Sustained Release Locally Applied Antimicrobials

Indications and Contraindications

THE NEXT DDS

Scaling and root planning (SRP) procedures have been used for years by dental professionals to reduce periodontal pocket depths in adults with periodontitis. More recently, locally applied antimicrobials (LAAs) have been approved as an adjunct to SRP for managing such patients. Broad-spectrum antibiotics, such as minocycline hydrochloride, and antiseptic agents enable clinicians to create a healthy environment that promotes healing and to target microorganisms associated with periodontal infection. For the dental student learner, this article will present the indications and contraindications for LAAs.

Risk Factors for Periodontal Disease:

• Poor oral hygiene
• Smoking
• Age
• Malnutrition
• Genetic predisposition
• Certain medications
• Complicating systemic diseases

Oral Health Linked to Overall Health
Approximately 50% of American adults over the age of 30 have some form of periodontal disease, ranging from mild gingivitis to advanced periodontitis.¹ Only a limited number of affected people seek treatment—approximately 3 percent (Figures 1 and 2).² With increasing evidence indicating that periodontal disease is linked to overall health, proper oral hygiene and infection treatment is critical.

A healthy mouth is one that has a balance of “healthy” and “unhealthy” bacteria. Poor oral hygiene and other risk factors cause the periodontopathogenic bacteria, including red complex bacteria, to dominate. Periodontal disease occurs when biofilms build up at or below the gingiva (Figure 3). The body’s response to the bacteria and their byproducts is inflammation. However, these microorganisms are resistant to natural antibodies and proteins intrinsic in the inflammation and therefore require treatment.

While gingivitis is an infection limited to the gingival tissues, periodontitis is a chronic and destructive condition that can cause the decay of bone and tooth loss. Periodontitis occurs when infection spreads from the gingiva to the ligaments and bone that hold the teeth in place. As the gingiva pulls away from the teeth due to infection, the teeth become loose and may eventually fall out.

As periodontitis progresses, the bacteria thrive in the periodontal pockets caused by the disease. The inflammatory response of the gingiva may make it easy for bacteria and their byproducts to enter the bloodstream.³ Chronic periodontal disease has been associated with a multitude of other diseases and conditions, including heart and lung diseases, diabetes, rheumatoid arthritis, and premature birth.^4,5

The Surgeon General has declared that ‘‘oral health is essential to the general health and well-being of all Americans.’’ The Surgeon General’s report on oral health encourages researchers to find new ways to prevent and treat oral diseases.⁵ Since the report was issued in 2000, sustained-release LAAs have been approved for treating periodontitis. 

SRP Plus LAA and Pocket Depth Reduction

Scaling and root planing (SRP) procedures have long been the standard treatment for periodontal disease. For patients with gingivitis (≤ 4mm pocket depth) or mild periodontitis (4mm - 5mm pocket depth), SRP may be the only treatment that is needed.

Non-surgical treatments, such as such as hand or ultrasonic scaling and laser debridement, are not effective in treating moderate-to-severe cases of periodontitis (pocket depth >5mm). Research indicates that SRP alone is not effective in eliminating all bacteria.⁶ In addition, instrumentation may not reach the furcation region (Figure 4), leaving some bacteria behind.⁷ The remaining bacteria can multiply and return to pre-treatment levels within days.⁸  

Locally applied antimicrobials are antibiotic or antiseptic agents aimed at reducing bacteria subgingivally (Figures 5 and 6). Sustained-released LAAs have been proven to reduce pocket depth in adults with periodontitis when used in conjunction with SRP.^9-11 Sustained-release formulas allow the agents to keep working postapplication so the pocket has time to heal without reinfection (Figures 7 and 8).

There are three sustained-release LLA products currently approved for the treatment of periodontitis: minocycline HCl (Figures 9-10-11-12), doxycycline hyclate, and chlorhexidine gluconate. LAAs can be applied in general practice or by a periodontist.

Monocycline HCl
Monocycline HCl is a sustained-release antibiotic in the form of microspheres that continue working for up to 21 days.¹² It is a fine powder delivered using a blunt-tip cannula directly into the pocket. Monocycline HCl should not be used in patients with a known sensitivity to minocycline or tetracyclines. It should not be used in children or pregnant or nursing women.⁹  

Doxycycline Hyclate
Doxycycline hyclate is a sustained-release antibiotic that continues working for up to 21 days. It is additionally indicated for gain in clinical attachment and reduction in bleeding on probing. The drug requires mixing prior to delivery. Syringe A contains a gel-like material into which the antibiotic (syringe B) is injected. The agent is then delivered directly into the pocket using a blunt-tip cannula. The gel turns into a waxy consistency when exposed to water or oral fluids. Doxycycline hyclate should not be used in patients with a known sensitivity to doxycycline or tetracyclines. It should not be used in children or pregnant or nursing women.¹⁰

Chlorhexidine Gluconate
Chlorhexidine gluconate is a sustained-release antiseptic chip that continues working for up to 7 days. Proponents argue that it is favorable because it cannot cause antibiotic-resistant bacteria. The chip is applied directly to pockets using forceps. Because of the chip’s size, it can only be used in pockets 5mm or greater. Chlorhexidine gluconate should not be used in patients with a known sensitivity to chlorhexidine.¹¹  

When to Refer to a Specialist

The American Academy of Periodontology recommends that adults undergo an annual comprehensive periodontal evaluation. This includes the evaluation of: teeth, calculus, gingiva, occlusion, bone structure, and risk factors.¹³ This comprehensive evaluation should be conducted by the hygienist and dentist during regularly scheduled cleanings. Should gingivitis or mild periodontitis be identified, SRP is recommended. This can be done in general practice or by a periodontist.

Patients should be referred to a specialist for the treatment of periodontitis in the following cases:

• There is an extreme amount of plaque present.
• There are complications of systemic disease, such as diabetes.
• Patient is not responding to treatment provided in the general practice.
• Patient requires conscious sedation for treatment.
• Patient requires surgical treatment or dental implants.
• Patient requires perio-systemic management.

More and more patients are presenting with signs of periodontal disease. Ongoing research indicates that periodontal disease is linked to other chronic diseases; therefore, periodontal treatment may require a greater understanding and increased level of expertise by a trained specialist. Patients who present with moderate or severe levels of periodontal disease, or patients with more complex cases, are best managed in partnership between the dentist and periodontist.

References

• Eke PI, Dye B, Wei L, Thornton-Evans G, Genco R. Prevalence of Periodontitis in Adults in the United States: 2009 and 2010. J Dent Res. 2012;91(10):914-920.
• Dispelling Myths about Gum Disease: The Truth Behind Healthy Teeth and Gums. American Academy of Periodontology. http://www.perio.org/consumer/gum-disease-myths. Accessed March 18, 2014.
• American Academy of Periodontology. Periodontal Disease as a Potential Risk Factor for Systemic Diseases. J Periodontol. 1998;69:841-850.
• Periodontal Disease Fact Sheet. American Academy of Periodontology. http://www.perio.org/newsroom/periodontal-disease-fact-sheet. Accessed March 18, 2014.
• U.S. Department of Health and Human Services. Oral health in America: A Report of the Surgeon General. DHHS, Rockville, MD. 2000. Pages 1, 13.
• Goodson JM, Gunsolley JC, Grossi SG, et al. Minocycline HCL microspheres reduce red-complex bacteria in periodontal disease therapy. J Periodontol. 2007;78(8):1568-1579.
• Cobb CM. Non-surgical pocket therapy: mechanical. Ann Periodontol. 1996;1(1):443-490.
• Socransky SS, Haffajee AD. Biofilms: difficult therapeutic targets. Periodontol 2000. 2002;28:12-55.
• ARESTIN (minocycline hydrochloride) Microspheres, 1 mg [Prescribing Information]. Warminster, PA: OraPharma, Inc.; 2011.
• Aridox (doxycycline hyclate). http://www.rxlist.com/atridox-drug.htm. Accessed March 18, 2014.
• PerioChip (Chlorhexidine gluconate) 2.5 mg [Prescribing Information]. Yokneam, Isreal: Dexcel Pharma Technologies Ltd.; 2012.
• Christersson LA, Norderyd OM, Puchalsky CS. Topical application of tetracycline-HCl in human periodontitis. J Clin Periodontol. 1993;20:88-95.
• Comprehensive Periodontal Evaluation. American Academy of Periodentology. http://www.perio.org/consumer/perio-evaluation.htm. Accessed March 18, 2014.