ANTIMICROBIAL PERIODONTAL THERAPY
IN GENERAL DENTISTRY
by Michael Donahue, RDH, BA
With special thanks to:
Jørgen Slots, DDS, DMD, Ph.D, MS, MBA
www.uscomtl.org
Jørgen Slots, DDS, DMD, Ph.D, MS, MBA
www.uscomtl.org
TABLE OF CONTENTS
click link to go to section
IntroductionBackground
Diagnosis: Gingivitis
Gingivitis Treatment
Diagnosis: Mild Periodontitis
Mild Periodontitis Treatment
Diagnosis: Aggressive Periodontitis
Aggressive Periodontitis Treatment
Oral antibiotics for treating periodontal disease; efficacy and safety review
Oral irrigation with dilute sodium hypochlorite solution; efficacy and safety review
Oral irrigation with dilute GSE; quaternary ammonium salts, benzethonium chloride, benzalkonium chloride solution; efficacy and safety review.
Grapefruit seed extract (GSE) ingredient labeling
Oral irrigation with dilute povidone iodine solution; efficacy and safety review
References
COURSE OBJECTIVE
Recognize the contagious aspect of periodontal disease
Be able to identify gingivitis
Become familiar with using an antimicrobial solution in an oral irrigator
Be able to identify mild periodontitis
Become familiar with effective treatments of mild periodontitis
Be able to identify aggressive periodontitis
Become familiar with subgingival irrigation with povidone iodine solution
Become familiar with periodontal microbial sampling procedures
Become familiar with the treatment protocol for aggressive periodontitis
Become familiar with long-term homecare regimen for patients with a history of periodontitis
Know how to respond if they encounter a case of periodontal disease recurrence
Oral antibiotics for treating periodontal disease; efficacy and safety review
Oral irrigation with dilute sodium hypochlorite solution; efficacy and safety review
Oral irrigation with dilute GSE; quaternary ammonium salts, benzethonium chloride, benzalkonium chloride solution; efficacy and safety review
Grapefruit seed extract (GSE) ingredient labeling
Oral irrigation with dilute povidone iodine solution; efficacy and safety review
Recent advances in laboratory DNA analysis have enabled dental researchers to identify specific bacteria and virus responsible for periodontal disease and to evaluate the effectiveness of periodontal treatments that seek to eliminate periodontal microbial pathogens from the oral cavity and elsewhere where they may be residing in the patient’s body. Utilizing non-surgical treatment protocols that can be rendered in a general dental office setting, it is now possible to eliminate all periodontal pathogens with near 100 percent predictability. Once the periodontal pathogens are eliminated, the disease process is halted and healing begins.
This course will review the diagnosing criteria for gingivitis, early periodontitis, and aggressive periodontitis. Specific treatment guidelines appropriate for each diagnosis will be clearly delineated. Traditional treatments, scaling, rootplaning, and periodontal surgery frequently fail to effectively eliminate periodontal pathogens. A relatively high proportion of patients who receive traditional therapies experience disease recurrence. Haffajee and colleagues found loss of clinical attachment in 32 percent of patients with adult periodontitis who had received three or more hours of scaling and rootplaning and then maintenance scaling with oral hygiene instruction every three months over a nine-month period.
The objective of this course is to provide clearly defined treatment protocols that will dramatically decrease the incidence of disease recurrence. If a patient experiences disease recurrence, this course will give the practitioner specific additional treatments to employ to help insure that the disease does not recur in the future.
BACKGROUND
Periodontal disease is a contagious disease passed from person to person by direct and indirect transmission. A recent study by Asikainen and colleagues found evidence of transmission of A. actinomycetemcomitans in 36 percent of married couples. Another study also by Asikainen and colleagues found evidence of transmission of P. gingivalis in 20 percent of married couples as well as parent-to-child transmission of A. actinomycetemcomitans at a rate of 32 percent.
Virtually all periodontal disease is caused by one or more of the following 14 microorganisms: A. actinomycetemcomitans, P. gingivalis, P. intermedia, B. forsythus, Campylobacter species, Eubacterium species, Fusobacterium species, P. Micros, Enteric gram negative rods, Beta hemolytic streptococci, Yeast, Eikenella corrodens, Staphylococcus species, D. pneumosintes, and the herpes virus Cytomegalovirus. These bacterial and viral pathogens play a direct and indirect role in destructive periodontal disease. Recent studies have found the body’s immune response to bacterial pathogens are responsible for the majority of connective tissue breakdown contributing to periodontitis. Exposure to these pathogens does not assure that an individual will contract periodontal disease. The number of pathogens one is exposed to and the individual’s susceptibility play important roles.
DIAGNOSIS: GingivitiS
Gingivitis may be defined by inflamed gingival tissues with periodontal probings generally 4 mm or less. There may be bleeding on probing, but no exudate. Tooth mobility is normal. There is no apical migration of the epithermal attachment. There is no sign of radiographic bone loss.
Gingivitis Treatment
Routine scaling and review of the patient’s homecare. The rare case of gingivitis that does not resolve with routine prophylaxis may clear up by simply instructing the patient to use an oral irrigator with an antimicrobial agent two times a week. It is important to instruct the patient to brush, floss, and use the oral irrigator with antimicrobial agent last. Brushing and flossing removes most of the disease-causing organisms, but also importantly disturbs their protective biofilm, leaving them vulnerable to chemical assault. Patients with bridges or splints who are reluctant to floss should be encouraged to use a perioaid or proxabrush prior to oral irrigation.
There are several oral irrigators on the market. Interplak Oral Irrigator ($29), Waterpik ($39), and Hydrofloss ($70). These three brands are user-friendly and operate at pressures that do not expose the patient to potential injury, even if misused. Cobb and colleagues reported that in clinical and microbiological studies, pulsed oral irrigation at high pressure disrupted subgingival plaque to at least 6 mm into periodontal pockets without inducing soft-tissue injury or forced penetration of microorganisms into gingival tissue.
There are two economical antimicrobial agents that have a broad spectrum of antimicrobial and antiviral activity:
1) sodium hypochlorite (bleach)
2) benzethonium chloride, benzalkonium chloride mix of quaternary ammonium
salts, grapefruit seed extract (GSE)
A sodium hypochlorite solution for subgingival irrigation can be prepared from household bleach that usually contains 6% available chlorine. A working concentration of about .125% or 1250 parts-per-million (ppm) of chlorine can be obtained by adding 1 teaspoon (5 ml) of household bleach to 8 ounces (240 ml) water. Patients can be instructed to fill an 8-ounce glass with warm water, add 1 teaspoon bleach, stir briefly, and add solution to an oral irrigator. Patients using an oral irrigator with bleach solution for the first time may be advised to do so without clothes in an uncarpeted room. This bleach solution is strong enough to cause permanent damage to carpet and garments, including white garments. This bleach solution is corrosive. Patients should be instructed to rinse the oral irrigator with fresh water after using it with a bleach solution. It is helpful to mention: “Put the nozzle of the oral irrigator in your mouth before turning it on.”
A quaternary ammonium salt solution for subgingival irrigation can be prepared from Nutribiotic® brand grapefruit seed extract, GSE, that contains approximately 8% quaternary ammonium salts, primarily benzethonium chloride and benzalkonium chloride. A working concentration of about .25% or 250 parts-per-million benzethonium chloride and benzalkonium chloride can be obtained by adding 15 drops of GSE to 8 ounces (240 ml) water. Patients can be instructed to fill an 8-ounce glass with warm water, add 15 drops of grapefruit seed extract, stir briefly, and add solution to the oral irrigator.
After using an oral irrigator with bleach or GSE for several weeks, the dental professional can expect to observe a significant improvement in tissue health. The improvements in tissue health are very similar for both bleach and GSE. Occasionally an increase in supragingival stain may be observed. This is dead plaque that has absorbed extrinsic stain and is readily polished off. This staining is an indication of ineffective plaque removal prior to using an oral irrigator. The author has found that when given a choice, approximately 9 out of 10 patients choose to use GSE over bleach. Studies have found an association between water chlorination and bladder cancer in humans. Oral irrigation with a GSE solution can be fairly portrayed as a healthier alternative to a bleach solution. It is recommended that patients taste the GSE before making a selection. Simply add 1 drop of GSE to 1 tablespoon of water and stir briefly. Most patients comment on the mild citrus flavor, however about 5 percent think the taste is atrocious. These patients have no option other than bleach. Other solutions, such as dilute mouthwash or hydrogen peroxide, are ineffective. There is nothing in the periodontal literature to indicate that a bleach or GSE solution is unsuitable for use during pregnancy. However, because GSE is labeled by the manufacturer for human consumption, it is probably a safer choice for use during pregnancy. Whether using a bleach or GSE solution, patients may be advised to rinse with their favorite mouthwash for fresh taste. Patients with a high carries incidence should be instructed to brush a second time with a high fluoride dentifrice following the oral irrigation.
DIAGNOSIS: MILD PERIODONTITIS
Mild periodontitis may be defined as exhibiting 4 mm to 5 mm pockets. Bleeding on probing may be present, but no exudate. There is a definite loss of connective tissue attachment, but no radiographic evidence of alveolar bone loss. Mobilities are within normal range and there is no furcation involvement.
MILD PERIODONTITIS TREATMENT:
Routine scaling and review of the patient’s homecare. Occasionally a second scaling appointment may be necessary to remove all calculus from tooth surfaces. In cases where there are areas of increasing pocket depths, bleeding on probing, or moderate bleeding on scaling, one can infer that periodontal pathogens are present.
At the conclusion of the routine scaling appointment, a subgingival irrigation of 10% povidone iodine (betadine®) solution is applied carefully, insuring that the excess is evacuated while irrigating. The patient is instructed to rinse following the irrigation. A 3 ml endodontic irrigating syringe with a 23-gauge blunt tip is used for administering the iodine solution. It is important to ascertain that the patient is not allergic to iodine or shell fish prior to administering betadine subgingival irrigation.
The antibacterial properties of povidone iodine are well established. More recently studies have demonstrated that povidone iodine exerts marked anti-cytomegalovirus activity. Cytomegalovirus is a herpes virus implicated in the pathogenesis of periodontitis. Povidone-iodine is water-soluble, does not irritate healthy or diseased oral mucosa, and exhibits no adverse side effects. Povidone iodine has an unpleasant medicine taste. The taste is improved somewhat by mixing 1 ounce peppermint extract with 9 ounces 10% povidone iodine to yield a 9% solution. The recommended procedure is to express small amounts of povidone iodine subgingivally repeatedly throughout the mouth in order to obtain a contact time of approximately 5 minutes. Nakagawa and colleagues reported that subgingival irrigation with 10% povidone iodine reduced the total number of cultivable bacteria in untreated periodontitis by 98 percent. Chlorhexedine gluconate has been shown to be ineffective as a subgingival irrigant.
The patient is instructed to use an oral irrigator with bleach not more than two times a week, after first brushing and flossing. It is advisable for periodontitis patients to use an oral irrigator with GSE once a day, after brushing and flossing. A substantial improvement may be observed in many patients who use an oral irrigator with GSE just two times a week. A four-month recall schedule is recommended until a healthy and stable periodontal status is achieved. A healthy periodontal status may be defined as stable or reduced periodontal probings. No bleeding on probing and no more than light bleeding on scaling. Once a healthy status is achieved, a six-month recall interval may be resumed.
DIAGNOSIS: AGGRESSIVE PERIODONTITIS
Aggressive periodontitis may be defined as multiple pockets in the 6 mm to 7 mm range, Class I or Class II furcation involvement, bleeding on probing. Exudate may be present. Tooth mobilities may be beyond the normal range. Alveolar bone loss is radiographically evident.
AGGRESSIVE PERIODONTITIS TREATMENT
In virtually all cases of aggressive periodontitis, the patient has become infected with one or more of the following periodontal pathogens: A. actinomycetemcomitans, P. gingivalis, P. intermedia, B. forsythus, Campylobacter species, Eubacterium species, Fusobacterium species, P. Micros, Enteric gram negative rods, Beta hemolytic streptococci, Yeast, Eikenella corrodens, Staphylococcus species, or D. pneumosintes.
Effective treatment of aggressive periodontitis requires the elimination of all periodontal pathogens from the patient’s body. This is unlikely to occur with scaling, rootplaning, and the application of topical antimicrobial agents alone. Aggressive periodontitis is a serious disease that may put the patient at significantly increased risk for heart disease, stroke, diabetes, pulmonary ailments, having a premature birth, and other diseases as well. The timing and sequence of professionally administered antimicrobial therapy is critical to achieving effective treatment. Treating periodontal disease is similar to treating other infectious diseases. It is imperative that 100 percent of the pathogens are eliminated from the patient’s body. Simply eliminating 99 percent of periodontal pathogens will achieve temporary clinical stability while virtually assuring future disease recurrence.
Microbial testing is recommended for cases of aggressive periodontitis. Microbial testing is a simple in-office procedure that can be accomplished in a 20-minute appointment. Small stiff paper points are placed in the deepest active periodontal pockets for a few seconds. These paper points are placed into a sealed sterile vile and sent via overnight delivery to a microbial testing laboratory for analysis. Allow approximately three weeks to receive the microbiological lab report. The report will identify the specific pathogens and recommend one or more antibiotics to be taken over an eight-day period.
Systemic antibiotic therapy has specific advantages over topical application of antimicrobial agents. They offer easy administration of the drug to multiple sites of disease activity. Eliminating periodontal pathogens from the entire mouth reduces the risk of recurrent disease.
Microbial samples should be taken prior to the initiation of professional treatment. The patient should be instructed to refrain from using an oral irrigator for one week prior to the taking of specimens. Microbial samples should not be taken if the patient has taken antibiotics of any kind in the past eight weeks, or if she is pregnant. The medical history should be reviewed with attention paid to any allergies to antibiotics.
The periodontal status of the patient’s spouse or significant other should be evaluated because untreated aggressive periodontal disease in a spouse or significant other is a common reason for post-treatment disease recurrence. It is reasonable to assume that the same periodontal pathogens will be present in the spouse. Therefore, the spouse would be prescribed the same antibiotics as the patient. It is important that both patient and spouse take the antibiotics during the same eight-day period.
Finally, any endodontically infected teeth must be treated or extracted, and any periodontally hopeless teeth must be extracted prior to microbial sampling. This is in agreement with good medical practice that dictates that the bacterial load should be reduced as much as possible before the administration of antibiotic therapy. A conservative and selective approach is recommended for periodontal antibiotic therapy. Indiscriminate antibiotic administration is contrary to sound clinical practice and may cause overgrowth of resistant pathogens and other health problems.
In the event the patient’s spouse has periodontitis, a health history for the spouse is necessary with special attention to allergies to antibiotics.
The typical treatment involves four quadrants of rootplaning, and after each rootplaning a thorough full-mouth subgingival irrigation with a betadine solution.
It is critical that the patient begin taking the antibiotics indicated by the lab report four days prior to the final rootplaning appointment. During the eight days the patient is taking the antibiotics, it is important that they brush, floss, and use an oral irrigator with either a bleach or GSE solution daily. If the antibiotics are prescribed and the patient elects not to have rootplaning, then it is recommended to have the patient schedule an office visit on day four of the antibiotic regimen for a brief polish, floss, and subgingival betadine irrigation. This can be accomplished in a 20-minute appointment. This small step significantly improves the probability that 100% of periodontal pathogens are eliminated from the oral cavity insuring a favorable long term outcome. If the spouse is also taking the antibiotics, they should adhere to the same homecare regimen as their partner.
On the final rootplaning appointment that is scheduled to coincide with day four of the antibiotic treatment, it is recommended that the previously rootplaned quadrants be briefly rescaled with an ultrasonic scaler prior to the subgingival application of betadine.
This treatment protocol is generally effective even if the patient is only partially compliant with homecare recommendations. In the rare instance of disease recurrence (refractory periodontitis), the general dentist can reasonably assume that the same periodontal pathogens have returned and simply ask the patient to retake the antibiotics a second time. This is also a good time to re-evaluate having the spouse or significant other also take the antibiotics simultaneously. Occasionally a person with a relatively healthy periodontal status is found to harbor periodontal pathogens that have the potential to infect others.
American Academy of Periodontology guidelines call for a discriminating and selective approach for the application of periodontal antibiotic therapy. Antibiotic therapy must be reserved for patients with aggressive periodontitis or those who exhibit disease recurrence following traditional scaling and rootplaning. Patients who are unwilling or unable to comply with homecare instructions and those who are unlikely to follow through with professional care at recommended intervals are unsuitable candidates for periodontal antibiotic therapy.
At this time the American Academy of Periodontology Guidelines for reapplication of antibiotic therapy once a diagnosis of refractory periodontitis has been made are as follows:
“Once the diagnosis of refractory periodontitis has been made, the following steps may be taken:
- Collection of subgingival microbial samples from selected sites for analyses, possibly including antibiotic-sensitivity testing.
- Selection and administration of an appropriate antibiotic regimen.
- In conjunction with the administration of an antimicrobial regimen, conventional periodontal therapies may be used.
- Reevaluation with microbiological testing as indicated.”
A busy general practice office may have a small number of patients with Class III furcations and 6 mm, 7 mm, or 8 mm pockets who will probably derive significant benefit by receiving polish, floss, and subgingival betadine irrigation appointment midway between the three-month recall appointments. Frequently these patients are best served by a periodontist.
Irrigating with a 10% povidone solution has been shown to significantly reduce tooth decay in carries-prone individuals.
Long-term homecare should include using an oral irrigator with a bleach solution two times a week or a GSE solution daily.
The Oral Microbiology Testing Laboratory at USC School of Dentistry offers free periodontal culture kits. The basic selective periodontal pathogen culture costs $105. A check for $105 must accompany the specimen. Microbial specimens should be shipped via overnight delivery.
To order a package of free culture kits, call (213) 740-3163, or write:
Oral Microbiology Testing Laboratory
University of Southern California
School of Dentistry, Room 4111
925 W. 34th Street
Los Angeles, CA 90089-0641
All patients who have identifiable periodontal pathogens will need to take one or more of the following: Metronidazole, Amoxicillin, Clindamycin, or Cipro. A significant number of patients will need to take two antibiotics simultaneously, usually Metronidazole and Amoxicillin or Cipro and Amoxicillin, all of which work synergistically. The usual treatment is 3 times daily for 8 days.
A small portion of patients who take Metronidazole will experience minor stomach upset. Usually this is a response to consuming tiny amounts of alcohol. These persons can be counseled to avoid mouthwash or fruit juices that are not freshly made. There have been reports of topical isopropyl alcohol from perfume or aftershave causing mild stomach upset in sensitive individuals.
A small fraction of people who take two antibiotics simultaneously will develop oral thrush caused by the overgrowth of Yeast Candida Albicans. This is manifested by a soft white plaque frequently occurring on the tongue, buccal or labial mucosa. This white film may be stripped or scraped off, whereas the majority of other white plaque-like lesions involving oral mucosa, such as leukoplakia, leukedema and lichen planus cannot be stripped or scraped off. A simple treatment is to instruct the patient to rinse with a GSE solution 3 to 5 times daily. The same mix: 15 drops to one cup warm water works well. This is very effective. There are prescription Nystatin suspensions and lozenges that are also very effective.
On occasion a woman taking two antibiotics simultaneously will develop an itchy vaginal Yeast infection. A simple and effective treatment is douching with a GSE solution: 15 drops to one cup warm water. There are also a number of over-the-counter products that work quite well.
Harvest Dental Supply wholesales GSE to dental offices in boxes of 20 bottles. Each bottle contains approximately 2,000 drops of GSE. Harvest Dental Supply sells a box of 20 bottles for $168, including shipping.
Contact: Tony Arsanis
Tel: 805-466-3202
M-F 9:00 a.m. to 6:00 p.m. Pacific time
Sat. 9:30 a.m. to 5:00 p.m. Pacific time
Harvest Dental Supply
6985 San Luis Avenue
Atascadero, CA 93422
ORAL ANTIBIOTICS EFFICACY
DNA probe analysis of periodontal bacteria has allowed periodontal researchers to empirically document the efficacy of various treatment interventions including the taking of oral antibiotics.
There is clear and convincing evidence that taking oral antibiotics as indicated by laboratory microbial analysis can eliminate all periodontal pathogens from the oral cavity in almost all cases. The probability of successful removal of all periodontal pathogens is increased if all abscessed or hopeless teeth are treated or extracted prior to commencing antibiotic therapy. In addition, the successful removal of all pathogens is further enhanced by concurrent professional treatment, i.e., scaling, rootplaning, and subgingival irrigation with a dilute povidone iodine solution.
Antibiotics are delivered to the periodontal tissues via the blood supply and to a lesser extent through saliva. Antibiotic therapy may be ineffective if large untreated abscesses or heavy supragingival plaque deposits are present. Patients who receive ongoing professional care and are generally compliant with home care instructions seldom experience disease recurrence.
ORAL ANIBIOTICS SAFETY
Oral antibiotics have a well-established safety record. The incidence of serious adverse reactions is rare, and the incidence of fatal reactions to oral antibiotics properly prescribed is extremely rare. A 22 year long Danish study identified 8 cases where oral antibiotics were identified as a cause of death from 1968 to 1990 out of a population of approximately five million.
A study published in the Journal of the American Medical Association in 2004 found that women who took between 1 and 25 antibiotic prescriptions over the previous 17 years were 150% more likely to be diagnosed with breast cancer than women who did not take antibiotics. Women who took more than 25 prescriptions over the 17-year period were more than 200% more likely to develop breast cancer than women who did not take any antibiotics.
“It’s as strong as any of the risk factors we know,” said Dr. Roberta Ness of the University of Pittsburgh Graduate School of Public Health, who is author of an editorial accompanying the study. “To put it into perspective, the risk of developing breast cancer from hormone replacement is about a 30% to 40% increase in risk. And here we are talking about doubling the risk in those women who are using chronic antibiotics,” she said.
More than 200,000 U.S. women are diagnosed with breast cancer each year, and 40,000 die from the disease, making it the second leading cause of cancer deaths among women.
This study compared the antibiotic use of 2,266 women with breast cancer with almost 8,000 without the disease. The study found increased risk for breast cancer for all antibiotics studied. This is especially interesting because different classes of antibiotics are chemically unrelated and have different mechanisms of action.
“These results only show that there is an association between the two,” [antibiotic use and breast cancer] said co-author Dr. Stephen Taplin of the National Cancer Institute.” This study is not the first to show an association between antibiotic use and a higher risk of breast cancer. In 1999 a Finnish study of almost 10,000 women found similar results.
The implications of this study’s finding: that even one course of antibiotic therapy can elevate a woman’s risk of developing breast cancer, on dental office antibiotic prescribing protocol, is substantial. This study underscores the need for a conservative and selective approach when evaluating patients for antibiotic therapy. It reinforces the wisdom of microbial testing to take the guesswork out of the practice of prescribing antibiotics. The study’s authors hypothesize that one reason for the association of diverse classes of antibiotics with an increase in breast cancer may be due to alterations of bacteria in the intestine. Another hypothesis is that women with chronic Epstein-Barr viral infection are much more prone to respiratory infection and are therefore more frequent antibiotic users. This author feels that the antibiotic-breast cancer association may be similar to the antibiotic-prostate cancer association. There is an established association between prostate cancer and bacterial sexually transmitted disease (STD). It is thought that the STDs create stress and irritation to the prostate enabling cancer cells to proliferate. There is no discussion in the literature that the antibiotics used to treat the STDs are a factor in the development of prostate cancer. The antibiotic-breast cancer association may be specious just as the antibiotic-prostate cancer association now appears to be.
The American Academy of Periodontology suggests that antibiotic therapy may be readministered each time a diagnosis of refractory periodontitis (disease recurrence) has been made. This can occur in as little as 9 to 18 months after completion of the previous course of antibiotic therapy.
At this time there is insufficient data to quantify the effect of untreated advanced periodontal disease on human health and life expectancy. Likewise, there is not nearly enough data to measure the impact of oral antibiotic therapy on human health and lifespan. A relative risk assessment cannot be made. Many years may elapse before meaningful treatment guidelines can be established.
EFFICACY OF ORAL IRRIGATION WITH A DILUTE SOLUTIONS OF
SODIUM HYPOCHLORITE
Municipal water districts have been adding chlorine to the public water supply in the United States since 1908. This disinfection of water for safe use is considered one of the greatest achievements of the twentieth century. Before cities began treating water with chlorine, cholera, typhoid fever,dysentery, and hepatitis-A killed thousands of U.S. residents annually.
The U.S. Environmental Protection Agency (EPA) standard maximum chlorination for municipal water districts is 4 parts per million. This is roughly equal to 1 teaspoon of household bleach in 19.5 gallons of pure water. This very dilute chlorine solution is sufficient to kill all known bacterial and viral pathogens except cryptosporidium and giardia lamblia within a few hours under normal conditions. Prions are not inactivated by sodium hypochlorite.
The mechanism of action sodium hypochlorite has on bacteria and virus is well understood. Hypochlorous acid molecules, due to their small size, easily diffuse through the cell walls of bacteria. This changes the oxidation-reduction potential of the cell, thus inactivating the enzyme triosephosphate dehydrogenase. Triosephosphate dehydrogenase is essential for the digestion of glucose. This effectively destroys the microorganisms’ ability to function.
The recommended dilution of 6% sodium hypochlorite is 1 teaspoon per cup of water, or 1,250 parts-per-million. This dilution with warm water has the potential to kill periodontal pathogens in a matter of seconds. The effectiveness of oral irrigation with a solution of sodium hypochlorite is further enhanced if the bacterial cell wall slime coating and biofilms are mechanically disturbed by brushing and flossing prior to oral irrigation.
The author has found the use of oral irrigation with a sodium hypochlorite solution by dental patients with a history of active periodontitis to confer improvements in the condition of periodontal tissues that are readily observable in a general dental office setting.
SAFETY OF ORAL IRRIGATION WITH A DILUTE SOLUTION OF SODIUM
HYPOCHLORITE
Allegations that municipal water chlorination causes numerous health problems have been made since water chlorination began in 1908. The alleged health problems range from various types of cancer to atherosclerosis and miscarriage. In the 1970s, studies came out suggesting an association between drinking chlorinated water and bladder cancers. This correlation has been confirmed by numerous studies in more recent years. Partly as a result of this information, the government of Peru stopped mandating the chlorination of municipal water supplies in 1991. The result: a five-year epidemic of cholera. This epidemic caused over one million illnesses and 12,000 deaths before the Peruvian water chlorination program was restored. In 1992 a meta-analysis of several researches showed a positive correlation with water chlorination and human bladder and anal cancer. The authors attributed 9% of all bladder cancer and 15% of all anal cancer to chlorinated drinking water and disinfection byproducts amounting to 10,000 cases annually. According to Dr. Kenneth Cantor, spokesperson for the Federal National Cancer Institute, drinking chlorinated water appears to increase a person’s risk of developing bladder cancer by as much as 80%.
About 45,000 Americans are diagnosed with bladder cancer each year, and over 10,000 will die from it, according to the American Cancer Society.
Chlorine reacts with minute amounts of organic material in the water to produce chemicals called trihalomethanes (THMs). Years of human and animal studies suggest but do not establish a causal relationship between THMs and cancer. The Environmental Protection Agency (EPA) suspects that THMs cause bladder cancer in humans, and as a result set a limit for THM concentrations in 1979 at 100 parts-per-billion (PPB). The EPA lowered this limit to 80 PPB effective January 2002. The EPA now encourages water districts to have less than 60 PPB THM concentrations, and there are indications that the limits may be lowered again in the future. (To appreciate the toxicity of THMs, 80 parts per billion is equivalent to 80 drops in a 10,560 gallon swimming pool.) There is a trend especially in Western Europe for water districts to adopt alternate methods of water disinfection that do not involve chlorination or THMs.
The well-established association of consumption of chlorinated water with the increased incidence of bladder cancer has implications for dental office oral irrigation home care guidelines.
The author has observed that careful use of an oral irrigator will result in more than 97% of the solution going down the drain and less than 3% ingested. Certainly there is a wide range of individual variation with respect to the amount of solution ingested.
3% of 1 cup is 7.2 ml (a bit less than 1½ teaspoons). 7.2 ml of 1250 PPM chlorine solution is equal to 2.25 liters or 9.3 cups of 4 PPM (the EPA maximum) municipal drinking water. There is insufficient time for the bleach solution to react with minute organic impurities in tap water to produce THMs, however the bleach solution may react with a high concentration of organic material present in the stomach and produce THMs. Much more research needs to be done before definitive safety guidelines can be established.
A few patients will on their own deviate from recommended treatment guidelines. The potential exists for such patients to inadvertently create a solution that contains enormous quantities of highly carcinogenic THMs. For example, a patient decides to mix up a gallon of bleach solution and adds his favorite mouthwash, mint flavoring, or anything other than pure water, to be used in his oral irrigator two times weekly for the next two months. The concentration of THMs created in this example is increased exponentially.
EFFICACY OF ORAL IRRIGATION WITH A DILUTE SOLUTION OF GSE,
BENZETHONIUM CHLORIDE / BENZALKONIUM CHLORIDE
Benzethonium chloride and benzalkonium chloride are quaternary ammonium salts. They are chemically similar and have nearly identical physical and antimicrobial properties. Quaternary ammonium compounds, including benzalkonium chloride, have been used as disinfectants in the United States since 1935.
In May 2001 Infection Control Today compared hand wash soaps for healthcare professionals for antimicrobial efficacy and skin irritation. Hand wash soaps comparing .3% trilosan, 4% chlorhexedine gluconate, 7.5% povidone iodine, .2% benzethonium chloride, and 62% ethyl alcohol. The authors concluded that the antimicrobial efficacy (log reduction of microorganisms) of .2% benzethonium chloride was superior to .3% trilosan and 62% ethyl alcohol gel. They also found the benzethonium chloride and 62% alcohol gel to be the least irritating.
Log Reduction for Five Active Ingredients for Antimicrobial Healthcare
Personal Hand Wash and Hand Rinse Active Ingredients
1st Initial Hand Wash and Ranked by Log Reduction after 7th Wash
(Higher Numbers Indicate Higher Log Reduction Levels of Microorganisms)
Ingredient
|
Initial Log Reduction
1st Wash |
Log Reduction
7th Wash |
|
1
|
CHG 4% |
2.80
|
4.28
|
2
|
7.5% povidone iodine |
3.49
|
3.43
|
3
|
0.2% benzethonium chloride |
2.40
|
3.35
|
4
|
62% ethyl alcohol gel |
3.16
|
3.06
|
5
|
Trilosan 0.3% |
2.14
|
2.31
|
In March 2004 a research team at the University of Southern California Los Angeles reported that a .1% benzalkonium chloride mouthwash effectively reduced gingivitis (as measured by bleeding on probing) in 56 subjects during the 3 month study period.
Benzethonium chloride and benzalkonium chloride are antimicrobial agents used in a wide variety of products, including irrigation of deep infected wounds, bladder and urethral irrigation, irrigant for oozing and open infections, mouthwash, eye drops and contact lens cleaners, nasal sprays, shampoo, foot powder, vaginal sponge for the prevention of STDS, including A.I.D.S., spermicides, hand wash soaps, and hard surface disinfectants. Cold sterile solutions utilizing benzalkonium chloride are still in use today in some third-world countries. They are no longer in use in the United States because they are ineffective against mycobacterium tuberculosis spores and do not inactivate prions.
The mechanisms of action for the antibacterial properties of benzethonium chloride and benzalkonium chloride are unknown. Both agents have a broad spectrum of antibacterial activity at 250 PPM concentration, however they are ineffective against mycobacterium tuberculosis spores. Both agents have a Broad spectrum of antiviral activity, including herpes virus, cytomegalovirus, and A.I.D.S. However, they are ineffective against hepatitis-B virus at this concentration. The effectiveness of oral irrigation with a dilute solution of GSE, benzethonium chloride/benzalkonium chloride is enhanced if the bacterial cell wall slime and biofilms are mechanically disturbed by brushing and flossing prior to oral irrigation.
The author has found the use of oral irrigation with a dilute solution of GSE, benzethonium chloride/benzalkonium chloride by dental patients with a history of active periodontitis to confer improvements in the condition of periodontal tissues that are readily observable in a general dental office setting.
SAFETY OF ORAL IRRIGATION WITH A DILUTE SOLUTION OF GSE,
BENZETHONIUM CHLORIDE / BENZALKONIUM CHLORIDE
Both benzethonium chloride and benzalkonium chloride have been very well studied with respect to carcinogenicity. Laboratory animals have been exposed to extremely high doses of these agents. At this time all data indicates these compounds are not a recognized or suspected carcinogen. This seems to be an established fact and there appears to be no controversy about this in the literature.
Benzethonium chloride and benzalkonium chloride are bio-compatible and non-irritating topically and systemically when diluted appropriately. In July 2005 the European Union Scientific Committee on Cosmetic Products approved benzethonium chloride at .1% for use in all cosmetic products. In the United States the FDA has approved benzethonium chloride at 250 PPM concentration as an approved preservative for injectable drugs and vaccines.
Nutribiotic® grapefruit seed extract has been sold in the United States and around the world since 1980 as a food supplement. Nutribiotic literature states the suggested use: 5 to 15 drops mixed in 5 ounces of water or juice to be consumed 2-3 times daily. They indicate GSE is suitable for adults and children age 5 and older.
Dental Office Implications:
The safety of grapefruit seed extract, GSE, is well established. The consumption of 3% of an 8 ounce solution of dilute GSE does not constitute any risk to human health whatsoever. GSE is unsuitable for persons who have a citrus fruit allergy. Occasionally a patient will say, “My physician told me I cannot eat grapefruit now that I am taking this medication.” These patients can be told the amount of grapefruit seed is so minute it has no effect on their medication. Each drop of GSE is composed of just 33% grapefruit seed derivatives and 67% vegetable glycerin.
Perhaps the most important dental implication is that current data suggest oral irrigation with GSE, benzethonium chloride / benzalkonium chloride is completely safe. Some patients will deviate from the recommended treatment guidelines. If such a patient decides to drink the 8 ounces of GSE solution, there is no risk to health. Oral irrigation with a GSE solution is completely safe. All periodontitis patients can be encouraged to use an oral irrigator with GSE solution. Patients can be encouraged to use an oral irrigator with bleach solution only if they are unwilling or unable to use a GSE solution.
GRAPEFRUIT SEED EXTRACT INGREDIENT LABELING
Many people wonder how it is that GSE can have approximately 8% benzethonium chloride/benzalkonium chloride and related quaternary ammonium salts yet these items are not listed as ingredients.
No quaternary ammonium salts are added to GSE. They are produced in a proprietary process that may involve cooking under vacuum and an infusion of nitrogen. If nitrogen is added, why is that not a listed ingredient? Nitrogen is an atmospheric gas and there is no requirement to list it as an ingredient. The simple act of cooking almost any food causes generally minor changes in the chemistry of the food. It is not unusual that the oxygen or nitrogen content is altered.
Raw grapefruit seeds exhibit zero antimicrobial activity. Modern food processing technology has enabled food processors to substantially alter the biological properties of some food products. The author has stated that “Nutribiotics® GSE is as similar to raw grapefruit seeds as Splenda’s® Sucrolose is to raw sugar.”
EFFICACY OF SUBGINGIVAL IRRIGATION OF 10% POVIDONE IODINE
Povidone iodine has a broad spectrum of antimicrobial and antiviral activity. The contact kill time in vitro of periodontal pathogens to a 10% povidone iodine ranges from 15 to 120 seconds. Nakagawa and colleagues reported that subgingival irrigation with povidone iodine reduced the number of cultivable bacteria by 98%. Hoang, et al, and others have reported that the efficacy of 10% povidone iodine irrigation is substantially enhanced as it follows scaling or rootplaning. The herpes virus cytomegalovirus is particularly sensitive to povidone iodine. Mycobacterium tuberculosis and clostridium sporogenes are especially resistant to povidone iodine.
The author has found the subgingival irrigation of 9% povidone iodine in patients with a history of active periodontitis to confer improvements in the periodontal tissues that are readily observable in the general dental office setting.
Compliant patients with refractory periodontitis have shown remarkable improvement and stability when a polish, floss, and povidone iodine irrigation appointment is added midway between the three-month prophylaxis schedule. Some dental practitioners feel that these refractory patients are better served by oral irrigation with a GSE solution 6 times a week and bleach solution 1 time a week.
SAFETY OF SUBGINGIVAL IRRIGATION OF 10% POVIDONE IODINE
SOLUTION IN THE GENERAL DENTAL OFFICE
This treatment guideline calls for the subgingival irrigation of a 10% povidone iodine solution in a manner insuring that the excesses are carefully evacuated while irrigating. The patient is instructed to rinse following the irrigation. A 3 ml endodontic irrigating syringe is used for the procedure.
If this irrigation is performed as directed, less than 3% of the povidone iodine solution will be ingested by the dental patient. An inattentive clinician or perhaps someone performing the procedure for the first time could conceivably allow as much as 10% of the solution to be ingested.
In the example where 3% of the solution is ingested, a total of .009 mg of iodine is consumed. In the example where 10% is ingested, a total of .03 mg of iodine is consumed.
3% of 3 ml is .09 ml or 10% of 3 ml is .3 ml
.09 ml = .09 mg of 10% solution or .3 ml = .3 mg of 10% solution
10% of .09 mg is .009 mg of iodine or 10% of .3 mg = .03 mg of iodine
In the highly unlikely event that 100% of the irrigation solution is ingested, a total of .3 mg of iodine would be consumed.
Iodine has been used for disinfection since 1839. Numerous studies have been conducted evaluating its effects on human health. All data indicates that iodine is not a recognized or suspected carcinogen. This seems to be an established fact and there appears to be no controversy about this in the literature.
In August 2000, Joe Hollowell of the National Center for Environmental Health and the Center for Disease Control and Prevention (CDC), together with Howard Backer of University of California San Francisco and Berkley, conducted an extensive search of the literature and published a position paper on iodine toxicity and maximum recommended dose. The authors conclude that water disinfection techniques that provide “1 to 2 mg of iodine per liter of water can be safely used for years.” They state that up to 32 mg of iodine per liter can be safely used daily for periods up to 3 months.
One resource these authors used in making this determination was a series of studies by Freund, et al, and Thomas, et al, who iodinated the water in three Florida prisons continuously over a period of 15 years. These researchers added 1 mg iodine per liter of water and estimated the average iodine intake to be at least 2 mg per day. These investigators did not find any subjects in whom the use of iodinated water caused a decrease in serum concentrations of thyroxin below normal values. There were no instances of neonatal goiter in 181 full-term infants born to women who were incarcerated while pregnant and who delivered their infants while in prison.
Dental Office Implications of Professionally Administered Subgingival Irrigation of a
Povidone Iodine Solution:
It is important to note that the maximum recommended dose of iodine (1 to 2 mg per liter) is for long-term daily consumption. This contrasts with a dental office procedure performed several times a year that involves the consumption of .009 to .03 mg of iodine. Drinking just one 12-ounce glass of iodinated water at 1 mg per liter (equal to what the Florida prisoners drank) would involve the ingestion of .375 mg of iodine. This .375 mg of iodine is more than 10 times greater than the dental patient received who swallowed 10% of the contents of the irrigating syringe, and more iodine even than the hypothetical patient who drank the entire contents of the irrigating syringe. A person who drank one 12‑ounce glass of water iodinated at the maximum short-term safe dose of 32 mg per liter would ingest 12 mg of iodine.
A dental patient who receives a subgingival povidone iodine irrigation every 6 weeks and ingests 10% of the solution on average would need to make 400 dental office visits (over a period of 46 years) to receive the same amount of iodine as a person who drank one 12‑ounce glass of iodinated water at the “maximum safe level for short‑term use” (90 days) of 32 mg per liter as designated in this CDC sponsored position paper.
Iodine is an important nutrient essential for human health. The Food and Nutrition Board of the U.S. National Academy of Sciences has established the Recommended Daily Allowance (RDA) of iodine to be:
Adults and children ages 11 and older .15 mg
Pregnant women .175 mg
Lactating women .2 mg
The World Health Organization has established the recommended daily dietary intake to be:
Adults and children ages 12 and older .15 mg
Pregnant women .2 mg
Lactating women .2 mg
Considering that the typical dental patient receiving a povidone iodine irrigation ingests about .009 mg of iodine, this author has concluded that the procedure is quite safe for all patients except those with a known hypersensitivity to iodine. In the event subgingival irrigation of povidone iodine is administered to a person with a hypersensitivity to iodine, a temporary gingival irritation will result that lasts several days to as long as a week. Studies have shown active periodontitis during pregnancy to be associated with premature birth and low birth weight babies. Pregnant women have an increased need for iodine. Irrigation of povidone iodine can safely be performed on women with active periodontitis during pregnancy.
APPENDIX A
To order a package of free culture kits, call (213) 740-3163, or write:
Oral Microbiology Testing Laboratory
University of Southern California
School of Dentistry, Room 4111
925 W. 34th Street
Los Angeles, CA 90089-0641
Harvest Dental Supply wholesales GSE to dental offices in boxes of 20 bottles. Each bottle contains approximately 2,000 drops of GSE. Harvest Dental Supply sells a box of 20 bottles for $168, including shipping.
Contact: Tony Arsanis
Tel: (805) 466-3202
M-F 9:00 a.m. to 6:00 p.m. Pacific time
Sat. 9:30 a.m. to 5:00 p.m. Pacific time
Harvest Dental Supply
6985 San Luis Avenue
Atascadero, CA 93422
APPENDIX B
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