Clinical P RACTIC E Systemic Antibiotic Therapy in the Treatment of Periodontitis Contact Author Philippe Bidault, DCD, MSc, FRCD(C); Fatiha Chandad, PhD; Daniel Grenier, PhD Dr. Grenier Email: Daniel.Grenier@ greb.ulaval.ca ABSTRACT Periodontitis is characterized by a general inflammation of the tooth-supporting tissues, which leads to apical migration of the junctional epithelium along the root surface and progressive destruction of the periodontal ligament and the alveolar bone. Although the bacteria present within the subgingival dental biofilm constitute the primary etio- logic agents of periodontitis, the host’s immune response modulates development of the condition toward either destruction or healing. Given the infectious nature of periodontal diseases and the limited results with conventional mechanical therapies for the treatment of certain forms of periodontitis (aggressive and refractory), the use of antibiotics is warranted in certain cases. This article provides an update on systemic antibiotic therapy for the treatment of periodontitis. For citation purposes, the electronic version is the definitive version of this article: www.cda-adc.ca/jcda/vol-73/issue-6/515.html eriodontal disease is one of the most of Periodontology, published in 1999, the common microbial infections in adults. various forms of periodontal disease were clas- PIt is an inflammatory disease of bacterial sified on the basis of cause, severity and site of origin that affects the tooth-supporting tissues. disease.1 Experts now distinguish among gen- There are 2 major types of periodontal disease: eralized and localized chronic periodontitis, gingivitis and periodontitis. Gingivitis in- generalized and localized aggressive peri- volves limited inflammation of the unattached odontitis, periodontitis associated with sys- gingiva and is a relatively common and re- temic diseases, periodontitis associated with versible condition. In contrast, periodontitis endodontic lesions and necrotizing ulcerative is characterized by a general inflammation of periodontitis. Of these, chronic periodontitis the periodontal tissues, which leads to apical is the most frequently encountered in the migration of the junctional epithelium along adult population. the root surface and progressive destruction Epidemiologic studies have shown that 5% of the periodontal ligament and the alveolar to 20% of the North American population bone. Periodontitis progresses in cyclical suffers from a severe and generalized form of phases of exacerbation, remission and latency, periodontitis.2 The prevalence of the disease a phenomenon that is closely linked to the ef- varies with sex, ethnic background, geographic fectiveness of the host’s immune response. region and socioeconomic status. In addition, The classification of periodontal diseases certain conditions may be predisposing or ag- has evolved a great deal over the years. In the gravating factors for periodontitis, including most recent report of the American Academy accumulation of subgingival plaque, smoking ���JCDA • www.cda-adc.ca/jcda • July/August 2007, Vol. 73, No. 6 • 515 ––– Grenier ––– and conditions associated with an immune disorder (e.g., diabetes mellitus, AIDS).3 In particular, the risk of peri- Immunodeficiency odontitis is 2.5 to 6.0 times higher for smokers than for nonsmokers.4 Furthermore, periodontal treatments often 5 Modification of prove less effective among patients who smoke. Finally, Bacterial environmental interactions numerous studies have demonstrated that periodontitis conditions may constitute a significant risk factor for other systemic disorders, including atherosclerosis, aspiration pneu- 6,7 Proliferation of monia and preterm births. periodontal pathogenic bacteria Etiology of Periodontal Disease More than 500 microbial species have been identified Action of virulence in subgingival plaque, which can thus be considered to factors represent a complex ecological niche.8 Under the influ- ence of local and systemic factors, some of these bacterial species in the subgingival dental biofilm constitute the Increased primary etiologic agents of periodontal disease. The ac- inflammatory Neutralization of the response cumulation and proliferation of these bacterial species host’s defence in the periodontal pocket are the initiating steps in the mechanism s Tissue destruction onset and progression of periodontal lesions. These poly- Tissue destruction microbial infections involve bacteria called periodontal pathogens, most of them gram-negative and strictly anaerobic, which act in synergy. Among these species, the most important are Aggregatibacter actinomycetem- Periodontitis comitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Prevo- tella intermedia, Prevotella nigrescens, Campylobacter rectus, Eikenella corrodens and Peptostreptococcus Figure 1: Pathogenesis of periodontitis. micros.9,10 These bacteria produce a wide variety of viru- lence factors that enable them to colonize subgingival sites, resist the host’s defence mechanisms and cause tissue destruction.16,17 In fact, these mediators can acti- 11 destruction of the periodontal tissues (Fig. 1). Although vate one or more tissue degradation factors, notably matrix A. actinomycetemcomitans is associated with localized metalloproteinases, plasminogen and polymorphonuclear aggressive periodontitis (Figs. 2a and 2b), P. gingivalis serine proteases, which cause bone resorption18,19 is considered the major etiologic agent of chronic peri- 9,12 It has recently been suggested that certain viruses odontitis. Recent studies have demonstrated specific of the family Herpesviridae, including cytomegalovirus, associations among periodontal pathogenic bacteria in- Epstein-Barr virus and the herpes simplex virus, could volved in the onset and progression of the disease. For have a causative role in periodontal disease.20 The pres- example, a highly significant association between T. for- ence of these viruses in periodontal lesions may con- sythia and C. rectus was reported in cases of aggres- tribute to tissue destruction through their lytic activity sive periodontitis.13 Socransky and others14 demonstrated directed against structural and immune cells. However, that the bacterial complex composed of P. gingivalis, additional studies will be required to confirm the partici- T. denticola and T. forsythia, called “Red Complex,” is strongly associated with the active destruction phases of pation of these viruses in the pathogenesis of periodontal chronic periodontitis. disease. Although the presence of periodontal pathogens is es- sential for the onset of periodontitis, these organisms are Mechanical Therapy not sufficient for the disease to progress. In fact, the host’s Mechanical debridement of the dental biofilm and immune response modulates progression of the disease elimination of local irritating factors are the basis of toward destruction or healing.15 Various inflammatory initial periodontal therapies. Longitudinal studies have mediators produced by the immune cells normally con- demonstrated the effectiveness of this approach, which tribute to tissue homeostasis. However, overproduction is based on scaling and root planing, reinforcement of of certain mediators, such as interleukin-1β, tumour the patient’s oral hygiene practices and regular follow-up necrosis factor alpha and prostaglandins, lead to the to eliminate new deposits.21,22 The effectiveness of this chronic, persistent inflammation that is at the origin of treatment is reflected by the disappearance of clinical 516 JCDA • www.cda-adc.ca/jcda • July/August 2007, Vol. 73, No. 6 • ––– Systemic Antibiotic ––– In deciding whether to use cura- tive systemic antibiotic therapy, it is important to consider the potential benefits and side effects. The benefits may allow treatment of patients who have had limited response to con- ventional mechanical therapy and those with multiple diseased sites presenting refractory periodontitis. The potential risks include develop- Figure 2a: Panoramic radiograph showing Figure 2b: Localized deep probing on ment of resistant bacterial species, localized aggressive periodontitis in a 13- the same patient reveals little plaque emergence of fungal opportunistic or calculus. year-old patient. infections or Pseudomonas infection, and allergic reactions.23,24 Several studies have evaluated the use of antibiotics to stop or re- symptoms, the reduction or elimination of periodontal duce the progression of periodontitis.25–29 Systemically pathogens and the return of beneficial bacterial flora. administered antibiotics show a statistically significantly However, this treatment protocol does have limitations. greater gain in attachment and reduction in depth of peri- Not all patients or all sites respond uniformly and fa- odontal pockets, regardless of initial probing methods or vourably to conventional mechanical therapy. Reduced therapeutic modalities (antibiotic therapy alone, in con- effectiveness of the therapy may be explained by a series junction with scaling and root planing, or in conjunction of patient-related factors (local or generalized), the extent with scaling and root planing plus surgical therapy). and nature of attachment loss, local anatomic variations, However, the therapeutic benefits observed are clinic- the form of the periodontal disease and the composition ally significant in only a limited number of situations. of the biofilm. Given the infectious nature of periodontal For example, attachment