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

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.

The Spectrum of Chromobacterium violaceum Infections from a Single Geographic Location

“…There is a precedent with other tropical water-associated bacteria such as Burkholderia pseudomallei having geographic strain differences 29 ; or 3) As the Top End of the Northern Territory is an endemic zone for B. pseudomallei, the bacteria that causes melioidosis, protocols for sepsis include the early empiric use of meropenem. These measures have improved outcomes in patients presenting with septic presentations of melioidosis, 30 and our low C. violaceum mortality may be an unexpected side benefit. Meropenem usually has excellent activity against C. violaceum and may explain the lower mortality seen.…”

The epidemiology and clinical features of melioidosis in Far North Queensland: Implications for patient management

“…Admission to the Intensive Care Unit (ICU), the use of mechanical ventilation and renal replacement therapy (RRT) was documented; septic shock was defined as a requirement for vasopressors. The duration of the intensive and proposed eradication phase of treatment was also documented; this was compared to published recommendations from Darwin [10]. Adherence to eradication therapy was determined from the medical record and outpatient letters.…”

“…This relatively high rate of relapse—and the recognition that there is frequently poor adherence to the long course of oral therapy—has led to a suggestion that patients may benefit from an extended phase of intravenous therapy. A longer phase of intravenous therapy was associated with very low relapse rates in a recent series from Darwin [10]. However, while there are plausible arguments for this strategy, it has not been evaluated in other locations.…”

Antibiotic resistance in Burkholderia species

“…Current recommended therapy for melioidosis consists of two weeks of intravenous ceftazidime or a carbapenem, followed by up to six months of oral trimethoprim+sulfamethoxazole (co-trimoxazole)(Chetchotisakd et al, 2014; Dance, 2014; Lipsitz et al, 2012; Pitman et al, 2015). In either phase of therapy, the administration of amoxicillin+clavulanate (co-amoxiclav) is used in instances where other drugs are contraindicated (Dance, 2014; Lipsitz et al, 2012; McLeod et al, 2015).…”