What are the treatment and management options for Lyme disease?

Lyme Disease Treatment and Management

For early Lyme disease with erythema migrans, treat adults with doxycycline 100 mg twice daily for 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 Oral Regimens for Adults

• Doxycycline 100 mg twice daily for 14 days is the preferred treatment, with the advantage of also covering potential coinfection with Anaplasma phagocytophilum (human granulocytic anaplasmosis) 1, 3
• Amoxicillin 500 mg three times daily for 14-21 days is an effective alternative, particularly for pregnant or lactating women 1, 3
• Cefuroxime axetil 500 mg twice daily for 14-21 days is another first-line option 1, 3

Pediatric Dosing (Children Under 8 Years)

• Amoxicillin 50 mg/kg/day in 3 divided doses (maximum 500 mg per dose) for 14 days is the preferred treatment 1, 2
• Cefuroxime axetil 30 mg/kg/day in 2 divided doses (maximum 500 mg per dose) for 14 days is an alternative 1, 2

Children 8 Years and Older

• Doxycycline 4 mg/kg/day in 2 divided doses (maximum 100 mg per dose) for 14 days is recommended 1, 2
• Note that 10 days of doxycycline therapy is sufficient, whereas β-lactam antibiotics require the full 14-day course due to shorter half-life 1, 2

Important Doxycycline Considerations

• Take with 8 ounces of fluid to reduce esophageal irritation and with food to reduce gastrointestinal intolerance 2, 4
• Patients must avoid sun exposure due to photosensitivity risk 2, 4
• Absorption is impaired by antacids containing aluminum, calcium, or magnesium, iron-containing preparations, and bismuth subsalicylate 4

Macrolides (Less Effective - Use Only When First-Line Agents Cannot Be Tolerated)

• Azithromycin 500 mg daily for 7-10 days (pediatric: 10 mg/kg/day, maximum 500 mg) 1
• Clarithromycin 500 mg twice daily for 14-21 days (pediatric: 7.5 mg/kg twice daily, maximum 500 mg per dose) - contraindicated in pregnancy 1
• Patients on macrolides require close observation to ensure resolution of clinical manifestations 1, 2

Early Neurologic Disease

Meningitis or Radiculopathy

• Ceftriaxone 2 g IV once daily for 14 days (range 10-28 days) is the preferred parenteral regimen 1, 3
• Pediatric dosing: 50-75 mg/kg IV daily (maximum 2 g) 1, 2
• Alternative parenteral options include:
  • Cefotaxime 2 g IV every 8 hours (pediatric: 150-200 mg/kg/day in 3-4 divided doses, maximum 6 g/day) 1, 3
  • Penicillin G 18-24 million units/day IV divided every 4 hours (pediatric: 200,000-400,000 units/kg/day, maximum 18-24 million units/day) 1, 3

Cranial Nerve Palsy (Including Facial Nerve Palsy)

• Oral regimen (same as erythema migrans) for 14-21 days can be used for isolated cranial nerve palsy without meningitis 1, 5
• Lumbar puncture is indicated when there is strong clinical suspicion of CNS involvement (severe or prolonged headache, nuchal rigidity) 1
• Patients with both clinical and laboratory evidence of meningitis should receive parenteral therapy 1
• Antibiotics should be given even though they may not hasten resolution of seventh cranial nerve palsy, as they prevent further sequelae 1

Lyme Carditis

Management Approach

• Either oral or parenteral antibiotic therapy for 14 days (range 14-21 days) 1
• Hospitalization with continuous monitoring is required for:
  • Symptomatic patients (syncope, dyspnea, chest pain) 1
  • Second- or third-degree atrioventricular block 1
  • First-degree heart block with PR interval ≥30 milliseconds (block may worsen rapidly) 1

Treatment Regimen

• Start with parenteral ceftriaxone (same dosing as meningitis) for hospitalized patients 1
• Switch to oral regimen (same as erythema migrans) for completion of therapy or for outpatients 1
• Temporary pacemaker may be required for advanced heart block; discontinue when block resolves 1

Late Disease

Lyme Arthritis

• Oral regimen for 28 days (same agents as erythema migrans) 1
• For recurrent arthritis after oral regimen: Consider second 28-day oral course or switch to parenteral therapy for 14-28 days 1
• Antibiotic-refractory arthritis is defined as persistent synovitis for ≥2 months after completing IV ceftriaxone (or two 4-week oral courses) with negative PCR for B. burgdorferi 1
• For refractory cases: Symptomatic therapy with NSAIDs, intra-articular corticosteroids, or DMARDs (e.g., hydroxychloroquine) with rheumatology consultation 1
• Arthroscopic synovectomy can reduce inflammation period if persistent synovitis causes significant pain or functional limitation 1

Late Neurologic Disease

• Parenteral regimen for 14-28 days (same as early neurologic disease) 1, 3
• Response to treatment is typically slow and may be incomplete 3, 5

Acrodermatitis Chronica Atrophicans

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

Special Populations

Pregnancy and Lactation

• Treat identically to non-pregnant patients with the same disease manifestation, except avoid doxycycline 1
• Use amoxicillin or cefuroxime axetil for oral therapy 1
• Use parenteral ceftriaxone, cefotaxime, or penicillin G for neurologic disease 1

Tick Bite Prophylaxis

Single-Dose Doxycycline Prophylaxis

Offer doxycycline 200 mg single dose (pediatric: 4 mg/kg for children ≥8 years) ONLY when ALL of the following criteria are met: 1

• Attached tick reliably identified as adult or nymphal Ixodes scapularis 1
• Estimated attachment ≥36 hours based on degree of engorgement 1
• Prophylaxis can start within 72 hours of tick removal 1
• Local infection rate of ticks with B. burgdorferi is ≥20% 1
• Doxycycline not contraindicated 1

Coinfection Considerations

Consider coinfection with Babesia microti or Anaplasma phagocytophilum when: 1, 3, 5

• More severe initial symptoms than typical for Lyme disease alone 1
• High-grade fever persisting ≥48 hours despite appropriate Lyme therapy 1
• Unexplained leukopenia, thrombocytopenia, or anemia 1
• Erythema migrans resolved but viral-like symptoms persist or worsen 1

Critical Pitfalls to Avoid

Ineffective or Harmful Treatments - DO NOT USE:

• First-generation cephalosporins (e.g., cephalexin) - ineffective against B. burgdorferi 1, 2, 3
• Fluoroquinolones, carbapenems, vancomycin - lack efficacy 1, 3
• Metronidazole, tinidazole, trimethoprim-sulfamethoxazole - ineffective 1, 3
• Benzathine penicillin G - inadequate tissue levels 1
• Long-term antibiotic therapy beyond recommended durations - no proven benefit and potential for harm 1, 3
• Combination antimicrobial therapy - not recommended 1, 3
• Pulsed-dosing regimens (antibiotics on some days but not others) - ineffective 1
• Multiple repeated courses for the same episode - not indicated 1, 3

Monitoring and Follow-Up Considerations

• Do not use serologic testing to monitor treatment response - antibodies remain positive for months to years after successful treatment and do not correlate with clinical response 3, 5
• Complete response to treatment may be delayed beyond treatment duration 1
• Jarisch-Herxheimer reaction may occur within 1-2 hours of initiating therapy in patients with spirochetal infections, characterized by fever, chills, myalgias, headache, and mild hypotension; it resolves within 12-24 hours 6
• Most patients respond promptly to appropriate therapy, but <10% may have persistent objective manifestations 2
• Patients who are more systemically ill at diagnosis may take longer for complete response 2