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)

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.

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.

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

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

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

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.

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 18-24 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.

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).

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.

Prevention Strategies (CDC) Risk-based approach: women with identifiable risk factors for EOD. Universal screening approach: all GBS carriers at 35-37 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.

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

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.

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 - 1996) Combined maternal & neonatal prophylaxis (IV Amp for mother and 1 dose IV Pen for neonate.) Pediatrics Mar 2003.

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.

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.

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)

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: 858-60 Overall incidence of GBS at NJH: 1.16/1000 LB. Rate sig higher in 1998 c/t 1995-7. 70% 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.

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