What is the treatment for melioidosis?

Treatment of Melioidosis

Treat melioidosis 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

Initial 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
• All clinical B. pseudomallei isolates show consistent susceptibility to carbapenems 1
• Minimum duration is 14 days for uncomplicated cases 1, 2

Extended Intensive Phase Duration

Extend intravenous therapy beyond 14 days for:

• Critical illness or septic shock 1, 2
• Extensive pulmonary disease (multi-lobar pneumonia): minimum 3 weeks if single lobe with bacteremia, or bilateral/multi-lobar disease without bacteremia 3
• Multi-lobar pneumonia with concurrent bacteremia: minimum 4 weeks 3
• Deep-seated abscesses or organ collections 1, 2
• Osteomyelitis or septic arthritis 1, 2
• Neurologic involvement 1, 2

Alternative Intensive Phase Agent

• Ceftazidime (100 mg/kg/day) is acceptable if carbapenems are unavailable, though observational data favor meropenem for severe disease 1, 4
• Ceftazidime shows 100% susceptibility in microbial testing 5

Adjunctive Therapy for Severe Disease

• Consider adding G-CSF 300 mg IV for 10 days in melioidosis-induced septic shock 1, 4

Eradication Phase (Oral Therapy)

Standard Regimen

TMP-SMX is the drug of choice for eradication therapy 1, 2, 4

Weight-based dosing:

• <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

Duration:

• Standard: 3-6 months 1, 2, 6
• Extended to 4-8 months or longer for CNS involvement, osteomyelitis, or septic arthritis 1

Add folic acid 0.1 mg/kg up to 5 mg daily to prevent antifolate effects 1

Evidence Supporting TMP-SMX Monotherapy

• TMP-SMX monotherapy for 20 weeks is as effective as combination therapy with TMP-SMX plus doxycycline in preventing recurrence 1, 4
• The prolonged duration is critical for eradicating intracellular bacteria and preventing the 13% relapse rate seen over 10 years 1, 6

Alternative Eradication Regimens

If TMP-SMX is contraindicated or not tolerated:

• 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 with TMP-SMX intolerance 1, 4, 6
• Important caveat: Amoxicillin-clavulanate is significantly less effective than TMP-SMX 1, 4
• Doxycycline can be used as an alternative 1, 2

Special Consideration for CNS Involvement

• For CNS melioidosis, add TMP-SMX 8/40 mg/kg IV/PO every 12 hours up to 320/1600 mg 1

Critical Resistance Patterns and Antibiotics to Avoid

Inherent Resistance

B. pseudomallei is inherently resistant to:

• Penicillin, ampicillin 1, 2, 4
• First- and second-generation cephalosporins 1, 2, 4
• Gentamicin, streptomycin, polymyxin 1, 2, 4
• Ertapenem (despite being a carbapenem) 1, 4
• Azithromycin and moxifloxacin 1, 4

High-Risk Antibiotics

Avoid ceftriaxone and cefotaxime—these third-generation cephalosporins are associated with higher mortality rates compared to ceftazidime 1

Acquired Resistance Rates

• TMP-SMX resistance: approximately 2.5% in Australia and 13-16% in Thailand 6
• Resistance to ceftazidime and carbapenems remains rare 6, 5

Post-Exposure Prophylaxis

Administer TMP-SMX (co-trimoxazole) within 24 hours of exposure for post-exposure prophylaxis, particularly for:

• Immunosuppressed patients 1, 4
• Potential biological attack scenarios 1, 2, 4
• Animal studies demonstrate 100% survival when administered within 24 hours post-infection 4

Common Pitfalls to Avoid

Diagnostic Delays

• Average time to culture confirmation is 5.8 days, but only 39.4% of patients receive appropriate empirical therapy (ceftazidime or carbapenem) before confirmation 5
• In endemic areas with compatible clinical presentation, start empirical anti-melioidosis therapy early rather than waiting for culture confirmation 1, 5

Inadequate Treatment Duration

• Premature discontinuation of eradication therapy leads to relapse 1, 6
• Unrecognized osteomyelitis is an important cause of relapse—ensure thorough evaluation for bone involvement 3
• Persisting osteomyelitis requiring surgery is a key reason for recrudescence 3

Inappropriate Antibiotic Selection

• Do not use ertapenem despite it being a carbapenem—B. pseudomallei is inherently resistant 1, 4
• Amoxicillin-clavulanic acid is not suitable as prophylaxis 4

High-Risk Presentations

• Melioidosis carries high mortality (19-52% depending on region), especially with lung involvement and bacteremia 6, 5
• ICU admission rate is 46% 5
• Maintain high clinical suspicion in endemic areas, particularly for patients with diabetes mellitus (71% of cases), agricultural workers, and those with pneumonia or sepsis 5