title: Effectiveness of rifampicin-streptomycin for treatment of Buruli ulcer: a systematic review.
abstract: Buruli ulcer (BU) disease is a chronic ulcerative skin disease caused by Mycobacterium ulcerans, which can lead to extensive destruction of the skin, soft tissues and occasionally of bones. Although several antibiotics have demonstrated bactericidal activity against M. ulcerans in vitro, no consensus on their clinical efficacy against M. ulcerans in humans has been reached.
  
  
  
  The objective of the systematic review was to examine the clinical effectiveness of various antibiotic regimens for the treatment of BUs.
  
  
  
  The current review considered trials that included patients of all ages with BUs.
  
  
  
  The current review considered trials that evaluated antibiotic regimens compared to no antibiotics or surgery in patients with BUs.
  
  
  
  The current review considered randomized and non-randomized controlled trials (RCTs). In the absence of RCTs, other research designs such as before and after trials and clinical trials with only an intervention arm were considered for inclusion in a narrative summary.
  
  
  
  The primary outcome of interest were the treatment success rates among the various antibiotics used. Secondary outcomes included changes in lesion size, recurrence of ulcers and incidence of adverse events.
  
  
  
  The search strategy aimed to find both published and unpublished trials. A three-step search strategy was utilized in this review and included English language trials published after 1990. A search across the major databases was conducted up to December 2014.
  
  
  
  Using the Joanna Briggs Institute (JBI) standardized appraisal tool, two reviewers independently assessed the methodological quality of the trials. A third independent reviewer was available to appraise trials if the two original reviewers disagreed in their assessments. There were no disagreements in findings between the two independent reviewers.
  
  
  
  Data were extracted using the standardized JBI data extraction instruments.
  
  
  
  Statistical pooling was not possible due to heterogeneity, hence results have been presented in the narrative form.
  
  
  
  Seven studies involving a total of 712 patients were included in the final review. Higher treatment success rates ranging from 96% to 100% at the six months follow-up were reported among patients treated with rifampicin-streptomycin for eight weeks (RS8) in two studies. Treatment success with rifampicin-streptomycin for 12 weeks, with surgery at the 12 weeks follow-up, was 91%. In the two studies that investigated the effect of rifampicin-streptomycin for two weeks followed by rifampicin-clarithromycin for six weeks and rifampicin-streptomycin for four weeks followed by rifampicin-clarithromycin for four weeks, treatment success was reported to be 93% and 91%, respectively, at the 12 months follow-up. A significant decrease in the median lesion size at the eight weeks follow-up was reported in patients who were treated with RS8, and a 10-30% decrease in lesion size was reported in those treated with RS12 at the four weeks follow-up.
  
  
  
  Treatment success and reduction in lesion size were higher in patients treated with RS8 in the only RCT that compared rifampicin-streptomycin for four weeks followed by rifampicin-clarithromycin for six weeks to RS8, and there was no difference in outcomes, which indicates that local preferences could dictate the treatment option. Evidence obtained from this systematic review indicates that surgery will remain necessary for some ulcers; however, detection of early lesions and treatment with antibiotics would have a greater impact on the control of M. ulcerans disease. Further large multicenter RCTs investigating the type and optimal duration of oral antibiotic treatment for patients with M. ulcerans disease are urgently needed.
authors.affiliation: 1The Cameroon Centre for Evidence Based Health Care: a Joanna Briggs Institute Centre of Excellence, Yaounde, Cameroon, Africa 2Centre for Behavioral and Social Research, Yaounde, Cameroon, Africa 3Centre for Evidence Based Initiatives in Health Care: a Joanna Briggs Institute Centre of Excellence, University of Wollongong, Wollongong, New South Wales, Australia 4St George Hospital, Sydney, New South Wales, Australia.
authors.forename: Asahngwa
authors.initials: A
authors.lastname: Tanywe
authors.forename: Ritin S
authors.initials: RS
authors.lastname: Fernandez
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D054312:Buruli Ulcer / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D019911:Mycobacterium ulcerans / Q000187:drug effects / Q000302:isolation & purification; D012293:Rifampin / Q000627:therapeutic use*; D013307:Streptomycin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D012293:Rifampin; D013307:Streptomycin