Therapeutic bacteriophage compositions for treating
The present disclosure relates to a bacteriophage composition comprising one or more (suitably two or more, or three) obligately lytic bacteriophages capable of infecting and lysing Staphylococcus aureus , and use of the same for treating Staphylococcus aureus bacterial infections.
1. A method of treating a human with a bacterial infection comprising administration to said human a composition comprising one or more distinct bacteriophages that infect and lyse Staphylococcus aureus and having a genome comprising a polynucleotide sequence having at least 95% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3; wherein the bacterial infection is caused by Staphylococcus aureus.
2. The method of claim 1 , wherein the composition comprises at least three distinct bacteriophages selected from a bacteriophage having a genome comprising a polynucleotide sequence having at least 95% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
3. The method of claim 1 , wherein the bacterial infection is rhinosinusitis, urinary tract infection, intra-abdominal infection, skin infection, skin structure infection, bacteremia, septicemia, endocarditis, or an implant infection.
4. The method of claim 3 , wherein the implant infection is a cardiac implant infection, prosthetic joint infection, or prosthetic valve endocarditis.
5. The method of claim 4 , wherein the cardiac implant infection is a ventricular assist device infection or a pacemaker infection.
6. The method of claim 1 , wherein the bacterial infection is resistant to an antibiotic.
7. The method of claim 1 , wherein the composition comprises a combination of bacteriophages Sa87, J-Sa36, and Sa83, said bacteriophages comprising the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively.
8. The method of claim 1 , wherein the composition is substantially pure of endotoxin.
9. The method of claim 1 , wherein the composition is substantially pure of bacterial host cell protein.
10. The method of claim 1 , wherein the composition further comprises a pharmaceutically acceptable excipient, a carrier, or a combination thereof.
11. The method of claim 10 , wherein the pharmaceutically acceptable excipient, carrier, or combination thereof comprises a calcium salt or magnesium salt.
12. The method of claim 1 , wherein the composition is a liquid, semi-liquid, solid, frozen, or lyophilized formulation.
13. The method of claim 1 , wherein the composition comprises 3×10 5 to 3×10 11 plaque forming units (PFU) of total bacteriophages.
14. The method of claim 1 , wherein the composition comprises between 1×10 5 and 1×10 11 PFU of each bacteriophage.
15. The method of claim 1 , wherein the composition is administered in a dosage of one milliliter comprising 3×10 9 PFU total bacteriophage.
16. The method of claim 1 , wherein the composition further comprises an antibiotic.
17. The method of claim 16 , wherein the antibiotic is from an antibiotic class selected from the group consisting of a fluoroquinolone, carbapenem, aminoglycoside, ansamycin, cephalosporin, penicillin, beta-lactam, beta-lactamase inhibitor, folate pathway inhibitor, fucidane, glycopeptide, glycylcycline, lincosamide, lipopeptide, macrolide, oxazolidinone, phenicol phosphonic acid, streptogramin, and tetracycline.
18. The method of claim 1 , wherein the bacterial infection is an infection characterized by the presence of a bacterial biofilm.
19. The method of claim 1 wherein the composition is administered via the intra-articular route.
20. The method of claim 1 , wherein the composition is administered at least every 6 hours.
21. The method of claim 1 , wherein the composition is administered at least every 12 hours.
22. The method of claim 1 , wherein the composition is administered at least every 24 hours.
23. The method of claim 1 , wherein the composition is administered for at least 7 days.
24. A method of treating a human with a confirmed non-pulmonary S. aureus infection comprising administration to said human of a composition comprising at least two distinct bacteriophages that infect and lyse Staphylococcus aureus and said at least two bacteriophages comprising a genome comprising a nucleotide sequence having at least 95% identity to any of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, wherein the infection is not a pulmonary S. aureus infection.
25. A method of modifying the microbial flora in a human comprising administering to said human a composition comprising at least two distinct bacteriophages having lytic activity to Staphylococcus aureus bacteria, said at least two distinct bacteriophages being selected from the bacteriophages having a genome comprising a nucleotide sequence having at least 95% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
26. The method of claim 25 , further comprising administering an antibiotic to the subject.
27. The method of claim 26 , wherein the antibiotic is a fluoroquinolone, carbapenem, aminoglycoside, cephalosporin, penicillin, beta-lactam, or beta-lactamase inhibitor.
28. The method of claim 25 , wherein the composition is administered intravenously.