Treatment of Melioidosis
Treat melioidosis with a two-phase approach: an intensive phase using IV meropenem or imipenem for at least 14 days, followed by an eradication phase with weight-based TMP-SMX for 3-6 months. 1
Intensive Phase (Initial Treatment)
First-Line Therapy
- Carbapenems (meropenem or imipenem) are the preferred agents for severe melioidosis, demonstrating superior clinical outcomes compared to ceftazidime 1
- Administer IV meropenem or imipenem for a minimum of 14 days 1, 2
- All clinical B. pseudomallei isolates show consistent susceptibility to carbapenems 1
Extended Intensive Phase Duration
Extend IV carbapenem therapy to 4-8 weeks or longer for: 1
- Deep-seated abscesses or organ collections
- Osteomyelitis or septic arthritis
- Central nervous system involvement
- Extensive pulmonary disease
- Critical illness or septic shock
Alternative Intensive Phase Agent
- Ceftazidime 100 mg/kg/day IV is an acceptable alternative if carbapenems are unavailable, though observational data favor meropenem for severe disease 1
- Continue ceftazidime for at least 14 days 1
Adjunctive Therapy for Septic Shock
- Consider adding G-CSF 300 mg IV for 10 days during the intensive phase for melioidosis-induced septic shock 1, 3
Eradication Phase (Maintenance Treatment)
Standard Regimen
TMP-SMX monotherapy is the drug of choice for eradication, with weight-based dosing for 3-6 months: 1, 2
- <40 kg: 160/800 mg (1 double-strength tablet) twice daily
- 40-60 kg: 240/1200 mg (1.5 double-strength tablets) twice daily
- >60 kg: 320/1600 mg (2 double-strength tablets) twice daily
Critical Supplementation
- Add folic acid 0.1 mg/kg up to 5 mg daily to prevent antifolate effects without compromising antimicrobial activity 1
Evidence Supporting Duration
- TMP-SMX monotherapy for 20 weeks is as effective as combination therapy with TMP-SMX plus doxycycline in preventing recurrence 1
- The 3-6 month duration is critical for eradicating intracellular bacteria and preventing the 13% relapse rate seen over 10 years 1
Extended Eradication Phase
Extend eradication therapy to 4-8 weeks or longer for: 1
- Central nervous system involvement (use higher TMP-SMX dosing: 8/40 mg/kg IV/PO every 12 hours up to 320/1600 mg)
- Osteomyelitis or septic arthritis
Alternative Eradication Regimens
For TMP-SMX Intolerance or Contraindications
- Amoxicillin-clavulanate 20/5 mg/kg every 8 hours (maximum 1500/375 mg every 8 hours) is the preferred alternative for pregnant women, children, or patients intolerant to TMP-SMX 1
- Important caveat: Amoxicillin-clavulanate is significantly less effective than TMP-SMX 1, 3
- Doxycycline 100 mg twice daily can be used as an alternative if TMP-SMX is contraindicated 1
Critical Resistance Patterns to Avoid
B. pseudomallei is inherently resistant to: 1, 2
- Penicillin and ampicillin
- First- and second-generation cephalosporins
- Gentamicin and streptomycin
- Polymyxin
- Ertapenem (despite being a carbapenem)
- Azithromycin and moxifloxacin
Specific Agents Associated with Higher Mortality
- Avoid ceftriaxone and cefotaxime, as these agents are associated with higher mortality rates compared to ceftazidime 1
Post-Exposure Prophylaxis
- Administer TMP-SMX (co-trimoxazole) within 24 hours of exposure for post-exposure prophylaxis 1, 2
- Particularly important for immunosuppressed patients or following potential biological attack 1, 2
- Animal studies demonstrate 100% survival when co-trimoxazole is administered within 24 hours post-infection 3
Common Pitfalls
Diagnostic Delays
- B. pseudomallei can be misidentified by automated systems like VITEK, leading to delays in appropriate therapy and poor outcomes 1
- Treatment should be continued until confirmation by more reliable methods 1
Inadequate Treatment Duration
- The lengthy eradication phase is essential; premature discontinuation leads to relapse 1
- Do not use "step-down" dosing—maintain full therapeutic doses throughout the eradication phase 1