Microbiological effects of amoxicillin plus metronidazole in the treatment of young patients with Stages III and IV periodontitis: A secondary analysis from a 1-year double-blinded placebo-controlled randomized clinical trial.

BACKGROUND: Despite the body of evidence supporting the clinical benefits of metronidazole (MTZ) and amoxicillin (AMX) in the treatment of young patients with periodontitis, the microbiological outcomes of this antibiotic protocol have been less explored. This study evaluated the microbiological effects of adjunctive MTZ+AMX in the treatment of young patients with periodontitis. METHODS: Subjects with periodontitis Stages III or IV and ≤30 years old were randomly allocated to receive scaling and root planing (SRP) with placebo (n = 15) or with MTZ (400 mg) and AMX (500 mg) three times a day for 14 days (n = 15). Nine subgingival biofilm samples per subject (three samples from each probing depth (PD) category: ≤3, 4-6, and ≥7 mm) were collected at baseline and 3-, 6-, and 12-months post-treatment and individually analyzed for 40 bacterial species by checkerboard DNA-DNA hybridization. RESULTS: Thirty subjects (15/group) with mean ages 27.6 ± 3.5 (control) and 26.8 ± 3.9 (test) were included. At 12 months post-therapy, the antibiotic group harbored lower proportions of red complex (1.3%) than the placebo group (12.5%) (p < 0.05). SRP + MTZ+AMX was more effective than mechanical treatment in reducing levels/proportions of several pathogens and increasing proportions of Actinomyces species (p < 0.05). Levels/proportions of Aggregatibacter actinomycetemcomitans were only reduced in the antibiotic group (p < 0.05). This group also exhibited greater reduction in the number of sites with PD ≥5 mm and higher percentage of subjects reaching the clinical end point for treatment (≤4 sites with PD ≥5 mm) than the control group (p < 0.05). CONCLUSION: SRP+MTZ+AMX allowed for establishing a long-term healthier subgingival biofilm community and periodontal clinical condition, than SRP only.

Adverse events of metronidazole and amoxicillin: Retrospective analysis of a large data set of five randomized clinical trials.

AIM: To evaluate the frequency of side effects associated with intake of metronidazole (MTZ) + amoxicillin (AMX) in periodontal treatment, and to explore associations between these events and patients' features. MATERIALS AND METHODS: Data of five randomized clinical trials testing MTZ + AMX adjunctive to mechanical therapy were evaluated. Volunteers answered an adverse event questionnaire. RESULTS: Information from 656 subjects was assessed. The frequency of side effects in the antibiotic- and placebo-treated groups ranged from 1.0% to 17.7% and 0.9% to 13.7%, respectively. The events more frequently observed in the antibiotic than in the placebo group were diarrhoea and metallic taste (p < .05). Diabetes significantly raised the odds of a patient reporting discomfort (odds ratio [OR] = 2.6), diarrhoea (OR = 4.0), weakness (OR = 6.0) and excessive sleepiness (OR = 2.9). In systemically healthy volunteers, using antibiotics 3 months post-mechanical treatment (healing phase) (OR = 3.0), being a woman (OR = 3.9) and aged ≤49 (OR = 4.5) significantly increased the chances of reporting adverse events. CONCLUSIONS: The occurrence of side effects during MTZ + AMX treatment ranged from uncommon (1%) to very common (17.7%). The main factors raising the chances of a patient reporting adverse events were diabetes and taking antibiotics in the healing phase, instead of in the active phase of treatment. Patients ≤ 49 years old and females also tend to report more side effects.

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.

Effects of periodontal therapy on GCF cytokines in generalized aggressive periodontitis subjects.

AIM: To examine changes in levels of gingival crevicular fluid (GCF) cytokines, after periodontal therapy of generalized aggressive periodontitis (GAgP). MATERIALS AND METHODS: Twenty-five periodontally healthy and 24 GAgP subjects had periodontal clinical parameters measured and gingival crevicular fluid (GCF) samples collected from up to 14 sites/subject. GCF samples were analysed using multiplex bead immunoassay for: GM-CSF, IFN-γ, IL-10, IL-1ß, IL-2, IL-6 and TNF-α. Aggressive periodontitis subjects were randomly assigned to either scaling and root planing (SRP) alone or SRP plus systemic amoxicillin (500 mg) and metronidazole (400 mg) 3 times a day for 14 days. Clinical parameters and GCF cytokines were re-measured 6 months after treatment. Differences over time were analysed using the Wilcoxon test and between groups using the Mann-Whitney test. RESULTS: Significant reductions in GCF GM-CSF, IL-1ß and the ratio IL-1ß/IL-10 and increases in GCF IL-6 were detected after therapy. The mean change in GCF cytokines did not differ significantly between groups. CONCLUSIONS: Periodontal therapy improved GCF cytokine profiles by lowering IL-1ß and increasing IL-10 levels. The reduction in GCF GM-CSF after therapy implicates this cytokine in the pathogenesis of GAgP. There was no difference between therapies in changes of GCF cytokines.

Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis.

AIM: The aim of this study was to evaluate the clinical and microbiological effects of scaling and root planing (SRP) alone or combined with metronidazole (MTZ) and amoxicillin (AMX) in the treatment of subjects with generalized aggressive periodontitis (GAgP). MATERIALS AND METHODS: A double-blind, placebo-controlled, randomized clinical trial was conducted in 30 subjects receiving SRP alone or combined with MTZ (400 mg 3 x per day) and AMX (500 mg 3 x per day) for 14 days. Clinical and microbiological examinations were performed at baseline and 3 months post-SRP. Nine subgingival plaque samples per subject were analysed using checkerboard DNA-DNA hybridization. RESULTS: Subjects receiving MTZ and AMX showed the greatest improvements in the mean full-mouth probing depth and clinical attachment level and at initially intermediate and deep sites. The most beneficial changes in the microbial profile were also observed in the MTZ+AMX group, which showed the lowest proportions of the red complex as well as a significant decrease in the proportions of the orange complex after treatment. The antibiotic therapy also reduced the levels of Aggregatibacter actinomycetemcomitans at initially deep sites. CONCLUSION: Subjects with GAgP significantly benefit from the adjunctive use of MTZ and AMX. The short-term advantages are observed in the clinical and microbiological parameters.

Serum levels of cytokines in subjects with generalized chronic and aggressive periodontitis before and after non-surgical periodontal therapy: a pilot study.

BACKGROUND: The emergence of periodontal medicine has increased interest in defining the serologic profiles of inflammatory mediators in subjects with periodontitis. Thus, the aim of this pilot study is to evaluate the serum levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and interleukin (IL)-4, -17, and -23 in subjects with generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP) before and after non-surgical periodontal therapy. METHODS: Cytokines were measured by enzyme-linked immunosorbent assay in serum samples taken from 42 systemically healthy subjects divided according to periodontal status into subjects with GAgP (n = 14) and GCP (n = 14) and periodontally healthy (PH) subjects (n = 14). In addition, the levels of cytokines were reassessed at 6 months after periodontal therapy in the periodontitis groups. Clinical parameters were also evaluated at baseline and 6 months post-therapy. RESULTS: After therapy, both periodontitis groups demonstrated a significant improvement in clinical periodontal status (P <0.05). At baseline, concentrations of TNF-alpha (P = 0.0006) and IL-17 (P = 0.02) were significantly higher in the GAgP group compared to the other groups. There was a significant decrease in serum concentrations of TNF-alpha (P = 0.03) and IL-17 (P = 0.04) at 6 months post-therapy in the GAgP group (P <0.05). The concentration of TNF-alpha remained elevated in the GAgP group compared to the PH group at 6 months post-therapy (P = 0.04). CONCLUSIONS: Subjects with GAgP presented higher levels of TNF-alpha and IL-17 than subjects with GCP and PH subjects. In addition, although the serum levels of these cytokines improved significantly as a result of periodontal therapy, the levels of TNF-alpha remained higher in subjects with GAgP compared to PH subjects.

Microbiological profile of untreated subjects with localized aggressive periodontitis.

AIM: The microbial profile of localized aggressive periodontitis (LAgP) has not yet been determined. Therefore, the aim of this study was to evaluate the subgingival microbial composition of LAgP. MATERIAL AND METHODS: One hundred and twenty subjects with LAgP (n=15), generalized aggressive periodontitis (GAgP, n=25), chronic periodontitis (ChP, n=30) or periodontal health (PH, n=50) underwent clinical and microbiological assessment. Nine subgingival plaque samples were collected from each subject and analysed for their content of 38 bacterial species using checkerboard DNA-DNA hybridization. RESULTS: Red complex and some orange complex species are the most numerous and prevalent periodontal pathogens in LAgP. The proportions of Aggregatibacter actinomycetemcomitans were elevated in shallow and intermediate pockets of LAgP subjects in comparison with those with GAgP or ChP, but not in deep sites. This species also showed a negative correlation with age and with the proportions of red complex pathogens. The host-compatible Actinomyces species were reduced in LAgP. CONCLUSION: A. actinomycetemcomitans seems to be associated with the onset of LAgP, and Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Campylobacter gracilis, Eubacterium nodatum and Prevotella intermedia play an important role in disease progression. Successful treatment of LAgP would involve a reduction in these pathogens and an increase in the Actinomyces species.