In vitro activity of antibiotics alone and in combination against Actinobacillus actinomycetemcomitans

The MICs for 90% of the organisms tested (MIC₉₀s) of 11 antibiotics against 24 clinical isolates of Actinobacillus actinomycetemcomitans were determined by the MIC 2000 system. The lowest MIC₉₀s (16 μg/ml) were observed with ceftriaxone and rifampin. The next lowest MIC₉₀s were found with cephapirin, tetracycline, and chloramphenicol (3.12 μg/ml). The MIC₉₀s of penicillin, ampicillin, ticarcillin, piperacillin, and amikacin were each ≥12.5 μg/ml. Antibiotic synergy was studied by the killing curve method and was defined as a ≥2 log₁₀ reduction in CFU when two antibiotics were used in combination at one-fourth the MBC for each compared with the effect of each antibiotic alone at one-half the MBC. Synergism between rifampin and penicillin, cephapirin, or ceftriaxone was tested for with 12 A. actinomycetemcomitans strains. In 7 of 37 instances, synergism was demonstrated for the combinations rifampin plus ceftriaxone (n = 3) or rifampin plus penicillin (n = 4); in 9 instances, an additive effect was noted, and impaired killing with drug combinations compared with the effect of a single antibiotic was suggested in 4 strains. The majority of strains were indifferent to the combinations. Similarly, variable results were observed when the combination of trimethoprim and cephapirin was tested against eight A. actinomycetemcomitans strains. Our data suggest that rifampin and cephapirin are the most active of the 11 antibiotics studied against A. actinomycetemcomitans. In addition, in vitro synergism between rifampin and other antibiotics or between trimethoprim and cephapirin was not consistently demonstrable.