Quantitative comparison of the cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts

The cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts (Pel cells) vas studied. Pel cells were exposed for 48 h to erythromycin (EM). clarithromycin (CAM), roxithromycin (RXM), azithromycin (AZM), josamycin (JM). midecamycin (MDM), and rokitamycin (RKM), and allotted to form colonies. The cytocidal effect of the macrolicles was measured as a decrease in colony-forming efficiency and as found to increase with the concentration, To obtain a quantitative measure of the cytocidal effect, the LD50, i.e. the concentration that decreases colony-forming efficiency 50% relative to control cells. was extrapolated from the concentration-response curves. The rank of the macrolides according to their cytocidal effect (LD50) vas RKM > RXM > CAM > AZM > JM > MDM : EM. RKM, RXM. CAM. AZM. and JM cre at least 1 7 12.2 times more cytocidal than MDM or EM. When extrapolated from the concentration-response curves, the relative survival of the Pel cells exposed to each of the macrolides at the MIC90 concentrations for periodontopathic hacteria was estimated to be: greater than or equal to 53.8% for RKM, greater than or equal to 92.7% for RXM, greater than or equal to 94.6% for CAM. greater than or equal to 97.1% for AZM. and greater than or equal to 86.2% for EM. The effect of the antibiotics on the mRNA expression of alkaline phosphatase (ALP) and type I procollagen (COL) was examined in Pel cells exposed for 48 h to RXM. CAM. AZM. and EM, which exhibited strong, moderate, and weak cytocidal activity. The constitutive levels of both ALP and COL mRNA were retained in cells exposed to RXM at less than or equal to 3 muM. CAM at less than or equal to 10 muM. and AZM or EM at less than or equal to 3 muM, The MIC90 against periodontopathic bacteria is less than or equal to 4.8 muM for RXM, 5.3 muM for CAM. 2.7 muM for AZM, and 21.8 muM for EM. These results suggest that topical administration of CAM or AZM to the gingival crevice at their MIC90 concentration for periodontopathic bacteria would have little adverse effect on the growth and differentiation of the periodontal ligament. It is important to note, however that these findings have yet to be extrapolated to in vivo conditions.