Clinical, microbiological, and immunological effects of systemic probiotics in periodontal treatment: study protocol for a randomized controlled trial.

BACKGROUND: The association of scaling and root planing (SRP) with systemic metronidazole (MTZ) plus amoxicillin (AMX) has shown to be an effective treatment protocol, particularly for periodontitis stages III and IV, generalized. More recently, probiotics have also been suggested as a promising adjunctive treatment for periodontal diseases due to their antimicrobial and anti-inflammatory properties. Therefore, the aim of this randomized clinical trial (RCT) is to evaluate the clinical, microbiological, and immunological effects of probiotics as adjuncts to SRP alone or with MTZ+AMX in the treatment of periodontitis. METHODS: Subjects with periodontitis are being randomly assigned to receive (i) SRP alone, or with (ii) two probiotic lozenges/day for 90 days (Prob), (iii) MTZ (400 mg) and AMX (500 mg) thrice a day (TID) for 14 days (MTZ+AMX), or (iv) Prob and MTZ+AMX. Subjects are being monitored for up to 12 months post-treatment. Nine subgingival plaque samples per patient are being collected at baseline and at 3, 6, and 12 months post-therapy and analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species. Peripheral blood and gingival crevicular fluid (GCF) of four randomly selected periodontal sites will be analyzed by means of a multiplex fluorescent bead-based immunoassay for 17 cyto/chemokines. STATISTICAL ANALYSES: The significance of differences in each group (over the course of the study) will be sought using repeated measures ANOVA or Friedman tests and among groups (at each time point) using either ANOVA/ANCOVA or Kruskal-Wallis tests, depending on normality of the data. The chi-square test will be used to compare differences in the frequency of subjects achieving the clinical endpoint for treatment (≤ 4 sites with PD ≥ 5 mm) at 1 year and of self-perceived adverse effects. A stepwise forward logistic regression analysis will be performed in order to investigate the impact of different predictor variables on the percentage of patients achieving the clinical endpoint for treatment. The Number Needed to Treat (NNT) with different treatment protocols will be also calculated. Statistical significance will be set at 5%. TRIAL REGISTRATION: ClinicalTrials.gov NCT03733379. Registered on November 7, 2018.

Does subgingival bacterial colonization differ between implants and teeth? A systematic review.

The aim was of this study was to determine the current weight of evidence for the existence of specific differences between the microbiota of healthy teeth and healthy implants, or of teeth with periodontitis and implants with peri-implantitis. A systematic review was conducted according to the PRISMA statement. The MEDLINE, EMBASE and Cochrane databases were searched up to February 2018 for studies comparing microbiological data of biofilm samples collected from healthy teeth and implants or from teeth with periodontitis and implants with peri-implantitis. The weight of evidence was defined in three categories (strong, moderate and mild/some), according to the difference in number of studies showing statistically significantly higher counts and/or proportions and/or abundance and/or prevalence of microorganisms in health or in disease. Of the 132 articles identified, 8 were included. A wide range of microorganisms were present in different conditions but no microorganisms showed strong, moderate or mild/some evidence for a specific association with either teeth or implants. The results of this systematic review indicated that there is insufficient evidence in the literature to support specific differences between microorganisms colonizing teeth and implants, either in health or in disease.

Does subgingival bacterial colonization differ between implants and teeth? A systematic review

Abstract The aim was of this study was to determine the current weight of evidence for the existence of specific differences between the microbiota of healthy teeth and healthy implants, or of teeth with periodontitis and implants with peri-implantitis. A systematic review was conducted according to the PRISMA statement. The MEDLINE, EMBASE and Cochrane databases were searched up to February 2018 for studies comparing microbiological data of biofilm samples collected from healthy teeth and implants or from teeth with periodontitis and implants with peri-implantitis. The weight of evidence was defined in three categories (strong, moderate and mild/some), according to the difference in number of studies showing statistically significantly higher counts and/or proportions and/or abundance and/or prevalence of microorganisms in health or in disease. Of the 132 articles identified, 8 were included. A wide range of microorganisms were present in different conditions but no microorganisms showed strong, moderate or mild/some evidence for a specific association with either teeth or implants. The results of this systematic review indicated that there is insufficient evidence in the literature to support specific differences between microorganisms colonizing teeth and implants, either in health or in disease.

The ideal time of systemic metronidazole and amoxicillin administration in the treatment of severe periodontitis: study protocol for a randomized controlled trial.

BACKGROUND: The combination of systemic metronidazole (MTZ) and amoxicillin (AMX) with scaling and root planing (SRP) has shown to be an effective periodontal treatment. However, some essential issues associated with the use of these antibiotics remain unanswered, such as the ideal time of administration during the course of periodontal treatment. Although these agents are often prescribed after the healing phase of the SRP procedure, there is biological plausibility to support its use in conjunction with the mechanical treatment. However, to date, no placebo controlled randomized clinical trial (RCT) has directly compared these two protocols. Therefore, the aim of this RCT is to compare the clinical, microbiological and immunological effects of the adjunctive systemic MTZ + AMX administered in different phases of the treatment of severe periodontitis. METHODS: Subjects with severe periodontitis (n = 180) are being randomly assigned into three groups (n = 60/group): (i) SRP-only (control group), SRP in combination with 400 mg MTZ + 500 mg AMX, starting (ii) at the first SRP session (active phase group), or (iii) after 3 months of its completion (healing phase group). All volunteers are receiving clinical and microbiological evaluation at baseline, 3, 6 and 12 months, and immunological assessment at baseline and 12 months post-therapy. Nine subgingival biofilm samples are being collected per subject and analyzed for counts and proportions of 40 bacterial species by checkerboard DNA-DNA hybridization, and six gingival crevicular fluid samples are being collected and analyzed for the levels of 20 chemokines by multiplex immunoassay. The primary outcome variable is the number of volunteers reaching the clinical endpoint for treatment (≤ 4 sites with probing depth ≥5 mm) at 1 year post-therapy. Differences in clinical, microbiological and immunological parameters among groups and over time will be evaluated using analysis of variance, analysis of covariance and the Chi-square and Tukey tests. Microbiological and immunological analyses will be performed using adjustments for multiple comparisons. Statistical significance will be set at 5%. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02954393 . Registered on 3 November 2016.

Evaluation of Enterococcus faecalis, Staphylococcus warneri and Staphylococcus aureus species in adults with generalized chronic periodontitis / Avaliação das espécies Enterococcus faecalis, Staphylococcus warneri e Staphylococcus aureus em adultos com periodontite crônica generalizada

ABSTRACT Objective: To identify and quantify the levels of three bacterial species that have recently been identified as potential "new" periodontal pathogens (Enterococcus faecalis, Staphylococcus aureus and Staphylococcus warneri) in subjects with periodontal health and generalized chronic periodontitis. Methods: Thirty adults with generalized chronic periodontitis and 10 periodontally healthy were included in this study. Nine subgingival biofilm samples were collected per subject and individually analyzed by checkerboard DNA-DNA hybridization technique. Results: The mean levels of E. faecalis and S. warneri were higher in chronic periodontitis than in periodontal health (p<0.05). Furthermore, a higher percentage of subjects with periodontitis were colonized by the three species evaluated in comparison with healthy subjects (p<0.05). This represented a difference of 40 percentage points between the two groups, for E. faecalis (present in 90% of individuals with periodontitis and 50% of the healthy individuals) and S. warneri (100% and 60%, respectively), and 26 percentage points for S. aureus (86% and 60%, respectively). Conclusion: E. faecalis and S. warneri have the potential to be periodontal pathogens. The role of S. aureus was less evident, since this species was more prevalent and at relatively higher levels in health than the other two species. These data might guide future studies on the role of these microorganisms in the etiology of periodontitis and help to establish more effective treatments for these infections.

RESUMO Objetivo: Identificar e quantificar os níveis de três espécies bacterianas que foram recentemente apontadas como possíveis "novos" patógenos periodontais (Enterococcus faecalis, Staphylococcus warneri e Staphylococcus aureus), em indivíduos periodontalmente saudáveis e com periodontite crônica generalizada. Métodos: A amostra foi composta por 30 indivíduos adultos com periodontite crônica generalizada e 10 periodontalmente saudáveis. Nove amostras de biofilme subgengival foram coletadas por indivíduo e analisadas individualmente pela técnica de checkerboard DNA-DNA hybridization. Resultados: Os níveis médios de E. faecalis e S. warneri foram maiores no grupo com periodontite crônica do que no de saúde periodontal (p<0,05). Além disso, um maior percentual de indivíduos com periodontite estavam colonizados pelas três espécies avaliadas em comparação com os indivíduos saudáveis (p<0,05). Essa diferença entre os dois grupos foi de 40 pontos percentuais para E. faecalis (presente em 90% dos indivíduos com periodontite e 50% dos saudáveis) e S. warneri (100% e 60%, respectivamente), e de 26 pontos percentuais para S. aureus (86% e 60%, respectivamente). Conclusão: E. faecalis e S. warneri tem potencial para serem patógenos periodontais. O papel do S. aureus foi menos evidente, uma vez que esta espécie estava mais prevalente e em níveis relativamente mais altos do que as outras duas espécies em saúde. Estes dados podem guiar futuros estudos sobre o papel dessas espécies na etiologia das periodontites e ajudar a estabelecer tratamentos mais eficazes para essas infecções.

The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review.

OBJECTIVE: The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. MATERIAL AND METHODS: An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT) that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP) at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. RESULTS: The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm) than subjects taking antibiotics after healing (p<0.05). This comparison was conducted 2 months after antibiotic intake, at the healing phase. CONCLUSION: To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods.

The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review

Objective The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. Material and Methods An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT) that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP) at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. Results The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm) than subjects taking antibiotics after healing (p<0.05). This comparison was conducted 2 months after antibiotic intake, at the healing phase. Conclusion To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods. .