1. Perinatal Transmission of Group B Streptococcus (GBS)
Part 2 : Case Presentation of late-onset neonatal GBS disease at NJH.
Ranmini Kularatne
(Part 1 presented by Natalie Beylis)

2. Colonization
GBS isolated from genital & lower GIT of pregnant females at rates of 5-40%
Principal reservoir is lower GIT – genital colonization reflects contamination from rectum.
Rates of colonization similar for pregnant and non-pregnant females. Higher in DM.

3. Vertical Transmission
Occurs either in utero by ascending route or at time of delivery. Rate – 50%.
Required for early-onset neonatal disease. 1-2% of all infants born to GBS carriers will develop EOD.
Major risk for late-onset infections.

4. Risks for EOD Maternal factors: African-American origin
Age younger than 20 yrs
H/O previous miscarriages
H/O previous GBS disease in infant

5. Risks for EOD Obstetrical Factors
Heavy genital inoculum at time of delivery.
GBS bacteriuria – assoc with heavy genital inoculum
Preterm labour – prematurity.
Premature ROM (<37/52)
Prolonged ROM (> 18 hrs)
Intrapartum fever or amnionitis

6. Risks for EOD Neonatal Factors: LBW
Heavy surface colonization with GBS.

7. Antenatal Screening
Prenatal screening cultures will not correctly ID all intrapartum GBS carriage. The later in pregnancy – the closer the correlation with IP carriage status (100% concordance when cultures done <5/52 before delivery).
However, late screening will not cater for premature deliveries.
Rapid detection kits – variable (usu. low) sensitivities and dependant on heavy genital inoculum.

8. Antenatal Screening Optimal ID dependant on technique:
culture appropriate sites (rectum+vaginal introitus)
timing – as close to delivery as feasible
culture medium - enriched + selective (SBM or Lim) broth. Todd Hewitt modification with colistin & nalidixic acid. Incubated at RT for hrs, then subcultured onto blood agar.
For transport from peripheral centre : Amies’ transport medium – GBS from RV swabs will survive at RT for upto 96 hrs.

9. Prevention : Chemoprophylaxis
Antepartum:
Oral antibiotics during 3rd trimester fail to eradicate IP GBS carriage in 70% of cases.
Postpartum:
Too late – 80% of EOD presents within few hrs of birth.
Intrapartum:
Initiated at least >4 hrs before delivery & at high doses for adequate concentrations in foetal circulation (15-30 mins after IV Rx) and amniotic fluid (2-4 hrs after IV Rx).

10. IP Chemoprophylaxis
IV Pen G : 5 megaunits stat; 2.5 megaunits 4 hrly till delivery OR
IV Amp: 2g stat; 1g 4 hrly till delivery
Pen G preferred – narrower spectrum and greater in vitro activity.
Efficacy improved when interval between initial dose and delivery >4 hrs.
(In serious Pen allergy Clindamycin or Cefazolin recommended).
Prevent EOD. Not shown to prevent LOD.
Reduce postpartum maternal febrile morbidity.

11. Prevention Strategies (CDC)
Risk-based approach: women with identifiable risk factors for EOD.
Universal screening approach: all GBS carriers at wks identified by screening cultures. Will identify vast majority of IP GBS colonizers.
Women with GBS bacteruria or previous GBS infected infant always offered prophylaxis.

12. Risk-based vs. Screening -based
Universal
Screening IP
Prophylaxis
% Pop
Targetted
% Cases
Prevented
Yes
All carriers
20-25 95 No
High risk
cases
15-25 68

13. Universal Screening Increases the proportion of prevented EOD by 30%.
DISADV:
Logistical concerns related to screening & cost.
Increase in adverse rxns to antibiotics.
Increased emergence of resistant organisms.
Not effective where antenatal care/records absent.
Increased antibiotic use & prolonged hospital stay for neonate.

14. Combination Approaches
Screening- based strategy + strategy focused on prematurity (all preterm labour + PROM cases). If IP GBS carrier status unknown, include all those at high risk. (CDC+ACOG )
Combined maternal & neonatal prophylaxis (IV Amp for mother and 1 dose IV Pen for neonate.) Pediatrics Mar 2003.

15. Vaccine……
Risk of EOD assoc with low maternal Abs to type-specific capsular polysaccharide.
Purified capsular polysacc. evokes poor immune response.
Conjugate vaccines using carrier proteins or tetanus toxoid sig better.
Type III + TT: given in 3rd trimester induce IgG Abs which cross placenta and offer type-specific protection. Abs persist for 2 months in neonate.
Trials underway with multivalent polysacc – TT conjugate vaccine.

16. Treatment
DOC = Pen G.
S: Amp/Glycopeptides/1st,2nd,3rd gen Cephs(except cefoxitin)/carbapenems
R: Nal/TMP-SMX/Met/AG. 3-15% resist. to Eryth/Clinda.
Meningitis in infants – high dose Pen G:
MIC of Pen G for GBS 4-10 times greater than for GAS.
Required for bactericidal activity in vivo as intitial inoculum size may be high.

17. Treatment Diagnosis Neonate Adult Duration Bacteraemia+ soft tissue
Amp(150mg/kg/d) +Genta, then
Pen G 200,000U/kg/d
Pen G
10-12 MU/d
10 d
Meningitis
Amp(300mg/kg/d)+ Genta, then
500,000U/kg/d
20-30
MU/d
14-21d
(min)

18. Is prophylaxis appropriate for SA???
Risk-based approach: broad spectrum antibiotics (Amp+Flagyl) for:
PROM : > 6 hrs if 34+ weeks and for all cases < 34 weeks.
Preterm labour if maternal/foetal infection or gestation < 34 weeks.
Bomela et al SAMJ 2001 Oct; 91:
Overall incidence of GBS at NJH: 1.16/1000 LB. Rate sig higher in 1998 c/t % preterm, 60% admitted to ICU(total 81 d). Cost of screening &. risk-based approaches : R 10 million & R 31,000 respectively. Prophylaxis would save R 52,000 if ICU stay halved. EOD sufficiently prevalent to justify risk-based prophylaxis.

19. NEONATAL MANAGEMENT ALGORITHM
Maternal IAP
Maternal IAP
YES
Full evaluation
Empiric therapy
YES
Neonatal Sepsis NO
Gestational age
<35 wks
> 35 wks
Limited evaluation
Observe + 48 hrs
Duration of IAP
<4 hrs
>4 hrs
No evaluation
Observe + 48 hrs