What is the recommended dose of Septarn (co-trimoxazole) for the treatment of melioidosis?

Dosing of Trimethoprim-Sulfamethoxazole (Septarn) for Melioidosis

For the eradication phase of melioidosis treatment, the recommended dose of Septarn (co-trimoxazole) for adults is a double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) twice daily for 3-6 months. 1

Treatment Protocol for Melioidosis

Melioidosis treatment consists of two distinct phases:

Initial Intensive Phase

• Intravenous antibiotics for at least 14 days 2, 1
• First-line options include:
  • Ceftazidime (100 mg/kg/day) 2
  • Meropenem or imipenem (preferred for severe cases) 3, 1
• Longer intensive treatment required for:
  • Critical illness 1
  • Extensive pulmonary disease 1
  • Deep-seated collections or organ abscesses 1
  • Osteomyelitis 1
  • Septic arthritis 1
  • Neurologic melioidosis 1

Eradication Phase

• TMP-SMX (Septarn) is the drug of choice for the eradication phase 1, 4
• Weight-based dosing recommendations:
  • <40 kg: 160/800 mg (TMP/SMX) twice daily 5
  • 40-60 kg: 240/1,200 mg (TMP/SMX) twice daily 5

  • 60 kg: 320/1,600 mg (TMP/SMX) twice daily 5

• Duration: 3-6 months 2, 1

Evidence Supporting TMP-SMX Use

• TMP-SMX monotherapy for 20 weeks has been shown to be as effective as combination therapy with TMP-SMX plus doxycycline in preventing relapse 2
• A randomized trial demonstrated that a three-drug regimen (TMP-SMX and doxycycline) was as effective as and better tolerated than a four-drug regimen (TMP-SMX, doxycycline, and chloramphenicol) 4
• Pharmacokinetic studies show that weight-based dosing achieves adequate concentrations for strains with MICs ≤1/19 mg/liter 5

Alternative Treatment Options

• If TMP-SMX is not tolerated or contraindicated, alternatives include:
  • Amoxicillin-clavulanate 2, 1
  • Doxycycline 2, 1

Important Clinical Considerations

• B. pseudomallei is inherently resistant to many antibiotics, including penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, streptomycin, and polymyxin 2, 1
• Duration of oral therapy significantly affects relapse rates; patients receiving less than 12 weeks of therapy have a 5.7-fold increase in relapse or death 4
• In vitro studies have shown that trimethoprim and sulfamethoxazole can antagonize the bacteriostatic activity of chloramphenicol and doxycycline, which may affect combination therapy choices 6

Special Populations

• For pregnant women with Q fever (which has similar treatment considerations), long-term co-trimoxazole therapy (320 mg trimethoprim and 1600 mg sulfamethoxazole for 35 days) is recommended to decrease the risk of complications 2
• For children, the WHO recommends co-trimoxazole at a dose of 4 mg/kg trimethoprim plus 20 mg/kg sulfamethoxazole twice daily for various infections 2

Monitoring and Follow-up

• Regular monitoring for adverse effects is essential as TMP-SMX can cause rash, gastrointestinal disturbances, and hematological abnormalities 4
• In clinical trials, 19% of patients required a switch in therapy due to side effects of the three-drug regimen (TMP-SMX plus doxycycline) 4