Bacteriophage-containing therapeutic agents
The present invention relates in its broadest aspect to combined phage/antibiotic therapy. More particularly, it relates to use of (i) one or more bacteriophages and (ii) one or more antibiotics in the manufacture of a combined product for simultaneous, separate or sequential administration of (i) and (ii) to treat a bacterial infection characterized by biofilm formation, for example an infection comprising or consisting of P. aeruginosa . Treatment in this context may be either therapeutic or prophylactic treatment. Also provided are deposited bacteriophages each exhibiting different strain specificity against P. aeruginosa and combinations of such bacteriophages, e.g. a panel of six deposited bacteriophages which was found to be effective against a high percentage of clinical isolates of P. aeruginosa from canine ear infections.
1. A panel of isolated bacteriophages for treating a Pseudomonas aeruginosa bacterial infection, wherein the panel comprises two or more bacteriophages selected from the group consisting of:
(i) mutants of deposited strains NCIMB 41174, NCIMB 41175, NCIMB 41176, NCIMB 41177, NCIMB 41178, NCIMB 41179, NCIMB 41180, and NCIMB 41181 that retain the ability to infect P. aeruginosa,
wherein the mutant has at least 90% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain, and each member of the panel has a different strain specificity for P. aeruginosa.
2. The panel of claim 1 , wherein the mutant has at least 95% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain.
3. The panel of claim 1 , wherein the mutant has at least 97% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain.
4. The panel of claim 1 , wherein the mutant has at least 98% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain.
5. The panel of claim 1 , wherein the mutant has at least 99% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain.
6. The panel of claim 1 , comprising six bacteriophages selected from the group consisting of:
(i) mutants of deposited strains NCIMB 41174, NCIMB 41175, NCIMB 41176, NCIMB 41177, NCIMB 41178, and NCIMB 41179 that retain the ability to infect P. aeruginosa.
7. The panel of claim 6 , wherein the mutant has at least 95% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain.
8. The panel of claim 6 , wherein the mutant has at least 97% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain.
9. The panel of claim 6 , wherein the mutant has at least 98% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain.
10. The panel of claim 6 , wherein the mutant has at least 99% nucleotide sequence identity across its whole genome as compared to the genome of the deposited strain.
11. A pharmaceutical composition comprising the panel of claim 1 , and a pharmaceutical carrier or diluent.
12. A pharmaceutical composition comprising the panel of claim 6 , and a pharmaceutical carrier or diluent.
13. A method for treating a Pseudomonas aeruginosa bacterial infection, the method comprising administering to a human or non-human animal in need thereof the pharmaceutical composition of claim 11 .
14. A method for treating a Pseudomonas aeruginosa bacterial infection, the method comprising administering to a human or non-human animal in need thereof the pharmaceutical composition of claim 12 .
15. The method of claim 13 , further comprising administering one or more antibiotics sequentially to the administering of the pharmaceutical composition.
16. The method of claim 13 , further comprising administering alginase.
17. The method of claim 13 , wherein the infection is selected from an infection of a skin burn or other skin wound, a lung infection, an ocular infection, an ear infection or a urinary tract infection.
18. The method of claim 13 , wherein the infection is a canine ear infection.
19. The method of claim 13 , wherein the human or non-human animal has a medical implant.