Antimicrobial compositions comprising a hyaluronic acid binding peptide and a β-lactam antibiotic
Compositions and methods for the treatment of antibiotic resistant Staphylococcus aureus infections are provided comprising β-lactam antibiotics, as well as a hyaluronic acid binding peptide. The antibiotics include cephalosporins as well as the ηoη-β lactam antibiotic vancomycin. The methods provide administering the composition to the subject in an amount effective to reduce or eliminate the infection.
1. A method for the prevention or treatment of antibiotic resistant S. aureus infection or reinfection, comprising administering a therapeutically effective amount of a beta-lactam antibiotic and a hyaluronic acid binding peptide comprising the amino acid sequence SEQ ID NO: 2.
2. The method of claim 1 wherein the S. aureus is a methicillin resistant variant (MRSA), a vancomycin resistant variant (VRSA), or a vancomycin intermediate resistant variant (VISA).
3. The method of claim 1 wherein the beta-lactam antibiotic and the hyaluronic acid binding peptide are administered within 15 minutes of each other.
4. The method of claim 1 wherein the beta-lactam antibiotic is a cephalosporin.
5. The method of claim 1 wherein the cephalosporin is a first generation cephalosporin.
6. The method of claim 1 wherein the cephalosporin is a second, third, fourth or fifth generation cephalosporin.
7. The method of claim 4 wherein the cephalosporin is selected from the group consisting of: cefacetrile, Cefadroxil, Cephalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazaflur, Cefazedone, Cefazolin, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefonicid, Cefprozil, Cefuroxime, Cefuzonam, Cefmetazole, Cefotetan, Cefoxitin, Carbacephems, Cephamycins, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefixime, Cefmenoxime, Cefodizime Cefotaxime, Cefovecin, Cefpimizole, Cefpodoxime Cefteram, Ceftibuten, Ceftiofur, Ceftiolene, Ceftizoxime, Ceftriaxone, Cefoperazone, Ceftazidime, Oxacephems, Cefclidine, Cefepime, Cefluprenam, Cefoselis, Cefozopran, Cefpirome, Cefquinome, Oxacephems, Ceftobiprole, medocaril, Ceftaroline, Cefaloram, Cefaparole, Cefcanel, Cefedrolor, Cefempidone, Cefetrizole, Cefivitril, Cefmatilen, Cefmepidium, Cefoxazole, Cefrotil, Cefsumide, Ceftaroline, Ceftioxide, and Cefuracetime.
8. The method of claim 1 wherein the antibiotic is selected from the group consisting of methicillin, vancomycin, meropenem, and piperacillin/tazobactam.
9. The method of claim 1 wherein the hyaluronic acid binding peptide consists of the amino acid sequence SEQ ID NO: 2.
10. A method of potentiating a beta-lactam antibiotic against antibiotic resistant S. aureus comprising administering a hyaluronic acid binding peptide, comprising the amino acid sequence SEQ ID NO: 2, with the beta-lactam antibiotic.
11. The method of claim 10 wherein the antibiotic resistant S. aureus is a methicillin resistant variant (MRSA), a vancomycin resistant variant (VRSA) or a vancomycin intermediate resistant variant (VISA).
12. The method of claim 10 wherein the beta-lactam antibiotic and the hyaluronic acid binding peptide are administered simultaneously or concurrently.
13. The method of claim 12 wherein the beta-lactam antibiotic and the hyaluronic acid binding peptide are for administration within 15 minutes of each other.
14. The method of claim 12 wherein the beta-lactam antibiotic is a cephalosporin.
15. The method of claim 14 wherein the cephalosporin is a first generation cephalosporin.
16. The method of claim 14 wherein the cephalosporin is a second, third, fourth or fifth generation cephalosporin.
17. The method of claim 14 wherein the cephalosporin is selected from the group consisting of: cefacetrile, Cefadroxil, Cephalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazaflur, Cefazedone, Cefazolin, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefonicid, Cefprozil, Cefuroxime, Cefuzonam, Cefmetazole, Cefotetan, Cefoxitin, Carbacephems, Cephamycins, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefixime, Cefmenoxime, Cefodizime, Cefotaxime, Cefovecin, Cefpimizole, Cefpodoxime, Cefteram, Ceftibuten, Ceftiofur, Ceftiolene, Ceftizoxime, Ceftriaxone, Cefoperazone, Ceftazidime, Oxacephems, Cefclidine, Cefepime, Cefluprenam, Cefoselis, Cefozopran, Cefpirome, Cefquinome, Oxacephems, Ceftobiprole, medocaril, Ceftaroline, Cefaloram, Cefaparole, Cefcanel, Cefedrolor, Cefempidone, Cefetrizole, Cefivitril, Cefmatilen, Cefmepidium, Cefoxazole, Cefrotil, Cefsumide, Ceftaroline, Ceftioxide, and Cefuracetime.
18. The method of claim 12 wherein the antibiotic is selected from the group consisting of methicillin, vancomycin, meropenem, and piperacillin/tazobactam.
19. The method of claim 12 wherein the hyaluronic acid binding peptide consists of the amino acid sequence SEQ ID NO: 2.
20. A composition comprising a beta-lactam antibiotic and a hyaluronic acid binding peptide comprising the amino acid sequence SEQ ID NO: 2.
21. The composition of claim 20 wherein the beta-lactam antibiotic is a cephalosporin.
22. The composition of claim 21 wherein the cephalosporin is a first generation cephalosporin.
23. The composition of claim 21 wherein the cephalosporin is a second, third, fourth or fifth generation cephalosporin.
24. The composition of claim 21 wherein the cephalosporin is selected from the group consisting of: cefacetrile, Cefadroxil, Cephalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazaflur, Cefazedone, Cefazolin, Cefradine, Cefroxadine, Ceftezole, Cofactor, Cefonicid, Cefprozil, Cefuroxime, Cefuzonam, Cefmetazole, Cefotetan, Cefoxitin, Carbacephems, Cephamycins, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefixime, Cefmenoxime, Cefodizime, Cefotaxime, Cefovecin, Cefpimizole, Cefpodoxime, Cefteram, Ceftibuten, Ceftiofur, Ceftiolene, Ceftizoxime, Ceftriaxone, Cefoperazone, Ceftazidime, Oxacephems, Cefclidine, Cefepime, Cefluprenam, Cefoselis, Cefozopran, Cefpirome, Cefquinome, Oxacephems, Ceftobiprole, medocaril, Ceftaroline, Cefaloram, Cefaparole, Cefcanel, Cefedrolor, Cefempidone, Cefetrizole, Cefivitril, Cefmatilen, Cefmepidium, Cefoxazole, Cefrotil, Cefsumide, Ceftaroline, Ceftioxide, and Cefuracetime.
25. The composition of claim 20 wherein the antibiotic is selected from the group consisting of methicillin, vancomycin, meropenem, and piperacillin/tazobactam.
26. The composition of claim 20 wherein the hyaluronic acid binding peptide consists of the amino acid sequence SEQ ID NO: 2.
27. The method of claim 2 , wherein the combination of the hyaluronic acid binding protein with the antibiotic reduces the minimum inhibitory concentration of the MRSA strain.
28. The method of claim 2 , wherein the combination of the hyaluronic acid binding protein with the antibiotic reduces the minimum inhibitory concentration of the MRSA strain 2-256 fold.
29. The method of claim 2 , wherein the combination of the hyaluronic acid binding protein with the antibiotic reverts the minimum inhibitory concentration of the MRSA strain to susceptible (≦8 ug/mL).