What is the Yale protocol for treating Lyme disease?

The "Yale Protocol" Does Not Exist as a Formal Treatment Guideline

There is no established "Yale protocol" for Lyme disease treatment in current medical literature or guidelines. The term may be a misnomer or confusion with standard evidence-based treatment approaches developed by major medical societies.

What You Should Actually Follow

The current standard of care is defined by the 2020 IDSA/AAN/ACR guidelines, which represent the most authoritative and recent recommendations for Lyme disease management. 1

Evidence-Based Treatment Algorithm

Early Localized Disease (Erythema Migrans)

• Adults: Doxycycline 100 mg twice daily for 14 days 2
• Children <8 years: Amoxicillin 50 mg/kg/day divided three times daily for 14 days 2
• Pregnant/lactating women: Amoxicillin 500 mg three times daily for 14-21 days 2

Doxycycline is preferred because it also covers potential Anaplasma phagocytophilum coinfection 2. The 14-day duration is sufficient—extending treatment to 20 days provides no additional benefit 3.

Early Neurologic Disease

• Meningitis or radiculopathy: Ceftriaxone 2 g IV once daily for 14 days (range 10-28 days) 2, 1
• Pediatric dosing: 50-75 mg/kg IV daily (maximum 2 g) 2
• Facial nerve palsy alone (without meningitis): Oral antibiotics as for erythema migrans 1

Lyme Carditis

First, determine if hospitalization is needed:

• Admit if PR interval >300 milliseconds, other arrhythmias, or clinical manifestations of myopericarditis 1, 4
• Continuous cardiac monitoring is mandatory for these patients 1

Treatment approach:

• Outpatients: Oral antibiotics (doxycycline, amoxicillin, cefuroxime axetil, or azithromycin) for 14-21 days 1, 2
• Hospitalized patients: Start IV ceftriaxone until clinical improvement, then switch to oral antibiotics to complete 14-21 days total 1, 4
• Symptomatic bradycardia: Use temporary pacing, NOT permanent pacemaker 1, 4

Lyme Arthritis

Initial treatment: Oral antibiotics for 28 days (same agents as erythema migrans) 1, 2

If partial response (mild residual swelling):

• Consider second 28-day oral course OR observation 1
• Factors to consider: medication adherence, duration before treatment, degree of synovial proliferation 1

If no/minimal response (moderate-severe swelling):

• IV ceftriaxone for 2-4 weeks 1

If failed both oral and IV courses:

• Refer to rheumatology for DMARDs, biologics, intra-articular steroids, or arthroscopic synovectomy 1
• Do NOT continue antibiotics beyond 8 weeks total if treatment included IV therapy 1

Late Neurologic Disease (CNS/PNS Involvement)

• Treatment: IV ceftriaxone for 2-4 weeks 1
• Alternatives: IV cefotaxime or penicillin G 1
• Response is typically slow and may be incomplete 1

Critical Post-Treatment Management

For persistent nonspecific symptoms (fatigue, pain, cognitive impairment) WITHOUT objective signs of active disease:

Do NOT prescribe additional antibiotics 1, 5. This is a strong recommendation with moderate-quality evidence. The treatment failure rate with appropriate initial therapy is approximately 1% 5.

Objective signs that would warrant retreatment include:

• Documented arthritis with joint swelling and effusion 5
• Meningitis with CSF abnormalities 5
• Neuropathy with objective neurologic findings 5
• Carditis with documented conduction abnormalities 5

A positive IgM test after treatment does NOT indicate treatment failure and should not prompt additional antibiotics in the absence of objective clinical signs 5. IgM antibodies commonly persist for months or years after successful treatment 5.

What to Absolutely Avoid

The IDSA explicitly recommends against these ineffective or harmful treatments 2:

• First-generation cephalosporins
• Fluoroquinolones
• Carbapenems
• Vancomycin
• Metronidazole or tinidazole
• Trimethoprim-sulfamethoxazole
• Benzathine penicillin G
• Long-term antibiotic therapy
• Combination antimicrobial therapy (except in research settings 6)
• Pulsed-dosing regimens

Common Pitfalls

Do not dismiss orthostatic symptoms without cardiac evaluation—these may represent life-threatening Lyme carditis requiring immediate treatment 4. Obtain an ECG in any patient with lightheadedness, syncope, palpitations, dyspnea, chest pain, or edema 4.

Do not confuse persistent antibodies with persistent infection—serologic testing cannot distinguish between past treated infection and active disease 5. Approximately 99% of appropriately treated patients achieve cure 5.

Do not place permanent pacemakers in acute Lyme carditis—conduction abnormalities typically resolve with antibiotic treatment, and temporary pacing is sufficient 4.