A study to determine if a lower dose of the antibiotic trimethoprim/sulfamethoxazole will result in the same clinical cure and fewer side effects as the currently recommended higher dose of trimethoprim/sulfamethoxazole for the treatment of adults with melioidosis.

Lower dose therapy group: Intravenous meropenem or ceftazidime, adjusted for renal function and dosed in accordance with the Australian Therapeutic Guidelines for 14 to 42 days as determined by the treating clinician. The duration of intravenous phase will be determined by the antibiotic duration determining focus and the treating clinician will be encouraged to follow the 2024 Revised Darwin melioidosis guideline except for participants with isolated cutaneous disease (skin abscess) where clinicians may opt to omit the intensive phase antibiotics entirely. Intravenous meropenem will be dosed at 1-2g three times per day, adjusted for renal function as determined by the treating clinician. Intravenous ceftazidime will be dosed at 2g four times a day adjusted for renal function as determined by the treating clinician. For the purposes of outpatient parenteral antibiotic therapy, ceftazidime will be administered as a 24-hour intravenous infusion. Following completion of the intensive phase antibiotics, the eradication phase will begin; oral trimethoprim/sulfamethoxazole (TMP/SMX) will be commenced at a dose of 160/800 mg 12-hourly, adjusted for renal function and weight as determined by the treating clinician. For the purposes of the study, the duration of the eradication phase will be 90 to 180 days (rather than three to six months) from the end of the intensive phase antibiotics and commence immediately after completion of the intensive phase antibiotics. Concurrent administration of intravenous antibiotics and oral TMP/SMX will be discouraged with the exception of initiation of oral TMP/SMX towards the end of the intensive phase to ensure tolerability of the oral antibiotic as is current common practice at Cairns Hospital. For patients managed entirely at Cairns Hospital, all oral TMP/SMX will be dispensed by Cairns Hospital Pharmacy. For patients transferred from Cairns Hospital to another facility, oral TMP/SMX will be dispensed by the treating hospital with clear written instructions regarding treatment duration on the discharge summary completed when leaving Cairns Hospital. Adherence to oral TMP/SMX will be assessed by self reporting during weekly telephone or in-person review and by monitoring trough sulfamethoxazole concentrations.