Preventing early-onset group B Streptococcal infection in newborn babies January 2009 Charity No. 1112065 Company Reg No 5587535

Preventing early-onset group B Streptococcal infection

in newborn babies

January 2009 Charity No. 1112065 Company Reg No 5587535

Charity No. 1112065 Company Reg No 5587535 2

Group B Streptococcus – overview 1

Streptococcus agalactiae Group B Strep, Strep B, beta haemolytic Strep

First recognised as a major perinatal pathogen in the 1970s

Incidence of GBS infection increasing in the UK

0 500 1000 1500

2002

2003

2004

2005

2006

2007

Culture proven cases of GBS infection (all ages) in England, Wales & NI

Source: Health Protection Agency


Group B Streptococcus – overview 2

Commonest cause of bacterial infection in newborn babies

Underlying rate estimated at 1:1000 newborn babies in the UK UK research suggests actual rate 3.5 per 1000 (Luck et al, 2003)

Mortality rate approximately 11% 50% of survivors of GBS meningitis will have neurological sequelae

Early-onset and late-onset presentation of GBS infection

Up to 90% GBS infection apparent within 48 hours of birth

Remains uniformly sensitive to penicillin Some tolerance to other antibiotics

Clindamycin around 8% is resistant Erythromycin around 11% is resistant


Reported cases of GBS bacteraemia in infants*, England & Wales 2000-2007

Source: Health Protection Agency, 2008 *excludes a small number of infants with imprecise age data

0

50

100

150

200

250

300

350

400

450

2000 2001 2002 2003 2004 2005 2006 2007

6-11 months

3-5 months

1-2 months

1-3 weeks

<1week


GBS – Colonisation

Normal flora in intestinal tract and vagina Carriage can be intermittent Carriage is asymptomatic Up to 30% adults carry GBS in intestines Up to 25% of women carry GBS in the vagina Occasionally in the throat (around 5%)

90% of adults do not have protective antibodies to GBS

GBS can cross intact amniotic membranes GBS grows well in amniotic fluid

GBS survives well on skin of newborn infants

GBS colonisation at delivery – risk factor for early-onset GBS disease Cultures late in pregnancy can predict GBS colonisation status at delivery


Testing Antenatally for GBS carriage

Between 35 and 37 weeks

GBS carriage can be intermittent so best to swab close to delivery.

Sensitive tests taken within 5 weeks of delivery are highly predictive of carriage at delivery (Yancey et al 1996)

Must take vaginal and rectal swabs

Low vaginal plus anorectal swabs (can use either one or two swabs) are much more effective than high vaginal swabs

Must use selective enrichment medium to

culture swabs

LIM broth (10mL Todd-Hewitt broth supplemented with 10µg/mL colistin and 15µg/mL nalidixic acid) then subcultured to blood agar)

Recognised as optimal for detecting GBS carriage by the Royal College of Obstetricians & Gynaecologists and The Health Protection Agency (BSOP 58)

Available privately and from a handful of NHS hospitals (contact GBSS for availability)

STANDARD CULTURE METHOD TOO INSENSITIVE

FOR testing

Standard culture method (direct plating) instead of using enriched culture medium reduces detection by 50%


Options to reduce GBS infection in newborn babies

Waiting & treating babies after delivery Too late for some & won’t prevent most GBS infection Difficult to justify

Intravenous antibiotics in labour (IAL) Only effective method of prevention available at present Largest study performed in Chicago (Boyer et al. N Eng J Med

1986;314:1665) Penicillin G recommended (Clindamycin for penicillin-allergic women)

Oral antibiotics Don’t eradicate colonisation or reduce infection Likely to increase resistance Exception is GBS cultured from urine (treat with oral antibiotics and offer

IAL)

Intramuscular antibiotics Theory – reduces GBS presence ≤6 weeks, so given at 35+ weeks One small study – poorly designed & no GBS grown in control or active

group


Who should be offered intravenous antibiotics in labour (IAL)?

women who have one or more risk factors (including incidental finding of GBS carriage or GBS +ve urine culture) during the current pregnancy OR

women identified as GBS carriers through testing (using enriched culture media) at 35-37 weeks of pregnancy OR

women identified as GBS carriers through enriched culture media testing at 35-37 weeks of pregnancy and who have one or more other risk factors OR

women found to carry GBS through enriched culture media testing at 35-37 weeks of pregnancy PLUS women who have one or more other risk factors

Women should be offered an informed choice


Option 1: Risk Factor ApproachIAL offered to all women with one or more risk factors

Offer intravenous antibiotics in labour (IAL) to women who have:

a previous baby with GBS infection

GBS bacteria found in the urine during the current pregnancy (which should be treated at the time of diagnosis)

GBS found on a vaginal or rectal swab during the current pregnancy

a raised temperature (≥37.8°C) during labour

preterm labour or membrane rupture (<37 completed weeks of pregnancy)

prolonged rupture of membranes (≥18 hours before delivery)

>40% of cases will still occur, since this will only prevent GBS infections where risk factors are apparent in time for IAL to be offered

Supported by RCOG Green Top Guideline No 36

Not tested in a trial

Relatively cheap to introduce & operate (no bacteriological testing costs involved)

Relatively large amounts of antibiotics prescribed (about 30% of all women)

Pros and Cons


Up to 80% potential cases prevented A few women will acquire carriage

between testing and delivery*; some carriers will miss or decline testing and some will deliver before test result available

Not tested in a trial ECM testing for GBS carriage not

routinely or widely available in the NHS (despite being recognised as optimal by RCOG & HPA)

More expensive to introduce Relatively large amounts of antibiotics

prescribed (~30% of women)

Option 2: Testing ApproachIAL offered only to women identified as GBS carriers

Offer sensitive enriched culture medium (ECM) testing to all women at 35-37 weeks of pregnancy

Offer intravenous antibiotics in labour (IAL) to women identified as GBS carriers during their current pregnancy

Pros and Cons

* Yancey research found 4% of women with negative results at 35-37 weeks of pregnancy would become positive and 13% of women with positive results would become negative


Option 3: Combined Approach 1IAL offered to GBS carriers with a risk factor

Offer all women sensitive enriched culture medium (ECM) testing at 35-37 weeks

Offer intravenous antibiotics in labour (IAL) to those identified as GBS carriers during the current pregnancy who also have one or more risk factors:

Preterm labour or membrane rupture (<37 completed weeks of pregnancy)

Prolonged rupture of membranes (≥18 hours before delivery)

Maternal pyrexia (≥ 37.8oC)

GBS from a urine culture during the current pregnancy

Previous baby with GBS infection

>40% of cases will still occur – this can only prevent GBS infection where risk factors are apparent in time for IAL to be offered

A few women will acquire carriage between testing and delivery (see

previous slide), some carriers will miss or decline testing and some will deliver before test result is available

Well researched

ECM testing for GBS carriage not routinely or widely available in the NHS (despite being recognised as optimal by RCOG & HPA)

More expensive to introduce

Fewer women receive antibiotics ~5%

Pros and Cons


Option 4: Combined Approach 2IAL to GBS carriers & to women with 1+ risk factors

Offer all women sensitive enriched culture medium (ECM) testing at 35-37 weeks

Offer intravenous antibiotics in labour (IAL) to those identified as GBS carriers during the current pregnancy plus to any with one or more risk factors:

Preterm labour or membrane rupture (<37 completed weeks)

Prolonged rupture of membranes (≥18 hours before delivery)

Maternal pyrexia (≥ 37.8oC)

GBS from a urine culture during the current pregnancy

Previous baby with GBS infection

Most >80% potential cases prevented

Not tested in a trial

ECM testing for GBS carriage not routinely or widely available in the NHS (despite being recognised as optimal by RCOG & HPA)

Less expensive – fewer women offered sensitive testing as higher-risk women offered IAL without testing

Relatively large amounts of antibiotics prescribed (~30% of pregnant women)

Pros and Cons


Incidence of EO and LO GBS in 3 active surveillance areas in USA

00.20.40.60.81

1.21.41.61.82

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

early-onset

late-onset

Source: N Engl J Med 2000;342:15-20 & p.c. A Schuchat


UK Guidelines for Prevention: NICE Antenatal Care Guideline CG6 Oct 03 - 1

Don’t recommend screening as “evidence of its clinical effectiveness and cost effectiveness remains uncertain.”

All the evidence shows testing and offering intravenous antibiotics in labour (IAL) to higher-risk women is clinically effective. Where introduced, reductions of over 70% in incidence, including the US, Australia, New Zealand, Belgium, France, Spain & Italy.

The cost/benefit analysis sponsored by the HTA, published September 2007 shows current practice is not cost effective – testing low-risk women and offering IAL to high risk women was shown to be most cost effective while limiting antibiotic use (Preventative strategies for group B streptococcal and other bacterial infections in early infancy: cost effectiveness and value of information analyses. BMJ. 2007 Sep. Colbourn et al)

Guideline updated March 2008 - No update to GBS sections despite significant new evidence since 2003 and despite requests by a number of stakeholders. Next review due March 2010


UK Guidelines for Prevention:NICE Antenatal Care Guideline CG6 Oct 03 - 2

“Pregnant women should be offered information based on the current available evidence together with support to enable them to make informed decisions about their care..” Yet information on GBS is not widely nor routinely available.

Sensitive tests for GBS are only available privately and from a handful of NHS hospitals.

Women are not told about the availability of sensitive tests for detecting GBS late in pregnancy.

How can women make an informed decision when they’re not being given the information?

Guideline updated March 2008 - No update to GBS sections despite significant new evidence since 2003 and despite requests by a number of stakeholders. Next review due March 2010


UK Guidelines for Prevention: Royal College of Obstetricians & Gynaecologists 1

Risk factor approach Estimates relative risk for morbidity or mortality for

recognised risk factors Incidence assumptions significantly underestimate GBS

infection, so underestimate the relative risks and overestimate the numbers needed to treat for benefit

Authors of the source of incidence figures (Heath et all, 2004) estimate under-reporting of 21-42%

Incidence figures exclude probable cases of GBS infection (Luck et al 2002), including only cases where GBS was culture-proven from a normally sterile site, eg CSF or blood

Incidence of GBS infection in babies increasing (HPA)

RCOG Green Top Guideline No 36 "Prevention of early onset neonatal Group B streptococcal disease" 2003 (currently being reviewed - due 2010)


UK Guidelines for Prevention:Royal College of Obstetricians & Gynaecologists 2

Will prevent most lethal cases of EOGBS infection when fully implemented RCOG audit Jan 2007 shows few hospitals fully comply

Until sensitive testing is routinely available for all pregnant women, GBSS endorses these guidelines They are a key starting position to preventing early onset GBS

infection More infections in babies could be prevented by offering sensitive

testing to pregnant women

RCOG Green Top Guideline No 36 "Prevention of early onset neonatal Group B streptococcal disease" 2003 (currently being reviewed - due 2010)


GBSS Recommendation: 1

identified as GBS carriers in the current pregnancy with ≥ 1 other risk factors (no testing required)

previous baby with GBS infection positive urine sample during this pregnancy preterm labour or rupture of membranes <37 completed weeks of pregnancy prolonged rupture of membranes ≥18 hours before delivery maternal pyrexia ≥ 37.8oC

Sensitive (enriched culture medium) tests for GBS carriage using rectal & vaginal swabs should be freely

available to all low-risk women at 35-37 weeks of pregnancy

Pregnant women should be informed about GBS, including about testing, as a routine part of their antenatal

care

Intravenous antibiotics in labour should be offered to women:


GBSS Recommendation: 2

Pregnant women should be informed about GBS as a routine part of their antenatal care

Where sensitive GBS tests are unavailable in the NHS, pregnant women should be informed how to obtain them privately

Intravenous antibiotics in labour should be offered to women: who have previously had a GBS baby where GBS is found in the urine during the current pregnancy (also

treated at diagnosis) identified as carriers (any test method) during the pregnancy not tested using sensitive tests but with ≥ 1 other risk factors:

Prolonged rupture of membranes ≥18 hours before delivery Preterm labour or membrane rupture <37 completed weeks of pregnancy Maternal pyrexia ≥ 37.8oC

Until sensitive tests for GBS carriage are freely and routinely available to all women at 35-37 weeks of pregnancy:


Intrapartum Antimicrobial Prophylaxis

Penicillin G

3 g (or 5 mU) IV initially and then 1.5 g (or 2.5 mU) at 4-hourly intervals until delivery.

Clindamycin

For women who are allergic to penicillin, 900 mg IV every 8 hours until delivery.

Intravenous antibiotics should be given for at least

4 hours before delivery, where possible lesser times are better than nothing and 2+

hours should give considerable reassurance.


Option 6: Intravenous Antibiotics in Labour Chart

OfferIntravenous antibiotics at the start of, and at

intervals during, labour to women at raised risk of their baby developing GBS infection

Strongly recommend Intravenous antibiotics at the onset of, and

during, labour to women at particularly high risk of their baby developing GBS infection

One of: Women found to carry GBS during

pregnancy

GBS found in urine during pregnancy

Preterm labour or membrane rupture <37 weeks of pregnancy

Prolonged rupture of membranes ≥ 18-24 hours before delivery

Maternal pyrexia 37.8°C or higher during labour*

Two or more of above risk factors

Previous baby developed GBS infection

*In the presence of an epidural, a slightly raised temperature may be of less significance than in a woman without


Paediatric prevention strategy for babies born at higher risk

Signs of possible infection in neonate or mother

Gestational age ≤ 35 weeks of pregnancy

Maternal intravenous antibiotics pre-delivery < 4 hours

Maternal intravenous antibiotics Pre-delivery > 4 hours AND mother with no signs of infection

YES

YES

YES

YES

NO

NO

NO

Full work up

Intravenous antibiotics

Review at 48 hours

Full work up


Review at 48 hours

Full work up


Review at 48 hours

No work upBaby dischargedParental awareness of early signs of infectionHandout

BABY WORK UP

FBC (Full Blood Count)

CRP (C reactive protein) x2, 12 – 24 hours apart

Blood Culture

2 swabs – throat and periumbilical

Urine antigen Optional, according to availability and personal preference


Babies Colonised with GBS

Culture results are ‘history’

Swabs from baby Vaginal swab at time of delivery

Antibiotic treatment for a healthy colonised baby is not indicated

Can send baby home, but ‘educate’ parents

what symptoms to watch for what to do if they develop


Transmission of GBS to baby

0.6%Ear ly-o nset G B S in fectio n

(septicaem ia, pneum o n ia and /o r m en ingit is)

99.4%A sym pto m atic

50%B aby co lo n ised w ith G B S

50%N ew bo r n baby no t co lo n ised

M o ther co lo n ised w ith G B S at deliver y(up to 30% o f w o m en)

Mother colonised with GBS at delivery

(up to 30% of women)

50%Baby colonised with GBS

50%Newborn baby not colonised

0.6%Early-onset GBS infection septicaemia, pneumonia and/or

meningitis

99.4%Asymptomatic


Types of GBS infection (1)

Apparent within first 6 days of life, and usually within 12 -24 hours of delivery

Usually septicaemia with pneumonia

Typical symptoms

Grunting Poor feeding Lethargy Low blood pressure Irritability Low blood sugar

Even with the best medical care, 10% of babies with EOGBS die

Early-onset GBS infection (EOGBS)

Abnormally high or low temperature Abnormally high or low heart rates Abnormally high or low breathing rates


Types of GBS infection (2)

Develops 6 days - 3 months

Usually meningitis with septicaemia

Typical symptoms of late-onset GBS infection

Fever Poor feeding and/or vomiting Impaired consciousness Plus any symptoms of meningitis

Even with the best medical care

5% of babies sick with LOGBS die up to 50% of survivors of GBS meningitis suffer long term handicaps

Late-onset GBS infection (LOGBS)


Baby successfully treated for GBS infection

GBS infections have a relatively high incidence of

recurrence (1-3%)

Consider low dose oral penicillin daily for 3

months


The Future

Rapid Near Patient Testing

Better than testing at 35-37 weeks in informing which women are carrying GBS in labour

Unfortunately, no tests currently both fast and accurate enough More costly than enriched culture medium testing

Vaccine

Best approach for preventing both EOGBS and LOGBS infection, plus maternal GBS infection and other adult GBS infection

Target would be pregnant women or women before they become pregnant

Vaccine needs to be multivalent Research is urgently needed into developing a viable vaccine for

group B Strep infection Decades away – big concerns re medico-legal issues


Key References

Centers for Disease Control & Prevention. Prevention of Perinatal Group B Streptococcal Disease: Revised Guidelines from CDC. MMWR Reports & Recommendations Vol. 51(No. RR 11) 16 August 2002.

Heath PT, Balfour G, Weisner AM, Efstratiou A, Lamagni TL, Tighe H, O'Connell LAF, Cafferkey M, Verlander NQ, Nicoll A & McCartney AC on behalf of the PHLS GBS Working Group. Group B streptococcal disease in UK and Irish Infants <90 days of age. Lancet 2004 Jan 24, Vol 363(9405):292.

Luck S, Torny M, d'Agapeyeff K, Pitt A, Heath P, Breathnach A & Bedford Russell A. Estimated early-onset group B streptococcal neonatal disease. Lancet, 2003 Jun 07; 361(9373): 1953-1954

PHLS Communicable Disease Surveillance Unit. Incidence of group B streptococcal disease in infants aged less than 90 days. CDR weekly Vol. 12(No 16):3. 18 April 2002.

Colbourn TE, Asseburg C, Bojke L, Philips Z, Welton NJ, Claxton K, Ades AE, and Gilbert RE. Preventive strategies for group B streptococcal and other bacterial infections in early infancy: cost effectiveness and value of information analyses. BMJ 2007 335: 655

Royal College of Obstetricians & Gynaecologists Clinical Green Top Guideline. Prevention of Early Onset Neonatal Group B Streptococcal Disease (36) – Nov 2003

Law MR, Palomaki G, Alfirevic Z, Gilbert G, Heath P, McCartney C, Reid T, Schrag S on behalf of the Medical Screening Society Working Group on GBS disease. The prevention of neonatal group B streptococcal disease. J Med Screen 2005;12:60-68.

Yancey MK, Schuchat A, Brown LK, Ventura VL, Markenson GR. The accuracy of late antenatal screening cultures in predicting genital GBS colonization at delivery. Obstet Gynecol Nov 1996; 88(5):811-5.


Group B Strep Support

Registered charity set up in 1996

Aims:

Funded by donations

To inform health professionals and individuals how most EOGBS infection can be prevented; and

To offer information and support to families affected by GBS;

To generate continued support for research

into preventing GBS infections.


GBSS Materials Available

LEAFLETS GBS & pregnancy (introduction for pregnant

women)

Congratulations on the safe arrival of your baby (introduction for parents of a healthy baby)

Understanding your baby’s GBS infection (introduction for parents of a GBS baby)

For women who carry GBS (detailed leaflet for women who know they carry GBS)

If your baby was infected by GBS (detailed leaflet for parents of babies affected by GBS)

GBS: The Facts (detailed leaflet, including medical reference list)

POSTERS Pregnant? (for pregnant women)

Labour & Delivery Prevention Guidelines Understanding your baby’s GBS

infection – for SCBUs

Saving Babies’ Lives – A2

STICKERS GBS Alert - 35 per page for pregnant women’s notes

I am GBS Aware - 35 per page for pregnant women’s notes


GBSS Medical Advisory Panel

Professor Philip Steer, BSc, MD, FRCOG (Chair)

Emeritus professor at Imperial College and consultant obstetrician at the Chelsea and Westminster Hospital in London

Dr Alison Bedford-Russell MRCP

Consultant Neonatologist, Birmingham Heartlands Hospital

Dr A Christine McCartney OBE FRCPath

Director, Regional Microbiology Network, Health Protection Agency Central Office


What it’s all about ….

……. healthy babies

Documents

Preventing early-onset group B Streptococcal infection in newborn babies January 2009 Charity No. 1112065 Company Reg No 5587535