Increased therapeutic efficacy of combination of azithromycin and ceftazidime on Pseudomonas aeruginosa biofilm in an animal model of ureteral stent infection

Abstract

Background: Infection caused by ureteral stent indwelling is one of the most difficult medical problems, since once bacteria reside in biofilms they are extremely resistant to antibiotics as well as to the host immune defences. In this study we assessed the in vitro and in vivo efficacy of azithromycin and ceftazidime in preventing ureteral stent infection by Pseudomonas aeruginosa. Results: The susceptibility testing with adherent bacteria showed that the biofilm was strongly inhibited by azithromycin treatment, ceftazidime against adherent bacteria in the presence of azithromycin showed the minimum inhibitory concentrations (MICs) and minimum bacteriocidal concentrations (MBCs) dramatically lower than those obtained in the absence of azithromycin. Moreover, ceftazidime plus azithromycin reduced twitching motility and production of rhamnolipid. For the single-treatment groups, in vivo intravenous injection of ceftazidime showed the highest inhibitory effect on bacterial load. Azithromycin prophylactic injection combined with ceftazidime showed increased inhibitory effect on bacterial load than that of each single antibiotic. Conclusions: Combination of azithromycin and ceftazidime effectively prevent the formation of biofilm and reduced bacteria load of Pseudomonas aeruginosa compared to separate treatment of either of these two antibiotics. This combined treatment option have the potential to contribute to the success of Pseudomonas biofilm elimination in the clinical environment.