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


METHODS
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 24h. In addition, ofloxacin concentrations were assessed in each sample withdrawn for the CCB using bioassay method.


RESULTS
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.


CONCLUSIONS
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.
Noreddin
Ayman M
AM
School of Pharmacy, Hampton University, Hampton, VA 23668, USA.
Elkhatib
Walid F
WF
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects*; D019149:Bioreactors; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D015242:Ofloxacin / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D010933:Plankton / Q000187:drug effects; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology
D000900:Anti-Bacterial Agents; D015242:Ofloxacin