Page W. Caufield, D.D.S., Ph.D.:
Because dental caries is an infectious disease of bacterial origin, antimicrobial agents constitute a reasonable approach toward attenuating not only the bacterial biofilm in situ but also its transmission from host to host. This approach, while based upon certain constraints inherit to the oral cavity, has its roots in early attempts at plaque control and extends from mechanical to chemical approaches.
Although the extension of this approach to present-day chemotherapeutic tactics seems well-reasoned and grounded in the best traditions of the "medical model," several assumptions that underpin the chemotherapeutic approach need re-examination. For example, a global reduction of the plaque biofilm mass may not lead to the desired effect of selectively eliminating or reducing the caries-associated microorganism. The exception to this may be fluoride, since differential suppression of mutans streptococci has been shown in artificial plaque models. Thus, the aim of the antimicrobial approach for the control of caries should not be toward elimination of all plaque organisms but toward effecting an ecological shift from a cariogenic to a noncariogenic biofilm. To date, the antibacterial effects of chemotherapeutic agents have been assessed mainly by monitoring the levels of mutans streptococci. It is likely, however, that other microbes in the plaque biofilm must be affected in order to cause an ecological shift. Monitoring the change in the ratio of mutans streptococci to S. sanguinis is one example of using an ecological shift as a surrogate predictor of efficacy.
The last 30 years have been seen a focus on defining and then targeting specific members of the oral microbial flora in the tradition of Koch�s tenet of "one bug, one disease, one bullet." On closer inspection, however, we find that most (if not all) chemotherapeutic applications to the oral cavity are nonspecific in terms of their spectrum of antimicrobial activity and methods of application. Broad spectrum antimicrobials, such as chlorhexidine, iodine, and various formulations of fluoride continue to enjoy widespread acceptance as antimicrobials. Careful examination of the published literature, however, shows that these agents, when topically applied, produce only short-term effects on cariogenic bacteria, with marginal or small reductions in caries outcome. Presumably, the plaque biofilm recolonizes tooth surfaces following disinfection. Reservoirs for cariogenic as well as noncariogenic organisms may exist within areas unaffected by disinfection, including the tongue and the subsurface lesions, fissures, and margins of existing restorations. In fact, one study showed that after treatment, cariogenic mutans streptococci appeared in numbers higher than before treatment. It was hypothesized that the antibiotic affected the exposed microbes, while those buried deep in the caries lesion were not affected. Disinfecting or obtunding (e.g., sealants) these potential reservoirs of recolonization should be considered in future antimicrobial approaches to caries prevention.
In addition, antimicrobial suppression of all the microbes in dental plaque may be unrealistic or undesirable for ecological reasons. Because plaque microorganisms are members of the indigenous biota of humans, they constitute a well-organized "multicellular organism" that has enjoyed a long-term coevolution with its human host. It seems likely that most of the nearly 1,000 different microbes in dental plaque are benign symbionts that confer some selective benefits to their host. One example of this may be the elaboration of peptide antibiotics, such as the mutacins, that may play a role in preventing overt, nonindigenous pathogens from colonizing the oral cavity.
Because chemotherapeutic agents that are safe for oral use are applied to the entire plaque community, all microbes are presumable affected. One possible exception to this may be fluoride compounds that selectively affect homofermentative acid producers via enolase inhibition. Disruption of enolase displays varying effects on different bacterial groups, depending on their primary modes of catabolism and inherent resistance to fluoride action or uptake. Experiments using in vitro artificial plaque models suggest that the proportions of acidogenic bacteria, such as the mutans streptococci, in the oral cavity can be altered by the presence of relatively small amounts of fluoride. Effecting an ecological shift by selectively depressing acid-producing bacteria constitutes a rational approach to caries control, and the translation of these findings to the human has been underexploited. Practical questions, such as the scheduling of applications and the dosage needed for successful clinical trials, have not yet been answered.
Another use of chemotherapeutic agents could be to suppress the transmission of cariogenic organisms from mother to child. Studies by Swedish investigators show that treating mothers with chlorhexidine gels affects both the infectivity of mutans streptococci in their children as well as the latter�s caries experience. Efforts to affirm this approach, however, have led to various outcomes, mostly to no effect. Timing of the treatment to the mother at the time of acquisition of cariogenic bacteria may be an ecologically sound approach to suppressing transfer, and knowledge as to when the indigenous biota are transferred will contribute to eventual success. Although colonization of mutans streptococci follows the emergence of primary teeth during what has been termed the "window of infectivity," the initial transfer of indigenous biota may occur at birth, with the tooth-dependent colonizers existing in yet-to-be-discovered reservoirs, such as the tonsils, tongue, or gastro-intestinal tract. Thus, chemotherapeutic applications to the mother around the time of birth may alter the transmission of indigenous biota, including cariogenic bacteria.
In summary, rational use of chemotherapeutic agents to control or prevent dental caries will necessitate a more holistic understanding of the plaque microcommunity. Shotgun suppression of the entire flora without acknowledging the overall effect on ecology is unlikely to succeed. Chemotherapeutic approaches must be better targeted against specific microbes, with the goal of reestablishing an ecologically stable noncariogenic plaque. In addition, chemotherapy will need to be coupled with mechanical measures to reduce or eliminate reservoirs for recolonization.