What are the recommended treatments for Lyme disease?

Lyme Disease Treatment Recommendations

For early Lyme disease with erythema migrans, treat with oral doxycycline 100 mg twice daily, amoxicillin 500 mg three times daily, or cefuroxime axetil 500 mg twice daily for 14-21 days; for neurologic manifestations without brain/spinal cord involvement, use IV ceftriaxone, cefotaxime, penicillin G, or oral doxycycline for 14-21 days; and for Lyme arthritis, use oral antibiotics for 28 days. 1, 2

Early Lyme Disease (Erythema Migrans)

Oral antibiotic regimens are the standard of care for early localized or early disseminated Lyme disease:

• Doxycycline 100 mg twice daily for 14-21 days is a first-line option for adults and children ≥8 years 3, 4
• Amoxicillin 500 mg three times daily for 14-21 days is preferred for children <8 years, pregnant women, and those who cannot tolerate doxycycline 3, 5, 4
• Cefuroxime axetil 500 mg twice daily for 20 days is an alternative option with proven efficacy comparable to doxycycline 3
• Azithromycin 500 mg on day 1, then 250 mg daily for 4 days is less preferred but can be used when other options are contraindicated 4

Key Clinical Considerations for Early Disease

• Even patients with severe early manifestations should receive oral therapy initially 5
• Borrelial lymphocytoma requires 14 days of oral doxycycline, amoxicillin, or cefuroxime axetil 2, 6
• Treatment duration beyond 21 days has never been shown to provide additional benefit and is not indicated 5

Neurologic Lyme Disease

Without Brain or Spinal Cord Parenchymal Involvement

For meningitis, cranial neuropathy (especially facial nerve palsy), radiculoneuropathy, or other peripheral nervous system manifestations:

• IV ceftriaxone, cefotaxime, penicillin G, OR oral doxycycline for 14-21 days are all equally recommended 1, 2
• The choice between IV and oral should be based on side effect profile, ease of administration, ability to tolerate oral medication, and compliance concerns—not effectiveness 1
• Treatment route may be switched from IV to oral during the course 1

With Brain or Spinal Cord Parenchymal Involvement

IV antibiotics are strongly preferred over oral antibiotics when there is documented parenchymal involvement of the brain or spinal cord 1

Special Case: Isolated Facial Nerve Palsy

• If the patient has isolated seventh cranial nerve palsy with no other signs/symptoms of Lyme disease and normal cerebrospinal fluid, oral therapy is usually sufficient 5
• No recommendation is made regarding corticosteroid use in Lyme-associated facial nerve palsy 1

Lyme Carditis

Outpatient Management

Oral antibiotics are preferred over IV antibiotics for outpatients with Lyme carditis 1

• Oral options include doxycycline, amoxicillin, cefuroxime axetil, and azithromycin 1, 2
• Total duration: 14-21 days 1, 2

Inpatient Management

Hospitalize patients with severe cardiac complications:

• PR interval >300 milliseconds 1
• Other arrhythmias 1
• Clinical manifestations of myopericarditis (exercise intolerance, palpitations, presyncope, syncope, pericarditic pain, pericardial effusion, elevated troponin, edema, shortness of breath) 1

For hospitalized patients:

• Start with IV ceftriaxone until clinical improvement, then switch to oral antibiotics to complete 14-21 days total 1
• For symptomatic bradycardia requiring pacing, use temporary pacing rather than permanent pacemaker implantation 1

Lyme Arthritis

Oral antibiotics for 28 days are the recommended treatment 2

• Oral options include doxycycline, amoxicillin, or cefuroxime axetil 2
• If partial response to initial treatment, consider observation or a second 28-day course of oral antibiotics 7
• If no or minimal response to initial treatment, consider 2-4 weeks of IV ceftriaxone 7

Post-Treatment Lyme Disease: Critical Pitfalls

What NOT to Do

Do not treat based on persistent positive IgM serology alone:

• IgM antibodies commonly persist for months or years after successful treatment and do not indicate active infection 7
• Positive IgM without objective clinical signs does not warrant additional antibiotics 7

Do not provide additional antibiotics for nonspecific symptoms:

• For patients with persistent nonspecific symptoms (fatigue, myalgias, cognitive complaints) but lacking objective evidence of reinfection or treatment failure, additional antibiotic therapy is strongly not recommended 7, 2
• Treatment failure rate with appropriate initial therapy is approximately 1% 7
• Serologic testing cannot distinguish between past treated infection and active disease 7

When to Consider Retreatment

Only proceed with additional treatment if objective findings are present:

• Arthritis with documented joint swelling and effusion 7
• Meningitis with CSF abnormalities 7
• Neuropathy with objective neurologic findings 7
• Carditis with documented conduction abnormalities 7

Common Pitfall to Avoid

Never confuse persistent antibodies with persistent infection—approximately 99% of appropriately treated patients achieve cure, and most persistent symptoms represent post-infectious phenomena (similar to fibromyalgia) that are not antibiotic-sensitive 7, 5