Abstract
The in vitro resistance of selected red/orange complex periodontal pathogens to tinidazole was compared with four other antibiotics. Subgingival biofilm samples from 88 adults with severe periodontitis were anaerobically incubated on enriched Brucella blood agar with and without supplementation with tinidazole (16 mg/L), metronidazole (16 mg/L), amoxicillin (8 mg/L), doxycycline (4 mg/L), or clindamycin (4 mg/L). Growth of Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia/nigrescens, Parvimonas micra, Fusobacterium nucleatum, Streptococcus constellatus, or Campylobacter rectus on antibiotic-supplemented plates indicated their in vitro antibiotic resistance. Tinidazole inhibited all test species, except P. intermedia/nigrescens, P. micra, and S. constellatus in 3.8%, 10.2%, and 88.9% of species-positive patients, respectively. Significantly fewer patients yielded tinidazole-resistant test species, and had significantly lower subgingival proportions of tinidazole-resistant organisms, than patients with amoxicillin, doxycycline, or clindamycin-resistant species, but not those with metronidazole-resistant strains. Joint in vitro species resistance to tinidazole and amoxicillin, or metronidazole and amoxicillin, was rare. Tinidazole performed in vitro similar to metronidazole, and markedly better than amoxicillin, doxycycline, or clindamycin, against fresh clinical isolates of red/orange complex periodontal pathogens. As a result of its similar antimicrobial spectrum, and more convenient once-a-day oral dosing, tinidazole should be considered in place of metronidazole for systemic periodontitis drug therapy.
Highlights
Human periodontitis is a destructive form of periodontal disease that is triggered by pathogenic bacterial biofilms, possibly in synergy with certain lytic herpesviruses [1], and mediated by dysregulated host hyper-inflammatory responses, causing progressive connective tissue attachment loss and alveolar bone resorption around teeth, leading to their loss from the oral cavity [2].Among the approximately 700 known microbial species and uncultivated phylotypes that inhabit the human oral cavity, only a subset is associated with a pathogenic subgingival microbial dysbiosis in periodontitis-affected patients [3]
(34 male, 54 female; mean age = 57.2 ± 13.3 years; age range = 35–83 years old) with severe periodontitis from whom subgingival samples were consecutively submitted by USA private practicing periodontists for microbiological analysis and antibiotic resistance testing to metronidazole, amoxicillin, doxycycline, and clindamycin at the Oral Microbiology Testing Service (OMTS) Laboratory at Temple University School of Dentistry, Philadelphia, PA, USA, which is licensed for high complexity bacteriological analysis by the Pennsylvania Department of Health
The major finding from this study is that tinidazole performed similar to metronidazole, and markedly better than amoxicillin, doxycycline, and clindamycin, with regard to in vitro inhibition of fresh clinical isolates of red/orange complex periodontal pathogens recovered from adults with severe periodontitis
Summary
Among the approximately 700 known microbial species and uncultivated phylotypes that inhabit the human oral cavity, only a subset is associated with a pathogenic subgingival microbial dysbiosis in periodontitis-affected patients [3]. Oral administration of metronidazole, which is highly active against anaerobic bacteria, is beneficial in enhancing therapeutic outcomes in severe periodontitis patients beyond that attained by conventional mechanically-based forms of periodontal therapy alone [8,9,10,11,12,13], due in large part to a significantly greater suppression of subgingival red/orange complex species achieved with systemic metronidazole therapy [14,15,16,17]
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