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

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.

Synthesis and biological activity of dehydrophos derivatives.

The synthesis of dehydrophos derivatives featuring modified peptide chains, characterized by the presence of substituents in the vinyl moiety, or possessing a phosphonic acid monoalkyl ester other than the monomethyl ester one, has been accomplished by a versatile procedure based on Horner-Wadsworth-Emmons olefination with suitable aldehydes and on the selective hydrolysis of the dialkyl phosphonate group. Such derivatives have been tested against a series of bacterial strains, using the naturally occurring peptide, dehydrophos, for comparison. Thus, the effects of the aforementioned structural variations on antimicrobial activity have been studied.