In Vitro Killing Activity of Crevicular Concentrations of Tinidazole Plus Common Oral Antibiotics Against High‐Density Mixed Inocula of Periodontal Pathogens in Strict Anaerobic Conditions

Abstract

Background: Odontogenic infections are polymicrobial. This study explores the in vitro killing activity by concentrations similar to those found in crevicular fluid of tinidazole in combination with amoxicillin/clavulanic acid, clindamycin and levofloxacin against four groups of high-density mixed inocula of anaerobes (Prevotella buccae, Fusobacterium nucleatum, and Veillonella spp.) and facultative (Capnocytophaga spp. and Streptococcus spp.) isolates of periodontal pathogens.

Methods: Killing curves were assessed under strict anaerobic conditions with antibiotics alone and in combination with tinidazole at concentrations similar to those achieved in crevicular fluid against ∼107 colony forming units (CFU)/ml inoculum (1:1:1:1:1 proportion of the five bacterial isolates) of the four bacterial groups. Group 1 did not include β-lactamase–producing strains; groups 2, 3, and 4 included one, two, and three β-lactamase–producing strains, respectively.

Results: In single-drug experiments, at 48 hours, tinidazole alone did not show significant killing of the entire bacterial population, whereas reductions in the initial inocula ≥2.09 log10 CFU/ml with clindamycin, ≥3.26 log10 CFU/ml with amoxicillin/clavulanic acid, and ≥3.83 log10 CFU/ml with levofloxacin were obtained. When combined with tinidazole, reductions were significantly higher for all antibiotics: ≥5.28 log10 CFU/ml with clindamycin, ≥4.78 log10 CFU/ml with amoxicillin/clavulanic acid, and ≥6.17 log10 CFU/ml with levofloxacin.

Conclusion: In addition to its high activity against anaerobic periodontal pathogens, tinidazole offered synergism with other antibiotics against the large strict anaerobic subpopulation and the small facultative subpopulation of a high-density mixed inocula of odontogenic pathogens under strict anaerobic conditions, similar to those of odontogenic infections.