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Long-term low-dose use of antimicrobials for periodontal therapy does not produce drug resistance. The guidelines for prescribing antibiotics in dentistry have changed significantly in recent years. Today, the American Dental Association has drastically reduced the number and types of patients who require prophylactic antibiotics before dental procedures to avoid producing oral bacteria with drug resistance. However, periodontists are currently prescribing long-term low doses of doxycycline for many of their recalcitrant periodontal patients. Does long-term doxycycline create resistant strains of bacteria? This issue was evaluated in the Journal of Periodontolgy (2000;71:1472–1483). This article compared 4 previous studies by the authors(Thomas J, Walker C, Bradshaw M.) in which subantimicrobial doses of doxycycline were given to adult periodontitis patients. In all studies, up to 20 mg of doxycycline were given 4 times a day to these patients. Then the resistance of oral microbes was evaluated with a variety of tests. The results of this study show that there were no statistically significant differences in the proportion of doxycycline-resistant bacteria among the treatment groups and no evidence of multiantibiotic resistance. In conclusion, long-term subantimicrobial doses of doxycycline do not alter or contribute to alterations in the antibiotic susceptibility of the subgingival microflora compared with a placebo.