Bactrim Single Strength Dosing for Melioidosis
For melioidosis eradication therapy, single-strength Bactrim tablets (80 mg trimethoprim/400 mg sulfamethoxazole) should be dosed based on body weight: patients <40 kg receive 2 tablets (160/800 mg) twice daily, patients 40-60 kg receive 3 tablets (240/1200 mg) twice daily, and patients >60 kg receive 4 tablets (320/1600 mg) twice daily for 3-6 months. 1
Weight-Based Dosing Algorithm
The current evidence-based approach uses weight stratification to optimize therapeutic drug levels:
- <40 kg body weight: 2 single-strength tablets (160/800 mg total) twice daily 1
- 40-60 kg body weight: 3 single-strength tablets (240/1200 mg total) twice daily 1
- >60 kg body weight: 4 single-strength tablets (320/1600 mg total) twice daily 1
This weight-based regimen replaced the older fixed-dose Thai protocol (160/800 mg twice daily for all patients) because pharmacokinetic modeling demonstrated that the previous regimen failed to achieve adequate drug concentrations for strains with MIC ≥1/19 mg/liter in many patients. 2
Treatment Duration and Phase
Eradication phase duration: The standard duration is 3-6 months following completion of the intensive intravenous phase. 1, 3 Recent high-quality evidence from a randomized controlled trial of 658 patients demonstrated that 12 weeks of TMP-SMX monotherapy is non-inferior to 20 weeks for the composite endpoint of recurrence and mortality, with significantly lower all-cause mortality in the 12-week group (0.3% vs 3%, HR 0.10). 4 However, extend treatment to 4-8 weeks or longer for CNS involvement, osteomyelitis, or septic arthritis. 1
Monotherapy is sufficient: TMP-SMX monotherapy for 20 weeks is as effective as combination therapy with TMP-SMX plus doxycycline in preventing relapse, with better tolerability. 5 A trial of 626 patients showed non-inferiority of TMP-SMX alone versus TMP-SMX plus doxycycline (5% vs 7% recurrence rate, HR 0.81), with fewer adverse reactions (39% vs 53%). 5
Folic Acid Supplementation
Add folic acid 0.1 mg/kg up to 5 mg daily to prevent antifolate effects without compromising antimicrobial activity. 1 This is particularly important given the prolonged treatment duration required for melioidosis eradication.
Special Populations and Alternatives
Pregnancy and sulfonamide allergy: If TMP-SMX is contraindicated, use amoxicillin-clavulanate 20/5 mg/kg every 8 hours (maximum 1500/375 mg every 8 hours), though this is significantly less effective than TMP-SMX. 1, 3 Doxycycline can be added to amoxicillin-clavulanate in non-pregnant patients with true sulfonamide allergy. 1
CNS involvement: For central nervous system melioidosis, increase TMP-SMX dosing to 8/40 mg/kg IV/PO every 12 hours (up to 320/1600 mg), which translates to 4 single-strength tablets every 12 hours for a 60 kg patient. 1 Extend duration to 4-8 weeks or longer. 1
Critical Pitfalls to Avoid
Do not use doxycycline monotherapy: A randomized trial of 87 evaluable patients demonstrated that doxycycline alone resulted in 25.6% culture-confirmed relapse versus 2.3% with the conventional regimen (P = 0.009). 6 Doxycycline monotherapy cannot be recommended as first-line therapy. 6
Avoid inadequate treatment duration: Patients receiving less than 12 weeks of oral therapy had a 5.7-fold increased risk of relapse or death after adjustment for confounders. 7 The 3-6 month duration is critical for eradicating intracellular bacteria and preventing the 13% relapse rate seen over 10 years. 1
Inherent resistance patterns: B. pseudomallei is inherently resistant to penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, streptomycin, polymyxin, ertapenem, azithromycin, and moxifloxacin. 1, 3 Never use these agents for melioidosis treatment.
Integration with Intensive Phase
The eradication phase with oral TMP-SMX follows at least 14 days of intravenous therapy with meropenem, imipenem, or ceftazidime. 1, 8 For severe melioidosis with septic shock, consider adding G-CSF 300 mg IV for 10 days during the intensive phase. 1