Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorom sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model.
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Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorom sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model. / Hultqvist, Louise Dahl; van Gennip, Maria; Jakobsen, Tim Holm; Alhede, Morten; Hougen, Hans Petter; Høiby, Niels; Bjarnsholt, Thomas; Givskov, Michael.
In: Journal of Antimicrobial Chemotherapy, Vol. 67, No. 5, 2012, p. 1198-1206.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorom sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model.
AU - Hultqvist, Louise Dahl
AU - van Gennip, Maria
AU - Jakobsen, Tim Holm
AU - Alhede, Morten
AU - Hougen, Hans Petter
AU - Høiby, Niels
AU - Bjarnsholt, Thomas
AU - Givskov, Michael
PY - 2012
Y1 - 2012
N2 - Objectives Quorum sensing (QS)-deficient Pseudomonas aeruginosa biofilms formed in vitro are more susceptible to tobramycin than QS-proficient P. aeruginosa biofilms, and combination treatment with a QS inhibitor (QSI) and tobramycin shows synergistic effects on the killing of in vitro biofilms. We extended these results to an in vivo P. aeruginosa foreign-body biofilm model. The effect of treatment initiated prophylactically was compared with treatment initiated 11 days post-insertion. Methods Silicone tube implants pre-colonized with wild-type P. aeruginosa were inserted into the peritoneal cavity of BALB/c mice. Mice were treated with intraperitoneal or subcutaneous injections of the QSIs furanone C-30, ajoene or horseradish juice extract in combination with tobramycin. Mice were euthanized on day 1, 2, 3 or 14 post-infection for the estimation of quantitative bacteriology, histopathology and cytokine measurements. Results Combination treatment of P. aeruginosa resulted in a significantly lower cfu per implant as compared with the placebo groups for all QSIs tested. For early-initiated treatment, a significant difference in clearing was also observed between the combination group and the single-treatment groups, and between the placebo group and the single-treatment groups. In one case a significant difference in clearing was found between the two single-treatment groups. Conclusions Synergistic antimicrobial efficacy could be achieved when treating mice with both a QSI and tobramycin, resulting in an increased clearance of P. aeruginosa in a foreign-body infection model. Our study highlights the important prospects in developing an early combinatory treatment strategy for chronic infections.
AB - Objectives Quorum sensing (QS)-deficient Pseudomonas aeruginosa biofilms formed in vitro are more susceptible to tobramycin than QS-proficient P. aeruginosa biofilms, and combination treatment with a QS inhibitor (QSI) and tobramycin shows synergistic effects on the killing of in vitro biofilms. We extended these results to an in vivo P. aeruginosa foreign-body biofilm model. The effect of treatment initiated prophylactically was compared with treatment initiated 11 days post-insertion. Methods Silicone tube implants pre-colonized with wild-type P. aeruginosa were inserted into the peritoneal cavity of BALB/c mice. Mice were treated with intraperitoneal or subcutaneous injections of the QSIs furanone C-30, ajoene or horseradish juice extract in combination with tobramycin. Mice were euthanized on day 1, 2, 3 or 14 post-infection for the estimation of quantitative bacteriology, histopathology and cytokine measurements. Results Combination treatment of P. aeruginosa resulted in a significantly lower cfu per implant as compared with the placebo groups for all QSIs tested. For early-initiated treatment, a significant difference in clearing was also observed between the combination group and the single-treatment groups, and between the placebo group and the single-treatment groups. In one case a significant difference in clearing was found between the two single-treatment groups. Conclusions Synergistic antimicrobial efficacy could be achieved when treating mice with both a QSI and tobramycin, resulting in an increased clearance of P. aeruginosa in a foreign-body infection model. Our study highlights the important prospects in developing an early combinatory treatment strategy for chronic infections.
U2 - 10.1093/jac/dks002
DO - 10.1093/jac/dks002
M3 - Journal article
VL - 67
SP - 1198
EP - 1206
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 5
ER -
ID: 45156693