1. NICU Case Presentation Jon Palma, MD Neonatology Fellow March 2010

2. Clinical scenario  You are called to attend a delivery in L&D for a diagnosis of maternal chorioamnionitis.  Upon entering the delivery room, what minimal information must you obtain (according to NRP guidelines)?

3. Question 1 Upon entering the delivery room, what minimal information must you obtain (according to NRP guidelines)? Singleton or multiple gestation Estimated gestational age Presence of meconium

4. Case (cont’d): in the delivery room  The OB team tells you:  Mom is a G1 P0 at 38 weeks, and meconium is not present.  You were called because chorioamnionitis was diagnosed for a fever of 38.3 celsius  Next questions:  What are the diagnostic criteria for chorioamnionitis?  In regards to sepsis risk factors, what items must you determine from mom’s history?  At LPCH, for what indications do we perform full sepsis evaluations on newborn infants?

5. Question 2 What are the diagnostic criteria for chorioamnionitis?  The essential clinical criteria is maternal fever > 38 degrees C (100.4 F); other criteria are insensitive.  For clinical research, diagnosis is typically based upon the presence of maternal fever and at least two of the following:  Maternal leukocytosis (>15,000 cells/cubic millimeter)  Maternal tachycardia (>100 beats/minute)  Fetal tachycardia (>160 beats/minute)  Uterine tenderness  Foul smelling amniotic fluid  Bottom line: chorioamnionitis is a clinical diagnosis made by the obstetrician. If they say it’s chorio, then it is.

6. Question 3: In regards to sepsis risk factors, what items must you determine from mom’s history?  Estimated gestation  Preterm labor  Rupture of membranes (ROM)  Prolonged ROM (PROM): >18 hrs  Premature preterm ROM (PPROM):  ROM prior to the onset of labor at a gestation of <37 weeks  GBS status  Including history of a prior infant with GBS infection

7. Odds Ratios for Neonatal Sepsis Associated with Maternal Risk Factors

8. Question 4: At LPCH, for what indications do we perform full sepsis evaluations on newborn infants?  Certain babies are at such high risk for infection that they should be admitted to the NICU, regardless of clinical appearance. They should undergo a complete evaluation for possible sepsis and be started on empiric antibiotic therapy until infection is ruled out. These babies include those whose mothers have:  premature pre-term ROM  chorioamnionitis  a history of having a prior infant with GBS infection * Source: NICU Manual *If mother received adequate IP prophylaxis, the CDC guidelines support observation, but clinicians and parents may opt for a complete diagnostic evaluation

9. CDC Guidelines Approach for empiric management of newborns born to women who receive intrapartum antibiotics to prevent early-onset GBS disease or to treat suspected chorioamnionitis Note: in the setting of adequate intrapartum antibiotic prophylaxis for GBS and no concern for chorio, labs are not required but a 48 hour observation period is recommended (no early discharge)

10.  Adequate IAP  Penicillin, ampicillin, or cefazolin > 4 hrs before delivery  Penicillin is the agent of choice (narrower spectrum)  Clindamycin or erythromycin > 4 hrs before delivery in:  Penicillin-allergic women at high risk for anaphylaxis  With GBS isolates sensitive to clinda or erythro  Vancomycin > 4 hrs before delivery in:  Penicillin-allergic women at high risk for anaphylaxis  When clinda or erythro are not options because of in vitro resistance or unknown susceptibility  Without susceptibility testing of GBS isolates clindamycin is not considered adequate IAP  Usually would not send screening labs, but use clinical judgment CDC Guidelines Intrapartum Antibiotic Prophylaxis (IAP)

11. Case (cont’d): over to the NICU  The baby required only routine resuscitation (warmth, drying, suctioning, and stimulation) and had APGAR scores of 8 at one minute and 9 at five minutes of life.  You proceed to the NICU to perform a full sepsis evaluation.  What constitutes a full sepsis evaluation of a newborn in the LPCH NICU, including laboratory studies and empiric antibiotics?

12. Question 5: What constitutes a full sepsis evaluation of a newborn in the LPCH NICU, including laboratory studies and empiric antibiotics?  CBC with differential, blood culture, glucose  2 CRPs at least 24h apart  The first CRP should be drawn at > 8h after birth or after the blood culture is drawn, whichever is later  Lumbar puncture  Tube 1: CSF glucose, protein  Tube 2: CSF culture/gram stain (changed to tube 2 to decrease false +’s)  Tube 3: CSF cell count/diff  Tube 4: if needed for other studies (e.g. HSV PCR)  Empiric antibiotics (while awaiting culture(s), CRPs)  Ampicillin 50mg/kg IV q6h (meningitic dose100 mg/kg IV q6h for sicker babies)  Gentamicin 4mg/kg IV loading dose, followed by 3 mg/kg IV q24h  For infants with respiratory symptoms  CXR  ETT aspirate (if intubated)

13. from Pediatrics 1998; 102 (4): e41 “Serial CRP levels are useful in the diagnostic evaluation of neonates with suspected infection. Two CRP levels <1 mg/dL obtained 24 hours apart, 8 to 48 hours after presentation, indicate that bacterial infection is unlikely.”

14. CRP has excellent negative predictive value In the study, CRP #2 was the lab sent at least 8 hours after the initial evaluation, and CRP #3 was sent 24 hours later. CRP #1 was done at the time of the initial evaluation.

15. What About ET Aspirates and Urine Specimens?  For babies who have just been intubated for respiratory distress and have an infiltrate on chest x-ray, culture of an endotracheal aspirate will be positive in approximately 8%. Fewer than half of these positive cultures are associated with positive blood cultures, so don’t forget to order an endotracheal aspirate Gram stain and culture.  Urine cultures are rarely positive in the first 48 hours of life. After that, they may be quite helpful. Because they are almost always contaminated, often with a single organism, bag urine specimens are useless. Specimens obtained by catheterization of the bladder are better, but also have a surprisingly high contamination rate. Learn to do suprapubic aspirates for urine cultures in neonates. Source: NICU Manual

16. Question 6: How do the LPCH NICU practices vary from CDC guidelines? * * The CDC will be revising its guidelines in 2010 to clarify that for infants who are admitted because of risk factors (chorio) but are well appearing, the lumbar puncture may be deferred

17. Question 6: How do the LPCH NICU practices vary from CDC guidelines?  CRP not part of CDC guidelines  Lumbar puncture is always performed when an infant demonstrates clinical symptoms of possible sepsis  Rationale: there is no surrogate blood test for meningitis; only CSF analysis provide diagnostic clues, and a diagnosis of meningitis impacts length of antibiotic therapy. Blood cultures are negative in about 1/3 of meningitis cases and thus should not be used in lieu of  Limited evaluation at LPCH does not include a blood culture  Rationale: if the index of suspicion is high enough to perform a blood culture, treatment with antibiotics is warranted  What is the approach to sepsis screening in the LPCH Well Baby Nursery?  LPCH Well Baby Nursey Website - Sepsis Screen LPCH Well Baby Nursey Website - Sepsis Screen

18. Practical Aspects of the Sepsis Evaluation  Draw the blood culture as soon as possible - preferably before antibiotics are given, but start treatment without delay. The initial dose of ampicillin can be given as an IV bolus, and the first dose of gentamicin can be given IM if the infant is not in shock.  As many as 50% of neonates with meningitis may have negative blood cultures, so the CSF culture may be the only source of a bacteriologic diagnosis. Do the LP as soon as possible; it is not appropriate to defer it for a few hours, either for the convenience of the caretakers or until the baby is more stable. Source: NICU Manual

19. Question 7: How are CRP results generally interpreted and managed in the LPCH NICU?  In an asymptomatic infant with negative cultures:  In a symptomatic infant with negative cultures:  Discuss with your attending CRP < 1negatived/c abx if CRP negative x 2 (24h apart) * CRP 1 – 2indeterminateFollow up CRP in 24 hours CRP > 2positiveDiscuss with your attending regarding duration of abx * Note: the NPV of serial CRPs means that antibiotics may be discontinued prior to the blood culture reaching 48 hours

20. Question 8: What is the duration of treatment for neonates with confirmed serious bacterial infections?  Positive blood culture *, UTI, or pneumonia  Coag-negative Staph: 7d  Other gram-positives: 10d  Gram-negatives: 14d  Candida: 21d  Meningitis #  Gram-positive: 14d  Gram-negative: 21d * Count should begin from first negative culture # Repeat lumbar puncture recommended to document negative culture prior to discontinuing antibiotics

21. Additional references  Uptodate.com (Intraamniotic infections)  Benitz. Suspected sepsis in newborn infants. NICU Manual.  http://www.cdc.gov/groupbstrep/guidelines/summary.htm  http://newborns.stanford.edu/ClinicalGuidelines.html