A Novel Combination of Tobramycin with a Potentiator for the Treatment of Chronic Pseudomonas aeruginosa Infections

Abstract

EBX-001, a combination of tobramycin with a bacterial metabolite as a potentiator, is being developed for the treatment of chronic P. aeruginosa infections in Cystic Fibrosis, non-CF bronchiectasis, and COPD patients. The combination utilizes an anti-persisters strategy and is aimed at reducing recurrent infections. P. aeruginosa cultures in planktonic stationary phase (PSP) were used to select for bacterial persisters, bacteria in a quasi-dormant state. In these PSP experiments, a range of tobramycin concentrations was tested with a range of metabolite concentrations to determine the potentiation effect of the metabolite under a variety of conditions. MICs were also determined for a variety of CF and COPD clinical isolates to select a diverse set of strains for inclusion in the study. Enhanced killing of up to 6 orders of magnitude of P. aeruginosa persisters for a range of strains was observed; see example for a mucoid CF isolate in the figure below. A combination of tobramycin with a potentiator remains an attractive therapeutic option for eliminating recurrent P. aeruginosa infections through the eradication of bacterial persisters, whether in CF, non-CF bronchiectasis, or COPD.