Correlation of microenvironmental drug concentration with inhibition of growth of microorganisms on surfaces

Methodologies have been developed to study the concept of microenvironmental drug concentration (C*) near or around microorganisms. C* may be calculated from data on drug release from a depot site by using appropriate diffusion relationships. By following C* and correlating this with the minimum inhibitory concentration (CMIC), one could attempt to predict the effectiveness of an antiplaque agent. When C* is less than CMIC, growth would be expected to occur; when C* is higher than or equal to CMIC, growth would not be expected. Chlorhexidine diacetate was chosen for this study, which used a system involving microorganisms present on the surface of drug-treated hydroxyapatite pellets. CMIC, defined as the lowest concentration to inhibit bacterial growth, was determined independently and under conditions similar to those used in the C* experiments. Surface growth of adhering microorganisms (Streptococcus mutans SL1) was followed by scanning electron microscopy. The parameters used in the calculation of C* were determined independently. Diffusion coefficients of the drugs and the diffusion layer thickness were determined under conditions similar to those employed in the release rate studies. Surface growth was generally found to be inhibited whenever C* was significantly greater than CMIC, and growth occurred whenever C* was significantly smaller than CMIC. These findings demonstrate how C* may determine the action of a topically administered antimicrobial agent and how the various physical and chemical factors play roles in influencing this quantity.