AZITHROMYCIN AS AN ADJUNCTIVE TREATMENT OF GENERALIZED SEVERE CHRONIC PERIODONTITIS: CLINICAL, MICROBIOLOGIC AND BIOCHEMICAL PARAMETERS Buket Han, Gulnur

Emingil, Guven Ozdermir JP 2012

INTRODUCTION

Chronic periodontitis is an infectious disease

characterized by occurrence of destruction of

periodontal supporting tissues that occurs over an extended period of time.

It is caused by the activity of specific periodontal pathogens that initiate the disease process. Host factors including infiltrating cell populations,

cytokines & matrix metalloproteinases are associated

with most periodontal tissue breakdown leading to clinical signs of the disease.

Azithromycin ( Macrolide) is a systemic antibiotic is mainly effective against Gram +ve organisms and is effective against certain Gram ve organisms including H. influenzae & C. trachomatis. It is a bacteriostatic agent with a t of over 50 hrs. It is used in periodontal therapy because of its favourable pharmacological properties and low incidence of adverse effects. Azithromycin produces potent inhibition of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis.( Goldstein et al 1999) Azithromycin is concentrated in the neutrophils, macrophages and fibroblasts all of which play a role in pathogenesis of periodontal diseases ( Amsden 2001)

Triple role of azithromycin: 1) Supresses periopathogens. 2) Anti- inflammatory activity 3) Improves clinical treatment outcome of patients with chronic & aggressive periodontitis. (Smith et al 2002) The concentration of azithromycin in inflammed gingiva is higher than in healthy gingiva. ( Burrell & Walters 2008)

AIM
This study examines the efficacy of azithromycin used in combination with non-surgical periodontal therapy on the clinical and microbiological parameters and GCF MMP-8 over a period of 6 months in patients with severe chronic generalized periodontitis.

MATERIALS & METHODS

STUDY DESIGN:

INCLUSION CRITERIA: 16 teeth present > 30% sites with 5mm CAL 2 sites with PPD 6 mm in each quadrant that had BOP

EXCLUSION CRITERIA: Severe medical disorders/ history of systemic illness. Known hypersensitivity to macrolide. Those who received antibiotics or undergone periodontal treatment in the past 6 months. Pregnant females Smokers ( > 10 cigarettes per day)

TREATMENT: Full mouth SRP was performed; per quadrant on 4 sequential visits. Post SRP Test group : SRP+ Azithromycin 500 mg [ 1 OD for 3 days] Control group: SRP+ Placebo Baseline sampling: 2 days after screening. GCF sampling : 2 weeks 1 month 3 months 6 months Microbiologic sampling: 2 weeks 1 month 6 months

Sites examined: PPD & CAL: 6 sites around each tooth was recorded for full mouth. GCF samples were taken from mesiobuccal aspects of single rooted teeth exhibiting PPD 6mm. MMP- 8 levels was measured in the GCF by immunofluorescence assay Subgingival plaque sampling was taken from two preselected single rooted teeth with PPD 6mm.

Quantitative real time PCR was performed with hydridization probes using species specific probes for 5 periodontopathic pathogens. Porphyromonas gingivalis Aggregatibacter actinomycetemcomitans Prevotella intermedia Tannerella forsythia and Fusobacterium nucleatum.

RESULTS
Group/Parameter Azithromycin group (n = 14) Mean PD (mm) Mean PD (4 to 6 mm) Mean PD (7 mm) Mean CAL (mm) Mean CAL (4 to 6 mm) Mean CAL (7 mm) % of sites with BOP 1.56 0.4* 2.18 0.2* 4.34 0.9* 1.47 0.3* 0.34 0.2* 1.99 3.0* 51.36 20.7* 1.79 0.4* 2.23 0.3 4.46 0.8* 1.58 0.4* 0.43 0.3* 1.25 1.9* 53.43 20.3* 1.81 0.5* 2.32 0.4 4.88 1.55 0.34 2.25 1.1* 0.5* 0.2* 3.1* Baseline to 1 Month Baseline to 3 Months Baseline to 6Months

54.08 19.3*

% pockets conver ting from

7 mm to <4 mm Placebo group (n = 14) Mean PD (mm) Mean PD (4 to 6 mm) Mean PD (7 mm) Mean CAL (mm) Mean CAL (4 to 6 mm) Mean CAL (7 mm) % of sites with BOP % pockets conver ting from 7 mm to <4 mm

64.43 23.5

65.92 22.1

79.33 24.7

1.44 0.5* 2.28 0.3* 4.11 0.5* 1.36 0.5* 0.33 0.2* 1.15 2.3 47.07 16.8* 67.0 26.3

1.54 0.4* 2.30 0.3 4.16 1.48 0.31 0.49 0.4* 0.6* 0.2* 0.7

1.66 0.5* 2.46 0.3 4.45 0.5* 1.54 0.5* 0.39 0.4* 0.54 0.5 50.29 17.2* 57.56 30.5

48.00 8.5* 58.7 26.1

Mean Percentage of Sites With Different PD and CAL Categories at Baseline and at Follow-Up Visits in the Azithromycin and Placebo Groups

Group/Parameter

Baseline

1 Month

3 Months

6 Months

Azithromycin group (n = 14) PD (7 mm) (%) PD (4 to 6 mm) (%) CAL (7 mm) (%) CAL (4 to 6 mm) (%) CAL (4 mm) (%) Placebo group (n = 14) PD (7 mm) (%) PD (4 to 6 mm) (%) CAL (7 mm) (%) CAL (4 to 6 mm) (%) CAL (4 mm) (%) 8.88 10.2 49.29 14.1 33.56 13.5 54.04 10.1 87.59 9.4 7.20 6.7 49.12 12.0 32.64 17.4 50.07 11.5 82.74 12.8 0.06 0.2* 9.16 10.5* 7.40 6.6* 60.31 13.3 67.71 17.3* 0.07 0.2* 9,87 8.5* 6.05 5.2* 57.48 16.6 63.52 19.9* 0.0 0.0* 8.41 10.0* 8.32 8.0* 60.45 15.8 68.75 17.3* 0.13 0.4* 10.97 8.9* 7.09 5.8* 59.39 13.1 66.42 17.2* 0.05 0.2* 7.95 10.2* 7.00 7.8* 62.19 15.3 69.19 18.5* 0.09 0.2* 6.91 7.5* 4.71 6.8* 54.03 14.2 58.79 16.8*

Total Bacteria at Baseline, Post-Treatment, 2 Weeks, 1 Month, and 6 Months in the Azithromycin and Placebo Groups

Baseline
Azithromycin group (n = 14) Aa n Pg n Pi n Fn n Tf n Placebo group (n = 14) Aa n Pg n % % 7.1 1.49E+01 5.56E+01 100 1.63E+04 3.83E+04 % % % % % 21.4 1.48E+03 5.35E+03 100 2.98E+03 4.74E+03 71.4 4.47E+03 8.45E+03 100 3.76E+04 6.45E+04 92.9 3.41E+04 6.65E+04

Post-Treatment

2 Weeks

1 Month

6 Months

14.3 1.49E+05 5.54E+05 85.7 1.36E+04 2.85E+04 35.7 8.01E+02 2.20E+03* 92.9

7.1 3.63E+01 1.36E+02 92.9 8.57E+01 8.63E+01* 21.4* 3.37E+03 1.19E+04* 92.9

0 0 85.7 8.49E+01 9.23 E+0 28.6 1.47 E+02 2.70E+02* 92.9 1.46E+04 4.69E+04* 78.6 1.45E+03 3.94 E+03*

0 0 100 1.34E+03 4.67E+03* 21.4* 5.55E+02 1.77E+03* 92.9 3.89E+04 8.97E+04 78.6 1.63E+04 4.58E+04*

2.87E+04 5.75E+04* 2.32E+04 4.54E+04* 78.6 3.44E+04 6.51E+04* 85.7 2.77E+03 8.41E+03*

14.3 2.63E+03 9.82E+03 100 4.85E+03 1.21E+04

21.4 3.07E+04 1.15E +05 100 1.30E+03 4.31E+03*

7.1 1.22E+03 4.57E+03 92.9 2.63E+02 4.74E+02*

7.1 3.26E+02 1.22E+03 100 1.96E+04 5.76E+04*

Pi
n Fn n Tf n

64.3
5.59E+03 7.93E+03

42.9
1.37E+04 2.80E+04* 100 3.97E+04 7.30E+04 78.6 1.56E+04 3.62E+04*

21.4*
6.84E+03 1.80E+04* 85.7 2.42E+04 3.70E+04 64.3 1.27E+04 4.46E+04*

28.6
1.92E+03 6.58E+03* 100 1.66E+04 2.35E+04 85.7 5.95E+03 2.06E+04*

28.6
3.33E+03 1.13E+04* 100 3.73E+04 5.95E+04 85.7 4.84E+04 1.53E+05*g

92.9 2.94E+04 3.27E+04

92.9 1.16E+05 2.73E+05

DISCUSSION

In sites of pocket 7 mm there was a reduction of approximately 4.4 mm and pockets initially 4 to 6 mm there was a reduction of approximately 2.4mm in both groups. Both the groups had almost same percentage of pockets converting from 7 mm to 4 mm. Both the groups had almost similar MMP 8 levels during the course of treatment. The decrease in MMP 8 level in both the groups after SRP suggests the effectiveness of non- surgical therapy in decreasing the bacterial load. Azithromycin does not have any additional effect on GCF MMP 8 levels. Among the periodontal pathogens investigated all tend to reappear 6 months after treatment. F. nucleatum alone shows greater reduction than the control group.

RELATED STUDIES
Effects of Full-Mouth Scaling and Root Planing in Conjunction With Systemically Administered Azithromycin Kazuhiro Gomi et al (JP 2007)

A double-blind placebo-controlled trial of azithromycin as an adjunct to non-surgical treatment of periodontitis in adults: clinical results. S. R. Smith et al (JCP 2002)

Azithromycin as an adjunct to scaling and root planing in the treatment ofPorphyromonas gingivalis-associated periodontitis: a pilot study
Alfonso Oteo et al (JCP 2010) Clinical and microbiological effects of azithromycin in the treatment of generalized chronic periodontitis: a randomized placebo-controlled clinical trial Eduardo Sampaio et al (JCP 2011) Mascarenhas (2005) & Traven.S (2007) showed that Azithromycin + SRP was beneficial in smokers with Chronic periodontitis.

CONCLUSION
Although Azithromycin

is a promising drug for treatment of various infections due to its easy dose regime and pharmacological actions, the data from the present studies suggests no added benefit in the treatment of chronic periodontitis.

The

effect on Azithromycin on Fusobacterium nucleatum may be beneficial to some extent.

et al suggested that rapid reduction in periopathogens and an increase in beneficial species ratio is needed to achieve major clinical benefits. This ratio is difficult to achieve using a bacteriostatic agent such as Azithromycin.

Teles