Accurate diagnosis of Lyme disease and the appropriate selection of therapy are critical for a good outcome. Borrelia burgdorferi, the causative spirochete, may disseminate to organs and the central nervous system early in the course of infection. Such patients appear clinically more ill than those who present with a history of a tick bite and the rash of erythema migrans. It is unclear, however, whether patients with systemic symptoms should be treated with an oral antibiotic or with parenteral ceftriaxone. Dattwyler and colleagues compared the effectiveness and tolerability of parenteral ceftriaxone and oral doxycycline in 140 patients with acute disseminated Lyme disease but without meningitis.

Patients eight years of age and older who had been in an area where Lyme disease was endemic and who had at least one expanding annular lesion 5 cm or greater in diameter were included in the open-label, randomized trial. Lyme disease was considered disseminated if at least one of the following was present: more than one erythema migrans lesion, carditis manifested by heart block, acute large-joint arthritis and neurologic abnormalities (including seventh-cranial-nerve palsy or radiculitis of less than three months' duration). The diagnosis of Lyme disease was serologically confirmed by enzyme-linked immunosorbent assay and Western blot testing.

Patients were randomly assigned to receive either ceftriaxone, 2 g intravenously or intra-muscularly daily for two weeks, or doxycycline, 100 mg orally twice daily for 21 days. The dosages in children were 50 mg per kg of ceftriaxone (up to 2 g daily) and 4.4 mg per kg of doxycyline (up to 100 mg twice daily).

A total of 68 patients received ceftriaxone, and 72 received doxycycline. Sixty-two study subjects in the ceftriaxone group and 71 in the doxycycline group had multiple erythema migrans lesions. The mean duration of the rash before treatment was nine days in the ceftriaxone group and 10 days in the doxycycline group. Patients were seen weekly during treatment and at three, six and nine months after completion of antibiotic therapy. At each follow-up visit the investigators classified the patient's clinical response as a “cure” (resolution of objective clinical findings of Lyme disease) or “treatment failure” (persistence of clinical findings, including arthritis and neurologic disease).

By the end of the study, 85 percent of the ceftriaxone group and 88 percent of the doxycycline group were cured. Treatment failure was noted in only one patient from each group, although assessment could not be performed in nine patients from the parenteral group and eight patients from the oral therapy group. Not surprisingly, 57 percent of the ceftriaxone group reported at least one adverse drug event, compared with 43 percent of the doxycycline group. Eighteen of 67 patients (27 percent) in the ceftriaxone group reported residual symptoms at the final evaluation; 14 had arthralgia and six reported fatigue. In contrast, 10 of 71 patients (14 percent) in the doxycycline group reported residual symptoms at the final evaluation; six had arthralgia and five reported fatigue.

The authors conclude that oral doxycycline should continue to be the first line of treatment for acute disseminated Lyme disease. Use of ceftriaxone should be reserved for patients with Lyme meningitis or for patients in whom tetracycline or penicillin is contraindicated.

In a related article, Eckman and colleagues performed a cost and quality-of-life analysis of data from multiple studies (including the Dattwyler study) that compared oral doxycycline with parenteral ceftriaxone in the treatment of Lyme disease. They concluded that intravenous ceftriaxone is no more effective than oral doxycycline, causes more complications and is substantially more expensive. The evidence is quite firm that oral therapy is appropriate in the majority of patients with Lyme disease.