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

• Main Authors: María Pilar Arenaz-Callao, Rubén González Del Río, Ainhoa Lucía Quintana, Charles J Thompson, Alfonso Mendoza-Losana, Santiago Ramón-García
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2019-01-01
• Series: PLoS Neglected Tropical Diseases
• Online Access: http://europepmc.org/articles/PMC6366712?pdf=render

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.