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In a randomized multicenter therapeutic trial, 32 patients with erythema migrans received oral azithromycin 500 mg once daily and 33 patients received phenoxymethylpenicillin (penicillin V) 1 million U three times daily for 10 days. Follow-up was for a median of 17 (range 3-32) months. Four weeks after initiation of therapy, 20 (62%) patients given azithromycin and 17 (51%) patients given penicillin V were completely free of all signs and symptoms and did not develop new ones subsequently (no significant difference). Three months after initiation of therapy, the corresponding figures were 25 (78%) azithromycin and 28 (85%) penicillin V recipients (no significant difference). There were only minor sequelae such as arthralgia, headache, fatigue, stiff neck and dysesthesia. Azithromycin led to a significantly faster resolution of the erythema migrans than penicillin V (p < 0.001). Significantly more patients with more severe compared with mild initial disease had an elevated IgM antibody titer prior to therapy (p < 0.001). Usually mild to moderate side effects occurred in 12 patients given azithromycin and five patients given penicillin V (p < 0.05). Azithromycin appears to be as effective as penicillin V for the treatment of early Lyme borreliosis and it seems to clear the erythema migrans more promptly.

In a prospective randomized multicenter trial for the therapy of erythema migrans, 40 patients received ceftriaxone 1 g daily for 5 days and 33 patients obtained phenoxymethylpenicillin, 1 million units 3 times daily, for 12 days. Follow-up was for a mean of 10 +/- 5 months. Eight oral penicillin recipients (24%) and six ceftriaxone recipients (15%) developed minor consecutive manifestations. Two ceftriaxone and one penicillin recipient(s) still had elevated IgG antibody titers 10 to 20 months after therapy. Borrelia burgdorferi could be isolated from the erythema migrans in 29 out of 56 patients (52%) before therapy and in one oral penicillin recipient but none of 24 other patients after therapy. Ceftriaxone was superior to oral penicillin in a subgroup of patients with more than one symptom prior to therapy (p less than 0.01), but not in the overall evaluation of clinical, serological and bacteriological outcome data. Ceftriaxone ought to be preferred to oral penicillin in patients with more severe early Lyme borreliosis.

In a study on 121 consecutive patients with erythema migrans, 65 patients obtained oral penicillin, 36 tetracyclines, and 20 amoxicillin-clavulanic-acid. Follow-up was carried out for a median of 29, 17, and 7 months, respectively. In another limited trial on 29 patients with acrodermatitis chronica atrophicans (ACA), 14 patients received oral penicillin, 9 parenteral penicillin, and 6 tetracyclines. There was no statistically significant difference among treatment groups in both therapeutic trials, with the exception of different follow-ups due to the nonrandomized study design and different occurrence of the Jarisch-Herxheimer reaction in patients with erythema migrans. Later extracutaneous manifestations developed in 27% of the patients with erythema migrans and in 47% of the patients with ACA despite antibiotic therapy. We could not prove the superiority of any antibiotic tested in either early or late European Lyme borreliosis.

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