What is the treatment for melioidosis?

Treatment of Melioidosis

Treat melioidosis with intravenous meropenem or imipenem for at least 14 days (intensive phase), followed by oral trimethoprim-sulfamethoxazole for 3-6 months (eradication phase), with carbapenems preferred over ceftazidime for severe disease based on superior clinical outcomes. 1

Intensive Phase Treatment (Initial Parenteral Therapy)

First-Line Agents

• Meropenem or imipenem are the preferred agents for severe melioidosis, demonstrating better clinical outcomes than ceftazidime in observational data 1
• All clinical B. pseudomallei isolates show consistent susceptibility to carbapenems 1
• Standard dosing: meropenem 1 g (or 25 mg/kg) IV every 8 hours for ≥14 days 2
• Ceftazidime (100 mg/kg/day) remains an acceptable alternative if carbapenems are unavailable, though it is now considered second-line 1

Duration Considerations

• Minimum 14 days for uncomplicated cases 1, 3
• Extend to 4-8 weeks or longer for:
  • Critical illness or septic shock 1
  • Extensive pulmonary disease 1
  • Deep-seated abscesses or organ collections 1
  • Osteomyelitis or septic arthritis 1
  • Central nervous system involvement 1
• Recent Australian data suggests median intensive phase duration of 26 days may reduce recrudescence rates to 5.1% 4

Adjunctive Therapy

• For melioidosis-induced septic shock, consider adding G-CSF 300 mg IV for 10 days during the intensive phase 1, 5

Eradication Phase Treatment (Oral Maintenance Therapy)

Standard Regimen

• TMP-SMX is the drug of choice for eradication therapy 1, 3
• Duration: 3-6 months (20 weeks standard) 1, 3
• TMP-SMX monotherapy for 20 weeks is as effective as combination therapy with doxycycline in preventing recurrence 1

Weight-Based Dosing of TMP-SMX

• <40 kg: 160/800 mg (1 double-strength tablet) twice daily 1
• 40-60 kg: 240/1200 mg (1.5 double-strength tablets) twice daily 1
• >60 kg: 320/1600 mg (2 double-strength tablets) twice daily 1
• Add folic acid 0.1 mg/kg up to 5 mg daily to prevent antifolate effects without compromising antimicrobial activity 1

Extended Duration Indications

• CNS involvement: Use higher TMP-SMX dosing at 8/40 mg/kg IV/PO every 12 hours (up to 320/1600 mg) and extend duration to 4-8 weeks or longer 1
• Osteomyelitis or septic arthritis: Extend both intensive and eradication phases 1

Alternative Eradication Regimens

• Amoxicillin-clavulanate is the preferred alternative for pregnant women, children, or patients intolerant to TMP-SMX, though it is significantly less effective than first-line therapy 1, 6
• Dosing: 20/5 mg/kg every 8 hours (maximum 1500/375 mg every 8 hours) 1
• Doxycycline 100 mg twice daily can be used as an alternative if TMP-SMX is contraindicated 1

Critical Resistance Patterns and Pitfalls

Inherent Resistance

• B. pseudomallei is inherently resistant to: penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, streptomycin, polymyxin, ertapenem, azithromycin, and moxifloxacin 1, 3
• Avoid ceftriaxone and cefotaxime as these agents are associated with higher mortality rates compared to ceftazidime 1

Common Pitfalls

• Delays in appropriate therapy lead to poor outcomes; treatment should begin immediately upon suspicion 1
• The 13% relapse rate seen over 10 years emphasizes the critical importance of completing the full 3-6 month eradication phase 1
• Recrudescence (recurrence during eradication phase) occurs in 5.1% of patients, with self-discharge during intensive phase being a major risk factor 4

Post-Exposure Prophylaxis

• Administer TMP-SMX (co-trimoxazole) within 24 hours of exposure for post-exposure prophylaxis, particularly for immunosuppressed patients or following potential biological attack 1, 5
• Animal studies demonstrate 100% survival when co-trimoxazole is given within 24 hours post-infection 5