Compositions Comprising Multiple Bioactive Agents, and Methods of Using the Same

Abstract

In part, the present invention is directed to compositions comprising a FabI inhibitor and at least one other bioactive agent. In another part, the present invention is directed to antibacterial compositions comprising a compound of formulas I-III and at least one other antibacterial agent.

1 . A composition comprising an antibacterial agent and an anti-infective agent wherein said antibacterial agent substantially inhibits Fab I. 
     
     
         2 . The composition of  claim 1 , wherein a fractional inhibitory concentration for the combination of said antibacterial agent and anti-infective agent is less than or equal to 4 as calculated against antibiotic resistant strains of bacteria. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said fractional inhibitory concentration is less than or equal to 2. 
     
     
         4 . The composition of  claim 2 , wherein said bacteria is  Staphylococcus.    
     
     
         5 . The composition of  claim 3 , wherein said antibacterial agent inhibits Fab I with a MIC of less than about 64 ug/ml. 
     
     
         6 . The composition of  claim 1  wherein the ratio of antibacterial agent to anti-infective agent is about 0.01:100 to about 100:0.01. 
     
     
         7 . The composition of  claim 1  further comprising a pharmaceutically acceptable carrier or excipient. 
     
     
         8 . The composition of  claim 1  wherein said anti-infective agent is an antibiotic. 
     
     
         9 . The composition of  claim 8 , wherein said anti-infective agent does not substantially inhibit Fab I. 
     
     
         10 . The composition of  claim 8 , wherein said antibiotic is selected from one or more of the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, penicillins and beta lactamase inhibitors, carbepenems, monobactams, macrolides, lincosamines, glycopeptides, rifampin, oxazolidonones, tetracyclines, aminoglycosides, streptogramins, or sulfonamides. 
     
     
         11 . The composition of  claim 8 , wherein said antibiotic is a cephalosporin. 
     
     
         12 .- 36 . (canceled) 
     
     
         37 . A method for treating a bacterial infection potentially caused by a drug resistant bacteria in a patient comprising administering to a patient in need of such treatment a composition comprising an antibacterial agent that substantially inhibits Fab I and at least one additional anti-infective agent. 
     
     
         38 . The method of  claim 37  wherein said treatment is carried out for 1 to 60 days. 
     
     
         39 . The method of  claim 37 , wherein said bacterial infection is a condition selected from the group consisting of endocarditis, osteomylelitis, meningitis, skin infections, pneumonias, bacteremias, intra-abdominal infections, genitourinary tract infections, abscesses, and necrotizing infections. 
     
     
         40 . The method of  claim 37 , wherein the antibacterial agent inhibits the Fab I activity of a microbe with a K, at least 1 order of magnitude lower than the K, for inhibiting enoyl CoA hydratase of a mammal. 
     
     
         41 . The method of  claim 40 , wherein the mammal is a human. 
     
     
         42 . A kit comprising the pharmaceutical composition of  claim 7  and instructions for use thereof.