Adjunctive Systemic Antibiotics Research Articles

The role of the oral microbiota in the causal effect of adjunctive antibiotics on clinical outcomes in stage III–IV periodontitis patients

BackgroundPeriodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota’s composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy’s efficacy, have lasting effects on the oral microbiome. However, the precise mechanism through which the oral microbiome influences clinical outcomes in periodontitis patients remains debated. This investigation explores the pivotal role of the oral microbiome's composition in mediating the outcomes of adjunctive systemic antibiotic treatment.MethodsSubgingival plaque samples from 10 periodontally healthy and 163 periodontitis patients from a randomized clinical trial on periodontal therapy were analyzed. Patients received either adjunctive amoxicillin/metronidazole or a placebo after mechanical periodontal treatment. Microbial samples were collected at various intervals up to 26 months post-therapy. Using topic models, we identified microbial communities associated with normobiotic and dysbiotic states, validated with 86 external and 40 internal samples. Logistic regression models evaluated the association between these microbial communities and clinical periodontitis parameters. A Directed Acyclic Graph (DAG) determined the mediating role of oral microbiota in the causal path of antibiotic treatment effects on clinical outcomes.ResultsWe identified clear distinctions between dysbiotic and normobiotic microbial communities, differentiating healthy from periodontitis subjects. Dysbiotic states consistently associated with below median %Pocket Probing Depth ≥ 5 mm (OR = 1.26, 95% CI [1.14–1.42]) and %Bleeding on Probing (OR = 1.09, 95% CI [1.00–1.18]). Factors like microbial response to treatment, smoking, and age were predictors of clinical attachment loss progression, whereas sex and antibiotic treatment were not. Further, we showed that the oral microbial treatment response plays a crucial role in the causal effect of antibiotic treatment on clinical treatment outcomes.ConclusionsThe shift towards a normobiotic subgingival microbiome, primarily induced by adjunctive antibiotics, underscores the potential for microbiome-targeted interventions to enhance therapeutic efficacy in chronic inflammatory conditions. This study reaffirms the importance of understanding the oral microbiome's role in periodontal health and paves the way for future research exploring personalized treatment strategies based on individual microbiome profiles.D_npUcg1WaKKucWMF28BqgVideo

The association between periodontal microbial biomarkers and primary therapy outcome

ObjectiveThis study aims to analyse the association between the baseline microbial load of selected periodontopathogenic bacteria collected from gingival crevicular fluid (GCF) and the primary outcome of steps I and II therapy.Materials and methods222 patients with stage III periodontitis were included into this retrospective analysis that received steps 1 and 2 periodontal therapy without adjunctive systemic antibiotics. Baseline GCF samples were quantitatively analysed using ELISA-based kits for levels of periodontopathogens (Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Treponema denticola (Td), and Tannerella forsythia (Tf)) and associated with the primary therapy outcome using a “treat-to-target” therapy endpoint (TE) defined as ≤ 4 sites with PD ≥ 5 mm six months after therapy.Results38.2% of the patients achieved TE. Patients failing to achieve TE revealed significantly increased levels of Pg, Fn, and Tf at baseline (Pg: p = 0.010, Fn: p = 0.008 Tf: p = 0.004). Multivariate binary logistic regression adjusted for sex, mean probing depth, diabetes, and current smoking status showed an independent relationship between Tf and the TE (aOR 2.570, p = 0.023).ConclusionIncreased microbial load is associated with decreased responsiveness to therapy. The findings suggest that specifically baseline Tf levels are associated with poorer treatment outcomes and might improve the accuracy of periodontal diagnosis.Clinical relevanceThe findings of this study support the concept of a critical biomass that is sufficient to induce and maintain an immune response within the periodontal pocket, which ultimately leads to irreversible tissue destruction. However, calculating this level in advance may serve as an early indicator for intervention.Key findingBaseline Tannerella forsythia levels are associated with poorer treatment outcome.

Do systemic amoxicillin and metronidazole during the non-surgical peri-implantitis treatment phase prevent the need for future surgical treatment? A retrospective long-term cohort study.

The aim of this retrospective long-term follow-up of a 3-month RCT was to assess whether non-surgical peri-implantitis treatment with adjunctive systemic antibiotics influenced the need for additional surgical treatment. Patients enrolled in an aftercare programme following non-surgical peri-implantitis treatment, with or without systemic amoxicillin and metronidazole, were analysed. Data had previously been collected pre-treatment (T0) and 3 months after treatment (T1) and were additionally collected during subsequent aftercare visits, until the final assessment (T2). Primary outcome was the need for additional surgical peri-implantitis therapy during the aftercare programme, analysed via Kaplan-Meier analysis and Cox regression. Secondary outcomes involved clinical parameters, assessed using parametric and non-parametric tests. Forty-five patients (22 AB- group, 23 AB+ group) were included. The mean follow-up time between T1 and T2 was 35.9 months (SD = 21.0). 73.9% of the AB+ group and 50.0% of the AB- group did not receive additional surgical therapy (log-rank test, p = .110). The adjusted Cox regression model did not provide a significant result for antibiotics (β = .441, 95% CI = 0.159-1.220, p = .115). Univariable regression analysis highlighted the influence of baseline peri-implant pocket depth on the need for surgical treatment (β = 1.446, 95% CI = 1.035-2.020, p = .031). Systemic amoxicillin and metronidazole administered during non-surgical peri-implantitis treatment do not seem to prevent the need for additional surgical therapy in the long term, during a structured aftercare programme.

Comparative Study of Systemic vs. Local Antibiotics with Subgingival Instrumentation in Stage III-IV Periodontitis: A Retrospective Analysis.

To improve the clinical and microbiological outcomes of non-surgical mechanical periodontal therapy, the adjunctive use of antimicrobials has been utilized in treating moderate-to-severe periodontitis. In our study, the retrospective design included previously collected health-related patient data, obtained from the printed and digital charts of patients who received systemic or local antibiotic adjuncts to SI (subgingival instrumentation). A total of 34 patients (diagnosed with generalized Stage III/IV periodontitis) met the inclusion and exclusion criteria and were evaluated. The samples were tested for the following bacterial strains: Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Porphyromonas gingivalis (P. gingivalis), Prevotella intermedia (P. intermedia), Tanererella forsythia (T. forsythia), and Treponema denticola (T. denticola). The inter-group comparisons of the bacterial species did not show statistically significant differences between groups. The present study aimed to evaluate the clinical effects after SI and the adjunctive use of systemically administered (SA) AMX (amoxicillin) + MET (metronidazole) (administered for 7 days), with locally delivered (LDD) piperacillin + tazobactam in step 2 of periodontal therapy. Results: Overall, all parameters were improved in the groups, with a significant difference in inter-group comparison regarding the full-mouth bleeding score (FMBS) (p < 0.05) in favor of the SA group, and the p-value < 0.05 was considered to be statistically significant. Statistically significant PPD (probing pocket depth) reductions and CAL (clinical attachment level) gains were observed in both groups at the 3-month follow-up. In conclusion, within the limitations, the outcomes of this study suggest that SI, with adjunctive local or systemic antibiotic therapy, provided comparable clinical improvements. Systemic AMX + MET protocols were more efficacious with regard to the reduction in FMBS. Follow-up studies with larger patient numbers are needed to further investigate this effect.

Systemic antibiotics in the surgical treatment of peri-implantitis: A randomized placebo-controlled trial.

To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics. Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis. A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups. Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.

Treatment of peri-implantitis with a flapless surgical access combined with implant surface decontamination and adjunctive systemic antibiotics: A retrospective case series study.

To evaluate the effectiveness of a flapless surgical approach in the treatment of peri-implantitis and to explore the factors influencing its outcome. The present retrospective study evaluated patients with at least one implant diagnosed with peri-implantitis and treated with a flapless surgical access, with or without systemic antimicrobials, curettage and, when needed, prostheses modification. Clinical and radiographic parameters were assessed at baseline and at 3 months and at least 12 months. The primary outcome was disease resolution (≤1 bleeding sites, probing depth [PD] ≤5 mm, no bone loss >0.5 mm). Multilevel regression analyses were used to identify predictors influencing the probability of attaining disease resolution. One hundred and seventeen patients with 338 implants were included. Disease resolution was attained in 54.4% of the 338 implants receiving flapless surgical access. At the end of the follow-up period, 111 patients (94.9%) with 295 implants (87.3%) did not require any further treatment, with 81.4% of these implants presenting PD ≤ 5 mm. History of periodontitis and PD at baseline were identified as negative predictors, while compliance with supportive peri-implant care, a machined surface and the adjunctive use of systemic azithromycin or metronidazole were identified as positive predictive factors for disease resolution. A flapless surgical approach led to disease resolution in 54.4% of the implants with peri-implantitis. Several risk/protective predictors for disease resolution were identified.

Recent developments in the diagnosis, treatment, and management of Papillon-Lefèvre Syndrome.

A systematic search of PubMed, LIVIVO, and Ovid was conducted up to March 2021. These databases were searched for relevant clinical studies on periodontal treatment success in individuals with Papillon-Lefèvre syndrome (PLS). Clinical studies reporting successful treatment outcomes defined as the loss of four or fewer permanent teeth due to periodontitis and the arrest of periodontitis or probing depths of 5 mm or less in individuals with PLS followed up for ≥24 months were included, and data extracted. Twelve studies reporting on nine PLS patients met the inclusion criteria. The extracted main outcomes in the studies reporting successful periodontal treatment in PLS were as follows: (1) clinical and genetic diagnosis of PLS; (2) age at baseline; (3) initial dental, periodontal parameters, and microbiological assessment, if available; (4) description of disease progression and applied therapies; and (5) outcome and follow-up. Twelve studies reporting nine individuals were included. The timely extraction of affected or all primary teeth, compliance with oral hygiene instructions, supra- and subgingival debridement within frequent supportive periodontal care intervals, and adjunctive systemic antibiotic therapy in most patients affected a halt in disease progression. Suppression of Aggregatibacter actinomycetemcomitans below detection limits was associated with periodontal stabilization. An intensive, multidisciplinary approach with strict compliance may enable the decelerated progression of PLS-associated periodontitis. The early diagnosis of PLS and the suppression of A. actinomycetemcomitans below the detection level might be critical factors for treatment success. It required significant effort and patient compliance. The study emphasized the importance of timely interventions, oral hygiene maintenance, regular professional dental care, and, in some cases, systemic antibiotics.

Antibiotics in the non-surgical treatment of peri-implantitis.

Four electronic databases (MEDLINE via Pubmed; EMBASE via Ovid; EBSCO Dentistry and Oral Science Source), in addition to six related journals (Clinical Implant Dentistry and Related Research; Clinical Oral Implants Research; International Journal of Oral and Maxillofacial Implants; International Journal of Oral Implantology; Journal of Clinical Periodontology; Journal of Periodontology), were searched for publications until 2022. Randomised controlled trials (RCTs), evaluating the effectiveness of local or systemic antibiotics as an adjunct in the non-surgical treatment (NST) for peri-implantitis (PI), were assessed. The eligibility criteria included RCTs with a parallel group, split-mouth design and appropriate NST interventions over a three to twelve month period. Data were extracted from RCTs to capture a multitude of primary outcomes, including: implant success rate, radiographic marginal bone loss rate, periodontal health changes and PI resolution. Risk of bias assessments were made using the Cochrane Collaboration's tool, by two authors independently and in duplicate. RCTs with similar observation periods and interventions were included in the meta-analyses. Random-effects meta-analyses of mean differences or relative risks with 95% confidence intervals were calculated, in additional to data heterogeneity calibration through I2 statistics. Following the screening of 270 papers, six RCTs were included, which resulted in the evaluation of 391 patients (375 implants). Adjunctive local antibiotic therapy at disease sites showed statistically significant periodontal outcomes; improvements in success rate (risk ratio = 9.89; 95% CI 2.39-40.84), probing pocket depth (mean difference (MD) = 0.6 mm; 95% CI 0.42-0.78) and bleeding on probing (MD = 0.15%; 95% CI 0.10-0.19). Conversely, adjunctive systemic antibiotics improved probing pocket depths (MD = 1.15 mm; 95% CI 0.31-1.99) and probing attachment levels only (MD = 1.10 mm; 95% CI 0.13-2.08). Across the six included RCTs, the bone loss rate and PI resolution rate determined no significant differences between the groups; mirrored in the single studies and in the meta-analysis. Disease resolution ranged from 2 to 65%. Two of the studies were found to be at low risk of bias and four presented with some concerns. Adjunctive antibiotics aid NST. However, the heterogeneity of study methods and low quality of current RCTs evidenced, deem their role in NSTs of PI as inconclusive.

Antibiotics as Adjunctive Therapy in the Non-Surgical Treatment of Peri-Implantitis: A Systematic Review and Meta-Analysis.

The role of antibiotics as adjunctive therapy in the non-surgical treatment of peri-implantitis is uncertain. The aim of this systematic review of randomized controlled trials was to assess the efficacy of antibiotic therapy, local or systemic, as an adjunctive to the non-surgical therapy of peri-implantitis. Primary outcomes were: implant success rate and complications, changes in radiographic bone level, probing pocket depth (PPD), probing attachment level (PAL), bleeding on probing (BOP) and peri-implantitis resolution. Six studies were included: two using topical and four systemic antibiotics. Adjunctive local antibiotics improved PPD (mean difference (MD) = 0.6 mm; 95% CI 0.42-0.78), BOP (MD = 0.15% (95% CI 0.10, 0.19)) and the success rate (risk ratio = 9.89; 95% CI 2.39-40.84). No significant difference in bone level and success rate were found with the use of systemic antibiotics, although they appeared to improve PPD (MD = 1.15 mm; 95% CI 0.31-1.99) and PAL (MD = 1.10 mm; 95% CI 0.13-2.08). Within the limitations of this review, the adjunctive local antibiotics showed improved outcomes in terms of success rate, PPD and BOP, while adjunctive systemic antibiotics improved PPD and PAL only. Peri-implantitis resolution was about 20-30% using adjunctive local antibiotics, whilst it ranged from 2% to 65% with adjunctive systemic antibiotics. Findings are still controversial, since they are based on few studies with high heterogeneity, at the uncertain or high risk of bias and involve few patients. Non-surgical debridement and maintenance periodontal support therapy remain pivotal and the adjunctive use of antibiotics for peri-implantitis cannot be routinely recommended, even considering the increasing concern on antibiotic resistance.

The Role of Polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 Genes in Non-Surgical Periodontal Therapy.

Periodontitis is a multifactorial disease. The aim of this explorative study was to investigate the role of Interleukin-(IL)-1, IL-4, GATA-3 and Cyclooxygenase-(COX)-2 polymorphisms after non-surgical periodontal therapy with adjunctive systemic antibiotics (amoxicillin/metronidazole) and subsequent maintenance in a Caucasian population. Analyses were performed using blood samples from periodontitis patients of a multi-center trial (ClinicalTrials.gov NCT00707369=ABPARO-study). Polymorphisms were analyzed using quantitative real-time PCR. Clinical attachment levels (CAL), percentage of sites showing further attachment loss (PSAL) ≥1.3 mm, bleeding on probing (BOP) and plaque score were assessed. Exploratory statistical analysis was performed. A total of 209 samples were genotyped. Patients carrying heterozygous genotypes and single-nucleotide-polymorphisms (SNP) on the GATA-3-IVS4 +1468 gene locus showed less CAL loss than patients carrying wild type. Heterozygous genotypes and SNPs on the IL-1A-889, IL-1B +3954, IL-4-34, IL-4-590, GATA-3-IVS4 +1468 and COX-2-1195 gene loci did not influence CAL. In multivariate analysis, CAL was lower in patients carrying GATA-3 heterozygous genotypes and SNPs than those carrying wild-types. For the first time, effects of different genotypes were analyzed in periodontitis progression after periodontal therapy and during supportive treatment using systemic antibiotics demonstrating a slight association of GATA-3 gene locus with CAL. This result suggests that GATA-3 genotypes are a contributory but non-essential risk factor for periodontal disease progression.

Long-term prognosis of teeth with class III furcation involvement.

Evaluation of survival of teeth with class III furcation involvement (FI) ≥5 years after active periodontal treatment (APT) and identification of prognostic factors. All charts of patients who completed APT at the Department of Periodontology of Goethe-University Frankfurt, Germany, beginning October 2004 were screened for teeth with class III FI. APT had to be accomplished for ≥5 years. Charts were analysed for data of class III FI teeth at baseline (T0), at accomplishment of APT (T1), and at the last supportive periodontal care (T2). Baseline radiographic bone loss (RBL) and treatment were assessed. One-hundred and sixty patients (age: 54.4 ± 9.8 years; 82 females; 39 active smokers; 9 diabetics, 85 stage III, 75 stage IV, 59 grade B, 101 grade C) presented 265 teeth with class III FI. Ninety-eight teeth (37%) were lost during 110, 78/137 (median, lower/upper quartile) months. Logistic mixed-model regression and mixed Cox proportional hazard model associated adjunctive systemic antibiotics with fewer tooth loss (26% vs. 42%; p=.019/.004) and RBL (p=.014/.024) and mean probing pocket depth (PPD) at T1 (p < .001) with more tooth loss. Subgingival instrumentation with adjunctive systemic antibiotics favours retention of class III furcation-involved teeth. Baseline RBL and PPD at T1 deteriorate long-term prognosis.

Effect of adjunctive systemic antibiotics on microbial populations compared with scaling and root planing alone for the treatment of periodontitis: A pilot randomized clinical trial.

To investigate the microbial shift after periodontitis being treated by scaling and root planing (SRP) with or without adjunctive antibiotics, and to assess the relationship between oral microbiota and systemic factors. A 6-month pilot randomized controlled trial recruited 14 subjects with severe periodontitis, divided into test group and control group to receive full-mouth SRP with or without amoxicillin (500mg) and metronidazole (200mg) (three times a day for 7 days). Clinical examination, collection of subgingival plaque and saliva, and blood tests were performed at baseline pre-treatment, 3 months, and 6 months post-treatment. The V3V4 region of 16S DNA was sequenced; taxonomic assignment was based on the Human Oral Microbiome Database. The periodontal condition significantly improved in both groups; the test group showed a greater improvement in plaque index, probing depth, and bleeding index than the control group. The test group demonstrated significantly lower microbial richness and diversity, and less abundant Porphyromonas than the control group at 3 months for both subgingival microbiome and salivary microbiome. However, the microbial differences narrowed within 6 months. The subgingival and salivary microbiota shifted synergistically. Glucose was positively related to subgingival Porphyromonas; mean platelet volume was positively related to subgingival Leptotrichia. Systemic administration of amoxicillin and metronidazole along with SRP had an advantage over SRP alone in clinical improvement and infection control in both the subgingival region and saliva 3 months post-treatment. Microbial advantage nearly disappeared at 6 months; however, the clinical advantage lasted longer. The use of antibiotics also has potential benefits for systemic inflammation and glucose.

Mechanical Debridement with Antibiotics in the Treatment of Chronic Periodontitis: Effect on Systemic Biomarkers-A Systematic Review.

In this systematic review, we assessed the effectiveness of systemic antibiotics as an adjunctive therapy to mechanical debridement in improving inflammatory systemic biomarkers, as compared to mechanical debridement alone, among adults with chronic periodontitis. We searched relevant electronic databases for eligible randomized controlled trials. Two review authors independently screened, extracted data, and assessed risk of bias. We conducted meta-analysis, assessed heterogeneity, and assessed certainty of evidence using GRADEPro software. We included 19 studies (n = 1350 participants), representing 18 randomized controlled trials and found very little or no impact of antibiotics on inflammatory biomarkers. A meta-analysis of eight studies demonstrated a mean reduction of 0.26 mm in the periodontal pockets at three months (mean difference [MD] −0.26, 95%CI: −0.36 to −0.17, n = 372 participants, moderate certainty of evidence) in favor of the antibiotics. However, results from five studies reporting clinical attachment level (mm) yielded little or no difference at three months (MD −0.16, 95% CI: −0.35 to 0.03, n = 217 participants) between antibiotic and placebo groups. There is little or no evidence that adjunctive systemic antibiotics therapy improves inflammatory systemic biomarkers, compared to mechanical debridement alone, among adults with chronic periodontitis.

Effect of nonsurgical periodontal therapy on haematological parameters in grades B and C periodontitis: an exploratory analysis

AimAssessment of the effect of nonsurgical periodontal therapy on haematological parameters in patients with grades B (BP) and C periodontitis (CP).MethodsEight BP and 46 CP patients received full-mouth periodontal debridement within 48 h, if positive for Aggregatibacter actinomycetemcomitans with adjunctive systemic antibiotics (4 BP, 17 CP). Clinical data were collected prior and 12 weeks after periodontal therapy. Blood was sampled prior to and 1 day as well as 6 and 12 weeks after the first SD visit. Erythrocyte count, haemoglobin value, haematocrit (HCT), mean erythrocyte volume (MCV), mean corpuscular haemoglobin (MCH), MCH concentration (MCHC), platelets (PLT) and heat shock protein 27 (Hsp27) were assessed.ResultsBoth groups showed significant clinical improvement (p < 0.05). Using univariate analysis, MCV was noticeably lower in CP than BP at all examinations, HCT only at baseline. For CP, MCHC was noticeably higher 12 weeks after SD than at baseline and 1 day (p ≤ 0.005) and Hsp27 increased noticeably at 1 day (p < 0.05). Repeated measures analysis of variance revealed African origin to be associated with lower MCV and female sex with lower MCHC.ConclusionBased on multivariate analysis, periodontal diagnosis (BP/CP) was not associated with haematological parameters measured in this study or serum Hsp27. In CP, nonsurgical periodontal therapy improved MCHC 12 weeks after SD. Also in CP Hsp27 was increased 1 day after SD.

Effects of timing of adjunctive systemic antibiotics on the clinical outcome of periodontal therapy: A systematic review.

BackgroundMany systematic reviews and meta-analysis have indicated beneficial effects of adjunctive systemic antibiotics in periodontal therapy in specific situations. However, some essential issues such as the ideal time of their administration during periodontal therapy remain unanswered. This systematic review aimed to determine at which phase of periodontal treatment would adjunctive systemic antibiotics lead to the best clinical outcomes, during the active phase or in the reevaluation phase. Material and MethodsSearches in the databases Medline, Scopus and Cochrane Library were conducted. The randomized clinical trials and retrospective cohort studies comparing the clinical benefits of adjunctive systemic antibiotic administration in the active phase of periodontal treatment versus their administration in the reevaluation phase were included. The primary outcomes assessed were differences in clinical changes in periodontal pocket depth and clinical attachment loss at all post-treatment phases. ResultsOf the 6209 records identified, two randomized clinical trials and two retrospective cohort studies were eligible according to inclusion criteria. Two studies suggested there were greater clinical benefits when systemic antibiotics were prescribed during the active phase of periodontal therapy than in the reevaluation phase while two other studies showed no significant difference in clinical outcomes at 6 months between these two different timing of administration. ConclusionsThe evidence available and evaluated in this systematic review is of heterogeneous quality and limited by the restricted number of studies and their dissimilarities in their study design and outcome reporting. Despite insufficient evidence to determine the ideal time to the adjunctive systemic antibiotic administration in the periodontal therapy, it seems that prescription of systemic antibiotic at the active phase of periodontal therapy leads to better clinical outcomes. Key words:Active phase; periodontal therapy, periodontitis, reevaluation, systemic antibiotics, timing.

Adjunctive antibiotic therapy in cases of periodontitis and peri-implantitis

Introduction Periodontitis and peri-implantitis are plaque-induced diseases, which are associated with certain bacteria. The conventional treatment aims primarily at tooth or implant surface debridement. In certain cases, surgical therapy is necessary. To improve the outcome of the treatment, systemic or topical antibiotics could be considered. Aim The aim of this review is to investigate the effect of the adjunctive systemically or topically delivered antibiotics on the outcome of the periodontitis and peri-implantitis treatment. Materials and Methods Articles related to the topic were searched in the PubMed database. Articles published from 2000 to 2019, only in English language, were included in the review. The search was conducted with a variety of keywords in different combinations being used. These were: “periodontitis”, “peri-implantitis”, “antibiotic”, “local”, “metronidazole”, “amoxicillin”, “azithromycin”, “tetracycline”. Results Forty-seven articles were included in the review. The selected articles described the adjunctive systemic and/or local delivery of metronidazole, azithromycin, the combination of metronidazole and amoxicillin and some representatives of the tetracycline group, such as doxycycline and minocycline in cases of periodontitis and peri-implantitis. Conclusion The adjunctive systemic and topical antibiotic therapy could benefit the outcome of periodontitis and peri-implantitis treatment.

Periodontal therapy increases neutrophil extracellular trap degradation.

In periodontitis, polymorphonuclear leucocytes (PMNs) are activated. They entrap and eliminate pathogens by releasing neutrophil extracellular traps (NETs). Abnormal NET degradation is part of a pro-inflammatory status, affecting co-morbidities such as cardiovascular disease. We aimed to investigate the ex vivo NET degradation capacity of plasma from periodontitis patients compared to controls (part 1) and to quantify NET degradation before and after periodontal therapy (part 2). Fresh NETs were obtained by stimulating blood-derived PMNs with phorbol 12-myristate 13-acetate. Plasma samples from untreated periodontitis patients and controls were incubated for 3 h onto freshly generated NETs (part 1). Similarly, for part 2, NET degradation was studied for 91 patients before and 3, 6 and 12 mo after non-surgical periodontal therapy with and without adjunctive systemic antibiotics. Finally, NET degradation was fluorospectrometrically quantified. NET degradation levels did not differ between periodontitis patients and controls, irrespective of subject-related background characteristics. NET degradation significantly increased from 65.6 ± 1.7% before periodontal treatment to 75.7 ± 1.2% at 3 mo post periodontal therapy, and this improvement was maintained at 6 and 12 mo, irrespective of systemic usage of antibiotics. Improved NET degradation after periodontitis treatment is another systemic biomarker reflecting a decreased pro-inflammatory status, which also contributes to an improved cardiovascular condition.

Nonsurgical Periodontal Therapy: a Review of Current Standards of Care and Innovations to Improve Gingival and Periodontal Health

Regular home care delivered by patients as well as professional mechanical debridement is a cornerstone of periodontal and peri-implant health. This report will examine current therapies for nonsurgical periodontal and peri-implant diseases, including oral hygiene measures and behavioral modification, scaling and root planing, adjunctive systemic and local antibiotic therapy, and novel pharmacologic and physical adjunctive treatments. Periodontitis is a highly prevalent, destructive disease and has been estimated to result in $54 billion of lost productivity yearly worldwide. Additionally, it is estimated that up to 5 million dental implants are placed each year and, with the increasing number of implants comes increasing numbers of cases of peri-implant mucositis and peri-implantitis. Nonsurgical therapy is the first line of treatment and long-term prevention for both of these conditions. Mechanical therapy requires a high level of operator skill and an understanding of expected results and the modifiers which may affect treatment outcomes. Proper patient selection, patient compliance, and assessment of optimal treatment options are required for successful results of therapy. Adjunctive therapy in high-risk patients, for example, smokers, may improve treatment outcomes, and care should be taken to select adjunctive therapies based upon their mechanisms of action and the deficits in host defense noted in patients with additional risk factors. Furthermore, long-term maintenance and surveillance of disease recurrence are necessary in the management of these chronic diseases. Nonsurgical therapy is a cost-effective intervention to address periodontal diseases, and patients with select risk factors may receive additional benefit when adjunctive therapies are employed during this phase of treatment.

Comparing the periodontal tissue response to non-surgical scaling and root planing alone, adjunctive azithromycin, or adjunctive amoxicillin plus metronidazole in generalized chronic moderate-to-severe periodontitis: a preliminary randomized controlled trial.

The usefulness of administrating adjunctive systemic antibiotics to expedite healing of periodontal tissues is a topic of interest given the lack of clear guidelines. To compare clinical outcomes in patients given adjunctive azithromycin (AZ), adjunctive amoxicillin plus metronidazole (AMX+MTZ), or scaling and root planing (SRP) alone in the treatment of moderate-to-severe chronic periodontitis. Thirty-eight patients were randomly assigned into: SRP alone; 500mg AMX plus 400mg MTZ three times per day for 7days; or 500mg AZ for 3days. Antibiotics were administered after the first SRP session and clinical parameters for full-mouth and baseline probing pocket depth (PPD) categories were reviewed 2-months post-treatment. Thirty-four of 38 patients completed the study. All groups experienced significant improvements in full-mouth clinical attachment level (CAL), probing pocket depth (PPD) and bleeding on probing. AZ exhibited greater reductions in PPD than SRP alone for baseline severe sites, whilst AMX+MTZ showed significant improvements in PPD and CAL than SRP alone for baseline moderate and severe sites. Of the two antibiotic therapies, AMX+MTZ showed greater reductions in PPD compared with AZ in baseline moderate sites only. For patients with moderate-to-severe periodontitis, adjunctive systemic antibiotics might result in greater clinical benefits.

Effect of Periodontal Treatment on HbA1c among Patients with Prediabetes

Evidence is limited regarding whether periodontal treatment improves hemoglobin A1c (HbA1c) among people with prediabetes and periodontal disease, and it is unknown whether improvement of metabolic status persists >3 mo. In an exploratory post hoc analysis of the multicenter randomized controlled trial “Antibiotika und Parodontitis” (Antibiotics and Periodontitis)—a prospective, stratified, double-blind study—we assessed whether nonsurgical periodontal treatment with or without an adjunctive systemic antibiotic treatment affects HbA1c and high-sensitivity C-reactive protein (hsCRP) levels among periodontitis patients with normal HbA1c (≤5.7%, n = 218), prediabetes (5.7% < HbA1c < 6.5%, n = 101), or unknown diabetes (HbA1c ≥ 6.5%, n = 8) over a period of 27.5 mo. Nonsurgical periodontal treatment reduced mean pocket probing depth by >1 mm in both groups. In the normal HbA1c group, HbA1c values remained unchanged at 5.0% (95% CI, 4.9% to 6.1%) during the observation period. Among periodontitis patients with prediabetes, HbA1c decreased from 5.9% (95% CI, 5.9% to 6.0%) to 5.4% (95% CI, 5.3% to 5.5%) at 15.5 mo and increased to 5.6% (95% CI, 5.4% to 5.7%) after 27.5 mo. At 27.5 mo, 46% of periodontitis patients with prediabetes had normal HbA1c levels, whereas 47.9% remained unchanged and 6.3% progressed to diabetes. Median hsCRP values were reduced in the normal HbA1c and prediabetes groups from 1.2 and 1.4 mg/L to 0.7 and 0.7 mg/L, respectively. Nonsurgical periodontal treatment may improve blood glucose values among periodontitis patients with prediabetes (ClinicalTrials.gov NCT00707369).