Pulmonary infections are the leading cause of mortality in cystic fibrosis (CF) patients (11,12). Pseudomonas aeruginosa is the most commonly isolated organism from these infections, (13) and the prevalence of multidrug-resistant (MDR) strains of this bacterium is increasing rapidly, with 20% of CF patients testing positive for MDR P. aeruginosa in 2009 (14).
Existing antibiotic therapies are unable to eradicate lung infections in CF patients, and current antibiotics are particularly ineffective against MDR strains of P. aeruginosa. Therefore, an urgent need exists for a therapeutic that will more effectively treat lung infections of CF patients.
Lung infections in CF patients are particularly recalcitrant to current therapeutic options due to the ability of bacteria to resist antibiotic treatment through biofilm formation and other drug resistance mechanisms (15,16).
Agile Sciences’ technology presents a novel solution to circumventing these bacterial defense mechanisms. Our proprietary 2-aminoimidazole (2-AI) small molecules, derived from a metabolite of a sea sponge, overcome antibiotic resistance by dispersing bacterial biofilms and lowering the minimum inhibitory concentration (MIC) values of antibiotics toward bacteria (17,18,19,20). When used in combination with current antibiotic therapies, such as tobramycin, the 2-AI compound has the potential to allow the antibiotic to work more effectively by eliminating biofilms and antibiotic resistance.
Agile Sciences is currently evaluating a lead compound as a combination treatment along with tobramycin for this application. The program is currently evaluating aerosol delivery of the compound in a mouse model of cystic fibrosis. The project has been funded by a Phase II STTR grant from the NIH.