Bacteriophage treatment and reduction in inflammatory response

Abstract

The present invention relates to the treatment of bacterial infections and the reduction of inflammatory response using bacteriophage compositions. In an aspect, provided herein are methods of treating a bacterial infection characterized by inflammation in a subject, the method comprising administering to the subject a bacteriophage composition that is essentially free of impurities, wherein the composition reduces inflammation

1 . A method of treating a bacterial infection characterized by inflammation in a subject, the method comprising administering to the subject a bacteriophage composition wherein the composition reduces inflammation. 
     
     
         2 . The method of  claim 1  wherein the bacterial infection is selected from bacteremia, septicemia, sepsis, septic shock, infective endocarditis, or an implant infection. 
     
     
         3 . The method of  claim 2  wherein the implant infection is a cardiac implant infection (e.g., ventricular assist device infection, pacemaker infection), prosthetic joint infection, infective endocarditis, or prosthetic valve endocarditis. 
     
     
         4 . The method of any one of the preceding claims wherein the bacteriophage composition comprises one or more bacteriophages selected from a bacteriophage belonging to the family Myoviridae, Siphoviridae, Podoviridae, Lipothrixviridae, Rudiviridae, Ampullaviridae, Bicaudaviridae, Clavaviridae, CorticoViridae, Cystoviridae, Fuselloviridae, Globaloviridae, Guttaviridae, Inoviridae, Leviviridae, Microviridae, Plasmaviridae, or Tectiviridae. 
     
     
         5 . The method of any one of the preceding claims wherein the composition is comprises pure bacteriophage free of impurities. 
     
     
         6 . The method of any one of the preceding claims wherein the bacteriophage composition comprises one or more bacteriophages selected Sa87, J-Sa36, Sa83, and mutants thereof, and wherein the bacterial infection is caused by  Staphylococcus.    
     
     
         7 . The method of any one of the preceding claims, wherein the bacteriophage composition comprises at least two bacteriophages selected from Sa87, J-Sa36, Sa83, or mutants thereof. 
     
     
         8 . The method of any one of the preceding claims, wherein the bacteriophage composition comprises at least three bacteriophages selected from Sa87, J-Sa36, Sa83, or mutants thereof. 
     
     
         9 . The method of any one of the preceding claims, wherein the bacteriophage composition comprises Sa87, J-Sa36, and Sa83, or mutants thereof. 
     
     
         10 . The method of any one of the preceding claims, wherein the bacterial infection comprises  Staphylococcus aureus.    
     
     
         11 . The method of any one of the preceding claims, further comprising administering an antibiotic (e.g., a chemical antibiotic) to the subject. 
     
     
         12 . The method of  claim 9 , wherein the antibiotic is a fluoroquinolone, carbapenem, aminoglycoside, cephalosporin, penicillin, beta lactam, or beta lactamase inhibitor. 
     
     
         13 . The composition or method of any one of the preceding claims, wherein the bacteriophage of the composition infect and lyse  Staphylococcus.    
     
     
         14 . The composition or method of any one of the preceding claims, wherein the bacteriophage of the composition infect and lyse  Staphylococcus aureus.    
     
     
         15 . The composition or method of any one of the preceding claims, wherein the bacteriophage of the composition infect and lyse methicillin-resistant  Staphylococcus aureus.    
     
     
         16 . The method of  claim 1  wherein the bacterial infection is selected from chronic rhinosinusitis, sinus infection, lung infection, urinary tract infection and intra-abdominal infection. 
     
     
         17 . The method of  claim 14  wherein the bacteriophage composition comprises two or more strictly lytic bacteriophage from the Myoviridae family and two or more strictly lytic bacteriophage from the Podoviridae family. 
     
     
         18 . The method of  claim 14  wherein the bacteriophage composition comprises one or more bacteriophages selected from: Pa223, Pa222, Pa193, and Pa204 and mutants thereof. 
     
     
         19 . The method of  claim 14  wherein the bacteriophage composition comprises at least two bacteriophages selected from: Pa223, Pa222, Pa193, and Pa204 and mutants thereof. 
     
     
         20 . The method of  claim 14  wherein the bacteriophage composition comprises at least three bacteriophages selected from: Pa223, Pa222, Pa193, and Pa204 and mutants thereof. 
     
     
         21 . The method of  claim 14  wherein the bacteriophage composition comprises bacteriophages Pa223, Pa222, Pa193, and Pa204 or mutants thereof. 
     
     
         22 . The method of  claim 14  wherein the bacteriophage composition consisting essentially of Pa223, Pa222, Pa193, and Pa204 or mutants thereof. 
     
     
         23 . The composition or method of any of  claims 14 - 20  wherein the bacteriophage of the composition infect and lyse  Pseudomonas.    
     
     
         24 . The composition or method of any of  claims 14 - 21  wherein the bacteriophage of the composition infect and lyse  Pseudomonas aeruginosa.    
     
     
         25 . The composition or method of any of  claims 14 - 22  wherein the bacteriophage of the composition infect and lyse multi-drug resistant  Pseudomonas aeruginosa.    
     
     
         26 . The method of any one of the preceding claims, wherein the composition further comprises an antibiotic (e.g., a chemical antibiotic). 
     
     
         27 . The method of  claim 21 , wherein the antibiotic is a fluoroquinolone, carbapenem, aminoglycoside, cephalosporin, penicillin, beta lactam, or beta lactamase inhibitor. 
     
     
         28 . The method of any one of the preceding claims, wherein the composition further comprises a pharmaceutically acceptable carrier, diluent, excipient or combinations thereof. 
     
     
         29 . The method according to  claim 23 , wherein the pharmaceutically acceptable carrier, diluent, excipient or combinations thereof comprises MgSO 4 . 
     
     
         30 . The method of any one of the preceding claims, wherein the bacterial infection is an infection characterized by an inflammatory gene expression profile. 
     
     
         31 . The method of any one of the preceding claims wherein the reduction in inflammation is measured as a downregulation of the inflammatory gene expression profile. 
     
     
         32 . The method of any one of the preceding claims, wherein the bacterial infection is resistant to antibiotics. 
     
     
         33 . A method for determining efficacy of a bacteriophage formulation in a subject receiving bacteriophage therapy to treat an inflammatory bacterial infection, comprising:
 a) obtaining a first gene expression profile for two or more informative genes in a first biological sample, wherein the first biological sample is obtained from the subject prior to administration of the bacteriophage therapy;   b) obtaining a subsequent gene expression profile for the two or more informative genes in a subsequent biological sample, wherein the subsequent biological sample is obtained from the subject after administration of the bacteriophage therapy; and   c) correlating the first gene expression profile and the subsequent gene expression profile, wherein said correlating step comprises assigning the difference in the first and subsequent gene expression profiles a positive, intermediate, or negative assay score; and   d) treating the patient based on the positive, intermediate, or negative assay score wherein comprises therapeutic intervention.