|Year : 2014 | Volume
| Issue : 3 | Page : 112-118
Comparative evaluation of amoxicillin plus metronidazole and doxycycline alone in the nonsurgical treatment of localized aggressive periodontitis
Rajasekhar Nutalapati1, Suresh Kumar Kasagani2, Narendra Dev Jampani3, Ramesh Babu Mutthineni4, Srikanth Chintala4, Venkata Satyanarayana Kode5
1 Department of Periodontics, Sree Sai Dental College and Research Institute, Srikakulam, India
2 Department of Periodontics, Rama Dental College and Hospital, Kanpur, Uttar Pradesh, India
3 Department of Periodontics, Government Dental College and Hospital, Vijayawada, India
4 Department of Periodontics, Mamata Dental College, Khammam, India
5 Department of Periodontics, MN Raju Dental College and Hospital, Sangareddy, Andhra Pradesh, India
|Date of Submission||27-Jun-2013|
|Date of Acceptance||12-May-2014|
|Date of Web Publication||12-Nov-2014|
Department of Periodontics, Sree Sai Dental College and Research Institute, Srikakulam, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Aim and Objective: To evaluate the effects of a combination of amoxicillin plus metronidazole and doxycycline alone in the nonsurgical treatment of localized aggressive periodontitis (LAP) and compare their effects on clinical and microbiological parameters during 90 days followup in patients with LAP.
Materials and Methods: A total of 20 patients with LAP were included in the study. Collection of subgingival plaque samples and recordings of clinical parameters, that is, plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment loss (CAL) was done at baseline. The subjects were randomly divided into two groups. Group I subjects were given a combination of amoxicillin plus metronidazole and Group II subjects were given doxycycline. Full-mouth scaling and root planing (SRP) was performed at day 10. Collection of subgingival plaque samples and recording of clinical parameters was repeated at days 10, 30, and 90.
Results: There was a statistically highly significant difference (P < 0.001) for both Group I and Group II at baseline and days 10, 30, and 90 for all the clinical parameters. With respect to PI and GI, there was a statistically significant difference in Group I at days 30 and 90 (P < 0.05) compared to Group II. For the PPD and CAL, there was a statistically significant difference in Group I at days 10, 30, and 90, (P < 0.05) compared to Group II.
Conclusion: Systemic administration of doxycycline with full mouth SRP resulted in a better improvement of periodontal parameters and elimination/suppression of putative periodontal pathogens such as Aa, Pg, and Tf, than amoxicillin plus metronidazole in patients with LAP.
Keywords: Amoxicillin, chemotherapy, doxycycline, localized aggressive periodontitis, metronidazole, microbiology
|How to cite this article:|
Nutalapati R, Kasagani SK, Jampani ND, Mutthineni RB, Chintala S, Kode VS. Comparative evaluation of amoxicillin plus metronidazole and doxycycline alone in the nonsurgical treatment of localized aggressive periodontitis
. Indian J Oral Sci 2014;5:112-8
|How to cite this URL:|
Nutalapati R, Kasagani SK, Jampani ND, Mutthineni RB, Chintala S, Kode VS. Comparative evaluation of amoxicillin plus metronidazole and doxycycline alone in the nonsurgical treatment of localized aggressive periodontitis
. Indian J Oral Sci [serial online] 2014 [cited 2019 Jul 22];5:112-8. Available from: http://www.indjos.com/text.asp?2014/5/3/112/144514
| Introduction|| |
Localized aggressive periodontitis (LAP) has been identified as a different disease entity, and results of clinical and microbiologic studies show that it has a complex etiology and pathogenesis in periodontal destruction. , Since the disease is characterized by a rapid destruction pattern, different treatment modalities besides conventional periodontal treatment are used.  The unique subgingival microflora of disease is one of the most important reasons for periodontal destruction. , Preliminary studies on the subgingival flora of patients with LAP demonstrate that Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) are the most encountered microorganisms in these patients.  Research studies on the microbiota of LAP patients reveal the presence of Aa and demonstrate that this organism plays a significant role in the etiology and the progression of the disease. ,
In periodontal infections and elsewhere, polymorphonuclear leukocytes (PMNs) migrate to the infection site, phagocytose the bacteria, and attempt to kill them with reactive oxygen metabolites and microbicidal proteins.  Although PMNs are highly effective in defending against bacterial infections, some pathogens are difficult to kill. For example, Aa resists phagocytic killing by PMNs. , The oxidative killing mechanisms of PMNs are not completely effective under anaerobic conditions. Therefore, antimicrobial agents are used to control these periodontal infections, which include - tetracyclines, ciprofloxacin, metronidazole, and synthetic penicillin, such as amoxicillin. , The main reason for choosing these antibiotics is their activity against anaerobic flora, availability in higher concentrations in gingival crevicular fluid, long duration in the tissues, and anticollagenolytic properties. , In addition to administration of tetracyclines or metronidazole alone in the treatment of periodontal infections, metronidazole has also been used in combination with amoxicillin because of the drug's synergistic effect. ,
The aim of this study was to evaluate the effects of a combination of amoxicillin plus metronidazole and systemic tetracycline derivative doxycycline alone in the nonsurgical treatment of localized aggressive periodontitis (LAP) and compare their effects on clinical and microbiological parameters during 90 days follow-up.
| Materials and Methods|| |
Twenty subjects, patients of the Department of Periodontics, Mamata Dental College and Hospital, Khammam, were recruited for the study. Each patient was given a detailed verbal description of the study. The research protocol was approved by the local ethical committee and the patients signed a consent form prior to commencement of the study. The subjects were diagnosed with LAP (according to 1999 international classification)  as assessed by their prestudy records, which included detailed medical and dental history, assessment of periodontal status, study models, radiographs, and photographs.
Inclusion criteria were - age between 16 and 30 when first diagnosed with LAP, systemically healthy patients, absence of any medication for the last 6 months, and no periodontal therapy for the previous 12 months. The criteria for exclusion were - pregnant or lactating women, presence of systemic diseases or drug allergies, patients on long-term anti-inflammatory therapy, patients having partially erupted or impacted teeth and those not willing to give consent for the study.
Orthopantomogram (OPG) or full-mouth IOPAs were taken for all the 20 subjects. The subjects were scheduled for collection of baseline samples of subgingival plaque and for recordings of baseline full-mouth clinical parameters, that is, plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment loss (CAL).
The subjects were divided into two equal groups (Group I and Group II) based on antibiotic regimen. Patients assigned to Group I (n = 10) were given combined antibiotic therapy with 500 mg amoxicillin (MOKKEM 500, Alkem Laboratories, Mumbai) plus 400 mg metronidazole (METROGYL 400, JB Chemicals and Pharmaceuticals Pvt. Ltd., Ankleshwar) three times a day for 10 days.  Patients assigned to Group II (n = 10) were given 100 mg doxycycline (DOXT® -100, Dr. Reddy's Laboratories Ltd., Yanam) for 10 days. The patients were prescribed two tablets on the first day and one tablet for the following 9 days. 
The subjects were recalled at day 10. Microbiologic sampling followed by the measurement of clinical parameters was repeated. During this visit, subjects were also given same-day full-mouth scaling and root planing under LA. Subjects were then recalled at days 30 and 90, for microbiologic sampling followed by the measurement of clinical parameters.
The following clinical parameters were recorded on four surfaces for all the fully-erupted teeth (buccal, lingual, mesial and distal) - Plaque Index (Silness and Loe, 1964),  Gingival Index (Loe and Silness, 1963),  Probing Pocket Depth (PPD) and Clinical Attachment Loss (CAL). The probing pocket depth was measured from the crest of the gingival margin to the base of the pocket using a graduated manual probe (UNC-15 mm probe; Hu-Friedy). CAL was recorded using a graduated manual probe (UNC-15 mm probe; Hu-Friedy). Any loss of attachment was calculated from two measurements as follows: CAL = PPD - distance from free gingival margin to CEJ. When the crest of the gingiva was on the root surface, the score was recorded as negative. When the crest of the gingiva was on the enamel, the score was recorded as positive.
Subgingival plaque samples were taken from the deepest pockets of mesial sites, either right or left, of maxillary first molar teeth from all the subjects (one site per subject). Prior to collection of the subgingival plaque samples, the supragingival areas of the teeth were cleaned with sterile sponges to avoid contaminating the subgingival specimens with supragingival organisms. The selected site was isolated using sterile cotton rolls to avoid salivary contamination. A sterile Gracey curette (No. 11/12 or No. 13/14) was inserted gently into the selected site up to the apical pocket limit and then drawn coronally with sufficient force to collect the most apically located subgingival plaque but not to plane the root [Figure 1]. Care was taken not to contaminate the plaque sample with blood that resulted due to bleeding while manipulating the instrument in the pocket.
Vials containing transfer media (thioglycollate broth with hemin and Vitamin K 1 ) were taken and the curette tip was vigorously agitated so as to dispense the entire plaque sample into the vial [Figure 2]. The vials were then closed tight and labeled according to the code number allotted to the particular patient. Within 72 h of sample collection, the vials were sent to the laboratory (Department of Microbiology, Maratha Mandal's NGH Institute of Dental Sciences and Research Centre, Belgaum, Karnataka) for culture. All samples were cultured for the three microorganisms - Porphyromonas gingivalis (Pg), Aggregetibacter actinomycetemcomitans (Aa) and Tanerella forsythia (Tf). The following culture media were used - Brewer's Anaerobic Agar [Figure 3] and Blood Agar (Brain Heart Infusion Agar + Sheep Blood) [Figure 4] for Pg and Aa, and Bacteroides Bile Esculin (BBE) Agar [Figure 5] for Tf. Identification of the three microorganisms was done according to standard protocol using key biochemical reactions. Following culture and identification, the number of colony forming units per ml (CFU/ml) for each microorganism was recorded [Figure 6].
The mean values of plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) were compared using the 'Student Unpaired "t" Test'. Intergroup comparisons were made by 'One-way ANOVA'. P value of <0.05 was considered as statistically 'significant' and P value < 0.001 was considered as statistically 'highly significant'. Significant differences between group means were determined using 'Bonferroni Test'.
| Results|| |
[Table 1], [Table 2], [Table 3], [Table 4] show the comparison of mean values and the statistical significance of PI, GI, PPD, and CAL scores, respectively, for both groups at baseline and days 10, 30, and 90. [Table 5] describes the microbiologic parameters.
|Table 5: Antimicrobial counts (Colony forming units-CFU/ml) obtained at baseline and day 10, day 30 and day 90 for group I and group II (in thousands)|
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| Discussion|| |
The furcation region of roots or the dentinal tubules act as a reservoir for persistent pathogenic bacteria even after periodontal surgical procedures alone. Soft tissue wall of the periodontal pocket also acts similarly. ,, Thus, along with mechanical periodontal therapy, an antibacterial treatment approach will suppress pathogenic bacteria and permit recolonization with healthy microorganisms.  Currently, data in the literature suggest that systemically administered antimicrobials can enhance the effects of mechanical treatment in the management of aggressive periodontitis as assessed by clinical parameters. However, because of the relative absence of randomized controlled clinical trials including microbiological data, no definitive guidelines exist regarding the most effective antibiotic regime and time of administration for this group of patients.  Therefore, this study was designed in order to evaluate the effects of a combination of amoxicillin plus metronidazole and systemic tetracycline derivative doxycycline alone in the nonsurgical treatment of localized aggressive periodontitis (LAP) and compare their effects on clinical and microbiological parameters during 90 days follow-up.
All patients were given detailed oral hygiene instructions during 90 days of follow-up. Doxycycline and amoxicillin plus metronidazole treated patients demonstrated a pattern of decrease in their PI and GI scores during the entire study period compared to baseline PI and GI values. Furthermore, patients treated with doxycycline showed a statically significant decrease in PI and GI scores compared to the PI and GI scores of amoxicillin plus metronidazole treated patients at days 30 and 90. This decrease in PI and GI scores can be attributed to the improved oral hygiene methods of the patients. This is in accordance with the results of studies by Akincibay et al. (who administered doxycycline or amoxicillin plus metronidazole) and Jenkins et al. (who administered metronidazole). However, studies performed by Christersson et al. failed to report any changes in GI scores. This variation in the results may be due to the differences in the study population in terms of their socioeconomic status, education level, and oral hygiene awareness.
It was seen that amoxicillin plus metronidazole and doxycycline-treated patients demonstrated a pattern of decrease in their PPD and CAL values during the entire study period compared to baseline PPD and CAL values. Furthermore, patients treated with doxycycline showed a statistically significant decrease in PPD and CAL values compared to the PPD and CAL values of amoxicillin plus metronidazole treated patients at days 10, 30, and 90. This decrease in PPD and CAL values in both groups can be attributed to the administration of antibiotics in addition to scaling and root planing. This is in accordance with the results of studies by van Winkelhoff  (who applied metronidazole plus amoxicillin with mechanical therapy to patients) and Akincibay et al. (who administered doxycycline or amoxicillin plus metronidazole).
Studies have reported the failures in the treatment of patients of LAP with mechanical treatment alone. Clinical and microbiological studies have concluded that treatment of LAP was not complete without the elimination of Aa, Pg, and Tf, and that the efficacy of mechanical treatment was limited. Thus, use of different antibiotics in combination with SRP has been recommended to successfully eliminate periodontal pathogens such as Aa, Pg, and Tf. , Studies concerning the use of a single antibiotic or combined antibiotics in addition to mechanical treatment have reported successful results to eliminate periodontal pathogens from periodontal pockets. ,,
In this study, patients with LAP positive for Aa, Pg, and Tf, were given doxycycline or amoxicillin plus metronidazole combination before SRP. The reason for administering antibiotics before the mechanical therapy was initiated to determine the efficacy of the antibiotics alone without the influence of mechanical therapy on the elimination of periodontal pathogens. Aa, Pg, and Tf were found in all patients sampled at the baseline. After antibiotics were given to all patients, only a partial growth was seen in the cultures of three patients given amoxicillin plus metronidazole at day 10. Aa, Pg, and Tf did not grow on bacterial cultures of the rest of the patients given doxycycline or amoxicillin plus metronidazole.
Kapoor et al.  and Prakasam et al.  have stressed the importance of the use of systemic antibiotics along with mechanical therapy and stated that adjunctive antibiotic treatment frequently results in a more favorable clinical response than mechanical therapy alone. The clinical findings of this study indicate that patients with LAP given doxycycline demonstrated significant improved clinical parameters compared to those given amoxicillin plus metronidazole during 90 days. Where the microbiologic results were concerned, doxycycline showed successful elimination/suppression of Aa, Pg, and Tf completely in 10 days, whereas amoxicillin plus metronidazole showed complete elimination of Pg and Tf but only 70% reduction of Aa in 10 days. However, at days 30 and 90, both antibiotic regimes showed complete elimination of Aa, Pg, and Tf. Baltacioğlu et al.  reported that treatment of aggressive periodontitis with SRP plus systemic antibiotics provided significant clinical benefits over treatment with SRP alone, which reduced the need for periodontal surgery. However, their comparison of amoxicillin plus metronidazole and doxycycline alone did not yield any statistically significant difference and no microbiologic parameters were included in their study.
A limitation of this study was that it did not include the socioeconomic status of the participating subjects. Also, there was no comparison with an 'only SRP' group.
| Conclusion|| |
When treating LAP, it is imperative that the dental professional employ several treatment modalities to halt further periodontal attachment loss. These modalities may include oral hygiene instructions/reinforcement and evaluation of the patient's plaque control, supra- and subgingival scaling and root planing to remove the bacterial biofilms, implementation of antimicrobials, and periodontal maintenance. The findings of this study indicate that in patients with LAP, systemic administration of doxycycline with full mouth scaling and root planing resulted in a better improvement of periodontal parameters and elimination/suppression of putative periodontal pathogens such as Aa, Pg, and Tf, compared to systemic administration of a combination of amoxicillin plus metronidazole with scaling and root planing.
| Acknowledgments|| |
The authors would like to sincerely thank Dr. Kishore G. Bhat, Professor and Head, Department of Mcirobiology, Maratha Mandal's NGH Institute of Dental Sciences and Research Center, Belgaum, for successfully culturing the anaerobic microorganisms mentioned in the study.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]