Influence of gender on periodontal outcomes: A retrospective analysis of eight randomized clinical trials.

AIMS: To explore the influence of gender on periodontal treatment outcomes in a dataset of eight RCTs conducted in Brazil, United States, and Germany. METHODS: Clinical parameters were compared between men and women with stages III/IV grades B/C generalized periodontitis at baseline and 1-year post-therapy, including scaling and root planing with or without antibiotics. RESULTS: Data from 1042 patients were analyzed. Men presented a tendency towards higher probing depth (p = .07, effect size = 0.11) and clinical attachment level (CAL) than women at baseline (p = .01, effect size = 0.16). Males also presented statistically significantly lower CAL gain at sites with CAL of 4-6 mm at 1-year post-therapy (p = .001, effect size = 0.20). Among patients with Grade B periodontitis who took antibiotics, a higher frequency of women achieved the endpoint for treatment (i.e., ≤4 sites PD ≥5 mm) at 1 year than men (p < .05, effect size = 0.12). CONCLUSION: Men enrolled in RCTs showed a slightly inferior clinical response to periodontal therapy in a limited number of sub-analyses when compared to women. These small differences did not appear to be clinically relevant. Although gender did not dictate the clinical response to periodontal treatment in this population, our findings suggest that future research should continue to explore this topic.

Effect of Processing Methods of Human Saliva on the Proteomic Profile and Protein-Mediated Biological Processes.

The use of saliva as a protein source prior to microbiological and biological assays requires previous processing. However, the effect of these processing methods on the proteomic profile of saliva has not been tested. Stimulated human saliva was collected from eight healthy volunteers. Non-processed saliva was compared with 0.22 µm filtered, 0.45 µm filtered, and pasteurized saliva, by liquid chromatography-mass spectrometry. Data are available via ProteomeXchange with identifier PXD039248. The effect of processed saliva on microbial adhesion was tested using bacterial and fungus species and in biological cell behavior using HaCaT immortalized human keratinocytes. Two hundred and seventy-eight proteins were identified in non-processed saliva, of which 54 proteins (≈19%) were exclusive. Saliva processing reduced identified proteins to 222 (≈80%) for the 0.22 µm group, 219 (≈79%) for the 0.45 µm group, and 201 (≈72%) for the pasteurized saliva, compared to non-processed saliva. The proteomic profile showed similar molecular functions and biological processes. The different saliva processing methods did not alter microbial adhesion (ANOVA, p > 0.05). Interestingly, pasteurized saliva reduced keratinocyte cell viability. Saliva processing methods tested reduced the proteomic profile diversity of saliva but maintained similar molecular functions and biological processes, not interfering with microbial adhesion and cell viability, except for pasteurization, which reduced cell viability.

Oral microbial colonization on titanium and polyetheretherketone dental implant healing abutments: An in vitro and in vivo study.

STATEMENT OF PROBLEM: Although polyetheretherketone (PEEK) implant healing abutments have become popular because of their esthetic, mechanical, and chemical properties, studies analyzing oral polymicrobial adhesion to PEEK abutments are lacking. PURPOSE: The purpose of this in vitro and in vivo study was to evaluate oral microbial adhesion and colonization on titanium (Ti) and PEEK healing abutments. MATERIAL AND METHODS: Ti (N=35) and PEEK substrates (N=35) were evaluated in vitro in terms of the initial adhesion (1 hour) or biofilm accumulation (48 hours) of Candida albicans and a polymicrobial inoculum using stimulated human saliva to mimic a diverse oral microbiome. Surface decontamination ability was evaluated after 24 hours of in vitro biofilm formation after exposure to an erbium-doped yttrium aluminum garnet (Er:YAG) laser. Conventional and flowable composite resin veneering on PEEK was also tested for microbial adhesion. In addition, an in vivo model with 3 healthy volunteers was conducted by using a palatal appliance containing the tested materials (3 or 4 specimens of each material per appliance) for 2 days to evaluate the effect of substrate on the microbial profile. Biofilms were evaluated by live cell counts and scanning electron microscopy images, and the microbial profile by Checkerboard deoxyribonucleic acid (DNA)-DNA hybridization. The t test and Mann-Whitney test were used to compare the groups (α=.05). RESULTS: PEEK and Ti materials showed similar fungal adhesion (P>.05). Although the PEEK surface limited the initial in vitro polymicrobial adhesion (approximately 2 times less) compared with Ti (P=.040), after 48 hours of biofilm accumulation, the microbial load was statistically similar (P=.209). Er:YAG laser decontamination was more effective on PEEK than on Ti surfaces, reducing approximately 11 times more microbial accumulation (P=.019). Both composite resins tested showed similar microbial adhesion (1 hour). In vivo, the PEEK material showed reduced levels of 6 bacterial species (P<.05), including the putative pathogen Treponema denticola. CONCLUSIONS: Although PEEK and Ti had similar bacterial and fungus biofilm attachment and accumulation, PEEK promoted a host-compatible microbial profile with a significantly reduced T. denticola load.

Systematic and scoping reviews to assess biological parameters.

INTRODUCTION: An evidence synthesis approach compiling biological/laboratory data is effective in advancing health-related knowledge. However, this approach is still underused in the oral health field. METHODS: This commentary discusses the opportunities and challenges of systematic and scoping reviews of laboratory data in dentistry. Special focus is on the potential of these reviews to elucidate etiological and treatment concepts of oral diseases, such as periodontitis and peri-implantitis. RESULTS: The following difficulties associated with such studies are discussed: (i) selection of ideal study design, (ii) assessment of "risk of bias" and definition of "certainty of evidence", (iii) evidence assembly and summary, and (iv) the paper review process. DISCUSSION: Despite those challenges, high-quality reviews integrating laboratory data may generate relevant scientific information and help identify new avenues for future investigations. Experts in different oral health topics should build a process capable of helping researchers assemble and interpret these types of data.

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.

Level of patient comfort and measurement reproducibility of three different probes: A cross-sectional study.

OBJECTIVE: To determine the comfort level and reproducibility assessment of the probing pocket depth obtained with three different probes. METHODS: A cross-sectional clinical study was conducted in accordance with the STROBE standards. Three different types of periodontal probes were selected: (1) University of North Carolina (UNC) probe, (2) World health organization (WHO) probe and (3) UNC12 COLORVUE probe. Three experienced and calibrated periodontists performed periodontal clinical assessments (probing depth) and pain assessment with the visual analogue scale (VAS). RESULTS: The clinical evaluations were carried out in 13 volunteers who attended the dental clinic of the Universidad Científica del Sur (Lima, Peru). A total of 2106 periodontal clinical measurements were obtained (702 measurements per examiner). Each examiner evaluated 234 sites for each type of probe. When patient comfort values during the periodontal evaluation performed with the 3 types of probes were compared, the patients evaluated with the UNC12 COLORVUE probe perceived less pain with a mean value of 0.61, followed by the WHO probe and the UNC probe. When evaluating the clinical measurements, the UNC probe was observed to obtain the greatest mean depth on probing 1.4 + 0.5 mm, while with the UNC12 Colorvue probe, the values obtained were 1.1 + 0.3 mm, and with the WHO probe, 1.2 + 0.4 mm. CONCLUSIONS: Based on the periodontal probe used, experience of the examiner and the patient, we can conclude that the UNC12 Colorvue probe was the instrument that promoted the greatest comfort or the slightest response to pain, followed by the WHO probe. However, the use of the WHO probe resulted in obtaining the lowest reproducibility among depths on probing. The UNC probe produced the highest response to pain in the patients.

Did Omics change periodontal therapy?

The starting point for defining effective treatment protocols is a clear understanding of the etiology and pathogenesis of a condition. In periodontal diseases, this understanding has been hindered by a number of factors, such as the difficulty in differentiating primary pathogens from nonpathogens in complex biofilm structures. The introduction of DNA sequencing technologies, including taxonomic and functional analyses, has allowed the oral microbiome to be investigated in much greater breadth and depth. This article aims to compile the results of studies, using next-generation sequencing techniques to evaluate the periodontal microbiome, in an attempt to determine how far the knowledge provided by these studies has brought us in terms of influencing the way we treat periodontitis. The taxonomic data provided, to date, by published association and elimination studies using next-generation sequencing confirm previous knowledge on the role of classic periodontal pathogens in the pathobiology of disease and include new species/genera. Conversely, species and genera already considered as host-compatible and others less explored were associated with periodontal health as their levels were elevated in healthy individuals and increased after therapy. Functional and transcriptomic analyses also demonstrated that periodontal biofilms are taxonomically diverse, functionally congruent, and highly cooperative. Very few interventional studies to date have examined the effects of treatment on the periodontal microbiome, and such studies are heterogeneous in terms of design, sample size, sampling method, treatment provided, and duration of follow-up. Hence, it is still difficult to draw meaningful conclusions from them. Thus, although OMICS knowledge has not yet changed the way we treat patients in daily practice, the information provided by these studies opens new avenues for future research in this field. As new pathogens and beneficial species become identified, future randomized clinical trials could monitor these species/genera more comprehensively. In addition, the metatranscriptomic data, although still embryonic, suggest that the interplay between the host and the oral microbiome may be our best opportunity to implement personalized periodontal treatments. Therapeutic schemes targeting particular bacterial protein products in subjects with specific genetic profiles, for example, may be the futuristic view of enhanced periodontal therapy.

Does enamel matrix derivative application provide additional clinical benefits in the treatment of maxillary Miller class I and II gingival recession? A systematic review and meta-analysis.

OBJECTIVE: This review aimed to evaluate the effects of enamel matrix derivative (EMD) in association with coronally advanced flap (CAF) or CAF + connective tissue graft (CTG) when compared with CAF alone or CAF + CTG for the treatment of gingival recessions (GR) in maxillary teeth. METHODS: Five databases and gray literature were searched up to April 2020, to find randomized clinical trials comparing the clinical effects of CAF + EMD versus CAF alone (first group) or CAF + CTG + EMD versus CAF + CTG (second group) in the treatment of Miller class I and II or Cairo type I gingival recessions (GR). Random effects model of mean differences was used to determine the GR reduction, gain in keratinized tissue width (KTW), and gain in clinical attachment level (CAL). The trial sequential analysis (TSA) was implemented to determine the optimal information size (OIS) and imprecision using the GRADE approach. Bayes factors were calculated as complementary statistical evidence of p value. RESULTS: From 1349 titles identified, 9 trials representing 336 GR were included. The meta-analysis showed a statistically significant difference for GR reduction and CAL gain in favor CAF + EMD (p ≤ 0.05). The additional effect of EMD showed a statistically significant difference in GR reduction in favor CAF + CTG + EMD (p ≤ 0.05). The differences in KTW gain proved to be not statistically significant in both comparison groups. The OIS were not met among meta-analyses. Evidence certainty according the GRADE approach proved to be moderate for GR reduction and gain in CAL, but very low for gain in KTW. CONCLUSION: The adjunctive application of EMD in the treatment of GR in maxillary teeth either with CAF or CTG provided moderate certainty evidence in favor of their use for reduction in GR and gain in CAL at 6 and 12 months. However, their effect on the increase in keratinized tissue band height showed very low evidence certainty for its use. CLINICAL RELEVANCE: To know if EMD could improve the results for root coverage.

Is the use of platelet-rich fibrin effective in the healing, control of pain, and postoperative bleeding in the palatal area after free gingival graft harvesting? A systematic review of randomized clinical studies.

OBJECTIVE: A systematic review (SR) was conducted to answer the following focused question based on PICO strategy: In patients who were submitted to harvesting palatal free gingival graft, could platelet-rich fibrin (PRF) application in comparison with another method improve the healing, pain, and control of postoperative bleeding in the palatal area in randomized clinical trials? METHODS: A SR was conducted according to the PRISMA guidelines. The MEDLINE (PubMed), Scopus, Embase, and Web of Science databases were searched, and hand searches were made, covering the period up to August 2020, for randomized clinical trials (RCTs) reporting the effect of PRF membrane in postoperative palatal healing management compared with any other methods. The risk of bias (RoB) of the studies included was assessed by using the RoB 2 tool. RESULTS: The electronic search strategy identified 150 articles. After title screening and abstract reading, 141 studies were excluded, and 9 full-text publications were comprehensively evaluated. Finally, 8 articles were included in the systematic review. Six studies showed that the PRF membrane was effective in improving wound healing during the first 2 weeks. As regards patient-centered outcomes, five studies showed that PRF promoted less postoperative pain. Finally, five studies that evaluated bleeding showed that the PRF membrane improved control of postoperative bleeding. RoB was classified as low in 4 studies, 3 with some concerns, and only one study did not describe the outcome data, and as this was missing, it was not possible to verify the protocol of data analysis for this study; therefore, it was classified as having high RoB. CONCLUSION: Within the limitations of this study, the collective evidence emerging from this SR may support the use of PRF membrane in the palatal area after free gingival graft harvesting. The results of this review must be interpreted with caution, due to the low number of RCTs included and high degree of heterogeneity among the PRF protocols. Further well-designed RCTs with accurate protocol and standard PRF parameters are required in order to gain clear understanding of the influence of PRF on wound healing and patient-centered outcomes. CLINICAL RELEVANCE: The use of PRF membrane for the protection of the palatal donor site following free gingival graft harvesting procedures improves wound healing and patients' quality of life.

Local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing in periodontitis: Randomized, placebo-controlled, double-blind split-mouth clinical trial.

OBJECTIVE: Assess a single local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing (SRP) in nonsurgical periodontal treatment (NPT). MATERIALS AND METHODS: Twenty healthy subjects with periodontitis received SRP+PLGA/PLA nanoparticles loaded with 50 µg of curcumin (N-Curc) or SRP+empty nanoparticles. Probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP) were monitored at baseline, 30, 90, and 180 days. IL-1α, IL-6, TNFα, and IL-10 in the gingival crevicular fluid (GCF) were assessed by ELISA, and counts of 40 bacterial species were determined by DNA hybridization at baseline, 3, 7, and 15 days post-therapy. RESULTS: PPD, CAL, and BOP were similarly and significantly improved in both experimental groups. There was no difference in GCF cytokine levels between experimental groups, although IL-6 was decreased at 3 days only in the N-Curc group. NPT reduced counts of red complex bacterial species in both groups. Veillonella Parvula counts increased significantly only in N-Curc group at 7 days, whereas Aggregatibacter actinomycetemcomitans counts increased significantly only in the control group from day 3 to day 15. CONCLUSION: We conclude that a single local administration of nanoencapsulated curcumin in periodontally diseased sites had no additive benefits to NPT. CLINICAL RELEVANCE: Our results showed that a single local application of curcumin-loaded nanoparticles associated with nonsurgical periodontal therapy did not improve clinical outcomes. Hence, our findings do not support the use of curcumin as an adjunct to nonsurgical periodontal therapy.

Titanium particles and ions favor dysbiosis in oral biofilms.

OBJECTIVE: To evaluate the effect of titanium (Ti) particles and ions on oral biofilm growth and composition. BACKGROUND: Particles and ions of Ti released from dental implants can trigger unfavorable biological responses in human cells. However, their effect on oral biofilms composition has not been tested. METHODS: In this blind in situ study, volunteers wore a palatal appliance containing Ti disks for 7 days to allow biofilm formation. Disks were then collected and biofilms were treated, in vitro, with Ti particles (0.75% and 1%), ions (10 and 20 ppm), or a combination of both (1% particles + 20 ppm ions). Biofilms exposed only to medium was used as control group. After 24 hours, biofilms were collected and analyzed by checkerboard DNA-DNA hybridization. Direct effects of Ti particles and ions on biofilm/cellular morphology were evaluated by transmission electron microscopy (TEM). RESULTS: Ti particles affected biofilm composition, increasing population of four bacterial species (P < .05), while Ti ions showed higher levels of putative pathogens from the orange complex with reduction in species from the yellow complex (P < .05), compared with control. The combination of particles + ions increased green complex and reduced yellow complex proportions (P < .05). TEM showed clusters of particles agglomerated in extracellular environment, while Ti ions were precipitated in both extracellular and intracellular sites. CONCLUSIONS: Ti products, especially Ti ions, have the potential to change the microbiological composition of biofilms formed on Ti surfaces. Therefore, the presence of Ti products around dental implants may contribute to microbial dysbiosis and peri-implantitis.

Extracellular biofilm matrix leads to microbial dysbiosis and reduces biofilm susceptibility to antimicrobials on titanium biomaterial: An in vitro and in situ study.

OBJECTIVES: To test the role of exopolysaccharide (EPS) polymers matrix to modulate the composition/virulence of biofilms growing on titanium (Ti) surfaces, the effect on antibiotic susceptibility, and whether a dual-targeting therapy approach for disrupted EPS matrix could improve the antimicrobial effect. MATERIALS AND METHODS: A microcosm biofilm model using human saliva as inoculum was used, and the microbial composition was assessed by checkerboard DNA-DNA hybridization. EPS-enriched biofilms virulence was tested using fibroblast monolayer. Povidone-iodine (PI) was used as EPS-targeting agent followed by amoxicillin + metronidazole antibiotic to reduce bacterial biomass using an in situ model. RESULTS: An EPS-enriched environment, obtained by sucrose exposure, promoted bacterial accumulation and led to a dysbiosis on biofilms, favoring the growth of Streptococcus, Fusobacterium, and Campylobacter species and even strict anaerobic species related to peri-implant infections, such as Porphyromonas gingivalis and Tannerella forsythia (~3-fold increase). EPS-enriched biofilm transitioned from a commensal aerobic to a pathogenic anaerobic profile. EPS increased biofilm virulence promoting higher host cell damage and reduced antimicrobial susceptibility, but the use of a dual-targeting approach with PI pre-treatment disrupted EPS matrix scaffold, increasing antibiotic effect on in situ biofilms. CONCLUSION: Altogether, our data provide new insights of how EPS matrix creates an environment that favors putative pathogens growth and shed light to a promising approach that uses matrix disruption as initial step to potentially improve implant-related infections treatment.

Acute periodontal lesions (periodontal abscesses and necrotizing periodontal diseases) and endo-periodontal lesions.

OBJECTIVE: To critically evaluate the existing literature on acute lesions occurring in the periodontium (periodontal abscesses [PA], necrotizing periodontal diseases [NPD], and endo-periodontal lesions [EPL]) to determine the weight of evidence for the existence of specific clinical conditions that may be grouped together according to common features. The ultimate goal is to support an objective classification system. IMPORTANCE: Although PA, NPD, and EPL occur with relatively low frequency, these lesions are of clinical relevance, because they require immediate management and might severely compromise the prognosis of the tooth. FINDINGS: In general, the evidence available to define these three conditions was considered limited. PA and EPL are normally associated with deep periodontal pockets, bleeding on probing, suppuration, and almost invariably, with pain. EPL are also associated with endodontic pathology. NPDs have three typical features: pain, bleeding, and ulceration of the gingival interdental papilla. The available data suggested that the prognosis of PA and EPL are worse in periodontitis than in nonperiodontitis patients. Lesions associated with root damage, such as fractures and perforations, had the worst prognosis. NPD progression, extent and severity mainly depended on host-related factors predisposing to these diseases. CONCLUSIONS: PA should be classified according to the etiological factors involved, with the most frequent being those occurring in pre-existing periodontal pockets. NPD are clearly associated with the host immune response, which should be considered in the classification system for these lesions. EPLs should be classified according to signs and symptoms that have direct impact on their prognosis and treatment, such as presence or absence of fractures and perforations, and presence or absence of periodontitis.

Clinical and microbiological effects of scaling and root planing, metronidazole and amoxicillin in the treatment of diabetic and non-diabetic subjects with periodontitis: A cohort study.

AIM: To evaluate if non-diabetic subjects with periodontitis respond better than subjects with type 2 diabetes to the treatment protocol of scaling and root planing (SRP), metronidazole (MTZ) and amoxicillin (AMX). MATERIAL AND METHODS: Diabetic and nondiabetic subjects with severe periodontitis received SRP + MTZ (400 mg/thrice a day [TID]) + AMX (500 mg/TID) for 14 days. Subgingival biofilm samples were analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species. Subjects were monitored at baseline, 3, 6 and 12 months post-therapy. RESULTS: Twenty-nine type 2 diabetics and 29 non-diabetic subjects participated of this study. Of the non-diabetics and diabetics, 68.9% and 75.9%, respectively, reached the clinical endpoint for treatment (≤4 sites with probing depth [PD] ≥5 mm) at 1 year post-therapy (p > 0.05). The diabetic group presented lower mean clinical attachment gain from baseline to 1 year post-therapy and higher mean proportions of the red and orange complexes than the non-diabetic group (p < 0.05). CONCLUSIONS: Non-diabetic subjects with severe periodontitis did not respond better than type 2 diabetic subjects to the treatment protocol of SRP + MTZ + AMX, both in terms of achieving the clinical endpoint for treatment and of PD improvement. Diabetic subjects exhibited a slightly worse microbiological response and showed a healing process more associated with gingival recession than the non-diabetics.

Effects of a toothpaste containing 0.3% triclosan in the maintenance phase of peri-implantitis treatment: 2-Year randomized clinical trial.

OBJECTIVE: To evaluate the effects of a toothpaste containing 0.3% triclosan in volunteers that have been treated for peri-implantitis and were enrolled in a maintenance program. MATERIAL AND METHODS: Subjects presenting at least one implant with peri-implantitis were selected. They received anti-infective surgical therapy, and sixty days post-surgery (baseline) were randomized into two groups, brushing twice/day for 2 years (a) with a toothpaste containing 0.3% triclosan+2.0% PVM/MA copolymer (GantrezTM )+1,450 ppm fluoride (test) or (b) with a toothpaste containing 1,450 ppm fluoride (control). They received clinical and microbiological monitoring at baseline, 3, 6, 12, 18, and 24 months, and professional maintenance every 3 months. RESULTS: A total of 102 subjects were enrolled (test: 48; control: 54). The control group showed loss of clinical attachment (CA) around treated implants over the course of the study (p < 0.05), while the test group was stable for this parameter. The difference between groups (0.55 mm) for CA change between baseline and 24 months (primary outcome variable) was statistically significant (p < 0.05). Red complex pathogens were only reduced in the test group at 24 months. The implants with no history of peri-implantitis in the test group had a significant reduction in the percentage of sites with bleeding on probing and in mean probing depth, throughout the study (p < 0.05). This improvement was not observed in the control group. CONCLUSION: A toothpaste containing 0.3% triclosan was more effective than a toothpaste without triclosan in maintaining a healthy peri-implant environment around treated implants and implants with no history of peri-implantitis during a 2-year maintenance program (ClinicalTrials.govNCT03191721).

Different antibiotic protocols in the treatment of severe chronic periodontitis: A 1-year randomized trial.

AIM: To evaluate the clinical effects of different dosages of metronidazole (MTZ) and durations of MTZ + amoxicillin (AMX) in the treatment of generalized chronic periodontitis (GChP). MATERIAL AND METHODS: Subjects with severe GChP were randomly assigned to receive scaling and root planing (SRP)-only, or combined with 250 or 400 mg of MTZ + AMX (500 mg) thrice a day (TID), for 7 or 14 days. Subjects were monitored for 1 year. RESULTS: One hundred and nine subjects were enrolled. At 1 year, 61.9% and 63.6% of the subjects receiving AMX + 250 or 400 mg of MTZ for 14 days, respectively, reached the clinical endpoint for treatment (≤4 sites with probing depth ≥5 mm), against 31.8% of those taking 250 or 400 mg of MTZ for 7 days (p < .05) and 13.6% of those receiving SRP-only (p < .05). Fourteen days of MTZ + AMX was the only significant predictor of subjects reaching the clinical endpoint at 1 year (OR, 5.26; 95% CI, 2.3-12.1, p = .0000). The frequency of adverse events did not differ among treatment groups (p > .05). CONCLUSION: The adjunctive use of 400 or 250 mg of MTZ plus 500 mg of AMX/TID/14 days offers statistically significant and clinically relevant benefits over those achieved with SRP alone in the treatment of severe GChP. The added benefits of the 7-days regimen in this population were less evident. (ClinicalTrials.gov NCT02735395).

Metronidazole may display anti-inflammatory features in periodontitis treatment: A scoping review.

AIM: Metronidazole (MTZ) is an antimicrobial agent used to treat anaerobic infections. It has been hypothesized that MTZ may also have anti-inflammatory properties, but the evidence is limited and has not been previously reviewed. Thus, this scoping review aimed to answer the following question: "What is the evidence supporting anti-inflammatory properties of metronidazole that are not mediated by its antimicrobial effects?" METHODS: A scoping review was conducted according to the PRISMA-ScR statement. Five databases were searched up to January 2023 for studies evaluating the anti-inflammatory properties of MTZ used as monotherapy for treating infectious and inflammatory diseases. RESULTS: A total of 719 records were identified, and 27 studies (21 in vivo and 6 in vitro) were included. The studies reported experimental evidence of MTZ anti-inflammatory effects on (1) innate immunity (barrier permeability, leukocyte adhesion, immune cell populations), (2) acquired immunity (lymphocyte proliferation, T-cell function, cytokine profile), and (3) wound healing/resolution of inflammation. CONCLUSION: Taken together, this scoping review supported a potential anti-inflammatory effect of MTZ in periodontitis treatment. We recommend that future clinical studies should be conducted to evaluate specific MTZ anti-inflammatory pathways in the treatment of periodontitis.

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.

Newly identified pathogens in periodontitis: evidence from an association and an elimination study.

We assessed the level of evidence for the presence of new periodontal pathogens by (i) comparing the occurrence of non-classical periodontal taxa between healthy vs. periodontitis patients (Association study); (ii) assessing the modifications in the prevalence and levels of these species after treatments (Elimination study). In the Association study, we compared the prevalence and levels of 39 novel bacterial species between periodontally healthy and periodontitis patients. In the Elimination study, we analyzed samples from periodontitis patients assigned to receive scaling and root planing alone or with metronidazole+ amoxicillin TID/ 14 days. Levels of 79 bacterial species (39 novel and 40 classic) were assessed at baseline, 3 and 12 months post-therapy. All samples were analyzed using Checkerboard DNA-DNA hybridization. Out of the 39 novel species evaluated, eight were categorized as having strong and four as having moderate association with periodontitis. Our findings suggest strong evidence supporting Lancefieldella rimae, Cronobacter sakazakii, Pluralibacter gergoviae, Enterococcus faecalis, Eubacterium limosum, Filifactor alocis, Haemophilus influenzae, and Staphylococcus warneri, and moderate evidence supporting Escherichia coli, Fusobacterium necrophorum, Spiroplasma ixodetis, and Staphylococcus aureus as periodontal pathogens. These findings contribute to a better understanding of the etiology of periodontitis and may guide future diagnostic and interventional studies.

Decontamination and Biomodification of Periodontally Affected Root Surface for Successful Regeneration: Is There Room for Improvement?

Periodontitis is a multifactorial inflammatory condition associated with an oral microbiome dysbiosis that results in gingival inflammation and clinical attachment loss. Periodontal therapies are based on scaling and root planing to disturb the bacterial biofilm mechanically and remove calculus and contaminated cementum. Research does not support the use of root modifiers for decontamination and biomodification of periodontally affected root surfaces. Standardized clinical trials in large populations, assessing biological and patient-reported outcome measures, are necessary to evaluate candidate biomaterials for decontamination and biomodification of periodontally affected root surfaces.