Antimicrobial Treatment of Mycobacterium ulcerans Infection

Till Frederik Omansen, Tjip S. van der Werf, Richard Odame Phillips, Gerd Pluschke, Katharina Röltgen, Till Frederik Omansen, Tjip S. van der Werf, Richard Odame Phillips, Gerd Pluschke, Katharina Röltgen

Excerpt

MacCallum and coworkers described Buruli ulcer (BU) as an infectious disease caused by Mycobacterium ulcerans in Victoria, Australia. They first considered the skin lesions in their patients to be caused by tuberculosis or leprosy, when they observed numerous acid-fast bacilli in the biopsy specimens [1]. The typical duration of illness was between 1 and 2 years; treatment was essentially surgical. With the advent of chemotherapy for tuberculosis [2–4], and later for leprosy, doctors made individual attempts to treat the lesions with anti-tuberculosis and anti-leprosy drugs. The anecdotal evidence suggested poor or no response to chemotherapy with rifampicin monotherapy [5], despite the fact that in vitro susceptibility of 33 strains of M. ulcerans was as good as for M. tuberculosis [6]. A randomized clinical trial by the British Medical Research Council in Buruli county (now called Nakasongola; Uganda) failed to show any benefit from clofazimine, a drug then first marketed for leprosy [7]. A small-sized trial with cotrimoxazole (18 participants; 12 evaluable) was inconclusive [8]. A small-sized randomized study in Côte d’Ivoire compared a combination of dapsone and rifampicin with placebo; the follow-up was limited; the ulcer size decreased slightly faster in the intervention group but the baseline characteristics of both groups differed, and the study did not allow to draw any firm conclusions about the effectiveness of these drugs [9]. By the turn of the millennium, the discrepancy between in vitro efficacy of rifampicin [6] or clarithromycin [10] and lack of clinical response prompted to stressing the need for well-designed and well-powered drug trials, but in the meantime, to also improve early detection and surgical treatment [11].

Copyright 2019, The Author(s).

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