CF Pathogen Defies Treatment Attempt with Novel Drug Combination

A new study revealed that treating P. aeruginosa biofilms with the antibiotic tobramycin together with mannitol — two well-known therapies in treating lung infections in CF — did not reduce overall bacterial load. The study entitled “Mannitol Does Not Enhance Tobramycin Killing of Pseudomonas aeruginosa in a Cystic Fibrosis Model System of Biofilm Formation” was published in PLOS One by researchers from Geisel School of Medicine at Dartmouth, New Hampshire, and Novartis Pharmaceutical Corporation, New Jersey.

Cystic fibrosis (CF) is a genetic disease that affects various organs such as the lungs and pancreas and is characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which results in regular infective pulmonary exacerbations with opportunistic pathogens such as Pseudomonas aeruginosa (P. aeruginosa). The disease is characterized by the accumulation of thick, sticky mucus in the airways, which results in chronic, lasting living bacterial biofilm infections which are difficult to eradicate with antibiotics. P. aeruginosa lung infection is associated with the deterioration of lung function and during chronic infections this pathogen transits into an antibiotic tolerant state.

Tobramycin is an aminoglycoside antibiotic used in the treatment of several bacterial infections, mainly Gram-negative infections. Tobramycin has been used to fight lung infections in patients with CF. However tobramycin is only successful at eradicating P. aeruginosa in the airways of young patients, and incapable of fully clearing the chronic P. aeruginosa infections in older patients. Recently, a study showed that the co-treatment of tobramycin and mannitol, an osmotic diuretic that naturally occurs as a sugar or sugar alcohol in fruits and vegetables, enhanced killing of P. aeruginosa grown in vitro as a biofilm on an abiotic (non-living) surface.

In this study, the research team used a model system of bacterial biofilms formed on the surface of airway cells originating in cystic fibrosis patients to see if mannitol would increase the antibacterial activity of tobramycin against P. aeruginosa developed on a more clinically significant surface. This model permitted the development of biofilms with elevated antibiotic tolerance similar to in vivo biofilms.

The authors, however, did not to find any experimental evidence for enhanced antibacterial activity of tobramycin together with mannitol. Their findings showed that the co-treatment did not successfully reduce P. aeruginosa bacterial load in a clinical context.

Bacteria such as P. aeruginosa pose a particular threat to those with CF due to the fact that the steady use of antibiotics can decrease their effectiveness in neutralizing infections. Confirming the effectiveness or ineffectiveness of therapies such as mannitol used with tobramycin prompts research to focus on new avenues in the search for optimal efficacy in treating those with the disease.