healthcare professionals continually seek ways to address the plaque
biofilm and excessive host response that are responsible for the
breakdown of connective tissue and bone associated with periodontal
diseases. While mechanical therapy (such as scaling, root planing and
power instrumentation) is considered the gold standard for biofilm
disruption and removal, the data tell us that clinicians rarely if ever
achieve complete removal of the putative pathogens that reside in the
biofilm from the surface.1 What scientists do know is that
the plaque biofilm is composed of a complex group of bacteria living
together in a multispecies community. The microbes in the biofilm are
stable, and tightly adhere to each other and to an oral substrate by
means of an extracellular matrix.2,3 Bacteria in biofilms are much more resistant to antimicrobial agents than those dispersed as single cells of the same species.
|Table 1. Desirable qualities in antimicrobial agents
• Effectiveness against specific pathogens
• Nontoxicity to oral tissues
• Does not cause overgrowth of other organisms
• Does not contribute to development of bacterial resistance
• Substantiveness: resists dilution
this helps us to understand why antibiotics utilized to address the
biofilm, either locally applied or systemi cally administered, are
considered adjuncts to mechanical therapy instead of monotherapies. What
this means to dental clinicians is that an optimal therapeutic approach
may include adjunctive therapies such as antiseptics and/or
antibiotics, as well as host modulation (in addition to mechanical
therapy) to best address a complex disease process. Devising a suitable
treatment plan would also depend, of course, on the patient's host
response and oral healthcare habits.
agents are used to eliminate, reduce or alter the effect of
microorganisms in the oral cavity and elevated levels of
pro-inflammatory mediators. The term antimicrobial refers to agents that
kill microbes or affect the growth and multiplication of
microorganisms.4 Several chemotherapeutic agents are
available to oral healthcare providers to assist in the control and
reduction of supragingival plaque and associated gingivitis. These
typically take the form of mouth rinses or dentifrices. Other agents
available for the control and treatment of chronic periodontitis, such
as locally applied antimicrobials/antibiotics and systemically
administered antimicrobials, are reserved for more aggressive cases.
noted in Table 1, a valuable quality in antimicrobial agents is
substantiveness, or the ability of an agent to remain in an area or site
and resist being diluted or washed away by gin gival crevicular fluid
or salivary action.5 In addition, a systemically administered
sub-antimicro bial dose of doxycycline (20 mg) has been approved by the
United States Food and Drug Administration (FDA) as an adjunctive host
modulatory therapy to reduce levels of enzymes and cytokines known to
drive the breakdown of connective tissue and bone metabolism changes
associated with periodontitis.
Mouthrinses and Dentrifices
designed to reduce plaque and gingivitis contain antiseptic
agentsâ€”chemical antimicrobial agents that are applied topically or
subgingivally to mucous membranes, wounds or intact dermal surfaces to
destroy microorganisms, inhibit their reproduction or inhibit their
metabolism. While most antiseptics are bactericidal (meaning, kills
bacteria), some are bacteriostatic (that is, they inhibit growth and
reproduction of bacteria without killing them). The most common active
ingredients in mouthrinses are essential oils of dentifrice:
chlorhexidine gluconate (CHXâ€”available by prescription only);
cetylpyridinium chloride (CPC) and stannous fluoride. These agents have
been evaluated in the laboratory (pre-clinically) and in clinical trials
for efficacy and safety. All are safe when used as directed.
Chemotherapeutic dentifrices in the U.S. primarily contain triclosan or
is a brief description of the active ingredients in common
chemotherapeutic mouthrinses and dentifrices used in the control of
plaque and gingivitis:
(CHX): The antiseptic CHX is one of the most effective anti
plaque/antigingivitis agents available to clinicians. It is sold in the
U.S. as a prescription mouthrinse at 0.12 percent concentration. Most
products contain 11.6 percent alcohol, although products without alcohol
are also available. The mechanism of action is related to an alteration
of bacterial adsorption, a reduction in pellicle formation and an
alteration of the bacterial cell wall causing lysis to occur. A major
advantage of CHX is that it is a very substantive agent that brings
reductions in plaque biofilm and gingivitis ranging from 22 to 61% and
18 to 44%, respectively.6 The disadvantages of CHX are teeth staining, alteration of taste and an increase in calcified deposits.
Oils: The three essential oils are a mixture of thymol, menthol and
eucalyptol combined with methyl salicylate. The alcohol content is 21.0
to 26.9%. The mechanism of action is related to alteration of the
bacterial cell wall. Studies have reported plaque and gingivitis
reductions ranging from 14 to 56% and 14 to 39%, respectively.6 The adverse effect is a burning sensation during use with certain formulations.
Chloride (CPC): CPC is classified as a quaternary ammonium compound.
The mechanisms of action include: rupture of cell walls; the promotion
of cell lysis; decreased cell metabolism; and the ability for bacteria
to attach to tooth surfaces. Studies have reported plaque and gingivitis
reductions of 15% and 24%, respectively.7,8 Reported side effects include staining, increased calculus formation and occasional burning.
Fluoride (SnF2): SnF2 products are available in rinses and dentifrices.
Formulations vary from 0.63% in rinses to 0.045% in dentifrices.
Previous reports showed a reduction in plaque biofilm and gingivitis for
short periods after use. A possible downside is that formulations have
received mixed reviews in the past due to the instability of stannous
fluoride (although new, more stable formulations are available).
Reported side effects include staining and altered taste.
This is a broad spectrum antibacterial agent. In the U.S., triclosan
(0.03%) is only available in a dentifrice with the copolymer Gantrez
(2.0%), which improves its efficacy. With the addition of 0.243 sodium
fluoride in a silica base, it has demonstrated efficacy in reducing
plaque, gingivitis calculus and dental caries.9 Reductions in plaque and gingivitis ranging from 12 to 59% and 22 to 25%, respectively, have been reported.10 Triclosan has been used safely for many years.
Chemotherapeutic Agents for Chronic Periodontitis
many patients will respond to thorough debridement and self-care
therapies such as described above, for patients who do not improve or
for whom their periodontal health continues to decline, stronger
adjunctive therapies may be necessary. Since the 1980s, locally applied
antimicrobials/ antibiotics (LAAs) have been available to dental
professionals. (See Table 2.)
three resorbable, site-specific locally administered
antimicrobial/antibiotics products approved by the FDA for the treatment
of chronic perio dontitis are available. They are: Arestin®
(OraPhar ma, Inc. Warminster, Penn.), minocycline microspheres;
Atridoxâ„¢ (Tolmar Inc. Ft. Collins, Colo.), a doxycycline gel; and
Perio Chip® (Dexcel Pharma, Alzenau, Germany), a
chlorhexidine based chip. PerioChip is the only antiseptic LAA; it is
not an antibiotic. Patients who have an allergy to the tetracycline
class of drugs or who are pregnant should have Perio Chip placed if an
LAA is indicated.
agents, used as an adjunct to scaling and root planing, deliver an
antiseptic or antibiotic to the base of the periodontal pocket with the
goal of improving pocket depth reductions, clinical attachment level
gains and reductions in bleeding on probing. The substantivity of the
agents vary (seven days for chlorhexidine glucontate11 and doxycycline;12 14 to 21 days for minocycline13).
However, all have greater substantivity than mouthrinses used
subgingivally as irrigants. The added benefit of the agents is the slow
release of the active ingredients at a higher minimal inhibitory
concentration (MIC) level than can be achieved by any other application.
The MIC represents the concentration of antibiotic required to inhibit
growth of a planktonic bacterial population. Locally delivered,
site-specific agents have a higher and longer substantivity and maintain
MIC long enough to significantly reduce the level of pathogens, leading
to improvements in the periodontal condition after single or multiple
all of the agents were studied in nine-month clinical trials for the
improvement of chronic periodontitis, more recent investigations
continue to show benefits for highrisk patients. For example, Goodson et
al demonstrated that Arestinâ„¢ significantly reduces periodontal
pathogens comprising the "red complex" (i.e., P gingivalis, T. forsythia
and T. denticola), compared to scaling and root planing alone by one
month, particularly in smokers.14 A two-year follow-up of
Atridoxâ„¢ and scaling and root planing in smokers demonstrated
sustained improvements in probing depth reductions and relative
attachment level gains beyond what was achieved with scaling and root
planing alone.15 These findings are important for clinicians
who strive to improve the periodontal condition of patients who do not
respond to mechanical therapy. Recent studies have demonstrated the
intensive periodontal therapy with locally applied antimicrobials also
results in significant reduction in the overall inflammatory burden,
with reduced risk for cardiovascular events.16,17
Other Locally Applied Products
(Periowave Dental Technologies, Inc. Toronto, Ontario, Canada),
currently not approved for use in the U.S., is a non-antibiotic therapy
intended to destroy gram negative bacteria without promoting the
development of bacterial resistance.18 Used in the treatment
of chronic periodontitis, it utilizes a cold (non-thermal), low-power
diode laser as the activating light. Indications for use are for
patients with 4 to 9 mm pockets that bleed on probing.
Marketed as a method to treat chronic periodontitis, Perio Protect®
(Perio Protect LLC, St. Louis, Mo.) relies on a custom-made tray to
deliver a solution (selected by the dentist) to chemically alter the
biofilm in the periodontal pocket and change the pocket's
microbiological environment to disrupt biofilm growth. In November 2009,
the American Academy of Periodontology (AAP) published a fact sheet on
its consumer website to educate the public about Perio Protect.19
The AAP reported that it was not aware of any randomized, controlled
clinical trials published in peer-reviewed scientific journals on the
efficacy of this therapy. FDA approval relative to this product is for
the tray as a device only.
the 1980s it was recognized that al though bacteria may initiate the
periodontal disease process, they were insufficient by themselves to
cause peridontitis. Research supported the fact that a person's response
to the perio dontal pathogens, known as the host re sponse, was key to
the development and progression of the disease. Elevations in
pro-inflammatory mediators (such as cytokines, pros tanoids and enzymes
known as matrix me tal loproteinases) were driving the disease process,
leading to the connective tissue breakdown and bone metabolism changes
patho-gnomonic of periodontitis. These findings resulted in the
development of an FDA-approved host modulatory therapy known as
Periostat. This therapy evolved as a new use for an old drug,
doxycycline, which when used at a sub-antimicrobial dose (20mg) could
inhibit the destructive enzymes and reduce the excessive levels of
cytokines associated with active disease.
administered at this sub-antimicrobial dose, doxycycline does not cause
the long-term side effects seen with high doses of antibiotics such as
gastrointestinal upset, the overgrowth of yeast and the de velopment of
bacterial resistance. Periostat was tested in multiple randomized double
blind placebo controlled clinical trials and found to be an effective
adjunct to scaling and root planing, contributing to significant
improvements in probing depth reductions, clinical attachment level
gains, and reductions in bleeding on probing with no adverse effects.20 It has been shown to boost the effects of locally applied antimicrobials such as Atridox.21 Recent clinical studies have supported its use in high-risk patients who are more difficult to manage, such as smokers,22 people with diabetes23 and women with osteoporosis/ osteo penia,24 as well as those at risk for cardiovascular disease.25 It is available in a generic form by prescription only and should be used for a minimum of three months.
professionals have come a long way in developing strategies that help
in the prevention and treatment of periodontitis. Treatment strategies
combining the use of mechanical therapies and adjunctive
chemotherapeutics enable us to better manage both gingivitis and
periodontitis. The use of antiseptics, antibiotics and host modulatory
therapy as adjuncts to brushing, ultrasonics, scaling and root planing
have made non-surgical therapies more predictable, resulting in
improvements in plaque control, pocket depth reductions, clinical
attachment levels and bleeding.
implementation of intensive periodontal therapy may not only improve the
oral condition of patients, but may also have a positive impact on
their overall health. Re-evaluation and constant monitoring of patients
is essential when managing a chronic progressive disease, and clinicians
must recognize that when nonsurgical therapy is not enough, they must
consider surgical approaches to manage periodontal diseases. We are
fortunate to be practicing in an era where we have the tools to treat a
wide array of patients with varying risk for the development and
progression of peridontitis. It is up to us to plan treatment strategies
that address the unique needs of each patient.
Rebecca S. Wilder, RDH, MS,
is a professor and director of the Master of Science Degree Program in
Dental Hygiene Education and director of Faculty Development at the
University of North Carolina at Chapel Hill School of Dentistry. She is
also the editor in chief of the Journal of Dental Hygiene. She speaks
internationally in the areas of periodontics, oral systemic health, risk
and practice management. Wilder is also an editorial advisory board
member for Dimensions.
Maria Emanuel Ryan, DDS, PhD,
is a professor in the Department of Oral Biology and Pathology at the
School of Dental Medicine, a member of the medical staff at University
Hospital at Stony Brook University Medical Center, and serves as the
associate dean for Strategic Planning and External Affairs. Ryan serves
on several scientific, dental and medical advisory boards. She is an
internationally known speaker and author, and has published more than 75
original scholarly works.
1. Kepic TJ, O'Leary TJ, Kafrawy AH. Total calculus removal: an attainable objective? Periodontol. 1990; 61:16-20.
2. Listgarten MA. Structure of the microbial flora associated with periodontal health and diseases in man. J Periodontol. 1976;47:1-18.
3. Cobb CM, Killoy WJ. Microbial colonization in human periodontal
disease: an illustrated tutorial on selected ultrastructural and
ecologic considerations. Scan Microsc. 1990;4:675-691.
4. American Academy of Periodontology: AAP guidelines for periodontal therapy. J Periodontal. 2001;72:1624-1628.
5. Elworthy A, Greenman J, Doherty FM et al. The substantivity of a
number of oral hygiene products determined by the duration of effects on
salivary bacteria. J Peroidontal. 1996;76;572-576.
6. Addy M. Chlorhexidine compared with other locally delivered antimicrobials. J Clin Periodontol. 1986;13:957-964.
7. Lobene RR, Lobene S, Soparkar PM. The effect of a cetylpyridinium chloride mouthwash on plaque and gingivitis. J Dent Res. 1977;56:595.
8. Allen DR, Davies R, Bradshaw B et al. Efficacy of a mouthrinse
containing 0.05% cetylpyridinium chloride for the control of plaque and
gingivitis: a six-month study in adults. Compend Contin Educ Dent. 1998;19:20-26.
9. Volpe AR, Petrone ME, DeVizio W et al. A review of plaque,
gingivitis, calculus and caries clinical efficacy with a dentifrice
containing triclosan and PVM/MA Copolymer. J Clin Dent. 1993;4:31-41.
10. Cubells AB, Dalmau LB, Petrone ME et al. The effect of a
triclosan/copolymer/fluoride dentifrice on plaque formation and
gingivitis: a six-month study. J Clint Dent. 1991;2:63-69.
11. Jeffcoat MK, Bray KS, Ciancio SG et al. Adjunctive use of a a
subgingival controlled-release chlorhexidine chip reduces probing depth
and improves attachment level compared with scaling and root planing
along. J Periodontol. 1998;69:989-997.
12. Stoller NH, Johnson LR, Trapnell S et al. The pharmacokinetic
profile of a biodegradable controlled release delivery system containing
doxycycline compared to systemically delivered doxycycline in gingival
crevicular fluid, saliva, and serum. J Periodontol. 1998;69:1085-91.
13. Christersson LA. Tissue response and release of minocycline after
subgingival deposition by use of a resorbable polymer. Warminster, Pa:
OraPharma Inc; 1988.
14. Goodson JM, Gunsolley JC, Grossi SG et al. Minocycline HCI
microspheres reduce red-complex bacteria in periodontal disease therapy. J Periodontol. 2007;78:1568-79.
15. Machion L, Andia DC, Lecio G et al. Locally delivered doxycycline
as an adjunctive therapy to scaling and root planing in the treatment of
smokers: a two-year follow-up. J Periodontol. 2006 Apr;77(4):606-13.
16. D'Aiuto F, Parkar M, Nibali L et al. Periodontal infections cause
changes in traditional and novel cardiovascular risk factors: results
from a randomized controlled clinical trial. Am Heart J. 2006 May; 151(5):977-84.
17. Tonetti MS, D'Aiuto F, Nibali L et al. Treatment of periodontitis and endothelial function. N Engl J Med. 2007 Mar 1;356(9):911-20.
18. http://www.periowave.com. Accessed April 16, 2010.
19. http://www.perioprotect.com/whatIs.asp. Accessed April 16, 2010.
20. Ciancio S, Ashley R. Safety and efficacy of sub-antimicrobial-dose
doxycycline therapy in patients with adult periodontitis. Adv Dent Res. 1998 Nov;12(2):27-31.
21. Novak MJ, Dawson DR 3rd, Magnusson I et al. Combining host
modulation and topical antimicrobial therapy in the management of
moderate to severe periodontitis: a randomized multicenter trial. J Periodontol. 2008 Jan;79(1):33-41.
22. Preshaw PM, Hefti AF, Bradshaw MH et al. Adjunctive
subantimicrobial dose doxycycline in smokers and non-smokers with
chronic periodontitis. J Clin Periodontol. 2005 Jun;32(6):610-6.
23. Martorelli de Lima AF, Cury CC et al. Therapy with adjunctive
doxycycline local delivery in patients with type 1 diabetes mellitus and
periodontitis. J Clin Periodonol. 2004 Aug;31(8):648-53.
24. Reinhardt RA, Stoner JA, Golub LM et al. Efficacy of
sub-antimicrobial dose doxycycline in post menopausal women: clinical
outcomes. J Clin Periodontol. 2007 Sep;34(9):768-75.
25. Brown DL, Desai KK, Vakili BA. Et al. Clinical and Biochemical
Results of the Metalloproteinase Inhibition with Subantimicrobial Doses
of Doxycycline to Prevent Acute Coronary Syndromes (MIDAS) Pilot Trial. Arterioscler Thromb Vasc Biol. 2004;24:733-738.
From Dimensions of Dental Hygiene. June 2010; 8(6): 44-46, 48.