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Screening van Zwangeren op Groep B Streptokokken. W.B.A. Mei 2003

Screening van Zwangeren op Groep B Streptokokken. W.B.A. Mei 2003. L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen. Inhoud. Epidemiologie Microbiologie Kliniek Pathogenese Preventie mogelijkheden Toestand in Vlaanderen Richtlijnen. The Disease - USA.

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Screening van Zwangeren op Groep B Streptokokken. W.B.A. Mei 2003

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  1. Screening van Zwangeren op Groep B Streptokokken.W.B.A. Mei 2003 L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  2. Inhoud • Epidemiologie • Microbiologie • Kliniek • Pathogenese • Preventie mogelijkheden • Toestand in Vlaanderen • Richtlijnen

  3. The Disease - USA • GBS emerged as an important pathogen in the 1970s • Leading cause of sepsis in neonates • Incidence: 0.4-4/1000. (Belgium= 2/1000) • Motality > 14% • Belgium: • 240 cases/year • 48 deads/ year L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  4. Comparison with other Killers in Childhood. • Meningococcal Invasive Disease • Incidence 2.3/100.000 children • Dead 0.2/100.000 children • Road Accidents • Incidence 2.5 deads/ 100.000 children • GBS invasive disease • Incidence 220/ 100.000 newborns • Deads 33/100.000 newborns Neonatal GBS is an underestimated Public Health Problem.

  5. Invasive GBS Disease Incidence by Age Group and Race MMWR Vol. 41 (No. SS-6) 1992

  6. GBS Disease in Infants A Schuchat. Clin Micro Rev 1998;11:497-513. L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  7. Early-Onset Neonatal GBS Disease A Schuchat. Clin Micro Rev 1998;11:497-513. L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  8. Clinical Manifestations of Group B Streptococcus Infection

  9. Early-Onset Infection • < 6 days of life • 85% :within 24 hours of birth • case:fatality ratio 5-10%  low 5 min Apgar, shock, neutropenia, pleural effusion, apnea, delay treatment, low birth weight, prematurity

  10. Early-Onset Infectionbacteremia without focus • 25-40% • respiratory signs = initial clinical findings (apnea, grunting respirations, tachypnea, cyanosis) • hypotension • associated signs: • lethargy, poor feeding, hypothermia or fever, abdominal distention, pallor, tachycardia, jaundice

  11. Early-Onset Infectionmeningitis • 5-10%, especially serotype III strains • clinical presentation ~ bacteremia • most common sign = Convulsions THUS: CSF !! • persistent seizures, (semi)coma = poor prognosis

  12. Early-Onset Infectionpneumonia • 35 - 55% • acute respiratory signs: grunting, tachypnea, apnea • often at birth, most < 24h • low Apgar (<5 at 1min) • X-ray abnormalities: • > 50% HMD • 30% infiltrates • occasionally absent (~ persistent fetal circulation)

  13. Early-Onset Infectionpersistent fetal circulation • Profound progressive hypoxemia that is usually out of proportion to the radiographic evidence of pulmonary disease

  14. Early-Onset Infectionpneumonia

  15. Late-Onset Infection • 7 days - 12 weeks postnatal age • case:fatality ratio 2-6% • serotype III strains • “clusters” in NICU (~ early onset) • manifestations: • meningitis • bacteremia without focus • focal: osteomyelitis, septic arthritis, cellulitis, adenitis

  16. Late-Onset Infectionosteomyelitis / septic arthritis

  17. GBS DiseaseBig Disease with a Little Name • low incidence, high morbidity disease • EOS = Pneumonia PFC hypoxia death • LOS = Meningitis

  18. Risk Factors Maternal to Infant Transmission GBS colonized mother 50% 50% Non-colonized newborn Colonized newborn 98% 2% Early-onset sepsis, pneumonia, meningitis Asymptomatic L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  19. Early-Onset Infectionrisk factors • GBS strain virulence • Genital inoculum • GBS bacteriuria • Delivery <37 weeks’ gestation • Premature rupture of membranes • Rupture of membranes >18 hours • Low levels of CPS-specific IgG • Complement component deficiency • Immature WBC function

  20. GBS Maternal Colonization • GBS Carriers • 10% - 30% of women (Belgium= 13-25%) • higher in African Americans and nonsmokers • clinical signs not predictive (Asymptomatic) • dynamic condition • When to culture? • culture at delivery -- too late • prenatal cultures predict delivery status L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  21. Prevention with Antibiotics • WHEN are antibiotics most effective? • Antenatal • Postnatal • Intrapartum • WHO should receive antibiotics ? • GBS carriers • OB risk factors • GBS carriers with OB risk factors L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  22. Consensus Guidelines • Key Issues • predictive value of prenatal cultures • culture methods • disease in the asymptomatic carrier • risk stratification of women • cost-effectiveness

  23. GBS Screening WHEN ? L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  24. Predictive Value of Antenatal Cultures by Interval to Delivery > N=826; 26.5% GBS carriers Yancey et al., OB GYN 1996;88:811-5. L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  25. Sensitivity and Specificity of Late Antenatal Cultures > N=826 Yancey et al., OB GYN 1996;88:811-5. L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  26. GBS screening WHERE ? L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  27. GBS Carriage by Culture Site * P <0.05 both vs. vaginal only L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  28. Specimen technique • Lower vagina + Rectum (through anal sphincter) • One swab • Without speculum • Out patient setting or patient herself • Transport • non-nutritive medium (Amies, Stuart’s without charcoal) • Store at room t° or in fridge (max. 48h)

  29. GBS culture HOW ? L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  30. GBS Carriage by Culture Method * P <0.05 selective broth vs. blood agar L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  31. What is ‘Selective Broth Medium’? • 1. Incubatie overnight on 35-37°C: • Todd-Hewitt broth supplemented with: • nalidixic acid (15 mg/L) and colistin (10 mg/L) • Appropriate media are commercially available (e.g. LIM broth [BD]) • 2. Subculture 18-24h: • Granada medium agar (Biomedics, Spain or distr. by International Medical) • (anaerobically or glass coverslip) L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  32. Granada mediumOrange colonies

  33. Is Intrapartum Screening an Alternative?

  34. Intrapartum screening • Sensitivity should be > 85% (= culture) • Rapid • Covenient for laboratory • 24h a day • 7 days a week • Alternatives

  35. GBS antigen test. Sensitivity to low (65%) Positive= heavy colonization. Negative = Unknown colonization. Real time PCR. Sensitivity 97%, Specificity 96.9% 45 min. Maximum Not available on 24h basis Not available in every Lab. Intrapartum GBS Screening- Alternatives At Present No Good Alternative

  36. Communication • To laboratory; • Clearly request “GBS screening” • Expected site of delivery • Expected time of delivery • To Clinician; • address of expected delivery (Fax?) • Physician’s office. • Report only QUALITATIVE (Positive or Negative)

  37. GBS screening WHO ? L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  38. CDC’s Prevention Recommendations 1996 PICK EITHER APPROACH: Screening-based approach • 35-37 wk culture, offer IAP to preterm and to GBS carriers Risk-based approach • IAP to preterm, ROM > 18 h, or intrapartum fever (T > 38 C) L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  39. Prevention Strategy Using Risk-Based Approach • Any of the following: • Delivery < 37 wks gestation* • ROM > 18 hrs • Intrapartum temp > 38C (100.4 F) • Previous infant w/GBS disease • GBS bacteriuria this pregnancy Give intrapartum penicillin YES NO No intrapartum antibiotics • * For ROM w/out labor at <37 wks, collect GBS culture and EITHER: • treat until cultures complete and negative • or begin treatment once positive culture results available

  40. Obstetric Risk Factors Among Women with GBS Infants n = 245 * no obstetric risk factors * obstetric risk factors * premature < 37 wk, ROM > 18 hr, temp > 100.4 F (38 C) Rosenstein N. OB GYN 1997;90:901-6.

  41. Rates of Early-Onset GBS Disease by Prenatal Colonization & Risk Factors Col: prenatal vag/rect culture RF: risk factors (gest. <37 wks, ROM >12 hr, fever > 37.5 C) Boyer & Gotoff, Antibiot Chemother 1985.

  42. Advantages of the Risk-Based Strategy • Logistically easier • Potentially less expensive • Particularly applicable to settings with low prenatal care L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  43. Prevention Strategy Using Screening-Based Approach • Risk factors: • Previous infant w/GBS disease • GBS bacteriuria this pregnancy • Delivery < 37 wks gestation Give intrapartum penicillin YES NO Offer intrapartum penicillin GBS+ Collect rectal & vaginal swab at 35-37 wks Not done, incomplete, or results unknown • Risk factors: • Intrapartum fever > 38C • ROM > 18 hrs GBS- YES Give intrapartum penicillin NO No intrapartum prophylaxis needed L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  44. Advantages of the Screening-Based Strategy • Optimizes prenatal screening • fewer false negatives • less pressure on physicians to treat • Antibiotics to all GBS carriers • antibiotics start earlier before development of risk factors • adequate time for antibiotic effectiveness L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  45. Comparison of Prevention Strategies * fever, ROM > 12 hr, gestation < 37 wks Rouse et al., OB GYN 1994;83:483-94.

  46. Potential Impact of Each Strategy Early-onset GBS disease by Year, Area A Risk-Based Approach Screening-Based Approach Rosenstein N, et al., OB GYN 1997;90:901-6.

  47. GBS chemoprophylaxis WHEN to Start ? L. Mahieu, Dienst Neonatologie, U. Z. Antwerpen

  48. Timing of Intrapartum Ampicillin and Transmission of GBS De Cueto et al., OB GYN 1998;91:112-4.

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