THEORETICAL ASPECTS OF ANTIBIOTIC DIFFUSION INTO MICROBIAL BIOFILMS

Antibiotic penetration into microbial biofilm was investigated theoret ically by the solution of mathematical equations describing various co mbinations of the processes of diffusion, sorption, and reaction, Unst eady material balances on the antibiotic and on a reactive or sorptive biomass constituent, along with associated boundary and initial condi tions, constitute the mathematical formulations, Five cases were exami ned: diffusion of a noninteracting solute; diffusion of a reversibly s orbing, nonreacting solute; diffusion of an irreversibly sorbing, nonr eacting solute; diffusion of a stoichiometrically reacting solute; and diffusion of a catalytically reacting solute, A noninteracting solute was predicted to penetrate biofilms of up to 1 mm in thickness relati vely quickly, within a matter of seconds or minutes, In the case of a solute that does not sorb or react in the biofilm, therefore, the diff usion barrier is not nearly large enough to account for the reduced su sceptibility of biofilms to antibiotics, Reversible and irreversible s orption retards antibiotic penetration, On the basis of data available in the literature at this point, the extent of retardation of antibio tic diffusion due to sorption does not appear to be sufficient to acco unt for reduced biofilm susceptibility, A catalytic (e,g,, enzymatic) reaction, provided it is sufficiently rapid, can lead to severe antibi otic penetration failure, For example, calculation of p-lactam penetra tion indicated that the reaction-diffusion mechanism may be a viable e xplanation for failure of certain of these agents to control biofilm i nfections, The theory presented in this study provides a framework for the design and analysis of experiments to test these mechanisms of re duced biofilm susceptibility to antibiotics.