What are the recommended antibiotic regimens for Lyme disease in adults with early localized infection, in children under 8 years, in pregnant women, and for severe neurologic or cardiac involvement?

Treatment for Lyme Disease

Early Localized Disease (Erythema Migrans)

For adults with early localized Lyme disease, treat with doxycycline 100 mg orally twice daily for 14 days, which is the preferred first-line regimen. 1, 2

• Doxycycline offers the critical advantage of covering potential coinfection with Anaplasma phagocytophilum, which commonly occurs in Lyme-endemic areas. 1
• The treatment duration is 14 days, with an acceptable range of 10-21 days based on clinical response. 2
• Patients must take doxycycline with 8 ounces of fluid to prevent esophageal irritation and should avoid sun exposure due to photosensitivity risk. 2

Alternative oral regimens for adults include:

• Amoxicillin 500 mg orally three times daily for 14-21 days 1, 2
• Cefuroxime axetil 500 mg orally twice daily for 14-21 days 2

These alternatives demonstrate comparable efficacy to doxycycline, with complete response rates exceeding 83% at 30 months. 2

Pediatric Treatment

For children under 8 years of age, treat with amoxicillin 50 mg/kg/day divided into three doses (maximum 500 mg per dose) for 14 days. 1, 2

• Doxycycline is contraindicated in children under 8 years due to dental staining risk. 2
• For children 8 years and older, doxycycline 4 mg/kg per day in 2 divided doses (maximum 100 mg per dose) for 14 days is appropriate. 2
• Cefuroxime axetil 30 mg/kg/day divided into 2 doses (maximum 500 mg per dose) for 14 days is an effective alternative when amoxicillin is not tolerated. 2

Pregnant Women

Treat pregnant women identically to non-pregnant patients with the same disease manifestation, but avoid doxycycline. 3, 1

• Amoxicillin 500 mg three times daily for 14-21 days is the preferred oral regimen for pregnant women with early localized disease. 1
• For disseminated disease requiring parenteral therapy, use ceftriaxone 2 g IV daily for 14 days. 4
• The "wait and watch" strategy is appropriate after tick bites in pregnancy rather than prophylactic antibiotics, with early treatment initiated only if clinical signs develop. 4

Early Neurologic Disease

For meningitis or radiculopathy, treat with ceftriaxone 2 g IV once daily for 14 days (range 10-28 days). 1

• Pediatric dosing is 50-75 mg/kg IV daily (maximum 2 g). 1
• Alternative parenteral options include cefotaxime 2 g IV every 8 hours or penicillin G 18-24 million units per day IV divided every 4 hours. 5

For isolated cranial nerve palsy (especially facial nerve palsy) without other neurologic signs and with normal cerebrospinal fluid, oral antibiotic therapy is sufficient. 3, 5

• Use the same oral regimens as for erythema migrans (doxycycline, amoxicillin, or cefuroxime axetil) for 14-21 days. 3
• IV therapy is not necessary for isolated cranial nerve palsy when CSF is normal. 5

Lyme Carditis

For Lyme carditis, use either oral or parenteral antibiotic therapy for 14-21 days depending on severity. 1

• Hospitalization with continuous cardiac monitoring is mandatory for symptomatic patients, those with second- or third-degree atrioventricular block, or those with first-degree heart block with PR interval ≥300 milliseconds. 1
• Oral regimens (doxycycline, amoxicillin, or cefuroxime axetil) are appropriate for mild carditis without significant conduction abnormalities. 3
• Parenteral ceftriaxone 2 g IV daily is indicated for severe cardiac involvement with advanced heart block. 3

Late Disease (Lyme Arthritis)

For Lyme arthritis without neurologic involvement, treat with oral antibiotics for 28 days using the same agents as for erythema migrans. 1

• For recurrent arthritis after the initial oral regimen, consider either a second 28-day oral course or switch to parenteral therapy (ceftriaxone 2 g IV daily) for 14-28 days. 1
• For antibiotic-refractory arthritis (persistent joint inflammation after two courses of antibiotics), switch to symptomatic therapy rather than additional antibiotics. 3

For late neurologic disease (central or peripheral nervous system involvement), use parenteral ceftriaxone 2 g IV daily for 14-28 days. 1

• Response to treatment for late neurologic manifestations is typically slow and may be incomplete. 5

Tick Bite Prophylaxis

Offer single-dose doxycycline 200 mg (pediatric: 4 mg/kg for children ≥8 years) for tick bite prophylaxis only when ALL of the following criteria are met: 1

1. The attached tick is reliably identified as an adult or nymphal Ixodes scapularis tick
2. The tick is estimated to have been attached for ≥36 hours based on degree of engorgement
3. Prophylaxis can be started within 72 hours of tick removal
4. Local infection rate of ticks with Borrelia burgdorferi is ≥20% 3, 1

Otherwise, use the "wait and watch" strategy with early treatment if clinical signs develop. 4

Coinfection Considerations

Consider coinfection with Babesia microti or Anaplasma phagocytophilum in patients who present with more severe initial symptoms than typically seen with Lyme disease alone. 3

• Specific indicators include high-grade fever persisting for ≥48 hours despite appropriate Lyme therapy, or unexplained leukopenia, thrombocytopenia, or anemia. 3
• A 10-day course of doxycycline simultaneously treats both Lyme disease and anaplasmosis. 5
• Active babesiosis requires specific antimicrobial therapy to prevent serious complications, and exchange transfusion may be needed for high-grade parasitemia (≥10%). 5

Critical Pitfalls to Avoid

Never use the following ineffective or harmful treatments for Lyme disease: 3, 1

• First-generation cephalosporins (e.g., cephalexin) are completely inactive against B. burgdorferi 2
• Fluoroquinolones, carbapenems, vancomycin 3, 1
• Metronidazole, tinidazole, trimethoprim-sulfamethoxazole 3, 1
• Benzathine penicillin G 3, 1
• Long-term antibiotic therapy beyond recommended durations 3, 1, 5
• Combination antimicrobial therapy 3, 5
• Pulsed-dosing regimens (dosing on some days but not others) 3, 1

Macrolides (azithromycin, clarithromycin, erythromycin) are less effective than first-line regimens and should only be reserved for patients intolerant of all first-line options. 2, 5

Do not extend treatment beyond 21 days for early disease or 28 days for late disease, as this does not improve outcomes and increases risk of harm. 2

Do not use serologic testing to monitor treatment response, as antibodies often remain positive for months to years after successful treatment. 5