The continuing threat of multidrug resistant (MDR), particularly among gram-negative bacteria, is increasing due in part to a lack of development of new agents that are better designed to evade resistance mechanisms. Resistance is particularly challenging in the hospital environment due to the number of susceptible patients with underlying co-morbidities and/or who are immunocompromised. The most common nosocomial infections include pneumonia, urinary tract infections, bloodstream and surgical site infections, and risk of antibacterial resistance increases in patients with indwelling devices such as endotracheal and nasogastric tubes, urinary and venous catheters.
Antibiotic resistance is increasingly prevalent among the ESKAPE pathogens, namely Escherichia coli
, Staphylococcus aureus
, Klebsiella pneumonia
, Acinetobacter spp
. Pseudomonas aeruginosa
. In both hospital- and community-acquired pneumonia, the PEAK pathogens (Figure 1) are responsible for much of the increases in MDR gram-negative infections.
Compounds under development by Talon are designed to treat infections caused by multidrug-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae and those organisms harbouring extended-spectrum beta-lactamases. To minimize the development of bacterial resistance, several series of new chemical structures, incorporating pharmacophores acting via multiple mechanisms of action, are being synthesized.
Figure 1. Cases of Pneumonia resulting from PEAK Gram-negative Pathogens
Carbapenem resistant Enterobacteriaceae
(CRE), extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae
, and MDR P. aeruginosa
represent the most challenging resistant pathogens according to the CDC.
Table 1. Estimated incidence and mortality of problematic Antibiotic-resistant Gram-Negative Pathogens in the US.
Talon has designed two series of novel antibiotics to treat infections caused by MDR P. aeruginosa, CRE and ESBL pathogens. Talon is minimizing the development of resistance through the incorporation of multiple mechanisms of action and pharmacophores designed to evade resistance mechanisms.