Ingvar Magnusson

A Role for Antibiotics in the Treatment of Refractory Periodontitis

Refractory periodontitis is considered by many investigators to be a separate disease entity that is descriptive of a particular patient who has multiple sites, rather than a few individual sites, that do not respond to conventional periodontal treatment modalities. Such patients continue to demonstrate loss of attachment and alveolar bone despite frequent periodontal treatment which includes surgical intervention, scaling and root planing, and often systemically-administered tetracycline. Controlled clinical studies have demonstrated that both clindamycin-hydrochloride and amoxicillin/clavulanate potassium (Au) are beneficial when used in conjunction with periodontal scaling. Gordon et al. found improvements in attachment levels, inflammation, suppuration, and a decrease in pocket depths for up to 2 years following a 7-day course of Clindamycin given in conjunction with a full-mouth scaling. The incidence of disease activity decreased from an annual rate of 8% of all sites prior to antibiotic treatment to 0.5% after treatment. Magnusson, reporting on a similar group treated with a 14-day course of Au, found an average loss of attachment of 2.2 mm and an increase in pocket depth of 1.5 mm in sites demonstrating disease progression prior to antibiotic treatment. At 3 months post-antibiotic therapy, these sites had regained an average of 2 mm of attachment and pocket depths had decreased an equivalent amount. Both attachment levels and pocket depths remained relatively stable for up to 12 months post-therapy. In an ongoing study, 30 subjects with refractory Periodontitis were treated with either Clindamycin or Au in conjunction with scaling or scaling plus a placebo. Prior to antibiotic treatment, but while being scaled at 3-month intervals, sites with disease activity lost an average 2.4 mm of attachment. At 3 months post-treatment, the clindamycin-treated group showed an average gain of 2.1 mm, the Au-treated group gained 1.9 mm, and the scaling group gained 1.4 mm in attachment. The clindamycin group remained relatively stable for up to 21 months and the Au group remained stable for about 15 months without additional treatment. Five of the 6 subjects treated with scaling alone required additional treatment within 9 months. Preliminary analyses have indicated that at least two patterns or rates of attachment loss may be associated with refractory periodontitis and that each pattern may be indicative of a different microflora. The pattern associated with a relatively rapid loss of attachment was characterized by a Gram-negative flora which contained spirochetes, P. intermedia, and Fusobacterium species. A slow, continuous rate was associated with a predominantly Gram-positive flora containing a high proportion of S. intermedius and/or a S. intermedius-like organism. J Periodontol 1993; 64:772-781.

Dysbiosis and Alterations in Predicted Functions of the Subgingival Microbiome in Chronic Periodontitis

ABSTRACT Chronic periodontitis is an inflammatory disease of the periodontium affecting nearly 65 million adults in the United States. Changes in subgingival microbiota have long been associated with chronic periodontitis. Recent culture-independent molecular studies have revealed the immense richness and complexity of oral microbial communities. However, data sets across studies have not been directly compared, and whether the observed microbial variations are consistent across different studies is not known. Here, we used 16S rRNA sequencing to survey the subgingival microbiota in 25 subjects with chronic periodontal disease and 25 healthy controls and compared our data sets with those of three previously reported microbiome studies. Consistent with data from previous studies, our results demonstrate a significantly altered microbial community structure with decreased heterogeneity in periodontal disease. Comparison with data from three previously reported studies revealed that subgingival microbiota clustered by study. However, differences between periodontal health and disease were larger than the technical variations across studies. Using a prediction score and applying five different distance metrics, we observed two predominant clusters. One cluster was driven by Fusobacterium and Porphyromonas and was associated with clinically apparent periodontitis, and the second cluster was dominated by Rothia and Streptococcus in the majority of healthy sites. The predicted functional capabilities of the periodontitis microbiome were significantly altered. Genes involved in bacterial motility, energy metabolism, and lipopolysaccharide biosynthesis were overrepresented in periodontal disease, whereas genes associated with transporters, the phosphotransferase system, transcription factors, amino acid biosynthesis, and glycolysis/gluconeogenesis were enriched in healthy controls. These results demonstrate significant alterations in microbial composition and function in periodontitis and suggest genes and metabolic pathways associated with periodontal disease.

Local Inflammatory Markers and Systemic Endotoxin in Aggressive Periodontitis

While much research has focused on local and systemic factors contributing to periodontal disease, little is known regarding mechanisms linking these factors. We have previously reported a systemic hyper-inflammatory response to bacterial endotoxin in localized aggressive periodontitis (LAP). The objectives of this study were to delineate cyto/chemokines in gingival crevicular fluid (GCF) and evaluate systemic levels of endotoxin associated with LAP. Clinical parameters, GCF, and peripheral blood were collected from: 34 LAP, 10 healthy siblings, and nine healthy unrelated control individuals. Cyto/chemokines were quantified in GCF, systemic endotoxin levels were quantified in plasma, and correlation analysis was performed among all parameters. Nine mediators were elevated in LAP diseased sites as compared with healthy sites (TNFα, INFγ, IL1β, IL2, IL6, IL10, Il12p40, GMCSF, and MIP1α, p < 0.001), while MCP1, IL4, and IL8 were elevated in healthy sites (p < 0.01). Four- to five-fold-higher endotoxin levels were detected in LAP plasma compared with that from healthy participants (p < 0.0001), which correlated with all clinical parameters and most cyto/chemokines analyzed. In conclusion, higher systemic levels of endotoxin were found in LAP, which correlates with an exacerbated local inflammatory response and clinical signs of disease. (Clinicaltrials.gov number, NCT01330719).

Single site meta-analysis of 6% hydrogen peroxide whitening strip effectiveness and safety over 2 weeks

OBJECTIVES This research evaluated efficacy and safety of 6% hydrogen peroxide whitening strips from a clinical trials database accumulated over a multi-year period at a single site. METHODS The inclusive meta-analysis involved seven different randomized clinical trials at one dental school. Each study used 6% hydrogen peroxide whitening strips twice daily for 30min over a 2-week period. Common efficacy (digital images) and safety (examination and interview) methods were used across studies. Pooled subject-level data were analyzed using a general linear mixed model to determine overall response and effects of treatment duration on whitening. RESULTS The 148 treated subjects were 18-71 years old, with b* (yellowness) ranging from 12 to 22, and L* (lightness) ranging from 69 to 80. After 1-week strip use, the adjusted mean (S.E.) for Deltab* was -1.6 (0.08), differing significantly from baseline (p<0.0001). After 2 weeks, the adjusted mean (S.E.) for Deltab* was -2.3 (0.07), differing significantly from Week 1 (p<0.0001). The estimated correlation between Weeks 1 and 2 for Deltab* was 0.74. Study-to-study variation contributed less than 2% of Deltab* variability. Results were similar for DeltaL*, with Weeks 1 and 2 estimated means (S.E.) of 1.5 (0.13) and 2.0 (0.12). Occurrence of oral irritation (22%) and tooth sensitivity (20%) did not adversely affect whitening. Other side effects were unremarkable, and only 1 subject (0.7%) discontinued treatment early due to an adverse event. CONCLUSIONS The meta-analysis of multiple studies conducted at a single clinical site over several years establishes consistent, effective and safe vital bleaching with 6% hydrogen peroxide whitening strips.

Clinical comparison of two self‐directed bleaching systems

PURPOSE This randomized clinical trial compared the clinical efficacy and tolerability of 2 marketed self-directed vital tooth-whitening systems. MATERIALS AND METHODS Balancing for baseline tooth color, self-reported coffee/tea use, and age, 57 adult volunteers were randomized to either a whitening strip containing 6% hydrogen peroxide or a tray-based 10% carbamide peroxide/dentifrice/mouth rinse combination system. Following the manufacturers directions, the strip group bleached twice daily for 30 minutes, whereas the tray group bleached twice daily for 20-30 minutes, preceded by tooth brushing with a whitening dentifrice and followed by mouth rinsing with a whitening solution. Treatment extended for 14 days, with evaluation at day 7 and again at day 14. Whitening response was measured objectively as L*a*b* from standardized digital images of maxillary anterior teeth. Tolerability was assessed by oral examination and subject interview. Efficacy comparisons were made using analysis of covariance, whereas tolerability was compared using the nonparametric Wilcoxon rank-sum test. RESULTS Both treatments resulted in statistically significant (P < 0.01) improvements from baseline for all color parameters. For between-group comparisons, the 6% hydrogen peroxide strips yielded a nearly 3-fold reduction in yellowness (deltab*), a nearly 2-fold improvement in lightness (deltaL*), 2.6 times greater redness reduction (deltaa*), and a more than 2-fold change in overall color (deltaE*) compared to the tray-based combination system. Between-group comparisons were statistically significant for the all color parameters at both the day 7 and day 14 evaluations (P < 0.001). In general, 7-day use of the whitening strips provided significantly greater color improvement relative to the combination dentifrice/gel/rinse system at day 14. In addition, the groups differed significantly (P < 0.05) in bleaching tolerability severity-days, with the strip system demonstrating better overall tolerability compared to the combination system. CONCLUSIONS The single-step 6% hydrogen peroxide strips demonstrated better overall clinical response, in terms of both tooth-whitening efficacy and tolerability, than the multiple-step tray-based combination system.

Benefits of early systemic antibiotics in localized aggressive periodontitis: a retrospective study

BACKGROUND Treatment of localized aggressive periodontitis (LAP) may include systemic antibiotics, yet it is unclear at what stage of treatment planning antibiotics are most effective. AIM This retrospective analysis compared immediate versus delayed antibiotic therapy on clinical parameters and gingival crevicular fluid (GCF) inflammatory mediators. MATERIAL AND METHODS At baseline, 3 months and 6 months after treatment, clinical parameters [probing depth (PD), clinical attachment level (CAL), bleeding on probing (BoP) and plaque] and GCF were collected from LAP participants, who received a 7-day antibiotic regimen immediately (ImA) or 3 months following (DelA) mechanical therapy. RESULTS Although both groups presented significant CAL reductions at 6 months, only ImA resulted in a reduction in mean PD at both 3 and 6 months, along with reductions in CAL and BoP at 3 months following therapy. In addition, GCF mediators were higher in DelA group at 3 months post mechanical treatment, but were significantly reduced 6 months following antibiotic therapy. CONCLUSIONS ImA and DelA regimens were both effective in improving CAL by 6 months post therapy. However, ImA allowed for better improvement in overall clinical parameters early in the course of treatment, concomitant with lower levels of inflammatory mediators within the GCF.

Current concepts in diagnosis andtreatment of periodontitis

This article describes some areas of periodontal research and currentopinions regarding detection of disease progression, as well as risk indicators and risk factors associated with disease progression. Longitudinal probing of periodontal attachment level is considered the gold standard for detection of disease activity although there are problems with this concept. Digital subtraction radiography can assist in the detection of minor changes of alveolar bone height and density. Risk factors such as composition of subgingival plaque and gingival crevicular fluid, as well as the effect of smoking are discussed. Adjunctive treatment with both antibiotics and nonsteroidal anti-inflammatory drugs, systemic or local, seems to be helpful in some forms of disease. Immunization to prevent colonization of tooth surfaces and pockets by periodontal pathogens does not seem to be feasible in the near future.

Recent approaches to periodontal therapy.

Periodontal diseases encompass a variety of disease classifications, all involving inflammation of the supporting tissues of the teeth. When progressive, these diseases ultimately lead to the destruction of attachment apparatus including bone and periodontal ligament, culminating in eventual tooth loss. Inflammation extends from superficial gingival structures, effecting adjacent submerged bone and periodontal ligament. Progression modifies an initially highly favourable, reversible diagnosis of gingivitis to a less favourable, somewhat irreversible situation: periodontitis. Periodontal diseases manifest variable and sometimes unpredictable prognoses, are generally somewhat complicated and costly to treat and often require long-term follow-up for maintenance and monitoring. Treatment aims at restoration of health and control of future disease within a functional, albeit reduced, periodontium. In the strictest sense, periodontal diseases are not ‘cured’. The conventional, usually successful, approach to the treatment of patients with gingivitis or chronic periodontitis has involved non-surgical mechanical periodontal therapy [1,2]. Some patients manifest localised or generalised continuous attachment loss and periodontal destruction. These sites are prime candidates for alternative therapeutic regimens. This review highlights some of the recent advances in periodontal therapy and evokes some questions that should be addressed during future studies.