Intermediate metabolism products to potentiate aminoglycoside antibiotics in bacterial infections

Abstract

Provided herein are compositions and methods to improve treatment of chronic infections, and reduce, delay, or inhibit formation of biofilms, using specific combinations of aminoglycoside antibiotics and treatment with one or more proton motive force (PMF) stimulating compounds. These novel methods are easily adapted to clinical settings as toxicity and efficacy of the antibiotics and metabolites used have already been studied in vivo, and as dosing for both the antibiotics and metabolites are known.

We claim: 
     
         1 - 39 . (canceled) 
     
     
         40 . A pharmaceutical composition comprising a therapeutically effective amount of an aminoglycoside antibiotic in combination with a therapeutically effective amount of at least one metabolite or compound of a metabolic pathway selected from the group consisting of: the tricarboxylic acid cycle (TCA), beta oxidation, the urea cycle, amino acid catabolism, lipid catabolism, and combinations thereof. 
     
     
         41 . The composition of  claim 40 , wherein the aminoglycoside antibiotic is tobramycin. 
     
     
         42 . The composition of  claim 40 , wherein the metabolite or compound of the metabolic pathway is fumarate. 
     
     
         43 . The composition of  claim 40 , wherein the aminoglycoside antibiotic is tobramycin and the metabolite is fumarate. 
     
     
         44 . The composition of  claim 40 , the aminoglycoside antibiotic is tobramycin and the at least one metabolite or compound of the metabolic pathway is succinate, citrate, oxaloacetate, ribose, arabinose, gluconate, or propionate. 
     
     
         45 . The composition of  claim 44 , wherein the composition is formulated for local administration. 
     
     
         46 . The composition of  claim 40 , wherein the therapeutically effective amount of fumarate is between 5 mM and 30 mM. 
     
     
         47 . The composition of  claim 40 , wherein the therapeutically effective amount of fumarate is between 10 mM and 20 mM. 
     
     
         48 . Use of the composition of  claim 40  for the treatment of a chronic or persisting a bacterial infection. 
     
     
         49 . Use of the composition of  claim 40  for inhibiting or delaying biofilm formation or colonization on a surface.