Synergistic antimicrobial efficacy of furanone C30 and tobramycin against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model
Abstract number: P1566
Christensen L., van Gennip M., Alhede M., Kumar N., Kjelleberg S., Høiby N., Bjarnsholt T., Givskov M.
Objective:Pseudomonas aeruginosa biofilms are frequently linked to infections on foreign-body implants, which can cause serious complications. P. aeruginosa uses quorum sensing (QS) to regulate its virulence, and the biofilm mode of growth contributes to P. aeruginosa's tolerance towards the immune system and numerous antibiotics. Previously, we have shown that in vitro wild-type (WT) P. aeruginosa biofilms treated with either the QS inhibitor (QSI) furanone C30 or tobramycin alone had little effect on the eradication, but treatment with both C30 and tobramycin showed a synergistic effect and killed the biofilm. This synergistic effect was also tested in an in vivo biofilm model.
Methods: The pharmacokinetics of 30 mg/kg body weight (BW) tobramycin was estimated in non-infected BALB/c mice and the calculated half-life (t1/2) was 0.37 hours. We used a modified version of the in vivo foreign-body infection model introduced in 2007 and inserted silicone tube implants (id 4 mm, od 6 mm) instead of square implants in the mice. The implants were colonized with WT P. aeruginosa and inserted in the peritoneal cavity of BALB/c mice. Treatments consisted of i.p. injection of: (a) C30 (1 mg/kg BW, dissolved in 2.6% ethanol) every 8-hour, (b) 2.6% ethanol every 8 hour, (c) 30 mg/kg BW tobramycin, and (d) 0.9% NaCl. Treatment with C30 and tobramycin was initiated 1-hour and 24-hours post-insertion, respectively. After insertion the mice were divided into four groups: Gr. 1 (combination treatment) injection (a and c) (n = 11); Gr. 2 (C30 group) injection (a and d) (n = 8); Gr. 3 (tobramycin group) injection (b and c) (n = 10); Gr. 4 (placebo) injection (b and d) (n = 9). Implants were removed 48-hours post-insertion and the CFUs per implant were determined.
Results: Combination treatment of WT P. aeruginosa (Gr. 1) resulted in a significant clearing of the implants as compared to both the placebo and the single treatments groups (Gr. 2, Gr. 3) (p = 0.0002, p = 0.0003 and p = 0.001, respectively). A significant difference in clearing was also observed between the placebo group and the single treatment groups (p = 0.006 and p = 0.0003). We also found a significant difference in clearing between the two single treatment groups (p = 0.01).
Conclusion: The present results showed that a synergistic antimicrobial efficacy can be achieved when treating with a combination of furanone C30 and tobramycin, resulting in an increased clearance of P. aeruginosa during a foreign-body infection in mice.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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