What is the recommended treatment for Lyme disease?

Treatment of Lyme Disease

For early Lyme disease with erythema migrans, treat adults with doxycycline 100 mg twice daily for 10-14 days, and children under 8 years with amoxicillin 50 mg/kg/day divided three times daily for 14 days. 1, 2

Early Localized Disease (Erythema Migrans)

First-Line Treatment for Adults

• Doxycycline 100 mg twice daily for 14 days (range 10-21 days) is the preferred treatment for adults with early localized or early disseminated Lyme disease 1, 2
• Doxycycline has the critical advantage of also treating potential coinfection with Anaplasma phagocytophilum (human granulocytic anaplasmosis), which may occur simultaneously with Lyme disease 1, 2
• A 10-day course of doxycycline is sufficient based on randomized controlled trial evidence 1, 3

Alternative Oral Regimens for Adults

• Amoxicillin 500 mg three times daily for 14-21 days is equally effective and preferred for pregnant or lactating women 1, 2
• Cefuroxime axetil 500 mg twice daily for 14-21 days is another effective alternative 1, 2

Pediatric Treatment

• Children under 8 years: Amoxicillin 50 mg/kg/day in 3 divided doses (maximum 500 mg per dose) for 14 days 1, 4
• Children ≥8 years: Doxycycline 4 mg/kg/day in 2 divided doses (maximum 100 mg per dose) for 14 days 1, 4
• Cefuroxime axetil 30 mg/kg/day in 2 divided doses (maximum 500 mg per dose) for 14 days is an alternative for children under 8 years 1, 4

Macrolides: Last Resort Only

• Macrolides (azithromycin, clarithromycin, erythromycin) are NOT recommended as first-line therapy because they are less effective 1
• Reserve macrolides only for patients who cannot tolerate doxycycline, amoxicillin, AND cefuroxime axetil 1, 5
• If macrolides must be used: azithromycin 500 mg daily for 7-10 days, clarithromycin 500 mg twice daily for 14-21 days, or erythromycin 500 mg four times daily for 14-21 days 1
• Patients on macrolides require close monitoring to ensure clinical resolution 1, 4

Early Neurologic Disease

Meningitis or Radiculopathy

• Intravenous ceftriaxone 2 g once daily for 14 days (range 10-28 days) is the preferred treatment for adults with Lyme meningitis or radiculopathy 1, 2, 5
• Pediatric dosing: ceftriaxone 50-75 mg/kg/day (maximum 2 g) as a single daily IV dose 1, 2, 4
• Alternative parenteral options: cefotaxime 2 g IV every 8 hours or penicillin G 18-24 million units/day IV divided every 4 hours 1, 5

Oral Doxycycline for Neurologic Disease

• Recent high-quality evidence demonstrates oral doxycycline 200 mg daily for 14-28 days is equally effective as IV ceftriaxone for Lyme neuroborreliosis 6, 7
• A 2021 randomized equivalence trial showed oral doxycycline 100 mg twice daily for 4 weeks was equivalent to IV ceftriaxone 2 g daily for 3 weeks 6
• A 2008 double-blind randomized trial confirmed oral doxycycline 200 mg daily for 14 days was non-inferior to IV ceftriaxone 2 g daily for 14 days 7
• This represents a major shift from older guidelines, offering a more convenient and cost-effective option for many patients with neurologic Lyme disease 6, 7

Facial Nerve Palsy (Cranial Nerve VII)

• Isolated facial nerve palsy without meningitis can be treated with oral antibiotics (same regimens as erythema migrans) 1, 8
• A prospective study showed oral doxycycline 200-400 mg daily for 9-17 days resulted in 90% complete recovery within 6 months 8
• The 2020 guidelines make no recommendation on corticosteroids for facial nerve palsy 1

Lyme Carditis

Treatment Approach

• Outpatients: Oral antibiotics (same regimens as erythema migrans) for 14-21 days 1, 2
• Hospitalized patients: Start with IV ceftriaxone 2 g daily until clinical improvement, then switch to oral antibiotics to complete 14-21 days total 1, 2

Hospitalization Criteria

• Admit patients with symptomatic bradycardia, PR interval >300 milliseconds, second- or third-degree AV block, or clinical manifestations of myopericarditis 1, 2
• Continuous ECG monitoring is required for hospitalized patients 1, 2
• For symptomatic bradycardia requiring intervention, use temporary pacing rather than permanent pacemaker implantation 1, 2

Late Disease (Lyme Arthritis)

Initial Treatment

• Oral antibiotics (same regimens as erythema migrans) for 28 days 1, 2
• Use doxycycline, amoxicillin, or cefuroxime axetil at standard doses 1, 2

Recurrent or Persistent Arthritis

• For recurrent arthritis after initial oral course: Either repeat 28-day oral course OR switch to IV ceftriaxone 2 g daily for 14-28 days 1, 2, 5
• Consider other causes of joint swelling before additional antibiotic treatment 5

Tick Bite Prophylaxis

When to Offer Prophylaxis

Single-dose doxycycline 200 mg (pediatric: 4 mg/kg for children ≥8 years) is recommended ONLY when ALL of the following criteria are met: 1, 2

• Attached tick reliably identified as adult or nymphal Ixodes scapularis 1, 2
• Estimated attachment ≥36 hours (based on degree of engorgement or known time of attachment) 1, 2
• Prophylaxis can be started within 72 hours of tick removal 1, 2
• Doxycycline is not contraindicated 1, 2
• Local Lyme disease risk is ≥20% 1

When NOT to Use Prophylaxis

• Do NOT substitute amoxicillin for doxycycline prophylaxis - there is no evidence for an effective short-course regimen 1
• Prophylaxis is generally not necessary for Ixodes pacificus (West Coast) tick bites 1

Critical Pitfalls to Avoid

Ineffective Antibiotics

The following antibiotics are INEFFECTIVE for Lyme disease and should NEVER be used: 1, 2, 5, 4

• First-generation cephalosporins (e.g., cephalexin) 1, 2, 4
• Fluoroquinolones 2, 5, 4
• Carbapenems 2, 5
• Vancomycin 2, 5
• Metronidazole 2, 5
• Tinidazole 2, 5
• Trimethoprim-sulfamethoxazole 2
• Benzathine penicillin G 2

Inappropriate Treatment Strategies

The following treatment approaches are NOT recommended and may cause harm: 2, 5

• Long-term antibiotic therapy beyond recommended durations 2, 5, 4
• Combination antimicrobial therapy 2, 5
• Pulsed-dosing regimens 2, 5

Post-Treatment Monitoring

• Do NOT use serologic testing to monitor treatment response - antibodies remain positive for months to years after successful treatment 5
• Antibody levels do not correlate with clinical response 5
• Clinical improvement is the most reliable indicator of treatment success 5
• Persistent positive serology does NOT indicate ongoing infection or treatment failure 5

Special Populations

Pregnancy

• Treat pregnant patients identically to non-pregnant patients with the same disease manifestation, but avoid doxycycline 1, 2
• Use amoxicillin or cefuroxime axetil for early disease 1
• Use IV ceftriaxone for neurologic or cardiac involvement 1, 2

Coinfections

• Consider coinfection with Anaplasma phagocytophilum or Babesia microti in patients with fever after tick bite or persistent symptoms despite appropriate therapy 1, 5
• Doxycycline treats both Lyme disease and anaplasmosis but NOT babesiosis 1
• Babesiosis requires atovaquone plus azithromycin for 7-10 days (mild disease) or clindamycin plus quinine (severe disease) 1, 3