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

• 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

Neonatal Meningitis

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

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

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

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

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

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.

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

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

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%)

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

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

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

Conclusions

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