Combination comprising zidovudine and polymyxin
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9757427-B2
Publication Date
2017-09-12
Expiration Date
Abstract
The present invention relates to the use of a combination of an anti-retroviral agent such as zidovudine and an anti-microbial agent for killing clinically latent microorganisms associated with microbial infections and to novel combinations comprising an anti-retroviral agent such as zidovudine and an anti-microbial agent for the treatment of microbial infections.
Core Innovation
The invention relates to a therapeutic concept of combining zidovudine (AZT) with a polymyxin antimicrobial, selected from colistin or polymyxin B, to kill clinically latent and/or multiplying bacterial subpopulations. The approach is directed to gram-negative bacterial infection contexts in which bacterial populations include clinically latent microorganisms that are metabolically active but slow-growing, and log phase bacteria that are multiplying. The combination is presented as intended to improve antibacterial activity relative to monotherapy.
The problem being solved is described in terms of killing clinically latent and/or multiplying bacterial subpopulations associated with a gram-negative bacterial infection, including drug-resistant bacteria and carbapenemase/NDM-1 strains. The background emphasis is on achieving synergistic antibacterial activity against multiplying bacteria while addressing the emergence of resistance as a goal of the combination therapy. The concept defines clinically latent microorganisms as metabolically active but slow-growing and contrasts them with multiplying bacteria.
The document reports biological test concepts and supports the concept with in vitro example data. In combination with HT0120663 (zidovudine), chequerboard analysis against 91 gram-negative antibiotic-resistant isolates is described, including NDM-1 strains, showing synergistic antibacterial activity with a low FIC index value (FICI=0.156) and a distribution including synergistic interactions. Time-kill results for Klebsiella are described as showing removal of 10^7 bacteria at 24 hours and synergistic bactericidal activity.
Claims Coverage
The partial content includes two independent claims. Both independent claims center on a zidovudine plus a polymyxin selected from colistin and polymyxin B combination, where the combination exhibits synergistic antibacterial activity against multiplying bacteria associated with a gram-negative bacterial infection caused by Escherichia coli, Klebsiella, or Enterobacter.
Zidovudine and polymyxin combination for killing multiplying bacteria with synergistic antibacterial activity
A method of killing multiplying bacteria associated with a gram-negative bacterial infection by administering to a mammal a combination of zidovudine and a polymyxin selected from colistin and polymyxin B (or a pharmaceutically acceptable salt thereof), where the combination exhibits synergistic antibacterial activity against the multiplying bacteria caused by Escherichia coli, Klebsiella, or Enterobacter.
Pharmaceutical composition of zidovudine with polymyxin for synergistic antibacterial activity against multiplying bacteria
A pharmaceutical composition comprising zidovudine in combination with a polymyxin selected from colistin and polymyxin B, and a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, diluent or carrier, where the combination exhibits synergistic antibacterial activity against multiplying bacteria associated with a gram-negative bacterial infection caused by Escherichia coli, Klebsiella, or Enterobacter.
Across the independent claims, the inventive core is administering or formulating a zidovudine (AZT/HT0120663) combination with a selected polymyxin (colistin or polymyxin B) such that the combination exhibits synergistic antibacterial activity against multiplying bacteria in gram-negative bacterial infections caused by Escherichia coli, Klebsiella, or Enterobacter.
Stated Advantages
Improves antibacterial activity versus monotherapy, as presented in the therapeutic concept.
Exhibits synergistic antibacterial activity against clinically latent and/or multiplying bacterial subpopulations associated with gram-negative bacterial infection contexts.
Aims to kill multiplying bacteria and reduce resistance emergence, as described in the problem statement of the concept.
Documented Applications
Killing multiplying bacteria associated with a gram-negative bacterial infection in a mammal by administering zidovudine and a polymyxin selected from colistin or polymyxin B, for infections caused by Escherichia coli, Klebsiella, or Enterobacter.
Treating gram-negative bacterial infections via a pharmaceutical composition comprising zidovudine with a polymyxin selected from colistin or polymyxin B, where the combination exhibits synergistic antibacterial activity against multiplying bacteria caused by Escherichia coli, Klebsiella, or Enterobacter.
Interested in licensing this patent?