Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomized, controlled trial.
OBJECTIVE
To determine whether azithromycin or amoxicillin is more efficacious for the treatment of erythema migrans skin lesions, which are characteristic of Lyme disease.


METHODS
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.


METHODS
12 outpatient centers in eight states.


METHODS
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.


METHODS
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 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%).
Luft
B J
BJ
Department of Medicine, State University of New York at Stony Brook, NY 11794-8160 USA.
Dattwyler
R J
RJ
Johnson
R C
RC
Luger
S W
SW
Bosler
E M
EM
Rahn
D W
DW
Masters
E J
EJ
Grunwaldt
E
E
Gadgil
S D
SD
D000328:Adult; D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D015787:Erythema Chronicum Migrans / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D010406:Penicillins / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence; D017211:Treatment Failure
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D010406:Penicillins; D000658:Amoxicillin; D017963:Azithromycin