Clinical and Bacteriological Efficacy of Rifampin-Streptomycin Combination for Two Weeks followed by Rifampin and Clarithromycin for Six Weeks for Treatment of Mycobacterium ulcerans Disease

Phillips, Richard Odame; Sarfo, Fred Stephen; Abass, Mohammed K.; Abotsi, Justice; Wilson, Tracey E.; Forson, Mark; Amoako, Yaw Ampem; Thompson, W. A.; Asiedu, Kingsley; Wansbrough‐Jones, Mark

doi:10.1128/aac.02165-13

Cited by 59 publications

(69 citation statements)

References 35 publications

(42 reference statements)

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“…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. Reported adverse effects associated with treatment in African populations appear less common . However this is likely influenced by significant differences between the populations – African cohorts are younger and have less comorbidities and potential drug interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Reported adverse effects associated with treatment in African populations appear less common. 8,18 However this is likely influenced by significant differences between the populations -African cohorts are younger 19,20 and have less comorbidities and potential drug interactions. Severe antibiotic complications occurred throughout the antibiotic course.…”

Section: Discussionmentioning

confidence: 99%

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

O’Brien

Friedman

Hughes

et al. 2017

Internal Medicine Journal

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

O’Brien

Friedman

Hughes

et al. 2017

Internal Medicine Journal

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“…The efficacy of the treatment regime is more than 90% [47, 48]. Nevertheless the healing process varies widely.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Mycobacterium ulcerans-specific T-cell cytokines for diagnosis of Buruli ulcer disease and as potential indicator for disease progression

et al. 2017

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BackgroundBuruli ulcer disease (BUD), caused by Mycobacterium (M.) ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy. BUD causes necrotic skin lesions and is a significant problem for health care in the affected countries. As for other mycobacterial infections, T cell mediated immune responses are important for protection and recovery during treatment, but detailed studies investigating these immune responses in BUD patients are scarce. In this study, we aimed to characterise M. ulcerans-specific CD4+ T cell responses in BUD patients and to analyse specific cytokine-producing T cells in the context of disease severity and progression.Methodology/Principal findingsFor this case-control study, whole blood samples of BUD patients (N = 36, 1.5–17 years of age) and healthy contacts (N = 22, 3–15 years of age) were stimulated with antigen prepared from M. ulcerans and CD4+ T cells were analysed for the expression of TNFα, IFNγ and CD40L by flow cytometry. The proportions and profile of cytokine producing CD4+ T cells was compared between the two study groups and correlated with disease progression and severity. Proportions of cytokine double-positive IFNγ+TNFα+, TNFα+CD40L+, IFNγ+CD40L+ (p = 0.014, p = 0.010, p = 0.002, respectively) and triple positive IFNγ+TNFα+CD40L+ (p = 0.010) producing CD4+ T cell subsets were increased in BUD patients. In addition, TNFα+CD40L-IFNγ- CD4+ T cells differed between patients and controls (p = 0.034). TNFα+CD40L-IFNγ- CD4+ T cells were correlated with lesion size (p = 0.010) and proportion were higher in ‘slow’ healers compared to ‘fast healers’ (p = 0.030).ConclusionsWe were able to identify M. ulcerans-specific CD4+ T cell subsets with specific cytokine profiles. In particular a CD4+ T cell subset, producing TNFα but not IFNγ and CD40L, showed association with lesion size and healing progress. Further studies are required to investigate, if the identified CD4+ T cell subset has the potential to be used as biomarker for diagnosis, severity and/or progression of disease.

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“…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).…”

mentioning

confidence: 99%

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

Friedman

Athan

Walton

et al. 2016

Antimicrob Agents Chemother

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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...

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Clinical and Bacteriological Efficacy of Rifampin-Streptomycin Combination for Two Weeks followed by Rifampin and Clarithromycin for Six Weeks for Treatment of Mycobacterium ulcerans Disease

Cited by 59 publications

References 35 publications

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

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

Analysis of Mycobacterium ulcerans-specific T-cell cytokines for diagnosis of Buruli ulcer disease and as potential indicator for disease progression

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

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