Colistin-Tobramycin Combinations Are Superior to Monotherapy Concerning the Killing of Biofilm Pseudomonas aeruginosa

G. Herrmann, Liang Yang, H. Wu, Z.J. Song, H.Z. Wang, N. Hoiby, M. Ulrich, Søren Molin, J. Riethmuller, G. Doring

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    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 sulphatetobramycin 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 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.
    Original languageEnglish
    JournalJournal of Infectious Diseases
    Volume202
    Issue number10
    Pages (from-to)1585-1592
    ISSN0022-1899
    DOIs
    Publication statusPublished - 2010

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