What is the treatment for Naegleria fowleri meningitis?

Treatment for Naegleria fowleri Meningitis

The treatment of Naegleria fowleri meningitis should include a combination therapy with amphotericin B (intravenous and intrathecal), miltefosine, and rifampin, administered as soon as possible after diagnosis is suspected. 1, 2, 3

Understanding Naegleria fowleri Infection

Naegleria fowleri is a free-living amoeba that causes primary amoebic meningoencephalitis (PAM), a fulminant and nearly always fatal infection of the brain. The mortality rate exceeds 95%, with only a few documented survivors worldwide 1. This thermophilic organism thrives in warm freshwater, with most infections occurring after exposure to standing bodies of freshwater during summer months.

Clinical Presentation

PAM presents similarly to bacterial meningitis but does not respond to standard antibiotic therapy. Key features include:

• Rapid onset of symptoms after water exposure
• Headache, fever, nausea, vomiting
• Altered mental status progressing to coma
• Death typically occurs within 5 days of symptom onset due to cerebral edema 1

Diagnostic Approach

Early diagnosis is critical for survival. Consider PAM in any patient with:

• Rapidly progressive meningoencephalitis
• Recent freshwater exposure (swimming, diving, nasal irrigation)
• CSF showing pleocytosis with negative bacterial cultures

Diagnosis is confirmed by identification of motile amoebae in CSF wet mount preparations.

Treatment Protocol

First-line Therapy (Start Immediately)

1. Amphotericin B:

   • Intravenous: 1.5 mg/kg/day in divided doses
   • Intrathecal: 1-1.5 mg daily 1, 4

2. Miltefosine:

   • Adults >45 kg: 50 mg orally three times daily
   • Children and adults <45 kg: 50 mg orally twice daily 2, 3, 5

3. Rifampin:

   • 10 mg/kg/day (maximum 600 mg daily) 1, 4

Additional Agents to Consider

• Azithromycin or other macrolides
• Fluconazole
• Sulfadiazine

Management of Complications

Aggressive management of increased intracranial pressure is essential:

• Therapeutic hypothermia
• Hyperventilation
• Osmotic diuretics (mannitol)
• External ventricular drainage if hydrocephalus develops 2

Factors Associated with Survival

Recent survivor cases suggest several critical factors for successful treatment:

1. Early diagnosis and rapid initiation of treatment
2. Use of combination antimicrobial therapy including miltefosine
3. Aggressive management of increased intracranial pressure 2, 5

Monitoring and Follow-up

• Daily neurological examinations
• Serial neuroimaging to assess for complications
• Audiological evaluation during recovery (hearing loss is a common sequela of CNS infections) 6

Prevention Strategies

• Avoid swimming in warm freshwater during hot periods
• Use nose clips when swimming in freshwater
• Do not use untreated tap water for nasal irrigation or religious nasal ablution 1

Important Caveats

1. Treatment must be initiated as early as possible, ideally within hours of presentation
2. The combination of amphotericin B, miltefosine, and rifampin has been associated with the highest survival rates in recent cases
3. Miltefosine has emerged as a crucial component of successful treatment regimens and should be obtained emergently if PAM is suspected 3, 5

PAM remains an extremely challenging infection with high mortality, but recent survivor cases demonstrate that with prompt diagnosis, aggressive combination antimicrobial therapy, and management of increased intracranial pressure, survival is possible.