Therapeutic combination of daptomycin and protein synthesis inhibitor antibiotic, and methods of use
A therapeutic combination comprises an antibacterially effective amount of daptomycin, and an amount of protein synthesis inhibitor antibiotic effective to prevent the development of daptomycin non-susceptibility in bacteria. Related combination therapies and methods are also included.
1. A therapeutic combination comprising
(i) an antibacterially effective amount of daptomycin; and
(ii) a compound of formula
wherein R 7 is H, PO(OH) 2 or PO(O) 2 −2 (M + ) 2 , and wherein M + is Na + ,
wherein the dosage of the compound of part (ii) is no more than about 1 mg/kg of body weight and wherein the dosage is effective to prevent the development of daptomycin non-susceptible bacterial strains.
2. The therapeutic combination of claim 1 , wherein the compound of Formula (I) is
3. The therapeutic combination of claim 1 ,
wherein the combination of the daptomycin and the compound do not act synergistically to enhance antibacterial potency, wherein the FICI is >0.50.
4. The therapeutic combination of claim 1 ,
wherein each component of the therapeutic combination is formulated for separate or sequential administration.
5. The therapeutic combination of claim 1 ,
wherein the therapeutic combination is formulated for simultaneous administration.
6. A method of treating a methicillin resistant S. aureus (MRSA) infection in a subject, comprising administering to the subject the therapeutic combination of claim 1 .
7. A method of treating a methicillin resistant S. aureus (MRSA) infection in a subject, comprising administering to the subject the therapeutic combination of claim 2 .
8. The method of claim 6 , wherein the bacterially infected subject has a bacterial infection that requires treatment for greater than two weeks.
9. The method of claim 7 , wherein the bacterially infected subject has a bacterial infection that requires treatment for greater than two weeks.
10. The method of claim 6 , wherein the bacterial infection is a bacterial skin and skin structure infection or bacteremia.
11. The method of claim 6 , wherein the subject has endocarditis.
12. The method of claim 9 , wherein the administering step further comprises administering the therapeutic combination for at least two weeks.
13. The method of claim 7 , wherein the administering step further comprises administering the same amount of daptomycin until the infection is resolved.
14. The therapeutic combination of claim 2 ,
wherein each component of the therapeutic combination is formulated for separate or sequential administration.
15. The therapeutic combination of claim 2 ,
wherein the therapeutic combination is formulated for simultaneous administration.
16. The therapeutic combination of claim 2 , wherein the dosage of the compound of Formula (I) is no more than about 0.5 mg/kg.
17. The method of claim 7 , wherein the bacterial infection is a bacterial skin and skin structure infection or bacteremia.
18. The method of claim 7 , wherein the subject has endocarditis.