Research Article: Intravenous Therapy Duration and Outcomes in Melioidosis: A New Treatment Paradigm

Date Published: March 26, 2015

Publisher: Public Library of Science

Author(s): Matthew C. Pitman, Tara Luck, Catherine S. Marshall, Nicholas M. Anstey, Linda Ward, Bart J. Currie, Joseph M. Vinetz.

Abstract: BackgroundInternational melioidosis treatment guidelines recommend a minimum 10 to 14 days’ intravenous antibiotic therapy (intensive phase), followed by 3 to 6 months’ oral therapy (eradication phase). This approach is associated with rates of relapse, defined as recurrence following the eradication phase, that can exceed 5%. Rates of recrudescence, defined as recurrence during the eradication phase, have not previously been reported. In response to low eradication phase completion rates in Australia, a local guideline has evolved over the last ten years recommending a longer minimum intensive phase duration for many cases of melioidosis.Methodology/ Principal FindingsThis retrospective cohort study reviews antibiotic duration for the first episode of care for all patients diagnosed with melioidosis and surviving the intensive phase during a recent three year period in the tropical north of Australia’s Northern Territory; we also review adherence to the current local guideline and treatment outcomes. Of 215 first episodes of melioidosis surviving the intensive phase, the median (interquartile range) intensive phase duration was 26 (14-34) days. One hundred and eight (50.2%) patients completed eradication therapy; 58 (27.0%) patients took no eradication therapy. At 28 months’ follow-up, one (0.5%) relapse and eleven (5.1%) recrudescences had occurred. On exact logistic regression analysis, the only independent risk factors for recrudescence were self-discharge during the intensive phase (odds ratio 6.2 [95% confidence interval 1.2-30.0]) and septic shock (odds ratio 5.3 [95% confidence interval 1.1-25.7]).Conclusions/ SignificanceRelapsed melioidosis is rare in patients who receive a minimum intensive phase duration specified by our guideline and extended according to clinical progress. Recrudescence rates may improve with reductions in rates of self-discharge. Given the low relapse rate despite a high rate of eradication therapy non-adherence, the duration and necessity of eradication therapy for different patients after guideline-concordant intensive therapy should be evaluated further.

Partial Text: Burkholderia pseudomallei, the cause of melioidosis, is a soil- and water-borne bacterium endemic to northern Australia and parts of south-east Asia [1]. It most commonly causes pneumonia, bacteremia without evident focus, deep-seated abscesses and skin infection but can affect almost any part of the body [2]. It causes more serious disease in patients with impaired innate immunity such as those with diabetes and has a high mortality rate ranging from 9% to 49% [3–5]. It is intrinsically resistant to most antibiotics and requires prolonged therapy for cure [5–8].

The evolving therapy of melioidosis over the last 25 years has largely been informed by sequential randomized controlled trials from Thailand [11,13–17,22–27]. All trials assessing intensive phase therapy in melioidosis have had mortality as a primary endpoint; none has included relapse as an endpoint [11,13,22,23,25–27]. Minimum duration of intensive therapy in these studies has been 7–14 days with a median of 7–15 days’ therapy actually administered. No study has randomized patients to different intensive phase durations. All randomized controlled trials assessing eradication therapy have had relapse as a primary endpoint [14–17,24]; these studies have repeatedly found that eradication therapy choice, duration and compliance affect relapse rate whereas intensive phase choice and duration do not.



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