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Details for Patent: 7,595,328

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Details for Patent: 7,595,328

Title:Methods of use of quinolone compounds against pneumococcal and Haemophilus bacteria
Abstract: This invention relates, in part, to newly identified methods of using quinolone antibiotics, particularly a gemifloxacin compound against certain pathogenic bacteria, particularly quinolone resistant S. pneumoniae and rare H. influenzae strains.
Inventor(s): Appelbaum; Peter C. (Hershey, PA), Credito; Kim L. (Hershey, PA), Davies; Todd (Hershey, PA), Hoellman; Dianne B. (Hershey, PA), Kelly; Linda M. (Hershey, PA), Pankuch; Glenn A. (Hershey, PA)
Assignee: LG Life Sciences Limited (KR)
Filing Date:Mar 24, 2003
Application Number:10/395,461
Claims:1. A method for modulating inhibiting the growth of a Haemophilus influenzae strain comprising contacting the H. influenzae strain with a composition comprising an antibacterially effective amount of gemifloxacin, gemifloxacin mesylate, or gemifloxacin mesylate sesquihydrate, wherein the H. influenzae strain comprises a mutation in parE that results in at least one of the following changes in the amino acid sequence of the ParE protein: replacement of Gly at position 405 with Ser, replacement of Asp at position 420 with Asn, replacement of Ser at position 458 with Leu, replacement of Ser at position 458 with Ala, insertion of a Ser between the Ser at position 458 and the Thr at position 459, and replacement of the Ser at position 474 with Asn.

2. A method of treating a bacterial infection by a Haemophilus influenzae strain comprising administering a composition comprising an antibacterially effective amount of gemifloxacin, gemifloxacin mesylate, or gemifloxacin mesylate sesquihydrate to a mammal having an infection with a H. influenzae strain comprising a mutation in parE that results in at least one of the following changes in the amino acid sequence of the ParE protein: replacement of Gly at position 405 with Ser, replacement of Asp at position 420 with Asn, replacement of Ser at position 458 with Leu, replacement of Ser at position 458 with Ala, insertion of a Ser between the Ser at position 458 and the Thr at position 459, and replacement of the Ser at position 474 with Asn.

3. The method of claim 1, wherein inhibiting the growth kills the H. influenzae strain.

4. The method of claim 1, wherein the H. influenza strain is contacted with the composition by administering the composition to a mammal infected with the H. influenzae strain.

5. The method of claim 2, wherein the mammal is a human.

6. The method of claim 4, wherein the mammal is a human.

7. The method of claim 2, wherein the mammal is a human suffering from acute exacerbations of chronic bronchitis caused by H. influenzae.

8. The method of claim 2, wherein the mammal is a human suffering from acute otitis media caused by H. influenzae.

9. The method of claim 2, wherein the mammal is a human suffering from sinusitis caused by H. influenzae.

10. The method of claim 2, wherein the mammal is a human suffering from a community-acquired respiratory tract infection caused by H. influenzae.

11. The method of claim 1, wherein the composition comprises an antibacterially effective amount of gemifloxacin mesylate.

12. The method of claim 1, wherein the composition comprises an antibacterially effective amount of gemifloxacin mesylate sesquihydrate.

13. The method of claim 2, wherein the composition comprises an antibacterially effective amount of gemifloxacin mesylate.

14. The method of claim 2, wherein the composition comprises an antibacterially effective amount of gemifloxacin mesylate sesquihydrate.

15. The method of claim 2, wherein the H. influenzae strain is a strain that has a ParC protein that is unmutated, a ParE protein that contains the mutation Ser.sup.458 to Leu, a GyrA protein that contains the mutation Ser.sup.84 to Phe, and a GyrB protein that is unmutated.

16. The method of claim 2, wherein the H. influenzae strain is a strain that has a ParC protein that contains the mutation Asp.sup.83 to Asn, a ParE protein that contains an insertion of a Ser between the Ser at position 458 and the Thr at position 459, a GyrA protein that contains the mutations Ser.sup.84 to Phe and Asp.sup.88 to Asn, and a GyrB protein that contains the mutation Gln.sup.84 to Arg.

17. The method of claim 2, wherein the H. influenzae strain is a strain that has a ParC protein that contains the mutation Glu.sup.88 to Lys, a ParE protein that contains the mutation Gly.sup.405 to Ser, a GyrA protein that contains the mutation Ser.sup.84 to Tyr, and a GyrB protein that is unmutated.

18. The method of claim 2, wherein the H. influenzae strain is a strain that has a ParC protein that contains the mutation Ser.sup.84 to Arg, a ParE protein that contains the mutation Asp.sup.420 to Asn, a GyrA protein that contains the mutations Ser.sup.84 to Leu and Ala.sup.117 to Glu, and a GyrB protein that is unmutated.

19. The method of claim 2, wherein the H. influenzae strain is a strain that has a ParC protein that contains the mutations Ser.sup.84 to Arg and Asn.sup.138 to Ser, a ParE protein that contains the mutations Ser.sup.458 to Ala and Ser.sup.474 to Asn, a GyrA protein that contains the mutations Ser.sup.84 to Phe and Asp.sup.88 to Tyr, and a GyrB protein that is unmutated.

20. The method of claim 1, wherein the H. influenzae strain is a strain that has a ParC protein that is unmutated, a ParE protein that contains the mutation Ser.sup.458 to Leu, a GyrA protein that contains the mutation Ser.sup.84 to Phe, and a GyrB protein that is unmutated.

21. The method of claim 1, wherein the H. influenzae strain is a strain that has a ParC protein that contains the mutation Asp.sup.83 to Asn, a ParE protein that contains an insertion of a Ser between the Ser at position 458 and the Thr at position 459, a GyrA protein that contains the mutations Ser.sup.84 to Phe and Asp.sup.88 to Asn, and a GyrB protein that contains the mutation Gln.sup.84 to Arg.

22. The method of claim 1, wherein the H. influenzae strain is a strain that has a ParC protein that contains the mutation Glu.sup.88 to Lys, a ParE protein that contains the mutation Gly.sup.405 to Ser, a GyrA protein that contains the mutation Ser.sup.84 to Tyr, and a GyrB protein that is unmutated.

23. The method of claim 1, wherein the H. influenzae strain is a strain that has a ParC protein that contains the mutation Ser.sup.84 to Arg, a ParE protein that contains the mutation Asp.sup.420 to Asn, a GyrA protein that contains the mutations Ser.sup.84 to Leu and Ala.sup.117 to Glu, and a GyrB protein that is unmutated.

24. The method of claim 1, wherein the H. influenzae strain is a strain that has a ParC protein that contains the mutations Ser.sup.84 to Arg and Asn.sup.138 to Ser, a ParE protein that contains the mutations Ser.sup.458 to Ala and Ser.sup.474 to Asn, a GyrA protein that contains the mutations Ser.sup.84 to Phe and Asp.sup.88 to Tyr, and a GyrB protein that is unmutated.
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