What is the recommended treatment for Lyme disease?

Treatment of Lyme Disease

The treatment of Lyme disease depends on the clinical manifestation, with oral antibiotics (doxycycline, amoxicillin, or cefuroxime axetil) as first-line therapy for most presentations, and IV antibiotics reserved for neurologic disease with CNS involvement or treatment-refractory cases. 1, 2

Early Localized Disease (Erythema Migrans)

For patients with erythema migrans, oral antibiotic therapy is the standard of care. 3, 4

• Doxycycline 100 mg twice daily is the preferred first-line agent 3, 4
• Amoxicillin 500 mg three to four times daily (with or without probenecid 500 mg three times daily) is an alternative 3, 4
• Cefuroxime axetil is another oral option 1, 2
• Treatment duration is 10-21 days for early disease 3, 5

Important Considerations for Early Disease:

• Even patients with severe early manifestations should receive oral therapy initially 3
• Azithromycin has been studied but is generally less preferred than doxycycline or amoxicillin 4
• Doxycycline can be used safely in children, though amoxicillin remains preferred for non-neurological manifestations in young children 6

Lyme Arthritis

For Lyme arthritis, oral antibiotic therapy for 28 days is strongly recommended as initial treatment. 1, 2

• First course: 28 days of oral antibiotics (doxycycline, amoxicillin, or cefuroxime axetil) 1
• Partial response (mild residual joint swelling): Consider observation versus a second 28-day course of oral antibiotics 1
• No or minimal response (moderate to severe persistent swelling): Switch to IV ceftriaxone for 2-4 weeks 1
• Post-antibiotic Lyme arthritis (failed both oral and IV courses): Refer to rheumatology for disease-modifying antirheumatic drugs or biologics 1

Critical Pitfall:

Do not continue indefinite antibiotic courses for persistent joint symptoms without objective evidence of active infection—consider alternative diagnoses and inflammatory arthritis 1, 3

Neurologic Lyme Disease

The route of antibiotic administration depends on whether there is CNS parenchymal involvement. 1, 2

Indications for Testing and Treatment:

Test patients presenting with: 1

• Acute meningitis
• Painful radiculoneuritis
• Mononeuropathy multiplex
• Acute cranial neuropathies (especially CN VII, VIII)
• Spinal cord or brain inflammation with radiculitis

Treatment Approach:

• CNS parenchymal involvement (meningitis, encephalitis, myelitis): IV antibiotics strongly recommended over oral 1, 2

  • IV ceftriaxone, cefotaxime, or penicillin G for 14-21 days 2
  • Oral doxycycline is an alternative for some neurologic manifestations 2

• Isolated facial nerve palsy without other neurologic signs and normal CSF: Oral antibiotics are usually sufficient 3

  • No recommendation for or against corticosteroids 1

Do NOT routinely test for Lyme disease in: 1

• Typical ALS, relapsing-remitting MS, Parkinson's disease
• Dementia or cognitive decline alone
• New-onset seizures
• Psychiatric illness alone
• Nonspecific brain MRI white matter changes

Lyme Carditis

Treatment intensity depends on severity and whether the patient requires hospitalization. 1, 2

Hospitalization Criteria:

Admit patients with: 1

• PR interval >300 milliseconds
• Other arrhythmias
• Clinical manifestations of myopericarditis (chest pain, elevated troponin, pericardial effusion, dyspnea, edema)

Treatment Algorithm:

• Outpatients: Oral antibiotics preferred (doxycycline, amoxicillin, cefuroxime axetil, or azithromycin) 1, 2
• Hospitalized patients: Start with IV ceftriaxone, then switch to oral antibiotics once clinically improved 1
• Total duration: 14-21 days 1, 2

Cardiac Management:

• Symptomatic bradycardia: Use temporary pacing, NOT permanent pacemaker (conduction abnormalities typically resolve with antibiotics) 1
• Continuous ECG monitoring for high-risk patients 1

Cutaneous Manifestations

Borrelial Lymphocytoma:

• Oral antibiotics for 14 days (doxycycline, amoxicillin, or cefuroxime axetil) 1, 2, 7

Acrodermatitis Chronica Atrophicans:

• Oral antibiotics for 21-28 days 1

Post-Treatment Lyme Disease Syndrome

Do NOT prescribe additional antibiotics for persistent nonspecific symptoms without objective evidence of active infection. 1, 2

• Patients with fatigue, pain, or cognitive impairment after completing appropriate treatment should NOT receive further antibiotics 1, 2
• This is a strong recommendation based on moderate-quality evidence showing no benefit and potential harm from prolonged antibiotic therapy 1, 2
• Objective evidence of treatment failure includes: arthritis, meningitis, neuropathy—not subjective symptoms alone 1, 2

Critical Pitfall:

Avoid the trap of prescribing "chronic Lyme disease" treatment with prolonged or indefinite antibiotics for fibromyalgia-like symptoms or nonspecific complaints 3. This represents a major clinical error that exposes patients to antibiotic risks without benefit.

Key Drug Considerations

Doxycycline Precautions: 8

• Advise patients to avoid excessive sunlight (phototoxicity risk)
• Take with adequate fluids to prevent esophageal irritation
• May increase vaginal candidiasis incidence
• Absorption reduced by antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate
• Decreases effectiveness of oral contraceptives

Drug Interactions: 8

• May require downward adjustment of anticoagulant dosage
• Avoid concurrent use with penicillin (bacteriostatic vs bactericidal interaction)
• Barbiturates, carbamazepine, and phenytoin decrease doxycycline half-life