The in vitro susceptibilities of Actinobacilus actinomycetemcomitans to 14 antimicrobial combinations were studied by using the checkerboard titration technique. The results, expressed as the range of the fractional inhibitory concentration indices, were as follows: for metronidazole or its hydroxymetabolite combined with cefixime, 0.2 to 0.6; for moxalactam, 0.2 to 0.6; for penicillin G, 0.3 to 0.6; for tobramycin, 0.8 to 2.0; for erythromycin, 0.8 to 1.7; for ciprofloxacin, 0.2 to 0.6; for tetracycline, 0.8 to 1.2. Our observations indicated that the 1-lactam antibiotics as well as ciprofloxacin act synergistically with both metronidazole and its hydroxymetabolite againstA. acinomycetemcomians. Synergistic interactions were independent ofthe individual MICs of the antibiotics tested. Erythromycin, tobramycin, and tetracycline combined with either metronidazole or its hydroxymetabolite showed additive to indifferent effects against the five strains ofA. actdnmycetemcomians, with the fractional inhibitory concentration indices ranging from 0.8 to 2.0. A. actinomycetemomitan was found to be hily susceptible to ciprofloxacin (MIC of ciprofloxacin for 90%o of strains tested, 0.010 p.g/ml) and cefixime (MIC of cefxime for 901% of strains tested, 0.8 ,ug/ml). The results indicate that in patients who are allergic to penicillin, cefixime and ciprofloxacin may be useful alternative antibiotics in combination with metronidazole for the treatment ofA. acdnomycetemcomians-associated periodontitis.Actinobacillus actinomycetemcomitans, a rod-shaped gram-negative coccobacillus, is a pathogen in several nonoral diseases (9,13,14,21,36) and a putative pathogen in periodontal disease (4,7,15,25,29,30,36). Treatment ofA. actinomycetemcomitans-associated periodontitis by subgingival debridement has appeared ineffective with regard to eradication ofA. actinomycetemcomitans from the periodontal area (23,24,31 (34) showed that mechanical treatment followed by a regimen of metronidazole and amoxicillin for 7 days is effective in eliminating A. actinomycetemcomitans from the infected sites. Recently, this was confirmed in a large patient group, in which more than 95% eradication of the microorganism was reported (35). An explanation for the in vivo efficacy may be the in vitro synergism against A. actinomycetemcomitans not only between metronidazole and amoxicillin but also between metronidazole and its hydroxymetabolite as well as between amoxicillin and the hydroxymetabolite of metronidazole (20). However, in some patients, effective treatment with the metronidazole-amoxicillin combination is contraindicated for several reasons; patients can suffer from serious adverse effects caused by amoxicillin, and patients can have allergies toward 3-lactam antibiotics. An alternative antibiotic therapy for these patients is still not available.The aim of the study described here was to investigate the interactions between several antibiotic combinations by using the checkerboard titration technique (3) low-up to this study, the in vitro susc...