Oral eradication therapy for melioidosis: Important but not without risks

Abstract

The purpose of this study was to quantify the adverse effects from oral eradication therapy for melioidosis, which is usually with high dose trimethoprim-sulfamethoxazole for 3-6 months. Methods: This retrospective cohort study reviewed side effects from oral eradication therapy in patients presenting with first episode culture-confirmed melioidosis in the tropical north of Australia's Northern Territory between 1st October 2012 and 1st January 2017. Results: 234 patients presented for the first time with culture-confirmed melioidosis. Of these, 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital. Of the remaining 212 patients, 203 (95.8%) were initially prescribed trimethoprimsulfamethoxazole as oral eradication therapy, 6 (2.8%) were prescribed doxycycline and 3 (1.4%) had no eradication therapy. Of the 203 prescribed trimethoprim-sulfamethoxazole, 61 (30.0%) experienced adverse effects, which necessitated a cessation, a change in antibiotic or reduction in dose. Conclusions: In patients treated for melioidosis in northern Australia there are high rates of adverse effects from oral trimethoprim-sulfamethoxazole, frequently necessitating a change in therapy or a reduction in dose. Given the side effects and low rates of oral therapy completion in our region we emphasise the importance of the prior often prolonged intensive phase intravenous therapy and using weight based trimethoprim-sulfamethoxazole dosing for eradication therapy.

Melioidosis after a long silence in Sri Lanka: an environmental hazard and dilemma in diagnosis, with recovery and longitudinal follow-up for 13 years: a case report

“…Being a saprophyte, B. pseudomallei is generally resistant to many antibiotics. However, there are antibiotics that are effective against it, including tetracycline, trimethoprim-sulfamethoxazole, chloramphenicol, thirdgeneration cephalosporins, amoxicillin-clavulanic acid, ureidopenicillins, carbapenem, cefoperazone/sulbactam, and azithromycin [17,18]. Despite long delay in confirming the diagnosis, our patient responded to high-dose IV meropenem followed by imipenem.…”

2020 Review and revision of the 2015 Darwin melioidosis treatment guideline; paradigm drift not shift

“…All patients presenting with first episode culture-confirmed melioidosis in the tropical north of Australia's Northern Territory between 1 st October 2012 and 1 st January 2017, as reported (16). These dates immediately follow the dates of the prior guidelines analysis as published in 2015 [9], while ensuring adequate follow up to detect relapse after 1 st January 2017, well exceeding the local median time to relapse of 8 months [5].…”

“…There were 234 patients presenting for the first time with culture-confirmed melioidosis between 1 st October 2012 and 1 st January 2017 [16]. Of these, 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital (See Fig 1).…”

“…Of these, 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital (See Fig 1). Baseline characteristics of the remaining 212 patients, are given in Table 1 [16], with 97 (45.8%) having pneumonia as their antibiotic duration determining focus.…”

“…Indeed, large studies from Thailand have shown relapse to be more common in patients with severe disease compared with those with localised melioidosis [22]. Other causes for clinician prolongation of intravenous therapy may include intolerance to first line eradication therapy with trimethoprim-sulfamethoxazole, common in these at-risk groups with comorbidities [16], and a perceived need to extend induction therapy when there is use of second-line oral eradication therapy with doxycycline. Of the 61 patients who experienced oral therapy side effects [16], the median duration of intravenous therapy was 28 days (IQR 15-42).…”