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Management of Neonatal Sepsis

Management of Neonatal Sepsis. Niki Kosmetatos, MD Anthony Piazza, MD Ira Adams-Chapman, MD J. Devn Cornish, MD Emory University Department of Pediatrics. Note: Dr. Cornish does not have any financial relationships to disclose nor will he discuss any non-approved drug or device uses.

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Management of Neonatal Sepsis

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  1. Management of Neonatal Sepsis Niki Kosmetatos, MD Anthony Piazza, MD Ira Adams-Chapman, MD J. Devn Cornish, MD Emory University Department of Pediatrics Note: Dr. Cornish does not have any financial relationships to disclose nor will he discuss any non-approved drug or device uses.

  2. Babies and Bacteria… Gram positive bacteria (anthrax) Gram negative bacteria (pseudomonas)

  3. …Don’t mix!

  4. Incidence • Mortality • 13-69% world wide • 13-15% of all neonatal deaths (US) (8th cause) • Meningitis • 0.4-2.8/1000 live births (US 0.2-0.4/1000) • Mortality 13-59%; US 4% of all neonatal deaths • Sepsis • 1-21/1000 world wide; US,1-2/1000 live births • Culture proven 2/1000 (3-8% of infants evaluated for sepsis); 10-20/1000 VLBW • Prematures <1000 g 26/1000 1000 - 2000 g 8-9/1000

  5. Predisposing Factors General Host Factors Prematurity (OR 25 if < 1,000 gms) Race – GBS sepsis blacks>whites (x4) Sex – sepsis & meningitis more common in males, esp. gram negative infections Birth asphyxia, meconium staining, stress Breaks in skin & mucous membrane integrity (e.g. omphalocoele, meningomyelocoele) Environmental exposure Procedures (e.g. lines, ET-tubes)

  6. Predisposing Factors • Maternal/Obstetrical Factors • General– socioeconomic status, poor prenatal care, vaginal flora, maternal substance abuse, known exposures, prematurity, twins • Maternal infections –chorioamnionitis (1-10% of pregnancies), fever (>38° C/100.4° F), sustained fetal tachycardia, venereal diseases, UTI/bacteriuria, foul smelling lochia, GBS+ (OR 204), other infections • Obstetrical manipulation – amniocentesis, amnioinfusion, prolonged labor, fetal monitoring, digital exams, previa/abruption? • Premature & Prolonged ROM, preterm labor

  7. Predisposing Factors Overall sepsis rate 2/1000 Maternal Fever 4/1000 PROM 10-13/1000 Fever & PROM 87/1000

  8. Preterm Labor/PROM • Prematurity (~10%) 15-25% due to maternal infection • >18-24h term; >12-18h preterm • Bacterial infection •  synthesis of PG • Macrophage TNF/IL stimulate PG synthesis, cytokine release** • Release of collagenase & elastase ROM • + Amniotic fluid cultures 15% (with intact membranes)

  9. SEPSIS ORGANISMS (all babies) • Group B strep (most common G+) 41% • Other strep 23% • Coliforms(E. coli most common G-) 17% • Staph aureus 4% • Listeria2% • Nosocomial infections • Candida • Note: 73% G+ and 27% G-

  10. SEPSIS ORGANISMS (VLBW) • Group B strep (most common G+) 12% • Other strep 9% • Coliforms(E. coli most common G-) 41% • CONS 15% • Listeria2% • Nosocomial infections • Candida 2% • Note: 45% G+ and 53% G- Source: Stoll et al PedInfDis 2005, 24:635

  11. Routes of Infection • Transplacental/Hematogenous • Ascending/Birth Canal • Aspiration • Device Associated Infection • Nosocomial • Epidemic

  12. Transplacental/Hematogenous • Organisms (Not just “TORCHS”) Toxoplasmosis Parvovirus Rubella Gonorrhea Cytomegalovirus Mumps Herpes* TB Syphilis Varicella Acute Viruses HIV Coxsackie Polio Adenovirus GBS Echo Malaria Enterovirus Lyme

  13. Ascending/Birth Canal • Organisms - GI/GU flora, Cervical/Blood E. Coli Herpes GBS Candida Chlamydia HIV UreaplasmaMycoplasma Listeria Hepatitis Enterococcus Anaerobes Gonorrhea Syphilis HPV

  14. Nosocomial • Organisms – Skin Flora, Equipment/Environment Staphylococcus – Coagulaseneg & pos MRSA Klebsiella Pseudomonas Proteus Enterobacter Serratia Rotavirus Clostridium – C dificile Fungi

  15. Infection Timing • Onset • Early Onset 1st 24 hrs 85 % 24-48 hrs 5% • Late Onset 7-90 days

  16. Symptoms • Non-specific/Common • Respiratory distress (90%) - RR, apnea (55%), hypoxia/vent need (36%), flaring/grunting • Temperature instability, feeding problems • Lethargy-irritability (23%) • Gastrointestinal – poor feeding, vomiting, abdominal distention, ileus, diarrhea • Color—Jaundice, pallor, mottling • Hypo- or hyperglycemia • Cardiovascular – Hypotension(5%), hypoperfusion, tachycardia • Metabolic acidosis NICHD data

  17. Symptoms • Less common • Seizures • DIC • Petechiae • Hepatosplenomegaly • Sclerema • Meningitis symptoms • Irritability, lethargy, poorly responsive • Changes in muscle tone, etc.

  18. Evaluation • Non-specific • CBC/diff, platelets – ANC, I/T ratio • Radiographs • CRP • Fluid analysis – LP, U/A • Glucose, lytes, gases • Specific – Cultures, stains • Other – immunoassays, PCR, DNA microarray

  19. Results “Trigger Points” • CBC • WBC <5.0, abs neutro <1,750, bands >2.0 • I/T ratio > 0.2* • Platelets < 100,000 • CRP > 1.0 mg/dl • CSF > 20 WBC’s with few or no RBC’s • Radiographs: infiltrates on CXR, ileus on KUB, periosteal elevation, etc.

  20. Treatment • Prevention – vaccines, GBS prophylaxis, HAND-WASHING • Supportive – respiratory, metabolic, thermal, nutrition, monitoring drug levels/toxicity • Specific – antimicrobials, immune globulins • Non-specific – IVIG, NO inhibitors & inflammatory mediators

  21. Neonatal Sepsis:the special case ofGroup B Strep Sepsis

  22. Mother to Infant Transmission GBS colonized mother (20-30% in US) 50% 50% Non-colonized newborn Colonized newborn 98% 2% Early-onset sepsis, pneumonia, meningitis Asymptomatic

  23. GBS SEPSIS RISK FACTORS • Previous GBS-infected baby • Gestational age <37 wks • Maternal disease (esp. GBS UTI) • Ruptured membranes > 18 hours • Location of delivery (e.g., home) • Infant/Fetal symptommatology • Clinical suspicion Note: incidence has fallen 80% since CDC prevention guidelines were published in 1996

  24. Mothers in labor or with ROM should be treated if: • Chorioamnionitis • History of previous GBS+ baby • Mother GBS+ or GBS-UTI this preg. • Mother’s GBS status unknown and: • < 37 wks gestation • ROM ≥ 18 hrs • Maternal temp ≥ 38o (100.4oF)

  25. Group B Strep Association formed 1st ACOG & AAP statements CDC draft guidelines published Rate of Early- and Late-onset GBS Disease in the 1990s, U.S. Consensus guidelines Schrag, New Engl J Med 2000 342: 15-20

  26. GBS SEPSIS INFANTS TO BE SCREENED • Maternal “chorioamnionitis” • Maternal illness (i.e. UTI, pneumonia) • Maternal peripartum fever > 38o(100.4oF) • Prolonged ROM ≥ 18 hrs (≥ 12 hrs preterm) • Mother GBS+ with inadequate treatment (< 4 hrs) • No screening necessary if C-section delivery with intact membranes

  27. GBS SEPSIS INFANTS TO BE SCREENED • Prolonged labor (> 20 hrs) • Home or contaminated delivery • “Chocolate-colored”/foul smelling amniotic fluid • Persistent fetal tachycardia • SYMPTOMATIC INFANT • treat immediately (in DR if possible)

  28. GBS SEPSIS SEPSIS SCREEN • CBC with differential • Platelet count • Blood culture x 1-2 (ideally 1 ml) • Chest X-ray &/or LP if symptommatic • Close observation and frequent clinical evaluation • Role of CRP

  29. Algorithm for Neonate whose MotherReceivedIntrapartum Antibiotics Maternal Rx for GBS? Maternal antibiotics for suspected chorioamnionitis? Signs of neonatal sepsis? Full diagnostic evaluation * Empiric therapy++ Gestational age <35 weeks? Limited evaluation$ & Observe ≥ 48 hours If sepsis is suspected, full diagnostic evaluation and empiric therapy ++ Duration of IAP before delivery < 4 hours # No evaluation No therapy Observe ≥ 48 hours** YES YES YES NO NO * CBC, blood cx, & CXR if resp sx. If ill consider LP. ++ Duration of therapy may be 48 hrs if no sx. $ CBC with differential and blood culture # Applies only to penicillin, Ampicillin, or cefazolin. ** If healthy & ≥ 38 wks & mother got ≥ 4 hours IAP, may D/C at 24 hrs. NO

  30. Careful Observation & Immediate Antibiotics Careful Observation pending review of screen • Symptomatic INFANT • Maternal intrapartum fever > 38.6o • “Chocolate” or foul smelling fluid • Ill mother • Fetal tachycardia • Home delivery • Maternal fever < 38.6o • PROM • Mat GBS with < 2 dose abx (-) Screen(+) Screen(-) Screen(+) Screen Cont abx until bld cx neg for 48o if asympt. Use clini-cal judgement for cessation of abx if pt is/was sympt d/c abx; careful obs and monit bld cx until d/c Careful obs and monit bld cx until d/c Initiate abx & cont until bl cx (-) for 48o. Clinical judgement for cessation of abx if pt sympt Blood Culture Positive Initiate, resume or continue abx therapy and treat for 7-10 days for gram pos organism or longer if gram neg organism cultured. LP may be performed at the discretion of attending, especially in seriously symptomatic pt

  31. SEPSIS SIGNS and SYMPTOMS • temp instability • lethargy • poor feeding/residuals • resp distress • glucose instability • poor perfusion • hypotension • bloody stools • abdominal distention • bilious emesis • apnea • tachycardia • skin/joint findings

  32. SEPSIS LABORATORY EVALUATION • Provide added value when results are normal • high negative predictive value • low positive predictive value • abnl results could be due to other reasons and not infection • IT < 0.3, ANC > 1,500 (normal) do not start abx, or d/c abx if started, if pt remains clinically stable • IT > 0.3, ANC < 1,500 consider initiation of abx pending bldcx in “at-risk” pt who was not already begun on antibiotics for other factors

  33. SEPSIS LABORATORY EVALUATION • Positive screen • total WBC < 5,000 – I/T > 0.3 • ANC < 1,500 – platelets < 100,000 • Additional work-up • CXR, urine cx, and LP as clinically indicated • CRP • no added value for diagnosis of early onset sepsis • best for negativepredicativevalue or when used serially • not to be used to decide about rx, duration of rx or need for LP • positive results for a single value obtained at 24 hrs ranges > 4.0 - 10.0 mg/dL

  34. SEPSIS TREATMENT • Review protocol • Antibiotics • Ampicillin 100 mg/kg/dose IV q 12 hours • Gentamicin 4 mg/kg/dose IV q 24 hours • IM route may be used in asymptomatic pt on whom abx are initiated for maternal risk factors or to avoid delays when there is difficulty obtaining IV • For meningitis: Ampicillin 200-300 mg/kg/d • Symptomatic management • respiratory, cardiovascular, fluid support

  35. Prognosis • Fatality rate 2-4 times higher in LBW than in term neonates • Overall mortality rate 15-40% • Survival less likely if also granulocytopenic (I:T > 0.80 correlates with death and may justify granulocyte transfusion).

  36. Infection and Outcome • Leviton, et al, Ped Res 1999 • 1078 infants <1500 grams and/or <32 wks • Infants with IUI were more likely to have PVL • Chorioamnionitis was associated with a 4-fold increased risk of CP (17% vs. 3%) • Nelson, et al reported increased cytokine response in population based study of term but not preterm infants

  37. Infection and ND Outcome • IUI and postnatal infection both appear to increase the risk for adverse ND outcome • Role of inflammatory mediators/SIRS in brain injury in the preterm infant • Pressure passive CNS circulation • Direct cytotoxicity to the developing brain • Inherent vulnerability of the oligodendrocyte precursor

  38. Postnatal Infection and ND Outcome: PDI < 70 Infection Groups Compared to Uninfected by Logistic Regression Clinical Infection (N=1415) Sepsis Alone (N=1740) Sepsis+NEC (N=252) Sepsis+Meningitis (N=152) 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Adjusted Odds Ratios and 95% CIs Stoll, JAMA 2004

  39. Postnatal Infection and ND Outcome: Cerebral Palsy Infection Groups Compared to Uninfected by Logistic Regression Clinical Infection (N=1415) Sepsis Alone (N=1740) Sepsis+NEC (N=252) Sepsis+Meningitis (N=152) 0.0 1.5 2.5 3.0 3.5 0.5 1.0 2.0 Adjusted Odds Ratios and 95% CIs Stoll, JAMA 2004

  40. Late Onset Infection • Majority of ELBW infants will develop late onset sepsis • Significant associated morbidity and mortality • CONS still the most common pathogen • Gram-negative pathogens increasing in prevelance and are associated with higher mortality rate

  41. Neonatal Infection and Outcome • Increased risk of adverse ND outcome in ELBW infants with LOS • Increased risk of poor growth at 18 months AA in ELBW with LOS • Poor outcome associated with NEC • ?Role of cytokines and inflammatory mediators in CNS

  42. Prevention of Nosocomial Infections • HANDWASHING • HANDWASHING • Universal precautions • Limit use devices and catheters • Minimize catheter manipulation • Nursery design • Meticulous skin care • Education

  43. Thank You!!

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