What is the recommended treatment for melioidosis?

Treatment of Melioidosis

The recommended treatment for melioidosis consists of an initial intensive phase with intravenous ceftazidime or a carbapenem (meropenem or imipenem) for at least 14 days, followed by an eradication phase with oral trimethoprim-sulfamethoxazole (TMP-SMX) for 3-6 months. 1, 2, 3, 4

Initial Intensive Phase

• For severe melioidosis, intravenous meropenem is preferred due to better clinical outcomes compared to ceftazidime 1, 3, 4

• Ceftazidime (100 mg/kg/day) is an effective first-line option when carbapenems are not available 2, 3

• Minimum duration is 14 days, but longer treatment is required for patients with: 2, 3, 4

  • Critical illness
  • Extensive pulmonary disease
  • Deep-seated collections or organ abscesses
  • Osteomyelitis
  • Septic arthritis
  • Neurologic melioidosis

• For patients with melioidosis-induced septic shock, meropenem plus granulocyte colony-stimulating factor (G-CSF) has been used successfully 1

• All clinical isolates of B. pseudomallei have shown consistent susceptibility to carbapenems 3, 5

Eradication Phase

• TMP-SMX is the drug of choice for the eradication phase to prevent recrudescence or relapses 1, 2, 3, 4
• Standard dosing for adults: double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) twice daily 4
• Duration of eradication phase: 3-6 months 1, 2, 3, 4
• TMP-SMX monotherapy for 20 weeks has been shown to be as effective as combination therapy with TMP-SMX plus doxycycline 1, 2

Alternative Treatment Options

• For patients who cannot tolerate TMP-SMX, alternatives include: 1, 2, 4

  • Amoxicillin-clavulanate (less effective)
  • Doxycycline

• For pregnant women, children, and patients with intolerance to first-line therapy, amoxicillin-clavulanate is recommended 1

Important Clinical Considerations

• B. pseudomallei is inherently resistant to many antibiotics, including: 1, 3, 4

  • Penicillin
  • Ampicillin
  • First- and second-generation cephalosporins
  • Gentamicin
  • Streptomycin
  • Polymyxin

• Most strains are resistant to ertapenem, azithromycin, and moxifloxacin, which should not be used for treatment 1

• Drainage of abscesses is crucial whenever possible 6

• Despite the low frequency of β-lactam resistance (caused by penA alterations), resistant variants may emerge during antibiotic therapy 5

• Treatment failures with ceftriaxone or cefotaxime have been reported despite in vitro susceptibility, so these agents should be avoided 1

Treatment Algorithm

1. Assess severity:

   • For severe disease (septic shock, extensive pulmonary involvement, neurologic involvement): Start with meropenem 1, 3
   • For less severe disease: Start with ceftazidime 2, 4

2. Initial intensive phase:

   • Continue IV antibiotics for minimum 14 days 1, 2, 3
   • Extend treatment for complicated cases (deep abscesses, osteomyelitis, etc.) 2, 4

3. Transition to eradication phase:

   • Switch to oral TMP-SMX when clinically improved 1, 2, 4
   • Continue for 3-6 months 1, 4

4. Monitor for treatment failure:

   • If clinical deterioration occurs, switch to meropenem if patient was on ceftazidime 3, 5
   • Consider drug resistance if poor response to appropriate therapy 5