Systems and methods for treating bacterial infection
Therapeutic methods, kits, dosing regimens and uses as medicament are provided, for example, for the treatment of bacterial infection. The therapeutic methods can comprise intravenously administering to a subject who has a bacterial infection a pharmaceutical composition comprising a fixed amount of iclaprim. The administration of the fixed amount can achieve a C max(ss) below about 800 ng/mL, a T>MIC of between about 30% to about 95% and a ratio of AUC/MIC of about 20 to about 85, and the bacterial infection can be treated. The fixed amount can be about 70 mg to about 100 mg. The pharmaceutical composition can be infused into the subject about 1 to about 3 times a day daily over a time period of about 0.75 hours to about 4 hours.
1. A therapeutic method consisting of:
intravenously administering to a subject who has a bacterial infection a pharmaceutical composition consisting of a fixed amount of iclaprim,
wherein administration of the fixed amount achieves a C max(ss) below 800 ng/mL, a T>MIC of between 30% to 95% and a ratio of AUC/MIC of 20 to 80,
wherein the fixed amount is 80 mg,
wherein the intravenous administration consists of infusing the pharmaceutical composition into the subject over a time period of 2 hours,
and wherein the bacterial infection is treated.
2. The therapeutic method of claim 1 , wherein the C max(ss) is 500 ng/ml to 700 ng/ml and the T>MIC is between 40% to 70%.
3. The therapeutic method of claim 1 , wherein the administration of the fixed amount further achieves a ratio of AUC/MIC of 30 to 60.
4. The therapeutic method of claim 1 , wherein the intravenous administration comprises infusing the pharmaceutical composition into the subject about 1 to about 3 times a day.
5. The therapeutic method of claim 1 , wherein the pharmaceutical composition comprises an aqueous and/or ethanolic solution.
6. The therapeutic method of claim 5 , wherein the pharmaceutical composition is reconstituted or diluted in a sterile, pharmaceutically acceptable solution prior to administration to the subject.
7. The therapeutic method of claim 6 , wherein the sterile, pharmaceutically acceptable solution is selected from the group consisting of water, saline, lactated ringer's solution, and ringer's acetate solution.
8. The therapeutic method of claim 1 , wherein administration of the fixed amount to a population of subjects achieves substantially no occurrences of clinically significant QTc prolongation.
9. The therapeutic method of claim 1 , wherein administration of the fixed amount to a population of subjects achieves substantially no occurrences of hepatotoxicity.
10. The therapeutic method of claim 1 , wherein the subject has mild to moderate hepatic impairment.
11. The therapeutic method of claim 1 , wherein the bacterial infection is due to Gram-positive pathogens.
12. The therapeutic method of claim 1 , wherein the bacterial infection comprises acute bacterial skin and skin structure infection.
13. A dosing regimen consisting of:
intravenously administering to a subject who has a bacterial infection a pharmaceutical composition consisting of a fixed amount of iclaprim,
wherein administration of the fixed amount achieves a C max(ss) below 800 ng/mL, a T>MIC of between 30% to 95% and a ratio of AUC/MIC of 20 to 80,
wherein the fixed amount is 80 mg,
wherein the fixed amount is infused into the subject 2 to 3 times a day with each infusion taking place over a time period of 2 hours,
and wherein the bacterial infection is treated.
14. The dosing regimen of claim 13 , wherein the administration of the fixed amount further achieves a ratio of AUC/MIC of 30 to 60.
15. The dosing regimen of claim 13 , wherein the bacterial infection is due to Gram-positive pathogens.
16. The dosing regimen of claim 13 , wherein the bacterial infection comprises acute bacterial skin and skin structure infections, or hospital acquired bacterial pneumonia.
17. A therapeutic method consisting of:
intravenously administering to a subject who has a bacterial infection a pharmaceutical composition consisting of a fixed amount of iclaprim,
wherein administration of the fixed amount achieves a C max(ss) below 800 ng/mL, a T>MIC of 30% to 95% and a ratio of AUC/MIC of 20 to 80,
wherein the fixed amount is 80 mg and wherein the fixed amount is infused into the subject 2 to 3 times a day with each infusion taking place over a time period of 2 hours,
and wherein the bacterial infection is treated.
18. The therapeutic method of claim 17 , wherein the pharmaceutical composition comprises an aqueous and/or ethanolic solution.
19. The therapeutic method of claim 17 , wherein the pharmaceutical composition is reconstituted or diluted in a sterile, pharmaceutically acceptable solution prior to administration to the subject.
20. The therapeutic method of claim 17 , wherein the sterile, pharmaceutically acceptable solution is selected from the group consisting of water, saline, lactated ringer's solution, and ringer's acetate solution.
21. The therapeutic method of claim 17 , wherein administration of the fixed amount to a population of subjects achieves substantially no occurrences of clinically significant QTc prolongation.
22. The therapeutic method of claim 17 , wherein administration of the fixed amount to a population of subjects achieves substantially no occurrences of hepatotoxicity.
23. The therapeutic method of claim 17 , wherein the subject has mild to moderate hepatic impairment.
24. The therapeutic method of claim 17 , wherein the bacterial infection is due to Gram-positive pathogens.
25. The therapeutic method of claim 17 , wherein the bacterial infection comprises acute bacterial skin and skin structure infection, or hospital acquired bacterial pneumonia.
26. The therapeutic method of claim 17 , wherein the intravenous administration comprises infusing the pharmaceutical composition into the subject about 1 to about 3 times a day, for a period of 5 to 14 days.
27. The therapeutic method of claim 26 , wherein the intravenous administration comprises infusing the pharmaceutical composition into the subject 2 times a day, for a period of 5 to 14 days.
28. The therapeutic method of claim 5 , wherein the intravenous administration comprises infusing the pharmaceutical composition into the subject about 1 to about 3 times a day, for a period of 5 to 14 days.
29. The dosing regimen of claim 18 , wherein the subject is administered an infusion 2 to 3 times a day for a period of 5 to 14 days.