Lyme Disease Treatment Guidelines

Introduction to Treatment

The Infectious Diseases Society of America recommends oral antibiotic therapy with doxycycline (100 mg twice daily), amoxicillin (500 mg three times daily), or cefuroxime axetil (500 mg twice daily) for 14 days for patients presenting with a target rash (erythema migrans) suggestive of Lyme disease 1
Prompt treatment is essential to prevent progression to disseminated disease, and treatment should not be delayed while awaiting laboratory confirmation when erythema migrans is present, as recommended by the American College of Rheumatology 2, 1

Doxycycline is effective for both Lyme disease and potential coinfection with Anaplasma phagocytophilum, and a shorter course (10 days) may be sufficient 1
Amoxicillin or cefuroxime axetil is preferred for pregnant or lactating women, and children under 8 years of age, and requires a full 14-day course 1
The dosage for amoxicillin is 50 mg/kg/day in 3 divided doses (maximum 500 mg per dose) for 14 days, and for cefuroxime axetil, age-appropriate dosing is recommended for 14 days 1
Doxycycline dosage is 4 mg/kg/day in 2 divided doses (if ≥8 years of age) for 14 days 1

Doxycycline is contraindicated in pregnancy or lactation, children under 8 years of age, and known allergy 1
Macrolide antibiotics (azithromycin, clarithromycin, erythromycin) are not recommended as first-line therapy and should be reserved only for patients who cannot take doxycycline, amoxicillin, or cefuroxime axetil, and require close monitoring due to lower efficacy 1

First-generation cephalosporins (e.g., cephalexin), fluoroquinolones, extended courses beyond recommended durations, and combination antibiotic therapy are ineffective treatments to avoid 1

Most patients respond promptly and completely to treatment, but some may have persistent subjective complaints despite curative therapy, and less than 10% fail to respond to initial antibiotic therapy 1
Consider coinfection if patient presents with more severe initial symptoms than typical for Lyme disease alone, high-grade fever persisting >48 hours despite appropriate antibiotics, or unexplained leukopenia, thrombocytopenia, or anemia 1

Pregnant women should avoid doxycycline and use amoxicillin or cefuroxime axetil 1
Children under 8 years of age should avoid doxycycline and use amoxicillin or cefuroxime axetil 1
Patients with penicillin allergy should use doxycycline or cefuroxime axetil 1

Single-dose doxycycline prophylaxis (200 mg for adults) may be offered to patients with tick bite but no symptoms yet, if all criteria are met, including attached tick identified as Ixodes scapularis, estimated attachment duration ≥36 hours, prophylaxis can be started within 72 hours of tick removal, local infection rate of ticks with B. burgdorferi is ≥20%, and no contraindication to doxycycline 3