What is melioidosis and how is it treated?

Melioidosis: Clinical Overview and Treatment

Melioidosis is an infectious disease caused by the environmental bacterium Burkholderia pseudomallei that requires a two-phase treatment approach with an initial intensive phase of intravenous antibiotics followed by an oral eradication phase to prevent relapse. 1, 2

Disease Characteristics

• Melioidosis is endemic in tropical regions, particularly Southeast Asia and northern Australia, causing significant morbidity and mortality 3
• The disease is caused by Burkholderia pseudomallei, a gram-negative bacillus found in soil and water in endemic regions 4
• Clinical presentations vary widely, with pneumonia (35.7%), intra-abdominal abscess (18.3%), and sepsis (18%) being the most common manifestations 3
• Melioidosis has a high global burden, estimated at 4.6 million disability-adjusted life-years in 2015, with 98.9% attributed to years of life lost 3
• Despite its significant impact, melioidosis is not officially classified as a neglected tropical disease by the WHO 5

Risk Factors and Transmission

• Diabetes mellitus is a major risk factor for developing melioidosis, as demonstrated in cases like isolated adrenal abscess 6
• Domestic gardens in endemic areas pose a significant risk for exposure, with irrigation consistently increasing B. pseudomallei occurrence 7
• Fertilizers can affect bacterial presence depending on soil type - nitrates and urea increase B. pseudomallei in sandy soil, while phosphates increase it in clay 7
• Immunosuppression increases susceptibility and severity of infection 2

Treatment Protocol

Initial Intensive Phase

• For severe melioidosis, intravenous meropenem or imipenem is recommended for at least 14 days, as these have demonstrated better clinical outcomes than ceftazidime 1, 8
• Ceftazidime (100 mg/kg/day) is an acceptable alternative if carbapenems are not available 1, 2
• Longer intensive treatment is required for critical illness, extensive pulmonary disease, deep-seated collections, organ abscesses, osteomyelitis, septic arthritis, and neurologic melioidosis 2, 8
• For patients with melioidosis-induced septic shock, meropenem plus granulocyte colony-stimulating factor (G-CSF) has been used successfully 9

Eradication Phase

• Trimethoprim-sulfamethoxazole (TMP-SMX) is the standard treatment for the eradication phase, with a recommended duration of 3-6 months 1, 2, 8
• The standard adult dosing is one double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) twice daily 2, 8
• TMP-SMX monotherapy has been shown to be as effective as combination therapy with TMP-SMX plus doxycycline in preventing relapse 2
• Alternative treatments for patients who cannot tolerate TMP-SMX include amoxicillin-clavulanate and doxycycline 1, 8

Important Clinical Considerations

• B. pseudomallei is inherently resistant to many antibiotics, including penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, streptomycin, and polymyxin 1, 2, 8
• In vitro testing has shown that B. pseudomallei isolates are sensitive to meropenem and imipenem but resistant to ertapenem, azithromycin, and moxifloxacin 9
• Amoxicillin-clavulanate is less effective than first-line options but may be used for pregnant women, children, and patients with intolerance to first-line therapy 9
• Delays in appropriate therapy significantly increase mortality, highlighting the importance of early recognition and treatment 1
• There is a marked difference in mortality rates between high-income and lower-income countries, suggesting a need for affordable strategies to reduce deaths from severe sepsis in resource-restricted settings 4

Prophylaxis

• TMP-SMX is recommended for post-exposure prophylaxis in case of biological attack and for immunosuppressed patients 9, 8
• When administered within 24 hours post-infection, co-trimoxazole has shown 100% survival rates in animal studies 9
• As pre-exposure prophylaxis, doxycycline and co-trimoxazole have demonstrated survival rates of 80% and 100% respectively in animal models 9
• Amoxicillin-clavulanic acid is not suitable as a prophylactic against melioidosis based on animal studies 9

Novel Therapeutic Approaches

• Phage-displayed non-immune human single-chain Fv antibody libraries against B. pseudomallei have identified potential therapeutic reagents 9
• A Taiwanese patient with life-threatening melioidosis was successfully treated with a combination of meropenem and recombinant-activated protein C (rhAPC) 9
• Various vaccine candidates are being developed, including B. pseudomallei surface proteins and proteins of the ATP-binding cassette system 9