What is the recommended treatment for melioidosis?

Melioidosis Treatment

Treat melioidosis with a two-phase approach: an intensive phase using intravenous meropenem or imipenem for at least 14 days, followed by an eradication phase with oral trimethoprim-sulfamethoxazole (TMP-SMX) for 3-6 months. 1

Intensive Phase (Intravenous Therapy)

First-Line Treatment

• Carbapenems (meropenem or imipenem) are the preferred agents for severe melioidosis, demonstrating superior clinical outcomes compared to ceftazidime 1, 2
• Administer for a minimum of 14 days, but extend duration for patients with:
  • Critical illness or septic shock 1
  • Extensive pulmonary disease 1
  • Deep-seated abscesses or organ involvement 1
  • Osteomyelitis or septic arthritis 1
  • Central nervous system involvement 1

Alternative Intensive Phase Options

• Ceftazidime (100 mg/kg/day) remains acceptable if carbapenems are unavailable, though observational data favor meropenem in severe disease 1
• Amoxicillin-clavulanate is significantly less effective but may be used as second-line therapy 1, 3

Critical Resistance Patterns to Avoid

• Never use ertapenem, azithromycin, or moxifloxacin due to inherent resistance 1, 3
• Avoid ceftriaxone and cefotaxime, as these are associated with higher mortality rates 1
• B. pseudomallei is inherently resistant to penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, streptomycin, and polymyxin 1, 2

Adjunctive Therapy for Severe Disease

• For melioidosis-induced septic shock, consider adding granulocyte colony-stimulating factor (G-CSF) 300 mg IV for 10 days during the intensive phase 1, 3

Eradication Phase (Oral Therapy)

Standard Eradication Regimen

• TMP-SMX is the drug of choice for the eradication phase, administered for 3-6 months to prevent the 13% relapse rate seen over 10 years 1, 2
• TMP-SMX monotherapy for 20 weeks is as effective as combination therapy with TMP-SMX plus doxycycline 1

Weight-Based TMP-SMX Dosing

• Adults <40 kg: 160/800 mg (1 double-strength tablet) twice daily 1
• Adults 40-60 kg: 240/1200 mg (1.5 double-strength tablets) twice daily 1
• Adults >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

• Extend eradication phase to 4-8 months or longer for:
  • Central nervous system involvement (use TMP-SMX 8/40 mg/kg IV/PO every 12 hours up to 320/1600 mg) 1
  • Osteomyelitis or septic arthritis 1

Alternative Eradication Regimens

• 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, though significantly less effective than first-line therapy 1, 3
• Doxycycline can be used as an alternative if TMP-SMX is contraindicated 1, 2

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, 3
• Animal studies demonstrate 100% survival when co-trimoxazole is given within 24 hours post-infection 3
• Amoxicillin-clavulanic acid is not suitable as prophylaxis based on animal studies 3

Common Pitfalls

• Delays in appropriate therapy lead to poor outcomes; treatment should begin immediately upon suspicion, even before confirmation by reliable identification methods 1
• B. pseudomallei can be misidentified by automated systems like VITEK, leading to inappropriate antibiotic selection 1
• Selective culture media such as Ashdown's agar significantly increases yield from clinical specimens in endemic areas 1
• The two-phase treatment approach is critical—premature discontinuation of eradication therapy increases relapse risk 1, 4