What is the recommended treatment for a patient with Lyme disease, particularly for adults and children, including those with allergies or pregnant women?

Treatment of Lyme Disease

For adults with early Lyme disease (erythema migrans), treat with doxycycline 100 mg twice daily for 14 days, amoxicillin 500 mg three times daily for 14-21 days, or cefuroxime axetil 500 mg twice daily for 14-21 days. 1

First-Line Oral Therapy for Early Lyme Disease (Erythema Migrans)

Adults

• Doxycycline 100 mg twice daily for 14 days (range 10-21 days) is the preferred first-line agent 1

  • Has the added benefit of treating human granulocytic anaplasmosis (HGA), which can occur as a coinfection 1
  • Can be shortened to 10 days if doxycycline is used 1
  • Contraindicated in pregnancy, lactation, and children <8 years of age 1

• Amoxicillin 500 mg three times daily for 14-21 days is equally effective 1

  • Safe for pregnant women and young children 1
  • Should not be given twice daily despite convenience, as efficacy data only supports three-times-daily dosing 1

• Cefuroxime axetil 500 mg twice daily for 14-21 days is another first-line option 1

  • Equally effective to doxycycline and amoxicillin 1

Children

• Amoxicillin 50 mg/kg/day in 3 divided doses (maximum 500 mg per dose) for 14-21 days is the preferred agent for children <8 years 1, 2

• Cefuroxime axetil 30 mg/kg/day in 2 divided doses (maximum 500 mg per dose) for 14-21 days is an alternative 1, 2

• For children ≥8 years, doxycycline 4 mg/kg/day in 2 divided doses (maximum 100 mg per dose) for 14-21 days can be used 1, 2

Alternative Therapy for Patients with Allergies

Macrolide antibiotics are NOT first-line therapy and should only be used when patients cannot tolerate doxycycline, amoxicillin, AND cefuroxime axetil, as they are less effective. 1

Adults with Multiple Drug Intolerances

• Azithromycin 500 mg orally daily for 7-10 days 1
• Clarithromycin 500 mg orally twice daily for 14-21 days (avoid in pregnancy) 1
• Erythromycin 500 mg orally four times daily for 14-21 days 1
• Patients on macrolides require close monitoring to ensure clinical resolution 1

Children with Multiple Drug Intolerances

• Azithromycin 10 mg/kg/day (maximum 500 mg/day) 1
• Clarithromycin 7.5 mg/kg twice daily (maximum 500 mg per dose) 1
• Erythromycin 12.5 mg/kg four times daily (maximum 500 mg per dose) 1

Pregnant Women

Pregnant women should be treated identically to non-pregnant patients with the same disease manifestation, except doxycycline must be avoided. 1

• Amoxicillin 500 mg three times daily for 14-21 days is the treatment of choice 1
• Cefuroxime axetil 500 mg twice daily for 14-21 days is an alternative 1
• Clarithromycin should be avoided in pregnancy 1

Neurologic Lyme Disease

Early Neurologic Disease (Meningitis or Radiculopathy)

Parenteral therapy is required for CNS involvement with meningitis or radiculopathy. 1

Adults

• Ceftriaxone 2 g IV once daily for 14 days (range 10-28 days) is the preferred agent 1
• Cefotaxime 2 g IV every 8 hours for 14 days (range 10-28 days) is an alternative 1
• Penicillin G 18-24 million units/day IV divided every 4 hours for 14 days (range 10-28 days) is another option 1
• Doxycycline 200-400 mg/day orally or IV for 10-28 days may be adequate for non-pregnant adults intolerant of β-lactams 1

Children

• Ceftriaxone 50-75 mg/kg/day IV once daily (maximum 2 g) for 14 days (range 10-28 days) 1
• Cefotaxime 150-200 mg/kg/day IV in 3-4 divided doses (maximum 6 g/day) for 14 days (range 10-28 days) 1
• Penicillin G 200,000-400,000 units/kg/day IV divided every 4 hours (maximum 18-24 million units/day) for 14 days (range 10-28 days) 1
• Children ≥8 years can receive oral doxycycline 4-8 mg/kg/day in 2 divided doses (maximum 100-200 mg per dose) 1

Cranial Nerve Palsy (Including Facial Nerve Palsy)

Oral therapy is sufficient for isolated cranial nerve palsy without meningeal signs. 1

• Use standard oral regimens (doxycycline, amoxicillin, or cefuroxime axetil) for 14-21 days 1
• Antibiotics should be given to prevent further sequelae, even though they may not hasten resolution of the palsy itself 1
• Lumbar puncture is indicated if there is strong clinical suspicion of CNS involvement (severe headache, nuchal rigidity) 1

Late Lyme Disease

Lyme Arthritis

• Oral regimen (doxycycline, amoxicillin, or cefuroxime axetil) for 28 days 1
• For recurrent arthritis after oral therapy, consider repeat oral or parenteral regimen for 14-28 days 1

Late Neurologic Disease

• Parenteral regimen (ceftriaxone, cefotaxime, or penicillin G) for 14-28 days 1

Cardiac Lyme Disease

Oral or parenteral regimen for 14-21 days depending on severity of heart block. 1

• Advanced atrioventricular heart block may require parenteral therapy 1

Tick Bite Prophylaxis

A single dose of doxycycline 200 mg (4 mg/kg for children ≥8 years, maximum 200 mg) may be offered within 72 hours of tick removal ONLY when ALL of the following criteria are met: 1, 2, 3

1. The tick is reliably identified as an adult or nymphal Ixodes scapularis tick 1, 2, 3
2. The tick is estimated to have been attached ≥36 hours based on engorgement 1, 2, 3
3. Prophylaxis can be started within 72 hours of tick removal 1, 2, 3
4. The local infection rate of ticks with Borrelia burgdorferi is ≥20% 1, 2, 3
5. Doxycycline is not contraindicated 1, 2, 3

Amoxicillin is NOT recommended for prophylaxis in pregnant women or young children who cannot take doxycycline, due to lack of data on effective short-course regimens. 3

Critical Pitfalls to Avoid

The following agents are NOT recommended for any manifestation of Lyme disease: 1

• First-generation cephalosporins (e.g., cephalexin) 1, 2
• Fluoroquinolones 1
• Trimethoprim-sulfamethoxazole 1
• Benzathine penicillin G 1
• Long-term antibiotic therapy 1
• Combination antimicrobial therapy 1

Ceftriaxone should NOT be used for uncomplicated erythema migrans without neurologic involvement, as oral agents are equally effective and safer. 1

Coinfection Considerations

Consider coinfection with Anaplasma phagocytophilum (HGA) or Babesia microti in patients with: 1

• High-grade fever persisting >48 hours despite appropriate Lyme therapy 1
• Unexplained leukopenia, thrombocytopenia, or anemia 1
• More severe initial symptoms than typical for Lyme disease alone 1

Doxycycline treats both Lyme disease and HGA but not babesiosis 1

Monitoring After Treatment

Patients should monitor for symptoms for 30 days after tick bite or treatment completion. 3

• Complete response to treatment may be delayed beyond the treatment duration 1
• Relapse can occur with any regimen; patients with objective signs of relapse may need a second course 1
• Seek immediate medical attention if expanding skin lesions or new symptoms develop 3