September 2007 Charity No. 1112065 Company Reg No 5587535 1 Preventing early-onset group B...

September 2007 Charity No. 1112065 Company Reg No 5587535 1

Preventing early-onset group B Streptococcal infection

in newborn babies

September 2007 Charity No. 1112065 Company Reg No 5587535

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Group B Streptococcus

Streptococcus agalactiae Gram positive coccus Normal body commensal of intestines and vagina First recognised as a major perinatal pathogen in the 1970s Commonest cause of bacterial infection in newborn babies

Underlying rate estimated as one per 1,000 newborn babies in the UK– UK research suggests the true incidence may be as high as 3.5 per 1000 (Luck et al, 2003)

Mortality rate approximately 10% 30% of survivors of GBS meningitis will have neurological sequelae

Early and late onset presentations Up to 90% GBS infection apparent within 48 hours of birth Remains uniformly sensitive to penicillin (some tolerance to

clindamycin)


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Reported cases of GBS infection in England &

Wales 1990-95

0

50

100

150

200

250

300

350

400

1990 1991 1992 1993 1994 1995

Year

Cases p

er

Year

Infants

6 - 11 months

3 - 5 months

1 - 2 months

1 - 3 weeks

<1 week

Source: CDSC


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GBS – Colonisation

Normal flora in intestinal tract and vagina 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%)

Colonisation can be intermittent 90% of adults do not have protective antibodies to

GBS GBS can traverse macroscopically intact amniotic

membranes GBS grows well in amniotic fluid GBS survives well on skin of newborn infant


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Screening Antenatally for GBS carriage

Between 35 and 37 weeks GBS carriage can be intermittent so best to swab close to delivery.

– Research shows reliable tests done 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 are much more effective than HVS

Must use selective method with enrichment medium Recognised as optimal for detecting GBS carriage by the Royal College of

Obstetricians and The Health Protection Agency (BSOP 58)

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

STANDARD CULTURE METHOD TOO INSENSITIVE FOR SCREENING Standard culture method (direct plating) instead of using enriched culture

medium reduces detection by 50%


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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

Intrapartum antimicrobial prophylaxis (IAP) Only 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 recommended for penicillin-allergic women


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Options for selecting which women receive IAP

1. IAP to all women who have one or more risk factors (including incidental finding of GBS carriage/UTI)

2. IAP to all women identified as GBS carriers through screening (using enriched culture media) at 35-37 weeks

3. IAP only to women where a rapid test is positive

4. IAP to all women identified as GBS carriers through screening (using enriched culture media) who also have one or more risk factors

5. IAP to all women found to carry GBS through screening AND ALSO to women with one or more risk factors


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

IAP to all women with one or more of the following recognised risk factors: pregnant woman has had a baby who developed a GBS infection pregnant woman has GBS bacteria in her urine during the current

pregnancy (which should be treated at the time of diagnosis) pregnant woman has been found to carry GBS during the current

pregnancy pregnant woman has a raised temperature (≥37.8°C) during labour labour or membrane rupture is preterm (<37 completed weeks of

pregnancy) prolonged rupture of membranes (≥18 hours before delivery)

Advantages/disadvantages Cheap (no bacteriological screening costs involved)

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

A significant number of cases will still occur (estimated 40%+)

Not tested in a trial


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Option 2: Screening ApproachIAP to all women identified as GBS carriers

IAP to all women identified as GBS carriers through screening (using enriched broth media) at 35+ weeks’ gestation

Advantages/disadvantages Selective enriched culture media is not routinely or widely available in

the NHS when testing for GBS carriage, though recognised as optimal by RCOG & HPA

Relatively large amounts of antibiotics prescribed Not tested in a trial Most potential cases would be covered, but not all

A few women will be –ve when tested but +ve at delivery – Yancey research found 4% of women with negative results would become positive

and 13% of women with positive results would become negative Some carriers will miss or refuse screening Some carriers will deliver before test conducted/test results

available


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Option 3: Intrapartum Screening ApproachScreen all women for GBS at onset of labour

IAP only to women where a rapid test for GBS taken at the onset of labour is positive

Advantages/disadvantages Less antibiotic use, targetting only women carrying GBS at delivery

Relatively expensive

Will miss a significant number of cases EXISTING RELIABLE TESTS ARE NOT FAST ENOUGH (taking 48 hours or

more for the results to be available)– Most women would deliver before the results are available

EXISTING FAST TESTS ARE NOT RELIABLE ENOUGH– Too many women would be incorrectly told they don’t carry GBS



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Option 4: Combined Approach 1IAP to all GBS carriers with a risk factor

IAP to all women identified as GBS carriers through screening (using enriched culture media) who also have one or more of the following risk factors:

– Preterm labour or membrane rupture (<37 completed weeks of pregnancy)– Prolonged rupture of membranes (≥18 hours before delivery)– Maternal pyrexia (≥ 37.8oC)– Previous baby with GBS infection

Advantages/disadvantages Expensive

Well researched

Smaller proportion of women receiving IAP

Mass screening using enriched culture method culture is more expensive

Many cases will still occur (estimated 40%+)


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Option 5: Combined Approach 2IAP to GBS carriers & to women with 1+ risk

factors

IAP to all women found to carry GBS through sensitive screening in the current pregnancy AND to women with one or more risk factor, regardless of screening test result

– Preterm labour or membrane rupture (<37 completed weeks of pregnancy)– Prolonged rupture of membranes (≥18 hours before delivery)– Maternal pyrexia (≥ 37.8oC)– Previous GBS baby

More expensive

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

More potential cases of GBS infection covered than restricting IAP to women with risk factors or carriage alone – estimated 80-90% prevention



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UK Guidelines for Prevention: 1 - HPA

HPA GBS Working Group

In 1998, the then Public Health Laboratory Service (PHLS) (subsequently incorporated into the Health Protection Agency (HPA)) established a multi-disciplinary GBS Working Group, whose remit was to produce evidence-based national guidelines for the control and prevention of invasive neonatal GBS disease

In June 2001, they issued their interim “good practice’ recommendations, advocating a risk based approach


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UK Guidelines for Prevention: 2 – NICE

Antenatal CareNICE’S Antenatal Care Guidelines CG6, Oct 03 Don’t recommend screening as “evidence of its clinical effectiveness and

cost effectiveness remains uncertain.” Yet all the evidence shows screening and offering IV antibiotics in labour to

higher-risk women is clinically effective. – Where such programmes have been introduced, there have been dramatic reductions in incidence, including

the US, Australia, New Zealand, Belgium, France, Spain & Italy.

The cost effectiveness issue is less clear – a cost/benefit analysis of sponsored by the HTA, published September 2007 shows current practice is not cost

effective – testing low-risk women and offering IAP to high risk women was shown to be most cost effective while limiting antibiotic use (Colbourne paper)

“pregnant women should be offered evidence based information and support to enable them to make informed decisions regarding their care … addressing women’s choices should be recognised as being integral to the decision making process.” Yet information on GBS is not widely nor routinely available. And reliable tests

are only available privately.


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UK Guidelines for Prevention: 3 - RCOG

Royal College of Obstetricians & Gynaecologists Green Top Guideline No 36 "Prevention of early onset neonatal Group B streptococcal disease" 2003 (due for review November 2006)

Risk factor approach Gives estimates of relative risk for morbidity or mortality for recognised risk factors

Calculations significantly underestimate true incidence of GBS infection in the UK and so underestimate the relative risks while overestimating the numbers needed to treat for benefit Authors of the source of incidence figures (Heath et all, 2004) estimates an under-reporting of 21-42% Incidence figures take no account of probable cases of GBS infection (Luck et al 2002)

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

Until sensitive screening is routinely available for all pregnant women, GBSS endorses these guidelines This is a key starting position to preventing early onset GBS infection, but even more cases could be

prevented through offering sensitive screening to pregnant women


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GBSS Recommendation: 1

Sensitive tests for GBS carriage using rectal & vaginal swabs taken should be freely available to all women at 35-37 weeks of pregnancy

IAP should be offered to all women identified as GBS carriers in the current

pregnancy, all women who have previously had a GBS baby, and all women who deliver < 37 completed weeks of

pregnancy where a sensitive test result for GBS carriage is either positive or unavailable


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GBSS Recommendation: 2

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

Pregnant women should be informed about GBS Pregnant women should be informed that a sensitive test for

GBS is available privately, and given information on how to obtain it

IAP should be offered to All women who have previously had a GBS baby All women found during the current pregnancy to have GBS in the urine (which

should be treated at the time of diagnosis) All women identified as carriers (using any screening method) during the current

pregnancy All women not screened using sensitive tests who have one or more of the

following risk factors– Prolonged rupture of membranes (≥18 hours before delivery)– Preterm labour or membrane rupture (<37 completed weeks of pregnancy)– Maternal pyrexia (≥ 37.8oC)


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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.


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Option 6: IAP Chart


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Paediatric prevention strategy for babies born at

higher risk


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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

‘Educate’ parents what symptoms to watch for what to do if they develop


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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)


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Types of GBS infection (1)

Early-onset GBS infection (EOGBS) 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– Abnormally high or low temperature– Abnormally high or low heart rates – Abnormally high or low breathing rates

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


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Types of GBS infection (2)

Late-onset GBS infection (LOGBS) 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– 10% of babies sick with LOGBS die – up to 50% of survivors of GBS meningitis suffer long term

handicaps


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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


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The Future: Vaccination

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

Target would be pregnant women or women before they become pregnant

Vaccine needs to be multivalent

Medical research is urgently needed into developing a viable vaccine for group B Strep infection


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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.


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Group B Strep Support

Registered charity set up in 1996

Aims: 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.

Funded by donations


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GBSS Materials Available

LEAFLETS GBS & pregnancy (introduction for

pregnant women)

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


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GBSS Medical Advisory Panel

Professor Philip Steer, BSc, MD, FRCOG (Chair) Professor of Obstetrics, Academic Department of

Obstetrics and Gynaecology, Imperial College Faculty of Medicine, Chelsea and Westminster Hospital

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

September 2007 Charity No. 1112065 Company Reg No 5587535 1 Preventing early-onset group B...

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