Approach

Mortality in melioidosis without specific antibiotic therapy can be >50% overall and >90% in septic shock cases. Even with appropriate antibiotics, delayed diagnosis and lack of access to state-of-the-art intensive care therapy is currently associated with overall mortality rates of around 40% in many endemic locations.[65]

The priority in melioidosis-endemic regions is to have adequate laboratory microbiology (most critically blood culture capability) to enable timely diagnosis by culture and identification of Burkholderia pseudomallei. Once a diagnosis is made, the antibiotic therapy is divided into the intensive intravenous phase, followed by the oral eradication phase. The therapy of glanders in humans follows the same recommendations as for melioidosis.

Healthcare workers caring for infected patients should use standard contact precautions. The US Centers for Disease Control and Prevention (CDC) recommends the use of standard and airborne precautions when treating patients with glanders.[83]

In some endemic areas, melioidosis and glanders are statutorily notifiable diseases which must be reported to local health authorities. In non-endemic areas this is now also a common requirement in the light of their potential use as biothreat agents; in the US bothBurkholderia mallei and B pseudomallei are categorised as Tier 1 select agents.[5]

Intensive intravenous antibiotic therapy

Intravenous antibiotic therapy with ceftazidime, meropenem, or imipenem/cilastatin should be administered in non-localised disease or patients who are systemically unwell.[8][43][84][57][85]

In patients with a collection (including skin ulcers/abscesses and abscesses in internal organs), and in bone/joint, genitourinary, and CNS infections (but not for pneumonia), intravenous (if available) or oral trimethoprim/sulfamethoxazole may be added.[8][86] Concomitant administration of folic acid should be considered when giving trimethoprim/sulfamethoxazole in high doses for a long duration to reduce potential adverse effects associated with the drug’s anti-folate effect (e.g., bone marrow toxicity).[8]

Duration of therapy is determined by the severity and nature of the clinical features.[8][84] Minimum duration is 10 to 14 days, which should be extended to 4 weeks if:

  • Pneumonia requiring ICU or associated with mediastinal lymphadenopathy or extensive bilateral chest x-ray changes

  • Presence of internal organ abscesses, septic arthritis, or other deep-seated collections, with 4-week duration timed from last aspiration of pus (e.g., with prostatic abscesses or septic arthritis).

Duration should be extended to 6 weeks (minimum) if osteomyelitis is present.

Duration should be extended to 8 weeks if the patient has neurological melioidosis or mycotic aneurysm.

In resource-poor settings it may not be affordable to extend treatment, but a minimum of 10 to 14 days of intensive treatment is recommended.[57][87] In this situation the importance of completing a full course of oral eradication therapy is paramount.

Oral eradication therapy

Oral trimethoprim/sulfamethoxazole is the treatment of choice after intensive intravenous antibiotic therapy, or in patients with localised disease who are systemically well.[8][43][84][57][85][88][89] Concomitant administration of folic acid should be considered when giving trimethoprim/sulfamethoxazole in high doses for a long duration to reduce potential adverse effects associated with the drug’s anti-folate effect (e.g., bone marrow toxicity).[8] However, bone marrow suppression, rash, and hyperkalaemia and elevated creatinine are not uncommonly seen in melioidosis patients treated with trimethoprim/sulfamethoxazole. One study found that 30% of patients treated with trimethoprim/sulfamethoxazole experienced adverse effects which required cessation, a reduction in dose, or change in antibiotic.[90] Alternative eradication therapy for these patients is amoxicillin/clavulanate, or doxycycline (in adults only).[91]

In children older than 2 months of age and pregnant women, trimethoprim/sulfamethoxazole remains the drug of choice, although delaying the use of trimethoprim/sulfamethoxazole until beyond the first trimester can be considered because of concerns of teratogenicity. Amoxicillin/clavulanate is an alternative, although it has been associated with a relatively high risk of recurrence.[85]

Eradication therapy should be continued for a minimum of 3 months, and extended to 6 months if neurological melioidosis or osteomyelitis are present.[8][43][84][85]

Some patients with localised disease (confirmed by imaging to exclude other foci) who are systemically well may safely be treated with oral eradication therapy alone.[10][85]

Treatment of abscesses

Collections should be drained where practicable (especially prostate and muscle abscesses and larger liver abscesses), but splenic abscesses usually do not require drainage.

Duration of intravenous therapy is best timed from last culture-positive drainage of pus.[84]

Melioidosis septic shock

State-of-the-art resuscitation and intensive care therapy with severe sepsis guidelines are necessary to reach the current best-care overall mortality of 10%.[65]

The mortality benefit of adding granulocyte-colony stimulating factor (G-CSF) to the treatment regimen in patients with melioidosis septic shock remains unproven, but it is used in some intensive care units experienced in treating melioidosis.[8][92][93]

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