First in class compounds that break resistance in bacteria and rejuvenate several classes of antibiotics
Inventors: Adesh Ramsubhag, Antonio Ramkissoon, Jayaraj Jayaraman, Anderson Maxwell
Managing infectious diseases has become a major challenge globally due to the emergence and rapid spread of antibiotic resistance among pathogenic microorganisms. The WHO’s Global Antimicrobial Surveillance System (GLASS) 2016 –2017 report highlighted this problem in many regions around the world, where widespread occurrence of multi-drug resistance in different infectious organisms was noted. Consequently, an increasing number of infections are becoming difficult or impossible to treat, leading to high morbidity and mortality rates. There is an urgent need to develop new antibiotics, but drug discovery and development pipelines have had little success in providing novel therapeutics for effectively combating these emerging pathogens.
An interesting approach is not only to search for new antibiotics but also to make those established antibiotics useful again. One way in which this can be achieved is by developing adjuvants that potentiate antibiotics. The inventors have discovered and developed lead compounds that break bacterial resistance to several classes of antibiotic drugs. These compounds have been validated for potent adjuvant activity against panels of reference and clinical strains of antibiotic resistant bacteria in in vitro studies. The inventors further evaluated one of the compounds (CMPD X) and showed it was able to clear MRSA infections in both lethal and non-lethal murine septicemia models when co-administered with an antibiotic that the pathogen displayed resistance to. This innovation presents a potential utility in treating infections caused by antibiotic resistant bacteria by developing therapeutic formulations that combine the novel adjuvant compounds with antibiotics. It may also be possible to use these compounds to repurpose and rejuvenate those drugs that have been discontinued due to their ineffectiveness in treating these types of infections.
- Co-administration with antibiotics to treat drug resistant bacteria.<
- Treatment of many species of drug resistant bacteria
- Old antibiotics can be reintroduced since compound breaks resistance to established drugs
- Synergy with many classes of antibiotics · High potency and low toxicity
- No selection pressure as compounds do not directly kill bacteria by themselves
- Low rates of development of resistance expected since putative bacterial target is well conserved domain
- Numerous analogues for development
PCT application filed.