Effect of the combination of clarithromycin and amikacin on Pseudomonas aeruginosa biofilm in an animal model of ureteral stent infection

Abstract

An experimental study was performed to evaluate both in vitro and in vivo the efficacy of clarithromycin coating combined with systemic amikacin in preventing ureteral stent biofilm infection due to Pseudomonas aeruginosa. The activities of the two antibiotics were studied in vitro in the absence or in the presence of biofilm. For the in vivo study we evaluated a control group without bacterial challenge to evaluate the sterility of the surgical procedure, a challenged control group that did not receive any antibiotic prophylaxis and three challenged groups that received (i) 15 mg/kg intraperitoneal amikacin immediately after stent implantation, (ii) clarithromycin-coated ureteral stents where 0.2 cm² sterile ureteral stents were incubated in 10 mg/L clarithromycin solution for 30 min immediately before implantation, and (iii) intraperitoneal amikacin plus a clarithromycin-coated ureteral stent at the above concentrations. The in vitro studies showed that the biofilm was strongly affected by the presence of clarithromycin and, in its presence, amikacin had MICs and MBCs lower than those obtained in the absence of clarithromycin. For the singly treated groups, intraperitoneal amikacin showed the strongest effect on bacterial numbers. A clarithromycin coating combined with systemic amikacin showed an efficacy that was higher than that of each single compound. The prevention of ureteral stent Pseudomonas biofilm infection was enhanced by impregnation of the stent with clarithromycin combined with systemic amikacin.