ASM Microbe 2016
A Novel Combination of Tobramycin with a Potentiator for the Treatment of Chronic Pseudomonas aeruginosa Infections
M. Koeva, A. D. Gutu, F. M. Ausubel, D. Joseph-McCarthy
ABSTRACT | Background: 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 patients. The combination utilizes an anti-persisters strategy and is aimed at reducing recurrent infections. Methods: P. aeruginosa cultures in the 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 clinical isolates to select a diverse set of strains for inclusion in the study. Results: Enhanced killing of up to 6 orders of magnitude of P. aeruginosa persisters for a range of strains was observed (see example in the figure below). Conclusions: A combination of tobramycin with a potentiator remains an attractive therapeutic option for eliminating recurrent P. aeruginosa infections through the eradication of bacterial persisters.