Study protocol:~This randomized clinical study will include 40 patients diagnosed with periodontitis stages 2 and 3. The investigation will be conducted at the Department of Periodontology and Oral Medicine, Faculty of Dental Medicine, University of Belgrade. The laboratory part of the research will be carried out at the Department of Human genetics at the Institutes of the Faculty of Dental Medicine in Belgrade. Patients will be divided into two groups. The test group will consist of 20 patients who will be prescribed a local antibiotic (LA group), while the control group will consist of 20 patients who will be prescribed systemic antibiotic therapy (SA group). The division of patients into groups will be done with randomization envelopes after the diagnostic procedure.~Upon clinical examination, clinical periodontal parameters such as periodontal probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI) will be recorded for each patient around every tooth. Previous to treatment, subgingival crevicular fluid will be sampled with paper points from periodontal pockets for laboratory analysis.~Sampling will be performed as follows: first, a relatively dry working field will be established using paper water rollers and air jets, and then 3 paper points (number 30 - marked in blue) will be applied for 30 seconds in the periodontal pocket area of the selected premolar/molar tooth with a depth of more than 5mm. The procedure will be repeated immediately in the same region, in order to obtain duplicate samples. After that, the paper points will be placed in Eppendorf tubes and immediately transported to the basic research laboratory, where they will be stored at a temperature of -80 Celsius degrees and where microbiological and molecular analyzes will be carried out.~After sampling, all patients will undergo a non-surgical (causal) phase of periodontal therapy, following a Full-mouth disinfection protocol. Three months after the NSPT, at the follow-up, clinical examination, detection of clinical parameters, and sampling procedure will be repeated. In the LA group, antibiotic will be applied after the NSPT, while in the SA group therapy will be prescribed at the beginning of the treatment. Locally will be applied a combination of piperacillin and tazobactam in gel form (Gelcide ®, Italmed MedTechDental, Florence, Italy) designed for use in the subgingival region. The local antibiotic will be applied using a syringe and a flexible blunt needle into the periodontal pockets 24 hours after the NSPT to achieve a relatively dry working field and avoid blood contamination. The administration will be done by quadrants and after application to one region, the dry field should be maintained for 5 minutes. After that, the patient should not rinse the oral cavity for 15 minutes. For systemic use in the SA group, patients will be prescribed a combination of Amoxicillin (Amoxicillin ®, 500mg, 3 times a day, 14 days) and Metronidazole (Orvagyl ®, 400mg, 3 times a day, 14 days).~Total bacterial count (TBC) and REL of proinflammatory cytokines TNF-α and IL-17 will be detected using the quantitative real-time polymerase chain reaction (qPCR) in a basic research laboratory at the Department of Human genetics, at the Institutes of the Faculty of Dental Medicine in Belgrade.
The main treatment of every patient with periodontitis is non-surgical periodontal treatment (NSPT) with the ultimate goal to arrest inflammation. Given the biofilm microorganisms associated etiology of the periodontitis, NSPT can be combined with adjunctive antimicrobial therapy. Hence, this randomized clinical trial aims to compare the clinical and microbiological effectiveness and relative expression levels (REL) of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) between local and systemic antibiotics as adjunctive therapy to NSPT in patents with periodontitis stages 2 and 3.