What is the recommended antimicrobial treatment for early disseminated neurologic Lyme disease (e.g., meningitis, cranial nerve palsy, radiculitis, peripheral neuropathy)?

Treatment for Early Disseminated Neurologic Lyme Disease

For early disseminated neurologic Lyme disease with meningitis or radiculopathy, use IV ceftriaxone, cefotaxime, penicillin G, or oral doxycycline for 14-21 days; for isolated cranial nerve palsy without CNS involvement, oral antibiotics alone are sufficient. 1

Treatment Based on Neurologic Manifestation

Meningitis or Radiculopathy (CNS Involvement)

Parenteral therapy is the standard approach for patients with Lyme meningitis or radiculopathy, though oral doxycycline is now recognized as equally effective. 1

First-line options include:

• IV ceftriaxone 2g daily (most commonly used) 1, 2
• IV cefotaxime 2g every 8 hours 1, 2
• IV penicillin G in meningeal doses (14g in divided doses) 1, 3
• Oral doxycycline 200-400 mg daily (divided doses) 1, 2

Treatment duration: 14 days (range 10-28 days) 1

The 2020 IDSA/AAN/ACR guidelines represent a significant update from 2006, now giving oral doxycycline equal standing with IV antibiotics for meningitis and radiculopathy. 1 The choice between oral and IV should be based on individual factors including side effect profile, ease of administration, ability to tolerate oral medication, and compliance concerns—not effectiveness. 1 You may switch from IV to oral during treatment. 1

Isolated Cranial Nerve Palsy (Especially Facial Nerve)

Oral antibiotics are sufficient for isolated cranial neuropathy without evidence of CNS involvement. 1

Recommended oral regimens:

• Doxycycline 100 mg twice daily 1, 2
• Amoxicillin 500-1000 mg three times daily 2, 3
• Cefuroxime axetil 500 mg twice daily 1

Treatment duration: 14-21 days 1

Critical decision point: Perform lumbar puncture if there is strong clinical suspicion of CNS involvement (severe or prolonged headache, nuchal rigidity). 1 Cranial nerve palsies in Lyme disease are often associated with CSF pleocytosis even without meningeal symptoms. 1 If CSF shows pleocytosis or other evidence of CNS infection, treat as meningitis with parenteral therapy or oral doxycycline. 1

Peripheral Neuropathy and Radiculoneuritis

For painful radiculoneuritis, mononeuropathy multiplex, or confluent mononeuropathy multiplex, use the same regimens as for meningitis (IV ceftriaxone, cefotaxime, penicillin G, or oral doxycycline for 14-21 days). 1, 4

For indolent peripheral neuropathies without acute features, a trial of oral antibiotics (doxycycline 100 mg 2-3 times daily or amoxicillin 500-1000 mg three times daily for 21-30 days) is reasonable. 2 If oral therapy fails, switch to parenteral antibiotics. 2

Special Populations

Pregnant and Lactating Patients

Treat identically to non-pregnant patients with the same neurologic manifestation, but avoid doxycycline. 1 Use amoxicillin or IV ceftriaxone/cefotaxime instead. 1

Children Under 8 Years

Use amoxicillin 50 mg/kg/day in 3 divided doses or cefuroxime axetil 30 mg/kg/day in 2 divided doses for isolated cranial nerve palsy. 5 For meningitis or radiculopathy, use IV ceftriaxone 50-75 mg/kg/day (maximum 2g daily). 5

Children 8 Years and Older

Doxycycline 4 mg/kg/day in 2 divided doses is appropriate for isolated cranial nerve palsy. 5 For CNS involvement, use IV ceftriaxone at pediatric dosing. 5

Common Pitfalls to Avoid

Do not use these ineffective or inappropriate agents: 1

• First-generation cephalosporins (e.g., cephalexin)
• Fluoroquinolones
• Carbapenems
• Vancomycin
• Metronidazole
• Benzathine penicillin G
• Macrolides as first-line therapy (reserve only for patients intolerant of tetracyclines, penicillins, and cephalosporins)

Do not prescribe prolonged or repeated courses of antibiotics beyond the recommended 14-28 day duration for the same episode of neurologic Lyme disease. 1 Complete response may be delayed beyond treatment duration, but this does not indicate need for additional antibiotics. 1

Do not dismiss the need for cardiac evaluation if patients have orthostatic symptoms, lightheadedness, syncope, palpitations, dyspnea, or chest pain—obtain an ECG to rule out Lyme carditis. 6

Monitoring and Expected Response

Most patients respond promptly to appropriate antibiotic therapy, though neurologic recovery may be slow, particularly for chronic manifestations. 4 Recovery from acute Lyme meningoradiculoneuritis is typically good with 2-4 weeks of treatment. 4 Patients with more severe initial symptoms or longer duration of illness before treatment may take longer to recover completely. 5

Consider coinfection with Babesia microti or Anaplasma phagocytophilum in patients with high-grade fever persisting >48 hours despite appropriate Lyme treatment, or unexplained leukopenia, thrombocytopenia, or anemia. 1