Treatment of Early Lyme Disease

Am J Med. 1992 Apr;92(4):396-403. doi: 10.1016/0002-9343(92)90270-l.


Purpose: To compare the safety and efficacy of azithromycin, amoxicillin/probenecid, and doxycycline for the treatment of early Lyme disease, to identify risk factors for treatment failure, and to describe the serologic response in treated patients.

Patients and methods: Fifty-five patients with erythema migrans and two patients with flu-like symptoms alone and fourfold changes in antibody titers to Borrelia burgdorferi were randomized to receive (1) oral azithromycin, 500 mg on the first day followed by 250 mg once a day for 4 days; (2) oral amoxicillin 500 mg and probenecid 500 mg, three times a day for each for 10 days; or (3) doxcycline, 100 mg twice a day for 10 days. If symptoms were still present at 10 days, treatment was extended with amoxicillin/probenecid or doxycycline for 10 more days. Evaluations were done at study entry and 10, 30, and 180 days later.

Results: Three of the patients who initially had symptoms suggestive of spread of the spirochete to the nervous system, one from each antibiotic treatment group, subsequently developed neurologic abnormalities, but symptoms in the other 54 patients resolved within 3 to 30 days after study entry. Six of the 19 patients (32%) (95% confidence interval, 13% to 57%) given amoxicillin/probenecid developed a drug eruption, whereas none of the patients given azithromycin or doxycycline had this complication. The presence of dysesthesias at study entry was the only risk factor significantly associated with treatment failure (p less than 0.001). By convalescence, 72% of the patients were seropositive, and 56% still had detectable IgM responses to the spirochete 6 months later.

Conclusions: The three antibiotic regimens tested in this study were generally effective for the treatment of early Lyme disease, but the regimens differ in the frequency of side effects and in ease of administration.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amoxicillin / adverse effects
  • Amoxicillin / therapeutic use*
  • Antibodies, Bacterial / analysis
  • Azithromycin
  • Borrelia burgdorferi Group / immunology
  • Doxycycline / adverse effects
  • Doxycycline / therapeutic use*
  • Erythema Chronicum Migrans / drug therapy
  • Erythromycin / adverse effects
  • Erythromycin / analogs & derivatives*
  • Erythromycin / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin M / analysis
  • Lyme Disease / drug therapy*
  • Lyme Disease / physiopathology
  • Male
  • Middle Aged
  • Nervous System Diseases / etiology
  • Pilot Projects
  • Probenecid / adverse effects
  • Probenecid / therapeutic use*
  • Sensation
  • Treatment Outcome


  • Antibodies, Bacterial
  • Immunoglobulin G
  • Immunoglobulin M
  • Erythromycin
  • Amoxicillin
  • Azithromycin
  • Doxycycline
  • Probenecid