Reducing Risks of Bacterial Endocarditis from Dental Procedures With Oral Time-Released Xylitol

In April 2007, the ADA and its Council on Scientific Affairs published a position paper that provides newly revised guidelines for the prevention of infective endocarditis (IE).1 These guidelines, endorsed by the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Heart Association (AHA), among others, reflected current research assessing dental procedure related bacteremia, endocarditis prevention, and the most common pathogens associated with the condition. The new guidelines reduce the classes of patients for whom antibiotic prophylaxis is recommended because the risk of morbidity resulting from antibiotic use outweighs its probable benefits. However, the guidelines also suggest that dental manipulation of any type may result in the introduction of potentially pathogenic bacteria into the bloodstream. This raises an important question whether less risky approaches to controlling oral bacteria prior to dental procedures and general oral care might be a useful preventative strategy for individuals previously defined as at-risk for IE and where antibiotics are not now recommended. Given this, the following discussion is directed toward a possible new approach for reducing the oral bacteria associated with blood born infection using xylitol incorporated into a time release disk that adheres to the gingiva and/or teeth.

Factors in the Pathogenesis of Infective Endocarditis

The pathogenesis of IE is complex and involves a number of different factors. There must be vessel turbulence leading to platelet deposition and damage to the endothelium of the cardiac valve or surgically constructed pulmonary shunt or conduit, combined with a bacteremia arising from oral trauma with microorganisms that are capable of adhering to the site (typically streptococci, staphylococci, and enterococci), and bacterial proliferation at the site of adherence.2

Multiple studies suggest that procedures such as tooth extraction, periodontal surgery, tooth cleaning and scaling, rubber dam placement, and root canal therapy can cause a bacteremia.‎3-5 Even though there is evidence that bacteremia follows dental treatment and dental hygiene procedures, because of potential allergy, resistance, and cost-effectiveness, among other factors, the counsel restricted the classes of patients for whom short-term antibiotic prophylaxis before dental procedures are recommended. Prevention via systemic antibiotic application is generally discouraged because, in addition to the above, there is a lack of viable supportive research and further, there are contradictory results. Additionally, limited studies assessing topical antiseptic rinses or germicides as a strategy for reducing bacteremia arising from dental procedures suggest that they are not likely to be effective.8,9

To control the risk of IE in patients for whom antibiotic prophylaxis is no longer recommended, the ADA recommends that individuals simply maintain good oral hygiene and avail themselves of professional dental care. The underlying assumption is that good oral hygiene will reduce overall bacterial counts leading in turn to a reduction in the number of bacteria introduced during dental or hygiene procedures. Good oral hygiene includes daily tooth brushing, flossing, and minimizing sugars that feed resident bacteria. While this proposal makes eminent sense, from a public health standpoint it is not all that clear that the majority of people will follow good preventative practices and present for routine dental care. In fact, based on the US Surgeon General’s Report in 2000,10,11 there remains a substantial discrepancy between American children, young adults, and older adults in terms of access to preventative and other dental care services based on ethnicity, income, education, and special needs status. It is estimated that the fastest growing populations in the US (eg, Black, Hispanic) have the highest disease rates and lowest access to dental care12 even in the face of current National Health Insurance Programs.13 In addition, there appears to be considerable disparity between states with respect to implementation of the State Child Health Insurance Program and comparisons of children in states with and without the plan suggesting that there is over a 24% difference in terms of likelihood of preventative care based on this variable alone.14 The issue concerning adults may even be worse. Thus, many people in the US will not receive the preventative training and skills development necessary to satisfy the ADA’s basic requirements for prevention of IE associated with routine home care.

Other Methods to Reduce Oral Bacterial Burden

Among many of the other continuing and unanswered questions in relation to the introduction of bacteria into the bloodstream and potential IE is whether there are low risk methods besides “good oral hygiene” for reducing the overall burden of oral bacteria prior to dental procedures, specifically the bacteria that are known to cause bacteremia and IE, and whether such a reduction in these disease causing bacteria might result in a drop in the incidence of IE and its associated morbidity or mortality, particularly in the aged and disabled. To date, there have been no prospective, controlled, randomized studies to assess these issues. In a review of IE and dental procedures, it is concluded that, given the current evidence regarding pathogenesis and prevention of endocarditis, novel strategies need to be developed as alternatives to current approaches using antibiotic prophylaxis.15

Assuming, as has been suggested by the AHA’s report, that it might be helpful to reduce the oral bacterial burden prior to dental procedures in individuals where antibiotic prophylaxis is not recommended, the literature regarding xylitol, a sugar substitute that occurs widely in nature which can be delivered topically in the mouth, offers a potential means for achieving this end. Specifically, in a number of dental studies addressing control of caries, it has been found that delivery of xylitol in a controlled manner with chewing gum significantly reduces salivary Streptococcus (Streptococcus mutans) counts.16-18 This is of particular significance not only in the arena of public dental health and caries but also because recent research completed by a group of investigators from Japan, with their findings published by the Journal of Clinical Microbiology, has revealed that S mutans (presumed to be derived from the oral cavity) is the most numerous specie in heart valve and atheromatous plaque specimens.19

Use of xylitol chewing gum four or five times per day has been shown to reduce not only S mutans but also Streptococcus salivarius and Streptococcus sanguis,20 and regular consumption by mothers has been shown to reduce mother-child transmission.21 Further, a xylitol induced reduction in bacterial counts has been shown to continue for a prolonged period of time (age 3 to age 6 years) in children studied.22 Xylitol has also demonstrated efficacy in reducing counts of Streptococcus sobrinus, Lactobacillus rhamnosus, Actinomyces viscosus, Porphyromonas gingivalis, and Fusobacterium nucleatum that have been experimentally incorporated into model biofilms,23 in reducing counts of Porphyromonas aeruginosa in maxillary sinus specimens,24 in altering the viability of strep pheumococci responsible for acute otitis media,25 and in altering cytokine expression induced by P gingivalis (one of many bacteria suspected in periodontal disease).26 These as well as other studies provide a potential medical use for xylitol in reducing bacterial counts potentially involved in cardiac disease and suggest an adjunctive application in the management of IE and other infective diseases (eg, sinus infection, middle ear infection, gingivitis, and periodontitis).

Presently, xylitol is primarily delivered via chewing gum.15,27-29 but it has also been incorporated into lozenges and syrup. In a study assessing the effect of xylitol on hunger, xylitol has been put into yogurt,30 and it is also found in other food products.31 However, one of the problems with its incorporation into foods is whether an adequate concentration can be maintained over a long enough time in the mouth to effectively reduce oral bacteria. Delivery of xylitol via gum appears to be effective in this regard. However, xylitol released from gum is dissipated in about 15 minutes,34 new 32 which requires that it be used 5 times or more per day to be effective and be used in larger quantities than desired.

Xylitol has also recently been incorporated into a time-release adhering disc called XyliMelts (OraHealth Corporation) that can be adhered to the teeth or adjoining gingiva to time-release 500 mg of xylitol. Xylitol delivered in this manner is very likely to be present in the mouth for longer periods of time (30 to 120 minutes—based on reports from subjects in a pilot study) and may be more tolerated by patients unwilling or unable to chew gum (eg, the edentulous, those with temporomandibular joint disorder or disabilities). XyliMelts can also be used while sleeping, when saliva flow is lowest, potentially increasing the effectiveness of the overall antibacterial action. A similar oral adhering disc called Oramoist (Quantum) designed to adhere to the roof of the mouth and release flavor to stimulate saliva also contains xylitol but the amount of xylitol in each disc is not published by the manufacturer and is likely insignificant.

Studies suggest that a dose of xylitol in the range of 6.5 g per day to 10.3 g per day delivered with chewing gum over 4 or 5 uses per day is sufficient to reduce streptococci levels.27 Studies of quantities of xylitol that must be delivered with the time release discs to achieve the same effect have not been completed. One would expect the required dosage for an equal effect to be significantly lower and the effect of an equal dosage to be significantly greater. A preliminary study (which cannot be cited because of proprietary issues) has apparently shown that only one gram per day delivered over time by XyliMelts can significantly reduce S mutans counts.

While providing the required dosage in gum can be “cumbersome” as one of the above authors has suggested,27 delivery in a dissolving disc adhered to a molar or gingiva in the buccal vestibule is easily accomplished and could make the process considerably more palatable. To achieve an effect equal to 1.3 g of xylitol chewing gum used 5 times per day (6.5 g per day), the manufacturer (OraHealth) of XyliMelts suggests that a time release disc containing one-half g of xylitol should be used at bedtime and “after each meal, at least 4 discs per day,” for a minimum of 2 g per day. Until studies are completed to determine whether this usage is sufficient to obtain optimal reduction of pathogenic bacteria, to be conservative, based on prior chewing gum studies, one could increase the usage to 4 g per day (8 discs). As previously noted, this approach to the delivery of xylitol prior to dental procedures would likely be particularly worthwhile in those with physical or mental disabilities and in frail older people where maintenance of good oral health is often problematic and where bacterial endocarditis can be a significant problem.32,33 new 33,34

New American Heart Association Recommendations

The AHA now recommends antibiotic prophylaxis before dental procedures only in patients with high risk of IE where that risk outweighs the risks of problems from the antibiotics. (The cardiac conditions that present this level of risk include: prosthetic cardiac valves; congenital heart disease including unrepaired cyanotic coronary heart disease (CHD), including palliative shunts and conduits; completely repaired congenital heart defect with prosthetic material or devices, whether placed by surgery or by catheter intervention during the first 6 months after the procedure, repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device; and cardiac transplantation recipients who develop cardiac valvulopathy). Also included are individuals with a previous IE history. However, another problem associated with IE is the presence of comorbid disease. Hence, individuals with diabetes mellitus, immunosuppressive conditions, and kidney disease necessitating dialysis may have an increased risk of morbidity and mortality from IE. And as previously mentioned, disability and age may also confound the risk of developing the condition in susceptible individuals. However, antibiotics are no longer recommended for this cohort of patients.

New Questions for New Technology

Important questions raised by the new technology for time release of xylitol in the mouth are: (1) whether the XyliMelts discs should be used for several days or weeks before undergoing dental procedures; (2) whether this prophylaxis should be recommended for all dental procedures or only those where substantial bleeding is expected; (3) whether this prophylaxis should be recommended for all patients or only those with a moderate risk of IE; and (4) how patients with moderate risk are to be distinguished from patients with low risk. As an initial step in answering these questions, both in vivo and in vitro studies need to be pursued to assess the effect of xylitol delivered by time-release adhering disc on the oral carriage of the previously defined pathogens causing IE. Then additional prospective randomized controlled trials should be considered to assess the efficacy of this delivery system in preventing IE in select patient cohorts. Finally, it would also be useful to assess the effectiveness of xylitol delivered via adhering disc on other conditions identified as also being caused, in part, by the identified bacteria and where other xylitol-based applications have been found to prevent disease (eg, sinusitis, otitis media).29

Conclusion

Given what is now known regarding oral bacteria and their introduction into the bloodstream, until the above questions are answered, it would seem prudent for individuals with previously identified risk factors for IE who are not now prescribed antibiotics to use over-the-counter products including xylitol (eg, XyliMelts, xylitol gum) for as many days as practically achievable (one to 20 days) prior to dental procedures. These products might also be recommended by health care providers other than dentists for individuals who, for varying reasons, are not able to avail themselves of routine dental preventative care and where there is perceived risk.