Methods for preventing or treating infectious diseases caused by extracellular microorganisms, including antimicrobial-resistant strains thereof, using gallium compounds

Abstract

The present invention relates to methods for preventing or treating infectious diseases caused by extracellular microorganisms, such as bacteria and fungi, by systemically administering to a patient a compound containing gallium. The extracellular microorganisms targeted by the present methods include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), E. coli O157:H7, fluoroquinolone-resistant Salmonella typhi , and the like. Furthermore, in the present methods, gallium compounds can be co-administered with one or more conventional antimicrobial agents to treat infectious diseases with reduced risks of creating multi-drug resistant pathogens. The methods of the present invention is also applicable to those microorganisms, such as ulcer-causing Helicobacter pylori , complete eradication of which so far has been difficult to achieve.

We claim: 
     
         1 . A method for treating an infectious disease caused by methicillin-resistant  Staphylococcus aureus  (“MRSA”), vancomycin-resistant enterococci (“VRE”),  E. coli  O157:H7, fluoroquinolone-resistant  Salmonella typhi , ceftazidime-resistant  Klebsiella pneumoniae , or fluoroquinolone-resistant  Neisseria gonorrhoeae  in the bloodstream of a subject, the method comprising:
 administering to the subject a therapeutically effective amount of a gallium compound selected from the group consisting of gallium nitrate, gallium maltolate, gallium citrate, gallium phosphate, gallium chloride, gallium fluoride, gallium carbonate, gallium formate, gallium acetate, gallium sulfate, gallium tartrate, gallium oxalate, and gallium oxide, 
 wherein said therapeutically effective amount is sufficient to reduce the number of, to suppress the growth of, or to kill the methicillin-resistant  Staphylococcus aureus  (“MRSA”), vancomycin-resistant enterococci (“VRE”),  E. coli  O157:H7, fluoroquinolone-resistant  Salmonella typhi , ceftazidime-resistant  Klebsiella pneumoniae , or fluoroquinolone-resistant  Neisseria gonorrhoeae  in the bloodstream of the subject. 
 
     
     
         2 . The method of  claim 1 , further comprising co-administering a therapeutically effective amount of at least one additional antimicrobial agent. 
     
     
         3 . The method of  claim 2 , wherein the additional antimicrobial agent is vancomycin and/or linezolid. 
     
     
         4 . The method of  claim 1 , wherein the gallium compound is administered orally, intravenously, intramuscularly, subcutaneously, intraperitoneally, or by suppositories. 
     
     
         5 . A method for treating an infection in the bloodstream of a subject, the infection caused by methicillin-resistant  Staphylococcus aureus  (“MRSA”), vancomycin-resistant enterococci (“VRE”),  E. coli  O157:H7, fluoroquinolone-resistant  Salmonella typhi , ceftazidime-resistant  Klebsiella pneumoniae , or fluoroquinolone-resistant  Neisseria gonorrhoeae , said method comprising:
 administering to the subject a therapeutically effective amount of a gallium compound selected from the group consisting of gallium nitrate, gallium maltolate, gallium citrate, gallium phosphate, gallium chloride, gallium fluoride, gallium carbonate, gallium formate, gallium acetate, gallium sulfate, gallium tartrate, gallium oxalate, and gallium oxide, 
 wherein said therapeutically effective amount is sufficient to reduce the number of, to suppress the growth of, or to kill the methicillin-resistant  Staphylococcus aureus  (“MRSA”), vancomycin-resistant enterococci (“VRE”),  E. coli  O157:H7, fluoroquinolone-resistant  Salmonella typhi , ceftazidime-resistant  Klebsiella pneumoniae , or fluoroquinolone-resistant  Neisseria gonorrhoeae  in the bloodstream of the subject. 
 
     
     
         6 . The method of  claim 5 , further comprising co-administering a therapeutically effective amount of at least one additional antimicrobial agent. 
     
     
         7 . The method of  claim 6 , wherein the additional antimicrobial agent is vancomycin and/or linezolid. 
     
     
         8 . The method of  claim 5 , wherein the gallium compound is administered orally, intravenously, intramuscularly, subcutaneously, intraperitoneally, or by suppositories.