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Neonatal Sepsis Evaluation

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  1. Neonatal Sepsis Evaluation Eric Demers, M.D. Pediatrix Medical Group April 17, 2012

  2. Overview • Sepsis Definitions • Microbiology • Risk Factors/Chorioamnionitis • Evaluation • Treatment

  3. Sepsis Definitions • Early-Onset Sepsis (EOS): within first 7 days of life (3 days for preterm neonates) • Blood or CSF culture positive (CDC definition) • Late-Onset Sepsis (LOS): After 7 days of life • Incidence of ~ 2 per 1000 live births • 10-15% of neonates evaluated for sepsis • only 3-8% of these shown to be culture positive

  4. EOS Infection Organisms from maternal genital tract Typical to have multisystem involvement/pneumonia Higher mortality, particularly those infections evident within first 24 hrs Falciglia, G. et al. Neoreviews, 2012, 13(2):e86-93.

  5. LOS Infection Maternal genital tract or acquired Typically focal involvement (such as meningitis) Lower mortality Falciglia, G. et al. Neoreviews, 2012, 13(2):e86-93.

  6. Sepsis Evaluation • Perinatal Risk Factors • GBS • Chorioamnionitis • Neonatal Signs/Symptoms

  7. GBS • Common bacterium in population • 10-30% of pregnant women colonized • First Intra-partum guidelines in 1996 • Revised in 2002 and 2010 • “Leading infectious cause of morbidity and mortality among newborns in the United States” MMWR Nov 19, 2010; Vol 59: RR-10:1-32.

  8. GBS Incidence Survival: Term: ~95% Preterm: ~75% MMWR Nov 19, 2010; Vol 59: RR-10:1-32.

  9. GBS Sepsis: Signs/Symptoms • Respiratory Distress • Apnea • Hypotension • Temperature instability (hypo or hyperthermia) • Decreased activity level • Poor feeding • Hypoglycemia

  10. GBS: IAP Indications MMWR Nov 19, 2010; Vol 59: RR-10:1-32.

  11. GBS: Neonatal Management MMWR Nov 19, 2010; Vol 59: RR-10:1-32.

  12. Chorioamnionitis • 1-4% of all births in US • Diagnosis • Maternal Temp > 38 °C and at least one of: • Uterine Tenderness • Maternal or Fetal Tachycardia • Foul/Purulent Amniotic Fluid • ROM greater than 12-18 hrs • Elevated maternal WBC

  13. Sepsis Evaluation • Blood Culture • CBC with differential • Ancillary tests • CRP • Lumbar Puncture • Urine Culture (LOS infections)

  14. Blood Culture • Volume of 0.5 ml or more (ideally 1 ml or more) • >90% of positive cultures occur within 48 hrs of incubation

  15. CBC with Differential • No agreement on what constitutes “normal” • WBC < 4k or >25 to 30 K • Immature:Total neutrophil ration > 0.2 • Serial values, 8-12 hrs apart have high NPV • Band count

  16. CRP Acute phase reactant, stimulated by IL-6 Production occurs ~ 4-6 hrs after stimulation Peaks at 36-48 hrs Half Life of ~ 19 hrs Weitkamp, J-H and Aschner, J.L. Neoreviews, 2005, 6(11):e508-15

  17. CRP • Single level often not helpful in determining infection • Serial measurements may be beneficial in determining duration of antibiotics in certain cases (eg: maternal incomplete antibiotic treatment, high index of suspicion for sepsis but negative cultures) • Two CRP levels < 10 mg/L taken at least 8 hrs after presentation and 24 hrs apart have high NPV. (Benitz, W. et al. Pediatrics 1998, 102(e41):1-10)

  18. Lumbar Puncture • Incidence of neonatal meningitis 0.25 to 1 per 1000 live births • Blood culture negative in up to 50% of meningitis cases • Does not seem warranted in routine evaluations (for perinatal risk factors, mild symptoms) • Useful for those with evidence of sepsis (who can tolerate procedure and in those whom longer courses of antibiotics planned) Ray, B. ADC 2006, 91:1033-35.

  19. LP Considerations • Traumatic LP: > 1000 RBC/mm3 • 1 WBC:100 to 500 RBC in normal spinal fluid • Difficult to Interpret • WBC:RBC ratio • Observed:Predicted WBC Ratio based on peripheral blood ratio. • O:P <0.01, WBC:RBC < 1:100 and absence of pleocytosis high PPV for absence of meningitis Mazor, S. et al. Pediatrics 2003, 111:525-8.

  20. Treatment • Ampicillin 100 mg/kg/dose IV every 12 hrs • Gentamicin 4 mg/kg/dose IV every 24 hrs • Therapy tailored to specific organsim if positive culture • Remember Ampicillin and Gentamicin can both be give IM as well • Avoid prolonged use of antibiotics in culture negative patients

  21. Cefotaxime Use • Increased mortality • Evaluated ~ 129,000 neonates in Pediatrix database (~24, 000 received Amp/Cefotaxime and ~105,000 received Amp/Gent) • Increased death with A/C, odds ratio 1.5 (1.4, 1.7) • ? Surrogate marker or independent risk factor Clark, R. et al. Pediatrics 2006, 117(1):67-74

  22. Questions?