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


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
Single-center university hospital.


METHODS
180 patients with erythema migrans.


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


METHODS
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.
Division of Infectious Diseases, New York Medical College, Room 245, Munger Pavilion, Valhalla, New York 10595, USA.
Gary P
GP
Wormser
Roshan
R
Ramanathan
John
J
Nowakowski
Donna
D
McKenna
Diane
D
Holmgren
Paul
P
Visintainer
Rhea
R
Dornbush
Brij
B
Singh
Robert B
RB
Nadelman
D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000009:adverse effects; D003071:Cognition; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000009:adverse effects; D015787:Erythema Chronicum Migrans / Q000188:drug therapy / Q000523:psychology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008193:Lyme Disease / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D010919:Placebos; D002443:Ceftriaxone; D004318:Doxycycline