Spiramycin-Metronidazole Synergism Testing on Aggregatibacter actinomycetemcomitans

Background The potential synergism of spiramycin-metronidazole in combination against <i>Aggregatibacter</i> <i>actinomycetemcomitans</i>, a major pathogen in human periodontitis, peri-implantitis, and some non-oral infections, was studied in vitro in comparison to combinations of amoxicillin-metronidazole and ciprofloxacin-metronidazole. Methods Minimal inhibitory concentrations (MICs) for spiramycin, amoxicillin, ciprofloxacin, and metronidazole were determined individually against four periodontal <i>A. actinomycetemcomitans</i> clinical isolates. Synergism testing for the combinations of spiramycin-metronidazole, amoxicillin-metronidazole, and ciprofloxacin-metronidazole was performed with gradient diffusion strips for each antibiotic pair placed onto <i>A. actinomycetemcomitans</i>-inoculated <i>Haemophilus</i> test medium in a cross formation at the intersection of each of their individual MICs against <i>A. actinomycetemcomitans</i> <i>.</i>Fractional inhibitory concentration index values assessed the antibiotic interactions. Results Spiramycin and metronidazole individually had poor antimicrobial activity against <i>A. actinomycetemcomitans</i>. However, lower MIC values and less <i>A. actinomycetemcomitans</i> resistance were found for both antibiotics when tested in combination. Spiramycin-metronidazole synergism was additionally detected against one <i>A. actinomycetemcomitans</i> clinical isolate. In comparison, combinations of amoxicillin-metronidazole and ciprofloxacin-metronidazole exhibited antimicrobial synergism against all four <i>A. actinomycetemcomitans</i> strains. Conclusions Spiramycin and metronidazole exerted greater in vitro antimicrobial activity in combination than individually against <i>A. actinomycetemcomitans</i>. Antimicrobial synergism between spiramycin and metronidazole was also found with one <i>A. actinomycetemcomitans</i> clinical isolate, representing the first detection of spiramycin-metronidazole synergism against <i>A. actinomycetemcomitans</i>. However, antimicrobial synergism against <i>A. actinomycetemcomitans</i> was less frequently detected with spiramycin-metronidazole as compared to combinations of amoxicillin-metronidazole or ciprofloxacin-metronidazole. These findings may help clinicians in the selection of effective antimicrobial therapies against oral and non-oral infections involving <i>A. actinomycetemcomitans</i>.