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1. Neonatal sepsis Outlines Definitions Classifications Causative agents Risk factors Clinical features Diagnosis Management Prevention 1

2. Neonatal sepsis Definition:- Neonatal sepsis is a clinical syndrome characterized by systemic signs of infection, accompanied by bacteremia in an infant 28 days of life or younger. The more common viruses are CMV, HSV, and HIV Incidence : 1- 5 cases per 1,000 live births Mortality : 13-70% world wide Sex : Males > Females 2

3. Neonatal sepsis… Why Neonatal infections are unique in several ways? 3

4. Neonatal sepsis… Infectious agents from the mother Newborn infants are less capable of responding to infection Clinical manifestations varies and include subclinical infection, mild to severe manifestations Maternal infection is often undiagnosed during pregnancy A wide variety of etiologic agents: bacteria , viruses, fungi, protozoa, and mycoplasmas 4

5. Classifications Bacterial causes of systemic neonatal sepsis are classified as: Early onset (day of life 0 - 7 ) L ate on set day of life 8 -28) L ate late onset ( day of life 28-90) 5

6. Classifications… Early onset (day of life 0 - 7 ) is usually due to vertical transmission:- ascending contaminated amniotic fluid(increases from 1 to 4% in neonates born to mothers with chorioamnionitis) during vaginal delivery from bacteria colonizing or infecting the mother's lower genital tract 85 % present within 24 hours (median age of onset 6hr) 5% present at 24-48 hours a smaller percentage present within 48-72 hours Onset is most rapid in premature neonates 6

7. Late onset (day of life 8 or later ) can be acquired by the two mechanisms Maternal vertical transmission Horizontal transmission( direct contact with care providers or environmental sources ) is uncommonly associated with maternal obstetrical complications 7

8. Neonatal sepsis according to age at onset Characteristics Early onset Late onset Very late (nosocomial) onset Age at onset Birth to 7 days usually <72 hr 7-28 days >28 days Maternal obstetric complications Common Uncommon Varies Prematurity Frequent Varies Usual Organism source Maternal genital tract Maternal genital tract/environment Environment/community Manifestation Multisystem Multisystem or focal Multisystem or focal site Normal nursery, NICU, community NICU, community NICU, community 8

9. Etiologic agents     What are the etiologic agents for neonatal sepsis? 9

10. Early onset neonatal sepsis The microorganisms most commonly associated with: Group B  Streptococcus  ( GBS):- decreasing due to prenatal screening and treatment protocols Escherichia coli Coagulase-negative  Staphylococcus Haemophilus influenza Listeria monocytogenes 10

11. Late onset neonatal sepsis Coagulase- negative   Staphylococcus ( a cause of nosocomial infection in ill infants ) Staphylococcus aureus E coli Klebsiella Pseudomonas Enterobacter Candida GBS Serratia Acinetobacter Anaerobes 11

12. Summary of etiologic agents     Group B streptococcus (GBS) and Escherichia coli (E. coli) are the most common causes (for both) GBS and E. coli continue to account for ≈ 2/3 rd EOSNS 12

13. Common bacterial agents causing N. sepsis Bacterial species Frequency of isolation Early-onset Late-onset Group B  Streptococcus +++ +++ Escherichia coli +++ ++ Klebsiella   spp. + + Enterobacter  spp. + + Listeria monocytogenes + + Staphylococcus aureus + +++ Citrobacter   spp. + Coagulase-negative staphylococci + Enterococcus  spp. + +++ : commonly associated, ++ : frequently associated, + : occasionally associated, : rarely associated 13

14. Risk factors M aternal : Membrane rupture ≥18 hours Maternal fever>38 ºC Chorioamnionitis Maternal GBS colonization Fetal: Premature infant (< 37 weeks) Low APGAR (< 5 in 1 min.) low birth wt. (1500 grams) Twin gestation Sustained fetal tachycardia>160 beats/min 14

15. Pathophysiology Neonate is unable to respond effectively to infectious hazards because of deficits in the physiological response to infectious agents . Neonatal neutrophil or PMN cells are defective in chemotaxis & killing capacity because of decreased adherence to the endothelial lining of blood vessels reduce the ability to migrate into the tissues & once there they may fail to deaggregate in response to chemotactic factors 15

16. Macrophages chemotaxis is impaired & continues to exhibit decreased function in early childhood, the chemotactic & bactericidal activity & antigen presentation by these cells is not fully competent, cytotoxine production is decreased . T-cells are found in early gestation in fetal circulation & continue to increased in no. in the 1 st 6 months of life but these cells represent immature population & they do not effectively produce cytokines that is associated with B cells stimulation & differentiation Pathophysiology… 16

17. Pathophysiology… NK cells are found at greater level in neonates compared with adults but certain antigen expressed by the cell membranes is diminished thereby reducing cytotoxic activity. the fetus is capable of complement production at as early as 6 wks of gestational age but mature complement activity is not reached until infants are 6-8 months of age. the neonate receives IgG parentally after 16 wks of gestation however if the baby is premature or the mother is immune suppressed ,less IgG is received. 17

18. Pathophysiology … The neonate is able to synthesize IgM in utero at 10 wks of gestation but its level is low at birth. IgA is received by breastfeeding but not secreted until 2-5wks after birth The physical & chemical barriers to infection in the human body are present in the neonate but are functionally deficient Skin & mucus membranes are broken down easily in the premature infant Neonates who are ill &/or premature are additionally at risk because of the invasive procedures that breach their physical barriers to infection. 18

19. Clinical features Neonates with bacterial sepsis may have either nonspecific signs and symptoms or focal signs of infection. Nonspecific and empiric antibiotic therapy is started until blood culture results are available 19

20. Clinical features… 20 The initial manifestation may involve only limited symptomatology and only 1 system such as:- apnea alone or tachypnea with retractions, or tachycardia, or the infant may present with an acute catastrophic manifestation with multiorgan dysfunction.

21. Initial Signs and Symptoms of Infection in New-born Infants(Summary) 21

22. Clinical features… 22 Later complications of sepsis include respiratory failure, pulmonary hypertension, cardiac failure, shock, renal failure, liver dysfunction, cerebral edema or thrombosis, adrenal hemorrhage and/or insufficiency, bone marrow dysfunction (neutropenia, thrombocytopenia, anaemia), and disseminated intravascular coagulopathy (DIC).

23. Clinical findings in neonatal sepsis Finding Frequency Hyperthermia +++ Respiratory distress ++ Anorexia ++ Vomiting ++ Jaundice ++ Hepatomegaly ++ Lethargy ++ +++: commonly associated (≥50%of cases), ++: frequently associated (25-50 %), +: occasionally associated (<25 %). 23

24. Clinical findings in neonatal sepsis… Finding Frequency Cyanosis + Hypothermia + Irritability + Apnea + Abdominal distension + Diarrhea + +++: commonly associated (≥50%of cases), ++: frequently associated (25-50 % ), +: occasionally associated (<25 % ). 24

25. World Health Organization international criteria for bacterial sepsis. 25

26. DDX 26

27. DDX… 27

28. Investigations Septic work up includes:- CBC with differential Blood culture(definitive dx) Acute phase reactants (ESR, C-reactive protein ( CRP) ) CSF exam with culture ; if indicated Urine culture Chest X-ray 28

29. Investigations… A-CBC: obtained 6 to 12 hours after delivery may be helpful in the evaluation of early-onset sepsis absolute neutrophil and I/T ratio have been used as markers for neonatal sepsis absolute neutropenia (<1000 neutrophils/ microL ) and low white blood cell count (WBC) (<5000/ microL ) leucopenia (<5-10,000) or leukocytosis (>30-35,000 ) increased I:T( immature to total neutrophil count) ratio > 0.2, @Normal= 0.16 up to 60% of septic newborns have platelets count < 100,000. B-Blood Cultures:- positive in 85-90 % of patients. 29

30. Investigations… C-CSF: 20-25% of infants with neonatal sepsis also have meningitis and clinical signs suggesting meningitis can be lacking in young infants T he 2012 AAP recommends that LP: A positive blood culture Clinical findings that are highly suggestive of sepsis Laboratory data strongly suggestive of sepsis Worsening clinical status while on antibiotic therapy CSF findings are elevated WBC ,elevated protein, decreased glucose level & positive cultures. 30

31. Investigations… D- CRP: increases in inflammatory conditions, including sepsis CRP is elevated in 50-90% of infants with sepsis. Its usually rises within 24hrs & peaks within 2-3 days &remains till the inflammation is resolved. A CRP value that is greater than 1.0 mg/ dL  is 90% sensitive in detecting neonatal sepsis  E-Arterial blood gas analysis: Hypoxia metabolic acidosis 31

32. Investigations… F-Urine Culture: useful for late onset sepsis in compare with early onset(7.5%vs. 1.5 %). evaluation of an infant ≤6 days of age because a positive urine culture is a reflection of high-grade bacteremia rather than an isolated urinary tract infection suprapubic aspiration sample is the most preferred . pyuria(>10WBC/mm3) is present in 80% of those with positive cultures. G-Chest X-ray: should be obtained in an infant with respiratory distress It’s done to diagnose pneumonia which may turn out to have negative culture. 32

33. Secondary prevention early-onset GBS disease among newborns 33

34. Management intranasal oxygen correct hypoglycemia correct hypothermia confirm the diagnosis Antibiotic continue monitoring & antibiotics for 24 to 72 hr continue antibiotics for 10-14 days if symptomatic infant or positive blood culture. 34

35. Antibiotics for neonatal sepsis Primary antibiotic protocol : Ampicillin(50mg/kg/dose IV or IM q12hrs Plus Gentamicin(5mg/kg/dose IV/IM/ day) For suspected gram positive bacteria for 7-10 days & gram negative bacteria for 10-14 days Alternative protocol Ampicillin (dose as above) plus Cefotaxime (50mg/kg/dose IV/IM q12hrs) Ampicillin (dose as above) plus Ceftriaxone (50mg/kg IV/IM q24hrs) 35

36. Antibiotics… The duration of therapy should be :- 10 days for sepsis without a focus 14 to 21 days for meningitis 14 to 21 days for septic arthritis 21 to 28 days for osteomyelitis 36

37. Other methods of treatment E xchange transfusion: used particularly in hypertensive & metabolically acidosis infants to increase the levels of circulating Ig, decrease circulating endotoxin, increase Hg level & improve perfusion Fresh Frozen Plasma: may be helpful in reversing the heat stable & heat liable opsonin deficiencies in LBW infants 37

38. Other methods of treatment IV Ig: in preventing neonatal sepsis in high risk LBW infants Recombinant granulocyte colony-stimulating factor: to increase the number & function of neutrophil in infants with presumed sepsis Granulocyte transfusion. 38

39. Prevention Screening pregnant women for GBS colonization ( colonizes the gastrointestinal and genital tracts of 15 to 40% of pregnant women ) Treatment of all women during labor who have specific risk factors for early-onset GBS infection   Penicillin G 5 million units IV initial dose, then 2.5 to 3 million units intravenously every four hours until delivery is recommended for intrapartum antibiotic prophylaxis Ampicillin 2 g IV initial dose, then 1 g intravenously every four hours until delivery 39

40. Prevention Vaccination of all women when GBS vaccines become available Good antenatal care Maternal infections diagnosed and treated early Babies should be breastfed early Good basic hygiene and cleanliness during delivery of the baby ƒ Special attention to cord care and eye care 40

41. Prevention Strategies at the time of childbirth Infection prevention practices for every delivery: Hand washing Minimum manipulation High-level disinfected or sterile instruments 6 Cleans: Clean hands Clean surface Clean blade Clean tie Clean perineum Clean nails 41