1. Neonatal Sepsis Author: Sherrill Roskam RNC MN NNP CNS Updated presentation: Susan Greenleaf RNC, BSN

2. Objectives Identify major causative organisms and routes of transmission of sepsis. Discuss clinical manifestations and modalities used in diagnosis of sepsis. Describe antibiotic therapy used in the treatment of neonatal sepsis.

3. Sepsis Definition: A systemic response to an invasive organism. Frequently signified by a positive blood culture. A systemic illness due to the presence of bacteria and or bacterial toxins in the blood

4. Neonatal Immune System Sepsis occurs in 1-8:1000 term infants and 1:250 premature infants Neonates are immunocompromised even at term gestation The neonatal immune system is functional at birth, but not mature

5. Sepsis Two types of sepsis Early-onset sepsis, with in the first 72 hours of life Late-onset sepsis, those infections acquired later by horizontal transmission. Highest risk for the first month of life

6. Predisposing Factors: Pregnancy Prematurity PROM < 36 weeks Prolonged ROM Prolonged labor Excessive manipulation

7. Predisposing Factors: Maternal History of infection Bacterial Viral History of GBS bacteriuria History of previously affected infant Temperature in labor

8. Predisposing Factors: Neonatal Invasive procedures Resuscitation Intubation IV starts / PICC lines Umbilical Catheterization Skin colonization

9. Predisposing Factors: Nursery Humidifiers Respiratory therapy equipment Staff members Unsterile equipment Scales Stethoscopes Thermometers

10. Transmission Transplacental Ascending Birth Nosocomial Antibodies IgG IgM IgA

11. Human Immunoglobulins Antibodies are the immunoglobulins produced in response to specific antigens IgG is the only antibody that crosses the placenta and provides immuological protection over the first few months Transfer peaks at 32 weeks gestation

12. Immunoglobulins cont. IgM and IgA are directly responsible for antibodies against bacteria Neonatal IgM production starts at 30 weeks gestation and increases over the first year of life IgA passes through breast milk to provide early defense against infection. Found in the intestinal tract.

13. Causative Organisms: Bacterial Group B strep E Coli Haemophilus Influenzae Coagulase Negative Staph Staph Aureus Neisseria Meningitis Listeria

14. Causative Organisms: Viral Maternal in origin Toxoplasmosis Rubella Cytomegalovirus Herpes Hepatitis B HIV

15. Recognition: Clinical Signs Temperature instability Lethargy Pallor, mottling, poor cap refill Respiratory distress Poor feeding Apnea Neurologic Jaundice Hypoglycemia

16. Recognition Recognition is of utmost importance, because newborns with sepsis can get very sick very fast Be aware of risk factors – review maternal history

17. Diagnostic tests for sepsis CBC Cultures Blood ~ Most common Gold Standard Urine Surface - only indicates colonization CSF Lumbar puncture CRP

18. C-Reactive Protein What is CRP? Laboratory test that identifies an inflammatory response in the body. Binds to Calcium and phosphocholine sites; forming CRP-ligand complexes.

19. CRP CRP’s unique binding characteristics have led to the identification of elevated CRP levels in over 70 different infectious and noninfectious disorders. It is associated with acute and chronic inflammatory disorders.

20. CRP Continued... Paired mother and infant sampling shows that CRP does not cross the placenta. 4 types of inflammatory response to tissue injury Infectious, noninfectious, chemical, physical or immunologic toxins.

21. Use of CRP 2 schools of thought Early diagnostic tool for confirming sepsis Screening tool to r/o the presence of sepsis

22. CRP Levels: What is normal? In the neonatal period: Level of 10mg/L is considered normal Healthy full-term and preterm infants may range from 2 to 5mg/L during the first few days of life.

23. More than 1 Level? Conflicting information about obtaining more than one level Serial CRP levels drawn 12 to 24 hours after onset of S/S of sepsis may be superior to a single level.

24. More About the CBC: WBC White cell count Differential Neutrophils - bacteria fighting cells Polys, Segs - most mature Bands - immature Metas – really immature Absolute Neutrophil Count I:T Ratio

25. White Blood Cells The main defense against invading microorganisms Neutrophils (pack man cells) and macrophages(monocytes) Circulating cells that migrate to sites of inflamation, ingesting and killing foreign material or bacteria (phagocytosis) Small stores in neonates, not as effective in killing bacteria, quickly depleted

26. Differential of the WBC Mature Neutrophils – Segmented Immature Neutrophils – Bands Monocytes Basophils Eosinophils Lymphocytes

27. Neutrophils As mature neutrophols (polys, segs, neuts, or PMNs) are mobilized and consumed in the presence of a pathogen, their numbers decrease and immature cells are released from the bone marrow. Immature neutrophils (bands, metas or stabs)

28. Absolute Neutrophil Count (ANC) Helps determine how many neutrophils are available to fight bacterial infections Premature infants have lower ANC than term infants Must plot on the Manroe chart

29. How to calculate an ANC Identify the immature and the mature neutrophils on the CBC. Add the segs, bands and metas ( total number of neutrophils) together and turn it into a percentage Multiply this number by the total WBC This resulting number is the ANC

30. Manroe Chart

31. WBC: 20,000 Differential is expressed as a percent of total white cells Poly’s (Segs, Neuts): 48% Bands12% Lymphs:20% Monos:17% Eso: 3%

32. ANC: Absolute number of neutrophils WBC X % Neutrophils ANC WBC X % Neutrophils 20,000 X.6 (60%) = 12,000

33. Manroe Chart

34. Immature to Total Ratio (I:T) An Increased IT ratio is called a left shift. It show an increase in the number of immature sells An IT ratio of >.25 may indicate sepsis I/T ratio: Ratio of immature to total neutrophils ___Bands + Meta___ Polys + Bands + Meta

35. WBC: 20,000 Differential is expressed as a percent of total white cells Poly’s (Segs, Neuts): 48% Bands12% Lymphs:20% Monos:17% Eso: 3%

36. I/T ratio: Bands + Metas Polys + Bands + Metas 12/60=0.2 (not indicative of sepsis) If WBC 3000 Polys 30 and Bands 15: 15/45=0.33 (indicative of sepsis) 3,000 X.45 (45%) = 1,350

37. Platelet Count Normal Values VLBW – 275,000 +/- 60,000 Preterm – 290,000 +/- 60,000 Term – 310,000 +/- 60,000 Infants with infection may have a low platelet count

38. Management Support Systems Neutral Thermal Environment Monitor Cardiac/Respiratory Pulse Oximetry Vital signs Feedings IV

39. Management (con’t) Antibiotics Ampicillin 50-100 mg/kg/dose IV q8-12 hours Varies with gestation and age Gentamicin 4 mg/kg/dose IV q24-48 hours Varies with gestation Give over 30 minutes Monitor Gent levels Antiviral Acyclovir 20 mg/kg/dose IV q8 Give over 1 hour Do not refrigerate

40. Prognosis Prognosis depends on organism involved and when treatment started

41. A bit more practice CBC results WBC 10.4 Metamyelocytes 0 Band Neutrophils 14 Segmented neutrophils 5 Platelets 141,000 What is the ANC and the IT ratio?

42. CBC Practice CBC results WBC 1.3 Metamyelocytes 2 Band Neutrohils 17 Segmented Neutrophils 42 Platelets 262,000 Calculate the ANC and IT ratio

43. CBC Practice CBC results WBC 6.3 Metamyelocytes 6 Band Neutrophils 44 Segmented Neutrophils 23 Platelets 95,000 What is the ANC and the IT ratio?

44. Same patient, 6 hours later CBC results WBC 0.8 Metamyelocytes 2 Band Neutrophils 4 Segmented Neutrophils 2 Platelets 24,000 What is the ANC and IT ratio?

45. References Behrman, R. E., Kliegman, R.M.,Editors (1998) Nelson Essentials of Pediatrics, 3 rd Ed. Philadelphia: W.B. Saunders Co. Cloherty, J.P., Eichenwald, E.C., Stark, A.R. (2004) Manual of Neonatal Care, 5 th Ed. Philadelphia: Lippincott, Williams & Wilkins. Hengst, J.M., The Role of C-Reactive Protein in the Evaluation and Management of Infants with Suspected Sepsis. Advances in Neonatal Care. 2003;3(1):3-13.

46. References Karlsen, K.A. (2001) The S.TA.B.L.E. Program: Transporting Newborns the S.T.A.B.L.E.Way, Learner Manual, 8 th Ed. Merenstein, G.B., Gardner, S.L. (2002) Handbook of Neonatal Intensive Care, 5 th Ed. St. Louis:Mosby Inc.