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Neonatal Sepsis


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Neonatal Sepsis

  1. 1. Neonatal Sepsis Steve Spencer, MD
  2. 2. Objectives <ul><li>Review of terminologies associated with neonatal infections </li></ul><ul><li>Review risk factors for neonatal infections </li></ul><ul><li>Review presentations of neonatal sepsis </li></ul><ul><li>Review most common organisms and treatments </li></ul><ul><li>We will concentrate on the child <3 months of age </li></ul>
  3. 3. Cases <ul><li>You are on-call tonight when the ER calls with two kids </li></ul>
  4. 4. Cases <ul><li>Kid 1 </li></ul><ul><ul><li>9 week old, term baby </li></ul></ul><ul><ul><li>100.6 temp </li></ul></ul><ul><ul><li>Looks well </li></ul></ul><ul><ul><li>CBC WNL </li></ul></ul><ul><ul><li>UA clean </li></ul></ul><ul><ul><li>Everyone at home with colds </li></ul></ul><ul><li>Kid 2 </li></ul><ul><ul><li>12 day old, term baby </li></ul></ul><ul><ul><li>Fever to 101 </li></ul></ul><ul><ul><li>Jaundiced </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>WBC of 3.2 K </li></ul></ul><ul><ul><li>PLT of 89 </li></ul></ul>Do you treat these kids the same or different and why?
  5. 5. Your Text
  6. 6. Terminologies <ul><li>Rule out sepsis </li></ul><ul><li>Neonate with fever </li></ul><ul><li>Neonatal fever </li></ul><ul><li>Neonatal sepsis </li></ul><ul><li>Serious Bacterial Infection (SBI) </li></ul><ul><li>Occult Bacteremia </li></ul><ul><li>Neonate- the first month 28days of life </li></ul><ul><li>Infant- up to one year </li></ul>
  7. 7. Back When I was an Intern….. <ul><li>Any kid 3 months or less with fever got admitted </li></ul><ul><li>Kids stayed longer </li></ul><ul><li>If it sneezed, writhed, wiggled or wheezed, it got an LP </li></ul><ul><li>Kids had to crawl seven miles through the snow, up hill both ways, to daycare….. </li></ul>
  8. 8. Age Groups <ul><li>Currently ages 0-28 days automatically admitted by most clinicians </li></ul><ul><li>1-3 months is a grey zone guided by clinical opinion </li></ul><ul><li>Greater than three months generally not admitted </li></ul>
  9. 9. Why Have Recommendations Changed? <ul><li>GBS prophylaxis </li></ul><ul><li>Immunizations </li></ul><ul><ul><li>HIB, Pneumococcus </li></ul></ul><ul><li>Better understanding of neonatal physiology </li></ul><ul><li>Better laboratory techniques </li></ul><ul><li>Better understanding of the disease </li></ul><ul><li>Different antibiotics </li></ul>
  10. 10. Definition of Fever <ul><li>“Gold Standard” is generally thought of as 100.4 (38.0) rectally with a glass mercury thermometer </li></ul><ul><li>Lots of ways to take a baby’s temperature </li></ul><ul><ul><li>I recommend using a quality thermometer </li></ul></ul><ul><ul><li>When in doubt, let the pros sort it out </li></ul></ul><ul><ul><li>In Newborn Nursery, need to counsel parents about significance of fever in neonate </li></ul></ul>
  11. 11. Why the Worry? <ul><li>Neonatal immune system immature </li></ul><ul><li>Perinatal exposure to pathogens via birth canal </li></ul><ul><li>High rate of infection in kids less than 3 months with fevers </li></ul><ul><ul><li>>4% age 0-28 days with bacteremia or meningitis (drops to 1% by 3 months) </li></ul></ul><ul><ul><li>Almost 10% with UTI </li></ul></ul><ul><ul><li>Rates increase with degree of fever </li></ul></ul><ul><ul><ul><li>39C with >10% rate of bacteremia </li></ul></ul></ul><ul><li>Well appearing infant may have an infection </li></ul>
  12. 12. Why not admit everybody? <ul><li>Not without risk of hospital acquired infection </li></ul><ul><li>Cost </li></ul><ul><li>Lost time to parents at work </li></ul><ul><li>Family stress </li></ul><ul><li>etc </li></ul>
  13. 13. What data supports our practice? <ul><li>Rochester criteria </li></ul><ul><li>Philadelphia criteria </li></ul><ul><li>Boston criteria </li></ul><ul><li>Etc </li></ul>
  14. 14. Risk Factors <ul><li>Prematurity and low birth weight </li></ul><ul><li>Maternal GBS </li></ul><ul><li>Prolonged rupture of membranes </li></ul><ul><li>Maternal chorioamnionitis </li></ul><ul><li>Sibling with sepsis </li></ul><ul><li>Meconium at delivery </li></ul><ul><li>Need for resuscitation </li></ul><ul><li>Male child </li></ul><ul><li>Multiple gestation </li></ul>
  15. 15. “Early” Pathogens (first week) <ul><li>Group B Strep (GBS) </li></ul><ul><ul><li>Incidence used to be 4-6/1000 live births (0.4%) </li></ul></ul><ul><ul><li>Now <0.1% after prenatal screening guidelines </li></ul></ul><ul><li>E. coli </li></ul><ul><ul><li>Every few decades flips back and forth with GBS as most common cause </li></ul></ul><ul><li>Gram negative rods (esp. in urine) </li></ul><ul><ul><li>Occasional Salmonella sepsis </li></ul></ul><ul><li>Listeria monocytogenes </li></ul><ul><li>Herpes Simplex </li></ul><ul><li>Enterovirus </li></ul>
  16. 16. “Late” Pathogens (~1-2 weeks) <ul><li>GBS or group A strep </li></ul><ul><li>Enterics/Enterococcus in urine </li></ul><ul><li>HSV </li></ul><ul><li>Enterovirus, RSV, Flu </li></ul>
  17. 17. Community Acquired (after 4-6 weeks) <ul><li>Pneumococcus </li></ul><ul><li>Meningococcus </li></ul><ul><li>GABHS </li></ul><ul><li>Haemophilus influenzae (HIB) not really a problem anymore </li></ul>
  18. 18. Signs/Symptoms <ul><li>Temperature irregularity </li></ul><ul><ul><li>Fever </li></ul></ul><ul><ul><li>Hypothermia </li></ul></ul><ul><li>Tone and Behavior </li></ul><ul><ul><li>Poor tone </li></ul></ul><ul><ul><li>Weak suck </li></ul></ul><ul><ul><li>Shrill cry </li></ul></ul><ul><ul><li>Weak cry </li></ul></ul><ul><ul><li>Irritability </li></ul></ul><ul><li>Skin </li></ul><ul><ul><li>Poor perfusion </li></ul></ul><ul><ul><li>Cyanosis </li></ul></ul><ul><ul><li>Mottling </li></ul></ul><ul><ul><li>Pallor </li></ul></ul><ul><ul><li>Petechiae </li></ul></ul><ul><ul><li>Unexplained jaundice </li></ul></ul>Most by themselves mean little, but three (or two) strikes and you are Out!
  19. 19. Signs/Symptoms <ul><li>Feeding Problems </li></ul><ul><ul><li>Vomiting </li></ul></ul><ul><ul><li>Diarrhea </li></ul></ul><ul><ul><li>Abdominal distension </li></ul></ul><ul><ul><li>Hypo or Hyperglycemia </li></ul></ul><ul><li>Cardiopulmonary </li></ul><ul><ul><li>Tachypnea </li></ul></ul><ul><ul><li>Retractions </li></ul></ul><ul><ul><li>Tachycardia for age </li></ul></ul><ul><ul><li>Bradycardia in first few days of life </li></ul></ul><ul><ul><li>Hypotension for age </li></ul></ul><ul><ul><li>Low PO2 </li></ul></ul>
  20. 20. Signs/Symptoms <ul><li>Sunken fontanelle </li></ul><ul><li>Bulging or pulsating fontanelle </li></ul><ul><li>Neck stiffness CAN NOT be used </li></ul><ul><li>Babies can be bacteremic but look well </li></ul><ul><li>Presence of a “cold” does not change anything </li></ul>
  21. 21. PIDJ April 2005 <ul><li>Study in India found that any two of these signs had an almost 100% sensitivity for sepsis and over 90% mortality </li></ul><ul><li>Reduced sucking </li></ul><ul><li>Weak cry </li></ul><ul><li>Cool extremities </li></ul><ul><li>Vomiting </li></ul><ul><li>Poor tone </li></ul><ul><li>Retractions </li></ul>
  22. 22. Labs <ul><li>Normal WBC (5-15K) is better than high WBC is better than very high WBC (over 35K) which is better than very low WBC (<5K) </li></ul><ul><li>Less than 28 days- blood, urine, CSF cultures +/- stool </li></ul><ul><ul><li>Get urine culture, even if UA WNL </li></ul></ul><ul><li>>28 days see handout </li></ul><ul><li>CXR if respiratory symptoms </li></ul>
  23. 23. Lab Dilemmas- Urine collection <ul><li>Don’t use bag urines! </li></ul><ul><ul><li>A negative culture on a bag urine is negative </li></ul></ul><ul><ul><li>A positive means nothing </li></ul></ul><ul><li>Cath or Suprapubic aspirate? </li></ul><ul><ul><li>SPA- any growth is considered a positive </li></ul></ul><ul><ul><li>Cath </li></ul></ul><ul><ul><ul><li>Can have false positives, especially if uncirc’d male </li></ul></ul></ul><ul><ul><ul><li>New debates on what constitutes a positive culture </li></ul></ul></ul><ul><ul><ul><li>Most references use >10K CFU’s as positive, some use as little as 1K (equals one plaque) </li></ul></ul></ul><ul><ul><ul><li>Microbiologists feel we should use 100K on all samples regardless of source </li></ul></ul></ul>
  24. 24. Lab Dilemmas- The Bloody Tap
  25. 25. The Bloody Tap <ul><li>Don’t ask me, you should have gotten it right the first time </li></ul>
  26. 26. The Bloody Tap <ul><li>No right answer </li></ul><ul><li>Results can vary based on the amount of blood in amount of CSF, what is the HCT, what is the peripheral WBC count etc. Some use CBC to CSF ratios. </li></ul><ul><li>Sometimes seems like too many WBC’s or seems OK </li></ul><ul><li>Sometimes just need to re-tap </li></ul>
  27. 27. Treatment <ul><li>Age 0 to ~4-6 weeks </li></ul><ul><ul><li>Ampicillin/Aminoglycoside </li></ul></ul><ul><ul><li>Ampicillin/Cefotaxime </li></ul></ul><ul><li>Amp kills GBS and Listeria </li></ul><ul><li>Gent and Cefotaxime for GNR’s </li></ul><ul><ul><li>Ceftriaxone not used- causes neonatal hepatitis and biliary sludging </li></ul></ul>
  28. 28. Aminoglycosides <ul><li>Disadvantages </li></ul><ul><ul><li>Ototoxicity </li></ul></ul><ul><ul><li>Nephrotoxicity </li></ul></ul><ul><ul><li>Need for levels </li></ul></ul><ul><li>Advantages </li></ul><ul><ul><li>Little resistance </li></ul></ul><ul><ul><li>Cheap (30 cents or so a dose) </li></ul></ul><ul><ul><li>Highly concentrated in urine </li></ul></ul><ul><ul><li>No need for levels if QD dosing in a 48 hour admission </li></ul></ul>
  29. 29. Treatment <ul><li>After 4-6 weeks, ampicillin and a 3 rd generation cephalosporin </li></ul><ul><ul><li>Offers better coverage for community acquired organisms </li></ul></ul><ul><ul><li>At 4-8 weeks, switch to cephalosporin alone. </li></ul></ul>
  30. 30. What About Herpes? <ul><li>Some clinicians begin acyclovir on all neonatal admissions for fever </li></ul><ul><li>We use the guideline of “Fever Plus” </li></ul><ul><ul><li>HSV is rare & tends to present in certain ways </li></ul></ul><ul><ul><li>Fever in addition to </li></ul></ul><ul><ul><ul><li>Hepatitis/jaundice </li></ul></ul></ul><ul><ul><ul><li>Meningitis </li></ul></ul></ul><ul><ul><ul><li>Seizures </li></ul></ul></ul><ul><ul><ul><li>Thrombocytopenia </li></ul></ul></ul><ul><ul><ul><li>Vesicles </li></ul></ul></ul><ul><ul><ul><li>Rash/purpera </li></ul></ul></ul>
  31. 31. HSV Risk Factors <ul><li>Maternal history- only present in </li></ul><ul><ul><li>Maternal primary infection- as many as 50% of babies infected </li></ul></ul><ul><li>Active lesions </li></ul><ul><li>ROM > 4-6 hours </li></ul><ul><li>Fetal scalp electrode </li></ul><ul><li>Prematurity </li></ul><ul><li>Caregiver with cold sore/fever blister </li></ul>
  32. 32. HSV in Neonate <ul><li>Three types </li></ul><ul><ul><li>SEM (Skin, Eye, Mucous membranes)- 15% </li></ul></ul><ul><ul><li>Isolated CNS- 35% </li></ul></ul><ul><ul><li>Disseminated (+/- CNS)- 50% </li></ul></ul><ul><ul><li>75% HSV-2 25% HSV-1 </li></ul></ul><ul><ul><li>Incidence 1:1K-5K births </li></ul></ul>
  33. 33. HSV timing <ul><li>SEM (Skin, Eye, Mucous membranes)- can be early </li></ul><ul><li>Isolated CNS- 2-3 weeks </li></ul><ul><li>Disseminated (+/- CNS, +/-SEM)- ~1 week </li></ul>
  34. 35. HSV Labs- three points <ul><li>CSF PCR alone DOES NOT rule out HSV </li></ul><ul><li>CSF PCR alone DOES NOT rule out HSV </li></ul><ul><li>CSF PCR alone DOES NOT rule out HSV </li></ul>
  35. 36. HSV Labs- if do it, do it right <ul><li>CSF for PCR (>98% sensitive, >95% specific) and/or culture (30-50%) </li></ul><ul><li>CSF tends to be “bloody”– 100-200 RBC with elevated WBC </li></ul><ul><li>Mucous membrane cultures </li></ul><ul><ul><li>Eyes, ears, anus, mouth, nose, vesicles if present, some add urine </li></ul></ul><ul><ul><li>In nursery, wait 24 hours after birth to culture (indicates active infection) </li></ul></ul>
  36. 37. HSV Labs cont. <ul><li>LFT’s </li></ul><ul><ul><li>I now get for any R/O SBI kid that I am worried enough about to get a BMP </li></ul></ul><ul><li>Serial CBC’s </li></ul><ul><ul><li>Thrombocytopenia </li></ul></ul><ul><ul><li>Leukopenia </li></ul></ul><ul><li>Tzank smear of lesions(~40% sensitive, not specific) </li></ul><ul><li>DFA or EIA of lesions (80% sensitive) </li></ul><ul><li>Serology NOT useful </li></ul>
  37. 38. Imaging <ul><li>Classic CT/MRI - temporal lobe lesion but may have many presentations to include hydrocephalus </li></ul>
  38. 39. HSV treatment <ul><li>Acyclovir 20mg/kg/dose Q8 hrs </li></ul><ul><ul><li>SEM only- 14 days </li></ul></ul><ul><ul><li>Disseminated (no CNS)- 21 days </li></ul></ul><ul><ul><li>CNS- at least 21 days (PCR must clear) </li></ul></ul>
  39. 40. Cases <ul><li>Kid 1 </li></ul><ul><ul><li>9 week old, term baby </li></ul></ul><ul><ul><li>100.6 temp </li></ul></ul><ul><ul><li>Looks well </li></ul></ul><ul><ul><li>CBC WNL </li></ul></ul><ul><ul><li>UA clean </li></ul></ul><ul><ul><li>Everyone at home with colds </li></ul></ul><ul><li>Kid 2 </li></ul><ul><ul><li>12 day old, term baby </li></ul></ul><ul><ul><li>Fever to 101 </li></ul></ul><ul><ul><li>Jaundiced </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>WBC of 3.2 K </li></ul></ul><ul><ul><li>PLT of 89 </li></ul></ul>