Azithromycin Compared with Amoxicillin in the Treatment of Erythema Migrans: A Double-Blind, Randomized, Controlled Trial

doi:10.1059/0003-4819-124-9-199605010-00002

Azithromycin Compared with Amoxicillin in the Treatment of Erythema Migrans: A Double-Blind, Randomized, Controlled Trial

From State University of New York at Stony Brook, Stony Brook, New York; University of Minnesota, Minneapolis, Minnesota; Kaiser Permanente, Rocky Hill, Connecticut; Yale University, New Haven, Connecticut; Family Physician's Group, Cape Girardeau, Missouri; and Pfizer Central Research, Groton, Connecticut. Acknowledgments: The authors thank the following persons and institutions for their participation in this trial: R. Nadelman and G. Wormser (Westchester Medical Center, Valhalla, New York); J. Melski (Marshfield Clinic, Marshfield, Wisconsin); T. Rush (Briarcliff Manor, New York); L. Sigal (Robert Wood Johnson Medical School, New Brunswick, New Jersey); R. Messner (University of Minnesota, Minneapolis, Minnesota); P. Paparone (Absecon, New Jersey); E. Jost (Westerly Hospital, Westerley, Rhode Island); and J. Katzel (Ukiah, California). Grant Support: In part by a grant from Pfizer Central Research, Groton, Connecticut. Dr. Gadgil collaborated with the Project Leaders, Drs. Luft and Dattwyler, in designing the trial. Pfizer Central Research provided data management and biostatistical support. The interpretation and presentation of the results were the responsibility of the Project Leaders. Drs. Luft and Dattwyler and Ms. Bosler were supported in part by grants from New York State and the National Institutes of Health (AI32454). Requests for Reprints: Benjamin J. Luft, MD, Department of Medicine, HSC T-16, State University of New York at Stony Brook, Stony Brook, NY 11794-8160. Current Author Addresses: Dr. Luft and Ms. Bosler: Department of Medicine, HSC T-16, Room 020, State University of New York at Stony Brook, Stony Brook, NY 11794.

Abstract

Objective: To determine whether azithromycin or amoxicillin is more efficacious for the treatment of erythema migrans skin lesions, which are characteristic of Lyme disease.

Design: Randomized, double-blind, double-dummy, multicenter study. Acute manifestations and sequelae were assessed using a standardized format. Baseline clinical characteristics and response were correlated with serologic results. Patients were followed for 180 days.

Setting: 12 outpatient centers in eight states.

Patients: 246 adult patients with erythema migrans lesions at least 5 cm in diameter were enrolled and were stratified by the presence of flu-like symptoms (such as fever, chills, headache, malaise, fatigue, arthralgias, and myalgias) before randomization.

Intervention: Oral treatment with either amoxicillin, 500 mg three times daily for 20 days, or azithromycin, 500 mg once daily for 7 days. Patients who received azithromycin also received a dummy placebo so that the dosing schedules were identical.

Results: Of 217 evaluable patients, those treated with amoxicillin were significantly more likely than those treated with azithromycin to achieve complete resolution of disease at day 20, the end of therapy (88% compared with 76%; P = 0.024). More azithromycin recipients (16%) than amoxicillin recipients (4%) had relapse (P = 0.005). A partial response at day 20 was highly predictive of relapse (27% of partial responders had relapse compared with 6% of complete responders; P < 0.001). For patients treated with azithromycin, development of an antibody response increased the possibility of achieving a complete response (81% of seropositive patients achieved a complete response compared with 60% of seronegative patients; P = 0.043). Patients with multiple erythema migrans lesions were more likely than patients with single erythema migrans lesions (P < 0.001) to have a positive antibody titer at baseline (63% compared with 17% for IgM; 39% compared with 16% for IgG). Fifty-seven percent of patients who had relapse were seronegative at the time of relapse.

Conclusions: A 20-day course of amoxicillin was found to be an effective therapeutic regimen for erythema migrans. Most patients were seronegative for Borrelia burgdorferi at the time of presentation with erythema migrans (65%) and at the time of relapse (57%).