What is the treatment protocol for severe central nervous system (CNS) melioidosis?

Treatment Protocol for Severe Central Nervous System (CNS) Melioidosis

For severe CNS melioidosis, the recommended treatment protocol is intravenous meropenem for at least 14 days in the intensive phase, followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 3-6 months in the eradication phase. 1

Initial Intensive Phase Treatment

First-line therapy:

• Meropenem: 2g IV every 8 hours (preferred for CNS melioidosis)
  • Duration: Minimum 4 weeks for CNS involvement, may require longer based on clinical response
  • Rationale: Superior penetration into CNS and better outcomes than ceftazidime for severe melioidosis 1

Alternative options if meropenem unavailable:

• Ceftazidime: 2g IV every 6-8 hours
• Imipenem: 1g IV every 6-8 hours (use with caution due to increased risk of seizures in CNS infections)

Adjunctive treatments:

• Consider surgical drainage/debridement of brain abscesses if present
• Management of increased intracranial pressure if present
• Anticonvulsant therapy if seizures occur

Eradication Phase Treatment

After completion of intensive phase:

• TMP-SMX: 8/40 mg/kg/day divided into 2-3 doses orally
  • Duration: 3-6 months (minimum 3 months for CNS involvement)
  • Monitor for adverse effects: rash, bone marrow suppression, hyperkalemia

Alternative for TMP-SMX intolerance:

• Amoxicillin-clavulanate: Note that this is less effective than TMP-SMX 1
• Doxycycline (for patients >8 years old): Can be combined with TMP-SMX but not recommended as monotherapy 1

Monitoring During Treatment

• Regular neurological assessment
• Serial imaging (MRI preferred) to monitor abscess resolution
• Blood cultures to confirm clearance of bacteremia
• Renal function monitoring (especially with meropenem)
• Clinical parameters: fever, headache, focal neurological deficits

Special Considerations

Dosage adjustments:

• Adjust meropenem dosing based on renal function:

  Creatinine Clearance (mL/min)	Dose	Interval
  >50	Full dose	Every 8 hours
  26-50	Full dose	Every 12 hours
  10-25	Half dose	Every 12 hours
  <10	Half dose	Every 24 hours

Important caveats:

1. B. pseudomallei is inherently resistant to penicillin, ampicillin, first/second-generation cephalosporins, gentamicin, and polymyxin 1
2. Avoid ertapenem, azithromycin, and moxifloxacin as Malaysian isolates showed resistance to these agents 1
3. CNS melioidosis may initially mimic malignancy or stroke, requiring high clinical suspicion 2
4. Treatment failure rates are higher with ceftriaxone or cefotaxime compared to ceftazidime 1
5. Mortality remains high despite appropriate therapy, particularly with disseminated disease 3

Treatment Duration

• Intensive phase: Minimum 4 weeks for CNS involvement, longer if clinical improvement is slow
• Eradication phase: Minimum 3 months, typically 3-6 months 1
• Total treatment duration may extend beyond 6 months for persistent or recurrent disease

Outcome Measures

Monitor for:

• Resolution of fever and neurological symptoms
• Radiographic improvement on serial imaging
• Negative blood cultures
• Prevention of relapse (which carries high mortality)

Early diagnosis and aggressive treatment are critical for improving survival and reducing long-term neurological sequelae in patients with CNS melioidosis.