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.

Photodynamic therapy decrease immune-inflammatory mediators levels during periodontal maintenance.

Antimicrobial photodynamic therapy (aPDT) was introduced as a promising adjuvant therapy on the periodontal treatment. The aim of this study was to evaluate the effect of aPDT on inflammatory mediator levels in residual periodontal pockets of patients with severe chronic periodontitis under periodontal maintenance, during 12 months follow-up. A randomized controlled trial study was conducted in 28 patients with severe chronic periodontitis. After non-surgical periodontal treatment, patients with at least four teeth with residual pocket probing depth (PPD) ≥4 mm were randomly assigned to either aPDT or control group. The aPDT (low power laser: 660 nm, 40 mW, 90 J/cm2, methylene blue 0.01 %) was performed at baseline and 3, 6, and 9 months. Clinical parameters were collected before and 3 and 12 months after the intervention, and gingival crevicular fluid was collected in the same times, including 1 week after the intervention. Immunological evaluation was carried out using the Luminex assay which quantified the expression of ten cytokines: interleukin (IL)-1α, IL-1ß, IL-8, IL-1ra, fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-4, and IL-10. All clinical variables showed significant improvement for both groups, but there was no statistical difference between groups with no clinical benefits. IL-1α, IL-1ß, IL-8, and VEGF showed significant differences (p < 0.05) between groups, whereas IL-1ra mediators, IFN-γ, and IL-10 demonstrated a statistical difference (p < 0.01) over time in the same group. At any time, FGF, IL-4, and TNF-α showed no statistical difference between groups (p > 0.05). aPDT therapy can improve the benefits on inflammation control during the periodontal maintenance.