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Neonatal sepsis
- 2. Neonatal Sepsis Clinical syndrome of bacteraemia with systemic signs and symptoms of infection in the first four weeks of life.
- 3. Burden of Neonatal Sepsis Worldwide: 1.5-2 million deaths per year In developing world: 30-50% of neonatal deaths (4000-5000 deaths per day) Commonest cause of neonatal mortality and morbidity 20% of all neonates develop infection 1% of all neonates die of infection Sepsis related deaths are preventable
- 4. Incidence of neonatal sepsis Indian Data NNPD - Neonatal sepsis-38/1000 live births Meningitis- 0.5/1000 live births CMC – Neonatal sepsis 9.8/1000 live births
- 5. TERMINOLOGY At risk of sepsis: maternal risk factors for infection present, baby is clinically well, sepsis screen is negative Probable sepsis: baby has clinical features of sepsis, risk factors and screening tests ±, blood culture is negative Sepsis: baby has clinical features of sepsis and blood culture is positive Spectrum of illness Sepsis Pneumonia Meningitis Osteomyelitis
- 6. Early Vs Late Onset Sepsis EOS Onset <48 hours Source Maternal LOS >48 hours Environmental
- 7. Aetiological agents EOS LOS E.coli Klebsiella GBS Enterobacter Enterococcus Coagulase - Negative staphylococci
- 8. Risk factors for neonatal sepsis EOS Preterm premature rupture of membranes Prolonged rupture of membranes >24 hours Maternal fever Chorioamnionitis Foul-smelling liquor Urinary tract infection Multiple vaginal examinations LOS Preterm Low birth weight Formula feeding Invasive procedures Parenteral fluids Overcrowding Understaffing Lack of asepsis
- 9. Vulnerability Immature immune system Unavoidable exposure to pathogenic organisms in birth canal Peripartum stress Invasive procedures Exposure to highly resistant nosocomial organisms in NICU
- 10. Clinical Features Not breathing well Not feeding well Not looking well
- 11. Respiratory Dusky spells Tachypnea Apnea Increased Apnoea, Bradycardia episodes Feeding Not hungry Distension Residuals Vomiting Heme-positive stools Watery or mucousy stools
- 12. Appearance Lethargic Mottled Poor perfusion Temperature instability Early-onset jaundice Ominous Late Signs Apnea Seizures Hypotension/ Shock
- 13. Central Nervous System Lethargy / irritability Jitteriness / hyporeflexia Tremors / seizures Coma Full fontanelle Abnormal eye movements Hypotonia / increased tone Respiratory System Cyanosis Grunting Irregular respiration Tachypnoea / apnoea Retractions Haematopoietic System Jaundice Bleeding Purpura / ecchymosis Splenomegaly Skin Rashes / erythema Purpura Pustules / paronychia Omphalitis Sclerema Circulatory System Pallor / cyanosis / mottling Cold, clammy skin Tachycardia / arrhythmia Hypotension Oedema Gastrointestinal tract Poor feeding Vomiting (may be bile-stained) Diarrhoea /decreased stools Abdominal distension Oedema / erythema abdominal wall Hepatomegaly CLINICAL SIGNS OF NEONATAL SEPSIS
- 14. Diagnosis Gold standard: positive blood culture Goals of workup Recover organism Determine specific antibiotics Determine antibiotic doses Determine length of therapy Remember that 10 babies are worked up for each proven case
- 15. Screening Tests Sepsis Screen Leukopenia (TLC <5000/cu mm) Neutropenia (ANC <1800/cu mm) Immature to total neutrophil ratio (I/T) >0.2 CRP +ve >10 mcg/ml after 24 hrs Micro-ESR >15 mm in 1st hour *If two or more screening tests are positive, treat infant as neonatal sepsis
- 16. Other Tests CIE/ Latex agglutination for GBS Gastric aspirate/ ET aspirate Buffy coat Classic Septic Workup Blood culture Lumbar Puncture Urine (suprapubic aspirate) Endotracheal Tube aspirate (if intubated) Surface cultures – ear/skin/eye secretions Stool culture Chest X-Ray Abdominal X-ray
- 17. Meningitis 20-30% of cases have meningitis Meningitis can often be clinically missed LP must be done if there are clinical signs of meningitis and in all cases of bacteraemia
- 18. RECENT ADVANCES IN DIAGNOSIS Computer assisted automated blood culture system Procalcitonin Cytokine levels estimation - IL1β,IL 6, IL 8,TNF
- 19. Supportive care Thermoregulation Fluid and electrolyte balance Maintain normoglycemia Maintain tissue perfusion Avoid enteral feeds if baby is sick Provide adequate calories, TPN Support respiration Dopamine/ dobutamine Exchange transfusion
- 20. Choice of antibiotics EARLY ONSET SEPSIS Penicillin/ampicillin + Aminoglycoside (gentamicin/amikacin) LATE ONSET SEPSIS Cefotaxime Amikacin Ciprofloxacin Vancomycin Carbapenems
- 21. How long to treat? Negative cultures AND course not consistent with infection: 48-72 hours treatment Sepsis/ NEC 10-14 days treatment Meningitis 14 days (Gram-positive), 21 days (Gram-negative) Osteomyelitis prolonged treatment UTI 7-10 days treatment, screen for renal anomalies
- 22. Immunologic Therapy Intravenous Immunoglobulin (IVIG) Granulocyte - Colony Stimulating Factor (G-CSF), Granulocyte Macrophage - Colony Stimulating Factor (GM-CSF) Neutrophil transfusion Fresh Frozen Plasma Exchange transfusion
- 23. Targeting Inflammatory Mediators 1. Anti endotoxin 2. Anti cytokine therapy Anti TNF - antibody Interleukin-1 Receptor antibody (IL-1 RA) IL - 10 (Inhibits TNF, IL-1, IL-12) 3. PAF Antagonists 4. Nitric Oxide (NO) Synthase inhibitors 5. Guanylate Cyclase inhibitor Methylene blue
- 24. Outcome Birth weight, gestational age Treatment delay EOS or LOS Associated complications Perinatal centre Case Fatality Rate India, Pak, SE Asia : 27-69% Middle East: 13-28% Vellore: 14.4% EOS : 16.7% LOS : 13.6% Sepsis accounted for 19% of all deaths
- 25. Prevention Intrapartum Antibiotic Prophylaxis GBS carriers Mothers with PROM/PPROM Mothers with other recognisable risk factors for infection GBS vaccine 0.25% Chlorhexidine Washing birth canal during each vaginal examination Wiping the baby after delivery
- 26. General measures Handwashing Isolation? Bedside asepsis Disposal of waste products in separate bins Glucose, protein, and lipid solutions should not be re- used Intravenous in-line bacterial and viral filters Avoid overcrowding Adequate staff Periodic surveillance Regular cleaning of the unit Exclusive use of breast milk Treat LOS as a medical emergency
- 27. CONGENITAL INTRAUTERINE INFECTIONS Defn: Infection acquired transplacetally while inutero.
- 28. Aetiology Common organisms Toxoplasma Others: HIV,EBV, ParvoB19 Rubella Cytomegalovirus Herpes simplex Syphylis Uncommon organisms Varicella zoster Listeria Myc tuberculosis
- 29. Perinatal infections Infections transmitted just before delivery Clinical features are similar to any post natal infection Examples : Group B streptococcus Listeria Enteroviruses
- 30. Common clinical features of TORCH infections Growth retardation Hepatospleenomegaly Jaundice Hemolytic anaemia Petichae, echymosis Microcephaly Intra-cranial calcifications Pneumonitis Myocarditis Heart defects Chorioretinitis Cataract Glaucoma Hydrops
- 31. Clinical features suggesting a specific diagnosis Rubella : eye – cataract, keratitis, retinitis skin – “blueberry muffins” heart – PDA, pulmoic stenosis Deafness CMV: microcephaly with periventricular calcifications, petichae, thrombocytopenia Toxoplasma : hydrocephalus with diffuse intrcerebral calcifications Syphilis : bone and mucocutaneous lesions
- 32. Diagnostic approach Nonspecific tests CBC, platalet counts CSF analysis Xray of long bones CT scan of brain Eye checkup Hearing assesment Specific tests Viral culture: urine, blood, stool, csf Skinsmears: tzank sm. Specific serology
- 33. Congenital rubella syndrome Transplacental passage of virus early in pregnancy affects organogenesis in fetus Multisystem involvement Infection before 11th week – 90% chance Infection after 16th week – low risk Ask for low grade transient fever, posterior auricular and suboccipital tender lymphadenopathy, arthralgia and rashes in 1st trimester
- 34. CRS contd… Clinical features Diagnosis: 1. baby’s serum +ve for rubella Igm 2. viral culture of secretions 3. isolation from amniotic fluid – prenatally Prognosis: 1. Extensive involvement – grim prognosis 2. Fewer stigmata – better Prevention: 1. rubella/ MMR vaccine – 90% protective 2. Abortion / immunoglobulin in exposed seronegative mothers
- 35. Syphilis Transplacental infection at any stage of pregnancy – sply 1*, 2* or early latent phase 100 % transmission rates Perinatal death in 40% Risk factors in mother/father Classic perinatal history : 1st trimester abortion 2nd trimester aboprtion 3rd trimester fetal loss, FSB Early neonatal death Affected infant
- 36. Syphilis – clinical features Early signs(1st 2 years) Hepatospleenomegaly Lymphadenopathy Hemolytic anaemia Skin rash, peeling Snuffles Condylomata Pseudoparalysis Chorioretinitis Late signs-1st 2 decades Olympian brow Higoumenakis sign Saber shin Hutchison’s teeth, Mulberry molars Saddle nose, Rhagades Juvenile paresis Juvenile tabes Blindness Cluttons joints
- 37. Syphilis - diagnosis Whom to investigate: 1. All symptomatic babies 2. Asymptomatic babies whose mother is a suspect NONSPECIFIC TESTS:VDRL – baby’s titre 4 times that of mother, RPR SPECIFIC TESTS: FTA-abs, MHA-TP, TPI CSF VDRL : marker of neurosyphoilis
- 38. Syphilis - treatment Whom to treat? 1. Babies of untreated/partially treated mothers 2. Relapse/reinfection in mother 3. Physical evidence of active disease in the baby 4. Presence of radiological evidence 5. CSF VDRL found +ve 6. Baby’s VDRL titre >4 times of mother What to treat with? 1. Aq. C.penicillin G 1 lac u /kg/day in q12hX 7 days followed by q8h X 7 days 2. Neurosyphilis: 2 lac u /kg/day q6h X 14 days Prevention: routine antenatal screening prevention of STDs
- 39. THANKYOU
Notas del editor
- Through out the world about one and a half to two million newborn babies die every year due to sepsis. In developing world alone 4-5 thousand neonates die every day of sepsis
- Immature immune system (slow to react, decreased IgG and complement production, poor phagocytosis, poor migration)
- tachypnea - sensitive but nonspecific - but respiratory distress in term newborn is sepsis until proven otherwise. apnea in normal newborn - septic w/u and supportive measures should be knee-jerk reaction, then rule out other causes increased A&B episodes (growing premie)
- Temperature instability (not necessarily fever, but fever is more specific)
- PT/PTT suddenly abnormal Blood sugar may be high or low - change in pattern CIE or Latex fixation for GBS? Numerous false positives. Gastric aspirate or ET aspirate? Not very specific. Buffy coat? Rarely positive, but highly specific Classic Septic Workup (> 24 hours, < 30 days)
- Procalcitonin - earliest marker of favourable outcome
- Maintain tissue perfusion with plasma, albumin or normal saline Support respiration, if apnoeic or breathing inadequate Consider dopamine/dobutamine, if perfusion is persistently poor Exchange transfusion, if sepsis is fulminant
- Anti Endotoxin Monoclonal antibodies against Lipid A domain of LPS BPI - Bactericidal or permeability increasing protein Nitric Oxide (NO) Synthase inhibitors L-NMMA, L-NAME (Detrimental hemodynamic effects in newborn) Methylene blue (of proven benefit in septic shock) 1mg/kg IV over 1 hour
- Chlorhexidine Three fold decrease in incidence of EOS (NIH Study)