Theoretical aspects of antibiotic diffusion into microbial biofilms

Abstract

Antibiotic penetration into microbial biofilm was investigated theoretically by the solution of mathematical equations describing various combinations of the processes of diffusion, sorption, and reaction. Unsteady material balances on the antibiotic and on a reactive or sorptive biomass constituent, along with associated boundary and initial conditions, constitute the mathematical formulations. Five cases were examined: diffusion of a noninteracting solute; diffusion of a reversibly sorbing, nonreacting solute; diffusion of an irreversibly sorbing, nonreacting 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 relatively 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 diffusion barrier is not nearly large enough to account for the reduced susceptibility of biofilms to antibiotics. Reversible and irreversible sorption retards antibiotic penetration. On the basis of data available in the literature at this point, the extent of retardation of antibiotic diffusion due to sorption does not appear to be sufficient to account for reduced biofilm susceptibility. A catalytic (e.g., enzymatic) reaction, provided it is sufficiently rapid, can lead to severe antibiotic penetration failure. For example, calculation of beta-lactam penetration indicated that the reaction-diffusion mechanism may be a viable explanation for failure of certain of these agents to control biofilm infections. The theory presented in this study provides a framework for the design and analysis of experiments to test these mechanisms of reduced biofilm susceptibility to antibiotics.

Two-Fluid Model of Biofilm Disinfection

“…We consider three simulations: The first is a numerical experiment that is similar to the analytic results in Stewart (1996) where the bulk fluid is well mixed and there is no external flow. The second incorporates explicit treatment of the external fluid with a fixed interface, and the final includes the motion of the biofilm and the external fluid.…”

“…The region is separated into two sub-regions, Ω (1) , the bulk fluid region, and Ω (2) , the biofilm region, by an interface Γ . reduced within the biofilm (Stewart, 1996). The reduction factor is not common for all chemicals, but is thought to be due to reduced permeability through physical and chemical interactions with the EPS.…”

“…In particular, we would like to determine the effects the motion of the biofilm region and the external flow have on the survival curves and penetration times. In Stewart (1996), the author calculates the penetration time for various antimicrobial agents (e.g., nonreactive, reactive, sorbing) for a flat slab biofilm with no external flow. Instead, the concentration of the biocide is constant at the interface.…”

Biofilms: At the Interface between Biophysics and Microbiology

“…Physiological factors such as biofilm age [158], nutrient deficiency [162], and growth rate [163], have been suggested to affect the susceptibility to disinfectants. A second, more recent model proposes that physical properties of the biofilm limit the rate of transport and activity of sanitizers [113,[164][165][166][167][168]. Investigators suggested that transport of active agents from the delivery phase (typically the solvent) through the biofilm to the adhering interface (the surface of the medical or processing equipment) might be reduced due to physicochemical interactions of disinfectants with organic material or microorganisms in the upper layer of the biofilm matrix.…”

Microbial Degradation of Materials: General Processes

“…Biocide Resistance. Biofilms protect microorganisms from activity of biocides because mass transfer is diffusion limited within the biofilm [149][150][151][152][153][154][155][156][157][158]. In order to effectively eradicate biofilms on surfaces, higher concentrations of biocides are often used (Fig.…”