From clinical research and experimental data, it is clear that local antibiotic systems represent a valuable resource for the treatment of periodontal diseases. Local antibiotic systems cannot be relied upon for stand-alone therapy, but can be very useful in combination with traditional mechanical treatment of the root surface and adjacent soft tissue.

It is well established that periodontal diseases require both the presence of bacteria and a host response. The severity of the bacterial infection varies, in terms of both the number and species of organisms present. The quality of the host response may also vary from patient to patient. In addition, both the severity of infection and the host response can vary in the same patient from time to time.

Mechanical therapy
Traditional periodontal therapy has focused on mechanical treatment of the root surface and adjacent soft tissue. Time-honoured techniques to accomplish treatment of the destructive periodontal diseases are directed at removal of hard and soft deposits on the root surfaces. Depending on the extent of the periodontal disease and associated tissue destruction, access to remove these deposits may range from the  somewhat limited to essentially impossible, especially when furcation involvement has occurred. When nonsurgical periodontal therapies do not lead to resolution of the inflammatory lesion, and when persistent signs of inflammation and attachment loss are seen, additional treatment is often recommended. Such additional treatment frequently includes periodontal surgery to improve access to the root surfaces and thus increase the likelihood that all the bacterial deposits can be removed. Even with such surgical access, there are studies published indicating that frequently a complete removal of calculus is still not accomplished.

These treatment limitations, as well as the possibility that some patients may choose not to pursue surgical therapy or may not be able to pursue this option due to other health issues, provided the impetus for the development of alternate treatment routines. Since the bacterial component of periodontal disease is clearly established, an alternative treatment based on chemotherapeutic measures generated great interest.

Systemic antibiotic therapy
Systemic antibiotic therapy has been studied both as an adjunct to mechanical therapies and as a stand-alone therapy. Well-established concerns regarding systemic antibiotic therapy have made this a less attractive option for the treatment of periodontal disease. The possibility of microbes developing resistance to an antibiotic and thus making that antibiotic unavailable for the treatment of more serious infections is a genuine concern. It is also important to remember that periodontal disease does not comply with Koch’s postulates, which establish a relationship between a disease and an infectious agent. Far from being a single bacterial infection, patients with periodontal diseases often present with many different bacterial species. Estimates of the number of bacterial species that can be identified in the oral cavity range from 400 up to 700 species. With such a diverse bacterial population, choosing an antibiotic suitable for an individual patient’s flora is difficult.

Fortunately there is a large body of work focused on identifying the populations of bacteria associated with periodontal disease. These studies suggest that bacterial populations can be grouped according to their association with periodontal disease. Without the benefit of plaque sampling, culturing and sensitivity testing, the choice of an antibiotic must be experiential or based on published studies.

Notwithstanding those concerns, systemic antibiotic therapy for the treatment of periodontal disease has been found to be effective in many cases. It is rarely considered as a first-line treatment, and is very infrequently a reliable monotherapy. Rather it is considered when an adjunctive therapy
is sought.

Local antibiotic systems
The concerns regarding systemic antibiotic therapy helped provide the impetus for the development of local treatment routines. These include both antiseptics and antibiotics. The most widely studied and most effective antiseptic is chlorhexidine. It may be used as an oral rinse, an intrasulcular/intrapocket irrigant and in a solid form as a chlorhexidine chip. Chlorhexidine is without doubt the “gold standard” against which all other antiplaque agents are compared. Its use as an oral rinse is limited by its ability to enter the sulcus/pocket but it does provide remarkable plaque control effects. Its use as an intrasulcus/intrapocket irrigant is also limited by the extent to which it can enter the sulcus/pocket and reach deep plaque formation. The use of the solid form of chlorhexidine, the chlorhexidine chip, has been shown to be an effective adjunct to mechanical therapy. A study by Jeffcoat et al [1] provides documentation on the use of the chlorhexidine chip and its effectiveness at recall/maintenance visits. In this study, after initial scaling and root planing, the chip was placed in any site that initially bled on probing, and sites with probing depths of 5-8 mm, and the chip was again placed during maintenance visits at sites with probing depths of 5 mm or greater. This routine was shown to be effective for improving both probing depths and attachment levels over a nine month study.

An evolution has been seen in the development of antibiotic therapies, beginning with a tetracycline product within a nonresorbable fibre delivery system. The Actisite system, while now not commercially available, allowed dramatic improvements in both probing depths and signs of inflammation, namely bleeding on probing. The major drawbacks of Actisite were that the fibre could not adapt to all pocket topographies and the requirement that the fibre be removed ten days after placement.
The second stage in the evolution of local antibiotic therapies was a Doxycycline gel, namely Atridox, which was mixed in a two syringe system and delivered into the pocket with a blunt cannula. The gel form facilitated its delivery and adaptation to the pocket topography, after which it became semi-solid, releasing the antibiotic over a ten-day period.
Another currently available local antibiotic system is the Minocycline microsphere system known as Arestin. In this system the antibiotic is delivered with a syringe in single unit doses. The unit delivery system provides a blunt syringe tip with each dose.

Other local antibiotic systems include a metronidazole gel system (Elyzol) as well an Azithromycin system. Many of the features of these local antibiotic systems are summarised in Table 1.

Generally, local antibiotic systems produce improvements in many clinical symptoms including probing depths, attachment levels and bleeding on probing. The improvements, while statistically significant, are often referred to as clinically insignificant. As adjuncts to traditional mechanical therapies, local antibiotic therapies may provide their most important benefit in decreasing the inflammatory lesion. Table 2 summarises the results of several studies that used local antibiotic therapies.

Conclusions
It is clear from clinical research and experimental data that local antibiotic systems represent a valuable resource in the treatment options for periodontal diseases. It is also clear that no local antibiotic system can be relied upon as a stand-alone therapy but that such systems are best used in combination with traditional mechanical therapies. The search for the ideal antibiotic treatment continues. It should be stressed that although research data suggest minimal clinical changes such as attachment level changes and/or pocket depth changes, local antibiotics are important in decreasing inflammation. Our current level of understanding about the importance of oral inflammation as a possible contributor to systemic problems including pre-term and low birth weight pregnancy outcomes, cardiovascular disease and diabetes to name a few, makes the use of local antibiotics for periodontal diseases an important treatment option.

(Tables reprinted from Dental Clinics of North America, Vol 54(1), Krayer JW, Leite RS and Kirkwood KL. Nonsurgical Chemotherapeutic Treatment Strategies for the Management of Periodontal Disease, Pages 13-33,2010 with permission from Elsevier).

References
1. Jeffcoat MK et al. Adjunctive Use of a Subgingival Controlled Release Chlorhexidine Chip Reduces Probing Depths and Improves Attachment Level Compared with Scaling and Root Planing Alone. J Periodontol 1998; 69:989-997.
2. Goodson JM, Cugini MA, Kent RL et al. Multicenter evaluation of tetracycline fiber therapy: II. Clinical response. J Periodontal Res 1991; 26(4): 371-9.
3. Garrett S, Johnson L, Drisko CH et al. Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis. J Periodontol 1999; 70(5): 490-503.
4. Wennstrom JL, Newman HN, MacNeill SR et al. Utilisation of locally delivered doxycycline in non-surgical treatment of chronic periodontitis. A comparative multi-centre trial of 2 treatment approaches. J Clin Periodontol 2001; 28(8): 753-61.
5. 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 2-year follow-up. J Periodontol 2006; 77(4): 606-13.
6. Williams RC, Paquette DW, Offenbacher S et al. Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial. J Periodontol 2001; 72(11): 1535-44.
7. Goodson JM, Gunsolley JC, Grossi SG et al. Minocycline HCl microspheres reduce red-complex bacteria in periodontal disease therapy. J Periodontol 2007; 78(8): 1568-79.
8. Ainamo J, Lie T, Ellingsen BH et al. Clinical responses to subgingival application of a metronidazole 25% gel compared to the effect of subgingival scaling in adult periodontitis. J Clin Periodontol 1992; 19: 723-9.
9. Pradeep AR, Sagar SV, Daisy H. Clinical and microbiologic effects of subgingivally delivered 0.5% azithromycin in the treatment of chronic periodontitis. J Periodontol 2008; 79(11): 2125-35.

The author
Joe W. Krayer, D.D.S., M.S.
Assistant Professor
Director, Post-Doctoral Periodontics
Division of Periodontics
Department of Stomatology
College of Dental Medicine
Medical University of South Carolina
30 Bee St.  Room 115
Charleston, SC  29425
USA
Tel +1 843-792-7612
e-mail: krayer@musc.edu