What is the treatment for Lyme disease?

Treatment of Lyme Disease

Treat early Lyme disease (erythema migrans) with oral doxycycline 100 mg twice daily for 14 days in adults, or amoxicillin 500 mg three times daily for 14 days if doxycycline is contraindicated. 1, 2

Early Localized Disease (Erythema Migrans)

First-Line Oral Regimens for Adults

• Doxycycline 100 mg twice daily for 14 days is the preferred treatment, with the critical advantage of also covering potential coinfection with Anaplasma phagocytophilum (human granulocytic anaplasmosis), which commonly occurs in the same endemic areas 1, 2
• 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 days is an alternative option 1
• Ten days of doxycycline is sufficient, but the full 14-day course is recommended for amoxicillin and cefuroxime due to their shorter half-lives 1, 3

Pediatric Dosing

• Children ≥8 years: Doxycycline 4 mg/kg per day in 2 divided doses (maximum 200 mg/day) for 14 days 1, 4, 2
• Children <8 years: Amoxicillin 50 mg/kg per day in 3 divided doses (maximum 500 mg per dose) for 14 days 1, 4
• Alternative for children <8 years: Cefuroxime axetil 30 mg/kg per day in 2 divided doses (maximum 500 mg per dose) for 14 days 1, 4

Macrolides: Reserve Only for Intolerance

• Macrolides are significantly less effective and should NOT be first-line therapy 1, 2
• Use only when patients cannot tolerate doxycycline, amoxicillin, AND cefuroxime 1
• If prescribed: 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

• Parenteral therapy is required: Ceftriaxone 2 g IV once daily for 14 days (range 10-28 days) 1, 2
• Pediatric dosing: Ceftriaxone 50-75 mg/kg IV daily (maximum 2 g) 1, 4, 2
• Alternative for adults with β-lactam allergy: Doxycycline 200-400 mg/day IV in 2 divided doses 1
• Alternative parenteral options: Cefotaxime 2 g IV every 8 hours or penicillin G 18-24 million units/day IV divided every 4 hours 1

Isolated Cranial Nerve Palsy (Without Meningitis)

• Oral therapy is sufficient: Doxycycline 100 mg twice daily for 14-21 days 1, 5
• This applies only when there are no other neurologic signs and cerebrospinal fluid is normal 1, 6

Lyme Carditis

• Either oral OR parenteral regimens can be used for 14-21 days 1, 2
• Hospitalization with continuous cardiac monitoring is mandatory for symptomatic patients, any degree of atrioventricular block beyond first-degree, or first-degree block with PR interval ≥300 milliseconds 2
• Oral options: Same as erythema migrans (doxycycline, amoxicillin, or cefuroxime) 1
• Parenteral option: Ceftriaxone 2 g IV daily 1

Late Disease

Lyme Arthritis (Without Neurologic Involvement)

• Oral regimen for 28 days using the same agents as erythema migrans 1, 2
• For recurrent arthritis after initial oral treatment: Either repeat 28-day oral course OR switch to parenteral therapy (ceftriaxone 2 g IV daily) for 14-28 days 1, 2

Late Neurologic Disease

• Parenteral therapy required: Ceftriaxone 2 g IV daily for 14-28 days 1
• Response is typically slow and may be incomplete 5

Acrodermatitis Chronica Atrophicans

• Oral regimen for 21 days (range 14-28 days) 1

Tick Bite Prophylaxis

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

1. Attached tick reliably identified as adult or nymphal Ixodes scapularis
2. Estimated attachment ≥36 hours based on engorgement
3. Prophylaxis can be started within 72 hours of tick removal
4. Local infection rate of ticks with Borrelia burgdorferi is ≥20%
5. Doxycycline is not contraindicated

Otherwise, observation alone is recommended 1

Special Populations

• Pregnant and lactating patients: Treat identically to non-pregnant patients with the same disease manifestation, but avoid doxycycline 1, 2
• Use amoxicillin or cefuroxime for all stages where oral therapy is appropriate 1

Coinfection Considerations

Suspect coinfection with Babesia microti or Anaplasma phagocytophilum when: 1, 5

• More severe initial symptoms than typical for Lyme disease alone
• High-grade fever persisting >48 hours despite appropriate antibiotic therapy
• Unexplained leukopenia, thrombocytopenia, or anemia
• Erythema migrans resolved but viral-like symptoms persist or worsen

Doxycycline covers Anaplasma but NOT Babesia, making it the preferred agent in endemic areas 1, 4

Critical Pitfalls to Avoid

The following treatments are NEVER recommended and may cause harm: 1, 2

• First-generation cephalosporins (e.g., cephalexin) - completely ineffective 1, 4, 2
• Fluoroquinolones, carbapenems, vancomycin 1, 2
• Metronidazole, tinidazole, trimethoprim-sulfamethoxazole 1, 2
• Benzathine penicillin G 1, 2
• Long-term antibiotic therapy beyond recommended durations 1, 2
• Combination antimicrobial therapy 1, 2
• Pulsed-dosing regimens (dosing on some days but not others) 1, 2

Ceftriaxone is NOT superior to oral agents for early disease and carries higher risk of serious adverse effects, so it should not be used for uncomplicated erythema migrans 1

Treatment Response and Monitoring

• Most patients respond promptly and completely to appropriate therapy 1, 4
• Less than 10% fail to respond to initial appropriate antibiotic therapy, and rarely is re-treatment required 1, 4
• Patients who are more systemically ill at diagnosis take longer to achieve complete response 1, 4
• Complete response may be delayed beyond the treatment duration - this is normal and does not indicate treatment failure 1
• Do NOT use serologic testing to monitor treatment response - antibodies remain positive for months to years after successful treatment 5
• Treatment failure rate with 10-day doxycycline courses is exceedingly rare (approximately 1%), with outcomes similar to longer courses 3

Practical Considerations

• Doxycycline should be taken with 8 ounces of fluid to reduce esophageal irritation and with food to reduce gastrointestinal intolerance 1, 4
• Patients on doxycycline must avoid sun exposure due to photosensitivity risk 1, 4
• Doxycycline is relatively contraindicated in children <8 years and pregnant/lactating women 1
• When erythema migrans cannot be distinguished from bacterial cellulitis, treat with cefuroxime axetil or amoxicillin-clavulanate to cover both possibilities 1