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 - 69 . (canceled)
70 . A method for treating a bacterial infection comprising administering to a subject in need of treatment a bacteriophage composition comprising one or more bacteriophages selected from a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO:1, and a bacteriophage comprising a polynucleotide sequence with at least 90% identity to SEQ ID NO:2, wherein the composition comprises between 1×10 8 and 1×10 11 PFU of each bacteriophage.
71 . The method of claim 70 , wherein the composition is administered at a dosage of at least 1×10 9 PFU of total bacteriophages per milliliter.
72 . The method of claim 70 , wherein the bacterial infection comprises a pulmonary infection, rhinosinusitis, urinary tract infection, intra-abdominal infection, skin infection, skin structure infection, bacteremia, septicemia, endocarditis, or an implant infection.
73 . The method of claim 72 , wherein the implant infection comprises a cardiac implant infection, prosthetic joint infection, or prosthetic valve endocarditis.
74 . The method of claim 70 , wherein the method further comprises administration of an antibiotic to the subject.
75 . The method of claim 74 , 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.
76 . The method of claim 70 , wherein the bacterial infection is bacteremia.
77 . The method of claim 70 , wherein the bacterial infection is resistant to an antibiotic.
78 . The method of claim 70 , wherein the bacteriophage composition is administered intravenously, via intra-articular injection, via inhalation, or via nebulization.
79 . The method of claim 70 , wherein the bacteriophage is administered at least every 6 hours, at least every 12 hours, or at least every 24 hours.
80 . The method of claim 70 , wherein the bacteriophage is administered for at least 7 days.
81 . The method of any claim 70 , wherein the subject is human.
82 . The method of claim 70 , wherein the bacterial infection is caused by Staphylococcus aureus.
83 . The method of claim 70 , wherein at least about 80% of bacteriophages in the bacteriophage composition retain lytic activity after exposure to human plasma for a time period between about 10 minutes and about 120 minutes.
84 . The method of claim 70 , wherein the composition's target bacteria range is more effective than the sum of the efficacy of individual bacteriophages in the composition.
85 . The method of claim 70 , wherein the one or more bacteriophages comprise a bacteriophage comprising a polynucleotide sequence with at least 95% identity to SEQ ID NO:1.
86 . The method of claim 70 , wherein the one or more bacteriophages comprise a bacteriophage comprising a polynucleotide sequence with at least 95% identity to SEQ ID NO:2.
87 . The method of claim 70 , wherein the one or more bacteriophages comprise a bacteriophage comprising a polynucleotide sequence with at least 95% identity to SEQ ID NO:1, and a bacteriophage comprising a polynucleotide sequence with at least 95% identity to SEQ ID NO:2.
88 . The method of claim 70 , wherein the one or more bacteriophages are selected from a bacteriophage comprising the polynucleotide sequence of SEQ ID NO:1, and a bacteriophage comprising the polynucleotide sequence of SEQ ID NO:2.
89 . The method of claim 70 , wherein the one or more bacteriophages are resistant to blood complement inactivation.
90 . The method of claim 70 , wherein the one or more bacteriophages are resistant to complement C3 protein-mediated inactivation.
91 . The method of claim 70 , wherein the one or more bacteriophages belong to the genus Silviavirus.
92 . The method of claim 70 , wherein the composition further comprises a pharmaceutically acceptable carrier, diluent, excipient or combinations thereof.
93 . The method of claim 70 , wherein the composition is a liquid, semi-liquid, solid, frozen, or lyophilized formulation.
94 . The method of claim 70 , wherein the one or more bacteriophages of the composition target one or more of vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-resistant Staphylococcus aureus (VRSA), and methicillin-resistant (MRSA) Staphylococcus aureus.
95 . The method of claim 70 , wherein the sequence of at least one bacteriophage is genetically modified.
96 . The method of claim 70 , wherein the composition further comprises a storage medium for storage at a temperature at or below 8° C.
97 . The method of claim 70 , wherein the composition is substantially free of a bacterial component, and wherein the bacterial component comprises bacterial host protein.
98 . The method of claim 70 , wherein the composition is in a container containing from about 1 ml to about 5 ml of the composition, wherein the composition is an injectable solution.
99 . The method of claim 70 , wherein at least one bacteriophage is obligately lytic.