Severe melioidosis — DTM&H MCQ

Correct answer: C — IV meropenem eight-hourly for at least 14 days

The correct answer is C, IV meropenem eight-hourly for at least 14 days. The clinical picture (Aboriginal Australian man, poorly controlled diabetes, pneumonia with splenic abscess) and growth of a gram-negative bacillus on Ashdown agar are classic for Burkholderia pseudomallei, the causative organism of melioidosis. Diabetes is the single strongest risk factor for melioidosis and Ashdown agar (containing crystal violet and gentamicin) is a selective medium used specifically to isolate this intrinsically gentamicin-resistant organism. Current treatment protocols mandate an intravenous intensive phase with a carbapenem (meropenem or imipenem) or ceftazidime for a minimum of two weeks to control the acute, often multifocal, bacteraemic infection before stepping down to a prolonged oral eradication phase. Meropenem given eight-hourly is preferred over ceftazidime in severe disease, bacteraemia, or deep-seated collections such as splenic abscess because of superior tissue penetration and lower treatment failure rates. Why the other options are wrong: D. IV ceftriaxone 14 days: Ceftriaxone has no reliable activity against B. pseudomallei and is not part of any recognised melioidosis regimen; the organism's intrinsic beta-lactamases and efflux pumps confer resistance to many gram-negative agents that are otherwise broad-spectrum. A. Oral doxycycline for 20 weeks: Doxycycline-based regimens were historical eradication-phase options but are inferior to co-trimoxazole for oral maintenance therapy, and an oral agent alone is inadequate for the acute intensive phase of a bacteraemic, abscess-forming infection. B. IV gentamicin plus ampicillin 14 days: B. pseudomallei is intrinsically resistant to aminoglycosides such as gentamicin (the basis of its selective isolation on Ashdown agar), so this combination would fail to treat the infection. E. IV co-trimoxazole for 7 days: Co-trimoxazole is the standard oral eradication-phase agent given for a minimum of three months, not an intravenous intensive-phase drug, and 7 days is far too short for either phase of melioidosis therapy. Key point: Melioidosis (Ashdown agar, diabetic patient, splenic abscess) requires IV meropenem or ceftazidime for at least two weeks as intensive therapy, followed by prolonged oral co-trimoxazole eradication, because B. pseudomallei is intrinsically resistant to aminoglycosides and many beta-lactams.

Reference: Sullivan RP et al, 2020 Review and revision of the 2015 Darwin melioidosis treatment guideline, PLOS Neglected Tropical Diseases, 2020: intensive phase intravenous meropenem, imipenem or ceftazidime for a minimum of 14 days, followed by oral eradication with trimethoprim-sulfamethoxazole for at least 12 weeks. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008659