What antibiotics, other than doxycycline (Vibramycin), are used to treat Lyme disease?

Alternative Antibiotics for Lyme Disease Treatment

For patients who cannot take doxycycline, the recommended first-line alternatives for Lyme disease treatment are amoxicillin (500 mg three times daily for adults) or cefuroxime axetil (500 mg twice daily for adults) for 14 days. 1, 2

First-Line Alternatives to Doxycycline

Oral Options

• Amoxicillin: 500 mg three times daily for adults or 50 mg/kg/day in 3 divided doses for children (maximum 500 mg per dose) for 14-21 days 1, 3
• Cefuroxime axetil: 500 mg twice daily for adults or 30 mg/kg/day in 2 divided doses for children (maximum 500 mg per dose) for 14-21 days 1, 3

Parenteral Options (for neurological involvement)

• Ceftriaxone: 2 g once daily IV for adults or 50-75 mg/kg/day for children (maximum 2 g) 1, 2
• Cefotaxime: 2 g IV every 8 hours for adults or 150-200 mg/kg/day divided into 3-4 doses for children 1, 2
• Penicillin G: 18-24 million units per day IV divided every 4 hours 2

Second-Line Options (Macrolides)

Macrolide antibiotics are less effective than first-line options and should only be used when patients cannot tolerate doxycycline, amoxicillin, and cefuroxime axetil 1, 4:

• Azithromycin: 500 mg daily for adults or 10 mg/kg/day for children (maximum 500 mg) for 7-10 days 1, 4
• Clarithromycin: 500 mg twice daily for adults or 7.5 mg/kg twice daily for children (maximum 500 mg per dose) for 14-21 days 1, 4
• Erythromycin: 500 mg four times daily for adults or 12.5 mg/kg 4 times daily for children (maximum 500 mg per dose) for 14-21 days 1, 4

Treatment Selection Algorithm

1. First assessment: Can the patient take doxycycline? (contraindicated in pregnancy, lactation, children <8 years)

   • If yes: Use doxycycline (first choice)
   • If no: Proceed to step 2

2. Second assessment: Can the patient take beta-lactams (amoxicillin or cefuroxime)?

   • If yes: Use amoxicillin or cefuroxime axetil
   • If no: Proceed to step 3

3. Third assessment: Does the patient have neurological involvement?

   • If yes: Use IV ceftriaxone, cefotaxime, or penicillin G
   • If no: Use a macrolide (azithromycin, clarithromycin, or erythromycin)

Important Considerations

• Patients treated with macrolides should be closely monitored as these antibiotics have lower efficacy compared to first-line options 1, 4
• First-generation cephalosporins (e.g., cephalexin), fluoroquinolones, carbapenems, vancomycin, metronidazole, and tinidazole are ineffective against B. burgdorferi and should not be used 2
• A recent network meta-analysis found that oral amoxicillin, oral azithromycin, injectable ceftriaxone, and injectable cefotaxime were effective for treating Lyme disease 5
• For neurological manifestations of Lyme disease, parenteral therapy with ceftriaxone is preferred over oral antibiotics 1, 2
• For Lyme carditis in outpatients, oral antibiotics are preferred, while hospitalized patients may initially receive IV ceftriaxone until clinical improvement 1

Treatment Duration

• Standard duration for oral therapy in early Lyme disease is 14 days 3, 4
• For β-lactam antibiotics (amoxicillin, cefuroxime axetil), a full 14-day course is recommended due to their shorter half-life 3, 4
• For Lyme carditis, 14-21 days of total antibiotic therapy is suggested 1

Common Pitfalls to Avoid

• Using first-generation cephalosporins like cephalexin, which are ineffective against B. burgdorferi 2, 3
• Prescribing fluoroquinolones, which lack efficacy against Lyme disease 2
• Using long-term antibiotic therapy beyond recommended durations, which lacks supporting data and may cause harm 2, 6
• Failing to consider co-infections with Babesia microti or Anaplasma phagocytophilum in patients with persistent symptoms despite appropriate therapy 2