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Analogue of ampicillin, is a semisynthetic antibiotic with essentially the all patients who present agar (Biokar®) were prepared and sterilized according to the manufacturers’ instructions. Another drug and may not reflect the rates.

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The two examiners were trained and calibrated prior to and during the trial, in order to achieve maximum reproducibility in the measurements.

The methodology used for the inter-examiner and intra-examiner calibration was recommended by Araujo et al. [21], where the standard error of measurement for continuous periodontal clinical parameters (PD and CAL) is evaluated. For the other clinical variables, the average level of agreement between the examiners is determined and considered satisfactory when greater than 90% (Kappa test).

Clinical measurements and microbiological assessment are performed at baseline, 3, 6 and 12 months post-therapy. Immunological assessment is conducted at baseline and 12 months post-therapy.

The primary outcome variable is the number of volunteers reaching the clinical endpoint for treatment (? 4 sites with PD ?5 mm) at 1 year post-therapy [12, 14].

Secondary outcome variables are: difference between baseline and 12 months post-therapy for CAL gain and PD reduction (in the full mouth and in different PD categories), mean number and percentage of moderate (PD = 4–6 mm) and deep (PD ?7 mm) sites at 12 months; number and percentage of volunteers with 0, 1–2 or ? 3 sites with PD ?6 mm at 12 months post-therapy; number of sites with PD ?5 mm or ?6 mm at all post-treatment time points; differences in the occurrence of adverse events among therapeutic groups; differences in the counts and proportions of 40 bacterial species and in the counts of 20 chemokines in the GCF at all post-treatment time points.

Sample size calculation was based on the primary outcome (number of volunteers reaching the clinical endpoint of ?4 sites with PD ? 5 mm at 1 year post-therapy).

Considering a difference of 31 percentage points between groups (31% vs 62%) as regards the primary outcome [14], a significance level of 5%, and 90% power, 50 subjects per group would be necessary.

Considering a 20% rate of loss to follow up, it would be necessary to include 60 volunteers per group (total 180 subjects).

An investigator (C.M.P.), not involved in the inclusion and treatment of


patients, assigned the study participants to one of the three treatment groups by means of a computer-generated random sequence (Random Allocation Software,

Randomization is stratified by center with the use of permuted blocks of 3, 6 and 9.

The study coordinator organizes the bottles with the tablets in opaque plastic bags labeled with the volunteer number. The bags are handed directly to the volunteer by the study coordinator in the active and healing phases.

This sequence of procedures assures allocation concealment.

Microbiological monitoring (baseline, 3, 6 and 12 months) Sample collection.

Nine subgingival samples are being collected per volunteer, three in each of the following categories: shallow (PD ?3 mm), moderate (PD = 4–6 mm) and deep (PD ?7 mm).

The selected sites are located on non-contiguous interproximal dental surfaces and preferably distributed across the four quadrants. Sites located in teeth with amoxicillin for ear infection baby poorly adapted prostheses, furcation lesion, extensive caries and/or endo-periodontal lesion are not selected.

After the clinical assessment, the supragingival biofilm is removed and the subgingival sample is collected with individual sterile number 11/12 mini-five Gracey curettes, positioned at the most apical portion of the sites and with a single scaling movement in the apico-coronal orientation.

The samples are immediately placed in separate Eppendorf tubes containing 150 ?L of TE buffer solution (10 mM Tris-HCL, 1 mM EDTA, pH 7.6) and then 100 ?L of 0.5 M NaOH is added to each tube.

The tubes containing the samples are previously identified with the volunteer’s code, date and site collected.

The counts and proportions of 40 bacterial species will be determined in each individual sample using a modification [22] of the checkerboard DNA-DNA hybridization technique [23].

The microbiological analysis will be entirely performed at the Molecular Biology Laboratory of UNG.

In brief, the suspensions containing the bacterial biofilm samples collected are boiled for 10 min and neutralized by the addition of 0.8 mL of 5 M ammonium acetate, and the DNA is released in the solution.

The released DNA will be then placed into the extended slots of Minislot 30 apparatus (Immunetics, Cambridge, MA, USA) concentrated on a 15 ? 15 cm positively charged nylon membrane (Boehringer Mannheim, Indianapolis, IN, USA) and fixed to the membrane by boiling it at 120°C for 20 min. Subsequently, the membrane is placed in a Miniblotter 45 (Immunetics, Cambridge, MA, USA) with the lanes of DNA at 90 ° to the lanes of the device. Digoxigenin-labeled whole genomic DNA probes for 40 bacterial species are hybridized in individual lanes of the Miniblotter. After hybridization, the membrane is washed in highly astringent solution and the DNA probes are detected using the antibody to digoxigenin conjugated with alkaline phosphatase, and chemiluminescence detection.

The last two lanes in each run contain standards at concentrations of 10 5 and 10 6 cells of each species.

Signals will be evaluated visually by comparison with the standards for the test species on the same membrane by a calibrated examiner ( k test = 93%). The sensitivity of this assay will be adjusted to allow detection of 10 4 cells of a given species by adjusting the concentration of each DNA probe [22,23,24]. The mean counts (10 5 cells) of individual bacterial species will be averaged within each subject and then across subjects in each group. The percentage of the total DNA probe counts will be determined initially in each site, then per subject, and averaged across subjects in the three groups at each time point.

The sum of the individual mean proportion will be computed for each microbial complex described by Socransky et al.

Immunological monitoring (baseline and 12 months) Sample collection.

Six GCF samples are selected, two in each of the following categories: shallow (PD ?3 mm), intermediate (PD = 4–6 mm) and deep (PD ?7 mm). The selected sites are located on non-contiguous interproximal dental faces and preferably distributed among the four quadrants.

After removal of the supragingival biofilm with sterile cotton pellets, the sites are isolated with cotton rolls and gently dried with an air syringe to eliminate the possibility of contamination with saliva.

GCF is collected by inserting standard paper strips (Periopaper, Oraflow Inc., Smithtown, NY, USA), approximately 2 mm into the periodontal pocket for 20 s. Strips visually contaminated with blood are discarded.

The GCF volume is measured in a calibrated device (Periotron 8000, Proflow Inc., Amityville, NY, USA) and the readings are converted to an actual volume (microliter, ?L) by reference to a standard curve. Strips from the six selected sites are immediately placed into separate microcentrifuge tubes and stored at ? 80 °C for subsequent assays. The GCF samples will be evaluated for their content of 20 cytokines by Multiplex Bead Immunoassay (MAGPIX® System, Merck Millipore, Billerica, MA, USA): 75 uL of PBS will be placed in each microtube containing the individual samples and then they will be vortexed for 15 s and centrifuged for 5 min at 1500 ? g for elution.

Samples will be analyzed using a multi-analyte method by means of a 20-multiplex fluorescent bead-based immunoassay for 20 cytokines/chemokines (granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-? (INF-?), IL-1?, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17A, IL-21, IL-23, CXCL11 (ITAC), macrophage inflammatory protein (MIP)-1?, MIP-1?, MIP-3?, TNF-?) using commercially available kits (MILLIPLEX® MAP 384-Well High Sensitivity Human Cytokine Magnetic Bead Panel, EMD Millipore, Billerica, MA, USA) and a plate reader (MAGPIX® System, Merck Millipore, Billerica, MA, USA), according to the manufacturer’s recommendations. The amount of protein in each sample will be extrapolated from standards using appropriate software (Beadview EMD Millipore, Billerica, MA, USA).

The minimum detectable concentration of GM-CSF, IFN-?, IL-1?, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17A, IL-21, IL-23, ITAC, MIP-1?, MIP-1?, MIP-3?, TNF-? are 0.86 pg/ml, 0.37 pg/ml, 0.32 pg/ml, 0.26 pg/ml, 1.49 pg/ml, 0.31 pg/ml, 0.14 pg/ml, 0.38 pg/ml, 0.16 pg/ml, 0.98 pg/ml, 0.27 pg/ml, 0.16 pg/ml, 0.57 pg/ml, 0.19 pg/ml, 6.91 pg/ml, 1.06 pg/ml, 1.86 pg/ml, 0.71 pg/ml, 0.70 pg/ml and 0,24 pg/ml, respectively.

The results will be reported as concentrations of cytokines/chemokines per volume of GCF (pg/?L).

Clinical data are entered directly onto electronic spreadsheets (Microsoft® Excel 2011®, version 14.4.8, Copyright © 1990, Microsoft, Santa Rosa, California, USA), at the time of clinical examination, by a single investigator in each center. Data quality will be validated by checking missing data, out-of-range values and invalid responses. The mean percentage of sites with visible plaque, gingival bleeding, BOP, suppuration, number of sites with PD ?5 mm and PD ?6 mm, and mean PD and CAL are computed for each subject and then averaged across subjects in each group.

Generalized estimating equation (GEE) tests will be used to evaluate the differences within each group, among groups and in experimental times.

The data on reduction of the number of sites with PD ?5 mm and PD ?6 mm and on PD reduction and CAL gain in full-mouth assessment and initially intermediate (PD = 4–6 mm) and deep (PD ?7 mm) sites will be evaluated by multilevel analysis using the GEE test. The chi-square test will be used to compare differences in the frequency of the gender of patients exhibiting different categories of residual sites in post-therapy experimental times (low, moderate or high risk of disease progression) according to Feres et al.

The data will be evaluated using intention-to-treat analysis with last observation carried forward. Microbiological data will be expressed in counts (levels) and proportion counts of DNA probes.

The data will be expressed as counts ? 10 5 at each site by volunteers and then by volunteers within each group at each study time. The same way, the proportion and prevalence of each species will be computed for each site, then the means between the sites in each volunteer will be calculated, and then the volunteers of the same therapeutic group will be calculated at each experimental time.

The differences among the groups and between the experimental times will be evaluated by multi-level analysis using the GEE test.

Adjustments for multiple comparisons [26] will be performed when the 40 bacterial species will be evaluated simultaneously. The concentration, total count and proportion of each cytokine/chemokine in the GCF will be assessed per volunteer and then per volunteer within each group at each study time.

Similarly, the proportion will be computed for each site, then the means among the sites in each volunteer will be calculated, and then the volunteers of the same therapeutic group will be calculated in each experimental time.

The differences among the groups and within each group, among the experimental times will be evaluated by multi-level analysis using GEE. All analyses will be adjusted for multiple comparisons [25]. At the time of submission of this manuscript, 73 participants and 55 participants had been included at the UNG and USP-SP centers, respectively.

Amoxicillin (Amoxil®) versus Clarithromycin (Biaxin®) Based on "Antibiotic and Chemotherapy" written by Roger G.

Amoxicillin treatment course costs less than clarithromycin.

Clarithromycin has a broader antimicrobial spectrum than amoxicillin. Gram-negative bacteria • Haemophilus influenzae • Haemophilus parainfluenzae • Moraxella catarrhalis.

Other bacteria • Mycoplasma pneumoniae • Chlamydia pneumoniae • Mycobacterium avium complex (MAC) Head-to-head comparative studies. Clarithromycin and amoxicillin appear to have comparable effectiveness in the treatment of sinusitis 1 . Results of comparison of clarithromycin and amoxicillin in the treatment of acute maxillary sinusitis 1 . Amoxicillin Clarithromycin Regimen 500 mg 3 times daily for 7 to 14 days 500 mg 2 times daily for 7 to 14 days Clinical success rate (based on direct observation of the patient) 89% 91% Roentgenographic success rate 92% 78% Dropout rates 4% 3% Adverse effects mild gastrointestinal side effects. Amoxicillin and clarithromycin are equally effective in the treatment of community-acquired pneumonia in children.

In a randomized clinical trial 3 the mean hospital stay in patients treated with amoxicillin was 3.3 days and with clarithromycin was 3.2 days. About 97% patients in both treatment groups achieved symptoms improvement. Clarithromycin and amoxicillin are similarly effective in the treatment of acute ear infection (otitis media).

Results of single blind, randomized, multicenter clinical trial 2 comparing the safety and efficacy of clarithromycin and amoxicillin Amoxicillin suspension Clarithromycin suspension Clinical success (cure and symptoms improvement) rates at 0 to 4 days posttreatment 90% 93% Erythema migrans (the rash characteristic of Lyme disease) Clarithromycin works a little better than amoxicillin in the treatment of children with solitary erythema migrans. Results of comparative study 4 of children with solitary erythema migrans Amoxicillin Clarithromycin Average duration of erythema migrans after starting the antibiotic 4 days Duration of Lyme borreliosis symptoms 10 day 7 days Minor manifestations of Lyme borreliosis 16 of 54 patients (29.6%) 11 of 50 patients (22.0%) Major manifestations of Lyme borreliosis 2 patients (3.7%) Not detected Side effects 28.1% 24.2% Further reading. Amoxicillin vs Penicillin Amoxicillin vs Cefuroxime. Multicenter comparison of clarithromycin and amoxicillin in the treatment of acute maxillary sinusitis. amoxicillin suspensions in the treatment of pediatric patients with acute otitis media.

Comparative efficacy of amoxicillin, cefuroxime and clarithromycin in the treatment of community-acquired pneumonia in children.

Solitary erythema migrans in children: comparison of treatment with clarithromycin and amoxicillin. Published: October 25, 2017 Last updated: October 25, 2017.

About amoxicillin Key facts Who can and can't take amoxicillin How and when to take it Side effects How to cope with side effects Pregnancy and breastfeeding Cautions with other medicines Common questions.

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