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

Background Melioidosis therapy is divided into an intravenous intensive phase and an oral eradication phase. The Darwin melioidosis treatment guideline has evolved over two decades, with over 1150 consecutive patients with culture-confirmed melioidosis managed under the Darwin Prospective Melioidosis Study. The current guideline, published in 2015, has been associated with low rates of recrudescence, relapse and mortality, and together with the treatment trials in Thailand, forms the basis for consensus global guidelines. We aimed to reassess the Darwin guideline and determine if any adjustments to the recommendations better reflect current practice in melioidosis therapy at Royal Darwin Hospital. Methodology/Principal findings This retrospective cohort study reviews the characteristics, admission duration, duration of intravenous antibiotics, recrudescence, recurrence and mortality in all patients presenting with first episode culture-confirmed melioidosis in the tropical north of Australia's Northern Territory from 1(st)October 2012 until 1(st)January 2017. 234 patients were available for analysis. 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital, leaving 212 patients for analysis. Six (2.8%) patients had recrudescence during therapy and 10 (4.7%) had recurrent melioidosis (relapse or new infection) after completion of therapy. Persisting osteomyelitis requiring surgery was an important reason for recrudescence as was unrecognized osteomyelitis for relapse. For patients presenting with an antibiotic duration determining focus of pneumonia, durations of intravenous antibiotics were often prolonged beyond the current 2-week minimum treatment recommendation. Prolongation of therapy in pneumonia mostly occurred in patients presenting with multi-lobar disease or with concurrent blood culture positivity. Conclusions/Significance The 2015 Darwin melioidosis guideline is working well with low rates of recrudescence, relapse and mortality. Based on the practice of the treating clinicians, the 2020 revision of the guideline has been adjusted to include a duration of a minimum of 3 weeks of intravenous antibiotics for those with concurrent bacteraemia and pneumonia involving only a single lobe and those with bilateral and unilateral multi-lobar pneumonias who do not have bacteraemia. We also extend to a minimum of 4 weeks intravenous therapy for those with concurrent bacteraemia and bilateral or unilateral multi-lobar pneumonia. Author summary Melioidosis, caused by the Gram-negative bacteriumBurkholderia pseudomallei, is an infectious disease with diverse clinical presentations including pneumonia, localised cutaneous lesion, bacteraemia without evident focus, septic arthritis and osteomyelitis, and severe sepsis with multiple organ abscesses. Therapy is prolonged, consisting of an intensive intravenous phase and an oral eradication phase. Guidelines from northern Australia have evolved and now recommend an often-longer duration of intravenous antibiotics than in prior recommendations. The Darwin melioidosis guideline, which was first published internationally in 2015 and described as a new treatment paradigm, has been associated with relatively low rates of recrudescence and relapse. We have reassessed use of this guideline and have again demonstrated low rates of recrudescence, relapse and mortality. There has been a tendency for treating clinicians to prolong intravenous phase therapy beyond the 2-week recommendation in those presenting with concurrent bacteraemia and pneumonia and in those with multi-lobar pneumonia. The 2015 guideline remains the standard for treatment recommendations for our region, but the 2020 revision now includes multi-lobar pneumonia as an indication for a minimum of 3 weeks intravenous treatment if bacteraemia is not present and 4 weeks if bacteraemia is present, while a minimum of 3 weeks is recommended for those with concurrent bacteraemia and pneumonia involving only a single lobe.