What is the recommended treatment approach for melioidosis?

Melioidosis Treatment

For melioidosis, initiate treatment with intravenous meropenem or imipenem for at least 14 days (longer for severe disease), followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 3-6 months to prevent relapse. 1, 2

Intensive Phase (Initial Parenteral Therapy)

First-Line Agents

• Meropenem or imipenem are the preferred agents for severe melioidosis, demonstrating superior clinical outcomes compared to ceftazidime in severe disease 1, 2
• Standard dosing: Meropenem 2g IV every 8 hours or imipenem at equivalent dosing 3
• Minimum duration: 14 days, but extend for critical illness, extensive pulmonary disease, deep-seated abscesses, osteomyelitis, septic arthritis, or neurologic involvement 1, 2

Alternative Agent

• Ceftazidime 100 mg/kg/day (typically 2g every 6 hours) remains acceptable if carbapenems are unavailable, though observational data favor carbapenems 1, 2, 4
• Ceftazidime has been the historical standard based on Thai clinical trials over 25 years 4, 5

Adjunctive Therapy for Septic Shock

• Consider adding G-CSF 300 mg IV for 10 days in patients with melioidosis-induced septic shock 2, 6

Eradication Phase (Oral Maintenance Therapy)

First-Line Regimen

• TMP-SMX is the drug of choice for eradication phase 1, 2, 6
• Weight-based dosing for adults:
  • <40 kg: 160/800 mg (1 double-strength tablet) twice daily 2
  • 40-60 kg: 240/1200 mg (1.5 double-strength tablets) twice daily 2

  • 60 kg: 320/1600 mg (2 double-strength tablets) twice daily 2

• Add folic acid 0.1 mg/kg up to 5 mg daily to prevent antifolate effects 2
• Duration: 3-6 months (extend to 4-8 months for CNS involvement, osteomyelitis, or septic arthritis) 1, 2, 5

Evidence Supporting TMP-SMX Monotherapy

• TMP-SMX monotherapy for 20 weeks is as effective as combination therapy with TMP-SMX plus doxycycline in preventing the 13% relapse rate seen over 10 years 2, 5

Alternative Regimens

• Amoxicillin-clavulanate 20/5 mg/kg every 8 hours (maximum 1500/375 mg every 8 hours) for pregnant women, children, or patients intolerant to TMP-SMX, though significantly less effective than first-line therapy 1, 2, 6, 5
• Doxycycline can be used as an alternative if TMP-SMX is contraindicated 1, 2

Critical Antibiotic Resistance Patterns

Inherent Resistance (Avoid These Agents)

• B. pseudomallei is inherently resistant to: penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, streptomycin, polymyxin, ertapenem, azithromycin, and moxifloxacin 1, 2, 6
• Avoid ceftriaxone and cefotaxime, as these are associated with higher mortality rates compared to ceftazidime 2

Acquired Resistance

• TMP-SMX resistance rates: approximately 2.5% in Australia and 13-16% in Thailand 5
• Resistance to ceftazidime and carbapenems remains rare 5

Special Clinical Scenarios

Central Nervous System Involvement

• Add TMP-SMX 8/40 mg/kg IV/PO every 12 hours up to 320/1600 mg during intensive phase 2
• Extend eradication phase to 4-8 weeks or longer 2

Musculoskeletal Infections

• Sacroiliitis, osteomyelitis, and septic arthritis require extended intensive phase therapy and prolonged eradication (4-8 months) 2, 3
• Surgical drainage of abscesses is essential whenever possible 4, 3, 7

Pregnancy

• Use amoxicillin-clavulanate instead of TMP-SMX for eradication phase 2, 6, 5
• Carbapenems remain safe for intensive phase 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, 6
• Animal studies demonstrate 100% survival when co-trimoxazole is given within 24 hours post-infection 6
• Pre-exposure prophylaxis with doxycycline shows 80% survival and co-trimoxazole shows 100% survival in animal models 6
• Amoxicillin-clavulanic acid is not suitable as prophylaxis based on animal studies 6

Common Pitfalls to Avoid

• Do not use monotherapy with inadequate duration: the 3-6 month eradication phase is critical to prevent the 13% relapse rate 2, 5
• Do not delay appropriate therapy: misidentification by automated systems (e.g., VITEK) can lead to treatment delays and poor outcomes 2
• Do not use ertapenem: unlike meropenem and imipenem, B. pseudomallei is resistant to ertapenem 2, 6
• Do not dismiss as culture contaminant: B. pseudomallei can be confused with closely related bacteria and mistakenly dismissed 7

Diagnostic Considerations

• Use selective culture media such as Ashdown's agar to increase yield of B. pseudomallei from clinical specimens, which is highly cost-effective in endemic areas 2
• Blood, sputum, and other clinical samples readily grow B. pseudomallei, but reliable identification requires careful laboratory protocols 7
• Serological tests can support diagnosis but do not provide definitive confirmation 7