Over the counter amoxicillin for humans

The three groups exhibited improvements in most clinical parameters.

At three months, A+M showed a higher reduction in PPD compared to Az in the ‘all sites analysis’. Molars exhibited better reduction in BOP and PPD with A+M than SRP.

Pocket depth of the 4–6 mm category reduced more in the A+M than SRP.

A+M experienced a higher increase in the number of sites with PPD 1–3 mm than Az.

Adjunctive systemic antibiotics in the initial phase of treatment may result in improved clinical outcomes. Chronic periodontitis is an infectious disease resulting in inflammation within the supporting structures of teeth, progressive attachment loss and bone loss. 1 It results from an

imbalance

4, 5 However, SRP is not always sufficient in producing satisfactory periodontal clinical outcomes such as pocket depth reduction and gain of clinical attachment levels. In such cases, adjunctive treatment may be required.

Such adjuncts include: (1) the use of locally administered antimicrobial agents; (2) the use of systemic antibiotics; and (3) surgical procedures. This study assessed the usefulness amoxicillin and the pill of systemic antibiotics (AB) as an adjunct to the initial phase of periodontal treatment. The use of adjunctive systemic antibiotics in the treatment of periodontal disease has been a topic of interest since the 1980s.

The clinical and microbiological effects of different types of systemic antibiotics (AB) such as tetracycline, 6, 7 amoxicillin, 8 metronidazole, 9, 10 clindamycin, 11 azithromycin, 12-15 and combinations 16-18 have been tested on different forms of periodontal diseases including localized and generalized aggressive periodontitis, 19, 20 chronic periodontitis 6, 9, 13 and refractory periodontitis. 8, 21 Such extensive studies have resulted in prolific literature with a vast variability in study designs, results and take?home messages. Systematic reviews demonstrated that the use of adjunctive systemic antimicrobials in combination with SRP resulted in more gain in clinical attachment levels (CAL), more reduction in periodontal probing depth (PPD) and reduced risk for additional loss of attachment. 22-24 Such improvements were consistent for both chronic as well as aggressive periodontitis.

23 The literature generally agrees that if systemic AB are to be used, they should only be in conjunction with thorough mechanical periodontal debridement and not as a monotherapy. 24 Despite that, there is a lack of evidence based guidelines for their use in periodontitis patients.

Questions that remain unsolved relate to: (1) patient selection; (2) choice of antibiotics; (3) dosage of medication; and (4) timing of administration.

Amoxicillin and metronidazole (A+M) Numerous randomized controlled studies have tested the efficacy of A+M in chronic periodontitis (CP) and for aggressive periodontitis (AP) patients.

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 one Az capsule and 5 placebo capsules per day. For the remaining four days, all capsules were placebo. The time for taking the Az capsule during the first three days was also strictly standardized. At baseline, for all individuals, the following clinical parameters were measured: A full periodontal examination including periodontal pocket depth (PPD), recession, clinical attachment level (CAL) all measured on six surfaces per tooth. The measurements were carried manually using a Michigan graduated periodontal probe (Hu?Friedy, Chicago, IL, USA). 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 debridement sessions for oral

hygiene