Duration of Antibiotic Therapy for Early Lyme Disease

A Randomized, Double-Blind, Placebo-Controlled Trial

6 May 2003 | Volume 138 Issue 9 | Pages 697-704

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.

Editors' Notes Context Optimal antibiotic treatment for patients with early Lyme disease is unclear. Contribution This single-center randomized, double-blind, placebo-controlled trial found that patients with erythema migrans given any of the follwoing regimens had high response rates, defined as resolution of erythema migrans and symptoms at 30 months: 20 days of doxycycline, 83.9%; 10 days of doxycycline, 90.3%; and 10 days of doxycycline plus a single intravenous dose of ceftriaxone, 86.5%. Patients given doxycycline plus ceftriaxone more often had diarrhea than patients given doxycycline alone. Implications Oral doxycycline alone for 10 days is sufficient treatment for patients with early Lyme disease that manifests as erythema migrans. –The Editors

 

Author and Article Information

From New York Medical College, Valhalla, New York.

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.