Comparison of phenoxymethylpenicillin, amoxicillin, and doxycycline for erythema migrans in general practice. A randomized controlled trial with a 1-year follow-up

Clin Microbiol Infect. 2018 Dec;24(12):1290-1296. doi: 10.1016/j.cmi.2018.02.028. Epub 2018 Mar 2.


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

Methods: 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.govNCT01368341 and EU Clinical Trials Register 2010-023747-15.

Results: 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.

Conclusions: 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.

Keywords: Antibiotics; Early Lyme; Erythema migrans; General practice; Lyme borreliosis; Tick borne diseases.

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amoxicillin / administration & dosage
  • Amoxicillin / adverse effects
  • Amoxicillin / therapeutic use*
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Antibodies, Bacterial / blood
  • Doxycycline / administration & dosage
  • Doxycycline / adverse effects
  • Doxycycline / therapeutic use*
  • Erythema Chronicum Migrans / drug therapy*
  • Erythema Chronicum Migrans / epidemiology
  • Erythema Chronicum Migrans / microbiology
  • Female
  • Follow-Up Studies
  • General Practice / statistics & numerical data
  • Humans
  • Immunoglobulin G / blood
  • Lyme Disease / diagnosis
  • Lyme Disease / drug therapy*
  • Lyme Disease / epidemiology
  • Lyme Disease / microbiology
  • Male
  • Middle Aged
  • Norway / epidemiology
  • Penicillin V / administration & dosage
  • Penicillin V / adverse effects
  • Penicillin V / therapeutic use*
  • Primary Health Care / statistics & numerical data
  • Young Adult


  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • Immunoglobulin G
  • Amoxicillin
  • Doxycycline
  • Penicillin V

Associated data