Effect of Subgingival Placement of 0.5% Azithromycin Gel on Clinical Parameters in Molars of Patients with Chronic Periodontitis

J. Fazal Ilahi, M. Maria Subash Aaron^*, Arun P Maradi, Ritika Chhalani and Nimisha Gopal
^*Correspondence: M. Maria Subash Aaron, Department of Periodontics, Sri Ramakrishna Dental College and Hospital, Nava India, Peelamedu, Tamil Nadu, India, Email:

Keywords

Azithromycin •Local drug delivery •Scaling and root planning • Probing depth • Clinical Attachment Level

Introduction

Periodontitis is a microbial plaque induced inflammatory disease of periodontium. The Scaling and Root Planning (SRP) reduces bacterial mass, but major pathogens may escape due to tissue invasion or poor host defiance as well as due to complex anatomical factors. Systemic antimicrobials are useful in above situation, but have many drawbacks [1]. But, by using Local Drug Delivery (LDD), higher concentration of therapeutic agent can be achieved and maintained for long period without any systemic effects. Azithromycin (AZM) is effective against tissue invading pathogens and has immunomodulatory properties also. It has longer half-life and good tissue penetration. Systemic AZM as an adjuvant to SRP proved to be effective. 0.5% AZM as a LDD showed promising results. This is the first study to find the effectiveness of AZM as LDD in molars which has complex anatomical features. The aim of the study was to evaluate the effect of 0.5% AZM gel as an adjuvant to SRP on clinical parameters in 1^st and 2^nd molars [2-4].

Materials and Methods

This clinical study followed the principles in the Declaration of Helsinki. The study was approved by Institutional Review Board and Ethical Committee. Informed consent was obtained from each patient before enrolling them in the study. The outpatients who reported to the department of periodontics, Sri Ramakrishna dental college and hospital, Coimbatore were included in this study. In both test and control groups, systemically healthy patients with probing depth ≥ 5 mm and no antibiotic therapy or periodontal therapy in the preceding six months were included. Radiographic bone loss was recorded to select subjects with chronic periodontitis [5-7]. Exclusion criteria: In test group, patients with known or suspected allergy to the macrolide group were excluded. The smokers, alcoholics, and pregnant or lactating females were excluded in both the groups. Maxillary or Mandibular first or second molars were the teeth to be tested. Patient’s consent was obtained before including them in the study. Patients were allocated to two groups: control group (SRP only) and test group (SRP plus sub gingival AZM). Patients were recalled after 45 days post treatment for review. On baseline and post-operative examination, clinical parameters such as Gingival Index (GI), Conventional Probing Depth (PD), Clinical Attachment Level (CAL) and modified Sulcular Bleeding Index (mSBI) were recorded for the tooth to be tested [8-11].

Method for preparation of Azithromycin gel

0.5% AZM gel was prepared in Sri Ramakrishna college of Pharmacy, Coimbatore. Weighed amount of Poly Lactic-co-Glycolic Acid (PLGA-7502A Purac Biomaterials, PURASORBR, Gorinchem, the Netherlands) was placed in a glass vial, and solvent (N-Methyl-2-pyrrolidone) of required amount was added to it [12-14]. The vial was heated to 60ºC and agitated using a magnetic stirrer on an electromagnetic heater to obtain a clear solution. Azithromycin of required amount was added to the above polymer solution and dissolved completely to obtain a homogeneous phase of polymer, solvent and drug. The formulation constituents were N-methyl-2-pyrrolidinone as the biocompatible solvent and PLGA copolymer in a ratio of 75:25, with a molecular weight of 72 000 Dalton (72 kilo Dalton) and a microenvironment pH of 7.4 [15].

Local drug delivery

0.2 ml prepared AZM gel was injected into the periodontal pockets using a blunt cannula. Periodontal dressing wasn’t applied after delivery of the drug as the prepared formulation decreases in viscosity, which causes swelling and occlusion of the periodontal pocket. After gel placement, patients were instructed to avoid chewing hard or sticky foods, brushing near the treated areas, or using any interdental aids for 1 week [16]. Adverse effects were noted at recall visits, and any supragingival deposits if accumulated were removed.

Statistical analysis

The sample size was calculated with 95% confidence level using Slovin’s formula. The data were transferred to Microsoft excel sheet and statistical analysis were done using SPSS software (version 24.0). Mean values and standard errors for PD, CAL, GI, and mSBI were calculated for each subject at each time point. Differences between intragroup was done using paired t test and intergroup was done using independent sample t-test. Differences with a P value <0.05 at a confidence level of 95% were considered significant [17].

Results

Eighty patients were enrolled in this study. 40 patients were in the test group and their average age was 42.75 years. 40 patients were in the control group and their average age was 42.65 years. There were no statistically significant baseline differences between the groups for any demographic or clinical parameters (Table 1).

Table 1. Age and clinical parameters at baseline and six weeks after SRP, SRP with AZM gel placement in test and control groups.

No adverse drug reactions were reported. Intra-group comparison and inter-group comparison had been done. The mean GI (mGI) scores were found to be reduced in both test and control groups (p<0.05) with no difference between test and control groups (Table 2).

Table 2. Differences in clinical parameters at baseline and 6 weeks in test and control groups.

The mSBI scores were also found to be reduced in both test and control group (p<0.05) with no difference between test and control group (Table 2).

PD reduced in test-group significantly from 6.33 to 3.93 (p<0.05) and in control group from 7.38 to 5.55 (p<0.05) (Table 2).

Reduction in PD was more in test group when compared to control group (p<0.05) (Table 2). CAL gain was achieved in both test group as well as control group (p<0.05), with more gain in test group when compared to control group (p<0.05) (Table 2).

Discussion

SRP helps in the removal of plaque and contributing factors. Even though studies had justified the efficacy of SRP in improving the periodontal and systemic parameters, it has few limitations in case of complex anatomic factors. In such cases LDD plays a role. In our study, we evaluated the effect of 0.5% AZM gel as an adjuvant to scaling and root planning in treating maxillary and mandibular molars. In our study, all the clinical parameters such as mGI, mSBI, PD and CAL were significantly improved post operatively in test group and control group, with test group recording great improvement in PD and CAL when compared to control group [18].

In test group, PD significantly reduced by 2.4 mm (p<0.05) and in control group, PD reduced by 1.83 mm (p<0.05). Also, reduction in PD was more in test group when compared to control group (p<0.05).

In test group, CAL gain achieved was 1.48 mm (p<0.05) whereas in control group, CAL gain achieved was 1.22 mm (p<0.05).

In test group, mGI significantly reduced by 1.04 (p<0.05) and in control group, mGI reduced by 1.33 (p<0.05). The reduction in mGI was more in control group when compared to test group but not significant (p>0.05). But previous studies showed a marked reduction in mGI.

In test group, mSBI significantly reduced by 1.28 (p<0.05) and in control group mSBI reduced by 1.47 (p<0.05). The reduction in mSBI was slightly more in control group when compared to test group but not significant (p>0.05). There was reduction in bleeding in both test and control groups [19].

The results of our study supports the results of the previous studies with significant reduction in PD and CAL gain in test group when compared to control group. Here in our study all the clinical parameters had been checked which was not done in previous studies. This is the only and first study which had been done exclusively in molars.

The limitations of our study are 1) it was not a split mouth design, 2) patient selection was not randomized and also not blinded and 3) radiographic comparisons was not done in both groups [20].

Conclusion

Within the limitations of our study we can conclude that PD reduction and CAL gain improved with 0.5% AZM local drug delivery in 1^st and 2^nd molars. Further studies with much more samples and long term post-operative assessment are needed to substantiate our results.

References

1. Loesche, WJ. “Chemotherapy Of Dental Plaque Infections.” Oral Sci Rev 9 (1976): 65-107.

   [Google Scholar] [Pubmed]

2. Mombelli, Andrea, Schmid B, Rutar A, and Lang NP. “Persistence Patterns of Porphyromonas Gingivalis, Prevotella Intermedia/Nigrescens, and Actinobacillus Actinomycetemcomitans after Mechanical Therapy of Periodontal Disease.” J Periodontol 71 (2000): 14-21.

   [Crossref] [Google Scholar] [Pubmed]

3. Greenstein, G, and A Polson. “The Role of Local Drug Delivery in the Management of Periodontal Disease: A Comprehensive Review.” J Periodontol 69 (1998):507-520.

   [Google Scholar] [Crossref][Pubmed]

4. Soskolne, WA. “Subgingival Delivery of Therapeutic Agents in the Treatment of Periodontal Diseases.” Crit Rev Oral Biol Med 8 (1997):164-174.

   [Crossref] [Google Scholar] [Pubmed]

5. Pajukanta, R, Asikainen S, Saarela M, Alaluusua S, and Jousimies Somer H. “In Vitro Activity of Azithromycin Compared with that of Erythromycin against Actinobacillus actionmycetemcomitans.” Antimicrob Agents Chemother 36 (1992):1241-1243.

   [Crossref] [Google Scholar] [Pubmed]

6. Pajukanta, R. “In Vitro Antimicrobial Susceptibility of Porphyromonasgingivalis to Azithromycin, A Novel Macrolide.” Oral Microbiol Immunol 8 (1993):325-326.

   [Crossref] [Google Scholar] [Pubmed]

7. Tokgo¨z, B, Sari HI, Yildiz O, et al. “Effects of Azithromycin on Cyclosporine-Induced Gingival Hyperplasia in Renal Transplant Patients.” Transplant Proc 36 (2004): 2699-2702.

   [Crossref] [Google Scholar] [Pubmed]

8. Killoy, WJ. “Chemical Treatment of Periodontitis: Local Delivery of Antimicrobials.” Int Dent J 48 (1998): 305-315.

   [Crossref] [Google Scholar] [Pubmed]

9. McDonald PJ, and Pruul H. “Phagocytic Uptake and Transport of Azithromycin.” Eur J ClinMicrobiol Infect Dis 10 (1991):828-833.

   [Crossref] [Google Scholar] [Pubmed]

10. Gomi, K, Yashima A, Nagano T, Kanazashi M Maeda, and N Arai T. “Effects of Full-Mouth Scaling and Root Planning in Conjunction with Systemically Administered Azithromycin.” J Periodontol 2007;78, 422-429.

    [Crossref] [Google Scholar] [Pubmed]

11. Smith, SR, Foyle DM, Daniels J, Bechal J, and Smales S, et al. “A Double-Blind Placebo-Controlled Trial of Azithromycin as an Adjunct to Nonsurgical Treatment of Periodontitis in Adults: Clinical Results.” J Clin Periodontol 29 (2001): 54-61.

    [Crossref] [Google Scholar] [Pubmed]

12. Mascarenhas, P, Gapsi R, Al-Shammari K, Hill R, and Soehren S, et al. “Clinical Response of Azithromycin as an Adjunct to Nonsurgical Periodontal Therapy in Smokers.” J Periodontol 76 (2005): 426-436.

    [Crossref] [Google Scholar] [Pubmed]

13. Dastoor, SF, Travan S, Neiva RF, Rayburn LA, and Giannobile WV, et al. “Effect of Adjunctive Systemic Azithromycin with Periodontal Surgery in the Treatment of Chronic Periodontitis in Smokers: A Pilot Study.” J Periodontol (2007): 78: 1887-1896.

    [Crossref] [Google Scholar] [Pubmed]

14. Haas AN, de Castro GD, Moreno T, Susin C, and Albandar JM, et al. “Azithromycin as an Adjunctive in Treatment of Aggressive Periodontitis:12-Months Randomized Clinical Trial.” J Clin Periodontol 35 (2008): 696-704.

    [Crossref] [Google Scholar] [Pubmed]

15. Yashima, A, Gomi K, Maeda N, and Arai T. “One-Stage Full Mouth Versus Partial-Mouth Scaling and Root Planing during the Effective Half-Life of Systemically Administered Azithromycin.” J Periodontol 80 (2009): 1406-1413.

    [Crossref] [Google Scholar] [Pubmed]

16. Morozumi, T, Kubota T, Abe D, Shimizu T, and Komatsu Y, et al. “Effects of Irrigation with an Antiseptic and Oral Administration of Azithromycin on Bacteremia caused by Scaling and Root Planing.” J Periodontol 81 (2010): 1555-1563.

    [Crossref] [Google Scholar] [Pubmed]

17. Han B, Emingil G, Ozdemir G, Tervahartiala T, and Vural C, et al. “Azithromycin as an Adjunctive Treatment of Generalized Severe Chronic Periodontitis: Clinical, Microbiologic And Biochemical Parameters.” J Periodontol 83 (2012): 1480-1491.

    [Crossref] [Google Scholar] [Pubmed]

18. Pradeep, AR, Sagar SV, and Daisy H. “Clinical and Microbiologic Effects of Subgingivally Delivered 0.5% Azithromycin in the Treatment of Chronic Periodontitis.” J Periodontol 79 (2008):2125-2135.

    [Crossref] [Google Scholar] [Pubmed]

19. Pradeep, AR, Bajaj P, Agarwal E, Rao NS, and Naik SB, et al. “Local Drug Delivery of 0.5% Azithromycin in the Treatment of Chronic Periodontitis among Smokers.” Aust Dent J 58 (2013): 34-40.

    [Crossref] [Google Scholar] [Pubmed]

20. Agarwal, E, Pradeep AR, Bajaj P, and Naik SB. “Efficacy of Local Drug Delivery of 0.5% Clarithromycin Gel as an Adjunct to Nonsurgical Periodontal Therapy in the Treatment of Chronic Periodontitis Subjects among Smokers-A Randomized Controlled Clinical Trial.” J Periodontol 83 (2012):1155-1163.

    [Crossref] [Google Scholar] [Pubmed]