What is the recommended treatment for Lyme disease caused by Borrelia (B.) burgdorferi?

Treatment of Lyme Disease Caused by Borrelia burgdorferi

For early Lyme disease, 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 disseminated disease with CNS involvement, cardiac complications, or refractory arthritis, use intravenous ceftriaxone 2 g once daily for 14-28 days. 1, 2

Early Localized Disease (Erythema Migrans)

First-line oral antibiotics are highly effective and should be used for 14-21 days: 1, 2

• Doxycycline 100 mg twice daily is preferred for adults and children ≥8 years 1
• Amoxicillin 500 mg three times daily for adults (50 mg/kg/day in 3 divided doses for children, maximum 500 mg per dose) 1
• Cefuroxime axetil 500 mg twice daily for adults (30 mg/kg/day in 2 divided doses for children, maximum 500 mg per dose) 1

Important considerations for early disease:

• Most patients (>90%) respond promptly and completely to oral therapy 1, 2
• Treatment failure rate is approximately 1% when appropriate antibiotics are used 2
• Doxycycline should be avoided in pregnant/lactating women and children <8 years 1
• Take doxycycline with 8 ounces of fluid and food to reduce gastrointestinal side effects 1

Macrolides (azithromycin, clarithromycin, erythromycin) are less effective and reserved only for patients with documented allergies to penicillins, cephalosporins, and tetracyclines. 1 Patients treated with macrolides require close monitoring to ensure clinical resolution 1

Early Disseminated Disease

Neurologic Manifestations

For CNS involvement (meningitis, encephalitis, radiculopathy):

• Intravenous ceftriaxone 2 g once daily for 14-21 days 1, 2
• Alternative: IV cefotaxime 2 g every 8 hours or IV penicillin G 18-24 million units/day divided every 4 hours 1

For isolated cranial nerve palsy (especially facial nerve palsy) without meningitis:

• Oral antibiotics are sufficient (same regimens as early disease for 14-21 days) 1, 2
• Lumbar puncture should be performed if there are signs of meningitis 1

Cardiac Manifestations (Lyme Carditis)

For outpatients with mild carditis:

• Oral antibiotics (doxycycline, amoxicillin, or cefuroxime axetil) for 14-21 days 2, 3

For hospitalized patients requiring cardiac monitoring:

• Start with IV ceftriaxone, then switch to oral antibiotics once stable 1, 2
• Total treatment duration: 14-21 days 1, 3
• Temporary pacemaker may be required for advanced heart block 1

Late Disseminated Disease

Lyme Arthritis

Initial treatment:

• Oral antibiotics for 28 days (doxycycline, amoxicillin, or cefuroxime axetil at standard doses) 1, 2

For minimal response to oral therapy:

• IV ceftriaxone 2 g once daily for 2-4 weeks 2

For antibiotic-refractory arthritis (persistent synovitis ≥2 months after IV ceftriaxone with negative PCR):

• Anti-inflammatory agents and possibly arthroscopic synovectomy 1
• Additional antibiotics are NOT recommended 1
• This condition is associated with specific MHC II molecules and represents an autoimmune phenomenon rather than persistent infection 1

Late Neurologic Disease

For late CNS or peripheral nervous system involvement:

• IV ceftriaxone 2 g once daily for 14-28 days 1, 2

Special Populations

Pregnant women:

• Avoid doxycycline 1
• Use amoxicillin or cefuroxime axetil at standard doses 1
• No evidence that pregnant women require different treatment duration 1

Children <8 years:

• Amoxicillin 50 mg/kg/day in 3 divided doses (maximum 500 mg per dose) 1
• Cefuroxime axetil 30 mg/kg/day in 2 divided doses (maximum 500 mg per dose) 1
• Avoid doxycycline 1

Critical Pitfalls to Avoid

Do NOT use the following for Lyme disease treatment: 1

• First-generation cephalosporins (e.g., cephalexin) - inactive against B. burgdorferi 1
• Fluoroquinolones, carbapenems, vancomycin, metronidazole 1
• Multiple repeated courses of antibiotics for the same episode 1
• Prolonged antibiotic courses beyond recommended durations 1
• Combination antibiotic therapy (not supported by evidence in humans) 1

Persistent symptoms after appropriate treatment:

• Antibodies persist for months to years after successful treatment and do NOT indicate active infection 1, 4
• Approximately 10-20% of patients experience persistent subjective symptoms (fatigue, arthralgia, cognitive complaints) despite microbiologic cure 1, 5
• Additional antibiotic therapy is NOT recommended for persistent symptoms without objective evidence of active infection 1, 2
• These symptoms often represent post-infectious inflammatory processes or alternative diagnoses, not persistent infection 1

Serologic testing limitations:

• Positive serology alone cannot be used as a marker of active disease 1, 4
• Previous Lyme disease does not confer protective immunity; reinfection can occur 1, 4
• Early antibiotic treatment can blunt antibody response 1