Tinidazole inhibitory and cidal activity against anaerobic periodontal pathogens

The in vitro activity of tinidazole against anaerobic periodontal pathogens (25 Prevotella buccae, 18 Prevotella denticola, 10 Prevotella intermedia, 6 Prevotella melaninogenica, 5 Prevotella oralis, 10 Fusobacterium nucleatum and 8 Veillonella spp.) was determined by agar dilution. MIC90 values (minimum inhibitory concentration for 90% of the organisms) were 8 μg/mL for Veillonella spp., 4 μg/mL for P. intermedia, 2 μg/mL for P. buccae, 1 μg/mL for Fusobacterium spp. and 0.5 μg/mL for other Prevotella spp. Cidal activity was studied by killing curves with tinidazole and amoxicillin (alone and in combination) at concentrations similar to those achieved in crevicular fluid (41.2 μg/mL tinidazole and 14.05 μg/mL amoxicillin) against an inoculum of ca. 107 colony-forming units/mL of four bacterial groups, each one composed of four different strains of the following periodontal isolates: Prevotella spp., Fusobacterium spp. and Veillonella spp. (anaerobes) and one amoxicillin-susceptible Streptococcus spp. (facultative) in a proportion of 1:1:1:1. When only β-lactamase-negative Prevotella or Fusobacterium strains were tested, significantly higher reductions were found with amoxicillin (>4 log reduction at 48 h) versus controls. The presence of β-lactamase-positive Prevotella spp. or F. nucleatum strains rendered amoxicillin inactive (no reductions at 48 h), with no differences from controls. Amoxicillin + tinidazole produced >3 log reduction at 24 h and >4 log reduction at 48 h regardless of the presence or not of β-lactamase-positive strains. The presence in crevicular fluid of β-lactamases produced by β-lactamase-positive periodontal pathogens may have ecological and therapeutic consequences since it may protect β-lactamase-negative periodontal pathogens from amoxicillin treatment. In vitro, tinidazole offered high antianaerobic activity against β-lactamase-positive and -negative periodontal pathogens, avoiding amoxicillin inactivation.