylaxis (IAP): A single strategy
- Second line agents for IAP
- Management of planned cesarean deliveries
- Management of threatened preterm deliveries
- More detail on specimen collection and handling
- Neonatal management

**Notes:**
AREAS OF CHANGE
Identification of candidates for intrapartum antimicrobial prophylaxis (IAP): A single strategy
Second line agents for IAP
Management of planned cesarean deliveries
Management of threatened preterm deliveries
More detail on specimen collection and handling
Neonatal management

## Identifying Candidates for IAP

- Recommendation: Universal prenatal screening at 35-37 wks’ gestation
- Risk based strategy reserved for women with unknown GBS culture status at the time of labor

**Notes:**
IDENTIFYING CANDIDATES FOR IAP
Recommendation:  Universal prenatal screening at 35-37 weeks’ gestation
Risk based strategy reserved for women with unknown GBS culture status at the time of labor

## Indications for IAP under universal prenatal screening

** ****GBS bacteriuria during current pregnancy**
** ****Positive GBS screening culture 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)**

**Notes:**
Indications for IAP under universal prenatal screening
Previous infant with invasive GBS disease
 GBS bacteriuria during current pregnancy
 Positive GBS screening culture 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)

##  Intrapartum prophylaxis NOT indicated

**Previous pregnancy with a positive GBS screening culture (unless a culture was ALSO positive during the current pregnancy)**

**Planned cesarean delivery performed in the absence of labor or membrane rupture (regardless of maternal GBS culture status)**

**Negative vaginal and rectal GBS screening culture during the current pregnancy, regardless of intrapartum risk factors**** **

**Notes:**
Intrapartum prophylaxis NOT indicatedPrevious pregnancy with a positive GBS screening culture (unless a culture was ALSO positive during the current pregnancy)
Planned cesarean delivery performed in the absence of labor or membrane rupture (regardless of maternal GBS culture status)
Negative vaginal and rectal GBS screening culture during the current pregnancy, regardless of intrapartum risk factors 

## Method of Prenatal GBS Culture Collection (recommendations have not changed)

- Optimize cultures:
- Site: vagina and rectum
- single swab or two swabs
- through anal sphincter
- Timing: 35 to 37 weeks
- Collection: NOT by speculum
- self collection an option
- Processing: selective broth medium

**Notes:**
CDC’S RECOMMENDATIONS FOR PRENATAL GBS CULTURES
Every effort should be made to optimize the yield from the cultures.
Includes culturing both the vagina and the rectum at the appropriate time.
Culture 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.
Specimens should come from the lower third of the vagina, and the rectal swab should pass through the anal sphincter.
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.
Specimens should be processed using selective broth medium.  This is critical for increasing yield from prenatal cultures

## Agents for intrapartum prophylaxis

- Recommended agents for women with documented penicillin allergy:
- Not at high risk for anaphylaxis: cefazolin
- At high risk for anaphylaxis:
- Clindamycin or erythromycin if susceptibility testing feasible
- Vancomycin if erythromycin or clindamycin not options

- Rationale: concern about treatment failure due to increasing resistance among GBS to erythromycin and clindamycin

**Notes:**
AGENTS FOR INTRAPARTUM PROPHYLAXIS
Recommended agents for women with documented penicillin allergy:
Not at high risk for anaphylaxis: cefazolin
At high risk for anaphylaxis:
Clindamycin or erythromycin if susceptibility testing feasible
Vancomycin if erythromycin or clindamycin not options
Rationale: concern about treatment failure due to increasing resistance among GBS to erythromycin and clindamycin

## Planned Cesarean Deliveries

- IAP not routinely recommended in this circumstance
- In absence of labor and amniotic membrane rupture, risk for transmission very low
- Retrospective, single hospital study
- Review of CDC active surveillance data
- Individual risks and inconvenience of IAP appear to balance or outweigh benefits
- Prenatal screening still recommended because labor or membrane rupture might occur before scheduled surgery

**Notes:**
PLANNED CESAREAN DELIVERIES
Intrapartum antibiotic prophylaxis is not routinely recommend in this circumstance
In absence of labor and amniotic membrane rupture, risk for transmission very low
Retrospective, single hospital study
Review of CDC active surveillance data
Individual risks and inconvenience of IAP appear to balance or outweigh benefits
Prenatal screening is still needed for women intending to deliver by scheduled cesarean section because labor or rupture of membranes might occur before surgery.

## Threatened Preterm Delivery

- Suggested algorithm for management of threatened preterm delivery (labor or rupture of membranes at <37 weeks’ gestation) which does not proceed rapidly to delivery:
- Culture and start IV antibiotics
- Culture negative at 48 hrs: stop antibiotics
- Culture positive: no data on duration of antibiotics before active labor, when active labor begins give IAP
- Culture negative and undelivered within 4 wks: re-screen

**Notes:**
THREATENED PRETERM DELIVERY
Suggested algorithm for management of threatened preterm delivery (labor or rupture of membranes at <37 weeks’ gestation) which does not proceed rapidly to delivery:
Culture and start IV antibiotics
Culture negative at 48 hours: stop antibiotics
Culture positive: no data on duration of antibiotics before active labor, when active labor begins give IAP
Culture negative and undelivered within 4 weeks: re-screen

## Neonatal Management

- Maternal chorioamnionitis: full diagnostic evaluation & empiric broad-spectrum antibiotic coverage pending blood culture result
- LP if clinical signs of sepsis (if feasible)
- Consensus on adequacy of 4 hour duration of IAP (as opposed to 2 doses)
- Discharge after 24 hrs sometimes reasonable (asymptomatic, 4 hrs IAP, 38 wks’ gestation, adequate home observation, other criteria for discharge met)

**Notes:**
NEONATAL MANAGEMENT
If the mother has suspected chorioamnionitis: full diagnostic evaluation & empiric broad-spectrum antibiotic coverage pending blood culture result
Lumbar puncture if clinical signs of sepsis (if feasible)
Consensus on adequacy of 4 hour duration of IAP (as opposed to 2 doses)
Discharge after 24 hrs sometimes reasonable (asymptomatic, 4 or more hours IAP, 38 weeks’ gestation or more, adequate home observation, other criteria for discharge met)
The American Academy of Pediatrics will provide more detail on neonatal issues related to maternal chorioamnionitis and criteria for collecting lumbar punctures in AAP News in 2003 

## Things that remain the same

- Penicillin first-line agent for IAP (ampicillin an acceptable alternative)
- If culture results unknown at delivery, IAP if risk factors (fever, ROM >18 hrs, preterm) present
- Women with bacteriuria during pregnancy or previous infant with GBS disease should receive IAP
- Prenatal treatment only for symptomatic or asymptomatic GBS urinary tract infections

**Notes:**
THINGS THAT REMAIN THE SAME
Penicillin is the recommended first-line agent for IAP, ampicillin is an acceptable alternative
If culture results unknown at delivery, IAP if risk factors are present (fever, ROM > 18hrs, preterm delivery)
Women with bacteriuria during pregnancy or previous infant with GBS disease should receive IAP
Prenatal treatment only for symptomatic or asymptomatic GBS urinary tract infections 

## Guidelines from other organizations

**In October, 2002 AAP endorsed CDC’s August, 2002 guidelines**

**In December, 2002 ACOG released a new**
**Committee Opinion consistent with CDC’s**
**recommendations**

**ACNM will come out with revised guidelines consistent with the above in early 2003**

**Notes:**
Guidelines from other organizations
In October, 2002 AAP endorsed CDC’s August 16, 2002 guidelines
In December, 2002 ACOG released a new Committee Opinion with recommendations consistent with CDC’s recommendations
ACNM will come out with revised guidelines consistent with the above in early 2003

## What Can You Do to Help?

- Make sure your OB, Peds, and Microbiology colleagues know the new guidelines are out!
- Check if your lab is using selective broth medium
- Form a committee to plan steps needed for implementation in your facility

**Notes:**
What Can You Do to Help?
Make sure your OB, Peds, and Microbiology colleagues know the new guidelines are out!
Check if your lab is using selective broth medium  
Form a committee to plan steps needed for implementation in your facility

## Laboratory-specific issues

- Assess personnel/supplies re: anticipated increase in GBS prenatal cultures
- Plan how to report GBS from prenatal urine cultures (any concentration of GBS should be reported to provider)
- Plan how to perform susceptibility testing of GBS if Pen allergy
- Facilitate timely communication of results

**Notes:**
Laboratory-specific issues
Assess personnel/supplies re: anticipated increase in GBS prenatal cultures
Plan how to report GBS from prenatal urine cultures (any concentration of GBS should be reported to provider)
Plan how to perform susceptibility testing of GBS if Pen allergy
Facilitate timely communication of results

## Infection control contributions

- System for flagging GBS + results, Pen allergy
- Standing orders (eg. GBS carriers, GBS bacteriuria, previous GBS invasive disease, or unknown carriage and a RF)
- Patient education materials
- Evaluation of implementation indicators (eg, proportion of deliveries getting IAP, proportion of women GBS+, proportion of GBS+ getting IAP)
- Evaluation of early-onset cases for missed opportunities for prevention

**Notes:**
Infection control contributions
System for flagging GBS + results, Pen allergy
Standing orders (eg. GBS carriers, GBS bacteriuria, previous GBS invasive disease, or unknown carriage and a RF)
Patient education materials
Evaluation of implementation indicators (eg, proportion of deliveries getting IAP, proportion of women GBS+, proportion of GBS+ getting IAP)
Evaluation of early-onset cases for missed opportunities for prevention

## Key GBS Resources  

**2002 GBS guidelines **
**http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm**
**Schrag et. al, NEJM 2002; Vol. 347 (4):233-239**
**American College of Obstetricians and Gynecologists**
**http://www.acog.org**
**American Academy of Pediatrics**
**http://www.aap.org**
**Public Health Foundation**
**	**** ****- http://www.phf.org**
**CDC's GBS Internet page**
**http://www.cdc.gov/groupbstrep**

## Acknowledgments

**Katie Arnold, Katherine Bryant, Alicia Bustamante, Allen Craig,**
**Pam Daily, Barbara Damaske, Heather Linardos, Ruth Lynfield, **
**Janet Mohle-Boetani, Mike Nixon, Peggy Pass, Jean Rainbow,**
**Aaron Roome, Mary Snowden, Karen Stefonek, Rashmi Subbarao,**
**Shelley Zansky**

**• ****CDC:**

**•  ****ABCs/ EIP Network:**

**Kristi Fultz-Butts, Melanie Gamble, Tami Hilger, Anne Schuchat,**
**Elizabeth Zell, Katherine Robinson,Stephanie Schrag, **
**Rachel Gorwitz, Janine Cory, Marcqui Akins, Elizabeth Pishko**

**•  ****Consultants at November 2001 GBS Meeting**

**Notes:**
ACKNOWLEDGEMENTS
Consultants at November 2001 GBS Meeting
ABCs/EIP Network – Katie Arnold, Katherine Bryant, Alicia Bustamante, Allen Craig, Pam Daily, Barbara Damaske, Health Lindardos, Ruth Lynfield, Janet Mohle-Boetani, Mike Nixon, Peggy Pass, Jean Rainbow, Aaron Roome, Mary Snowden, Karen Stefonek, Rashmi Subbarao, Shelley Zansky
CDC – Kristi Fultz-Butts, Melanie Gamble, Tami Hilger, Anne Schuchat, Elizabeth Zell, Katherine Robison, Stephanie Schrag, Rachel Gorwitz, Janine Cory, Marcqui Akins, Elizabeth Pishko