Max Brinsmead MB BS PhD May 2015

Preamble  Group B Streptococcus is the most frequent cause of severe neonatal infection within 7 days of birth  Incidence 0.5 – 1.5 per 1000  Risk of death is 10 – 30% ○ And there is also morbidity in survivors  15 – 30% of pregnant women are carriers of GBS (Varies with climate)  50% of their infants will become colonised during birth and  1 – 2 % will develop sepsis  Intrapartum antibiotics significantly reduces the rate of neonatal GBS sepsis

Possible strategies  Identify and treat high risk patients – no screening ○ UK (unchanged view in 2012)  Screen all and treat all GBS carriers ○ USA and many Australian hospitals  Screen all and treat only those with additional risk factors ○ Canada

Before embarking on a program of screening all pregnant women a number of questions need to be answered...

Questions to be answered:  Will screening identify all those who need treatment?  Is treatment effective?  Is treatment safe?  Would another strategy be just as effective?

Does screening identify all who need treatment?  Must use selective culture medium  Best to use vaginal AND rectal swab  Best done at 35 – 37 weeks ○ High but not 100% correlation with carriage at term  And this does not detect those who labour before the swab result is available  And not required for all other risk groups: Previous GBS-affected baby Febrile in labour Incidentally-detected GBS

Does screening identify all who need treatment?  So the answer is basically NO

Does screening identify all at risk from GBS? But there’s more…  It is agreed that intrapartum antibiotics are effective only against early onset (EO) disease  Has no effect on the incidence of late onset GBS sepsis (>7 days of age)  The postpartum administration of antibiotics to the neonate is not an option  Rapid intrapartum testing or the antenatal detection of the high risk mother is the best option for the future  A role for immunisation?

Is treatment effective?  There are no RCTs  Observational studies show that intrapartum antibiotics reduce the risk of neonatal GBS sepsis by 50 – 95% Meta analysis by RCOG says 86% But this could be due to effects of antibiotics on the diagnosis No study has shown that Rx reduces overall rate of neonatal sepsis or death  Rate of GBS sepsis fell by 33 – 70% in the US after introduction of universal screening But rate of neonatal deaths from GBS is the same in the UK And rate of GBS sepsis in black US babies rose 70%

Is treatment effective?  Strictly speaking the answer is “unproven”

Is the treatment safe?  There are no RCTs  Some 15 – 30% of all women require treatment  You have to treat 714 women to prevent one case of neonatal sepsis  And 7000 women to prevent one neonatal death  Risk of fatal maternal anaphylaxis 1:100,000  This means one maternal death for every seven (7) babies saved  Unknown risks from non-fatal anaphylaxis  Unknown problems from antibiotic use

Is the treatment safe?  So the answer is “maybe NOT”

Disadvantages of universal screening  The medicalization of birth  Costs of screening and treatment  Potential effects of antibiotics on neonatal gut flora Use penicillin not Ampicillin or Amoxil  Emergence of resistant organisms

Other strategies?  Intrapartum rapid screening using PCR or optical immunoassay (OIA) Second to universal treatment with antibiotics this is the most cost effective  Immunization against GBS Looks promising

So why do I practise universal screening for GBS?  A personal close call with GBS sepsis in 2003 We call this a case series of one!  US experience of a universal screening policy ○ Has significantly reduced the incidence of early-onset GBS infection  Peer pressure Most large units in Australia now screening Any affected patient who is not screened is very unhappy  It’s easier to remember and…  It’s very acceptable to women

Case History Page 1 Olivia G Age 28 G 4 P 0  Black flashing eyes  Attending for 12m with recurrent miscarriage ○ Two in the first trimester ○ One in the second trimester  New partner  Spontaneous conception  Bleeding of unknown cause at 18 and 33w  Wedding at 36w  Admitted at 37w with “a few contractions”

Case History Page 2  Awake all night with fever, backache and sweats  Membranes intact  Temp 37.3 No uterine tenderness  CTG – Baseline 170 bpm & reduced STV  “Probably viraemia” but for FBC, HVS & UMCS  At 1200 hrs CTG improved & Olivia now afebrile  BUT WCC >25,0000 and 96% neutrophils  “A few gram pos cocci in the HVS”  Rx IV Ampicillin 1G at 12 midday

Case History Page 3  At 4 pm Olivia is in established labour  CTG – baseline 170 bpm and little STV  VE: 2 – 3 cm, effaced ARM Clear liqour  Rx IV Ampicillin 1G repeated  At 5 pm CTG and Cx unchanged  Making preparations for em CS but theatre busy until 6 pm anaesthetist meeting the mayor and assistant on the beach with 30 teenagers  At 5:45 pm – Olivia wants to push!

Case History Page 4  Delivery assisted by ventouse and forceps  Big episiotomy and lotsa stitches HB 63 two days later  Gram stain of gastric aspirate “teeming with gram positive cocci”  Neonatal FBC showing classic signs of bacterial sepsis  Maternal HVS, urine, fetal gastric aspirate, body swabs and blood all grew GBS  Baby treated with IV antibiotics and did well

New Engl J Med July 2002:  A multicentre retrospective cohort study of 629,912 livebirths  Selected 5144 births by random stratification  Risk of neonatal GBS sepsis was significantly lower in those hospitals where screening was practised compared to those where a risk-based approach was used (RR 0.46, 95% CI )  This difference could not be corrected by failure to treat for identified risk factors

2012 Update 1  Immunisation remains elusive because of the number of subtypes  Rapid testing with PCR proves disappointing but direct plating onto culture medium at the bedside can hasten the detection  Professional women in Hong Kong had a significantly higher rate of colonisation than “housewives”  Someone has shown that it is more cost effective to simply treat any woman who has previously been GBS colonised rather than re screen and treat  Self collection of swabs is as good as professional collection  The doses of Clindamycin previously recommended are not sufficient  In a retrospective cohort study of 254 early-onset GBS sepsis in neonates in the US 61% were born to women who were screen negative ○ The others occurred in patients who had not been screened

2012 Update 2 The US CDC has reviewed its guidelines, endorsed universal screening and made some further modifications…  RCT’s of vaginal chlorhexidine disappointing  Only 4 cases of non fatal anaphylaxis reported in the US since universal screening and treatment recommended in 1996 ○ 1 – 4 % of patients will have maculopapular rash  Penicillin-resistant GBS seen in Japan and ↑MIC noted elsewhere ○ 32% GBS resistant to Erythromycin and ○ 20% resistant to Clindamycin (same group) ○ Use Cephalosporin and Vancomycin  Urine colony count >10 5 significant (screening not required)  Women scheduled for elective CS should be screened at 35 – 37 weeks in case they have PROM  Revised doses of Penicillin and Clindamycin  Revised alogorithm for observation of GBS-exposed and intrapartum-treated babies (secondary prevention)

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