Duration of Antibiotic Therapy for Early Lyme Disease

A Randomized, Double-Blind, Placebo-Controlled Trial

  1. Gary P. Wormser, MD;
  2. Roshan Ramanathan, MD, MPH;
  3. John Nowakowski, MD;
  4. Donna McKenna, RN, ANP;
  5. Diane Holmgren, RN;
  6. Paul Visintainer, PhD;
  7. Rhea Dornbush, PhD;
  8. Brij Singh, MD; and
  9. Robert B. Nadelman, MD
  1. From New York Medical College, Valhalla, New York.

    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.

    Article and Author Information

    • Acknowledgments: The authors thank Eleanor Bramesco, Dominic Corbi, Susan Bittker, Denise Cooper, Charles Pavia, and Kathy O'Keefe for their assistance.

    • Grant Support: In part by a grant from the National Institutes of Health (RO1-AR41508) (Dr. Nadelman).

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Gary P. Wormser, MD, Division of Infectious Diseases, Room 245, Munger Pavilion, New York Medical College, Valhalla, NY 10595.

    • Current Author Addresses: Drs. Wormser, Nowakowski, and Nadelman, Ms. McKenna, and Ms. Holmgren: Division of Infectious Diseases, New York Medical College, Room 245, Munger Pavilion, Valhalla, NY 10595.

    • Dr. Ramanathan: Department of Medicine, State University of New York at Stony Brook. Health Sciences Center, T16, Room 020, Stony Brook, NY 11794.

    • Dr. Visintainer: New York Medical College, Learning Center, Room 213, Valhalla, NY 10595.

    • Dr. Dornbush: Behavioral Health, Westchester Medical Center, Room N326, Valhalla, NY 10595.

    • Dr. Singh: Department of Neurology, New York Medical College, Munger Pavilion, 4th Floor, Valhalla, NY 10595.

    • Author Contributions: Conception and design: G.P. Wormser, J. Nowakowski, B. Singh, R.B. Nadelman.

    • Analysis and interpretation of the data: G.P. Wormser, R. Ramanathan, J. Nowakowski, D. McKenna, P. Visintainer, R. Dornbush, R.B. Nadelman.

    • Drafting of the article: G.P. Wormser, R. Ramanathan, R.B. Nadelman.

    • Critical revision of the article for important intellectual content: G.P. Wormser, R. Ramanathan, J. Nowakowski, P. Visintainer, R.B. Nadelman.

    • Final approval of the article: G.P. Wormser, R. Ramanathan, J. Nowakowski, D. McKenna, D. Holmgren, P. Visintainer, R. Dornbush, B. Singh, R.B. Nadelman.

    • Provision of study materials or patients: G.P. Wormser, J. Nowakowski, R.B. Nadelman.

    • Statistical expertise: G.P. Wormser, R. Ramanathan, P. Visintainer, R. Dornbush.

    • Obtaining of funding: R.B. Nadelman.

    • Administrative, technical, or logistic support: G.P. Wormser, R. Ramanathan, D. McKenna, D. Holmgren, P. Visintainer, R. Dornbush, B. Singh, R.B. Nadelman.

    • Collection and assembly of data: G.P. Wormser, R. Ramanathan, J. Nowakowski, D. McKenna, D. Holmgren, P. Visintainer, B. Singh, R.B. Nadelman.

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    1. Ann Intern Med May 6, 2003 vol. 138 no. 9 697-704
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