Omitting the Eradication Phase of Treatment of Adults with Melioidosis: A Pilot, Single-Center Randomized Controlled Trial

Background: Contemporary Australian guidelines for the management of melioidosis recommend a longer duration of intravenous antibiotics during the intensive phase of treatment; recurrent disease is now far less common. A high rate of adverse drug reactions (ADRs) to the currently recommended minimum of 3 months of oral trimethoprim/sulfamethoxazole (TMP/SMX) eradication therapy questions the incremental value of this phase of treatment. Methods: In this pilot, single-center, open-label randomized controlled trial, adults with culture-confirmed melioidosis received either prolonged intravenous intensive-phase therapy followed by oral eradication-phase therapy with TMP/SMX (standard therapy) or prolonged intravenous intensive-phase therapy alone (short-course therapy). The primary outcome was culture-confirmed recurrence at 2 years. Secondary outcomes included clinical (culture-unconfirmed) recurrence and ADRs to TMP/SMX. Results: Among 33 participants, 5 had culture-confirmed recurrence: 0/16 in the standard therapy group and 5/17 (29%) in the short-course therapy group. One participant (6%) in the standard therapy group had clinical recurrence. An ADR to TMP/SMX occurred in 13/16 (81%) in the standard therapy group, necessitating TMP/SMX cessation in 7/13 (44%), hospitalization in 5/13 (38%), and intensive care unit admission in 1/13 (8%). Conclusions: Prolonged intravenous antibiotics alone will cure many patients with melioidosis; however, some still require oral eradication therapy. The potential for recurrence of life-threatening melioidosis must be balanced against the high rate of significant ADRs to high-dose TMP/SMX. This necessitates a greater understanding of the individuals at highest risk of recurrence and determination of the optimal dosing and duration of eradication therapy in those who need it.