Dartmouth Medical School researchers have come up with a novel approach for inhibiting relentless bacterial infections that thrive in the lungs of people with cystic fibrosis (CF).
The researchers have found that combining a mainstay antibiotic with certain drugs to deprive the bacteria of iron, which facilitates their persistent growth, appears to boost infection killing.
AdvertisementCystic fibrosis patients are plagued by infections of the bacteria Pseudomonas aeruginosa. Their mucous-clogged lungs are fertile incubators for the bacteria to breed and cluster in slimy communities called biofilms that become increasingly drug resistant and damaging.
Tobramycin, the antibiotic routinely used against the microbes, can control, but not efficiently eliminate Pseudomonas established on CF airway cells.
For the study, the team used two agents already approved by the Federal Drug Administration to treat acute iron poisoning or overload that can enhance the ability of tobramycin against Pseudomonas infection.
"The beauty is that we are mixing FDA-approved drugs-antibiotics and iron chelators-to potentiate the effect of tobramycin on biofilm formation," said lead author Dr. Sophie Moreau-Marquis, a research associate.
"It's an exciting translational framework that opens the door to potentially treating CF patients, taking the novel model we developed from the lab hopefully to the clinic," she added.
The team used two FDA-approved iron chelators, deferoxamine and deferasirox, that can remove excess iron from the system by binding to the metal in a process called chelation.
To mimic the clinical environment, they stuck to the maximum possible tobramycin dose of 1,000 micrograms per milliliter, mixed with a chelator.
The researchers found that the combination had a dramatic effect. It disrupted the mass of established and highly resistant bacteria in human airway cells by 90 percent and it also prevented formation of damaging biofilms.
In contrast, neither an iron chelator nor tobramycin alone had such success.
The study appears in the American Journal of Respiratory Cell and Molecular Biology.