This chapter aims to provide a contemporary review of both systemic and locally delivered medications that have been reported for use as adjunctive treatments in the management of periodontitis.
Having read this chapter, the reader should be aware of the systemic and locally delivered adjunctive treatments that are available for the management of periodontitis, and should be better able to make informed decisions about the application of adjunctive treatments.
“Adjunctive treatments” are those therapeutic interventions that are used in addition to conventional periodontal therapy. They can be divided into “systemic adjuncts”, which are systemic medications, and “locally delivered adjuncts”, which are delivered directly into the site of periodontal disease activity, via the periodontal pocket.
A variety of systemic medications have been investigated as adjunctive treatments in the management of periodontitis. Systemic medications in periodontal therapy can be divided into two main groups:
those that are directed against periodontal pathogens (this group includes the antibiotics)
those that modulate aspects of the host response.
Systemic antibiotics are used widely in medicine and dentistry in the management of bacterial infections. Ideally, the decision about which antibiotic to prescribe should be based on culture and sensitivity testing of the infecting organisms, which, in periodontitis, would necessitate analysis of a subgingival plaque sample. In the majority of cases, however, this is not practical because reliable and comprehensive systems for analysis of plaque bacteria are simply not available. Furthermore, periodontal infections are polymicrobial involving different bacterial species all with different sensitivities to different antibiotics, which renders decision-making with regard to prescribing antibiotics even more complex. Some of the problems associated with using antibiotics in periodontitis are listed in Box 6-1.
Box 6-1 Problems with antibiotic usage in periodontitis
More than 500 bacterial species have been identified in dental plaque, of which approximately 15–20 have been strongly associated with disease.
Most periodontal pathogens are indigenous to the oral cavity, and can be found (albeit in reduced numbers) in periodontally healthy patients.
Periodontal diseases are markedly heterogeneous, and present as a spectrum of change from health to severe disease.
Periodontitis is a clinical diagnosis, not a microbiological diagnosis.
Microbiological sampling systems for culture and sensitivity are not readily available.
There are relatively few randomised studies of the use of antibiotics in periodontitis.
The host response plays a major role in the pathogenesis of periodontitis.
It should be remembered that thorough conventional non-surgical periodontal therapy is effective for the vast majority of periodontitis patients. Therefore, to show an additive therapeutic effect when using adjunctive antibiotics would require research projects with very large numbers of subjects to detect statistically significant results. There has been a dearth of such studies in the periodontal literature.
A further problem relating to antibiotic use is that of bacterial resistance, which can be defined as “a decrease of susceptibility to an antibacterial to the extent that therapy is likely to fail when it is used clinically for a recommended indication”. Worldwide, the therapeutic advantages offered by antibiotics are being threatened by the emergence of resistant bacterial strains.
This has primarily occurred because of:
overuse of antimicrobials
misuse of antimicrobials
widespread use of antibiotics in agriculture and animal husbandry
lapses in infection control
an increase in the number of immunocompromised individuals.
The solution to this problem involves responsible antibiotic use and stringent infection-control policies. This requires changing the attitudes of health care workers, patients, and the pharmaceutical industry. There is often significant pressure exerted on clinicians by patients who expect a prescription to alleviate their symptoms. If there is no indication for antibiotics, the temptation to prescribe must be resisted and other more appropriate alternatives must be explored. Acute infective episodes are best managed by draining the infection and treating the source of infection rather than by prescription of antibiotics.
Systemic antibiotics are not indicated in the management of cases of chronic periodontitis. Studies have not established with any certainty whether RSI and systemic antibiotics result in any treatment benefit compared to RSI alone. This is because the microbiota associated with chronic periodontitis is relatively poorly defined, rates of disease progression differ between individuals, and there are difficulties in accurately measuring disease progression and response to treatment. Furthermore, recolonisation of periodontal pockets with periodontal pathogens occurs rapidly following antimicrobial therapy. Given that systemic antibiotics have not been shown to enhance long-term treatment outcomes in chronic periodontitis, they cannot be indicated in this condition.
Following the reclassification of periodontal diseases in 1999 (see Understanding Periodontal Diseases: Assessment and Diagnostic Procedure in Practice), the conditions previously termed “juvenile periodontitis” and “rapidly progressive periodontitis” were renamed “aggressive periodontitis”. It should be remembered that aggressive periodontitis is rare, affecting approximately 0.5% of the population, and therefore is rarely encountered in day-to-day dental practice.
Localised aggressive periodontitis is frequently associated with Actinobacillus actinomycetemcomitans (Aa) infection, an organism that is particularly virulent and possesses the ability to invade the gingival soft tissues. Invasion of the tissues affords the organism a degree of protection from root surface instrumentation (RSI) and allows for rapid recolonisation of the instrumented root surface. For this reason, systemic antibiotics are useful in suppressing this organism. Historically, 250mg tetracycline four times daily for three weeks as an adjunct to full-mouth RSI has been prescribed. Good clinical improvements have been reported, as Aa has tended to be particularly sensitive to tetracycline. However, the recent development of tetracycline-resistant strains of Aa has led some researchers to switch to an antibiotic regimen of metronidazole (400mg three times daily) and amoxicillin (250mg three times daily) for seven days as an adjunct to full mouth RSI. This combined antibiotic regimen has been shown to result in better clinical outcomes than tetracycline when both were used as adjuncts to RSI in the management of localised aggressive periodontitis.
Generalised aggressive periodontitis is also associated with infection by Aa, and also Porphyromonas gingivalis (Pg), another organism that possesses multiple virulence factors and has the ability to invade periodontal tissues. Research studies have reported conflicting data on the benefits of systemic antibiotics as an adjunct to RSI in treating this condition. In patients with aggressive disease, typically presenting with multiple periodontal abscesses, a combined regimen of metronidazole and amoxicillin (as above) can be used as an adjunct to full-mouth RSI. Ideally, full-mouth RSI should be conducted within a short time period (up to seven days) to coincide with the antibiotic therapy. This concept also can be incorporated into one-stage full mouth therapy (see Chapter 1).
Refractory periodontitis and recurrent periodontitis (see Understanding Periodontal Diseases: Assessment and Diagnostic Procedure in Practice) can be difficult to distinguish. Both tend to result in continued periodontal destruction despite conventional therapy. Given that patients have received appropriate treatment and are enrolled into an adequate supportive periodontal care programme (Chapter 7), refractory periodontitis is most likely to be due to a number of host factors, such as smoking, stress or specific immune defects rather than the presence of a particular microflora. Studies investigating adjunctive antibiotics in the treatment of refractory periodontitis have provided conflicting data. There is no clear answer as to whether adjunctive antibiotics are beneficial, or which antibiotic should be used. This is because of the variable nature of the periodontal microflora amongst patients diagnosed with refractory periodontitis, together with the importance of other host factors. In summary, therefore, adjunctive systemic antibiotics cannot be justified in this group of patients. Instead, the emphasis must be on excellent plaque control, reinstrumentation to disrupt subgingival biofilms, and risk factor management.
Patients who present with multiple periodontal abscesses may be treated with adjunctive antibiotics if there is evidence of spreading systemic infection (e.g. raised temperature and cellulitis). The aim of treatment of a periodontal abscess is to achieve drainage of pus, preferably via the periodontal pocket following RSI. If drainage can be achieved in this way, then in the majority of cases the need for systemic antibiotics will be negated. If antibiotics are required, however, amoxicillin 250mg, three times daily for seven days should be sufficient when used as an adjunct to RSI, but the need for systemic antibiotics is the exception rather than the rule.
Necrotising ulcerative gingivitis (NUG) is an acutely painful condition associated with fuso-spirochaetal infection, smoking, stress, poor diet and possibly HIV infection, characterised by gingival sloughing and blunting of interdental papillae. The condition is so painful that the patient may not be able to brush their teeth. Therapy in the first instance should involve full mouth supragingival ultrasonic instrumentation to reduce the plaque mass, together with chemical plaque control (chlorhexidine mouth rinse) and prescription of metronidazole 400mg three times daily for seven days. Following resolution of the acute symptoms, the patient should be seen for further RSI to remove all tooth deposits together with reinforcement of oral hygiene instruction (OHI). Necrotising ulcerative periodontitis (NUP) may have a similar early presentation although the lesion extends to affect the periodontal attachment apparatus. There may be exposure of alveolar bone, and the lesion is extremely painful. Referral to a specialist centre is appropriate, and treatment will involve local measures, systemic antibiotics, removal of necrotic bone, and possibly periodontal surgery to eliminate bony sequestrae.
The situations in which the use of adjunctive systemic antibiotics may be appropriate are listed in Box 6-2. The key point is that in all cases the use of antibiotics must be an adjunctive therapy. In general, antibiotics are rarely indicated for the management of periodontal diseases, and they are certainly not indicated in cases of chronic periodontitis or gingivitis. The strongest evidence to support the use of systemic antibiotics in periodontal conditions comes from studies of localised aggressive periodontitis, and, to a lesser extent, generalised aggressive periodontitis, both of which are relatively rare. The objectives of systemic antibiotic therapy (when used) are to reinforce RSI for bacterial elimination and to support the host defence system by killing subgingival pathogens not affected by RSI. Empirical use of antibiotics should be avoided. The plaque biofilm must be mechanically disrupted, as without this, antimicrobials have limited efficacy.
Box 6-2 Possible indications for adjunctive antibiotic use in periodontics
Aggressive forms of periodontitis (typically characterised by multiple suppurating pockets) to eliminate reservoirs of bacteria in the tissues.
Necrotising periodontal conditions.
Periodontal abscess, though the primary goal is drainage of pus, which can normally be achieved by RSI alone, thereby negating the need for antibiotics.
Spreading, severe infection with associated symptoms such as pyrexia, gross diffuse swelling, limited mouth opening, difficulty swallowing.
Host modulatory therapy (HMT) is a relatively new concept in the management of periodontitis, and has been driven by improved understanding of periodontal pathogenesis and awareness of the importance of the host response in periodontal disease. The goal of HMT is to enhance traditional periodontal therapies by modifying the destructive aspects of the host response so that periodontal breakdown is reduced and the periodontium is stabilised. Host response modulators are used as adjuncts to conventional periodontal therapy to maximise the treatment response. Careful selection of patients is key when considering any adjunctive therapy. To achieve best results, patients must be interested and well informed about their condition so that compliance is maximised.
HMT represents an emerging area of periodontal therapy. It is very likely that the next ten to twe/>