Lyme disease medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

The mainstay of therapy for Lyme disease is antimicrobial therapy. Antimicrobial therapy may include doxycycline, amoxicillin, cephalosporins, or macrolides. The choice of antimicrobial therapy depends on the stage of Lyme disease. Individuals who remove attached ticks should be monitored closely for signs and symptoms of tick-borne diseases for up to 30 days.

Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for treatment of Lyme disease^[1]

• 1 Stage 1 – early localized Lyme disease
  • 1.1 Erythema migrans
    • 1.1.1 Adult
      • Preferred regimen (1): Doxycycline 100 mg PO q12h for 10-21 days (avoid in pregnancy)
      • Preferred regimen (2): Amoxicillin 500 mg PO q8h for 14-21 days
      • Preferred regimen (3): Cefuroxime axetil 500 mg q12h for 14-21 days
      • Alternative regimen (1): Azithromycin 500 mg PO q6h for 7–10 days
      • Alternative regimen (2): Clarithromycin 500 mg PO q12h for 14–21 days (avoid in pregnancy)
      • Alternative regimen (3): Erythromycin 500 mg PO q6h for 14–21 days
    • 1.1.2 Pediatric
      • 1.1.2.1 Children < 8 years of age
        • Preferred regimen (1): Amoxicillin 50 mg/kg PO per day q8h (maximum, 500 mg per dose)
        • Preferred regimen (2): Cefuroxime axetil 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
        • Alternative regimen (1): Azithromycin 10 mg/kg PO q6h (maximum, 500 mg per day)
        • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
        • Alternative regimen (3): Erythromycin 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
      • 1.1.2.2 Children ≥ 8 years of age
        • Preferred regimen (1): Doxycycline 4 mg/kg/day PO q12h (maximum, 100 mg per dose）
        • Alternative regimen (1): Azithromycin 10 mg/kg PO q6h (maximum, 500 mg per day)
        • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
        • Alternative regimen (3): Erythromycin 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
  • 2.1 When erythema migrans cannot be reliably distinguished from community-acquired bacterial cellulitis
    • 2.1.1 Adult
      • Preferred regimen (1): Amoxicillin-Clavulanate 500 mg PO q8h
    • 2.1.2 Pediatric
      • Preferred regimen (1): Amoxicillin-Clavulanate 50 mg/kg/day PO q8h (maximum, 500 mg per dose)

• 2 Stage 2 – early disseminated Lyme disease
  • 2.1 Lyme carditis

    Note (1): A parenteral regimen is recommended at the start of therapy for patients who have been hospitalized for cardiac monitoring; oral regimen may be substituted to complete a course of therapy or to treat ambulatory patients.

    Note (2): A temporary pacemaker may be required for patients with advanced heart block.

    Note (3): Patients treated with macrolides should be closely observed to ensure resolution of the clinical manifest.

    • 2.1.1 Adult
      • Parenteral regimen
        • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 (14–21) days
        • Alternative regimen (1): Cefotaxime 2 g IV q8h for 14 (14–21) days
        • Alternative regimen (2): Penicillin G 18–24 MU/day IV q4h for 14 (14–21) days (patients with normal renal function)
      • Oral regimen
        • Preferred regimen (1): Amoxicillin 500 mg PO q8h for 14 (14–21) days
        • Preferred regimen (2): Doxycycline 100 mg PO q12h for 14 (14–21) days (avoid in pregnancy)
        • Preferred regimen (3): Cefuroxime 500 mg PO q12h for 14 (14–21) days
        • Alternative regimen (1): Azithromycin 500 mg PO q6h for 7–10 days
        • Alternative regimen (2): Clarithromycin 500 mg PO q12h for 14–21 days (avoid in pregnancy)
        • Alternative regimen (3): Erythromycin 500 mg PO q6h for 14–21 days
    • 2.1.2 Pediatric
      • Parenteral regimen
        • Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
        • Alternative regimen (1): Cefotaxime 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
        • Alternative regimen (2): Penicillin G 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) (patients with normal renal function)
      • Oral regimen
        • Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg per dose)
        • Preferred regimen (2): Doxycycline (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
        • Preferred regimen (3): Cefuroxime 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg per dose)
        • Alternative regimen (1): Azithromycin 10 mg/kg PO q6h 7–10 days (maximum, 500 mg per day)
        • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg per dose)
        • Alternative regimen (3):  Erythromycin 12.5 mg/kg PO q6h for 14–21 days (maximum,500 mg per dose)
  • 2.2 Borrelial lymphocytoma
    • The same regimens used to treat patients with erythema migrans (see above)

• 3 Stage 3 – Late disseminated Lyme Disease
  • 3.1 Lyme arthritis
    • 3.1.1 Adult
      • Preferred regimen (1): Doxycycline 100 mg PO q12h for 28 days (avoid in pregnancy)
      • Preferred regimen (2): Amoxicillin 500 mg PO q8h for 28 days
      • Preferred regimen (3): Cefuroxime axetil 500 mg PO q12h for 28 days
    • 3.1.2 Pediatric
      • Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h for 28 days  (maximum, 500 mg per dose)
      • Preferred regimen (1): Cefuroxime axetil 30 mg/kg/day PO q12h for 28 days (maximum, 500 mg per dose)
      • Preferred regimen (1): Doxycycline (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 28 days  (maximum, 100 mg per dose)

    Note: Patients with persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy are suggested re-treatment with another 4-week course of oral antibiotics or with a 2–4 week course of ceftriaxone.

  • 3.2 Patients with arthritis and objective evidence of neurologic disease
    • 3.2.1 Adult
      • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 2–4 weeks
      • Alternative regimen (1): Cefotaxime 2 g IV q8h for 2–4 weeks
      • Alternative regimen (2): Penicillin G 18–24 MU/day IV q4h for 2-4 weeks (patients with normal renal function)
    • 3.2.2 Pediatric
      • Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV q24h for 2–4 weeks (maximum, 2 g)
      • Preferred regimen (1): Cefotaxime 150–200 mg/kg/day IV q6–8h for 2–4 weeks (maximum, 6 g per day)
      • Alternative regimen (1): Penicillin G 200,000–400,000 U/kg/day IV q4h for 14 for 2–4 weeks (maximum, 18–24 million U per day) (patients with normal renal function)
  • 3.3 Acrodermatitis chronica atrophicans
    • Preferred regimen (1): Doxycycline 100 mg PO q12h for 21 days (avoid in pregnancy)
    • Preferred regimen (2): Amoxicillin 500 mg PO q8h for 21 days
    • Preferred regimen (3): Cefuroxime axetil 500 mg PO q12h for 21 days

• 4. Post–Lyme Disease Syndromes
  • Preferred regimen: Further antibiotic therapy for Lyme disease should not be given unless there are objective findings of active disease (including physical findings, abnormalities on cerebrospinal or synovial fluid analysis, or changes on formal neuropsychologic testing)

• 1. Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines^[1]
  • 1.1 Early neurologic disease (Stage 2 – early disseminated Lyme disease)
    • 1.1.1 Cranial nerve palsy
      • 1.1.1.1 Adult
        • Preferred regimen (1): Amoxicillin 500 mg PO q8h for 14 (14–21) days
        • Preferred regimen (2): Doxycycline 100 mg PO q12h for 14 (14–21) days (avoid in pregnancy)
        • Preferred regimen (3): Cefuroxime 500 mg PO q12h for 14 (14–21) days
        • Alternative regimen (1): Azithromycin 500 mg PO q6h for 7–10 days
        • Alternative regimen (2): Clarithromycin 500 mg PO q12h for 14–21 days
        • Alternative regimen (3): Erythromycin 500 mg PO q6h for 14–21 days
      • 1.1.1.2. Pediatric
        • Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg/dose)
        • Preferred regimen (2): Doxycycline (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg/dose)
        • Preferred regimen (3): Cefuroxime 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg/dose)
        • Alternative regimen (1): Azithromycin 10 mg/kg/day PO q6h for 7–10 days (maximum, 500 mg/day)
        • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg/dose)
        • Alternative regimen (3): Erythromycin 12.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg/dose)
    • 1.1.2 Meningitis or radiculopathy
      • 1.1.2.1 Adult
        • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 (10–28) days
        • Alternative regimen (1): Cefotaxime 2 g IV q6-8h for 14 (10–28) days
        • Alternative regimen (2): Penicillin G 18–24 MU/day IV q4h for 14 (10–28) days (patients with normal renal function)

      Note: For adult patients intolerant of β-lactam agents, doxycycline (avoid in pregnancy) 200–400 mg/day PO/IV q12h may be considered.

      • 1.1.2.2 Pediatric
        • Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV q24h for 14 (10–28) days (maximum, 2 g/day)
        • Alternative regimen (1): Cefotaxime 150–200 mg/kg/day IV q6-8h for 14 (10–28) days (maximum, 6 g/day)
        • Alternative regimen (2): Penicillin G 200,000–400,000 U/kg/day IV q4h for 14 (10–28) days (maximum, 18–24 MU/day) (patients with normal renal function)

      Note: For children intolerant of β-lactam agents, doxycycline (children aged ≥ 8 years) 4–8 mg/kg/day PO/IV q12h (maximum, 200–400 mg/day may be considered)

  • 1.2 Late neurologic disease (Stage 3 – late disseminated Lyme disease)
    • 1.2.1 Central or peripheral nervous system disease
      • 1.2.1.1 Adult
        • Preferred regimen: Ceftriaxone 2 g IV q24h for 14 (10–28) days
        • Alternative regimen (1): Cefotaxime 2 g IV q8h for 14 (10–28) days
        • Alternative regimen (2): Penicillin G 18–24 MU/day IV q4h for 14 (10–28) days (patients with normal renal function)
      • 1.2.1.2 Pediatric
        • Preferred regimen: Ceftriaxone 50–75 mg/kg IV q24h for 14 (10–28) days (maximum, 2 g/day)
        • Alternative regimen (1): Cefotaxime 150–200 mg/kg/day IV q6–8h for 14 (10–28) days (maximum, 6 g/day)
        • Alternative regimen (2): Penicillin G 200,000–400,000 U/kg/day IV q4h for 14 (10–28) days (maximum, 18–24 MU/day) (patients with normal renal function)

• 2 American Academy of Neurology (AAN) Practice Parameter^[2]
  • 2.1 Meningitis
    • 2.1.1 Adult
      • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 days
      • Preferred regimen (2): Cefotaxime 2 g IV q8h for 14 days
      • Preferred regimen (3): Penicillin G 18–24 MU/day q4h for 14 days (patients with normal renal function)
      • Alternative regimen (1): Doxycycline 100–200 mg q12h for 14 days (avoid in pregnancy)
    • 2.1.2 Pediatric
      • Preferred regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
      • Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
      • Preferred regimen (3): Penicillin G 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) (patients with normal renal function)
      • Alternative regimen (1): Doxycycline (for children aged ≥ 8 years) 4–8 mg/kg/day q12h (maximum 200 mg/day)
  • 2.2 Any neurologic syndrome with CSF pleocytosis
    • 2.2.1 Adult
      • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 days
      • Preferred regimen (2): Cefotaxime 2 g IV q8h for 14 days
      • Preferred regimen (3): Penicillin G 18–24 MU/day IV q4h for 14 days (patients with normal renal function)
      • Alternative regimen (1): Doxycycline 100–200 mg q12h for 14 days (avoid in pregnancy)
    • 2.2.2 Pediatric
      • Preferred regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
      • Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
      • Preferred regimen (2): Penicillin G 200,000–400,000 U/kg/day q4h (maximum, 18–24 MU/day) (patients with normal renal function)
      • Alternative regimen (1): Doxycycline (for children aged ≥ 8 years) 4–8 mg/kg/day q12h (maximum 200 mg/day)
  • 2.3 Peripheral nervous system disease (radiculopathy, diffuse neuropathy, mononeuropathy multiplex, cranial neuropathy; normal CSF)
    • 2.3.1 Adult
      • Preferred regimen (1): Doxycycline 100–200 mg q12h for 14 days (avoid in pregnancy)
      • Alternative regimen (1): Ceftriaxone 2 g IV q24h for 14 days
      • Alternative regimen (2): Cefotaxime 2 g IV q8h for 14 days
      • Alternative regimen (3): Penicillin G 18–24 MU/day IV q4h for 14 days (patients with normal renal function)
    • 2.3.2 Pediatric
      • Preferred regimen (1): Doxycycline (for children aged ≥ 8 years) 4–8 mg/kg/day q12h (maximum 200 mg/day)
      • Alternative regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
      • Alternative regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
      • Alternative regimen (3): Penicillin G 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) (patients with normal renal function)
  • 2.4 Encephalomyelitis
    • 2.4.1 Adult
      • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 days
      • Preferred regimen (2): Cefotaxime 2 g IV q8h for 14 days
      • Preferred regimen (3): Penicillin G 18–24 MU/day IV q4h for 14 days (patients with normal renal function)
    • 2.4.2 Pediatric
      • Preferred regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
      • Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
      • Preferred regimen (3): Penicillin G 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) (patients with normal renal function)
  • 2.5 Encephalopathy
    • 2.5.1 Adult
      • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 days
      • Preferred regimen (2): Cefotaxime 2 g IV q8h for 14 days
      • Preferred regimen (3): Penicillin G 18–24 MU/day IV q4h for 14 days (patients with normal renal function)
    • 2.5.2 Pediatric
      • Preferred regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
      • Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
      • Preferred regimen (3): Penicillin G 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) (patients with normal renal function)
  • 2.6 Post-treatment Lyme syndrome
    • Preferred regimen: symptomatic management

    Note: Antibiotic therapy is not indicated

• Approximately 10 to 20% of patients treated for Lyme disease with a recommended 2-4 week course of antibiotics will develop post-treatment Lyme disease syndrome (PTLDS). Patients report lingering symptoms of fatigue, pain, or joint and muscle aches. In some cases, these can last for more than 6 months.
• The majority of patients with post-treatment Lyme disease syndrome gradually improve over months/years of the primary infection.