What is the recommended dosing of Trimethoprim (TMP) / Sulphamethoxazole (SMX) for the treatment of Melioidosis?

Dosing of Trimethoprim-Sulfamethoxazole for Melioidosis

For melioidosis treatment, trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as the drug of choice for the eradication phase following an initial intensive phase of intravenous antibiotics, with a recommended duration of 3-6 months. 1

Treatment Protocol for Melioidosis

Initial Intensive Phase

• Treatment begins with an intensive phase of at least 14 days using intravenous antibiotics such as ceftazidime, meropenem, or imipenem 1
• Longer intensive treatment is required for patients with critical illness, extensive pulmonary disease, deep-seated collections or organ abscesses, osteomyelitis, septic arthritis, and neurologic melioidosis 1, 2
• Ceftazidime treatment has been shown to reduce mortality by 50% compared to conventional treatment with chloramphenicol, doxycycline, trimethoprim, and sulfamethoxazole 3
• For severe melioidosis, meropenem has demonstrated better clinical outcomes than ceftazidime 1, 2

Eradication Phase

• TMP-SMX is the drug of choice for the eradication phase to prevent recrudescence or relapses 1
• The recommended duration for the eradication phase is 3-6 months 1
• Recent evidence from a randomized controlled trial supports a 12-week regimen of TMP-SMX rather than the previously recommended 20-week regimen in Thailand 4
• TMP-SMX monotherapy is as effective as TMP-SMX plus doxycycline combination therapy, with fewer adverse effects 5

Specific Dosing Recommendations

• The standard dosing of TMP-SMX for melioidosis eradication phase is:

  • Trimethoprim 8 mg/kg/day and Sulfamethoxazole 40 mg/kg/day 6
  • This is typically administered in two divided doses daily 6

• For a typical adult, this translates to:

  • TMP-SMX double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) twice daily 1

Alternative Treatment Options

• Amoxicillin-clavulanate and doxycycline are recommended alternatives for eradication phase therapy if TMP-SMX is not tolerated or contraindicated 1
• Amoxicillin-clavulanate has been evaluated as an alternative oral maintenance treatment for melioidosis with a 67% success rate in a small study 7

Important Clinical Considerations

• B. pseudomallei is inherently resistant to many antibiotics, including penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, streptomycin, and polymyxin 1, 2
• TMP-SMX is also recommended for post-exposure prophylaxis in case of biological attack and for immunosuppressed patients 1
• Compliance with the full course of treatment is essential to prevent relapse, which is a common problem in melioidosis treatment 7

Monitoring and Follow-up

• Regular follow-up is necessary during the eradication phase to monitor for:
  • Treatment adherence 5
  • Adverse drug reactions, which occur in approximately 39% of patients on TMP-SMX monotherapy 5
  • Signs of recurrent infection 4, 5