Composition for the treatment of intracellular bacterial infection
A method of treating or preventing an intracellular bacterial infection, comprising contacting the cell(s) which are infected with an antibacterial agent and a photosensitizing agent and irradiating the cell(s) with light of a wavelength effective to activate the photosensitizing agent, wherein the antibacterial agent is released into the cytosol of the cell(s) and kills, damages or prevents the replication of bacteria in said cell(s) is described. Related uses, and compositions, products and kits for the same are further described.
1. A method of treating an intracellular bacterial infection, comprising contacting the cell(s) which are infected with an antibacterial agent and a photosensitizing agent and irradiating the cell(s) with light of a wavelength effective to activate the photosensitizing agent which releases the antibacterial agent into the cytosol of the cell(s) and the released antibacterial agent kills, damages or prevents the replication of bacteria in said cell(s).
2. The method as claimed in claim 1 wherein said method is performed in vivo and said cell(s) is in a subject.
3. The method as claimed in claim 1 wherein said contacting step is performed for 15 minutes to 4 hours.
4. The method as claimed in claim 1 wherein said photosensitizing agent is an amphiphilic porphyrin, chlorin, bacteriochlorin or phthalocyanine.
5. The method as claimed in claim 4 wherein said photosensitizing agent is selected from tetraphenyl chlorin disulfonate (TPCS 2a ), aluminium phthalocyanine disulfonate (AlPcS 2a ), tetraphenylporphine disulfonate (TPPS 2a ) and tetraphenyl bacteriochlorin disulfonate (TPBS 2a ).
6. The method as claimed in claim 1 comprising locally delivering the dose of photosensitizing agent in an amount ranging from 0.0025 to 250 μg.
7. The method as claimed in claim 1 wherein the cell(s) is irradiated for between 5 and 60 minutes.
8. The method as claimed in claim 1 comprising locally delivering the dose of the antibacterial agent in an amount ranging from 25 to 10000 μg.
9. The method as claimed in claim 1 wherein the antibacterial agent is an aminoglycoside, a glycopeptide or a macrolide.
10. The method as claimed in claim 1 wherein the bacterial infection is caused by a Staphylococcus, Mycobacterium, Pseudomonas or Escherichia bacteria.
11. The method as claimed in claim 1 wherein the bacterial infection is a biomaterial-associated infection.
12. The method as claimed in claim 1 wherein the bacterial infection is osteomyelitis, bacteremia, tuberculosis, Q-fever, endocarditis, a (sub)cutaneous skin or mucosal infection/damage, an oral and nasal infection or peri-implantitis.
13. The method as claimed in claim 1 wherein the cell(s) is present on, or adjacent to, a biomaterial.
14. The method as claimed in claim 13 , wherein the antibacterial agent and/or the photosensitizing agent is provided on or within the biomaterial.
15. The method as claimed in claim 2 wherein said subject is a mammal.
16. The method as claimed in claim 2 wherein said subject is a cow and the bacterial infection is S. aureus mastitis.
17. The method as claimed in claim 1 wherein said cell(s) is contacted with said antibacterial agent and photosensitizing agent simultaneously, separately or sequentially.
18. The method as claimed in claim 9 wherein the antibacterial agent is gentamicin or vancomycin.
19. The method as claimed in claim 1 comprising locally delivering the dose of photosensitizing agent in an amount ranging from 1 to 250 μg.
20. The method as claimed in claim 2 wherein said subject is a human.
21. The method as claimed in claim 17 wherein when said method is performed in vivo said contact is achieved by topical, intradermal, subcutaneous or intravenous administration of said antibacterial agent and said photosensitizing agent.
22. The method as claimed in claim 11 wherein the biomaterial is selected from the group consisting of a medical device, instrument, implement or equipment, a prosthetic or material, tissue and wound dressing.
23. The method as claimed in claim 13 wherein the biomaterial is selected from the group consisting of a medical device, instrument, implement or equipment, a prosthetic or material, tissue and wound dressing.