In vitro and in vivo effects of sub-MICs of pexiganan and imipenem on Pseudomonas aeruginosa adhesion and biofilm development.

An in vitro and in vivo study was performed to quantify adhesion and biofilm formation ability of Pseudomonas aeruginosa slime producer under the effect of sub-minimal inhibitory concentrations (MICs) of pexiganan and imipenem. To evaluate adherence, squares of ureteral stents were placed in six-well tissue-culture plates containing 6 ml of a cell suspension grown in the presence of sub-MICs of study antibiotics. To evaluate biofilm formation sterilized squares were placed in six-well tissue culture plates containing 6 ml of triptic soy broth (TSB) supplemented with 0.25% of glucose and the respective amount of antibiotic. For in vivo study a biofilm infection rat model was performed. The study included an uninfected control group to evaluate the sterility of surgical procedure, a group infected with a slime-producer P. aeruginosa strain not previously treated with antibiotics and two groups infected with the strain previously treated with imipenem or pexiganan. Adherence and biofilm in vitro formation was strongly affected by pre-treatment with pexiganan and imipenem, with the latter being the more effective antibiotic. The in vivo results showed a reduction in bacterial load on the ureteral stent tissue of the pre-treated strain. Differently, urine cultures showed no differences in bacterial growth for the pre-treated strain showing that it retained its ability to cause infection. This study suggests that sub-MIC imipenem and pexiganan could be a good strategy to target the adhesion process during the infection cycle.