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Intravenous therapy duration and outcomes in melioidosis: a new treatment paradigm
Matthew C Pitman1, Tara Luck1, Catherine S Marshall1
1Infectious Diseases Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
Background:
International 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 Findings:
This 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/ Significance:
Relapsed 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.
Insights
A longer intensive phase for melioidosis treatment, aligned with Australian guidelines, resulted in rare relapses. Recrudescence rates may decrease with fewer self-discharges, suggesting a need to re-evaluate eradication therapy duration.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Clinical Pharmacology
Background:
- International melioidosis guidelines recommend 10-14 days intravenous (IV) therapy followed by 3-6 months oral therapy.
- This standard approach has relapse rates exceeding 5% and has not previously reported recrudescence rates.
- Australian guidelines evolved to recommend longer IV intensive phase durations due to low eradication phase completion rates.
Purpose of the Study:
- To review antibiotic duration for melioidosis treatment in Australia.
- To assess adherence to local guidelines and treatment outcomes.
- To determine relapse and recrudescence rates associated with current treatment protocols.
Main Methods:
- Retrospective cohort study of melioidosis patients surviving the intensive phase over three years in Northern Australia.
- Analysis of antibiotic duration, eradication therapy completion, and adherence to local guidelines.
- Follow-up assessment for relapse and recrudescence, with logistic regression for risk factors.
Main Results:
- Median intensive phase duration was 26 days, exceeding the 10-14 day recommendation.
- Only 50.2% of patients completed eradication therapy; 27.0% received none.
- At 28 months, relapse occurred in 0.5% and recrudescence in 5.1%. Independent risk factors for recrudescence included self-discharge and septic shock.
Conclusions:
- Relapsed melioidosis is rare with guideline-concordant, clinically-guided intensive phase durations.
- Reducing self-discharge rates may lower recrudescence.
- Further evaluation of eradication therapy duration and necessity is warranted given low relapse rates despite non-adherence.
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