Alternative Antibiotic Regime in the Treatment of GAgP
Condition: Generalized Aggressive Periodontitis; Aggressive Periodontitis
MeSH terms: Periodontitis; Aggressive Periodontitis; Aggression
Study type: Interventional
Phase: Phase 4

Summary: 
      The objective of this randomized clinical study was to evaluate the effect of systemic
      administration of moxifloxacin compared to amoxicillin plus metronidazole combined with
      non-surgical treatment in patients with generalized aggressive periodontitis (GAgP) in
      6-month follow-up.

      A total of 40 systemically healthy patients with GAgP will evaluate in this randomized
      clinical trial. Periodontal parameters (plaque index, gingival index, probing depth, bleeding
      on probing, clinical attachment level) will be recorded at baseline, 1st, 3rd and 6th month.
      Patients will receive either 400 mg moxifloxacin per os once daily or 500 mg metronidazole
      and 500 mg amoxicillin per os three times daily for 7 days consecutively.
    

Detailed description: 
      The American Academy of Periodontology and the European Federation of Periodontology were
      reported that patients with GAgP may have benefit from adjunctive administration of
      antibiotics. Antibiotics are used as an adjunct to nonsurgical treatment either locally or
      systemically. Systemic antimicrobial agents as adjunct to nonsurgical treatment provide
      additional benefits over mechanical therapy alone in terms of probing depth reduction and
      periodontal attachment gain.

      Amoxicillin is a moderate spectrum, bacteriolytic β-lactam antibiotic, and metronidazole
      which is active against anaerobic bacteria is a nitroimidazole. scaling and root planing
      combination with metronidazole plus amoxicillin therapy was found to be more effective in
      suppressing P. gingivalis and eradication of A. actinomycetemcomitans and preventing
      re-colonization of A. actinomycetemcomitans because of the synergistic effect of this
      combination and their wide spectrum of activity. It was found to be superior to azithromycin,
      doxycycline, and metronidazole in the treatment of GAgP.

      Quinolones were introduced for use in urinary tract infections in the 1970s. Moxiflocaxin is
      a fourth generation fluoroquinolone antibiotic exhibits good tissue penetration and high oral
      bioavailability and has improved activity against Gram- positive, aerobic and anaerobes.
      Moxifloxacin is used in the systemic treatment of respiratory infections, acute sinusitis,
      odontogenic abscesses, osteomyelitis of the mandible and locally in the treatment of
      ophthalmic infections.

      Moxiflocaxin has good activity against putative periodontal pathogens, including
      Porphyromonas gingivalis, Tanneralla forsythia, Prevotella spp, Fusobacterium nucleatum,
      Actinomyces spp, Campylobacter rectus, Peptostreptococcus spp. and Aggregatibacter
      actinomycetemcomitans, located within biofilm or intracellulary. It was shown that A.a.
      strains were highly susceptible to fluoro-quinolones ciprofloxacin and moxifloxacin. Some of
      the adjunctive antibiotics are secreted in saliva in insufficient concentrations to inhibit
      A.a. Moxifloxacin seems to be secreted in saliva at higher levels than in plasma and may also
      concentrate at the site of infection since it penetrates polymorphonuclear granulocytes and
      epithelial cells. Moxifloxacin was found to be superior to clindamycin, metronidazole or
      doxycycline.

      Systemic administration of moxifloxacin as an adjunct to scaling and root planing was found
      to be more effective compared to scaling and root planing alone or scaling and root planing
      in conjunction with doxycycline in the treatment of severe chronic periodontitis. To best our
      knowledge, there is no study that evaluates the effect of moxifloxacin adjunct to scaling and
      root planing in the treatment of GAgP.

      The aim of this single center, randomized clinical study was to evaluate the impact of
      adjunctive systemic moxifloxacin compared to the use of adjunctive systemic amoxicillin and
      metronidazole during full-mouth scaling and root planing on the success of the treatment of
      patients with GAgP with 6-month follow-up. The hypothesis was the use of adjunctive systemic
      moxifloxacin would provide the similar clinical results as adjunct systemic amoxicillin and
      metronidazole during scaling and root planing.

      This study was a single-center, randomized, parallel-design clinical trial with 6 month
      follow-up. It was conducted at Kocaeli University, Faculty of Dentistry, Department of
      Periodontology between 2011-2013. The study protocol was approved by the Ethics Committee of
      the Medical Faculty of Kocaeli University (KOU KAEK 5/9) and was conducted in accordance with
      the Helsinki declaration of 1975, as revised in 2000.

      The GAgP patients were recruited from patients seeking periodontal treatment at Kocaeli
      University, Faculty of Dentistry, Department of Periodontology, Kocaeli, Turkey.
      Approximately, 12.000 patients were screened the dates between June 2011 and September 2012.
      A complete medical, dental, periodontal and radiographic examination was performed. The study
      protocol explained to the patients. From patients who willing to participate to the study,
      written informed consent was obtained and included the study.

      The periodontal diagnosis of subjects with GAgP was established on the basis of clinical and
      radiographic criteria defined by the 1999 International World Workshop for a Classification
      of Periodontal Diseases and Conditions. Patients were included if they were between 18 and 35
      years of age and otherwise healthy. The bone loss estimation was radiographically performed
      in each patient for the assessment of the extent and severity of alveolar bone loss. Medical
      and dental histories were questioned. Subjects were excluded if they had any known systemic
      diseases or conditions that can/could influence the periodontal status (cancer,
      cardiovascular and respiratory diseases), history of hepatitis or HIV infection,
      immunosuppressive chemotherapy, current pregnancy, planning a pregnancy or lactation,
      requirement for antibiotic prophylaxis, oral diseases other than GAgP, ongoing orthodontic
      therapy, a history of antibiotic therapy or periodontal treatment within the preceding six
      months. Subjects were excluded if they had known allergies to quinolones or penicillin or
      metronidazole.

      Periodontal Examination The full-mouth clinical periodontal measurements were recorded at 6
      sites per tooth (mesio-buccal, mid-buccal, disto-buccal, disto-lingual, mid-lingual, and
      mesio-lingual) including plaque index (PI), gingival index (GI), probing depth (PD), bleeding
      on probing (BOP) and clinical attachment level (CAL). CAL was calculated from the
      cement-enamel junction to the base of the periodontal pocket. Williams periodontal probe was
      used for periodontal measurements. All measurements and scaling and root planing were
      performed by the same single calibrated and trained periodontist in a standardized manner.

      Allocation concealment The patients were randomly assigned to one of the study groups. To
      ensure complete masking of allocation, before the recruitment of the patients, forty
      identical, opaque-colored, impermeable plastic bags which include toothbrush, interproximal
      brush, toothpaste and either moxifloxacin or amoxicillin and metronidazole were prepared and
      coded. A code number was given to each subject. Randomization codes were kept separately from
      the clinical evaluation forms by one of the authors until the treatment and follow-up visits
      were completed. The examiner who performed the treatment was unaware of the allocation.

      Prior to treatment, all subjects were gone through motivation sessions for oral hygiene.

      Following to periodontal measurements, full-mouth supragingival scaling using ultrasonic
      scaler and polishing were performed, and a toothbrush, toothpaste and an interproximal
      toothbrush were provided to all subjects. One week later, the patients were examined for
      plaque accumulation and oral hygiene. The patients who cannot maintain proper oral hygiene
      were excluded from the study. Only 39 patients fulfilled the qualification criteria for
      enrollment for the present study.

      Subjects were randomly assigned to receive one of the two treatment groups. Moxifloxacin
      group received scaling and root planing and an adjunctive systemic antibiotic, 400 mg
      moxifloxacin, once in a day for 7 days and amoxicillin and metronidazole group received a
      combination of 500 mg of amoxicillin and 500 mg metronidazole three times per day for 7 days.
      The subjects were instructed to take first dose of the antibiotics in the morning of the
      first session since the microorganisms are organized on the root surface and protected from
      antimicrobial agents. Scaling and root planing were performed on 2 consecutive days in 24
      hours under the local anesthesia. On each day, scaling and root planing were performed in 2
      quadrants using ultrasonic scalers and manual instruments . The endpoint of scaling and root
      planing was a tactile smooth root surface.

      The subjects were insistently informed about the intake of the antibiotics properly, and they
      asked to inform the researches if they needed to take another antibiotics or
      anti-inflammatory agents for another reason during and following the study for 6 months.

      Patients used a 0.2% chlorhexidine digluconate rinse twice a day for a month and brushed
      their teeth by tooth brushes and interproximal tooth brushes twice a day. Patients asked to
      report any adverse events and side effects of the antimicrobial agents as soon as possible.

      Subjects were monitored one week after the second scaling and root planing session. At this
      session, antibiotic intake, adverse events and side effects were questioned; oral hygiene and
      plaque accumulation were controlled. Subjects were screened at 1, 3 and 6 months after
      completion of nonsurgical treatment. During these sessions, clinical periodontal parameters,
      any medical history change, especially, whether antibiotic therapy had been prescribed for
      any reason was recorded. At the end of these sessions, supragingival scaling was performed,
      if needed.

      The present study was conducted within in the same clinic, and the patients were taken to the
      same dental chair and treated with a same experienced periodontist for to discard
      discrepancies and to provide standardized and controlled environment.

      Sample size calculation

      The primary outcome variable was probing depth changes. The sample size was calculated based
      on previous information from a study conducted in our department, using data relative to the
      mean difference and standard deviation (SD) between the experimental periods for the probing
      depth parameters.57 Considering a mean probing depth difference of 1.3 mm between evaluation
      periods, it was estimated that 13 patients for each group would be necessary to provide 95%
      power (0.54 SD, α error of 0.05, and β error of 0.2).58 However, we aimed to recruit 20
      patients to each group if we lose to follow the patients during the study.
    

Intervention name(s): Amoxicillin; Metronidazole; Moxifloxacin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 500 mg, 3 times per day for 7 days; 500 mg, 3 times per day, for 7 days; 400 mg, once in a day for 7 days.
Other intervention name(s): largopen; flagyl; pitoxil
Intervention MeSH terms: Amoxicillin; Moxifloxacin; Metronidazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Aggressive periodontitis; amoxicillin; metronidazole; moxifloxacin; nonsurgical periodontal debridement.