BACTERIOPHAGE COMPOSITIONS FOR TREATING STAPHYLOCOCCUS INFECTION
The present disclosure relates to bacteriophages and compositions capable of infecting and killing Staphylococcus , and use of the same for treating Staphylococcus , e.g. Staphylococcus aureus , bacterial infections.
1 . A method of treating a Staphylococcus aureus infection comprising administering a therapeutic composition to a subject in need of treatment, wherein the therapeutic composition comprises two or more bacteriophage comprising a bacteriophage comprising a polynucleotide sequence with at least 97% identity to SEQ ID NO:2.
2 . The method of claim 1 , wherein the two or more bacteriophage comprise a bacteriophage comprising a polynucleotide sequence with at least 97% identity to SEQ ID NO: 2, and a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO:1.
3 . The method of claim 1 , wherein the two or more bacteriophage comprise a bacteriophage comprising a polynucleotide sequence with at least 98% identity to SEQ ID NO: 2, and a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO:1.
4 . The method of claim 1 , wherein the two or more bacteriophage comprise a bacteriophage comprising a polynucleotide sequence with at least 99% identity to SEQ ID NO: 2, and a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO:1.
5 . The method of claim 1 , wherein the two or more bacteriophage comprise a bacteriophage comprising a polynucleotide sequence with at least 97% identity to SEQ ID NO: 2, and a polynucleotide sequence with at least 95% identity to SEQ ID NO:1.
6 . The method of claim 1 , wherein the two or more bacteriophage comprise a bacteriophage comprising the polynucleotide sequence of SEQ ID NO:2, and a bacteriophage comprising the polynucleotide sequence of SEQ ID NO:1.
7 . The method of claim 1 , wherein the two or more bacteriophage infect and kill Staphylococcus aureus.
8 . The method of claim 1 , wherein the two or more bacteriophage are resistant to blood complement inactivation.
9 . The method of claim 8 , wherein the bacteriophage are resistant to complement C3 protein-mediated inactivation.
10 . The method of claim 1 , wherein the two or more bacteriophage belong to the genus Silviavirus.
11 . The method of claim 1 , wherein the composition is substantially free of a bacterial component, wherein the bacterial component optionally comprises bacterial host protein.
12 . The method of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier, diluent, excipient or combinations thereof.
13 . The method of claim 1 , wherein the composition is a liquid, semi-liquid, solid, frozen, or lyophilized formulation.
14 . The method of claim 1 , wherein the two or more bacteriophage of the composition target one or more of vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-resistant Staphylococcus aureus (VRSA), methicillin-resistant (MRSA) Staphylococcus aureus.
15 . The method of claim 1 , wherein the composition comprises between 1×10 8 and 1×10 11 PFU of at least one of the bacteriophage in the composition.
16 . The method of claim 1 , wherein the composition administered at a dosage of at least 1×109 PFU of total bacteriophages per milliliter.
17 . The method of claim 1 , wherein at least one bacteriophage is obligately lytic.
18 . The method of claim 1 , wherein the Staphylococcus aureus infection comprises a pulmonary infection, rhinosinusitis, urinary tract infection, intra-abdominal infection, skin infection, skin structure infection, bacteremia, septicemia, endocarditis, wound infection, or an implant infection.
19 . The method of claim 18 , wherein the implant infection comprises a cardiac implant infection (e.g., ventricular assist device infection, pacemaker infection), prosthetic joint infection, or prosthetic valve endocarditis.
20 . The method of claim 1 , wherein the Staphylococcus aureus infection is bacteremia.
21 . The method of claim 1 , wherein the Staphylococcus aureus infection is resistant to an antibiotic.
22 . The method of claim 1 , wherein the composition is administered intravenously, via intra-articular injection, via inhalation, or via nebulization.
23 . The method of claim 1 , wherein the bacteriophage is administered at least every 6 hours, at least every 12 hours, or at least every 24 hours.
24 . The method of claim 1 , wherein the bacteriophage is administered for at least 5 days.
25 . The method of claim 1 , wherein the subject is human.
26 . A method of treating a Staphylococcus aureus infection comprising administering a therapeutic composition to a subject in need of treatment, wherein the therapeutic composition comprises one or more bacteriophage comprising a bacteriophage comprising a polynucleotide sequence with at least 97% identity to SEQ ID NO:2.
27 . The method of claim 26 , wherein the composition comprises between 1×10 8 and 1×10 11 PFU of the bacteriophage.
28 . An injectable therapeutic composition formulated for treating a Staphylococcus aureus infection in a human subject in need thereof comprising one or more bacteriophage comprising a bacteriophage comprising a polynucleotide sequence with at least 97% identity to SEQ ID NO: 2, wherein the composition comprises a single dosage between 1×10 8 and 1×10 11 PFU of each bacteriophage, and the composition comprises one or more pharmaceutically acceptable carriers, excipients, or diluents.
29 . The injectable therapeutic composition of claim 28 , further comprising a storage medium for storage at a temperature at or below 8° C.
30 . A bacterial manufacturing strain comprising a bacteriophage wherein said bacteriophage comprises a polynucleotide sequence selected from a polynucleotide sequence with at least 97% identity to SEQ ID NO:2, and a polynucleotide sequence with at least 90% identity to SEQ ID NO:1.