GBS WHY ARE WE TALKING ABOUT AN OLD PROBLEM? Dr. Chelsea Elwood - PowerPoint PPT Presentation

GBS WHY ARE WE TALKING ABOUT AN OLD PROBLEM? Dr. Chelsea Elwood Deborah Money, MD, FRCSC Julianne van Schalkwyk MD MSc FRCSC Reproductive Infectious Diseases Fellow Executive Vice-Dean and Reproductive Department Head, Obstetrics and Department of Obstetrics and Gynecology Infectious Diseases Specialist Gynecology, BCWH University of British Columbia Faculty of Medicine Clinical Associate Professor OBGYN and Chelsea.elwood@cw.bc.ca The University of British Columbia Reproductive Infectious Diseases Specialist

Disclosures and Collaborators DR. VANESSA PAQUETTE DR. JOCELYN SRIGLEY DR. NANCY KENT

OUTLINE •What is Early Onset GBS •What are approaches for screening •What are treatment options •Preterm GBS and PPROM 3

SCREENING/INDICATION INTERVENTION OUTCOME Intrapartum Antibiotic Prophylaxis Risk Factors 4

WHERE DOES THIS BUG COME FROM? MATERNAL GBS COLONIZATION • Streptococcus agalactiae • Gram positive cocci • part of normal vaginal microbiome (reservoir is rectum) • Colonization can be transient, chronic or intermittent • GBS bacteriuria • heavy maternal colonization (assoc. with neonatal disease) • Vaginal colonization in early pregnancy does not predict colonization at delivery 10-30% of women are colonized at delivery • (BCWH = 30%) 5

MATERNAL GBS COLONIZATION Preterm labour and PPROM assoc. with heavy colonization with GBS • (AJOG 1996;174:1354) OR 1.5 [1.1-1.9] • GBS bacteriuria - 2-4% of pregnancies • - assoc. with including risk of neonatal disease and maternal urinary disease • (Scand. J. I.D. 1986;18:525) Post partum morbidity endometritis and wound infections (18%) • (JID, 1999;179:1410) 6

EARLY ONSET NEONATAL GBS DISEASE •Occurs at < 7 days of age •5-20% neonatal mortality • 74% Bacteremia/sepsis • 12% pneumonia • 14% meningitis •25% of the cases occur in preterm infants (<37 wks) • tend to a higher mortality rate 7

NEONATAL GBS DISEASE Incidence of GBS neonatal disease prior to intrapartum antibiotic prophylaxis: • 2-3/1,000 in US in pre-antibiotic era • At BCWH 2.4/1,000 (1987-1992 ) Incidence post antibiotic prophylaxis • U.S. - 70% reduction in post-antibiotic era (1999) • 0.5/1,000 live births • B.C. - 0.1-0.7/1,000 1-2.4% of these infants develop early onset disease • (in the absence of prophylaxis) case fatality was 50% in the 1970 ’ s - now ~15% 8

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SCREENING/INDICATION INTERVENTION OUTCOME Intrapartum Antibiotic Prophylaxis Risk Factors 10

• 1981-1988 all public antenatal patients were screened 32 weeks' gestation • 30,197 livebirths screened public patients and 26 915 unscreened private patients • ZERO cases early onset neonatal GBS infections in infants of treated asymptomatic carrier mothers. • 27 infections and 8 deaths in unscreened patients

1997 – SOGC Guidelines 1997 American Academy of Pediatrics

Why was there a positive neonatal blood culture for GBS? Can we do better?

EARLY ONSET GBS AT BCWH Reviewed All cases of positive neonatal blood cultures and CSF cultures from 2008-2016 (October) Restricted to +Blood Cultures within 7 days of delivery • 15 Cases • 13 Cases had charts here adequate for full review GBS Received positiv GBS GBS Intrapartum Pen Eligible to Term Preterm e unknown negative Prophylaxis Allergy Receive Neonatal demise 7 6 7 4 2 0 1 10 1 14

WITHIN COHORT 1. Screening and treatment of GBS 2 cases of maternal screen GBS (-) with neonatal GBS disease positive patients? 2 cases of known GBS (+), treat based on risk factors 4 PPROM 2. What about intrapartum prophylaxis? 2 cases of precipitous deliveries 1 lethal anomaly 3. Screening and • Was NOT the GBS related demise treatment of PTL and/or PPROM? 15

SCREENING/INDICATION INTERVENTION OUTCOME Intrapartum Antibiotic Prophylaxis Risk Factors 16

HOW AND WHO DO WE SCREEN? What is the current gold standard test What are the different screening approaches 17

HOW IS SCREENING DONE? Vaginal Rectal Swab • Current screening method mean PPV 69%, mean NPV 94% • With population prevalence 30% may be as high as PPV 90%/NPV95% 18

WHAT MAY COME…. PCR based techniques • Sensitivities 90.7% and specificity 97.6% • Advantages • rapid, • higher sensitivity and specificity • Disadvantage • Does not provide antimicrobial sensitivities (Pen allergic), • false negative rate related to ROM, • ?cost? Potential role in women with PPROM? 19

SCREENING/INDICATION INTERVENTION OUTCOME Intrapartum Antibiotic Prophylaxis Risk Factors 20

WHAT ARE APPROACHES FOR SCREENING AND TREATMENT? Universal “Risk based” • Screen at 35-37 weeks by vag/rectal swab in enriched broth • Treat culture – If unknown status and > 18 hrs ruptured – If unknown status and < 37 • >37w provide intrapartum IV antibiotics at time of ROM and/or weeks at onset of labour: – Any women with previous – All women with + screen (and GBS affected infant induce if ROM) – Any women with previous GBS – Any woman with GBS affected infant bacteriuria – Any woman with GBS bacteriuria 21

• Incidence of GBS neonatal disease prior to • ZERO cases early onset intrapartum antibiotic prophylaxis: neonatal GBS infections in – At BCWH 2.4/1,000 infants of treated (1987-1992 ) asymptomatic carrier mothers. • 27 infections and 8 deaths in • Incidence post antibiotic prophylaxis unscreened patients – B.C. - 0.1-0.7/1,000

WHAT ABOUT TAKING TREATING BASED ON RISK FACTORS? RCOG 2017 • Does not recommend universal screening Lower population prevalence 0.5/1000 • matches the prevalence after initiation of screening and treatment in US and Canada Theoretical Risks of antibiotic use Significant screening burden costs in the UK for which infrastructure is not available 23

UNIVERSAL SCREENING VS RISK FACTOR BASED TESTING Retrospective Cohort Study of 612, 915 live birth 1998-1999 • Subset of 5144 live births • Stratified them for missed antibiotic opportunities • Compared Risk factor vs Universal Screening and Treatment RR 0.48 for early onset GBS disease No head to head trial comparing the two 24

WHAT IS THE EVIDENCE? Retrospective Cohort Study 1997-2002 single center in Sweden Universal Screening and treatment with one risk factor • Incidence was 1/1000 • Reduced 0.5/1000 Ontario College of Midwifery • At BCWH 2.4/1,000 • Post Universal Screening and treatment B.C. - 0.1- 0.7/1,000 25

CURRENT RECOMMENDATION Offer universal screening between 35-37w with culture including women with planned CS Provide IV antibiotics onset of labour or ROM • Positive swab • Previously infected infant • GBS bacteriuria regardless of CFU • <37 weeks requires 48h of GBS prophylaxis IV unless testing has been done within 5 weeks • Term PROM offer IOL • If GBS status is unknown treat based on risk factors 26

SCREENING/INDICATION INTERVENTION OUTCOME Intrapartum Antibiotic Prophylaxis Risk Factors 27

EARLY ONSET GBS AT BCWH Reviewed All cases of positive neonatal blood cultures and CSF cultures from 2008-2016 (October) Restricted to +Blood Cultures within 7 days of delivery • 15 Cases • 13 Cases had charts here adequate for full review GBS Received positiv GBS GBS Intrapartum Pen Eligible to Term Preterm e unknown negative Prophylaxis Allergy Receive Neonatal demise 7 6 7 4 2 0 1 10 1 28

WHAT IS APPROPRIATE ANTIBIOTIC THERAPY?

ANTIBIOTIC PHARMACOKINETICS Ancef Penicillin G : narrowest, most active agent in vitro Clinda • T ½: 30 minutes • Q4h interval of administration, do not delay re-dosing • Elimination: renal Vancomycin • Placental transfer: complete • Present in fetal serum and amniotic fluid within 5 minutes, reaching concentrations in fetal serum similar to maternal serum within 60 minutes (above the MIC for GBS) Ampicillin : • T ½: 60 minutes • Elimination: renal • Placental transfer: complete • Present in fetal serum and amniotic fluid within 5 minutes, reaching concentrations in the fetal serum similar to maternal serum within 60 minutes (above the MIC for GBS) Am J Obstet Gynecol 1966; 96: 938–42. Int J Clin Pharmacol Ther 2006; 44(2): 57-63 30

ANTIBIOTIC PHARMACODYNAMICS: WHY 4 HOURS? Data for improved neonatal outcome when IV antibiotics administered at least 4 hours prior to delivery Nadir of GBS colonization occurs approximately 3 hours after administration of IV penicillin G Am J Obstet Gynecol 2007; 197(6): 583.e1 Obstet Gynecol 1998; 91:112–4 31

WHAT ARE THE RISKS? Anaphylaxis • 1:10000 to 1:25 000 • fetus cannot have an anaphylactic reaction to Pen • Maternal IgE does not cross the placenta Cross reactivity 32