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Neonatal Sepsis

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  1. Neonatal Sepsis Abbey Rupe, MD 7.24.2012

  2. 2012 AAP Clinical Report: • Management of Neonates with Suspected or Proven Early-Onset Bacterial Sepsis (May 2012)

  3. Epidemiology • Overall incidence: 1-5/1000 live births • Term infants: 1-2/1000 live births

  4. Definitions • Neonatal sepsis • Infant 28 days of life or younger • Systemic signs of infection • And/or isolation of bacterial pathogen from bloodstream • Early-onset GBS disease • Birth to 6 days of age • (some sources: birth to 72 hours) • Late-onset GBS disease • Symptom onset at >72 hours or ≥ 7 days of age

  5. Transmission • Early-onset • Vertical transmission • Ascending contaminated amniotic fluid • after ROM or via occult tears in placenta • During vaginal delivery from bacteria colonizing or infecting mother’s lower genital tract

  6. Transmission • Late-onset sepsis • Vertical transmissionneonatal colonizationlater infection OR • Horizontal transmission via direct contact w/ care providers or environmental sources • Disruption of intact skin or mucosa increases risk of late-onset sepsis

  7. Risk factors Early-onset sepsis • Major risk factors: • Preterm birth • Maternal colonization w/ GBS • ROM > 18 hours • Maternal chorioamnionitis • Other: • Ethnicity (black women higher rate of GBS colonization • Low SES • Male gender • Low Apgar scores

  8. Chorioamnionitis • Risk factors: • Low parity • Spontaneous labor • Longer length of labor and membrane rupture • Multiple digital vaginal exams (esp w/ ruptured membranes) • Meconium-stained amniotic fluid • Internal fetal or uterine monitoring • Presence of genital tract microorganisms

  9. Chorioamnionitis • Definition: • Maternal fever (100.4 or higher), plus 2 of the following: • Maternal leukocytosis (>15,000) • Maternal tachycardia (>100 bpm) • Fetal tachycardia (>160 bpm) • Uterine tenderness • Foul odor of amniotic fluid

  10. Infectious agents • Early-onset: • GBS • E. coli • GBS and E. coli account for 2/3rds • GBS most-common cause in term newborns • E. coli most-common cause in preterm newborns • Other: Klebsiella, Enterobacter, Listeria

  11. Infectious agents • Late-onset: • GBS • E. coli • S. aureus (MSSA and MRSA) • Increasing in incidence • Typically associated with skin, bone, or joint infections • Other: Klebsiella, Enterobacter, Listeria

  12. GBS • 2002: CDC recommendation of universal, culture-based screening with intrapartum antibiotic prophylaxis (IAP) for GBS + women • 80% decrease in early-onset GBS infection • No change in late-onset disease • Guidelines updated in 2010

  13. GBS—indications for IAP • Mother GBS+ within preceding 5 weeks • GBS status unknown and ≥ 1 risk factor present: • < 37 WGA • ROM ≥ 18 hours • Maternal temp of ≥100.4 • GBS bacteriuria during current pregnancy • Hx of previous infant with GBS disease

  14. IAP • Penicillin—drug of choice • Ampicillin is acceptable alternative • PCN-allergic women at low-risk of anaphylaxis (no hx of anaphylaxis, angioedema, respiratory distress, or urticaria after PCN or cephalosportin administration) • Cefazolin • PCN-allergic women at high-risk of anaphylaxis • Clindamycin (if tested and susceptible) • Vancomycin

  15. IAP • “Adequate IAP” • PCN, Ampicillin, or cefazolin • First dose administered at least 4 hours prior to delivery • All three reach high intra-amniotic concentrations within 3 hours of administration • “All other antibiotics, doses, or durations are considered inadequate for the purposes of neonatal management”

  16. Clinical manifestations • Fetal/delivery room distress • Fetal tachycardia • Meconium-stained amniotic fluid • 2-fold increase for sepsis in infants who did not receive IAP • Low Apgar • One case-control study: infants with 5-minute Apgar of ≤6 had a 36-fold higher likelihood of sepsis compared to those with Apgar of 7 or higher

  17. Clinical manifestations • Fever (> 50%) • Respiratory distress • Poor feeding • Vomiting • Jaundice • Hepatomegaly • Lethargy • Other: cyanosis, hypothermia, irritability, apnea, abdominal distention, diarrhea

  18. Differential Diagnosis • Other infections • HSV, CMV, syphilis • Pulm: • TTN, RDS • CV: • Cyanotic congenital heart disease • Endo: • Inborn errors of metabolism

  19. Evaluation • Blood culture • x1 • Need at least 1 ml • Sensitivity to detect bacteremia approx 90% • Common pathogens: • 97% positive by 24 hours • 99% positive by 36 hours

  20. Evaluation • CBC with diff • WBC: • Preferable to obtain at 6-12 hours of age • More likely to be abnormal than if obtained at birth • I/T ratio: • Poor predictive accuracy, but very high negative predictive accuracy (99%) • Platelet count • often low in infected infants • Nonspecific, low sensitivity

  21. Evaluation • Acute-Phase Reactants • CRP • Increases within 6-8 hrs of infections episode and peaks at 24 hours • Sensitivity improves if first determined at 6-12 hours of age • If obtain 2 normal values (first between 8-24 hours of age, second 24 hours later), negative predictive accuracy of 99.7% • Could use to stop abx; data insufficient on how elevated (>1.0) CRP values should affect duration of abx therapy

  22. Evaluation • Acute-Phase Reactants: • Procalcitonin • Levels increase within 2 hours of infectious episode, peak at 12 hours, and normalize within 2-3 days (adult studies) • Slightly more sensitive than CRP, but less specific • Not routinely available in hospital labs

  23. Evaluation • Lumbar puncture • When???? Controversial • High-risk, healthy-appearing infant, likelihood of meningitis is “extremely low” • Infant with clinical signs attributable to a noninfectious condition (such as RDS), likelihood of meningitis low • Among bacteremic infants: incidence of meningitis as high as 23%

  24. Evaluation • LP: • Perform in: • Infant w/ positive blood culture • Infant whose clinical course or lab data strongly suggest bacterial sepsis • Infants who initially worsen with antimicrobial therapy • Threshold to tap gets lower as # of risk factors goes up • Critically ill or likely to have cardiovascular and/or respiratory compromise during the procedure, can defer until more stable (but don’t delay abx)

  25. Evaluation • LP • Send CSF for: • Gram stain • Culture • Cell count with diff • Protein • Glucose • other

  26. Evaluation • Urine culture • Not recommended in infant with suspected early-onset sepsis • UTIs in neonates are due to seeding of kidney during episode of bacteremia (not ascending infection, as in older infants) • Include in workup of any infant with suspected late-onset sepsis

  27. Evaluation • CXR • Obtain in infant with respiratory distress

  28. Treatment (early-onset) • Ampicillin and Gentamicin • Ampicillin: 75-150 mg/kg/day divided q8 • Gentamicin: 4 mg/kg/day div q24 • Alternate regimen: Amp + 3rd gen ceph (cefotaxime) • Not more effective • High risk for emergence of ceph-resistant strains

  29. Treatment • Duration of abx: • Culture-proven sepsis: 10 days • Meningitis: 14-21 days • Automated blood culture systems ID 97% of pathogens at 24 hours and 99% at 36 hours • Can discontinue empiric abx in well-appearing infant after 48 hours • Negative culture, but high clinical suspicion for systemic infection • Continue abx until another dx explains the situation OR to complete 10-day course • IAP could cause-negative culture

  30. Treatment (late-onset)7-28 day old infant • Re-admitted infant • Amp + gent OR amp + cefotaxime • Infant hospitalized since birth • Add vanc • HSV suspected • “ill-appearance,” mucocutaneous vesicles, seizures, or CSF pleocytosis • S. aureus suspected (soft tissue, skin, joint, or bone involvement) • Vanc + nafcillin + gent

  31. Outcome • GBS: overall 5-10% fatality rate • Term infants: • Early-onset: 2-3% • Late-onset: 1-2 % • E. coli: overall mortality rate 4-16% (higher in preterm infants)

  32. Neonatal management • Infant with signs of sepsis

  33. Neonatal management • Infant with signs of sepsis • Full diagnostic evaluation • Blood culture • CBC • CXR if indicated • LP • Antibiotic therapy

  34. Neonatal management • Well-appearing term infant • mother diagnosed with chorioamnionitis

  35. Neonatal management • Well-appearing term infant • mother diagnosed with chorioamnionitis • “Limited evaluation” • Blood culture at birth • CBC with diff at birth and/or 6-12 hours of life • NO lumbar puncture • Antibiotic therapy

  36. Neonatal management • Well-appearing term infant • mom GBS negative

  37. Neonatal management • Well-appearing term infant • mom GBS negative • Routine clinical care

  38. Neonatal management • Well-appearing term infant • mom GBS + • received ampicillin, PCN, or cefazolin ≥4 hours prior to delivery

  39. Neonatal management • Well-appearing term infant • mom GBS + • received ampicillin, PCN, or cefazolin ≥4 hours prior to delivery (“Adequate IAP”) • Observation for ≥ 48 hours • **If other discharge criteria are met, could discharge at 24 hours IF • Ready access to medical care • Person able to fully comply with instructions for home observation will be present

  40. Neonatal management • Term, well-appearing infant • Mom GBS + • Mom PCN-allergic and received Vanc • ROM < 18 hours

  41. Neonatal management • Term, well-appearing infant • Mom GBS + • Mom PCN-allergic and received Vanc • ROM < 18 hours • Observation for ≥48 hours

  42. Neonatal management • Term, well-appearing infant • Mom GBS + • Received 1 dose of ampicillin 2 hours before delivery • ROM < 18 hours

  43. Neonatal management • Term, well-appearing infant • Mom GBS + • Received 1 dose of ampicillin 2 hours before delivery • ROM < 18 hours • Observation for ≥48 hours

  44. Neonatal management • Term, well-appearing infant • Mom GBS + • Received inadequate IAP • ROM ≥18 hours

  45. Neonatal management • Term, well-appearing infant • Mom GBS + • Received inadequate IAP • ROM ≥18 hours • “Limited evaluation” • Blood culture at birth • CBC with diff at birth and/or 6-12 hours of life • Observation for ≥48 hours

  46. Neonatal management • Well appearing near-term infant • Mom received inadequate IAP • “Limited evaluation” • Blood culture at birth • CBC with diff at birth and/or 6-12 hours of life • Observation for ≥48 hours

  47. Neonatal management • Term newborn • Tachypneic, no O2 requirement • Mom GBS+, received appropriate IAP

  48. Neonatal management • Term newborn • Tachypneic, no O2 requirement • Mom GBS+, received appropriate IAP • DDx: TTN, pneumonia, sepsis • If clinically improving over first 6 hours of life, it is “reasonable” to withhold antibiotics and monitor closely • If worsens, obtain blood culture, CBC, and start abx