Novel in vitro pharmacodynamic model simulating ofloxacin pharmacokinetics in the treatment of Pseudomonas aeruginosa biofilm-associated infections

ABSTRACT

The conventional in vitro models simulate pharmacodynamics of antibiotics in the treatment of planktonic Pseudomonas aeruginosa. In this study, we propose a novel pharmacodynamic model of ofloxacin activity in the treatment of P. aeruginosa biofilm. P. aeruginosa biofilm carrying coupons were suspended in a continuous flow central compartment bioreactor [CCB]. In the CCB, the pharmacokinetics of different ofloxacin dosing regimens were simulated. Samples from the coupons and the CCB were assessed for viability of the biofilm and the shedding planktonic cells, respectively, over 24 h. In addition, ofloxacin concentrations were assessed in each sample withdrawn for the CCB using bioassay method. The microbiological outcomes on P. aeruginosa biofilm and the shedding planktonic cells in response to different ofloxacin dosing regimens were not parallel and this may explain the non-coincidence of microbiological and clinical outcomes with biofilm associated infections. The current study has introduced unprecedented novel dynamic model for the assessment of the microbiological outcome on both biofilm and shedding planktonic cells of P. aeruginosa in response to different dosing regimens of ofloxacin which in turn can simulate the clinical outcomes in biofilm associated infections of P. aeruginosa, e.g. cystic fibrosis. Furthermore, different scenarios of antibiotic dosing regimens against biofilm related infections can be mimicked using such model