Immediate Treatment for Suspected Lyme Disease
Start doxycycline immediately for suspected Lyme disease without waiting for serologic testing, and discontinue antibiotics if both IgG and IgM are negative and clinical suspicion is low. 1
When to Start Treatment Immediately
Do not delay treatment while awaiting laboratory confirmation in suspected cases. 1 The decision to start empiric doxycycline depends on clinical presentation:
- Start doxycycline 100 mg twice daily immediately if erythema migrans is present, as this is a clinical diagnosis that does not require laboratory confirmation 2, 3
- Begin treatment for typical erythema migrans (expanding red rash ≥5 cm with central clearing or homogeneous appearance) even with negative serology 2
- Doxycycline has the critical advantage of treating co-infection with Human Granulocytic Anaplasmosis (HGA), which may occur simultaneously with Lyme disease 2, 1
Interpreting Negative Serology
Serologic testing is often negative in early Lyme disease and should not be used to exclude the diagnosis when erythema migrans is present. 4
Stop antibiotics if:
- Both IgG and IgM are negative 4
- AND no erythema migrans rash is present 2
- AND no objective signs of disseminated disease (multiple skin lesions, cranial nerve palsy, carditis, arthritis) 2
- AND alternative diagnosis is identified 4
Continue antibiotics despite negative serology if:
- Classic erythema migrans is present (this is a clinical diagnosis) 2
- Objective neurologic manifestations exist (meningitis, cranial neuropathy, radiculopathy) 2
- Cardiac involvement is documented (heart block) 2
- Arthritis is present in endemic areas 2
Critical Timing Considerations
Antibody tests are unreliable in the first 2-4 weeks of infection because IgM antibodies typically appear 2-4 weeks after infection onset, and IgG antibodies appear even later. 4 Testing during the erythema migrans stage frequently yields false-negative results. 4
Treatment Duration
- Doxycycline 100 mg twice daily for 10-14 days for early localized or early disseminated Lyme disease with erythema migrans 2, 3, 1
- A 7-day course may be sufficient for solitary erythema migrans in adults, though this is based on European data 5
- Extend to minimum 10 days if concurrent anaplasmosis is suspected (high fever >48 hours despite treatment, leukopenia, thrombocytopenia) 2, 1
Common Pitfalls to Avoid
Never use first-generation cephalosporins (e.g., cephalexin) as they are completely ineffective against B. burgdorferi. 2, 3, 1 This is a critical error that leads to treatment failure.
Do not order serologic testing to "rule out" Lyme disease in patients without clinical findings suggestive of Lyme disease. 4 This leads to false-positive results and unnecessary treatment.
Do not retest serology after treatment to assess cure. 4 Antibodies remain positive for months to years after successful treatment and do not correlate with treatment response. 4
Avoid macrolides (azithromycin, clarithromycin, erythromycin) as first-line therapy as they are significantly less effective than doxycycline or amoxicillin. 2, 3 Reserve these only for patients who cannot tolerate doxycycline, amoxicillin, or cefuroxime axetil. 2
Alternative First-Line Agents
If doxycycline is contraindicated (pregnancy, lactation, children <8 years):
- Amoxicillin 500 mg three times daily for 14 days (adults) 2, 3
- Cefuroxime axetil 500 mg twice daily for 14 days (adults) 2, 3
- For children: amoxicillin 50 mg/kg/day in 3 divided doses (max 500 mg/dose) for 14 days 2, 3
When to Consider Treatment Failure
Reassess if objective signs persist or worsen after completing appropriate antibiotic therapy:
- Persistent or worsening erythema migrans after 14 days of treatment 2
- Development of new objective manifestations (arthritis, neurologic findings, carditis) 2
- Consider co-infection with Babesia or Anaplasma if high fever persists >48 hours despite appropriate antibiotics 2, 4
Do not interpret persistent nonspecific symptoms (fatigue, arthralgias) as treatment failure in the absence of objective findings, as these may represent post-infectious phenomena rather than ongoing infection. 4, 6