Ceftolozane antibiotic compositions
This disclosure provides pharmaceutical compositions comprising ceftolozane, pharmaceutical compositions comprising ceftolozane and tazobactam, methods of preparing those compositions, and related methods and uses of these compositions.
1. A method for treating an infection which is a nosocomial pneumonia infection in a human patient in need thereof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% of a compound of formula (III)
relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.
2. The method of claim 1 , wherein the infection is a hospital acquired bacterial pneumonia infection.
3. The method of claim 1 , wherein the infection is a ventilator-associated bacterial pneumonia infection.
4. The method of claim 1 , wherein the composition contains less than 0.1% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%.
5. The method of claim 1 , wherein the composition contains less than 0.03% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%.
6. The method of claim 1 , wherein the composition the amount of ceftolozane active is 2,000 mg and the amount of tazobactam active is 1,000 mg.
7. The method of claim 1 , wherein the composition is provided in a unit dosage form.
8. The method of claim 6 , wherein the composition is provided in a unit dosage form.
9. The method of claim 1 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by parenteral administration.
10. The method of claim 1 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.
11. The method of claim 2 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.
12. The method of claim 3 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.
13. The method of claim 6 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.
14. A method for treating an infection which is a nosocomial pneumonia infection in a human patient in need thereof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% of the compound of formula (III)
relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, and less than 1.5% of a compound of formula (IV)
relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 3 months at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.
15. The method of claim 14 , wherein the infection is a hospital acquired bacterial pneumonia infection.
16. The method of claim 14 , wherein the infection is a ventilator-associated bacterial pneumonia infection.
17. The method of claim 14 , wherein the composition contains less than 0.05% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 3 months at a temperature of 25° C. and at a relative humidity of 60%.
18. The method of claim 14 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.
19. A method for treating an infection which is a nosocomial pneumonia infection in a human patient in need thereof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% relative to ceftolozane sulfate of the compound having a mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight, wherein the structure of the compound depicted in the mass spectra of FIG. 14 is:
20. The method of claim 19 , wherein the infection is a hospital acquired bacterial pneumonia infection.
21. The method of claim 19 , wherein the infection is a ventilator-associated bacterial pneumonia infection.
22. The method of claim 19 , wherein the composition contains less than 0.1% relative to ceftolozane sulfate of the compound with the mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%.
23. The method of claim 19 , wherein the composition contains less than 0.03% relative to ceftolozane sulfate of the compound with the mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%.
24. The method of claim 19 , wherein the composition the amount of ceftolozane active is 2,000 mg and the amount of tazobactam active is 1,000 mg.
25. The method of claim 19 , wherein the composition is provided in a unit dosage form.
26. The method of claim 24 , wherein the composition is provided in a unit dosage form.
27. The method of claim 19 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.
28. A method for treating an infection which is a nosocomial pneumonia infection in a human patient in need thereof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% relative to ceftolozane sulfate of a compound having a mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, and less than 1.5% of a compound of formula (IV):
relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 3 months at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight, wherein the structure of the compound depicted in the mass spectra of FIG. 14 is:
29. The method of claim 28 , wherein the infection is a hospital acquired bacterial pneumonia infection.
30. The method of claim 28 , wherein the infection is a ventilator-associated bacterial pneumonia infection.
31. The method of claim 28 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.