Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial

Ann Intern Med. 2003 May 6;138(9):697-704. doi: 10.7326/0003-4819-138-9-200305060-00005.

Abstract

Background: Treatment of patients with early Lyme disease has trended toward longer duration despite the absence of supporting clinical trials.

Objective: To evaluate different durations of oral doxycycline treatment and the combination of oral doxycycline and a single intravenous dose of ceftriaxone for treatment of patients with early Lyme disease.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Single-center university hospital.

Patients: 180 patients with erythema migrans.

Intervention: Ten days of oral doxycycline, with or without a single intravenous dose of ceftriaxone, or 20 days of oral doxycycline.

Measurements: Outcome was based on clinical observations and neurocognitive testing. Efficacy was assessed at 20 days, 3 months, 12 months, and 30 months.

Results: At all time points, the complete response rate was similar for the three treatment groups in both on-study and intention-to-treat analyses. In the on-study analysis, the complete response rate at 30 months was 83.9% in the 20-day doxycycline group, 90.3% in the 10-day doxycycline group, and 86.5% in the doxycycline-ceftriaxone group (P > 0.2). The only patient with treatment failure (10-day doxycycline group) developed meningitis on day 18. There were no significant differences in the results of neurocognitive testing among the three treatment groups and a separate control group without Lyme disease. Diarrhea occurred significantly more often in the doxycycline-ceftriaxone group (35%) than in either of the other two groups (P < 0.001).

Conclusions: Extending treatment with doxycycline from 10 to 20 days or adding one dose of ceftriaxone to the beginning of a 10-day course of doxycycline did not enhance therapeutic efficacy in patients with erythema migrans. Regardless of regimen, objective evidence of treatment failure was extremely rare.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Ceftriaxone / administration & dosage*
  • Ceftriaxone / adverse effects
  • Cognition
  • Double-Blind Method
  • Doxycycline / administration & dosage*
  • Doxycycline / adverse effects
  • Drug Administration Schedule
  • Drug Therapy, Combination / administration & dosage*
  • Drug Therapy, Combination / adverse effects
  • Erythema Chronicum Migrans / drug therapy
  • Erythema Chronicum Migrans / psychology
  • Female
  • Humans
  • Injections, Intravenous
  • Lyme Disease / drug therapy*
  • Lyme Disease / psychology
  • Male
  • Middle Aged
  • Placebos
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Placebos
  • Ceftriaxone
  • Doxycycline