Antibiotic compositions and methods of use

Abstract

The present disclosure describes compositions comprising β-lactam antibiotics and branched poly-ethylenimines (BPEI), having efficacy against various Gram-positive bacteria, for example Gram-positive bacteria having resistance against βlactam antibiotics, one non-limiting example of which is Methicillin-resistant Staphylococcus aureus (MRSA). The compositions result in the resensitization of such resistant bacterial strains to traditional antibiotic therapies such as β-lactam antibiotics.

1 . An antibiotic composition, comprising: a β-lactam antibiotic, and a branched poly(ethylenimine) (BPEI) compound, wherein the antibiotic composition is effective against a bacterium which is resistant to the β-lactam antibiotic when the β-lactam antibiotic is administered alone, and wherein the β-lactam antibiotic and the BPEI compound of the antibiotic composition interact synergistically against the resistant bacterium. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The antibiotic composition of  claim 1 , wherein the antibiotic composition has a synergistic fractional inhibitory concentration (FIC) against the resistant bacterium, wherein the FIC≤0.5. 
     
     
         5 . (canceled) 
     
     
         6 . The antibiotic composition of  claim 1 , wherein the BPEI compound has a molecular weight in a range of 0.1 kilodalton (kDa) to 25 kDa. 
     
     
         7 . The antibiotic composition of  claim 1 , further comprising a pharmaceutically-acceptable carrier, vehicle, or diluent. 
     
     
         8 . The antibiotic composition of  claim 1 , wherein the resistant bacterium is a methicillin-resistant  Staphylococcus aureus  (MRSA). 
     
     
         9 . The antibiotic composition of  claim 1 , wherein the resistant bacterium is selected from the group consisting of  Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus , methicillin-resistant  Staphylococcus aureus  (MRSA), oxacillin-resistant  Staphylococcus aureus  (ORSA), vancomycin-resistant  Staphylococcus aureus  (VRSA), a  Streptococcus pneumonia, Streptococcus mutans, Streptococcus sanguinis, Staphylococcus epidermidis, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium botulinum , and  Listeria monocytogenes.    
     
     
         10 - 16 . (canceled) 
     
     
         17 . A method of treating a bacterial infection in a subject, comprising:
 administering to the subject a β-lactam antibiotic and a branched poly(ethylenimine) (BPEI) compound in amounts effective in inhibiting the bacterial infection in the subject, wherein the β-lactam antibiotic and the BPEI compound inhibit the bacterial infection by interacting synergistically against the bacterium causing the bacterial infection.   
     
     
         18 . The method of  claim 17 , wherein the bacterial infection is caused by a β-lactam antibiotic-resistant bacterium. 
     
     
         19 . The method of  claim 17 , wherein the β-lactam antibiotic and the BPEI compound are administered to the subject in sequential or simultaneous steps, or as a composition comprising both the β-lactam antibiotic and the BPEI compound. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 17 , wherein the β-lactam antibiotic and the BPEI compound together have a synergistic fractional inhibitory concentration (FIC) against the bacterium causing the bacterial infection, wherein the FIC≤0.5. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 17 , wherein the BPEI compound has a molecular weight in a range of 0.1 kilodalton (kDa) to 25 kDa. 
     
     
         24 . The method of  claim 17 , wherein the bacterial infection is caused by a methicillin-resistant  Staphylococcus aureus  (MRSA). 
     
     
         25 . The method of  claim 17 , wherein the bacterial infection is caused by a bacterium selected from the group consisting of  Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus , methicillin-resistant  Staphylococcus aureus  (MRSA), oxacillin-resistant  Staphylococcus aureus  (ORSA), vancomycin-resistant  Staphylococcus aureus  (VRSA), a  Streptococcus pneumonia, Streptococcus mutans, Streptococcus sanguinis, Staphylococcus epidermidis, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium botulinum , and  Listeria monocytogenes.    
     
     
         26 - 32 . (canceled) 
     
     
         33 . A method for treating a bacterial infection in a subject, comprising administering to the subject in need of such treatment an antibacterially-effective combination of a β-lactam antibiotic and a BPEI compound, wherein the antibacterially-effective combination has a fractional inhibitory concentration (FIC) and wherein the β-lactam antibiotic and the BPEI compound of the antibiotic composition interact synergistically against the bacterium. 
     
     
         34 . (canceled) 
     
     
         35 . The antibiotic composition of  claim 33 , wherein the BPEI compound has a molecular weight in a range of 0.1 kilodalton (kDa) to 25 kDa. 
     
     
         36 . The antibiotic composition of  claim 33 , further comprising a pharmaceutically-acceptable carrier, vehicle, or diluent. 
     
     
         37 . The antibiotic composition of  claim 33 , wherein the bacterium is a methicillin-resistant  Staphylococcus aureus  (MRSA). 
     
     
         38 . The antibiotic composition of  claim 33 , wherein the bacterium is selected from the group consisting of a β-lactam antibiotic resistant form of  Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus , methicillin-resistant  Staphylococcus aureus  (MRSA), oxacillin-resistant  Staphylococcus aureus  (ORSA), vancomycin-resistant  Staphylococcus aureus  (VRSA), a  Streptococcus pneumonia, Streptococcus mutans, Streptococcus sanguinis, Staphylococcus epidermidis, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium botulinum , and  Listeria monocytogenes.