Colistin-tobramycin Combinations Are Superior to Monotherapy Concerning the Killing of Biofilm Pseudomonas Aeruginosa

J Infect Dis. 2010 Nov 15;202(10):1585-92. doi: 10.1086/656788. Epub 2010 Oct 13.

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 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Biofilms / drug effects*
  • Colistin / administration & dosage
  • Colistin / therapeutic use*
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / microbiology
  • Drug Therapy, Combination
  • Female
  • Humans
  • Lung / microbiology
  • Male
  • Microbial Sensitivity Tests
  • Pilot Projects
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / physiology
  • Rats
  • Rats, Inbred Lew
  • Tobramycin / administration & dosage
  • Tobramycin / therapeutic use*
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Tobramycin
  • Colistin