To compare the three most commonly used antibiotics for erythema migrans (EM) in Norwegian primary care.

A randomized, parallel, controlled trial was carried out. Treatments were open to the patients, but blinded for the GPs and investigators. Patients eligible for inclusion were aged ≥18 years and clinically diagnosed with EM. Block randomization was processed in blocks of six. Patients were assigned to receive one of three antibiotic treatments for 14 days: phenoxymethylpenicillin (PCV), amoxicillin, or doxycycline. The primary outcome was the duration of EM in days in the three treatment groups. Patients kept a diary for the 14 days of treatment, in which they registered concomitant symptoms and side effects. The patients consulted their GP after 14 days of treatment and had a 1-year follow-up to monitor any development of disseminated Lyme borreliosis (LB). EMs with a duration of more than 14 days were followed until resolution. ClinicalTrials.gov NCT01368341 and EU Clinical Trials Register 2010-023747-15.

One hundred and eighty eight patients (PCV: n = 56, amoxicillin: n = 64, doxycycline: n = 68) were included by 44 Norwegian general practitioners (GPs) from June 2011 to November 2013. Follow-up was completed by December 2014. The median duration of EM was altogether 14 days (range 3–293). For the PCV group median duration was 14 days (range 5–91), for amoxicillin 13 days (range 4–179) and for doxycycline 14 days (range 3–293). The duration of EM did not differ significantly between the three antibiotic groups (p 0.277). None of the patients developed disseminated LB within the 1-year follow-up.

We did not find 14 days of PCV, doxycycline, and amoxicillin treatments to differ in effectiveness or safety in the treatment of clinically diagnosed EM in primary care.