These recommendations are based on evidence of the efficacy and safety of antibiotics for erythema migrans, guidelines by the Infectious Diseases Society of America (IDSA) on the treatment of Lyme disease [Wormser et al, 2006] which have been endorsed by the UK Health Protection Agency (HPA) [HPA, 2009e], and the British National Formulary (BNF) and BNF for Children [BNF 57, 2009; BNF for Children, 2009].

• Basis for recommending oral amoxicillin, doxycycline, or cefuroxime axetil
• IDSA guidelines recommend that adults and children with early localized or early disseminated Lyme disease associated with erythema migrans should be treated with doxycyline, amoxicillin, or cefuroxime axetil [Wormser et al, 2006].
• In adults, limited evidence from a systematic review, and one subsequently published open-label randomized controlled trial (RCT), suggests that oral tetracyclines, penicillins, and cefuroxime axetil (for 10–21 days) are equally effective in treating erythema migrans and preventing late complications of Lyme disease, and are superior to erythromycin or azithromycin. Following treatment, the risk of developing a major late complication (such as myocarditis, meningoencephalitis, or recurrent arthritis) is 0–8%, and the risk of developing a minor late complication (such as cranial neuropathy, transient arthritis, fatigue, or arthralgia) is 6–24%.
• In children, there is a lack of evidence on the efficacy and safety of antibiotics for the treatment of erythema migrans associated with Lyme disease. There is very limited evidence from two small RCTs that phenoxymethylpenicillin is similar in efficacy to cefuroxime axetil and azithromycin. Recommendations have been extrapolated from evidence in adults.
• Amoxicillin is not licensed for the treatment of Lyme disease in the UK. Doxycyline is licensed as a treatment for Lyme disease.
• Basis for recommending cefuroxime axetil only if amoxicillin and doxycycline cannot be given
• CKS only recommends cefuroxime axetil if doxycyline and amoxicillin are contraindicated, because it may be associated with an increased risk of Clostridium difficile-associated illness [HPA, 2009a], and it is currently more expensive than the other recommended antibiotics [BNF 57, 2009].
• Cefuroxime is licensed for the treatment of Lyme disease in the UK, but for a 20-day course of treatment.
• Basis for avoiding doxycycline in children younger than 12 years of age
• Due to the risk of its deposition in developing bone and teeth, doxycyline should not be given to children younger than 12 years of age [ABPI Medicines Compendium, 2008; BNF for Children, 2009].
• Basis for choice of antibiotic if bacterial cellulitis could be present
• IDSA guidelines recommend that if erythema migrans cannot be reliably distinguished from bacterial cellulitis, treatment should be with co-amoxiclav or cefuroxime [Wormser et al, 2006]. These guidelines have been endorsed by the HPA [HPA, 2009e].
• The option of adding flucloxacillin to amoxicillin is in line with national guidance on the treatment of cellulitis in primary care [HPA, 2009a]. It was recommended by one CKS expert reviewer because of the risk of Clostridium difficile associated with the use of cefuroxime and co-amoxiclav.