What is the recommended treatment for Lyme disease with a duration of infection greater than 10 days?

Treatment of Lyme Disease with Duration >10 Days

For Lyme disease with symptoms present for more than 10 days, oral doxycycline 100 mg twice daily for 14 days (or 10-21 days range) remains the first-line treatment for early localized or early disseminated disease without neurologic involvement, while late manifestations require extended courses: 28 days for arthritis or 14-28 days of IV ceftriaxone for neurologic disease. 1

Early Lyme Disease (>10 Days Duration)

First-Line Oral Therapy

Recommended regimens for adults: 1

• Doxycycline 100 mg twice daily for 14 days (range 10-21 days) - preferred option 1
• Amoxicillin 500 mg three times daily for 14 days (range 14-21 days) 1
• Cefuroxime axetil 500 mg twice daily for 14 days (range 14-21 days) 1

Key advantages of doxycycline: It provides coverage for human granulocytic anaplasmosis (HGA), which may occur as co-infection with Lyme disease 1, 2

For children: 2

• Under 8 years: Amoxicillin 50 mg/kg/day in 3 divided doses for 14 days (preferred)
• 8 years and older: Doxycycline 4 mg/kg/day in 2 divided doses for 14 days

Evidence Supporting Shorter Courses

A randomized controlled trial of 180 patients demonstrated that 10 days of doxycycline was equally effective as 20 days, with complete response rates of 90.3% versus 83.9% at 30 months (no significant difference) 3. A retrospective cohort study of 607 patients showed treatment failure rates of only 1%, with no difference between 10-day, 11-15 day, or 16-day courses 4. However, the 2006 and 2021 IDSA guidelines recommend 14 days for uniformity across all first-line oral agents, given the shorter half-life of β-lactam antibiotics compared to doxycycline 1.

Late Disseminated Lyme Disease

Lyme Arthritis

Initial treatment: Oral antibiotics for 28 days 1

• Doxycycline 100 mg twice daily for 28 days 1
• Amoxicillin 500 mg three times daily for 28 days 1
• Cefuroxime axetil 500 mg twice daily for 28 days 1

For partial response (mild residual joint swelling): 1

• Consider observation versus second course of oral antibiotics for up to 1 month
• Evaluate for medication adherence, other causes of swelling, and patient preferences

For no/minimal response (moderate to severe swelling): 1

• IV ceftriaxone 2 g daily for 2-4 weeks is suggested over second oral course 1

Post-antibiotic arthritis (failed oral + IV courses): 1

• Refer to rheumatologist for disease-modifying antirheumatic drugs, biologics, intra-articular steroids, or arthroscopic synovectomy
• Do not continue antibiotics beyond 8 weeks total if treatment included IV therapy 1

Late Neurologic Disease

For CNS or peripheral nervous system involvement: 1

• IV ceftriaxone 2 g once daily for 2-4 weeks (preferred) 1
• Alternative: IV cefotaxime or IV penicillin G 1
• Response is typically slow and may be incomplete 1

For children with late neurologic disease: 2

• IV ceftriaxone 50-75 mg/kg/day (maximum 2 g) for 14 days

Lyme Carditis

Outpatient management: Oral antibiotics (doxycycline, amoxicillin, cefuroxime axetil, or azithromycin) for 14-21 days total 1

Hospitalized patients: 1

• Start IV ceftriaxone 1-2 g daily until clinical improvement
• Switch to oral antibiotics to complete 14-21 days total

Indications for hospitalization: PR interval >300 milliseconds, other arrhythmias, or clinical manifestations of myopericarditis 1, 5

Critical Pitfalls to Avoid

Do not use ineffective antibiotics: 1, 2

• First-generation cephalosporins (cephalexin) are ineffective and should never be used
• Macrolides are inferior to first-line agents and reserved only for intolerance

Do not provide prolonged antibiotic therapy for post-treatment symptoms: 1

• For patients with persistent nonspecific symptoms (fatigue, pain, cognitive impairment) after standard treatment who lack objective evidence of reinfection or treatment failure, additional antibiotics are NOT recommended (strong recommendation, moderate-quality evidence)
• Objective signs of active infection (arthritis, meningitis, neuropathy) are required to justify retreatment

Do not dismiss subtle neurologic symptoms: 1

• Patients with Lyme arthritis may have subtle distal paresthesias or memory impairment indicating CNS involvement requiring IV therapy
• Five patients in one trial developed neuroborreliosis after oral treatment, four of whom had subtle neurologic symptoms at baseline

Avoid probenecid with amoxicillin: Probenecid may impair β-lactam penetration into brain parenchyma 1

Special Considerations

Doxycycline precautions: 2

• Take with 8 ounces of fluid to reduce esophageal irritation
• Take with food to reduce gastrointestinal intolerance
• Avoid sun exposure due to photosensitivity risk
• Relatively contraindicated in pregnancy, lactation, and children under 8 years 1

Monitoring expectations: 2

• Most patients respond promptly to appropriate therapy
• Less than 10% have persistent objective manifestations
• Patients who are more systemically ill at diagnosis may take longer to respond completely