What is the treatment for Lyme disease?

Treatment of Lyme Disease

For early Lyme disease with erythema migrans, start doxycycline 100 mg twice daily for 10-14 days immediately without waiting for serologic testing, as this is a clinical diagnosis. 1, 2

First-Line Oral Antibiotic Regimens for Early Lyme Disease

Adults

• Doxycycline 100 mg orally twice daily for 10-21 days (preferred agent) 1, 3
• Amoxicillin 500 mg orally three times daily for 14-21 days 1, 3
• Cefuroxime axetil 500 mg orally twice daily for 14-21 days 1, 3

Children

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

Key Advantages of Doxycycline

Doxycycline is the preferred first-line agent because it simultaneously treats Human Granulocytic Anaplasmosis (HGA), which frequently co-occurs with Lyme disease in endemic areas. 1, 2 This dual coverage is critical since coinfection should be suspected in patients with high-grade fever persisting >48 hours despite appropriate Lyme treatment, or unexplained leukopenia, thrombocytopenia, or anemia. 1

Administration Considerations for Doxycycline

• Take with 8 ounces of fluid to prevent esophageal irritation 1, 3
• Take with food to minimize gastrointestinal side effects 1, 3
• Avoid sun exposure due to photosensitivity risk 1, 3
• Contraindicated in pregnancy, lactation, and children <8 years 1, 3

Treatment Duration Rationale

Ten days of doxycycline is sufficient due to its longer half-life, but β-lactam antibiotics (amoxicillin, cefuroxime axetil) require a full 14-day course due to their shorter half-lives. 1, 4, 3 Multiple randomized controlled trials demonstrated comparable efficacy across all three first-line regimens, with complete response rates of 83.9-90.3% at 30 months. 3

Neurologic Lyme Disease

Early Neurologic Disease (Meningitis, Radiculopathy, Cranial Neuropathy)

Intravenous ceftriaxone is the treatment of choice for Lyme meningitis and other early neurologic manifestations. 1

• Adults: Ceftriaxone 2 g IV once daily for 14-21 days 1
• Children: Ceftriaxone 50-75 mg/kg IV once daily (maximum 2 g) for 14-21 days 4
• Alternatives: Cefotaxime or penicillin G IV 1

Isolated Facial Nerve Palsy

If the patient has isolated seventh cranial nerve palsy with no other signs/symptoms of Lyme disease and normal cerebrospinal fluid, oral antibiotics (same regimens as erythema migrans) are usually sufficient. 5 The guidelines make no recommendation regarding corticosteroid use for Lyme-associated facial nerve palsy. 1

Late Neurologic Disease

For late neurologic manifestations affecting the central or peripheral nervous system, use IV ceftriaxone for 2-4 weeks. 1 Response is typically slow and may be incomplete. 1

Lyme Carditis

Outpatient Management

For outpatients with Lyme carditis, oral antibiotics (doxycycline, amoxicillin, or cefuroxime axetil) are preferred over IV antibiotics. 1

Hospitalized Patients

• Initially use IV ceftriaxone until clinical improvement occurs, then switch to oral antibiotics to complete 14-21 days total therapy 1
• Hospital admission with continuous ECG monitoring is mandatory for patients with PR interval >300 milliseconds, other arrhythmias, or clinical manifestations of myopericarditis (exercise intolerance, palpitations, syncope, chest pain, elevated troponin, edema, dyspnea) 1
• For symptomatic bradycardia requiring pacing, use temporary pacing rather than permanent pacemaker implantation, as conduction abnormalities typically resolve with antibiotic treatment 1

Lyme Arthritis

Initial Treatment

Oral antibiotics for 28 days are recommended for Lyme arthritis. 1 Use the same oral regimens as for early Lyme disease (doxycycline, amoxicillin, or cefuroxime axetil). 1

Persistent Arthritis After First Course

If mild residual joint swelling persists after the first 28-day course, the guidelines make no recommendation for versus against a second course of oral antibiotics versus observation. 1 If arthritis persists despite oral therapy and synovial fluid/tissue PCR is negative for Borrelia burgdorferi, symptomatic treatment with NSAIDs, intra-articular corticosteroids, or DMARDs (hydroxychloroquine) is recommended rather than additional antibiotics. 1

Arthroscopic Synovectomy

May reduce the duration of joint inflammation in refractory cases. 1

Pregnancy and Lactation

Pregnant and lactating patients should be treated identically to non-pregnant patients with the same disease manifestation, except doxycycline must be avoided. 1 Use amoxicillin or cefuroxime axetil instead. 1

Babesiosis Coinfection

If babesiosis is suspected (high-grade fever >48 hours, hemolytic anemia, thrombocytopenia), add antiprotozoal therapy:

Mild-to-Moderate Babesiosis

• Atovaquone 750 mg orally every 12 hours PLUS azithromycin 500-1000 mg on day 1, then 250 mg daily for 7-10 days 1

Severe Babesiosis

• Clindamycin 600 mg IV every 8 hours PLUS quinine 650 mg orally every 6-8 hours for 7-10 days 1
• Partial or complete RBC exchange transfusion is indicated for parasitemia ≥10%, significant hemolysis, or renal/hepatic/pulmonary compromise 1

Critical Pitfalls to Avoid

Never Use These Antibiotics

• First-generation cephalosporins (cephalexin) are completely ineffective against B. burgdorferi and must never be used 1, 4, 2
• Fluoroquinolones and carbapenems are not recommended 4

Macrolides Are Inferior

Macrolides (azithromycin, clarithromycin, erythromycin) are significantly less effective than first-line agents and should only be reserved for patients who cannot tolerate doxycycline, amoxicillin, AND cefuroxime axetil. 1, 2, 3 When macrolides are used, patients must be closely monitored to ensure resolution of clinical manifestations. 1

Do Not Prolong Treatment

For patients with persistent nonspecific symptoms (fatigue, pain, cognitive impairment) following standard treatment but lacking objective evidence of reinfection or treatment failure, additional antibiotic therapy is strongly contraindicated. 1 Evidence of treatment failure requires objective signs such as arthritis, meningitis, or neuropathy—not subjective symptoms alone. 1 Extending treatment beyond 21 days for early disease or beyond recommended durations for disseminated disease is unsupported by evidence and may cause harm. 4, 3

Tick Bite Prophylaxis

Single-dose doxycycline 200 mg orally can be used as prophylaxis in selected patients, but prophylaxis is generally not necessary after I. pacificus bites. 1 Amoxicillin should not be substituted for doxycycline prophylaxis due to absence of data on effective short-course regimens. 1

Monitoring After Treatment

Patients should be monitored for up to 30 days after tick removal for development of erythema migrans or viral-like illness. 1 Most patients respond promptly and completely to appropriate therapy, but <10% may not respond to initial treatment as evidenced by persistent objective clinical manifestations. 1, 4 Patients who are more systemically ill at diagnosis may take longer to achieve complete response. 1, 4