Mox 500 for throat infection

For CP patients, A+M group showed significantly more clinical attachment gain and probing depth reduction than the placebo group in a multicentre two?year randomized controlled trial.

25 Furthermore, A+M subjects had a significantly lower mean number of pockets >4 mm and bleeding on probing in comparison to the control group. 16-18 Subjects who did not receive A+M had 7.5 times more bleeding pockets. 16 More patients treated with A+M experienced 10?fold reduction in the number of diseased sites (PPD >4 mm with BOP) and therefore less need for additional surgical therapy compared to placebo patients.

18 Molars benefited significantly more from the antibiotics than non?molars. In addition to clinical studies, histological and microbiological studies also showed the benefit of systemic administration of A+M in the form of suppression of periodontal pathogens such as Aa, Pg and Pi and reduction of the size of the inflammatory lesions. 26, 27 Similarly, for AP, the administration of systemic A+M resulted in significantly more CAL gain, PPD reduction, less persistent deep sites and more reduction in the percentage of bleeding sites. 28, 29 Systematic reviews also confirmed that the use of A+M resulted in greater periodontal probing depth (PPD) reduction and clinical attachment level (CAL) gain than scaling and root planing (SRP) for chronic periodontitis 30 and aggressive periodontitis.

31 It is important, however, to interpret these conclusions with caution due to the wide heterogeneity between the various studies in terms of patient selection, the criteria for AB selection, treatment strategies, the medication regimen and follow?up times. Azithromycin (Az) Several clinical and microbiological trials also examined the clinical and microbiological effect of a three?day regimen of azithromycin (Az) in conjunction with non?surgical periodontal treatment. The most accepted regimen for Az is 500 mg once every 24 hours for three days, which is associated with good patient compliance. 33 Azithromycin seems to have a triple role in the treatment and resolution of periodontal disease: (1) periodontopathogens suppression; (2) anti?inflammatory properties; and (3) healing potentials due to its presence in fibroblasts. The earliest double?blind placebo controlled study by Sefton et al .

34 showed a significant reduction in pigmented anaerobes after three and six weeks in patients who received Az compared to placebo. Azithromycin in moderate chronic periodontitis cases also led to more PPD reduction than control groups. 35 This was also true for AP patients, where the Az group showed significantly more reduction in mean PPD and a higher percentage of teeth with attachment gain ?1 mm compared with controls. 36 It must be noted however, that not all trials showed additional benefit of using Az. There are no evidence based guidelines for the use of systemic antibiotics in periodontitis patients.

It is not clear which patients will benefit from the drugs and which type of antibiotic is more effective and at what dose.

As demonstrated above, there is evidence that the A+M and Az regimens can be beneficial in the treatment of periodontitis. The aim of this preliminary study was to compare the clinical outcomes for patients with moderate to advanced chronic periodontitis (CP) treated with (1) scaling and root planing only (SRP); (2) SRP with adjunctive A+M; (3) SRP with adjunctive azithromycin (Az).

This preliminary study is a single centre, double?blinded randomized controlled clinical trial comparing the three different treatment modalities.

Ethics approval has been obtained from The University of Western Australia Human Research Ethics Committee (Reference number RA/4/1/6076). The protocol of the trial conforms to the provisions of the Declaration of Helsinki (as revised in Tokyo 2004).

All participants gave an informed consent prior to the commencement of the trial.

All subjects were diagnosed with generalized moderate to advanced chronic periodontitis.

All participants fulfilled the following inclusion criteria: age over 30 years, a minimum number of 20 teeth, a minimum of eight sites with PPD ?5 mm, clinical attachment loss ?5 mm and bleeding on probing (BOP), as well as radiographic evidence of bone loss of at least 1/3 of root length. 37, 38 Exclusion criteria included: smokers, uncontrolled diabetes, patients with cardiovascular diseases, patients on warfarin, pregnant or lactating females, patients who received systemic antibiotics or non?steroidal anti?inflammatory drugs the past six months, patients with known hypersensitivity to penicillin, metronidazole or azithromycin, patients diagnosed with aggressive periodontitis or periodontitis as a manifestation of systemic disease 37 and patients who received periodontal therapy the past six months. In accordance with Haffajee et al ., 39 the power calculations were based on sites with baseline PPDs >6 mm.

According to the authors, a difference of 1 mm between groups for clinical attachment level (CAL) change at these sites would be clinically significant. The standard deviation of CAL change at sites with baseline PPDs >6 mm was 1.1 mm. Based on these values, the study would require 19 subjects per group (57 patients in total) with ? of 0.05 and 80% power (using ANOVA).

This preliminary study included 12 subjects in the SRP group, 12 subjects in the Az group and 13 subjects in the A+M group (37 patients in total).

Each of the participating subjects was given a code number (1–37).

A computer generated table produced by the statistician divided the patients randomly into three coloured groups: blue group, green group and yellow group. The type of medication corresponding to each colour was not revealed until the statistical analyses were complete.

The following antibiotic regimens were followed: Azithromycin (Az) 500 mg, 1 capsule per 24 hours for three days; A+M Amoxicillin 500 mg and metronidazole 200 mg tds for seven days.

The prescribed regimens are in accordance with previous recommendations and are based on pharmacokinetic data and minimum inhibitory concentrations of the periodontal pathogens involved. 15, 33 For the study to be double?blind, all capsules looked identical in shape, size and colour. All patients were given the same number of capsules in a standardized regimen as follows: (1) A+M group – two capsules (one amoxicillin and one metronidazole) every eight hours (6 capsules/day) for seven days (total 42 capsules); (2) SRP group – two placebo capsules every eight hours (6 capsules/day) for seven days (total 42 placebo capsules); (3) Az group – two capsules every eight hours (6 capsules/day) for seven days (total 42 capsules).

For the first three days, there

was

PPD measurements were done with a manual force aiming to 25 N.

Furcation involvement in multi?rooted teeth using Nabers probe.

Sites with furcation involvement were further divided into grade I, II or III.

40 Full mouth bleeding score (FMBS) – bleeding on probing (dichotomous 0/1) was recorded for each tooth at six surfaces and the percentage BOP was then calculated. Full mouth plaque score (FMPS) – using a disclosing agent (PDS), presence or absence of plaque was recorded at four surfaces per tooth and a percentage was calculated.

Mobility – according to Miller's classification (grade I, II or III).

The initial phase of treatment was then carried out for all patients.

This included oral hygiene instructions, occlusal adjustments (where indicated), extraction of teeth that are irrational to retain and non?surgical periodontal debridement. Periodontal debridement was carried out in two to four sessions for each patient (approximately 90 minutes per session). Periodontal debridement was performed under local anaesthesia using both hand and power?driven ultrasonic instruments.

The endpoint for each SRP appointment was the ‘smoothness of the scaled roots’. At the end of the last SRP session, subjects received their medication with instructions.

Both the clinician and the patients were blinded to the medication that the patients received. All patients were seen by the dental hygienist six weeks

after

The purpose of this visit was solely educational and motivational to the patients (no measurements done).

Patients were then reviewed three months after the last SRP visit and the clinical measurements were repeated. All clinical measurements and treatment were performed by one clinician (AS).

The intra?class correlation (ICC) for the PPD was 0.896. Also, the reproducibility of the measurements between ?1 and +1 mm was 94%. The primary outcome variable was the change in CAL between baseline and 3 months.

The secondary outcome variables included the changes in PPD, FMBS, FMPS and the number of shallow, moderate and deep sites. Four different analyses were carried out: all sites analysis; molar only analysis; breakdown analysis of baseline PPDs categories; analysis of the number of sites with different PPD categories.

Within each treatment group, the significance of differences over time (baseline – three months) for the mean PPD, mean CAL, the FMBS and the FMPS was sought using paired t ?test.

The difference between the treatment groups at three months was assessed using the Tukey multiple comparisons of means test.

Molar plaque score (MPS) and molar bleeding score (MBS) were calculated instead of FMPS and FMBS. Sites were subset according to the baseline PPD into three categories: shallow (1–3 mm), moderate (4–6 mm) and deep (>6 mm). For each category, changes in PPD and CAL from baseline to three months within the treatment groups were determined (paired t ?test).

A comparison was also carried out between the treatment groups at three months for each category (using Tukey multiple comparisons of means test).

Analysis of the number of sites with different PPD categories. It is suggested that the efficacy endpoints in periodontal therapy should be evaluated in terms of the number of sites with persistent pocketing (>4 mm) rather than changes in mean PPD and CAL. 17 Therefore, the mean number of sites with PPD 1–3 mm, 4–6 mm and >6 mm were also calculated in each treatment group at baseline and at three months.

Paired t ?test was performed to show whether a significant change in the number of shallow, moderate and deep sites has occurred for each treatment group. The mean number of shallow, moderate and deep sites at three months was also compared between the treatment groups using the ANOVA test.

Finally, the magnitude of change in the mean number of sites for each PPD categories (number of sites at baseline minus number of sites at review) was compared between the treatment groups.

The rationale of this analysis is outlined in the Discussion section. This comparison was performed using the Tukey's post hoc comparison test.

For all of the above analysis, a difference was considered significant if the level of statistical significance was p. Subject retention, medication compliance and adverse effects. Figure 1 represents the flowchart of the study design. Thirty?seven patients entered the study at baseline and completed the initial phase of treatment. They were randomly allocated into three groups: SRP group (n = 12);

A+M

All patients completed the checklist to confirm compliance of the medication regimen. At review, five subjects were eliminated due to lack of compliance with the regimen. One out of the four did not complete the course of medication due to developing gastro?intestinal disturbance, nausea and vomiting.

The other four did not comply for other reasons not related to adverse effects of the medication. Hence, the sample size was reduced to 32 patients, all of which had completed the described regimen: SRP group (n = 10); A+M

group

In the A+M group, two patients reported stomach upset and nausea, one patient experienced diarrhoea during the intake of the drugs and two patients had both stomach upset together with diarrhoea.

In other words, 5 out of the 11 patients experienced at least one adverse effect of A+M.

In the Az group, 4 out of the 11 patients reported an adverse effect.

Two stated having stomach upset, one experienced diarrhoea and one experienced an increased frequency of urination.

No adverse events were reported by the group that took the placebo (10 patients). At baseline, no significant differences were observed between the groups for any of the demographic and clinical parameters (Table 1).

Variable SRP A+M Az p ?value Number of patients 12 13 12 ? Mean age (sd) 56.1 (12.8) 52.1 (12.2) 56.3 (9.9) 0.596 Male/Female ratio 5/7 4/9 4/8 0.910 Mean n of teeth 24.8 (3.0) 25.4 (2.8) 25.8 (1.8) 0.687 Mean n of molars 5.8 (2.7) 6.5 (2.6) 6.5 (1.4) 0.737 FMPS (%) 68.8 (17.3) 62.8 (17.9) 64.5 (16.4) 0.678 FMBS (%) 53.3 (12.5) 56.9 (21.0) 46.5 (18.8) 0.351 Mean PPD (mm) 3.93 (0.58) 3.94 (0.64) 3.67 (0.66) 0.505 Mean CAL (mm) 4.36 (0.57) 4.46 (0.77) 4.04 (0.61) 0.280 Mean n of PPD 1–3 mm 82.3 (24.1) 80.9 (27.2) 100.6 (22.1) 0.105 Mean n of PPD 4–6 mm 50.6 (16.6) 56.2 (23.8) 40.6 (15.0) 0.134 Mean n of PPD >6 mm 15.3 (15.8) 15.3 (15.5) 13.3 (17.2) 0.943. The significance of difference between the groups at baseline was assessed using one?way ANOVA test for all the features except for Male/Female ratio where Fisher's exact test was used.