Procedures for Establishing Efficacy of Antimicrobial Agents for Chemotherapeutic Caries Prevention

Abstract

s. Chemotherapeutics are presently considered for use in caries-preventive programs. The laboratory and in vivo testing of these agents, to some extent, parallels the methodology developed for the evaluation of fluoride products. However, fluoride is primarily effective by interfering with the deand remineralization balance between enamel and the oral fluids. Antimicrobial and chemotherapeutic agents interfere with the bacterial colonization, growth, and metabolism of dentalplaque. The initial selection of promising agents isdone, therefore, by determination of the minimum inhibitory concentration (MIC) against a wide range of relevant bacterial species, together with tests of the effects of sub-MIC levels on the expression of virulence factors. In the hierarchy of tests proposed in this paper, studies of bacterial adhesion and enamel caries models form the next phase in the evaluation of agents. Also, mixed-culture studies are recommended to determine how a treatment perturbs a stable microflora. A final stage before clinical testing might involve intra-oral studies on limited numbers of volunteers. These should be tests of intra-oral substantivity and activity of the agents in formulated products, and in situ models of enamel caries lesion formation and remineralization. The latter type of study seems particularly appropriate to ensure that new agents do not decrease the efficacy of the other active components (e.g., fluoride) in caries-preventive products.