What is the recommended treatment for Lyme disease?

Treatment for Lyme Disease

First-Line Oral Antibiotic Regimens

For early Lyme disease in adults and children ≥8 years old, doxycycline 100 mg twice daily for 10-14 days is the preferred first-line treatment, with amoxicillin and cefuroxime axetil as equally effective alternatives. 1, 2

Adult Dosing Options

• Doxycycline: 100 mg orally twice daily for 10-14 days (preferred due to shorter duration and coverage of co-infection with human granulocytic anaplasmosis) 3, 1
• Amoxicillin: 500 mg orally three times daily for 14-21 days 3, 1
• Cefuroxime axetil: 500 mg orally twice daily for 14-21 days 3, 1

All three regimens demonstrate comparable efficacy with complete response rates exceeding 83% at 30 months, with no significant differences in treatment outcomes. 4

Pediatric Dosing Considerations

For children <8 years old, amoxicillin is the preferred first-line agent at 50 mg/kg per day divided into 3 doses (maximum 500 mg per dose) for 14 days. 5

For children ≥8 years old, doxycycline is preferred at 4 mg/kg per day in 2 divided doses (maximum 100 mg per dose) for 14 days. 3, 5

Cefuroxime axetil is an alternative for children <8 years at 30 mg/kg per day in 2 divided doses for 14 days. 5

Recent evidence suggests doxycycline is safe and effective in children <8 years old for courses up to 3 weeks, though amoxicillin remains the preferred agent for this age group. 6, 7

Treatment Duration

Do not extend treatment beyond 21 days for early Lyme disease, as longer courses provide no additional benefit. 1, 4

• Doxycycline requires only 10 days of therapy due to its longer half-life 1, 2
• Beta-lactam antibiotics (amoxicillin, cefuroxime axetil) require a full 14-day course due to shorter half-lives 5
• Extending treatment from 10 to 20 days showed no improvement in efficacy (83.9% vs 90.3% complete response, P > 0.2) 4

Important Administration Guidelines

Doxycycline must be taken with 8 ounces of fluid to reduce esophageal irritation and with food to minimize gastrointestinal side effects. 1, 5

Patients taking doxycycline must avoid sun exposure due to photosensitivity risk. 1, 5

Doxycycline is contraindicated in pregnant or lactating women. 1

Second-Line Options (Use Only When First-Line Agents Cannot Be Tolerated)

Macrolide antibiotics are significantly less effective than first-line agents and should only be used when patients are intolerant of doxycycline, amoxicillin, AND cefuroxime axetil. 3, 1

Adult macrolide dosing (if absolutely necessary):

• Azithromycin: 500 mg orally daily for 7-10 days 3
• Clarithromycin: 500 mg orally twice daily for 14-21 days (not in pregnancy) 3
• Erythromycin: 500 mg orally four times daily for 14-21 days 3

Patients treated with macrolides require close observation to ensure clinical resolution. 3

Critical Pitfalls to Avoid

Never use first-generation cephalosporins (e.g., cephalexin) as they are completely inactive against Borrelia burgdorferi. 1, 5, 2

Do not prescribe fluoroquinolones or carbapenems, as they are not recommended for Lyme disease. 5

Avoid long-term antibiotic therapy beyond 21 days, which lacks supporting evidence and may cause harm. 5

Treatment failure is extremely rare (<10%) with appropriate antibiotic therapy, and objective evidence of treatment failure occurred in only 1 of 180 patients in a major randomized trial. 4

Special Clinical Scenarios

For neurological involvement (meningitis, radiculopathy), parenteral therapy with ceftriaxone 50-75 mg/kg per day (maximum 2g) is required. 5

For isolated facial nerve palsy without other neurological signs and normal cerebrospinal fluid, oral therapy is usually sufficient. 8

Patients with acute disseminated Lyme disease (multiple erythema migrans lesions) without meningitis can be treated with oral doxycycline rather than parenteral ceftriaxone, as both show equal efficacy (85% vs 88% cure rates). 9

Monitoring and Expected Outcomes

Most patients respond promptly and completely to appropriate antibiotic therapy. 5, 2

Patients should be monitored for 30 days after tick removal for development of erythema migrans or systemic symptoms. 3

Mild Jarisch-Herxheimer-like reactions may occur within the first 24 hours of treatment but are typically transient. 2

Residual symptoms (such as mild arthralgia) may persist in 14-27% of successfully treated patients but do not indicate treatment failure or need for additional antibiotics. 9