Increasing Experience with Primary Oral Medical Therapy for Mycobacterium ulcerans Disease in an Australian Cohort

Abstract

c Buruli ulcer (BU) is a necrotizing infection of subcutaneous tissue that is caused by Mycobacterium ulcerans and is responsible for disfiguring skin lesions. The disease is endemic to specific geographic regions in the state of Victoria in southeastern Australia. Growing evidence of the effectiveness of antibiotic therapy for M. ulcerans disease has evolved our practice to the use of primarily oral medical therapy. An observational cohort study was performed on all confirmed M. ulcerans cases treated with primary rifampin-based medical therapy at Barwon Health between October 2010 and December 2014 and receiving 12 months of follow-up. One hundred thirty-two patients were managed with primary medical therapy. The median age of patients was 49 years, and nearly 10% had diabetes mellitus. Lesions were ulcerative in 83.3% of patients and at WHO stage 1 in 78.8% of patients. The median duration of therapy was 56 days, with 22 patients (16.7%) completing fewer than 56 days of antimicrobial treatment. Antibiotic-associated complications requiring cessation of one or more antibiotics occurred in 21 (15.9%) patients. Limited surgical debridement was performed on 30 of these medically managed patients (22.7%). Cure was achieved, with healing within 12 months, in 131 of 132 patients (99.2%), and cosmetic outcomes were excellent. Primary rifampin-based oral medical therapy for M. ulcerans disease, combined with either clarithromycin or a fluoroquinolone, has an excellent rate of cure and an acceptable toxicity profile in Australian patients. We advocate for further research to determine the optimal and safest minimum duration of medical therapy for BU. B uruli ulcer (BU) is a necrotizing infection of subcutaneous tissue that is caused byMycobacterium ulcerans and is responsible for disfiguring skin lesions (1). While the disease is most common in West African countries (2), it is also endemic to specific geographic regions in the state of Victoria in southeastern Australia (3). Within the Bellarine Peninsula region of Victoria, BU is generally most common among older adults (3), in contrast to the affected demographic in West Africa, which is predominantly children (4).Antibiotics have been shown to be highly effective at sterilizing lesions and preventing disease recurrences when used alone or in combination with surgery (1, 5-9). Mounting evidence of the effectiveness of antibiotic therapy for M. ulcerans disease has substantially shifted the balance in favor of medical therapy over surgery, and our practice has evolved to using primarily oral medical therapy (1, 5). In 2013, we described the results of medical therapy in a group of 43 patients, among whom 42 patients (98%) healed without recurrence within 12 months (1). Here we provide details of our increasing experience with the use of primary oral medical therapy in a large observational Australian cohort. MATERIALS AND METHODSThis is an observational cohort study approved by Barwon Health's Human Research and Ethics Committee. All previously collected medical data...

Paediatric Buruli ulcer in Australia

“…The remaining child, a 17‐month‐old male, was initially treated with 56 days of oral antibiotic therapy (rifampicin and clarithromycin), although he experienced culture positive disease recurrence 4 months later. Retreatment with the same oral antibiotic regimen and duration was successful and the lesion healed by secondary intention 16 months after commencement of initial therapy …”

Antibiotic complications during the treatment of Mycobacterium ulcerans disease in Australian patients

“…In this study, we have shown that despite its known effectiveness, there is a significant toxicity associated with the antibiotic treatment of M . ulcerans in an Australian population.…”

“…In this study, we have shown that despite its known effectiveness, 7,8 there is a significant toxicity associated with the antibiotic treatment of M. ulcerans in an Australian population. More than one in five patients experienced an adverse effect severe enough to warrant cessation of an antibiotic, and a significant number required hospitalisation to manage their toxicity.…”

“…Antibiotics are the recommended first‐line treatment for M . ulcerans disease and are highly effective in curing lesions and preventing recurrences, alone or combined with surgery . Oral antibiotics have also reduced hospitalisations and the cost of treatment .…”

Treatment for Buruli ulcer: the long and winding road to antimicrobials-first

“…[13] Circumstantial evidence from observational studies suggests that fully oral treatment is highly e ective. [14] [15] The Cochrane Review is the first of its kind to formally assess the available evidence for drug treatment of Buruli ulcer. [4] The advantage of this formal evaluation of all peer-reviewed, published literature is that the many flaws in methodology are highlighted and suggestions for future trials are made.…”