• Citrobacter species are Gram-negative, facultatively anaerobic bacilli from the Enterobacteriaceae family.
  • They are rare but serious pathogens in neonates, predominantly affecting the central nervous system (CNS).

Common Species and CNS Involvement

  • Citrobacter koseri (formerly Citrobacter diversus) is responsible for over 90% of Citrobacter meningitis cases in neonates.
  • Citrobacter freundii contributes to about 6.4% of cases.
  • Unlike other Gram-negative meningitides, Citrobacter is associated with brain abscess formation in approximately 75% of affected neonates.

Pathogenesis and Neurovirulence

  • Infection usually begins with bacteremia and progresses to leptomeningitis, ventriculitis, and abscess formation.
  • Citrobacter can disrupt the ependymal lining and directly invade adjacent brain tissue.
  • C. freundii can invade and replicate in human brain microvascular endothelial cells.
  • Outer membrane proteins may contribute to the organism’s neurovirulence.

Modes of Transmission

  • Vertical transmission from the mother is suspected in early-onset disease and supported by evidence of maternal infection.
  • Horizontal (nosocomial) transmission is more common in late-onset disease and often linked to NICU outbreaks.
  • Outbreaks have been traced to contaminated infant formula and colonized hospital staff.
  • Case reports describe infections in dizygotic twins, highlighting risk to asymptomatic co-twins.

Imaging and Diagnosis

  • High risk of abscess mandates neuroimaging in all proven Citrobacter meningitis cases.
  • Bedside cranial ultrasound is useful for unstable neonates.
  • MRI is the preferred modality; CT can be used when MRI is unavailable.
  • Serial imaging helps monitor disease progression and response to treatment.

Antibiotic Therapy

  • Empiric antibiotics include:
    • Third-generation cephalosporins
    • Imipenem
    • Chloramphenicol
    • Trimethoprim–sulfamethoxazole
    • Gentamicin
  • Combination of ciprofloxacin and meropenem is suggested for brain abscess due to better CNS penetration and sensitivity profile.
  • Fluoroquinolones should be avoided in neonates due to risk of arthropathy in weight-bearing joints.
  • Duration of treatment:
    • Minimum of 21 days for meningitis (or 14 days after negative cultures).
    • 4–6 weeks of antibiotics for brain abscess.

Surgical Management

  • Neurosurgical consultation is essential for aspiration or drainage of abscesses.
  • Goals of surgery:
    • Relieve mass effect
    • Reduce bacterial load
    • Improve antibiotic efficacy
  • Aspiration may be difficult in cases with multiple or inaccessible abscesses.
  • Some cases may be successfully treated with antibiotics alone.
  • Intrathecal or intra-abscess antibiotics have not been proven to improve outcomes.

Outcomes and Prognosis

  • Mortality rate is approximately 30% despite therapy.
  • Nearly two-thirds of survivors have long-term neurological impairments.

Conclusion

  • Citrobacter meningitis is rare but devastating in neonates due to its strong association with brain abscess formation.
  • Early diagnosis, serial imaging, prompt antibiotic therapy, and surgical intervention are key to improving outcomes.
  • All survivors should undergo long-term neurodevelopmental follow-up.