Medication Summary
The antibiotic regimen for Lyme disease depends on the stage and manifestations of the disease, as well as on patient factors. Antimicrobial therapy typically focuses on Borrelia burgdorferi sensu lato, but should cover all likely pathogens in the context of the clinical setting. Coverage for co-infecting organisms, such as Ehrlichia species, should be considered, especially in patients with atypical clinical presentations.
Tetracyclines
Class Summary
Doxycycline is the preferred drug for oral treatment of Lyme disease in all patients except for pregnant and nursing women and children younger than 8 years of age.
Doxycycline (Vibramycin, Avidoxy, Monodox, Doxy 100, Doryx, Oracea, Adoxa)
Doxycycline is the drug of choice for early localized and early disseminated disease without evidence of central nervous system (CNS) involvement. It can be used for arthritis that is not persistent or recurrent. It has also been promoted for single-dose postexposure prophylaxis. Doxycycline has the key advantage of covering other tick-borne pathogens that may have been co-transmitted (eg, Ehrlichia species, Rickettsia species).
Doxycycline inhibits protein synthesis and thus bacterial growth by binding to the 30S and possibly the 50S ribosomal subunits of susceptible bacteria. This agent interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria.
Tetracycline
Tetracycline is used to treat gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. This agent inhibits bacterial protein synthesis by binding with the 30S and possibly 50S ribosomal subunits of susceptible bacteria. Tetracycline is an alternative drug to doxycycline. Because of its dosing schedule, doxycycline is preferred for compliance reasons; however, tetracycline may be less expensive.
Penicillins
Class Summary
Penicillins provide effective treatment of Lyme disease. These agents are used in patients who are intolerant of doxycycline and in pregnant women and children under the age of 8 years, in whom doxycycline is contraindicated. Intravenous formulations are used in patients who require parenteral therapy.
Penicillin VK
Penicillin VK inhibits the biosynthesis of cell wall mucopeptide. This agent is bactericidal against sensitive organisms when adequate concentrations are reached, and penicillin VK is most effective during the stage of active multiplication. Inadequate concentrations of this drug may produce a bacteriostatic effect only. In addition, penicillin VK can be used to treat erythema migrans, as it is safe in both pregnant and pediatric patients, although amoxicillin is used more commonly these patients.
Penicillin G aqueous (Pfizerpen-G)
Penicillin G is a penicillin antibiotic that inhibits cell-wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria. This agent is an alternative drug to ceftriaxone in patients requiring parenteral therapy for CNS infection, persistent or recurrent arthritis, and/or carditis. The usefulness of penicillin G is limited by the need to administer it six times a day.
Amoxicillin
Amoxicillin is the drug of choice for oral treatment for pregnant or nursing women and children younger than 8 years. It is used for early localized and early disseminated disease without evidence of central nervous system (CNS) involvement. It can be used for arthritis that is not persistent or recurrent. This agent interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.
Macrolides
Class Summary
Macrolides are second-line agents for treatment of Lyme disease. They are appropriate only for patients with intolerance or contraindications to the use of tetracycline and beta-lactam antibiotics.
Erythromycin ethylsuccinate (E.E.S., EryPed, PCE, Erythrocin)
Use of erythromycin should be limited to patients who cannot take tetracyclines or beta-lactam antibiotics, as erythromycin is inferior to those agents for treatment of Lyme disease. Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
In children, age, weight, and severity of infection determine the proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, double the dose.
Azithromycin (Zithromax, Zmax)
Azithromycin is a second-line drug. Like erythromycin, this agent has excellent in vitro sensitivities, but mixed data exist regarding its clinical efficacy in early Lyme disease. Because of its once-daily dosing, azithromycin can be considered in pregnant patients who are allergic to beta-lactams and in patients in whom compliance is a major issue.
Clarithromycin (Biaxin, Biaxin XL)
Clarithromycin is a macrolide antibiotic that inhibits protein synthesis by binding to the 50S ribosomal subunit. This drug is not first-line therapy but is an alternative agent for patients intolerant of doxycycline, amoxicillin, and cephalosporins.
Cephalosporins, 3rd Generation
Class Summary
Intravenously administered cephalosporins are drugs of choice for more severe manifestations of Lyme disease.
Ceftriaxone (Rocephin)
Ceftriaxone is a third-generation cephalosporin that is the preferred drug for intravenous therapy, as it has excellent activity against Borrelia burgdorferi and has favorable pharmacokinetics. It is the drug of choice for CNS infections (eg, meningitis, multiple cranioneuropathies), persistent (ie, minimal improvement within 7 d of initiating oral therapy) or recurrent arthritis, and carditis.
Ceftriaxone inhibits bacterial cell wall synthesis by binding to one or more penicillin-binding proteins. Bacteria eventually lyse because of ongoing activity of cell wall autolytic enzymes, while cell wall assembly is inhibited.
Cefotaxime (Claforan)
Cefotaxime is a third-generation cephalosporin that inhibits bacterial cell-wall synthesis. This agent is an alternative drug to ceftriaxone in patients requiring parenteral therapy.
Cephalosporins, 2nd Generation
Class Summary
Orally administered cefuroxime is an alternative to doxycycline, for patients with intolerance or contraindications to the use of tetracycline antibiotics.
Cefuroxime axetil (Ceftin, Zinacef)
Cefuroxime is a second-generation cephalosporin that is the only drug approved by the Food and Drug Administration (FDA) for use in Lyme disease. Cefuroxime is approved for use in adults. Its principal limitation is its expense. Cefuroxime binds to penicillin-binding proteins and inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death.
Aminoquinolines
Class Summary
Some agents in this class can be used to supplement nonsteroidal anti-inflammatory drugs in patients with Lyme arthritis that is unresponsive to antibiotic therapy, as the synovial inflammation in these patients may represent an autoimmune response. [22] Aminoquinolines may impair complement-dependent antigen-antibody reactions.
Hydroxychloroquine sulfate (Plaquenil)
The mechanism of action of hydroxychloroquine is unknown. This agent may impair complement-dependent antigen-antibody reactions; it inhibits locomotion of neutrophils and chemotaxis of eosinophils. Patients with rheumatic disease may take 4-6 months to show response to hydroxychloroquine; peak response takes several months.
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Lyme disease. The bacterium Borrelia burgdorferi (darkfield microscopy technique, 400X; courtesy of the US Centers for Disease Control and Prevention).
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Lyme disease. Magnified ticks at various stages of development.
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Ticks are the most common vectors for vector-borne diseases in the United States. In North America, tick bites can cause Lyme disease, human granulocytic and monocytic ehrlichiosis, babesiosis, relapsing fever, Rocky Mountain spotted fever, Colorado tick fever, tularemia, Q fever, and tick paralysis. Europe has a similar list of illnesses caused by ticks, but additional concerns include boutonneuse fever and tick-borne encephalitis. Lyme disease is one of the most prominent tick-borne diseases, and its main vector is the tick genus Ixodes, primarily Ixodes scapularis. Image courtesy of the US Centers of Disease Control and Prevention.
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Lyme disease. Approximate US distribution of Ixodes scapularis. Image courtesy of the US Centers for Disease Control and Prevention.
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Lyme disease. In general, Ixodes scapularis must be attached for at least 24 hours to transmit the spirochete to the host mammal. Prophylactic antibiotics are more likely to be helpful if feeding is longer. This photo shows 2 I scapularis nymphs. The one on the right is unfed; the other has been feeding for 48 hours. Note its larger size and the fact that the midgut diverticula (delicate brown linear areas on the body) are blurred. Photo by Darlyne Murawski; reproduced with permission.
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Lyme disease. Normal and engorged Ixodes ticks.
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Amblyomma americanum is the tick vector for monocytic ehrlichiosis and tularemia. An adult and a nymphal form are shown (common match shown for size comparison). Image by Darlyne Murawski; reproduced with permission.
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Approximate US distribution of Amblyomma americanum. Image courtesy of the US Centers for Disease Control and Prevention.
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The soft-bodied tick of the genus Ornithodoros transmits various Borrelia species that cause relapsing fever. Photo courtesy of Julie Rawlings, MPH, Texas Department of Health. Relapsing fever is characterized by recurrent acute episodes of fever (usually >39°C). It is a vector-borne illness spread by lice and ticks. The spirochete species Borrelia is responsible.
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The Ixodes scapularis tick is considerably smaller than the Dermacentor tick. The former is the vector for Lyme disease, granulocytic ehrlichiosis, and babesiosis. The latter is the vector for Rocky Mountain spotted fever. This photo displays an adult I scapularis tick (on the right) next to an adult Dermacentor variabilis; both are next to a common match displayed for scale. Photo by Darlyne Murawski; reproduced with permission.
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Approximate US distribution of Dermacentor andersoni. Image courtesy of the US Centers for Disease Control and Prevention.
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Rhipicephalus ticks are vectors for babesiosis and rickettsial infections, among others. Image courtesy of Dirk M. Elston, MD. In typical practice, testing ticks for tick-borne infectious organisms is not generally recommended. However, healthcare practitioners should become familiar with the clinical manifestations of tick-borne diseases (eg, Lyme disease, especially those practicing in endemic areas) and maintain a high index of suspicion during warmer months. Ticks can be placed in a sealed container with alcohol if they need to be transported and identified.
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To remove a tick, use fine-tipped forceps and wear gloves. Grasp the tick as close to the skin surface as possible, including the mouth parts, and pull upward with steady, even traction. Do not twist or jerk the tick because this may cause the mouth parts to break off and remain in the skin; however, note that the mouth parts themselves are not infectious. When removing, wear gloves to avoid possible infection.
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Lyme disease. This patient's erythema migrans rash demonstrates several key features of the rash, including size, location, and presence of a central punctum, which can be seen right at the lateral margin of the inferior gluteal fold. Note that the color is uniform; this pattern probably is more common than the classic pattern of central clearing. On history, this patient was found to live in an endemic area for ticks and to pull ticks off her dog daily.
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Erythema migrans, the characteristic rash of early Lyme disease.
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Lyme disease. The thorax and torso are typical locations for erythema migrans. The lesion is slightly darker in the center, a common variation. In addition, this patient worked outdoors in a highly endemic area. Physical examination also revealed a right axillary lymph node.
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Lyme disease. Photo of the left side of the neck of a patient who had pulled a tick from this region 7 days previously. Note the raised vesicular center, which is a variant of erythema migrans. The patient had a Jarisch-Herxheimer reaction approximately 18 hours after the first dose of doxycycline.
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Lyme disease. Classic target lesion with concentric rings of erythema, which often show central clearing. Although this morphology was emphasized in earlier North American literature, it only represents approximately 40% of erythema migrans lesions in the United States. This pattern is more common in Europe. Courtesy of Lyme Disease Foundation, Hartford, Conn.
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Typical appearance of erythema migrans, the bull's-eye rash of Lyme disease.
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Lyme disease. Bulls-eye rash.
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Lyme disease. Photo of erythema migrans on the right thigh of a toddler. The size and location are typical of erythema migrans, as is the history of the patient vacationing on Fire Island, NY, in the month of August. No tick bite had been noted at this location. Approximately 25% of patients with Lyme disease are children, which is the same percentage of patients who do not recall a tick bite. Courtesy of Dr John Hanrahan.
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Lyme disease. Multiple lesions of erythema migrans occur in approximately 20% of patients. A carpenter from Nantucket who worked predominantly outside had been treated with clotrimazole/betamethasone for 1 week for a presumed tineal infection, but the initial lesion grew, and new ones developed. He then presented to the emergency department with the rashes seen in this photo. The patient had no fever and only mild systemic symptoms. He was treated with a 3-week course of oral antibiotics.
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Lyme disease. The rash on the ankle seen in this photo is consistent with both cellulitis (deep red hue, acral location, mild tenderness) and erythema migrans (presentation in July, in an area highly endemic for Lyme disease). In this situation, treatment with a drug that covers both diseases (eg, cefuroxime or amoxicillin-clavulanate) is an effective strategy.
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Lyme disease. Borrelial lymphocytoma of the earlobe, which shows a bluish red discoloration. The location is typical in children, as opposed to the nipple in adults. This manifestation of Lyme disease is uncommon and occurs only in Europe. Courtesy of Lyme Disease Foundation, Hartford, Conn.
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A rarely reported noninfectious complication for tick bites is alopecia. It can begin within a week of tick removal and typically occurs in a 3- to 4-cm circle around a tick bite on the scalp. A moth-eaten alopecia of the scalp caused by bites of Dermacentor variabilis (the American dog tick) has also been described. No particular species appears more likely to cause alopecia. Hair regrowth typically occurs within 1-3 months, although permanent alopecia has been observed.
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Acrodermatitis chronica atrophicans is found almost exclusively in European patients and comprises an early inflammatory phase and a later atrophic phase. As the term suggests, the lesion occurs acrally and ultimately results in skin described as being like cigarette paper. Courtesy of Lyme Disease Foundation, Hartford, Conn.
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Blood smear showing likely babesiosis. Babesiosis can be difficult to distinguish from malaria on a blood smear.
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Life cycle of the Ixodes dammini tick. Courtesy of Elsevier.
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Lyme disease in the United States is concentrated heavily in the northeast and upper Midwest; it does not occur nationwide. Dots on the map indicate the infected person's county of residence, not the place where they were infected. Courtesy of the US Centers for Disease Control and Prevention (CDC).
Tables
- Table 1. Clinical presentation and therapy for the stages of Lyme disease
- Table 2. Adult and pediatric treatment options, dosages, and routes of administration
- Table 3. Comparison of Infectious Diseases Society of America (IDSA) and International Lyme and Associated Diseases Society (ILADS) recommendations for Lyme disease treatment
Disease Stage |
Clinical Manifestations |
Treatment |
Duration |
Early localized |
Erythema migrans |
Oral |
Doxycycline, 10 days Amoxicillin or cefuroxime axetil, 14 days Azithromycin, 7 days |
Early disseminated |
Multiple erythema migrans |
Oral |
14 days |
Isolated cranial nerve palsy |
Oral |
14-21 days |
|
Meningoradiculoneuritis |
Oral |
14-28 days |
|
Meningitis |
Intravenous or oral |
14-21 days |
|
Carditis |
|
|
|
-Ambulatory |
Oral |
14-21 days |
|
-Hospitalized |
Intravenous followed by oral |
14-21 days |
|
Borrelial lymphocytoma |
Oral |
14 days |
|
Late |
Arthritis |
Oral |
28 days |
Recurrent arthritis after oral therapy |
Oral or intravenous |
28 days or 14-28 days |
|
Encephalitis |
Intravenous |
14-28 days |
|
Acrodermatitis chronica atrophicans |
Oral |
21-28 days |
|
Treatment |
Adult Dose |
Pediatric Dose |
Oral Therapy |
Doxycycline (patients > 8 y) |
100 mg twice a day |
4 mg/kg (up to 100 mg) twice a day |
Amoxicillin |
500 mg three times a day |
50 mg/kg/day (up to 500 mg) in three divided doses |
|
Cefuroxime axetil |
500 mg twice a day |
30 mg/kg/day (up to 500 mg) in two divided doses |
|
Phenoxymethylpenicillin |
500 mg four times a day, or 1 gm three times a day |
50-100 mg/kg/day in three divided doses; maximum 1 g/dose |
|
Azithromycin (for patients unable to take doxycycline or beta-lactams) |
500 mg once a day
|
50-100 mg/kg/day in three divided doses; maximum 1 g/dose |
|
Intravenous therapy |
Ceftriaxone |
2 g once a day |
10 mg/kg/day (maximum, 500 mg/day) |
Cefotaxime |
2 g every 8 h |
150-200 mg/kg (up to 2 g) every 8 h |
|
Penicillin G |
18-24 million U/d divided every 4 h |
200,000-400,000 mg/kg (up to 2 g) every 8 h |
Treatment Focus |
IDSA |
ILADS |
Treatment of a tick bite without symptoms of Lyme disease |
Doxycycline, 200 mg as a single dose |
Doxycycline, 100 mg bid for 20 days |
Erythema migrans |
Doxycycline, amoxicillin, or cefuroxime for 14-21 days |
Doxycycline, amoxicillin, or cefuroxime for 28-42 days or azithromycin for at least 21 days |
“Persisting symptoms of Lyme disease” |
No antibiotic therapy |
Multiple agents (individually or in combination) are mentioned without specific doses or duration recommended |
