In vitro evaluation of tobramycin and aztreonam versus Pseudomonas aeruginosa biofilms on cystic fibrosis-derived human airway epithelial cells

OBJECTIVES: Aztreonam for inhalation solution (AZLI) was recently approved by the FDA for treating cystic fibrosis (CF) patients infected with Pseudomonas aeruginosa. Here we investigated the effect of aztreonam alone or in combination with tobramycin on P. aeruginosa biofilms grown on CF airway epithelial cells. METHODS: P. aeruginosa biofilms, produced by laboratory strains or clinical isolates, were formed on confluent CF airway cells before treatment overnight with aztreonam or tobramycin alone or in combination. Alternatively, antibiotics were added 1 h after bacterial inoculation to assess their ability to impair biofilm formation at 5 h. Bacterial cfu remaining after treatment were then determined by plate counting. RESULTS: In the absence of antibiotics, all strains developed biofilms that disrupted CF airway epithelial monolayers overnight. Tobramycin reduced the cfu of all strains grown as biofilms. Aztreonam reduced the cfu of some strains by ∼1 log unit without preserving the integrity of cystic fibrosis airway cell monolayers, while decreasing the biofilms of other clinical isolates by ∼4 log units and protecting the monolayers from being compromised. The combination of aztreonam and tobramycin reduced the cfu of two strains by an additional 0.5 and 2 log units, respectively. Of all the mechanisms explored, Psl exopolysaccharide production might explain the variations in biofilm tolerance to aztreonam in some of the strains. CONCLUSIONS: Effects of aztreonam on P. aeruginosa biofilms in the in vitro co-culture model are strain-dependent. The simultaneous application of aztreonam and tobramycin may be beneficial for a subset of CF patients by eliminating susceptible P. aeruginosa strains.