Abstract
The potential use of clinically approved beta-lactams for Buruli ulcer (BU) treatment was investigated with representative classes analyzed in vitro for activity against Mycobacterium ulcerans. Beta-lactams tested were effective alone and displayed a strong synergistic profile in combination with antibiotics currently used to treat BU, i.e. rifampicin and clarithromycin; this activity was further potentiated in the presence of the beta-lactamase inhibitor clavulanate. In addition, quadruple combinations of rifampicin, clarithromycin, clavulanate and beta-lactams resulted in multiplicative reductions in their minimal inhibitory concentration (MIC) values. The MIC of amoxicillin against a panel of clinical isolates decreased more than 200-fold within this quadruple combination. Amoxicillin/clavulanate formulations are readily available with clinical pedigree, low toxicity, and orally and pediatric available; thus, supporting its potential inclusion as a new anti-BU drug in current combination therapies.
Highlights
Buruli ulcer (BU) is a chronic debilitating mycobacterial disease of the skin and soft tissue
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
We describe for the first time the potential inclusion of beta-lactams in BU therapy
Summary
Buruli ulcer (BU) is a chronic debilitating mycobacterial disease of the skin and soft tissue. The lack of an efficacious oral treatment remained one of the main obstacles to decentralizing care at local level in rural areas. These limitations motivated the scientific community to evaluate alternative oral treatments and clinical studies demonstrated that fluoroquinolones [17] or clarithromycin [18,19,20] could be used in combination with rifampicin and were associated with fewer side effects compared to the injectable streptomycin. On March 24th, 2017, WHO recommended full oral treatment of 8 weeks daily combination therapy of rifampicin-clarithromycin [21]
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