Triple oral beta-lactam containing therapy for Buruli ulcer treatment shortening


Buruli ulcer (BU) is a chronic debilitating disease of the skin and soft tissue, mainly affecting children and young adults in tropical regions. Before 2004, the only treatment option was surgery; a major breakthrough was the discovery that BU could be cured in most cases with a standard treatment that involved 8 weeks of combination therapy with rifampicin and streptomycin. However, the use of streptomycin is often associated with severe side effects such as ototoxicity, nephrotoxicity, or hepatotoxicity. More recently, a clinical trial demonstrated equipotency of replacing the injectable streptomycin by the clarithromycin, which is orally available and with fewer side effects. Thus, BU treatment is now moving toward a full orally available treatment of clarithromycin-rifampicin. However, recent studies have reported the emergence of strains resistant to rifampicin and streptomycin. Since no alternatives to rifampin are available, it is considered the cornerstone drug for BU therapy. Strains resistant to clarithromycin could also eventually emerge. Thus, there is a need to find new therapies for BU.

In this work, we describe for the first time the potential inclusion of beta-lactams in BU therapy. More specifically, we propose the use of amoxicillin/clavulanate since it is oral, suitable for the treatment of children, and readily available with a long track record of clinical pedigree. Its inclusion in a triple oral therapy complementing current combinatorial rifampicin-clarithromycin treatment has the potential to counteract resistance development and to reduce length of treatment and time to cure.