[36] In a culture-proven case of melioidosis, it is important to rule out soft-tissue buy Sorafenib and visceral abscesses by computed tomography of abdomen and pelvis, irrespective of clinical presentation. Abdominal ultrasound is often recommended for children in order to minimize radiation exposure. All cases of melioidosis, irrespective of clinical severity, should be treated with at least 10–14 days (up to 8 weeks in patients with severe disease such as those with ongoing septic shock, deep-seated or organ abscesses, extensive lung disease, septic arthritis, osteomyelitis, or neurologic melioidosis) of initial intravenous intensive therapy, followed by eradication therapy with high-dose

trimethoprim–sulfamethoxazole (TMP + SMX) for a minimum of 3 months (Table 1).[2,

5, 28] Ceftazidime has been in use as the preferred intravenous agent subsequent to the open-label randomized trial from Thailand published in 1989 that demonstrated a significant 50% reduction in mortality rate of severe melioidosis with ceftazidime (120 mg/kg per day) compared with ‘conventional therapy’ (combination of chloramphenicol 100 mg/kg per day, doxycycline 4 mg/kg per day, TMP + SMX 10 + 50 mg/kg per day).[37] With the theoretical advantage of lower minimal inhibitory concentration and more favourable time-kill profile,[38] imipenem has alternatively been shown to be at least as effective as ceftazidime, with no difference in mortality rates in another open-label ITF2357 concentration randomized trial from Thailand.[39] Moreover, in a retrospective Cyclic nucleotide phosphodiesterase study from Australia,

the use of another carbapenem, meropenem has been shown to be associated with improved outcomes in patients with severe sepsis associated with melioidosis.[40] With the exception of doxycycline, the doses of antimicrobials need to be adjusted in patients with impaired renal function and in those receiving renal replacement therapy (Table 2).[41-45] Burkholderia pseudomallei is inherently resistance to penicillin, ampicillin, first-generation and second-generation cephalosporins, macrolides, quinolones and most aminoglycosides, thereby limiting therapeutic options. Primary resistance to ceftazidime is extremely uncommon but occasional secondary resistance has been reported from endemic locations, usually after prolonged therapy.[46-50] Resistance to carbapenems has not been reported yet. Hence, the use of these antimicrobials could be continued as empirical or first-line therapy for both primary and recurrent melioidosis infection, at least until antimicrobial susceptibility testing of the organism is available. The rate of resistance to TMP + SMX, as assessed with the use of Etest has been reported to be up to 2.5% for Australian isolates but much higher at up to 13% for Thai isolates, although current studies across the endemic region are reassessing this issue.