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Journal club 1
1. AZITHROMYCIN AS AN ADJUNCTIVE
TREATMENT OF GENERALIZED SEVERE
CHRONIC PERIODONTITIS:
CLINICAL, MICROBIOLOGIC AND BIOCHEMICAL
PARAMETERS
Buket Han, Gulnur Emingil, Guven Ozdermir
JP 2012
2. 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.
3. 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 ½ 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)
4. 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)
5. 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.
7. 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)
8. 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
9. 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.
10. 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.
11. RESULTS
Group/Parameter
Baseline to 1 Month
Baseline to 3 Months
Baseline to 6Months
Azithromycin group (n = 14)
Mean PD (mm)
1.56 ± 0.4*
1.79
0.4*
1.81
0.5*
Mean PD (4 to 6 mm)
2.18 ± 0.2*
2.23
0.3
Mean PD (‡7 mm)
Mean CAL (mm)
Mean CAL (4 to 6 mm)
Mean CAL (‡7 mm)
4.34 ± 0.9*
1.47 ± 0.3*
0.34 0.2*
1.99 3.0*
4.46
1.58
0.43
1.25
0.8*
0.4*
0.3*
1.9*
% of sites with BOP
51.36
20.7*
53.43
20.3*
54.08 19.3*
% pockets conver ting from
64.43
23.5
65.92
22.1
79.33
Mean PD (mm)
1.44
0.5*
1.54 0.4*
1.66
0.5*
Mean PD (4 to 6 mm)
2.28
0.3*
2.30
2.46
0.3
Mean PD (‡7 mm)
Mean CAL (mm)
Mean CAL (4 to 6 mm)
Mean CAL (‡7 mm)
4.11
1.36
0.33
1.15
0.5*
0.5*
0.2*
2.3
4.16
1.48
0.31
0.49
4.45
1.54
0.39
0.54
0.5*
0.5*
0.4*
0.5
% of sites with BOP
47.07
% pockets conver ting from
67.0
2.32
0.4
4.88
1.55
0.34
2.25
1.1*
0.5*
0.2*
3.1*
24.7
‡7 mm to <4 mm
Placebo group (n = 14)
‡7 mm to <4 mm
16.8*
26.3
48.00
58.7
0.3
0.4*
0.6*
0.2*
0.7
8.5*
26.1
50.29
17.2*
57.56
30.5
12. 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) (%)
8.88 – 10.2
49.29 – 14.1
33.56 – 13.5
54.04 – 10.1
0.06 – 0.2*
9.16 – 10.5*
7.40 – 6.6*
60.31 – 13.3
0.0 – 0.0*
8.41 – 10.0*
8.32 – 8.0*
60.45 – 15.8
0.05 – 0.2*
7.95 – 10.2*
7.00 – 7.8*
62.19 – 15.3
CAL (‡4 mm) (%)
Placebo group (n = 14)
87.59 – 9.4
67.71 – 17.3*
68.75 – 17.3*
69.19 – 18.5*
PD (‡7 mm) (%)
PD (4 to 6 mm) (%)
CAL (‡7 mm) (%)
CAL (4 to 6 mm) (%)
7.20 – 6.7
49.12 – 12.0
32.64 – 17.4
50.07 – 11.5
0.07 – 0.2*
9,87 – 8.5*
6.05 – 5.2*
57.48 – 16.6
0.13 – 0.4*
10.97 – 8.9*
7.09 – 5.8*
59.39 – 13.1
0.09 – 0.2*
6.91 – 7.5*
4.71 – 6.8*
54.03 – 14.2
CAL (‡4 mm) (%)
82.74 – 12.8
63.52 – 19.9*
66.42 – 17.2*
58.79 – 16.8*
15. 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.
16. 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.
17. 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.
Teles
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.