Colistin‐Tobramycin Combinations Are Superior to Monotherapy Concerning the Killing of BiofilmPseudomonas aeruginosa

BACKGROUND: Antibiotic combination therapy might be more efficient than single antibiotics to combat Pseudomonas aeruginosa biofilms in the airways of patients with cystic fibrosis. We tested the ability of colistin sulphate-tobramycin combinations and single antibiotics to kill P. aeruginosa biofilms. METHODS: P. aeruginosa biofilms were generated in vitro and in rat lungs. In a pilot study, 5 patients with cystic fibrosis inhaled colistin and then tobramycin for 4 weeks. The changes in P. aeruginosa counts and lung function were assessed before and after therapy. RESULTS: Antibiotic combination therapy significantly reduced the number of P. aeruginosa cells in P. aeruginosa biofilm models in vitro. When rats were challenged with 1 x 10(7) cfu of P. aeruginosa, which was embedded in alginate beads, mortality rates, lung pathologic findings, and bacterial colony-forming unit counts were significantly lower after 7 days in animals receiving antibiotic combination than in animals receiving single antibiotics. In patients with cystic fibrosis, inhaled colistin-tobramycin was well tolerated and resulted in a mean decrease of 2.52 + /- 2.5 log(10) cfu of P. aeruginosa per milliliter of sputum (P = .027). Measurements of forced expiratory volume in 1 s, obtained both before and after the study, did not differ significantly. CONCLUSION: Colistin-tobramycin combinations are more efficient than respective single antibiotics for killing P. aeruginosa in biofilms in vitro, and they significantly reduced P. aeruginosa cell counts in a rat lung infection model and in patients with cystic fibrosis.