What is the recommended treatment for Lyme disease?

Treatment for Lyme Disease

For early Lyme disease with erythema migrans, treat adults with doxycycline 100 mg twice daily for 14 days (range 10-21 days), which is the preferred first-line therapy. 1, 2

First-Line Oral Therapy for Early Lyme Disease (Erythema Migrans)

Adults

• Doxycycline 100 mg twice daily for 14 days is the preferred agent, with a treatment range of 10-21 days acceptable 1, 2
• Doxycycline has the distinct advantage of treating co-infection with human granulocytic anaplasmosis (HGA), which can occur simultaneously with Lyme disease 1, 3
• Alternative options if doxycycline is contraindicated:
  • Amoxicillin 500 mg three times daily for 14-21 days 1, 2
  • Cefuroxime axetil 500 mg twice daily for 14-21 days 1, 2

Children

• For children ≥8 years old: Doxycycline 4 mg/kg/day in 2 divided doses (maximum 100 mg per dose) for 14 days 1, 3
  • Recent evidence suggests doxycycline is generally well-tolerated and effective in children <8 years when needed, though alternative antibiotics remain preferred 4
• For children <8 years old: Amoxicillin 50 mg/kg/day in 3 divided doses (maximum 500 mg per dose) for 14 days 1, 3
  • Alternative: Cefuroxime axetil 30 mg/kg/day in 2 divided doses (maximum 500 mg per dose) for 14 days 1, 3

Important Administration Details

• Doxycycline should be taken with 8 ounces of fluid to reduce esophageal irritation and can be given with food to reduce gastrointestinal intolerance 5, 3
• Patients must avoid sun exposure due to photosensitivity risk 5, 3

Neurologic Lyme Disease

For Lyme meningitis or other CNS involvement, use intravenous ceftriaxone 2 g once daily for 14-28 days. 1, 2

Adults

• Ceftriaxone 2 g IV once daily for 14-28 days is the preferred parenteral regimen 1, 2
• Alternatives include:
  • Cefotaxime 2 g IV every 8 hours 1, 2
  • Penicillin G 18-24 million units per day IV divided every 4 hours 1, 2
• Oral doxycycline 200-400 mg/day in 2 divided doses for 10-28 days may be adequate for patients intolerant of β-lactam agents 1

Children

• Ceftriaxone 50-75 mg/kg/day (maximum 2 g) as a single daily IV dose 1, 3
• Alternatives:
  • Cefotaxime 150-200 mg/kg/day divided into 3-4 IV doses (maximum 6 g/day) 1
  • Penicillin G 200,000-400,000 units/kg/day (maximum 18-24 million units/day) divided every 4 hours 1
• Children ≥8 years can be treated with oral doxycycline 4-8 mg/kg/day in 2 divided doses (maximum 100-200 mg per dose) 1

Seventh Cranial Nerve Palsy

• Patients without clinical signs of meningitis may be treated with the same oral regimens used for erythema migrans for 14-21 days 1
• Those with CSF pleocytosis or clinical evidence of meningitis require parenteral therapy as described above 1
• Lumbar puncture is indicated when there is strong clinical suspicion of CNS involvement (severe/prolonged headache, nuchal rigidity) 1

Lyme Carditis

Hospitalized patients with cardiac involvement should receive initial parenteral therapy with ceftriaxone, then transition to oral therapy to complete 14-21 days total. 1

• Hospitalization with continuous monitoring is required for:
  • Symptomatic patients (syncope, dyspnea, chest pain) 1
  • Second- or third-degree atrioventricular block 1
  • First-degree heart block with PR interval ≥30 milliseconds (can rapidly progress) 1
• Start with parenteral ceftriaxone (same dosing as for meningitis) 1
• Transition to oral regimen (same as for erythema migrans) to complete 14-21 days total 1
• Temporary pacemaker may be required for advanced heart block; cardiology consultation recommended 1

Lyme Arthritis

Treat Lyme arthritis with oral doxycycline, amoxicillin, or cefuroxime axetil for 28 days using the same dosing as for erythema migrans. 1

• If arthritis has substantively improved but not completely resolved after the first course, a second 4-week course of oral antibiotics is favored 1
• Reserve IV ceftriaxone for patients with no response to oral therapy 1
• If arthritis persists despite IV therapy and PCR of synovial fluid/tissue is negative for B. burgdorferi, consider symptomatic treatment with NSAIDs, intra-articular corticosteroids, or DMARDs (e.g., hydroxychloroquine) with rheumatology consultation 1
• Wait several months before re-treatment due to anticipated slow resolution of inflammation 1

Special Populations

Pregnancy and Lactation

• Treat identically to non-pregnant patients with the same disease manifestation, except avoid doxycycline 1
• Use amoxicillin or cefuroxime axetil for early disease 1
• Use parenteral ceftriaxone for neurologic or cardiac involvement 1

Critical Pitfalls to Avoid

Ineffective Antibiotics (Do Not Use)

• First-generation cephalosporins (e.g., cephalexin) are completely ineffective against B. burgdorferi 1, 2, 5, 3
• Fluoroquinolones, carbapenems, vancomycin, metronidazole, tinidazole, trimethoprim-sulfamethoxazole are not effective 1, 2

Macrolides: Last Resort Only

• Azithromycin, clarithromycin, and erythromycin are less effective than first-line agents 1, 2, 3
• Reserve for patients who cannot tolerate doxycycline, amoxicillin, AND cefuroxime axetil 1, 2
• If used in adults: azithromycin 500 mg daily for 7-10 days, clarithromycin 500 mg twice daily for 14-21 days (not in pregnancy), or erythromycin 500 mg four times daily for 14-21 days 1
• Patients on macrolides require close observation to ensure clinical resolution 1, 3

Inappropriate Treatment Approaches

• Do not use prolonged or repeated courses of antibiotics beyond recommended durations 1, 2, 3
• Do not use combination antibiotic therapy 1, 2
• Do not use pulsed-dosing (antibiotics on some days but not others) 1
• Doses far in excess of recommended amounts are not indicated 1
• Long-term antibiotic therapy lacks supporting data and may cause harm 2, 3

Post-Treatment Considerations

Monitoring Response

• Clinical improvement is the most reliable indicator of treatment success, not laboratory testing 2
• Serologic tests often remain positive for months or years after successful treatment and should not be used to monitor treatment response 2
• Antibody levels do not correlate with clinical response 2

Persistent Symptoms

• For patients with persistent nonspecific symptoms following recommended treatment but without objective evidence of reinfection or treatment failure, additional antibiotic therapy is not recommended 2
• Response to treatment for late neurologic manifestations is typically slow and may be incomplete 2
• Consider that persistent symptoms may be due to post-infectious phenomena, autoimmune reactions, or unrelated conditions rather than ongoing infection 2

When to Consider Co-infections

• Evaluate for Babesia microti or Anaplasma phagocytophilum in patients with persistent fever or characteristic laboratory abnormalities (e.g., low blood cell counts) after appropriate Lyme therapy 2