BIOFILM ACCUMULATION MODEL THAT PREDICTS ANTIBIOTIC-RESISTANCE OF PSEUDOMONAS-AERUGINOSA BIOFILMS

A computer model of biofilm dynamics was adapted to incorporate the ac tivity of an antimicrobial agent on bacterial biofilm. The model was u sed to evaluate the plausibility of two mechanisms of biofilm antibiot ic resistance by qualitative comparison with data from a well-characte rized experimental system (H. Anwar, J. 1,. Strap, and J. W. Costerton , Antimicrob. Agents Chemother. 36:1208-1214, 1992). The two mechanism s involved either depletion of the antibiotic by reaction with biomass or physiological resistance due to reduced bacterial growth rates in the biofilm. Both mechanisms predicted the experimentally observed res istance of 7-day-old Pseudomonas aeruginosa biofilms compared with tha t of 2 day-old ones. A version of the model that incorporated growth r ate-dependent killing predicted reduced susceptibility of thicker biof ilms because oxygen was exhausted within these biofilms, leading to ve ry slow growth in part of the biofilm. A version of the model that inc orporated a destructive reaction of the antibiotic with biomass likewi se accounted for the relative resistance of thicker biofilms. Resistan ce in this latter case was due to depletion of the antibiotic in the b ulk fluid rather than development of a gradient in the antibiotic conc entration within the biofilm. The modeling results predicted differenc es between the two cases, such as in the survival profiles within the biofilm, that could permit these resistance mechanisms to be experimen tally distinguished.