Compositions and methods for treating bacterial infections

Abstract

Pharmaceutical compositions and methods for treating bacterial infections are disclosed.

1 . A pharmaceutical composition comprising: (a) at least one antibacterial agent or a pharmaceutically acceptable derivative thereof, and (b) an enhancer compound or a pharmaceutically acceptable derivative thereof; wherein the enhancer compound is: (i) beta-lactamase stable, and (ii) a selective and high affinity penicillin binding proteins (PBP) binder. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the antibacterial agent is selected from the group consisting of aminoglycosides, ansamycins, carbacephems, penems, carbapenems, cephalosporins, cephamycins, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, penicillins, polypeptides, quinolones, sulfonamides, tetracyclines, and oxazolidinone antibacterial agents. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the enhancer compound or pharmaceutically acceptable derivative thereof, is present in an amount from about 0.01 to 10 grams per gram of the antibacterial agent or a pharmaceutically acceptable derivative thereof. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the enhancer compound or pharmaceutically acceptable derivative thereof, is capable of selectively binding to one of the essential penicillin binding proteins (PBPs). 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein, the antibacterial agent or pharmaceutically acceptable derivative thereof, and the enhancer compound or pharmaceutically acceptable derivative thereof, are complementary PBP binding agents. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein the enhancer compound or pharmaceutically acceptable derivative thereof, and the antibacterial agent or pharmaceutically acceptable derivative thereof, are present in the concentrations lower than, or equal to, or higher than the corresponding minimum inhibitory concentrations. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the antibacterial agent or pharmaceutically acceptable derivative thereof, is present at its minimum filamentation concentration and the enhancer compound or a pharmaceutically acceptable derivative thereof, is present at its minimum spheroplasting concentration. 
     
     
         8 . A method of treating a bacterial infection in a subject comprising the step of administering to the subject an effective amount of a pharmaceutical composition according to one of  claims 1 - 7 . 
     
     
         9 . A method of treating a bacterial infection in a subject comprising the step of administering to the subject an effective amount of: (a) at least one antibacterial agent or pharmaceutically acceptable derivative thereof, and (b) an enhancer compound or a pharmaceutically acceptable derivative thereof; wherein the enhancer compound is: (i) beta-lactamase stable, and (ii) a selective and high affinity PBP binder. 
     
     
         10 . A method for increasing antibacterial effectiveness of an antibacterial agent in a subject, said method comprising co-administering said antibacterial agent or pharmaceutically acceptable derivative thereof, with an enhancer compound or a pharmaceutically acceptable derivative thereof; wherein the enhancer compound is: (i) beta-lactamase stable, and (ii) a selective and high affinity PBP binder. 
     
     
         11 . The method according to one of  claims 9 - 10 , wherein the antibacterial agent is selected from a group consisting of aminoglycosides, ansamycins, carbacephems, penems, carbapenems, cephalosporins, cephamycins, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, penicillins, polypeptides, quinolones, sulfonamides, tetracyclines, and oxazolidinone antibacterial agents. 
     
     
         12 . The method according to one of  claims 9 - 10 , wherein the enhancer compound or pharmaceutically acceptable derivative thereof, is present an amount from about 0.01 to 10 grams per gram of the antibacterial agent or pharmaceutically acceptable derivative thereof. 
     
     
         13 . The method according one of  claims 9 - 10 , wherein the enhancer compound or pharmaceutically acceptable derivative thereof, is capable of selectively binding to one of the essential PBPs. 
     
     
         14 . The method according one of  claims 9 - 10 , wherein the antibacterial agent or pharmaceutically acceptable derivative thereof, and the enhancer compound or pharmaceutically acceptable derivative thereof, are complementary PBP binding agents. 
     
     
         15 . The method according to one of  claims 9 - 10 , wherein the enhancer compound or pharmaceutically acceptable derivative thereof, and antibacterial agent or pharmaceutically acceptable derivative thereof, are present in the concentrations lower than, or equal to, or higher than the corresponding minimum inhibitory concentrations. 
     
     
         16 . The method according to one of  claims 9 - 10 , wherein the antibacterial agent or pharmaceutically acceptable derivative thereof, is present at its minimum filamentation concentration and the enhancer compound or a pharmaceutically acceptable derivative thereof, is present at its minimum spheroplasting concentration.