Jørgen Slots

Systemic antibiotics in periodontics.

This position paper addresses the role of systemic antibiotics in the treatment of periodontal disease. Topical antibiotic therapy is not discussed here. The paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. The document consists of three sections: 1) concept of antibiotic periodontal therapy; 2) efficacy of antibiotic periodontal therapy; and 3) practical aspects of antibiotic periodontal therapy. The conclusions drawn in this paper represent the position of the American Academy of Periodontology and are intended for the information of the dental profession. J Periodontol 2004;75:1553-1565.

Human viruses in periodontitis.

Periodontitis affects the majority of adults worldwide (4), but relatively few patients receive adequate treatment for the disease (9). Conventional periodontal therapy includes a stabilization phase and a maintenance phase. Stabilization of the disease is accomplished by periodontal mechanical depuration and the removal of calculus and other biofilmretentive factors, and may involve adjunctive antimicrobial medication and ⁄ or surgery. The long-term goals in the maintenance stage are to have patients exercise proper plaque control and to commit to professional antimicrobial treatment in order to minimize the likelihood of a clinical relapse. Current periodontal therapy is successful in combating initial and moderate types of periodontitis, but may show limited efficacy in resolving late-stage disease. Optimal periodontal care is often impeded by the lack of patient cooperation and by affordability issues. Periodontal treatment can entail substantial costs attributed to direct healthcare expenses and to loss of income during the time of professional therapy. A greater understanding of the etiopathogeny of periodontal disease seems to be a prerequisite for the development of preventive and therapeutic strategies that are more efficacious and less burdensome for patients. The task of determining the periodontopathic importance of suspected disease determinants is hampered by difficulty in identifying the initial stage of periodontitis and in distinguishing between progressive and stable phases of the disease. Differences in case definitions and diagnostic methods also complicate the interpretation of epidemiological findings in periodontal research. Periodontitis typically occurs in otherwise healthy individuals and is statistically associated with various environmental and demographic factors (3). The disease can also be linked to rare immunogenetic defects or be part of systemic diseases that primarily affect nonoral tissues (75). It is not clear if some of the proposed risk factors for periodontal disease reflect true genetic or immunological variations, or merely poor healthseeking behavior related to socioeconomic factors, lifestyles or cultural differences. Microbiological culture and culture-independent molecular studies have identified more than 1,200 bacterial species (140) and 19,000 phylotypes (91) in the oral cavity. At least 400 bacterial species inhabit subgingival sites (141), but despite the long list of different bacteria in periodontitis, fewer than 20 species are considered to be major periodontal pathogens (175, 185). Healthy periodontal sites harbor a scant microbiota of predominantly gram-positive facultative bacteria, whereas periodontitis lesions contain a large variety of gram-negative anaerobic species (171). The shift in the periodontal microbiota with disease development is the result of a multifaceted interaction of microbial-specific traits, host immune responses and ecosystem-based factors. It is not known why fastidious gram-negative anaerobic bacteria outcompete common oral gram-positive bacteria, and why relatively few suspected periodontopathogens are surging in numbers in periodontitis sites. Periodontopathogenicity is assessed primarily on the basis of an elevated occurrence of a given bacterial species in advanced periodontitis lesions. However, many anaerobic bacteria benefit from proteinaceous components that are present in the gingival crevice fluid and may merely be secondary invaders of periodontitis sites. Also, the cross-sectional design of most bacteria–periodontitis association studies prevents the pathogenetic importance of specific microorganisms from being firmly established. An important exception to this is Aggregatibacter actinomycetemcomitans in localized aggressive (juvenile) periodontitis (184). As expected for a true pathogen, the subgingival counts of A. actinomycetemcomitans have, in longitudinal studies, shown a dramatic increase immediately prior to clinical attachment loss and a marked decrease at the time of disease remission (16, 64). Theories proposed so far to explain the etiopathogeny of periodontitis have not been able to

In vitro antimicrobial susceptibility of Actinobacillus actinomycetemcomitans.

The agar dilution technique was used for determination of the antibiotic susceptibilities of 57 oral isolates and 2 nonoral isolates of Actinobacillus actinomycetemcomitans. Tetracycline, minocycline, and chloramphenicol inhibited more than 96% of the strains tested at a concentration of less than or equal to 2 micrograms/ml; 89% of the strains were inhibited by 2 micrograms of carbenicillin per ml. The other antimicrobial agents tested were less active. Approximately 10% of the A. actinomycetemcomitans strains were resistant to ampicillin, erythromycin, and penicillin G at concentrations of 32 to 64 micrograms/ml. These data suggest that tetracycline and minocycline may be valuable drugs in the treatment of A. actinomycetemcomitans infections.

Herpesviral-bacterial Coinfection in Periapical Pathosis

Two members of the herpesvirus family, human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), seem to be important putative pathogens of human periodontitis and symptomatic periapical lesions, causing pathosis either by inducing immunosuppression with a subsequent risk of aggressive bacterial infections or by infecting of periodontal cells directly. This study aimed to relate periapical occurrence of HCMV, EBV, and herpes simplex virus active infections to clinical characteristics of periapical lesions and periapical bacterial flora. Microbial samples were collected from 34 periapical lesions in conjunction with periapical surgery. Part of the periapical specimen was frozen for virologic examination, and another part was transferred to anaerobic transport medium for bacteriologic examination. RNA was isolated by means of a guanidinium isothiocyanate-acid phenol procedure, and cDNA was produced using herpesvirus-specific primers and reverse-transcription polymerase chain reaction amplification. Bacteriologic examination was performed according to established anaerobic culture methods. Of the 34 periapical lesions studied, 20 showed both HCMV and EBV, seven showed only HCMV, one showed only EBV, and six showed neither HCMV nor EBV. Herpes simplex virus was detected in two lesions. Higher occurrence of herpesvirus was detected in large versus small periapical lesions (p < 0.001) and in symptomatic versus asymptomatic periapical lesions (p < 0.001). A total of 18 microbial groups and an average of 2.1 to 3.0 bacterial groups were isolated from various categories of periapical lesions. The important finding of this study was that most teeth with necrotic pulp and periapical lesions harbored herpesviruses in periapical granulomatous tissue. Herpesvirus species in cooperation with endodontopathic bacteria may play major roles in the etiopathogenesis of aggressive types of periapical pathosis in humans.

Salivary infectious agents and periodontal disease status

BACKGROUND AND OBJECTIVES The potential of salivary microorganisms to diagnose periodontal disease and to guide periodontal treatment is a research topic of current interest. This study aimed to determine whether the salivary counts of periodontopathic microbes correlated with the periodontal pocket counts of the same infectious agents, and whether the salivary counts of the test infectious agents could distinguish among individuals with periodontal health and various types of periodontal disease. MATERIAL AND METHODS The study included 150 systemically healthy adults, of whom 37 were periodontally healthy, 31 had gingivitis, 46 had chronic periodontitis and 36 had aggressive periodontitis. Each study subject contributed microbial samples from the two deepest periodontal pockets of the dentition and from whole saliva. Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Epstein-Barr virus were identified using the TaqMan real-time PCR methodology. Statistical analysis was performed using the Mann-Whitney U-test and the receiver operating characteristic statistics. RESULTS C. rectus, F. nucleatum, P. gingivalis, P. intermedia and T. forsythia occurred with significantly higher copy-counts in salivary samples from patients with gingivitis, chronic periodontitis and aggressive periodontitis than from periodontally healthy individuals. A. actinomycetemcomitans only showed higher salivary copy-counts in subjects with aggressive periodontitis compared with subjects with healthy periodontium, and the salivary copy-counts of Epstein-Barr virus did not reveal any significant difference among the four subject groups studied. The diagnostic sensitivity for periodontitis was 89.19 for P. gingivalis and for T. forsythia and 86.49 for P. intermedia, with specificities ranging from 83.78 to 94.59. The optimal copy-counts per mL saliva for identifying periodontitis were 40,000 for P. gingivalis, 700,000 for T. forsythia and 910,000 for P. intermedia. CONCLUSION Salivary copy-counts of P. gingivalis, T. forsythia and P. intermedia appear to have the potential to identify the presence of periodontitis, whereas the salivary level of the other test infectious agents may possess little or no diagnostic utility. Longitudinal studies are warranted to determine the ability of salivary copy-counts of major periodontopathic bacteria to predict future periodontal breakdown.

Herpesviruses in periapical pathosis: an etiopathogenic relationship?

BACKGROUND Much remains to be learned about the etiopathogenesis of periapical pathosis, especially about the molecular events preceding and causing disease onset. Human cytomegalovirus and Epstein-Barr virus, 2 herpesviruses, are discussed in this review as they relate to apical periodontitis in humans. RESULTS Cytomegalovirus or Epstein-Barr virus active infections are detected in more than 90% of granulomas of symptomatic and large periapical lesions. Dual infection with cytomegalovirus and Epstein-Barr virus is closely associated with symptomatic lesions. Herpes simplex virus active infection has no apparent relationship to periapical disease. DISCUSSION The available evidence suggests the involvement of active cytomegalovirus and Epstein-Barr infections in the etiopathogenesis of apical periodontitis. In periapical pathosis, herpesviruses may cause the release of tissue-destructive cytokines, the overgrowth of pathogenic bacteria, and the initiation of cytotoxic or immunopathologic events. Immune impairment resulting from herpesvirus infection may aid bacteria at several stages of the pathogenesis of periapical lesions, including growth in the periapical environment, possible invasion of tissue, and direct damage to tissue. Unraveling the etiology and pathogenesis of periapical pathosis may require a broadening of our experimental approaches to include studies on interactions among herpesviruses, bacteria, and host immune reactions. Understanding the significance of herpesviruses in the development of periapical lesions may aid in the diagnosis, prevention, and treatment of the diseases.

Oral viral infections of adults

The field of virology has advanced greatly over the past two decades, mainly because of the introduction of sophisticated molecular tools, such as monoclonal antibodies, polymerase chain reaction (PCR)-based amplification, DNA sequencing, DNA and protein microarray chip assays, and rapid diagnostic tests. These technologies have been the driving force in the identification of viral bodies, proteins and nucleic acids in body fluids and tissue samples, and in determining the host response to viral infections. The 5th (2007) edition of Fields Virology provides an indepth description of viral methodology and medical virology, and is an important source of reference for this review (118). Viruses replicate only when present within eukaryotic (animals, plants, protists and fungi) or prokaryotic (bacteria and archaea) cells, not on their own. The extracellular virion particle ranges in size from 20 to 300 nm and consists of either DNA or RNA contained within a protective protein capsid. Some viruses have an additional envelope comprising a lipid bilayer derived from the outer cellular membrane, the internal nuclear membrane, or the endoplasmic reticulum membrane of the infected cell. Taxonomically, viruses are classified according to the presence of DNA or RNA, single-stranded or double-stranded nucleic acid, and an enveloped or nonenveloped nucleocapsid. Additional taxonomical criteria include mode of replication, type of host, capsid shape, immunological properties and disease association. The host recognizes and reacts to the infecting virus by innate and adaptive immune responses. Important cells of the innate immune system include macrophages, dendritic cells and natural killer cells. Viruses activate inflammatory cell types to release antiviral cytokines and cytotoxic agents, and to induce lymphocyte-mediated adaptive immunity. A significant cytokine release is stimulated through activation of the tumor necrosis factor-a receptor ⁄ nuclear factor-jB ⁄ extracellular signal-regulated kinase pathway (49). Virally derived proteins, which are presented by major histocompatibility complex molecules on the surface of infected cells, serve as epitopes for specific host immune cells. Nonenveloped viruses are mainly controlled by the humoral adaptive immunity. Enveloped viruses are controlled by the cellular immunity through the action of natural killer cells and cytotoxic CD8 T lymphocytes. After recognizing viral surface antigens on infected cells, cytotoxic T lymphocytes inhibit virus replication by cytolytic killing and by releasing interferons, chemokines, tumor necrosis factor-a or other pro-inflammatory mediators. Viral disease may be a direct result of cell destruction or a secondary consequence of host immune reactions against viral proteins. Proinflammatory cytokines play important roles in the antiviral immune response, but interleukin-1b, interleukin-6 and tumor necrosis factor-a cytokines can also contribute to disease manifestation. The host usually performs a delicate balancing act between promoting antiviral cytokine responses and limiting the amount of tissue damage. To counteract the immune attack, viruses employ sophisticated immunoevasive strategies to suppress antiviral host responses. For example, some viruses produce proteins that alter the major histocompatibility complex and hence the exposure of viral proteins on the surface of infected cells. Viruses may encode viral homologs of host cytokines and decoy receptors capable of binding and neutralizing host-derived cytokines. A rapid rate of mutation in critical viral genes can help viruses avoid the adaptive host defense. Other viral gene products inhibit apoptosis, which facilitates a prolonged state of replication of infected cells and spread of the virus. Viral diseases of the oral mucosa and the perioral region are often encountered in dental practice, but have received only limited research interest. Viruses are important ulcerogenic and tumorigenic agents of the human mouth. The finding of an abundance of mammalian viruses in periodontitis lesions may suggest a role for viruses in more oral diseases than

Periodontology: past, present, perspectives

Periodontitis is an infectious disease that affects the tooth-supporting tissues and exhibits a wide range of clinical, microbiological and immunological manifestations. The disease is associated with and is probably caused by a multifaceted dynamic interaction of specific infectious agents, host immune responses, harmful environmental exposure and genetic susceptibility factors. This volume of Periodontology 2000 covers key subdisciplines of periodontology, ranging from etiopathogeny to therapy, with emphasis on diagnosis, classification, epidemiology, risk factors, microbiology, immunology, systemic complications, anti-infective therapy, reparative treatment, self-care and affordability issues. Learned and unlearned concepts of periodontitis over the past 50 years have shaped our current understanding of the etiology of the disease and of clinical practice.

Clinical and microbiological determinants of ailing dental implants.

BACKGROUND The failure of the host tissue to establish or maintain osseointegration around dental implants is due to either occlusal or parafunctional forces, premature loading, ill-directed stress, or microbial infection. The long-term failure rate of dental implants is generally 5-10%. Although a variety of etiologies of early peri-implant bone loss (from implant placement to 1-year post-loading) have been proposed, factors associated with late implant failures are less well understood but are probably related to both the peri-implant microbial environment and host factors. Discriminating between causes of implant failure is of importance for instituting a successful implant therapy. PURPOSE The objective of this cross-sectional split-mouth study was to identify clinical, radiographic, and bacterial characteristics of peri-implant disease sites. MATERIALS AND METHODS Fifteen patients with bilateral implants (Brånemark, Nobel Biocare AB, Göteborg, Sweden; and 3i implant systems, Implant Innovations Inc., Palm Beach Gardens, FL, USA) participated in the study. Sites with peri-implant (radiographic bone loss beyond the third implant thread) and peri-implant healthy tissues (radiographic bone level above the first implant thread) were identified in periapical radiographs using a long-cone paralleling projection technique. Microbiological identification was carried out using established anaerobic culture techniques. A descriptive statistics based on means and standard deviations was reported. RESULTS Peri-implant bone loss was associated with the absence of radiographic crestal lamina dura, peri-implant pocket depth, pain on chewing, and the submucosal presence of the putative periodontopathogens Tannerella forsythia, Campylobacter species, and Peptostreptococcus micros. Pain was associated with P. micros, Fusobacterium species, and Eubacterium species. DISCUSSION AND CONCLUSION The absence of radiographic crestal lamina dura and the presence of suspected major periodontal pathogens seem to be associated to peri-implantitis.

Low-cost periodontal therapy

Periodontitis is a complex infectious disease that affects low-income individuals disproportionately. Periodontitis is associated with specific bacterial species and herpesviruses, and successful prevention and treatment of the disease is contingent upon effective control of these pathogens. This article presents an efficacious, highly safe, minimally invasive, practical and low-cost periodontal therapy that involves professional and patient-administered mechanical therapy and antimicrobial agents. The major components are scaling for calculus removal, periodontal pocket irrigation with potent antiseptics, and treatment with systemic antibiotics for advanced disease. Povidone-iodine and sodium hypochlorite have all the characteristics for becoming the first-choice antiseptics in the management of periodontal diseases. Both agents show excellent antibacterial and antiviral properties, are readily available throughout the world, have been safely used in periodontal therapy for decades, offer significant benefits for individuals with very limited financial resources, and are well accepted by most dental professionals and patients. Four per cent chlorhexidine applied with a toothbrush to the most posterior part to the tongue dorsum can markedly reduce or eliminate halitosis in most individuals. Systemic antibiotics are used to treat periodontopathic bacteria that are not readily reached by topical therapy, such as pathogens within gingival tissue, within furcation defects, at the base of periodontal pockets, and on the tongue, tonsils and buccal mucosae. Valuable antibiotic therapies are amoxicillin-metronidazole (250 mg of amoxicillin and 250 mg of metronidazole, three times daily for 8 days) for young and middle-aged patients, and ciprofloxacin-metronidazole (500 mg of each, twice daily for 8 days) for elderly patients and for patients in developing countries who frequently harbor enteric rods subgingivally. Scaling to remove dental calculus and the prudent use of inexpensive antimicrobial agents can significantly retard or arrest progressive periodontitis in the great majority of patients.