What is the recommended treatment for Lyme disease?

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Last updated: August 26, 2025View editorial policy

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Treatment of Lyme Disease

The recommended first-line treatment for Lyme disease is doxycycline 100mg twice daily for 28 days, with alternatives including amoxicillin or cefuroxime axetil for patients who cannot take doxycycline. 1

Antibiotic Treatment Options

Treatment should be tailored based on the stage and manifestation of Lyme disease:

Early Localized Disease (Erythema Migrans)

  • First-line: Doxycycline 100mg twice daily for 28 days 1
  • Alternatives:
    • Amoxicillin (dosage varies by patient factors)
    • Cefuroxime axetil (dosage varies by patient factors)

Neurological Manifestations

  • With meningitis or radiculopathy: IV ceftriaxone 2g daily for 14 days (range 10-28 days) 1
  • Facial nerve palsy without CSF abnormalities: Oral regimen as for erythema migrans for 14 days 1
  • Facial nerve palsy with CSF abnormalities: Treatment as for meningitis 1

Cardiac Manifestations

  • Hospitalized patients with symptomatic presentation, AV block, or myopericarditis: IV ceftriaxone 2g daily 1

Lyme Arthritis

  • Initial treatment: Same oral regimens as for early disease
  • Arthritis that has failed to improve or worsened: IV ceftriaxone 2g daily for 2-4 weeks 1

Evidence Strength and Treatment Duration

The IDSA, American College of Rheumatology (ACR), and CDC support these treatment recommendations with moderate-quality evidence 1. Clinical studies have demonstrated high efficacy rates for both doxycycline and cefuroxime axetil in treating early Lyme disease, with success rates of 91% for cefuroxime axetil and 93% for doxycycline at one month post-treatment 2.

Research has shown that shorter courses (10 days) of antibiotics may be effective for early Lyme disease 3, 4, but current guidelines from major infectious disease societies recommend a 28-day course for certain manifestations 1.

Important Considerations and Pitfalls

Avoid These Common Mistakes:

  • Extended antibiotic courses beyond recommended durations are explicitly discouraged as they have not shown additional benefit and may cause unnecessary side effects 1
  • Additional antibiotic therapy for patients with persistent symptoms after recommended treatment who lack objective evidence of reinfection or treatment failure 1
  • Using first-generation cephalosporins, which are ineffective against Lyme disease 1
  • Relying solely on serologic testing for diagnosis without clinical correlation 1

Special Considerations:

  • Post-Lyme Disease Syndrome: Some patients may experience persistent symptoms after appropriate antibiotic treatment, including fatigue, sleep disturbance, cognitive complaints, and musculoskeletal pain. This is not due to persistent infection and does not respond to additional antibiotics 1
  • Prophylaxis: A single dose of doxycycline is recommended for high-risk tick bites (identified Ixodes tick attached for ≥36 hours in areas where ≥20% of ticks carry B. burgdorferi) 1
  • Side effects: Doxycycline has a higher risk of photosensitivity reactions (9% vs 0% for cefuroxime), while cefuroxime axetil has a higher incidence of diarrhea (11% vs 3% for doxycycline) 2

Diagnosis must include objective clinical findings consistent with Lyme disease, and treatment should be initiated promptly once the diagnosis is established to prevent progression to later stages of disease 1.

References

Guideline

Lyme Disease Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Antibiotic treatment duration and long-term outcomes of patients with early lyme disease from a lyme disease-hyperendemic area.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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