Treatment of topical and systemic bacterial infections

Abstract

Bacteriophage covalently attached to a carrier particle with an average diameter of from 0.1 microns to 15 microns, are used in topical treatment of bacterial infection. Bacteriophage covalently attached to a carrier particle of average diameter 7 microns or less are used in systemic treatment of bacterial infection. A plurality of bacteriophages lytic against different bacterial strains gives wide antibacterial activity. A combination therapy comprises administration of antibiotic and bacteriophage covalently attached to a carrier particle.

1 - 50 . (canceled) 
     
     
         51 . A topical formulation, comprising a bacteriophage covalently attached to a carrier particle and a pharmaceutically acceptable carrier or excipient, wherein the topical formulation is formulated to treat a bacterial infection. 
     
     
         52 . The topical formulation of  claim 51 , wherein the topical formation is a gel, cream or lotion. 
     
     
         53 . The topical formulation of  claim 52 , further comprising one or more agents selected from the group consisting of:
 a gel-forming agent,   a cream-forming agent,   a wax,   an oil,   a surfactant, and   a binder.   
     
     
         54 . The topical formulation of  claim 51 , wherein the carrier particle has an average diameter of up to 20 microns. 
     
     
         55 . The topical formulation of  claim 51 , wherein the carrier particle has an average diameter of 0.1 microns to 15 microns. 
     
     
         56 . The topical formulation of  claim 51 , wherein the carrier particle has an average diameter of 0.5 microns to 10 microns. 
     
     
         57 . The topical formulation of  claim 52 , wherein:
 (a) the topical formulation is a cream or gel;   (b) the bacteriophage is lytic for P. acnes; and   (c) the carrier particle has an average diameter of up to 20 microns.   
     
     
         58 . The topical formulation of  claim 57 , wherein the bacteriophage is lytic for at least 3 different strains of  P. acnes.    
     
     
         59 . The topical formulation of  claim 52 , wherein:
 (a) the topical formulation is a cream or gel;   (b) the bacteriophage is lytic for  S. aureus;  and   (c) the carrier particle has an average diameter of up to 20 microns.   
     
     
         60 . The topical formulation of  claim 59 , wherein the bacteriophage is lytic for at least 3 different strains of  S. aureus.    
     
     
         61 . The topical formulation of  claim 51 , wherein the bacteriophage is at a concentration of 10 2  to 10 10  plaque-forming units (pfu) per ml. 
     
     
         62 . The topical formulation of  claim 61 , wherein the bacteriophage concentration is from 10 2  to 10 6  pfu per ml. 
     
     
         63 . The topical formulation of  claim 54 , wherein the average diameter is measured using a laser diffraction method. 
     
     
         64 . The topical formulation of  claim 51 , wherein the carrier particle comprises a material selected from the group consisting of: nylon, polymethyl methacrylate, polyethylene, ethylene/acrylate copolymer, polyurethane, silicone resin, silica, nylon-12, and nylon-1010. 
     
     
         65 . The topical formulation of  claim 51 , further comprising an antibiotic. 
     
     
         66 . The topical formulation of  claim 65 , wherein the antibiotic is ampicillin. 
     
     
         67 . The topical formulation of  claim 51 , wherein the bacteriophage comprises one or more of an ssRNA bacteriophage, a dsRNA bacteriophage, an ssDNA bacteriophage, and a dsDNA bacteriophage. 
     
     
         68 . The topical formulation of  claim 67 , wherein the bacteriophage has a circular or linear arraignment of its genetic material. 
     
     
         69 . The topical formulation of  claim 51 , wherein the bacteriophage is selected from the group consisting of: Bacteriophage K, Myoviridae, Siphoviridae, Podoviridae, Lipothrixviridea, Rudiviridae, Ampullaviridae, Bacilloviridae, Bicaudaviridae, Clavaviridae, Corticoviridae, Cystoviridae, Fusseloviridae, Globuloviridae, Guttavirus, Inoviridae, Leviviridae, Microviridae, Plasmaviridae, and Tectiviridae. 
     
     
         70 . The topical formulation of  claim 51 , comprising a plurality of bacteriophages, wherein each of the plurality of bacteriophages is covalently attached to a carrier particle. 
     
     
         71 . A method of treating a topical bacterial infection of a subject, comprising administering the topical formulation of  claim 51  to the subject. 
     
     
         72 . The method of  claim 71 , wherein the subject is a mammal, 
     
     
         73 . The method of  claim 72 , wherein the mammal is a human, 
     
     
         74 . The method of  claim 71 , wherein the carrier particle is approximately spherical and has an average diameter of up to 20 microns. 
     
     
         75 . The method of  claim 71 , wherein the topical bacterial infection is acne. 
     
     
         76 . The method of  claim 71 , wherein the topical formulation is free of salicylic acid and free of benzoyl peroxide. 
     
     
         77 . The method of  claim 71 , wherein the topical bacterial infection is:
 (a) impetigo caused by  S. aureus  and/or  S. pyogenes;      (b) folliculitis, furunculosis, or carbunculosis caused by  S. aureus  or  Pseudornonas aeruginosa;      (c) ecthyma caused by  S. aureus  or  S. pyogenes;  or   (d) erysipelas or cellulitis caused by group A β-hemolytic streptococcus (erysipelas),  S. aureus  (cellulitis), or  S. pyogenes.      
     
     
         78 . The method of  claim 71 , further comprising administering an antibiotic. 
     
     
         79 . The method of  claim 71 , wherein the topical formulation comprises a plurality of bacteriophages, wherein each of the plurality of bacteriophages is covalently attached to a carrier particle. 
     
     
         80 . A method of treating acne in a subject, comprising administering a topical formulation, wherein:
 (a) the topical formulation comprises a bacteriophage covalently attached to a carrier particle and a pharmaceutically acceptable carrier or excipient;   (b) the topical formulation is a gel, cream, or lotion; and   (c) the carrier particle has an average diameter of up to 10 microns.   
     
     
         81 . The method of  claim 80 , further comprising administering an antibiotic. 
     
     
         82 . A method of treating a systemic bacterial infection of a subject, comprising administering an antibiotic in combination with a topical formulation, wherein:
 (a) the topical formulation comprises a bacteriophage covalently attached to a carder particle; and   (b) the carrier particle has an average diameter of 7 microns or less.   
     
     
         83 . The method of  claim 82 , wherein the antibiotic is ampicillin, 
     
     
         84 . The method of  claim 82 , wherein the topical formulation comprises a plurality of bacteriophages lytic for 3 or more strains of bacteria, and wherein each of the plurality of bacteriophages is covalently attached to a carrier particle having an average diameter of 7 microns or less. 
     
     
         85 . The method of  claim 82 , wherein the topical formulation comprises a plurality of bacteriophages lytic for staphylococci, wherein each of the plurality of bacteriophages is covalently attached to carrier particle having an average diameter of 7 microns or less, and wherein the antibiotic is effective against staphylococci. 
     
     
         86 . The method of  claim 82 , wherein the topical formulation comprises a plurality of bacteriophages lytic for  S. aureus,  and wherein each of the plurality of bacteriophages is covalently attached to a carrier particle having an average diameter of 7 microns or less.