What is the recommended treatment for Borrelia (Borrelia) infections, such as Lyme disease?

Treatment of Borrelia (Lyme Disease) Infections

Early Localized Disease (Erythema Migrans)

For early Lyme disease with erythema migrans, oral antibiotics are the standard of care, with doxycycline, amoxicillin, or cefuroxime axetil as first-line options for 14 days. 1, 2

First-Line Oral Regimens

Adults:

• Doxycycline 100 mg twice daily for 10-14 days (preferred due to coverage of potential coinfection with Anaplasma) 1, 2
• Amoxicillin 500 mg three times daily for 14 days 1
• Cefuroxime axetil 500 mg twice daily for 14 days 1

Children:

• For children <8 years: Amoxicillin 50 mg/kg/day in 3 divided doses (max 500 mg/dose) for 14 days 1, 2
• For children ≥8 years: Doxycycline 4 mg/kg/day in 2 divided doses (max 100 mg/dose) for 10-14 days 1, 2
• Alternative: Cefuroxime axetil 30 mg/kg/day in 2 divided doses (max 500 mg/dose) for 14 days 1, 2

Critical Prescribing Considerations

• Doxycycline should be taken with 8 ounces of fluid to reduce esophageal irritation and with food to reduce GI intolerance 2, 3
• Patients on doxycycline must avoid sun exposure due to photosensitivity risk 2, 3
• Doxycycline is contraindicated in pregnant/lactating women and children <8 years 1
• First-generation cephalosporins (e.g., cephalexin) are completely ineffective and should never be used 1, 2

Second-Line Options (When First-Line Agents Cannot Be Used)

• Macrolides (azithromycin, clarithromycin) are significantly less effective and reserved only for patients intolerant of tetracyclines, penicillins, and cephalosporins 1, 2
• Patients treated with macrolides require close monitoring to ensure resolution 2

Lyme Carditis

For outpatients with Lyme carditis, oral antibiotics are preferred; hospitalized patients should receive IV ceftriaxone initially until clinical improvement, then switch to oral therapy for a total of 14-21 days. 1

Treatment Approach

• Outpatients: Oral antibiotics (doxycycline, amoxicillin, cefuroxime axetil, or azithromycin) for 14-21 days 1
• Hospitalized patients: IV ceftriaxone 2 g once daily until improvement, then switch to oral antibiotics to complete 14-21 days total 1
• For symptomatic bradycardia requiring intervention: Use temporary pacing rather than permanent pacemaker (strong recommendation) 1

When to Test for Lyme Carditis

• Test for Lyme disease in patients with acute myocarditis/pericarditis of unknown cause in endemic areas 1
• Do not routinely test patients with chronic cardiomyopathy of unknown cause 1

Lyme Arthritis

For Lyme arthritis, oral antibiotic therapy for 28 days is the recommended initial treatment. 1

Initial Treatment

• Oral antibiotics (doxycycline, amoxicillin, or cefuroxime axetil) for 28 days (strong recommendation) 1
• Serum antibody testing is preferred over PCR or culture of blood/synovial fluid for diagnosis 1
• For seropositive patients requiring definitive diagnosis, PCR of synovial fluid/tissue is preferred over culture 1

Management of Treatment Failure

Partial response (mild residual joint swelling):

• Consider observation versus second 28-day course of oral antibiotics 1
• Exclude other causes of joint swelling and assess medication adherence 1

No or minimal response (moderate-severe joint swelling):

• IV ceftriaxone 2 g daily for 2-4 weeks is preferred over second oral course 1

Post-antibiotic (antibiotic-refractory) arthritis:

• After failure of 1 oral course AND 1 IV course, refer to rheumatology for consideration of DMARDs, biologics, intraarticular steroids, or arthroscopic synovectomy 1
• Antibiotic therapy beyond 8 weeks (including 1 IV course) provides no additional benefit 1

Neurologic Lyme Disease

For neurologic manifestations including meningitis, radiculopathy, or neuropathy, parenteral therapy with ceftriaxone is recommended. 1, 2

Parenteral Regimens

Adults:

• Ceftriaxone 2 g IV once daily 1
• Alternative: Cefotaxime 2 g IV every 8 hours 1
• Alternative: Penicillin G 18-24 million units/day IV divided every 4 hours 1

Children:

• Ceftriaxone 50-75 mg/kg IV once daily (max 2 g) 1, 2
• Alternative: Cefotaxime 150-200 mg/kg/day IV in 3-4 divided doses (max 6 g/day) 1
• Alternative: Penicillin G 200,000-400,000 units/kg/day divided every 4 hours (max 18-24 million units/day) 1

Special Case: Isolated Facial Nerve Palsy

• If patient has isolated seventh cranial nerve palsy with no other signs/symptoms and normal CSF, oral therapy is usually sufficient 4
• Some clinicians add corticosteroids to hasten resolution, though this is not universally recommended 4

Other Manifestations

Borrelial lymphocytoma:

• Oral antibiotic therapy for 14 days 1

Acrodermatitis chronica atrophicans:

• Oral antibiotic therapy for 21-28 days 1

Post-Treatment Lyme Disease Syndrome

For patients with persistent nonspecific symptoms (fatigue, pain, cognitive impairment) after standard treatment but lacking objective evidence of active disease, additional antibiotics are strongly NOT recommended. 1, 5

Critical Decision Algorithm

Step 1: Assess for objective signs of active disease

• Objective findings include: documented joint swelling/effusion, CSF abnormalities, objective neurologic findings, or documented cardiac conduction abnormalities 5
• Without these objective findings, do NOT prescribe additional antibiotics 1, 5

Step 2: Understand serologic testing limitations

• Positive IgM after treatment does NOT indicate treatment failure or active infection 5
• IgM antibodies commonly persist for months to years after successful treatment 5
• Serologic testing cannot distinguish past treated infection from active disease 5
• Treatment failure rate with appropriate initial therapy is approximately 1% 5

Step 3: Only treat if objective disease activity is present

• Evidence of persistent infection requires objective signs such as arthritis, meningitis, or neuropathy 1, 5

Coinfection Evaluation

Assess for coinfection with Anaplasma phagocytophilum or Babesia microti in patients with high-grade fever or characteristic laboratory abnormalities in endemic regions. 1

• Investigate coinfection if fever persists >1 day while on antibiotic treatment for Lyme disease 1
• If fever persists despite doxycycline treatment, Babesia microti infection is an important consideration 1
• Characteristic laboratory abnormalities include thrombocytopenia 1

Prophylaxis After Tick Bite

For children ≥8 years and adults, a single dose of doxycycline 4 mg/kg (max 200 mg) within 72 hours of tick removal is recommended for high-risk tick bites. 3

Criteria for Prophylaxis (ALL must be met)

• Tick reliably identified as adult or nymphal Ixodes scapularis 3
• Tick estimated to have been attached ≥36 hours 3
• Prophylaxis can be started within 72 hours of tick removal 3
• Local rate of tick infection with B. burgdorferi ≥20% 3
• Doxycycline not contraindicated 3

Common Pitfalls to Avoid

• Never use first-generation cephalosporins (cephalexin)—they are completely ineffective against B. burgdorferi 1, 2, 3
• Never treat based on positive IgM serology alone without objective clinical findings—this leads to unnecessary antibiotic exposure and potential harm 5
• Never prescribe prolonged or repeated antibiotic courses for nonspecific symptoms without objective evidence of active disease 1, 5
• Do not confuse persistent antibodies with persistent infection 5
• Do not use fluoroquinolones or carbapenems—these are not recommended for Lyme disease 2
• Do not prescribe prophylaxis if tick attached <36 hours or if >72 hours have passed since removal 3
• Recognize that most patients (approximately 99%) respond to initial appropriate treatment 5