What is the treatment for Lyme disease?

Treatment of Lyme Disease

For early Lyme disease, oral doxycycline 100 mg twice daily for 10-14 days is the preferred first-line treatment in adults and children ≥8 years old, while amoxicillin 500 mg three times daily for 14 days is preferred for children <8 years, pregnant women, and those who cannot tolerate doxycycline. 1, 2, 3

Early Localized Lyme Disease (Erythema Migrans)

First-Line Oral Regimens for Adults:

• Doxycycline 100 mg twice daily for 10-14 days (range 10-21 days) 1, 3
• Amoxicillin 500 mg three times daily for 14-21 days 1, 3
• Cefuroxime axetil 500 mg twice daily for 14-21 days 1, 3

Pediatric Dosing:

• Children ≥8 years: Doxycycline 4 mg/kg/day in 2 divided doses (maximum 100 mg per dose) for 14 days 2, 3
• Children <8 years: Amoxicillin 50 mg/kg/day in 3 divided doses (maximum 500 mg per dose) for 14 days 2, 3
• Alternative for children <8 years: Cefuroxime axetil 30 mg/kg/day in 2 divided doses for 14 days 2

Key Advantages of Doxycycline:

Doxycycline has the critical advantage of treating coinfection with human granulocytic anaplasmosis (HGA), which may occur simultaneously with early Lyme disease 2. Patients should take doxycycline with 8 ounces of fluid to reduce esophageal irritation, with food to minimize gastrointestinal intolerance, and must avoid sun exposure due to photosensitivity risk 2, 3.

Special Populations:

Pregnant and lactating patients should be treated identically to non-pregnant patients except that doxycycline must be avoided; use amoxicillin or cefuroxime axetil instead 1.

Early Neurologic Lyme Disease

Meningitis or Radiculopathy:

Parenteral therapy is required: 1

• Ceftriaxone 2 g IV once daily for 14 days (range 10-28 days) 1
• Alternative: Cefotaxime 2 g IV every 8 hours 1
• Alternative: Penicillin G 18-24 million units/day IV divided every 4 hours 1

Pediatric dosing for neurologic disease: 1

• Ceftriaxone 50-75 mg/kg IV once daily (maximum 2 g) 1, 2
• Alternative: Cefotaxime 150-200 mg/kg/day IV divided into 3-4 doses (maximum 6 g/day) 1

Isolated Facial Nerve Palsy (Cranial Neuropathy):

If there are no signs of meningitis (no severe headache, nuchal rigidity) and CSF examination is normal or not performed due to lack of clinical suspicion, oral antibiotics are sufficient using the same regimens as for erythema migrans for 14-21 days 1. However, if CSF shows pleocytosis or there are signs of CNS involvement, treat with parenteral antibiotics as for meningitis 1.

Lyme Carditis

Outpatient Management:

Oral antibiotics (same regimens as erythema migrans) for 14-21 days 1

Hospitalized Patients:

• Initial IV ceftriaxone until clinical improvement, then switch to oral antibiotics to complete 14-21 days total 1
• Hospitalization with continuous ECG monitoring is mandatory for: 1
  • PR interval >300 milliseconds
  • Second- or third-degree atrioventricular block
  • First-degree block with PR ≥300 milliseconds
  • Symptomatic patients (syncope, dyspnea, chest pain, palpitations)

Temporary Pacing:

For symptomatic bradycardia that cannot be managed medically, use temporary pacing rather than permanent pacemaker implantation 1.

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

Partial Response After First Course:

If mild residual joint swelling persists after the first 28-day course, the 2020 IDSA/AAN/ACR guidelines make no specific recommendation for versus against a second course of oral antibiotics versus observation 1. However, the 2006 IDSA guidelines favor a second 28-day course of oral antibiotics for patients with substantial improvement but incomplete resolution, reserving IV therapy for treatment failures 1.

Antibiotic-Refractory Arthritis:

If arthritis persists despite IV therapy and PCR of synovial fluid/tissue is negative, symptomatic treatment is recommended rather than additional antibiotics 1. Options include NSAIDs, intra-articular corticosteroid injections, or DMARDs such as hydroxychloroquine; rheumatology consultation is recommended 1.

Late Neurologic Lyme Disease

For CNS or peripheral nervous system involvement occurring months to years after infection:

• Ceftriaxone 2 g IV once daily for 14-28 days 1
• Alternative: Cefotaxime or penicillin G IV 1

Response is typically slow and may be incomplete; re-treatment is not recommended unless objective relapse is documented 1.

Post-Treatment Lyme Disease Syndrome

For patients with persistent nonspecific symptoms (fatigue, pain, cognitive impairment) following standard treatment but lacking objective evidence of active infection, additional antibiotic therapy is NOT recommended. 1 This strong recommendation is based on moderate-quality evidence showing no benefit from prolonged antibiotic therapy and potential for harm 1.

Critical Pitfalls to Avoid

Ineffective Antibiotics (Never Use):

• First-generation cephalosporins (e.g., cephalexin) are completely inactive against B. burgdorferi 1, 2, 3
• Fluoroquinolones 1
• Carbapenems 1
• Vancomycin 1
• Metronidazole 1
• Trimethoprim-sulfamethoxazole 1

Macrolides (Last Resort Only):

Azithromycin, clarithromycin, and erythromycin are significantly less effective than first-line agents and should only be used when patients cannot tolerate doxycycline, amoxicillin, or cefuroxime axetil 2, 3. Patients treated with macrolides require close monitoring to ensure resolution 2.

Duration Errors:

• Do not extend treatment beyond recommended durations without objective evidence of treatment failure 1
• Long-term antibiotic therapy lacks supporting data and may cause harm 1, 2
• Pulsed-dosing regimens are not recommended 1

Coinfection Considerations

In endemic areas, consider coinfection with Babesia microti or Anaplasma phagocytophilum if patients have: 1

• High-grade fever persisting >48 hours despite appropriate Lyme treatment
• Unexplained leukopenia, thrombocytopenia, or anemia
• More severe initial symptoms than typical for Lyme disease alone

For confirmed HGA coinfection, doxycycline 100 mg twice daily for 10 days treats both infections simultaneously 1, 2. For babesiosis, add atovaquone 750 mg every 12 hours plus azithromycin 500-1000 mg on day 1, then 250 mg daily for 7-10 days 1.