6/21/2019 Treatment of Lyme disease - UpToDate

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Treatment of Lyme disease*

Drug Adult dosage Pediatric dosage

Erythema migrans (early disease) ¶Δ

Doxycycline פ 100 mg orally twice 4.4 mg/kg/day orally

daily for 10 days (range divided twice daily
10 to 21 days) (maximum 100 mg per
dose) for 10 days
(range 10 to 21 days)

or Amoxicillin 500 mg orally three 50 mg/kg/day orally

times daily for 14 days
(range 14 to 21 days)
divided three times
daily (maximum 500
mg per dose) for 14
days (range 14 to 21
days)

or Cefuroxime axetil 500 mg orally twice 30 mg/kg/day orally

daily for 14 days (range divided twice daily
14 to 21 days) (maximum 500 mg per
dose) for 14 days
(range 14 to 21 days)

Neurologic disease

Isolated facial nerve Doxycycline ◊¥‡ 100 mg orally twice 4.4 mg/kg/day orally
palsy, meningitis, or daily for 14 days (range divided twice daily
radiculoneuropathy 14 to 28 days) † (maximum 100 mg per
(early disseminated dose) for 14 days
disease) (range 14 to 28
days) †,**

More serious Ceftriaxone ΔΔ 2 g IV once daily for 14 50 to 75 mg/kg IV once

disease ¶¶ (eg, to 28 days † daily (maximum 2 g
encephalitis) per dose) for 14 to 28
days †

Carditis ◊◊

Mild (first-degree Doxycycline ◊ 100 mg orally twice 4.4 mg/kg/day orally

atrioventricular block daily for 14 to 21 days divided twice daily
with PR interval (maximum 100 mg per
<300 milliseconds) dose) for 14 to 21 days

or Amoxicillin 500 mg orally three 50 mg/kg/day orally

times daily for 14 to 21 divided three times
days daily (maximum 500
mg per dose) for 14 to
21 days

or Cefuroxime axetil 500 mg orally twice 30 mg/kg/day orally

daily for 14 to 21 days divided twice daily

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(maximum 500 mg per

dose) for 14 to 21 days

More serious disease Ceftriaxone ◊,ΔΔ,◊◊ 2 g IV once daily for 14 50 to 75 mg/kg IV once
(symptomatic, to 28 days ◊◊ daily (maximum 2 g
second- or third- per dose) for 14 to 28
degree days ◊◊
atrioventricular
block, first-degree
atrioventricular block
with PR interval
≥300
milliseconds) §§

Arthritis ¶¶

Arthritis without Doxycycline ◊ 100 mg orally twice ≥8 years: 4.4

neurologic disease daily for 28 days mg/kg/day orally
divided twice daily
(maximum 100 mg per
dose) for 28 days**

or Amoxicillin ¥¥ 500 mg orally three 50 mg/kg/day orally

times daily for 28 days divided three times
daily (maximum 500
mg per dose) for 28
days

Persistent arthritis Ceftriaxone 2 g IV once daily for 14 50 to 75 mg/kg IV once

with little or no to 28 days daily (maximum 2 g
response to oral per dose) for 14 to 28
antibiotics (despite days
adequate prior oral
or Doxycycline ◊ 100 mg orally twice ≥8 years: 4.4
therapy)
daily for 28 days mg/kg/day orally
divided twice daily
(maximum 100 mg per
dose) for 28 days**

or Amoxicillin ¥¥ 500 mg orally three 50 mg/kg/day orally

times daily for 28 days divided three times
daily (maximum 500
mg per dose) for 28
days

Acrodermatitis chronica atrophicans

Doxycycline ◊ 100 mg orally twice 4.4 mg/kg/day orally

daily for 21 days divided twice daily
(maximum 100 mg per
dose) for 21 days

or Amoxicillin 500 mg orally three 50 mg/kg/day orally

times daily for 21 days divided three times
daily (maximum 500
mg per dose) for 21
days

or Cefuroxime 500 mg orally twice 30 mg/kg/day orally

daily for 21 days divided twice daily
(maximum 500 mg per
dose) for 21 days

IV: intravenous.
* Regardless of the clinical manifestation of Lyme disease, complete response to treatment may be delayed
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6/21/2019 Treatment of Lyme disease - UpToDate

beyond the treatment duration. Relapse has occurred with all of these regimens; patients with objective
signs of relapse may need a second course of treatment.
¶ Alternative but less effective therapy for patients unable to tolerate preferred regimens, azithromycin (in
adults: 500 mg once daily; in children: 10 mg/kg per day) for 7 to 10 days; or clarithromycin (in adults: 500
mg twice daily; in children: 7.5 mg/kg twice per day) for 14 to 21 days; or erythromycin (in adults: 500 mg
four times daily; in children: 12.5 mg/kg four times daily) for 14 to 21 days.
Δ Patients with early disseminated disease who present with multiple erythema migrans lesions are generally
treated with an oral agent (preferably doxycycline) for 21 days, although shorter courses of 14 days may be
sufficient in many patients.
◊ For pregnant and lactating women, tetracyclines are generally avoided in favor of a beta-lactam (eg,
amoxicillin, cefuroxime). However, in the setting of contraindication to a beta-lactam, it may be reasonable
to administer doxycycline rather than a second-line agent (eg, azithromycin) when a short course is required.
Although most tetracyclines are contraindicated in pregnancy because of the risk of hepatotoxicity in the
mother and adverse effects on fetal bone and teeth, these events are extremely rare with doxycycline. Given
the limited data, the decision to use doxycycline during pregnancy must be decided on a case-by-case basis.
§ Doxycycline also has activity against coinfections such as Anaplasma phagocytophilum and Borrelia
miyamotoi, but not against Babesia microti.
¥ For patients with isolated facial nerve palsy, amoxicillin or cefuroxime are alternatives in patients with
contraindications to doxycycline. For patients with other forms of early disseminated disease, most experts
would initiate IV therapy (eg, ceftriaxone) if doxycycline cannot be used.
‡ Although 2006 IDSA guidelines recommend parenteral therapy for patients with acute neurologic
manifestations other than isolated facial nerve palsy (eg, meningitis, radiculoneuropathy), oral doxycycline is
generally preferred, particularly if the patient does not require hospitalization. The use of doxycycline in this
setting is based upon several studies from Europe; it has not been tested systematically in the United States.
† For patients with neurologic disease, there are no studies to help guide length of therapy within the range
suggested by the guidelines, and there are no diagnostic tests to determine clearance of infection or predict
the success of therapy. A 14-day course is adequate in selected patients with mild to moderate signs and
symptoms. In the United States, some practitioners favor using longer courses of antibiotics (eg, 28 days),
particularly for those with evidence of more severe infection or evidence of late-stage neurologic disease (eg,
encephalopathy).
** The American Academy of Pediatrics supports the use of doxycycline for children <8 years of age if it is
administered for ≤21 days. However, there are limited safety data when doxycycline is used for >21 days in
this population.
¶¶ More serious disease includes early disease with parenchymal involvement or late disseminated disease.
In late disease, the response to treatment may be delayed for several weeks or months.
ΔΔ Or cefotaxime 2 g IV every 8 hours for 14 to 28 days for adults and 150 to 200 mg/kg/day in three
divided doses (maximum 6 g per day) for children, or penicillin G 18 to 24 million units per day divided into
doses given every 4 hours in adults and 200,000 to 400,000 units/kg per day divided every 4 hours
(maximum 18 to 24 million units per day) in children. Doxycycline can be used in patients intolerant of beta-
lactam antibiotics.
◊◊ A parenteral antibiotic regimen is recommended for initiation of treatment for hospitalized patients. IV
antibiotics should be continued until high-grade atrioventricular block has resolved and the PR interval has
become less than 300 milliseconds. The patient may then be switched to oral therapy to complete therapy.
Although guidelines suggest a range of 14 to 21 days for patients with cardiac disease, some experts prefer
to extend the course for up to 28 days in those with more serious disease.
§§ A temporary pacemaker may be necessary.
¥¥ Cefuroxime may be used as an alternative in patients with contraindications to doxycycline and
amoxicillin, although it has not been assessed in clinical studies for this indication.

Adapted from:
1. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The Clinical Assessment, Treatment, and Prevention of
Lyme disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the
Infectious Diseases Society of America. Clin Infect Dis 2006; 43:1089.
2. Sanchez E, Vannier E, Wormser GP, Hu LT, et al. Diagnosis, treatment, and prevention of Lyme
disease, human granulocytic anaplasmosis, and babesiosis: a review. JAMA 2016; 315:1767.
3. American Academy of Pediatrics. Lyme disease. In: Red Book: 2018 Report of the Committee on
Infectious Diseases, 31st ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American
Academy of Pediatrics, 2018. p.515.

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