Perinatal GBS Disease: Background, Epidemiology, and Overview of Revised CDC Prevention Guidelines o

1
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
2
Background on GBS disease and prevention
3
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

4
Invasive GBS Disease Incidence by Age Group and
Race (1990)
per 1000 births
MMWR Vol. 41 (No. SS-6) 1992
5
GBS Disease in Infants Before Prevention Efforts
A Schuchat. Clin Micro Rev 199811497-513.
6
Early-Onset Neonatal GBS Disease Before
Prevention Efforts
A Schuchat. Clin Micro Rev 199811497-513.
7
Photo courtesy of Dr. Carol Baker Baylor
College of Medicine, Houston, TX
8
Photo courtesy of Dr. Carol Baker Baylor College
of Medicine, Houston, TX
9
Mother to Infant Transmission
GBS colonized mother
50
50
Non-colonized newborn
Colonized newborn
98
2
Early-onset sepsis, pneumonia, meningitis
Asymptomatic
10
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

11
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)

12
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?

13
Rates of Early-Onset GBS Disease by Prenatal
Colonization Risk Factors
Col prenatal vag/rect culture RF risk factors
(gest. lt37 wks, ROM gt12 hr, fever gt 37.5 C)
Boyer Gotoff, Antibiot Chemother 1985.
14

• 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 rupturegt18 hours, or
intrapartum fever (Tgt38C) Both strategies also
give IAP to women with GBS bacteriuria, or
previous infant with GBS disease
15
Implementation and impact of the 1996 consensus
guidelines
16
GBS Policies in US Hospitals Implementation by
Year
Consensus Guidelines Issued
Draft Guidelines Issued
ACOG, AAP Guidelines Issued
ABCs Hospitals, EIP Network MMWR 1998 47665-670
17
Change in incidence of early-onset GBS disease in
hospitals w/ and w/out new policies
P.26
P.006
Factor, Obstet Gynecol 200095377-82
18
Implementation of GBS prevention at hospitals,
1997 v. 1999
ABCs/Emerging Infections Program Network MMWR
Oct. 2000 49(41)936-940
19
GBS policies among ABCs hospitals vs. individual
ACOG members
Watt, Obstetr Gynecol 2001987-13
20

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

Group B Strep Association formed
1st ACOG AAP statements
CDC draft guidelines published
Consensus guidelines
Schrag, New Engl J Med 2000 342 15-20
21

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

22
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
23
Re-evaluation of the 1996 prevention guidelines
Central issues for reconsideration
24
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
25
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

26
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
Schrag et al, NEJM 2002, 347233-9
27
ABCs/ Emerging Infection Program Network for GBS
surveillance
Total pop. for 1998/1999 studies 26
million Approximately 300,000 live births annually
28
Results

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

• 5144 LD records representing 629,912 live
• births were abstracted

• 52 of all deliveries had prenatal GBS screening

Schrag et al, NEJM 2002, 347233-9
29
Factors associated with early-onset GBS disease
multivariable analysis
Schrag et al, NEJM 2002, 347233-9
30
Why is screening more protective than the
risk-based approach?

Broader coverage of at-risk population

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

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

Schrag et al, NEJM 2002, 347233-9
31
Anticipated intrapartum antibiotic use does not
differ between strategies
Screening based on use in screen negative, no
risk factors Risk based on use in risk factor
negative
Schrag et al, NEJM 2002, 347233-9
32
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

33
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

34
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

35
Ampicillin Susceptibility of E. coli from
Early-Onset Sepsis Cases, Full-Term Infants,
ABCs, Selected Counties CA and GA, 1998-2000
N22, p0.52, linear trend Hyde et al,
Pediatrics 2002110(4)690-5.
36
Ampicillin Susceptibility of E. coli from
Early-Onset Sepsis Cases Preterm Infants, ABCs,
Selected Counties CA and GA, 1998-2000
N37, p0.02, linear trend Hyde et al,
Pediatrics 2002110(4)690-5.
37
Ampicillin resistant E. coli in Women w/
Cystitis, 1992-1996, GHC-Puget Sound
Increase significant by linear trend (P lt0.001)
Gupta et al. JAMA 1999281736-8
38
Whats new in the 2002 GBS prevention
recommendations
39
The Recommendations MMWR, Vol 51 (RR-11)
40
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

41
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

42
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 lt37 weeks gestation
• Amniotic membrane rupture ?18 hours
• Intrapartum temperature ?100.4F (? 38.0 C)

43
 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
44
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

45
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
46
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

47
Threatened Preterm Delivery

• Suggested algorithm for management of threatened
  preterm delivery (labor or rupture of membranes
  at lt37 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

48
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)

49
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 gt18 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

50
Guidelines from other organizations
In October, 2002 AAP endorsed CDCs August, 2002
guidelines
In December, 2002 ACOG released a new Committee
Opinion consistent with CDCs recommendations
ACNM will come out with revised guidelines
consistent with the above in early 2003
51
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

52
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

53
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

54
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

55
Acknowledgments
Consultants at November 2001 GBS Meeting
ABCs/ EIP Network
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
Kristi Fultz-Butts, Melanie Gamble, Tami Hilger,
Anne Schuchat, Elizabeth Zell, Katherine
Robinson,Stephanie Schrag, Rachel Gorwitz,
Janine Cory, Marcqui Akins, Elizabeth Pishko