Use of lysin to restore/augment antibacterial activity in the presence of pulmonary surfactant of antibiotics inhibited thereby
AssigneeContrafect Corporation
InventorsMichael WITTEKIND, Raymond SCHUCH
Life of this patent
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Abstract
The present disclosure relates to methods for restoring or augmenting bactericidal activity of an antibiotic in an organ or tissue in which pulmonary surfactant is present. More specifically, the present disclosure describes that inhibition of antibiotics due to environmental factors, such as the presence of pulmonary surfactant in an organ or tissue such as the respiratory epithelium can be sidestepped or overcome and the effectiveness of the antibiotic in that milieu restored or augmented by co-administration of an antibiotic and a lysin.
Claims29
A method for treating a subject afflicted with a bacterial infection of an organ or tissue in which pulmonary surfactant is present, the method comprising regardless of order the following steps:
- a. administering to the subject a first amount of an antibiotic having antibacterial activity against the bacteria responsible for the infection which activity is inhibited by the pulmonary surfactant;
- b. co-administering to the subject a second amount of a lysin polypeptide, said lysin polypeptide having activity against the bacteria responsible for the infection;
- wherein said first and second amount in combination are effective to kill the bacteria responsible for the infection and thereby treat the infection.
(canceled)
A method for treating a subject afflicted with a Streptococcus or Staphylococcus bacterial infection of the lower respiratory tract in which pulmonary surfactant is present, the method comprising regardless of order the following steps:
- a. administering to the subject a first amount of an antibiotic having antibacterial activity against the bacteria responsible for the infection which activity is inhibited by the pulmonary surfactant;
- i. co-administering to the subject a second amount of at least one lysin polypeptide, selected from the group consisting of:
- CF-301, ClyS, lysostaphin, LysK, Sal-200, LysGH15, PlyV12, ClyH, MV-L, Ply, PlyPly, PlyGBS, LambdaSa1, LambdaSa2, Cpl1, Pal, active fragments thereof, and chimeric combinations thereof wherein the binding domain of one of the foregoing lysins or fragments has been fused to the catalytic domain of another
- wherein said first and second amount in combination are effective to kill the bacteria responsible for the infection and thereby treat the infection.
A method for restoring bactericidal activity of an antibiotic in an organ or tissue in which pulmonary surfactant is present in an amount that is or would be inhibitory of the activity of the antibiotic against a bacterial infection in said organ or tissue, the method comprising:
- administering to a subject afflicted with an infection of said organ or tissue a first amount of said antibiotic and co-administering to the subject a second amount of a lysin polypeptide having antibacterial activity against the bacterium responsible for the infection, the amounts in combination being effective to kill said bacterium and thereby treat the infection.
A method for treating a subject afflicted with a gram-positive or gram-negative bacterial infection of the lower respiratory tract in which pulmonary surfactant is present, which subject has already been administered an antibiotic suitable for treating the infection, the method comprising continuing administration of the antibiotic to the subject and commencing co-administration to the subject of a bactericidal activity-restoring amount of a lysin polypeptide having activity against the bacterium responsible for the infection in the subject and thereby restoring bactericidal activity of the antibiotic against the bacteria responsible for the infection of the lower respiratory tract of the subject.
The method of claim, 5 wherein the antibiotic is daptomycin.
Dependencies are inferred from the claim text.