Antibiotic therapy is the mainstay of treatment.
Post-exposure prophylaxis
Post-exposure prophylaxis with a single dose of doxycycline is recommended for significant exposures under the following circumstances:[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
High-risk tick bite: an Ixodes tick bite; at least an estimated 36 hours of attachment; and in an area highly endemic for Lyme disease.
Prophylaxis is started within 72 hours of tick removal.
Doxycycline is not contraindicated. Doxycycline is not recommended during pregnancy and lactation. In some countries outside of the US, doxycycline is not recommended in younger children (see below).
An area with Borrelia burgdorferi prevalence of >20% in local ticks is considered a highly endemic area.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Patients who cannot take doxycycline for post-exposure prophylaxis are started on treatment if early symptoms develop.
Erythema migrans
Treatment of Lyme disease associated with erythema migrans in the absence of cardiovascular and neurological manifestations is as follows:[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
[38]Steere AC, Malawista SE, Newman JH, et al. Antibiotic therapy in Lyme disease. Ann Intern Med. 1980 Jul;93(1):1-8.
http://www.ncbi.nlm.nih.gov/pubmed/6967272?tool=bestpractice.com
[39]Steere AC, Hutchinson GJ, Rahn DW, et al. Treatment of early manifestations of Lyme disease. Ann Intern Med. 1983 Jul;99(1):22-6.
http://www.ncbi.nlm.nih.gov/pubmed/6407378?tool=bestpractice.com
[40]Massarotti EM, Luger SW, Rahn DW, et al. Treatment of early Lyme disease. Am J Med. 1992 Apr;92(4):396-403.
http://www.ncbi.nlm.nih.gov/pubmed/1313637?tool=bestpractice.com
[41]Nadelman RB, Luger SW, Frank E, et al. Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. Ann Intern Med. 1992 Aug 15;117(4):273-80.
http://www.ncbi.nlm.nih.gov/pubmed/1637021?tool=bestpractice.com
[42]Luger SW, Paparone P, Wormser GP, et al. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. Antimicrob Agents Chemother. 1995 Mar;39(3):661-7.
http://aac.asm.org/cgi/reprint/39/3/661
http://www.ncbi.nlm.nih.gov/pubmed/7793869?tool=bestpractice.com
[43]Nowakowski J, Nadelman RB, Forseter G, et al. Doxycycline versus tetracycline therapy for Lyme disease associated with erythema migrans. J Am Acad Dermatol. 1995 Feb;32(2 Pt 1):223-7.
http://www.ncbi.nlm.nih.gov/pubmed/7829706?tool=bestpractice.com
[44]Eppes SC, Childs JA. Comparative study of cefuroxime axetil versus amoxicillin in children with early Lyme disease. Pediatrics. 2002 Jun;109(6):1173-7.
http://www.ncbi.nlm.nih.gov/pubmed/12042561?tool=bestpractice.com
[45]Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003 May 6;138(9):697-704.
http://www.ncbi.nlm.nih.gov/pubmed/12729423?tool=bestpractice.com
Doxycycline for 10 days; or amoxicillin or cefuroxime for 14 days. In the UK, longer courses of doxycycline and amoxicillin are recommended (21 days).[33]National Institute for Health and Care Excellence (UK). Lyme disease. October 2018 [internet publication].
https://www.nice.org.uk/guidance/ng95
A randomised, open-label trial of 300 adults in Slovenia with solitary erythema migrans found that oral doxycycline for 7 days was non-inferior to 14 days, raising the possibility of a shorter treatment course. Larger studies from different locales are required to validate this finding.[46]Stupica D, Collinet-Adler S, Blagus R, et al. Treatment of erythema migrans with doxycycline for 7 days versus 14 days in Slovenia: a randomised open-label non-inferiority trial. Lancet Infect Dis. 2023 Mar;23(3):371-9.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00528-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36209759?tool=bestpractice.com
Doxycycline is not recommended in pregnant or lactating women; amoxicillin for 14 days is the recommended treatment.
Doxycycline, amoxicillin, or cefuroxime may be used in children.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
[47]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
In some countries outside of the US, doxycycline is not recommended in younger children (see below).
Macrolides are not recommended for first-line treatment, but reserved for patients who are intolerant to all first-line antibiotics. Azithromycin can be used for 7-10 days in these cases. In the US, macrolides are generally felt to be less effective than amoxicillin, based upon findings from a randomised trial which demonstrated improved resolution of symptoms and reduced risk of relapse in patients treated with amoxicillin compared with those treated with azithromycin.[48]Luft BJ, Dattwyler RJ, Johnson RC, et al. Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomized, controlled trial. Ann Intern Med. 1996 May 1;124(9):785-91.
https://www.acpjournals.org/doi/10.7326/0003-4819-124-9-199605010-00002
http://www.ncbi.nlm.nih.gov/pubmed/8610947?tool=bestpractice.com
In the UK, longer courses of azithromycin are recommended (17 days).[33]National Institute for Health and Care Excellence (UK). Lyme disease. October 2018 [internet publication].
https://www.nice.org.uk/guidance/ng95
When erythema migrans cannot be distinguished from community-acquired cellulitis, cefuroxime or amoxicillin/clavulanate, effective for both conditions, is recommended.
Cardiac involvement
Hospitalisation, intravenous antibiotics, and continuous ECG monitoring are recommended for patients with, or at risk for, severe cardiac complications, including those with chest pain, syncope, dyspnoea, atrioventricular block, PR interval 300 milliseconds or longer, other arrhythmias, or clinical manifestations of myopericarditis.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Ceftriaxone is the drug of choice for both adults and children. Alternative agents include cefotaxime or benzylpenicillin. Doxycycline is an alternative agent for patients with cardiac complications who are intolerant of penicillins or cephalosporins, but it is not recommended during pregnancy and lactation. In some countries outside of the US, doxycycline is not recommended in younger children (see below). Patients may be switched to oral antibiotics when there is evidence of clinical improvement.
Temporary pacing is recommended for patients with symptomatic bradycardia who cannot be managed medically.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Patients with Lyme carditis who do not need to be hospitalised are treated with oral antibiotics.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Oral antibiotic options are doxycycline, amoxicillin, or cefuroxime.
Recommended duration of antibiotic therapy for Lyme carditis is 14-21 days.
Lyme arthritis
Treatment depends on the type and extent of infection:[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Patients with Lyme arthritis are treated with oral antibiotics including doxycycline, amoxicillin, or cefuroxime for 28 days; non-steroidal anti-inflammatory drugs (NSAIDs) may be used adjunctively for symptom relief.
Patients with recurrent or persistent joint swelling after an initial course of oral antibiotics should receive 2-4 weeks of parenteral therapy with intravenous ceftriaxone, rather than a second course of oral antibiotics.
Patients with arthritis who are non-responsive to antibiotic treatment should be referred to a rheumatologist for further work-up and appropriate treatment of other causes.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Neurological Lyme disease (neuroborreliosis)
Patients with acute neurological manifestations of Lyme disease should be treated with one of the following four antibiotics: intravenous ceftriaxone, cefotaxime, benzylpenicillin, or oral doxycycline for 2-3 weeks.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Although parenteral antibiotics are generally preferred for patients with neurological complications, oral doxycycline has been shown to be equally effective in early disease.[34]Mygland A, Ljøstad U, Fingerle V, et al; European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010 Jan;17(1):8-16;e1-4.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2009.02862.x/full
http://www.ncbi.nlm.nih.gov/pubmed/19930447?tool=bestpractice.com
Patients with early neurological Lyme disease confined to the meninges, cranial nerves, nerve roots, or peripheral nerves (Bannwarth syndrome) can be treated with a 2-week course of either an oral antibiotic (doxycycline) or an intravenous antibiotic (ceftriaxone, cefotaxime, or benzylpenicillin).[34]Mygland A, Ljøstad U, Fingerle V, et al; European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010 Jan;17(1):8-16;e1-4.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2009.02862.x/full
http://www.ncbi.nlm.nih.gov/pubmed/19930447?tool=bestpractice.com
Although rare, patients involvement of the brain parenchyma, such as those with focal findings or MRI findings, should be treated with intravenous antibiotics for 2-4 weeks.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Based on small studies, patients with early neuroborreliosis with manifestations such as myelitis, encephalitis, and vasculitis require intravenous antibiotics for 2 weeks.[34]Mygland A, Ljøstad U, Fingerle V, et al; European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010 Jan;17(1):8-16;e1-4.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2009.02862.x/full
http://www.ncbi.nlm.nih.gov/pubmed/19930447?tool=bestpractice.com
For late Lyme disease with peripheral neuropathy and acrodermatitis chronica atrophicans, treatment with either oral doxycycline or intravenous ceftriaxone is recommended.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
[34]Mygland A, Ljøstad U, Fingerle V, et al; European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010 Jan;17(1):8-16;e1-4.
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2009.02862.x/full
http://www.ncbi.nlm.nih.gov/pubmed/19930447?tool=bestpractice.com
However, if patients have central nervous system (CNS) manifestations, such as myelitis, encephalitis, and vasculitis, they should be treated with intravenous ceftriaxone.
Patients with Lyme disease-associated facial palsy should be treated with antibiotics; US guidelines recommend oral doxycycline.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Corticosteroids may have been started, as they are used for the treatment of idiopathic facial nerve palsy; however, they may be discontinued if the cause is identified as borreliosis.[25]Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice puidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021 Jan 23;72(1):e1-48.
https://academic.oup.com/cid/article/72/1/e1/6010652
http://www.ncbi.nlm.nih.gov/pubmed/33417672?tool=bestpractice.com
Prolonged antibiotic treatment (14 weeks) in patients with persistent Lyme borreliosis-attributed symptoms has not been shown to have a beneficial effect on cognitive performance, compared with short-term treatment (2 weeks).[49]Berende A, Ter Hofstede HJM, Vos FJ, et al. Effect of prolonged antibiotic treatment on cognition in patients with Lyme borreliosis. Neurology. 2019 Mar 26;92(13):e1447-55.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453770
http://www.ncbi.nlm.nih.gov/pubmed/30796143?tool=bestpractice.com
Doxycycline in children
Previously, the use of doxycycline was limited to children ≥8 years, but comparative data suggest it is not likely to cause visible teeth staining or enamel hypoplasia in younger children.[50]Todd SR, Dahlgren FS, Traeger MS, et al. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain spotted fever. J Pediatr. 2015 May;166(5):1246-51.
https://www.jpeds.com/article/S0022-3476(15)00135-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25794784?tool=bestpractice.com
One 2023 systematic review also concluded that early childhood doxycycline exposure is not associated with dental staining or enamel defects.[51]Ravindra D, Huang G, Hallett K, et al. Antibiotic exposure and dental health: a systematic review. Pediatrics. 2023 Jul 1;152(1):e2023061350.
https://publications.aap.org/pediatrics/article/152/1/e2023061350/191428/Antibiotic-Exposure-and-Dental-Health-A-Systematic
http://www.ncbi.nlm.nih.gov/pubmed/37264510?tool=bestpractice.com
While doxycycline is now recommended in the US for children <8 years for certain indications (including Lyme disease), in other countries there may still be age restrictions in place and you should consult your local guidance
Lyme disease in pregnancy
The data for vertical transmission of Lyme disease in pregnancy are inconclusive, and evidence on adverse birth outcomes is inconsistent. One meta-analysis of nine studies showed that the prevalence of adverse birth outcomes was significantly lower in women who were treated for gestational Lyme disease, compared with those who were not treated during pregnancy (11% vs. 50%). Therefore, prompt diagnosis and treatment of Lyme disease during pregnancy is recommended.[52]Waddell LA, Greig J, Lindsay LR, et al. A systematic review on the impact of gestational Lyme disease in humans on the fetus and newborn. PLoS One. 2018 Nov 12;13(11):e0207067.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231644
http://www.ncbi.nlm.nih.gov/pubmed/30419059?tool=bestpractice.com
Doxycycline is not recommended during pregnancy or lactation; amoxicillin is the recommended treatment.