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Clinical Consequences of Enterobacter sakazakii Infections

Clinical Consequences of Enterobacter sakazakii Infections. John Alexander, M.D., M.P.H. Division of Anti-Infective Drug Products, Center for Drug Evaluation and Research, FDA . Outline. Neonatal Meningitis Necrotizing Enterocolitis Bacteremia/Sepsis. Neonatal Meningitis.

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Clinical Consequences of Enterobacter sakazakii Infections

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  1. Clinical Consequences of Enterobacter sakazakii Infections John Alexander, M.D., M.P.H. Division of Anti-Infective Drug Products, Center for Drug Evaluation and Research, FDA

  2. Outline • Neonatal Meningitis • Necrotizing Enterocolitis • Bacteremia/Sepsis

  3. Neonatal Meningitis • Incidence: 0.25-1/1000 Live Births • Usual Pathogens: • Group B Streptococcus • Escherichia coli • Listeria monocytogenes • Enterobacter spp. < 4% of One Survey • Rare Organism in a Rare Disease

  4. Neonatal Meningitis • Clinical Manifestations • Non-Specific Findings • Fever/Temperature Instability • Lethargy/Poor Feeding • Respiratory Distress • Specific Findings (Infrequent) • Bulging Fontanelle • Stiff Neck/Opisthotonus • Convulsions

  5. Neonatal Meningitis • E. sakazakii • Based on Collected Literature • 55% of Neonates  2500g • 50% of Pediatric Cases  1 Week of Age • Almost 75% < 1 Month of Age Lai KK, Medicine 2001; 80(2):113-22

  6. Burdette et al., Pediatric Radiology (2000) 30:33-34

  7. Neonatal Meningitis • Outcome • 17% Case Fatality Rate for Gram (-) Meningitis • 45% for E. sakazakii Meningitis from Reports • Therapy • At least 3 weeks of IV Antibiotics • Longer for Persistent (+) Cultures

  8. Neonatal Meningitis • Sequelae of Gram (-) Meningitis in 58% • Developmental Delay (37%) • Seizure Disorder (36%) • Cerebral Palsy (31%) • Hydrocephalus (27%) • Hearing Loss (17%) Unhanand M et al., J Pediatrics 1993; 122(1): 15-21

  9. Necrotizing Enterocolitis • Disease of the GI Tract • Mostly in Pre-Term Infants • Approximately 10% of Affected Infants are Term Infants* • Up to 10% of NICU Admissions* • Multifactorial Disease • Outbreak - Association with Infection *Fanaroff and Martin: Neonatal-Perinatal Medicine, 7th edition, 2002.

  10. Necrotizing Enterocolitis • Bacteria • Coagulase-Negative Staphylococci, Escherichia coli (including ETEC), Enterobacter spp., Klebsiella spp., Pseudomonas aeruginosa, Salmonella spp., Clostridium difficile, Clostridium perfringens, Clostridium butyricum • Viruses • Rotavirus, Coronavirus Principles and Practice of Pediatric Infectious Diseases

  11. Necrotizing Enterocolitis • Clinical Manifestations • Wide Spectrum of Disease • Sudden or Insidious Onset • Non-Specific Findings • Feeding intolerance, Temperature instability, Lethargy, Apnea, Respiratory Distress, Metabolic Acidosis, Glucose instability, Leukocytosis, Neutropenia, Thrombocytopenia, Shock • GI Findings • Abdominal distention, tenderness and/or erythema, Bilious emesis, Blood in stools (Visible or Microscopic), Disorganized bowel gas pattern, Pneumatosis Intestinalis, Portal Venous Gas, Pneumoperitoneum, Peritoneal Ascites

  12. Necrotizing Enterocolitis • Therapy • Discontinue Feedings/Nasogastric Decompression • Serial Radiographic Examinations • Blood Culture and Antibiotics • IV Fluids/Supportive Care for Systemic Disease • Surgery for Advanced Disease (Roughly 20%)

  13. Necrotizing Enterocolitis • Outcomes • Overall Mortality Rates due to NEC in Last Decade: 9-28% * • Survival 98% for Medical Management • Surgical Mortality Rate 45% ** (range up to 60%) * • Inversely Related to Gestational Age and Size • GI strictures 25%-35%, after Medical or Surgical Therapy * • GI Dysfunction (10%) • Neurodevelopmental Sequelae (15-33%) • Short Gut Syndrome * Fanaroff and Martin: Neonatal-Perinatal Medicine, 7th edition, 2002. ** Grosfeld JL et al., J Pediatr Surg 1998 July;33(7):967-72

  14. Bacteremia/Sepsis • Bacteremia - Bacteria in the Blood • Occurs with Many Infections • Meningitis and NEC • Sepsis - Clinical Syndrome • Shock, Fever, Systemic Illness • Associated with Morbidity and Mortality

  15. Bacteremia/Sepsis • Opportunistic Pathogen • Neonate/Prematurity • Meningitis and NEC Cases; • 7 d/o with Fever/Sepsis; Hospitalized • Cancer/Central Line • 3 y/o Rhabdomyosarcoma; Recovered with Antibiotics and Line Removal • Altered Host Defense • 6 m/o Intestinal Resection; Recovered with Abx

  16. Conclusions • Enterobacter sakazakii • Cause of Meningitis, NEC, Bacteremia • Serious Morbidity and Mortality • Especially in Neonatal Disease

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