PROCEDURES FOR ESTABLISHING EFFICACY OF ANTIMICROBIAL AGENTS FOR CHEMOTHERAPEUTIC CARIES PREVENTION

Chemotherapeutics are presently considered for use in caries-preventiv e programs. The laboratory and in vivo testing of these agents, to som e extent, parallels the methodology developed for the evaluation of fl uoride products. However, fluoride is primarily effective by interferi ng with the de- and remineralization balance between enamel and the or al fluids. Antimicrobial and chemotherapeutic agents interfere with th e bacterial colonization, growth, and metabolism of dental plaque. The initial selection of promising agents is done, therefore, by determin ation of the minimum inhibitory concentration (MIC) against a wide ran ge of relevant bacterial species, together with tests of the effects o f sub-MIC levels on the expression of virulence factors. In the hierar chy 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 treatm ent perturbs a stable microflora. A final stage before clinical testin g might involve intra-oral studies on limited numbers of volunteers. T hese should be tests of intra-oral substantivity and activity of the a gents in formulated products, and in situ models of enamel caries lesi on formation and remineralization. The latter type of study seems part icularly appropriate to ensure that new agents do not decrease the eff icacy of the other active components (e.g., fluoride) in caries-preven tive products.