Combination products for the treatment of bacterial infections and methods of producing or dosing of same
Provided herein are methods of treating a bacterial infection, wherein the methods comprise administering (a) ceftibuten or a pharmaceutically acceptable salt thereof, or a hydrate of the foregoing; and (b) clavulanic acid, or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions, articles of manufacture, and kits comprising a) ceftibuten or a pharmaceutically acceptable salt thereof, or a hydrate of the foregoing; and (b) clavulanic acid, or a pharmaceutically acceptable salt thereof, and uses thereof.
1. A method of treating an Enterobacteriaceae bacterial infection, the method comprising orally administering to a human individual (a) ceftibuten or a pharmaceutically acceptable salt thereof, or a hydrate of the foregoing; and (b) clavulanic acid, or a pharmaceutically acceptable salt thereof, wherein:
the bacterial infection is caused by an Enterobacteriaceae that expresses an extended-spectrum beta-lactamase (ESBL); and
component (a) and component (b) are administered in three divided doses per day, wherein the divided dose of component (a) is about 300-400 mg of component (a) and the divided dose of component (b) is about 100-250 mg of component (b).
2. The method of claim 1 , wherein the bacterial infection is a complicated urinary tract infection (cUTI), acute pyelonephritis, uncomplicated UTI (uUTI), complicated intra-abdominal infection (cIAI) or community acquired pneumonia (CAP).
3. The method of claim 1 , wherein the bacterial infection is complicated urinary tract infection (cUTI) or acute pyelonephritis.
4. The method of claim 1 , wherein component (a) and component (b) are administered simultaneously.
5. The method of claim 1 , wherein component (a) and component (b) are administered sequentially.
6. The method of claim 1 , wherein the divided dose of component (b) is about 125-187.5 mg.
7. The method of claim 1 , wherein component (a) is ceftibuten dihydrate.
8. The method of claim 1 , wherein component (b) is potassium clavulanate.
9. The method of claim 1 , wherein component (a) and component (b) are administered for 7-10 days.
10. The method of claim 1 , wherein component (a) and component (b) are formulated as a capsule or a tablet.
11. The method of claim 1 , wherein the Enterobacteriaceae is a C. freundii, E. aerogenes, E. cloacae, E. coli, K. pneumoniae , or K. oxytoca.
12. The method of claim 1 , wherein the ESBL is a CTX-M.
13. A method of treating an Enterobacteriaceae bacterial infection, the method comprising orally administering to a human individual (a) ceftibuten, a pharmaceutically acceptable salt thereof, or a hydrate of the foregoing, wherein:
the bacterial infection is caused by an Enterobacteriaceae that expresses an extended-spectrum beta-lactamase (ESBL);
component (a) is administered in three divided doses per day, wherein the divided dose is about 300-400 mg; and
component (a) is administered with (b) clavulanic acid or a pharmaceutically acceptable salt thereof, wherein component (b) is orally administered in three divided doses per day and the divided dose of component (b) is about 100-250 mg.
14. The method of claim 13 , wherein the bacterial infection is a complicated urinary tract infection (cUTI), acute pyelonephritis, uncomplicated UTI (uUTI), complicated intra-abdominal infection (cIAI) or community acquired pneumonia (CAP).
15. The method of claim 13 , wherein the bacterial infection is complicated urinary tract infection (cUTI) or acute pyelonephritis.
16. The method of claim 13 , wherein component (a) is administered simultaneously with component (b).
17. The method of claim 13 , wherein component (a) is administered sequentially with component (b).
18. The method of claim 13 , wherein component (a) is ceftibuten dihydrate.
19. The method of claim 13 , wherein component (b) is potassium clavulanate.
20. A method of treating an Enterobacteriaceae bacterial infection, the method comprising orally administering to a human individual (b) clavulanic acid or a pharmaceutically acceptable salt thereof, wherein:
the bacterial infection is caused by an Enterobacteriaceae that expresses an extended-spectrum beta-lactamase (ESBL);
component (b) is administered in three divided doses per day, wherein the divided dose of component (b) is about 100-250 mg; and
component (b) is administered with (a) ceftibuten, a pharmaceutically acceptable salt thereof, or a hydrate of the foregoing, wherein component (a) is orally administered in three divided doses per day and the divided dose of component (a) is about 300-400 mg.
21. The method of claim 20 , wherein the divided dose of component (b) is about 125-187.5 mg.
22. The method of claim 20 , wherein the bacterial infection is a complicated urinary tract infection (cUTI), acute pyelonephritis, uncomplicated UTI (uUTI), complicated intra-abdominal infection (cIAI) or community acquired pneumonia (CAP).
23. The method of claim 20 , wherein the bacterial infection is complicated urinary tract infection (cUTI) or acute pyelonephritis.
24. The method of claim 20 , wherein component (b) is administered simultaneously with component (a).
25. The method of claim 20 , wherein component (b) is administered sequentially with component (a).
26. The method of claim 20 , wherein component (a) is ceftibuten dihydrate.
27. The method of claim 20 , wherein component (b) is potassium clavulanate.
28. The method of claim 13 , wherein component (a) and component (b) are administered for 7-10 days.
29. The method of claim 13 , wherein the ESBL is a CTX-M.
30. The method of claim 20 , wherein the ESBL is a CTX-M.