Clay Walker

Periodontitis and Porphyromonas gingivalis in Patients With Rheumatoid Arthritis

To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.

Antibiotic susceptibilities of periodontal bacteria. In vitro susceptibilities to eight antimicrobial agents.

In vitro susceptibilities of 369 to 966 bacterial isolates from periodontal lesions to eight antibiotics were determined by agar dilution technique as a means of determining which antimicrobial agents were inhibitory for bacteria frequently associated with destructive periodontal diseases. Although most bacteria were relatively susceptible to the penicillins, greater activity was generally noted with amoxicillin than with either penicillin or ampicillin with the exception of Selenomonas sputigena and Peptostreptococcus. Antibacterial activities obtained with minocycline were significantly higher than with tetracycline for Actinobacillus actinomycetemcomitans and Streptococcus but comparable for most other taxa. Clindamycin and metronidazole both demonstrated excellent activity against the anaerobic Gram-negative rods but were less effective against some of the capnophilic and facultative organisms. Eikenella corrodens was exceptionally resistant to both of these drugs; and A. actinomycetemcomitans was generally resistant to Clindamycin but relatively susceptible to metronidazole. Erythromycin was considerably less active than the other antibiotics against the majority of the periodontal bacteria. No single antibiotic, at concentrations equivalent to those achieved in body fluids, was uniformly effective in inhibiting all bacteria currently implicated or suspected as etiologic agents of periodontal diseases.

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.

Microbiological Characterization in Children with Aggressive Periodontitis

The objective of this study was to characterize the subgingival microbiota of African-American children with Localized Aggressive Periodontitis (LAP). Fifty-one children were included. Subgingival plaque samples were taken from diseased (DD) and healthy sites (DH) in LAP and from healthy sites in HS and HC and analyzed by 16S rRNA-based microarrays. Aggregatibacter actinomycetemcomitans (Aa) was the only species found to be both more prevalent (OR = 8.3, p = 0.0025) and abundant (p < 0.01) in DD. Filifactor alocis (Fa) was also found to be more prevalent in DD (OR 2.31, CI 1.06-5.01, p = 0.03). Most prevalent species in healthy sites were Selenomonas spp, Veillonella spp, Streptococcus spp, Bergeyella sp, and Kingella oralis. Overall, Streptococcus spp, Campylobacter gracilis, Capnocytophaga granulosa, Haemophilus parainfluenzae, and Lautropia mirabilis were most abundant in healthy children, while Aa, Fa, Tannerella sp, Solobacterium moorei, Parvimonas micra, and Capnocytophaga sp were most abundant in LAP. Based on a comprehensive analysis with 16S rRNA-based microarrays, Aa was strongly associated and site-specific in LAP. In contrast, other species were found to be associated with healthy sites and individuals (ClinicalTrials.gov number CT01330719). Abbreviations: healthy site in healthy sibling (HS); healthy site in healthy control child (HC).

Localization and identification of root canal bacteria in clinically asymptomatic periapical pathosis

Twenty-one teeth with clinically asymptomatic periapical pathosis (class 3) were extracted and the isolation, identification, and localization of bacteria in the root apex were examined. Mixtures involving several bacteria were isolated from more than 60% of the cases. Scanning electron microscopy revealed bacterial masses to be associated with the apical part of the root canal, but not with the area of apical foramen or on the surface of root apex. Our results indicate that the bacteria in class 3 cases may be derived from organisms which colonized before or during endodontic treatment, but not from anachoresis. The bacteria-positive cases of asymptomatic periapical pathosis have the potential to progress to symptomatic periapical pathosis.

Gingival crevicular fluid levels of clindamycin compared with its minimal inhibitory concentrations for periodontal bacteria.

Clindamycin concentrations in gingival crevicular fluid and in blood were determined over a 7-h period and were related to the minimal inhibitory concentrations of this agent for 340 bacterial strains isolated from diseased periodontal sites. The clindamycin levels after administration of single 300-mg oral doses were measured in gingival crevicular fluids by using an agar diffusion bioassay. Minimal inhibitory concentrations were determined by agar dilution techniques for 30 species of periodontal bacteria. With the exception of Eikenella corrodens and Actinobacillus actinomycetemcomitans, most of the bacteria were inhibited by a concentration of 1.0 microgram of clindamycin per ml or less. The peak concentrations in crevicular fluid (2.0 +/- 0.3 microgram/ml) and in blood (1.9 +/- 0.3 micrograms/ml) were approximately the same. However, crevicular fluid levels of 1.0 micrograms/ml and above were present for up to 6 h, whereas blood concentrations dropped below 1.0 micrograms/ml within 2 h after administration. Based on its minimal inhibitory concentrations, clindamycin at crevicular fluid levels of 1.0 micrograms/ml or above should inhibit most bacteria associated with diseased periodontal sites.

Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine

In 1983, it was first reported that tetracyclines (TCs) can modulate the host response, including (but not limited to) inhibition of pathologic matrix metalloproteinase (MMP) activity, and by mechanisms unrelated to the antibacterial properties of these drugs. Soon thereafter, strategies were developed to generate non-antibacterial formulations (subantimicrobial-dose doxycycline; SDD) and compositions (chemically modified tetracyclines; CMTs) of TCs as host-modulating drugs to treat periodontal and other inflammatory diseases. This review focuses on the history and rationale for the development of: (a) SDD which led to two government-approved medications, one for periodontitis and the other for acne/rosacea and (b) CMTs, which led to the identification of the active site of the drugs responsible for MMP inhibition and to studies demonstrating evidence of efficacy of the most potent of these, CMT-3, as an anti-angiogenesis agent in patients with the cancer, Kaposis sarcoma, and as a potential treatment for a fatal lung disease (acute respiratory distress syndrome; ARDS). In addition, this review discusses a number of clinical studies, some up to 2 years’ duration, demonstrating evidence of safety and efficacy of SDD formulations in humans with oral inflammatory diseases (periodontitis, pemphigoid) as well as medical diseases, including rheumatoid arthritis, post-menopausal osteopenia, type II diabetes, cardiovascular diseases, and a rare and fatal lung disease, lymphangioleiomyomatosis.

Sensitive assay for measuring tetracycline levels in gingival crevice fluid.

An increased interest in the clinical use of antibiotics as an adjunct to periodontal therapy has created a need to determine antibiotic concentrations in fluid obtained from the gingival crevice. For this purpose, an increase in sensitivity beyond that possible with current tetracycline assays is essential because sample volumes of gingival fluid typically obtained are less than 0.5 microliter. This report describes the development of an agar-diffusion assay technique capable of measuring the concentration of tetracycline in samples of gingival crevice fluid in the range of 0.1 to 4.0 microgram/ml. The assay will detect amounts of tetracycline in gingival crevice fluid samples as low as 50 pg. The high sensitivity of this assay was achieved by optimizing the medium depth, inoculum density, agar concentration, pH, period of prediffusion, and selection of basal medium. Use of this assay indicated that the concentration of tetracylcine in gingival crevice fluid was greater than that found in blood and persisted at elevated levels for longer periods.

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.

A comparative evaluation of the sealing ability of 2 root-end filling materials: an in vitro leakage study using Enterococcus faecalis.

OBJECTIVE The purpose of this study was to evaluate the sealing ability of EndoSequence Bioceramic Root-end Repair (BCRR) material when compared with white mineral trioxide aggregate (WMTA). STUDY DESIGN Forty single-rooted teeth were instrumented, obturated with gutta-percha, root-end resected, and retrofilled with 2 different materials: white ProRoot MTA (WMTA) (n = 15) and BCRR (n = 15). Unfilled specimens (n = 10) received no retrofill and were used as controls. All groups received E. faecalis in a created reservoir coronal to the root filling and the presence of microleakage was evaluated by counting the colony-forming units from each specimen. The results were analyzed with 1-way analysis of variance. RESULTS There was no significant difference in leakage between the 2 experimental groups, but there was a significant difference with the control (P ≤ .05). CONCLUSIONS This study suggests that BCRR is equivalent in sealing ability to WMTA when used as root-end filling material in vitro.