Use of Locally Delivered Antimicrobials in Periodontal Therapy

When treating periodontal disease, the use of locally delivered agents with antimicrobial properties remains controversial in the minds of some patients and practitioners. While not indicated for every patient, there are cases in which this modality should be considered as adjunctive therapy. For further clarification, Decisions in Dentistry turned to Keerthana Satheesh, DDS, MS, to see what the evidence says about locally delivered antimicrobials.

What does the evidence say regarding the adjunctive use of antimicrobials in treating periodontal disease?

Periodontal disease is an inflammatory disorder with a microbial etiology. The aim of periodontal therapy is to remove bacterial deposits by mechanical scaling and root planing (SRP) and potential surgical therapy. The goal is to shift the periodontal microflora to one compatible with periodontal health. Depending on the extent of the disease and other risk factors, conventional therapy may not always lead to complete resolution. Local delivery agents with antimicrobial properties were introduced to augment the clinical periodontal response of conventional SRP by increasing the concentration of the therapeutic agent locally.

One advantage of using local antimicrobials is that it eliminates numerous side effects associated with systemic antibiotics. The local tissue concentration of a drug can be enhanced by incorporating the agent into active or controlled-release delivery systems to be placed directly in the periodontal pocket.

Tetracycline fiber was the first product to be introduced in the United States. Other antimicrobials that have gained popularity include a chlorhexidine chip, doxycycline gel and minocycline microspheres. Several studies into the use of locally delivered antimicrobials and nonsurgical periodontal therapy (in comparison to SRP alone) have shown reductions in probing depths, with modest gains in clinical attachment levels. While the results were statistically significant, the effects of these agents’ antimicrobial properties must be critically evaluated in light of the additional cost associated with their use.

While most studies find the use of locally delivered antimicrobials as adjuncts to nonsurgical periodontal therapy safe and effective, routine application in all deep probing depths is not indicated. The specific indications for locally delivered antimicrobials are outlined below.

Which types of cases are indicated for use of adjunctive, locally delivered antimicrobials?

Resolution of inflammation is essential for glycemic control in patients with diabetes. Thus, individuals with periodontal disease and poorly controlled diabetes may benefit from locally delivered antimicrobials. Use of the tetracycline group of antimicrobials may be of particular value in this patient population, as tetracycline has been shown to inhibit collagenase.

Various adjuncts have been utilized for treating peri-implant mucositis and peri-implantitis. While mechanical therapy alone has been shown to produce minimal changes on peri-implant mucositis, the mechanical debridement of peri-implantitis lesions, together with adjunctive use of locally delivered antimicrobials, is considered to have some positive effect on mucosal inflammation. In addition, the combination has brought slight improvements in probing depths. Newer alternative therapies are also being evaluated in the management of peri-implant mucositis and peri-implantitis.

Smokers are at high risk for periodontitis. Tobacco users present several challenges, including less-than-optimal clinical and biological response to surgical periodontal therapy. The antimicrobial properties of locally delivered agents is concentrated in the gingival crevicular fluid, which offers an added advantage in patients who smoke. Compared to SRP alone, a recent meta-analyses evaluating the efficacy of locally delivered antimicrobials with SRP at sites presenting with probing depths ≥ 5 mm showed this approach may reduce probing depths and improve clinical attachment levels.

Like other facets of therapy, cost versus benefit must be assessed before a decision is made to use locally delivered antimicrobials. In the vast majority of patients, this approach should be limited to isolated areas following conventional nonsurgical periodontal therapy. This determination is made at the time of reevaluation following nonsurgical periodontal therapy. If there are multiple sites with residual probing depths ≥ 5 mm, other modes of therapy should be considered. For example, if periodontal surgery is contraindicated due to esthetics or a significant systemic condition, locally delivered antimicrobials may be considered. This adjunctive approach can also be utilized in isolated areas of breakdown in treated periodontal patients who are on recall.

What are the contraindications for using locally delivered antimicrobials?

Although the polymers utilized in the delivery devices are biocompatible and inert, allergies to the various antimicrobials used in these agents is a contraindication. If patients are sensitive to any of these products, it would preclude the use of these agents. As always, taking a thorough medical history, coupled with a solid understanding of the product, can help prevent complications.

Other conventional therapies must be considered if prior use of a locally delivered antimicrobial failed to control periodontitis. In the presence of multiple sites with deep probing depths and/​or infrabony defects, conventional surgical periodontal therapy should be considered.

Are there any new developments in this area for treating periodontal disease?

While several of these approaches are not available for periodontal therapy in the United States, statins are being used extensively as locally delivered agents in other countries. Simvastatin, order atorvastatin and rosuvastatin have been investigated as adjunctive therapies to SRP.

Bisphosphonates (such as alendronate) are being used for local delivery to inhibit osteoclasts, and studies show improvement in periodontal clinical parameters. Some studies have shown bone fill with the use of alendronate and simvastatin. The use of azithromycin as an adjunct to SRP significantly improves the efficacy of nonsurgical periodontal therapy in reducing probing depth and bleeding on probing, while improving attachment levels, particularly at deep probing sites. Other agents being assessed for local delivery in combatting periodontitis include aloe vera, curcumin, and several other anti-inflammatory medications.

While new approaches are being evaluated for local use in periodontal therapy, novel technologies for delivering the agent are also under investigation. For example, a biodegradable xanthan-based gel is being evaluated to deliver chlorhexidine and metronidazole. In addition, nanoparticulate delivery systems are the subject of intensive research. Compared to existing methods, nanoparticles are said have greater access to deep periodontal pockets due to their small size. Nano-sizing has also been shown to increase the absorption and bioavailability of drugs. This could show promise in patients with furcations and deep probing depths.

Regardless of which delivery methods are used to introduce local agents with antimicrobial properties, clinicians must ultimately remember that physical disruption of the biofilm via SRP remains the gold standard in nonsurgical periodontal therapy.

While the adjunctive use of this approach may have indications for some patients, locally delivered antimicrobials should be prescribed prudently.

REFERENCES

1. Chambrone L, Vargas M, Arboleda S, et al. Efficacy of local and systemic antimicrobials in the nonsurgical treatment of smokers with chronic periodontitis: A systematic review. J Periodontol. 2016;87:1320–1332.
2. American Academy of Periodontology Statement on Local Delivery of Sustained or Controlled Release Antimicrobials as Adjunctive Therapy in the Treatment of Periodontitis. Available at: http/​:/​/​aap.onlinelibrary.wiley.com/​doi/​pdf/​10.1902/​jop.2006.068001. Accessed April 3, 2020.
3. Heasman PA, Vernazza CR, Gaunt FL, Pennington MW. Cost-effectiveness of adjunctive antimicrobials in the treatment of periodontitis. Periodontol 2000. 2011;55:217–230.
4. Szulc M, Zakrzewska A, Zborowski J. Local drug delivery in periodontitis treatment: A review of contemporary literature. Dent Med Probl. 2018;55:333–342.

The author has no commercial conflicts of interest to disclose.

From Decisions in Dentistry. May 2020;6(5):12–13.