2. Background Neonatal sepsis is one of the leading problem of neonatal death, causes the neonatal morbidity and mortality. The incidences of neonatal death due to neonatal sepsis varies from 3 – 14 per 1000 newborns. It is higher in preterm babies(up to 26 per 1000 live babies). Incidence is even higher in the underdeveloped countries like Bangladesh, where the proper treatment facility is not sufficient

3. Definition Neonatal sepsis is a clinical syndrome of systemic illness accompanied by bacteremia in the first 28 day’s of life. Early Onset Sepsis (EOS): Culture proven infection within the first 72 hours of life 85% present within 24 hrs,5% present in between 24- 48 hrs, a small % present in between 48-72 hrs. Late Onset Sepsis (LOS): Culture proven infection after 72 hours of life

4. Etiology Infectious agents associated with neonatal sepsis have changed since the mid-20 th century 1950 - S. aurus, E. coli; later s. aurus replaced by GBS 1990 – GBS and E.coli Now – coagulase-negative S. epidamis frequently observed Can also be caused by adenovirus, enterovirus, coxsakie virus. Gonorrhea, syphilis, herpes simplex virus, CMV, hepatitis, HIV, TORCH infection have also been implicated in neonatal infection.

5. Early-onset Sepsis Associated with acquisition of microorganisms from the mother – transplacental infection or ascending infection Onset is most rapid in premature neonates GBS, E. coli, Coagulase-negative Staphylococcus, Stepto coccus, H. influenzae, L. monocytogenes are common pathogens. In Bangladesh context Klebsiella, Pseudomonas, E.coli, Acinobactor are common Pneumonia is more common in early-onset sepsis

6. Risk Factors of Early-onset Sepsis Maternal GBS colonization (especially if untreated during labor) Premature rupture of membranes (PROM) Prolonged rupture of membranes Prematurity Maternal urinary tract infection Chorioamnionitis

7. Acinetobacter Klebsiella E coli Serratia Pseudomonas S. aureus Enterobacter Candida GBS Anaerobes Coagulase negetive staphilococcus Etiology of Late-onset Sepsis Meningitis and bacteremia are more common in late-onset sepsis

8. Risk Factors of Late-onset Sepsis Prematurity Central venous catheterization (duration >10 days) Nasal cannula or continuous positive airway pressure (CPAP) H 2 -receptor blocker or proton pump inhibitor (PPI) GI tract pathology

9. Numerous host factors in Neonatal sepsis Cellular immunity Humeral immunity Complement factors And other Barrier function

10. Clinical Examination Clinical signs of neonatal sepsis are nonspecific and are associated with Characteristics of the causative organism Body’s response to the invasion. These nonspecific clinical signs are also associated with other neonatal diseases Respiratory distress syndrome (RDS) Metabolic disorders Intracranial hemorrhage Traumatic delivery

13. Clinical Symptoms Common /Non-specific 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,Metabolicacidosis Cardiovascular – Hypotension (5%), hypo perfusion, tachycardia,overt shock with pallor & odema. This late signs of shock are indicative of severe compromise & strongly associated with mortality NICHD data

14. Less com Seizure DIC Petechiae Hepatosplenomegaly Sclerema Meningitis symptoms Buiging anterior frontanele Irritability, lethargy, poorly responsive Changes in muscle tone, etc.

15. Differential Diagnoses Bowel Obstruction in the Newborn Congenital Pneumonia Heart Failure, Congestive Hemolytic Disease of Newborn Meconium Aspiration Syndrme Necrotizing Enterocolitis Pediatric Congenital Diaphragmatic Hernia Pediatric Infective Pericarditis Pulmonary Hypoplasia Imaging Respiratory Distress Syndrome

16. Approach Considerations Complete blood count (CBC) and differential Blood culture Quantity measurement of CRP and possibly other infection markers In some cases, serial CBC and CRP studies may be appropriate Gram stain provides early identification of the gram-negative or gram-positive status of the organism for preliminary identification CSF analysis and culture

17. Approach Considerations contd… Emerging technology using PCR could eventually help achieve faster identification of causative organism. Rapid pathogen detection with multiplex PCR may facilitate more timely selection of targeted antibiotic therapy while limiting exposure to broad-spectrum antibiotics Imaging studies may include: Chest radiography to evaluate pulmonary involvement CT scan, MRI and ultrasonography of the head in cases of meningitis

18. Results “Trigger Points” CBC WBC 22.0, abs neutro 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.

19. Treatment & Management When neonatal sepsis is suspected, treatment should be initiated immediately because of the neonate’s relative immunosuppression Begin antibiotics as soon as diagnostic tests are performed Cardiopulmonary support and parenteral nutrition may be required during the acute phase of the illness until the infant’s condition stabilizes Monitoring BP & vital signs, HCT, platelets, and coagulation studies is vital Not uncommonly, blood product transfusion, including packed red blood cells, platelets and FFP are indicated

20. Treatment & Management contd… Infant with temperature instability needs thermoregulatory support with a radiant warmer or incubator. Once the infant is stable from a cardiopulmonary point, parental contact is important, kangaroo management can be applicable in this regard Surgical consultation for central line placement may be necessary in infants who require prolonged IV antimicrobial therapy If an abscess is present, surgical drainage may be necessary; IV antibiotic therapy cannot adequately penetrate an abscess, and antibiotic treatment alone is ineffective

21. Treatment & Management contd… The infant may require transfer to a level III perinatal center, especially if he or she requires cardiopulmonary support, parenteral nutrition, or prolonged IV access. The multidisciplinary services available at larger centers may be necessary if the neonate’s condition is acutely compromised Additional therapies can be apply for the treatment of neonatal sepsis, including granulocyte transfusion, IVIg infusion, exchange transfusion, and the use of recombinant cytokines

22. Antibiotic Therapy In the United States and Canada, the current approach to the treatment of early-onset neonatal sepsis includes combined IV aminoglycoside and expanded-spectrum penicillin antibiotic therapy The specific antibiotics to be used are chosen on the basis of maternal history and prevalent trends of organism colonization and antibiotic susceptibility in individual nurseries

23. Antibiotic Therapy contd… If an infection appears to be nosocomial (late-onset sepsis), antibiotic coverage should be directed at organisms implicated in hospital-acquired infections, including S. aureus, S epidermidis, and pseudomenous sp. Vancomycin has been favored for this coverage; however, concern exists that overuse of this drug may lead to vancomycin-resistant organisms, For this reason, some clinicians prefer oxacillin therapy in this setting.

24. Antibiotic Therapy contd… Cephalosporins are attractive in the treatment of nosocomial infection because lack of dose-related toxicity and ability to reach adequate serum and CSF concentrations; however, their use has led to resistance in gram-negative organisms. Ceftriaxone displaces bilirubin from serum albumin and should be used with caution in infants with significant hyperbilirubinemia Aminoglycosides and vancomycin both have the potential to produce ototoxicity and nephrotoxicity and should therefore be used with caution

25. Prognosis Mortality from neonatal sepsis may be as high as 50% for infants who are not treated. Low birth weight and gram-negative infection are associated with adverse outcomes. In preterm infants who have had sepsis, impaired neurodevelopment is a concern. Residual neurologic damage occurs in 15-30% of neonates with septic meningitis. preterm infants with sepsis who did not have meningitis had higher rates of cognitive deficits, cerebral palsy, and other neuro developmental disabilities than infants who did not have sepsis. Infants with meningitis may acquire hydrocephalus or periventricular leukomalacia. They may also have complications associated with the use of aminoglycosides, such as hearing loss or nephrotoxicity.

26. Long time -Follow Up Follow up- The primary care provider (PCP) should evaluate the infant with neonatal sepsis within 1 week of discharge from the hospital. 1st week, Then Two weekly up to 3 Month Monthly up to 18 month If need to continue The PCP should evaluate growth and determine whether the feeding regimen and activity have returned to normal. ROP Screening, Hearing test- audiology test, audio screen RSV prophylaxis Neonatal sepsis is associated with meningitis, prolong hypoxia, ECMO therapy or brain abscess should be folowed for several yrs,

27. Prevention HAND-WASHING- the gold slandered measure for prevention Aseptic precaution during examination For GBS antibiotic treatment & prophylaxis during labor and delivery Pediatrician especially neonatologist all over the world continuously pay great attention to the unsolved questions of new born babies with sepsis, to reduce neonatal morbidity & mortality of this contingent of babies, hope to reduce to single digit.